{"_id": "Radiology$$$cbc99c0b-55b2-41dd-82cf-7873dd7e9ade", "text": "In November 1895, Wilhelm Conrad Roentgen discovered X-rays; in March 1896, Henri Becquerel discovered natural radioactivity; and in December 1898, Marie and Pierre Curie produced polonium and later radium."}
{"_id": "Radiology$$$16ab3bc9-13ad-428d-878a-742ad1df7201", "text": "Almost immediately after these discoveries, radiation biology, defined as the study of the effects in biological systems of exposure to radiation, began (Fig. 1.1).\n\nA timeline of the major milestones in radiation biology between 1900 and 2020. The milestones are divided into 4 categories: 1. Radiation is widely used and misused. 2. Gradual tightening of radiation safety norms. 3. Phase-out of non-oncological radiotherapy. 4. Modern radiotherapy.\n\nFig. 1.1\nMilestones of radiation biology"}
{"_id": "Radiology$$$4fc65484-0877-485f-a2be-df38ca37c936", "text": "A timeline of the major milestones in radiation biology between 1900 and 2020. The milestones are divided into 4 categories: 1. Radiation is widely used and misused. 2. Gradual tightening of radiation safety norms. 3. Phase-out of non-oncological radiotherapy. 4. Modern radiotherapy."}
{"_id": "Radiology$$$50e2d3a1-7632-424e-812d-5f1baa7da436", "text": "A plethora of clinical observations, initially on the skin, contributed to a better knowledge of the biological effects of ionizing radiation. The first molecular and cellular mechanistic models of the radiation action were proposed in the 1930s and 1940s and then after the discovery of the DNA structure in the 1950s. It is noteworthy that the first theories unifying molecular and cellular features of irradiated human cells emerged in the 1980s during which the first quantitative features of human radiosensitivity were pointed out [1\u20134]."}
{"_id": "Radiology$$$bc866e7c-2b0a-4c06-ae15-e548ef84aa3a", "text": "These great discoveries at the turn of the twentieth century initiated a new era in human history. Especially, medicine has greatly profited from their applications in diagnosis and treatment of various diseases, revolutionizing our understanding of diseases. The discoveries had a vast impact on society in general and on healthcare in particular."}
{"_id": "Radiology$$$4780855e-9db9-47f7-8aad-5d80f4c28c9d", "text": "In this chapter, we present the main landmarks in the history of X-rays and, more generally, of ionizing radiation. Brief biographies of the pioneers in this field are presented in a chronological description of the whole field and emphasis is placed on the continuity in the development of the application of ionizing radiation to human life."}
{"_id": "Radiology$$$fe580fe3-d01a-4952-9341-8e742001cd55", "text": "By the end of the nineteenth century, \u201cNewtonian\u201d physics had explained nearly all the phenomena involving mass, speed, electricity, and heat. However, some questions remained unanswered, notably the origin of the luminescence phenomena observed either in glass vacuum tubes subjected to a high voltage (e.g., the Crookes tubes\u2014Fig. 1.2) or on certain ores [4]. In both cases, one of the major questions was their inducibility vis-\u00e0-vis the sunlight. The German physicist Wilhelm Conrad Roentgen addressed the first challenge by putting some opaque boxes on the Crookes tube, while the Frenchman Henri Becquerel focused on the second one by studying light emitted by uranium ores in the darkness. The two series of experiments became legendary and led to two Nobel prizes in physics [4].\n\nA photograph of a cathode ray tube connected to wires and attached to smaller tubes.\n\nFig. 1.2\nCrookes, or cathode ray, tube. (Source: Wikimedia. Reproduced with permission)"}
{"_id": "Radiology$$$9f905cbf-dd08-4c35-9bb6-70cb161050b1", "text": "A photograph of a cathode ray tube connected to wires and attached to smaller tubes."}
{"_id": "Radiology$$$57bb6a64-1bec-4d8a-89cc-afb007400c21", "text": "In November 1895, Wilhelm Conrad R\u00f6ntgen (Roentgen) (1845\u20131923) detected electromagnetic radiation of a sub-nanometer wavelength range, today known as X- or Roentgen rays. For this discovery, he was awarded the first Nobel Prize in Physics in 1901. Although he investigated these X-rays and learned much about their interactions with matter, for a long time, he was not entirely convinced that he had made a real discovery [5] (Box 1.1)."}
{"_id": "Radiology$$$cb9bcb3b-08b2-4563-b64e-928c1a09edc9", "text": "Wilhelm Conrad R\u00f6ntgen (1845\u20131923) experimented with Crookes tubes and in November 1895 detected electromagnetic radiation of a sub-nanometer wavelength range (X-rays).\n\nHe earned the first Nobel Prize in Physics in 1901."}
{"_id": "Radiology$$$524a383d-2f1b-405f-abd0-f7beecc36d41", "text": "Wilhelm Conrad R\u00f6ntgen (1845\u20131923) experimented with Crookes tubes and in November 1895 detected electromagnetic radiation of a sub-nanometer wavelength range (X-rays)."}
{"_id": "Radiology$$$5174278d-233a-42bd-877f-2666ce8cf3d5", "text": "Roentgen was born in Lennep, Rhineland, Germany [6]. When he was 3 years old, his family moved to the Netherlands. He was an average student in the primary and secondary school, and in November 1865, he enrolled in the polytechnical school of Zurich, graduating as a mechanical engineer in 1868. After that, Roentgen remained at the University of Zurich as a postgraduate student in mathematics having August Kundt, an expert in the theory of light, as a mentor. Roentgen\u2019s first experiments in Zurich concerned the properties of gases and proved to be important for his subsequent discoveries. His doctoral thesis \u201cStudies on Gases\u201d led to his being awarded a PhD degree in 1869 and being appointed as an assistant to Kundt. In 1870, Roentgen, following Kundt, returned to Germany to the University of Wurzburg (Bavaria). In the autumn of 1893, he was elected Rector at the University of Wurzburg, having 44 publications and being highly respected by his colleagues and the larger academic community. Richard I. Frankel gives an excellent description of the life of W. C. Roentgen as a scientist and describes in detail the events leading up to his groundbreaking discovery."}
{"_id": "Radiology$$$1a308c9e-7dd8-4b75-a51a-3294e0406c61", "text": "On November 8, 1895, after experimenting with cathode rays produced in tubes developed by Johann Hittorf and William Crookes, Roentgen made his discovery. He repeated and expanded his work and gave the first description of the physical and chemical properties of X-rays. He demonstrated that these rays could penetrate not only glass and air but also other materials, including various metals. However, a thin sheet of lead completely blocked them. Roentgen inferred that the radiation he observed was in fact rays because it traveled in straight lines and created shadows of the type that would be created by rays (Fig. 1.3). While studying the ability of lead to stop the rays, Roentgen held a small piece of this metal between his thumb and index finger and placed it in the path of the rays. He noted that he could distinguish the outline of the two digits on the screen and that the bones appeared as shadows darker than the surrounding soft tissue. Roentgen continued his work over the next weeks, during which he made additional images and showed that the rays darkened a photographic plate. In his manuscript entitled \u201cUber eine neue Art von Strahlen\u201d (\u201cOn a New Kind of Rays\u201d) submitted to the Physikalisch-Medizinische Gesellschaft in Wurzburg on December 28, 1895, he used the term \u201cX-rays\u201d for the first time [5].\n\nA photograph on the left of Wilhelm Rontgen. An X ray of a hand with a large ring.\n\nFig. 1.3\nLeft: Wilhelm Conrad R\u00f6ntgen (1845\u20131923), a portrait by Nicola Perscheid, circa 1915. Right: The first roentgenogram\u2014the hand of R\u00f6ntgen\u2019s wife after its irradiation with X-rays (Dec 22, 1895)"}
{"_id": "Radiology$$$15e33a9a-f405-410c-b82b-186b26ce290b", "text": "A photograph on the left of Wilhelm Rontgen. An X ray of a hand with a large ring."}
{"_id": "Radiology$$$68b9b763-0bd4-4ec5-8ff7-fcfe87ed4db5", "text": "Roentgen did not leave any autobiography, so all information regarding people and events which had an influence on his work comes from his biographers. Scientists whose work had greatly influenced Roentgen were the physicist August Kundt (1839\u20131894), the physicist and mathematician Rudolf Clausius (1822\u20131888), and the physicist and physician Hermann Ludwig Ferdinand von Helmholtz (1821\u20131894), all three of German origin. Of importance is his lifelong friendship with the physicist Ludwig Zehnder who served as Roentgen\u2019s chief assistant and became an occasional co-author."}
{"_id": "Radiology$$$c1176948-bf10-4001-af10-dbd5f6a7af75", "text": "It is worth mentioning the relationship between Roentgen and his contemporary German experimental physicist Philipp Lenard (1862\u20131947), director of the Physical Institute at Heidelberg University. Lenard (Fig. 1.4) first published the results of his experiments on cathode rays in 1894 and was awarded for this the Nobel Prize in Physics in 1905. Prior to Roentgen\u2019s discovery, the two scientists exchanged several letters regarding the aspects of the cathode ray research, and Roentgen referenced Lenard in his initial publications on X-rays and used Lenard\u2019s modified tube for his experiments (Box 1.2).\n\nA photograph of Philipp Eduard Anton von Lenard.\n\nFig. 1.4\nPhilipp Eduard Anton von Lenard (1862\u20131947)"}
{"_id": "Radiology$$$4e582a52-a512-4f1a-aad2-713f6a0a3645", "text": "Philipp Lenard (1862\u20131947) was awarded the Nobel Prize in Physics in 1905 for \u201chis work on cathode rays.\u201d\n\nHowever, Lenard became extremely embittered by not winning the Prize in 1901. He became one of Adolf Hitler\u2019s most ardent supporters, eventually becoming \u201cChief of Aryan Physics\u201d under the Nazi regime.\n\nAfter World War II, he was not sentenced (for his prominent role in the Nazi regime) only due to his old age."}
{"_id": "Radiology$$$ae4845c2-3133-4df0-b5a8-c1d88a029752", "text": "Philipp Lenard (1862\u20131947) was awarded the Nobel Prize in Physics in 1905 for \u201chis work on cathode rays.\u201d"}
{"_id": "Radiology$$$d479c1e2-ab20-4c6b-8859-0eb46836fbcf", "text": "However, Lenard became extremely embittered by not winning the Prize in 1901. He became one of Adolf Hitler\u2019s most ardent supporters, eventually becoming \u201cChief of Aryan Physics\u201d under the Nazi regime."}
{"_id": "Radiology$$$47b5792c-90c7-403a-960f-bb56431d32fd", "text": "After World War II, he was not sentenced (for his prominent role in the Nazi regime) only due to his old age."}
{"_id": "Radiology$$$52f15822-7366-4cee-b47b-de27d39b3b29", "text": "However, when Roentgen alone was awarded the Nobel Prize in 1901 \u201cin recognition of the extraordinary services he has rendered by the discovery of the remarkable rays subsequently named after him,\u201d Lenard became extremely embittered, and for the rest of his life, he insisted that he had shown Roentgen the way to his discovery. Lenard became one of the early adherents of the National Socialism and one of Adolf Hitler\u2019s most ardent supporters, eventually becoming \u201cChief of Aryan Physics\u201d under the Nazi regime. In 1933, he published a book called \u201cGreat Men in Science\u201d in which he failed to mention not only Jews, such as Einstein or Bohr, but also non-Aryans like Marie Sk\u0142odowska-Curie and even Roentgen. When World War II ended, Lenard\u2019s prominent role in the Nazi regime led to his arrest, but due to his old age, instead of being sentenced to prison, he was sent to live in a small German village, where he died at the age of 83 [7, 8]."}
{"_id": "Radiology$$$ec53aae3-6cb9-4ab8-bad7-61ad7df06a45", "text": "A few months after the discovery of X-rays, radioactivity was described. Antoine-Henri Becquerel (1852\u20131908) (Fig. 1.5) was a member of a distinguished family of four generations of physicists, all being members of the French Acad\u00e9mie des Sciences. Becquerel\u2019s initial research was in phosphorescence, the emission of light of one color following a body\u2019s exposure to the light of another color. In early 1896, following R\u00f6ntgen\u2019s discovery, Becquerel \u201cbegan looking for a connection between the phosphorescence he had already been investigating and the newly discovered X-rays\u201d [9] and initially thought that phosphorescent materials, such as some uranium salts, might emit penetrating X-ray-like radiation, but only when illuminated by bright sunlight. By May 1896, after a series of experiments with non-phosphorescent uranium salts, he correctly concluded that the penetrating radiation came from the uranium itself, even without any external excitation. The intensive study of this phenomenon led Becquerel to publish seven papers in 1896 only. Becquerel\u2019s other experiments allowed him to figure out what happened when the \u201cemissions\u201d entered a magnetic field: \u201cWhen different radioactive substances were put in the magnetic field, they deflected in different directions or not at all, showing that there were three classes of radioactivity: negative, positive, and electrically neutral\u201d [10] (Box 1.3).\n\nA photograph on the left of Henri Becquerel. An image on the right with 2 dark patches and handwritten text at the top.\n\nFig. 1.5\nLeft: Henri Becquerel (1852\u20131908), circa 1905. Right: Becquerel\u2019s photographic plate exposed to a uranium salt"}
{"_id": "Radiology$$$5e91c457-32cd-47a8-b666-58d3ad45c64a", "text": "A photograph on the left of Henri Becquerel. An image on the right with 2 dark patches and handwritten text at the top."}
{"_id": "Radiology$$$5ea98b69-ec90-409a-8c5c-71b480fa2620", "text": "Henri Becquerel (1852\u20131908) discovered radioactivity in 1896 while studying phosphorescent uranium salts.\n\nLater in the same year, upon experimenting with non-phosphorescent uranium salts, he concluded that the penetrating radiation came from the uranium itself.\n\nHe was awarded the Nobel Prize in Physics in 1903."}
{"_id": "Radiology$$$d5d97f88-5d07-41ae-8516-c8e135415887", "text": "Henri Becquerel (1852\u20131908) discovered radioactivity in 1896 while studying phosphorescent uranium salts."}
{"_id": "Radiology$$$f241dba5-afaa-478d-85ff-053b54f3d432", "text": "Later in the same year, upon experimenting with non-phosphorescent uranium salts, he concluded that the penetrating radiation came from the uranium itself."}
{"_id": "Radiology$$$24d33429-e74e-45d0-87d7-5fc100b8df5b", "text": "Interestingly, radioactivity could have been discovered nearly four decades earlier. In 1857, the photographic investor Abel Ni\u00e9pce de Saint-Victor (1805\u20131870) observed that uranium salts emitted radiation that darkened photographic emulsions. Later in 1861, he realized that uranium salts produced invisible radiation. In 1868, Becquerel\u2019s father Edmond published a book entitled \u201cLa lumi\u00e8re: ses causes et ses effets (Light: Its causes and its effects),\u201d where he mentioned that Ni\u00e9pce de Saint-Victor had observed that some phosphorescent objects could expose photographic plates even when unexposed to sunlight. It is known that \u201cgamma rays\u201d emitted from radioactive materials were first observed in 1900 by the French chemist and physicist Paul Ulrich Villard (1860\u20131934). Villard investigated radiation from radium salts impinging onto a photographic plate from a shielded container through a narrow aperture. He used a thin layer of lead that was already known as alpha-absorber [11]. He was able to show that the remaining radiation consisted of a second and third type of rays. The second type was deflected by a magnetic field similar to the known \u201ccanal rays\u201d and could be identified with beta rays described by Ernest Rutherford. The third type, however, was very penetrating and had never been identified before [12]. Being a modest man, he did not suggest a specific name for the type of radiation he had discovered, and in 1903, it was Rutherford who proposed that Villard\u2019s rays should be called gamma rays [13]."}
{"_id": "Radiology$$$a65fedb0-7263-4cd5-a3db-ff4425b54d69", "text": "It is of great importance to read the following notes written by Becquerel on 2 March 1896: \u201cI will insist particularly upon the following fact, which seems to me quite important and beyond the phenomena which one could expect to observe: The same crystalline crusts (of potassium uranyl sulfate), arranged the same way with respect to the photographic plates, in the same conditions and through the same screens, but sheltered from the excitation of incident rays and kept in darkness, still produce the same photographic images. Here is how I was led to make this observation: among the preceding experiments, some had been prepared on Wednesday the 26th and Thursday the 27th of February, and since the sun was out only intermittently on these days, I kept the apparatuses prepared and returned the cases to the darkness of a bureau drawer, leaving in place the crusts of the uranium salt. Since the sun did not come out in the following days, I developed the photographic plates on the 1st of March, expecting to find the images very weak. Instead, the silhouettes appeared with great intensity \u2026\u201d Becquerel used an apparatus to show that the radiation he discovered was different from X-rays in the way that the new radiation emitted by radioactive materials was bent by the magnetic field so that the radiation was charged. When different radioactive substances were put in the magnetic field, their radiation was either not deflected or deflected in different directions. Becquerel discovered therefore three classes of radioactivity emitting negative, positive, and electrically neutral particles [14]."}
{"_id": "Radiology$$$0309f833-214d-4071-bd75-f21d0c93d076", "text": "A story like that of \u201cRoentgen and Lenard\u201d has developed between \u201cBecquerel and Thompson.\u201d In London, Professor of Physics Silvanus Thompson (1851\u20131916), the founding President of the Roentgen Society, had been experimenting with uranium nitrate and at the end of January 1896 (a few weeks before Becquerel) found that when the uranium salt was exposed to sunlight while placed on a shielded photographic plate, film blackening appeared beneath the uranium. Thompson delayed writing a communication to the Royal Society and so he lost the paternity of radioactivity!"}
{"_id": "Radiology$$$8eef4582-c694-4fa6-a96e-6ee5dbc1d6ab", "text": "Becquerel was awarded the 1903 Nobel Prize for Physics jointly with Pierre Curie (1859\u20131906) and Marie Curie (1867\u20131934) \u201cin recognition of the extraordinary services he has rendered by his discovery of spontaneous radioactivity.\u201d He received one-half of the Prize with the Curies receiving the other half [15]."}
{"_id": "Radiology$$$8704b2f1-0d23-406b-8f36-b283c1eb2fb9", "text": "The physicist Ernest Rutherford (1871\u20131937) is often credited as the father of nuclear physics. In his early work, he developed the concept of radioactive materials\u2019 half-life; discovered the radioactive element radon; named the radiation types alpha, beta, and gamma; and classified them by their ability to penetrate different materials. The abovementioned experiments were performed at McGill University in Montreal, Quebec, Canada (Fig. 1.6). In 1903, Rutherford and Frederick Soddy published the \u201cLaw of Radioactive Change\u201d to account for all their experiments with radioactive materials.\n\nA photograph on the left of Ernest Rutherford. A photograph on the right of Rutherford sitting on a chair in the laboratory, next to an experimental setup.\n\nFig. 1.6\nLeft: Ernest Rutherford (1871\u20131937). Right: Rutherford in his laboratory at McGill University (Canada), 1905. (Reproduced with permission)"}
{"_id": "Radiology$$$efd5a24a-1d28-4a68-a56b-ee5f9f91e9a3", "text": "A photograph on the left of Ernest Rutherford. A photograph on the right of Rutherford sitting on a chair in the laboratory, next to an experimental setup."}
{"_id": "Radiology$$$717cbe4d-8a84-48f4-b2d2-f51f5788354a", "text": "Though the Curies had already suggested that radioactivity was an intra-atomic phenomenon, the idea of the atoms of radioactive substances breaking up was principally new. Until then, atoms had even been assumed to be indivisible (Greek: a-tom), and it was Rutherford and Soddy who demonstrated that radioactivity involved spontaneous disintegration of \u201cradioactive\u201d atoms into other elements. The results of this work provided the basis for the Nobel Prize in Chemistry awarded to Rutherford in 1908 \u201cfor his investigations into the disintegration of the elements, and the chemistry of radioactive substances\u201d [16] (Box 1.4)."}
{"_id": "Radiology$$$b5731432-e7df-49cb-b75b-886de3411b1e", "text": "Ernest Rutherford (1871\u20131937) is known as the father of nuclear physics. He was the first to suggest the existence of nuclei.\n\nHe developed the idea that radioactivity involved spontaneous disintegration of atoms.\n\nIn 1908, he was awarded the Nobel Prize in Chemistry \u201cfor his investigations into the disintegration of the elements, and the chemistry of radioactive substances.\u201d"}
{"_id": "Radiology$$$31e47fa9-5970-43e4-b613-fbebc14af3db", "text": "Ernest Rutherford (1871\u20131937) is known as the father of nuclear physics. He was the first to suggest the existence of nuclei."}
{"_id": "Radiology$$$e8d5e18f-debe-4d8a-8e0a-9493e60f9f1e", "text": "He developed the idea that radioactivity involved spontaneous disintegration of atoms."}
{"_id": "Radiology$$$52f9e28d-456e-4107-9a55-78b3926f69a5", "text": "In 1908, he was awarded the Nobel Prize in Chemistry \u201cfor his investigations into the disintegration of the elements, and the chemistry of radioactive substances.\u201d"}
{"_id": "Radiology$$$898dcbe5-c9e5-4155-826e-3794e688c5a6", "text": "Pierre Curie (1859\u20131906) was a French physicist and a pioneer in crystallography and radioactivity. In 1900, he became Professor at the Faculty of Sciences, University of Paris, and in 1903, he received the Nobel Prize in Physics together with his wife Marie (Fig. 1.7), which they shared with Henri Becquerel. Notably, Marie had been Pierre\u2019s assistant at the City of Paris Industrial Physics and Chemistry Higher Educational Institution (ESPCI Paris).\n\nA photograph of Marie Curie and Pierre Curie in a laboratory. Marie Curie observes through a microscope.\n\nFig. 1.7\nMarie and Pierre Curie in their Laboratory, circa 1904"}
{"_id": "Radiology$$$f229f7f5-509a-4e70-809e-9cd5870323eb", "text": "A photograph of Marie Curie and Pierre Curie in a laboratory. Marie Curie observes through a microscope."}
{"_id": "Radiology$$$86106260-0869-43d4-bc88-d3dd9615b3ad", "text": "The term \u201cradioactivity\u201d was coined by Marie Curie, who together with her husband Pierre extracted uranium from pitchblende (uraninite). To their surprise, the leftover ore was more radioactive than pure uranium, and they assumed that other radioactive elements were present in the ore, a hypothesis which resulted in the discovery of the new elements, polonium and radium. However, 4 years of processing tons of the uranium ore had to pass before they isolated enough polonium and radium to determine their chemical properties. It should be noted that one ton of pitchblende contains only about 0.15\u00a0g of radium."}
{"_id": "Radiology$$$027d86cf-6695-428c-a987-ca183eefe37a", "text": "Pierre Curie and his student Albert Laborde discovered nuclear energy by identifying the continuous emission of heat from radium particles. Incidentally, as early as 1913, H. G. Wells coined the term \u201catomic bomb\u201d\u2014a bomb of unprecedented power based on the use of nuclear energy\u2014appearing in his novel \u201cThe World Set Free.\u201d It should be mentioned, however, that \u201chis\u201d atomic bomb had nearly nothing in common with the actual atomic bomb created three decades later."}
{"_id": "Radiology$$$364ee642-956a-4ecf-bac0-0414c61658fd", "text": "The curie (Ci) became the unit of radioactivity, originally named as such by the Radiology Congress in 1910, clearly in honor of Pierre Curie. Corresponding to the activity of about 1\u00a0g of radium, the Ci is not a SI unit, and in 1964, it was formally replaced by the becquerel (Bq, this time to honor Henri Becquerel), a SI unit which corresponds to one disintegration per second (Box 1.5)."}
{"_id": "Radiology$$$36d57ca3-03d0-4a6e-97e8-8905e8a09484", "text": "Pierre Curie (1859\u20131906) and his wife Marie Salomea Sk\u0142odowska-Curie (1867\u20131934) discovered the elements radium and polonium.\n\nThe term \u201cradioactivity\u201d was coined by Marie Curie.\n\nPierre Curie discovered nuclear energy by identifying the continuous emission of heat from radium particles.\n\nIn 1903, Pierre and Marie Curie were awarded the Nobel Prize in Physics (together with H. Becquerel) for the discovery of radioactivity.\n\nIn 1913, H. G. Wells coined the term \u201catomic bomb\u201d mentioned in his novel \u201cThe World Set Free.\u201d"}
{"_id": "Radiology$$$0f464a04-cb0d-4227-b109-d9aeeefe813b", "text": "Pierre Curie (1859\u20131906) and his wife Marie Salomea Sk\u0142odowska-Curie (1867\u20131934) discovered the elements radium and polonium."}
{"_id": "Radiology$$$cb387648-5ccc-41d3-b43e-0e02ff4ee92a", "text": "Pierre Curie discovered nuclear energy by identifying the continuous emission of heat from radium particles."}
{"_id": "Radiology$$$b66a28de-949c-4db0-82c3-9e6d937e2e83", "text": "In 1903, Pierre and Marie Curie were awarded the Nobel Prize in Physics (together with H. Becquerel) for the discovery of radioactivity."}
{"_id": "Radiology$$$6d509840-ec75-418b-950a-ed4ec4fe6986", "text": "In 1913, H. G. Wells coined the term \u201catomic bomb\u201d mentioned in his novel \u201cThe World Set Free.\u201d"}
{"_id": "Radiology$$$286f2b15-4fd1-4273-a17c-bb77310644e3", "text": "Marie Salomea Sk\u0142odowska-Curie, also known as Madame Curie (1867\u20131934), was a Polish physicist and chemist. She was the first woman to win the Nobel Prize (1903) and the first person to win it twice (1911) in two different scientific fields (physics and chemistry)."}
{"_id": "Radiology$$$fffe26b4-15b5-4af9-8911-d02d5ea6b2b7", "text": "In July 1898, Pierre and Marie Curie published a joint paper announcing the existence of a new element they named \u201cpolonium,\u201d and in December of the same year, they proclaimed the existence of another element, \u201cradium.\u201d Between 1898 and 1902, the Curies published a total of 32 scientific papers including one on the radiobiological effects of \u201cradium rays\u201d on normal and tumor cells [17]. Noteworthy, Mr. and Mrs. Curie did not patent their discoveries and benefited little from the increasingly profitable application of radium for the therapy of various ailments."}
{"_id": "Radiology$$$99eb25d3-64be-461f-b7ef-debd681bb43f", "text": "During World War I, the radiologist Antoine B\u00e9cl\u00e8re persuaded Marie Curie to use X-rays for the diagnosis of wounded soldiers on the front lines. She gave her full support to this project and, using her authority as a Nobel Prize winner, organized the Mobile Radiology Units (Fig. 1.8), 20 of which were installed in the first year of the war. She also designed needles containing \u201cradium emanation\u201d to be used for sterilizing infected tissues.\n\nA photograph of Marie Curie sitting in the passenger seat of a motor vehicle. The back of the vehicle is closed.\n\nFig. 1.8\nMarie Curie in a mobile military X-ray unit during the Great War (WWI), circa 1915"}
{"_id": "Radiology$$$7eb75178-a535-40bb-b25e-d35656211662", "text": "A photograph of Marie Curie sitting in the passenger seat of a motor vehicle. The back of the vehicle is closed."}
{"_id": "Radiology$$$d17ad5b5-9628-4218-8dd7-f700db30ff43", "text": "The half-life of radium 226 is 1600\u00a0years, which is very much shorter than that of uranium (4.5 \u00d7 109 years), so radiation of the former is much more intense. Hence, for the study of radioactivity, radium was much more convenient than the very weakly radioactive uranium. The rays emitted by radium proved also to be an excellent tool for exploring the microscopic structure of matter; radium became to be used for this purpose already at the end of 1901 (Box 1.6)."}
{"_id": "Radiology$$$6db4d91f-e298-4123-ae2c-f002390bd738", "text": "Marie Salomea Sk\u0142odowska-Curie (1867\u20131934) was the first woman to win a Nobel Prize (1903 in physics) and the first person to win the Nobel Prize twice (1911 in chemistry).\n\nDuring the Great War (WWI), she focused on the use of radiation to diagnose wounded soldiers. She developed and organized mobile X-ray units, 20 of which she installed in the first year of the war."}
{"_id": "Radiology$$$73bd7b1c-fcca-43e0-a1c2-9f0a985f6f31", "text": "Marie Salomea Sk\u0142odowska-Curie (1867\u20131934) was the first woman to win a Nobel Prize (1903 in physics) and the first person to win the Nobel Prize twice (1911 in chemistry)."}
{"_id": "Radiology$$$68026ae5-9cdd-4fa6-9a67-0c292490a85a", "text": "During the Great War (WWI), she focused on the use of radiation to diagnose wounded soldiers. She developed and organized mobile X-ray units, 20 of which she installed in the first year of the war."}
{"_id": "Radiology$$$dcfaffc7-a42d-4c8c-97cb-4b66cc8b3f15", "text": "While uranium was the first radioactive element to be discovered, radium was much more popular, as it was a spontaneously luminous material that emitted an incredible quantity of radiation. The popularity of radium is shown in a novel by Maurice Leblanc, \u201cThe Island of Thirty Coffins,\u201d published in 1919 where a central role is played by a stone \u201cshivering with radium, from where goes steadily a bombardment of invigorating and miraculous atoms.\u201d"}
{"_id": "Radiology$$$8ecdc24b-56d7-4843-860d-af8c1cd822fd", "text": "The research that led to the discovery of radium in 1898 was performed despite considerable difficulties, including inadequate lab and lack of funding. However, Pierre Curie managed to get uranium ore from Bohemia, which at the time belonged to Austria. The help of the Austrian Government, which gave one ton of pitchblende, as well as the help of the chairman of the Austrian Academy of Sciences, was gratefully acknowledged in a letter by Marie Curie, who wrote: \u201cThe preparation of radium has been very expensive. We thank the Acad\u00e9mie des sciences [...].\u201d After 2 years, however, the Curies became famous, and the situation had improved considerably."}
{"_id": "Radiology$$$31c7fdb7-95d6-4342-9367-de07fd64aa08", "text": "The collaboration between Pierre and Marie Curie is exemplary in many ways. These two people really complemented each other, as Pierre was dreamy and imaginative, ready to undertake various difficult projects, and Marie was full of energy pursuing her goals. Sadly, Marie Curie died at the Sancellemoz Sanatorium in Passy (Haute-Savoie), France, of aplastic anemia, presumably from exposure to radiation during her scientific research, compounded by her exposure to X-rays in the field radiology units during World War I."}
{"_id": "Radiology$$$17201ecb-2749-4cd9-9fdb-5a36de08a064", "text": "Immediately after the discovery of radium and polonium by Marie and Pierre Curie, the latter examined the possibility to use radium as a powerful therapeutic tool [18, 19]. First successful results were obtained in patients with lupus vulgaris, a form of tuberculosis of the skin. For patients with lesions situated in deeper organs, radium salts were used. In 1904, John MacLeod at Charing Cross Hospital designed one of the first glass radium applicators to treat throat cancer [20], and in 1917, Benjamin Barringer used needles containing radium salts for treating prostate cancer [21]. After World War I, a number of technological devices were proposed to treat a wide spectrum of tumors. This therapeutic approach was initially called curietherapy in Europe and brachytherapy in the USA [22]."}
{"_id": "Radiology$$$a31294fb-855a-4cf3-81c1-ae623cb771b4", "text": "Along with the first medical applications of X-rays or radium, the first radiation-induced tissue reactions were also observed. In the first decade of the nineteenth century, three major applications of X-rays were developed, namely radiography and radiotherapy, mainly against skin diseases such as lupus rather than cancers, as well as radiation-induced hair removal. From a number of these applications, numerous adverse tissue reactions directly due to radiation have been described. In this period, the term \u201cradiodermatitis\u201d was proposed [2]. In 1906, the participants of a Congress of Radiologists organized in Lyon (France) concluded that some patients may show some unexpected skin reactions probably due to radiation [23]. In 1911, the radiologist L\u00e9on Bouchacourt, based on the results of the application of radiation treatment for hypertrichosis to a couple of young people, published a paper with a premonitory title: \u201cAbout the sensitivity to Roentgen Rays of the skin of different individuals and, for a given individual, of the different part of the body\u201d [24, 25]. In this paper, Bouchacourt suggested not only that each individual may show a specific sensitivity to radiation but also that some tissues/organs may be characterized by a specific response to radiation [2]. It is clear that the radiation-induced adverse tissue reactions were documented very early and that the notion of individual radiosensitivity is an old concept [25]."}
{"_id": "Radiology$$$8836a34c-b019-46ad-b1bd-10a4d554a1e0", "text": "The toxicity of X-rays became apparent soon after their discovery by Roentgen (Fig. 1.9). Hair loss has been recognized by May 1896, and skin toxicity was noted a few months later. Early X-ray images required exposures of as long as 80\u00a0min, and thus early X-ray workers were among the most severely affected. Dr. Hall-Edwards, the British physician responsible for the first clinical X-ray \u201cphotograph\u201d in England in early 1896, developed cancer of the hands from radiation exposure incurred while holding patients\u2019 extremities on photographic plates. In 1896, a commercial demonstrator at Bloomingdale Brothers store in New York, whose X-ray machine ran continuously for 2\u20133\u00a0h a day, reported the development of dry skin, followed by changes like a strong sunburn and later scaliness of the skin. He also noted the cessation of fingernail growth and loss of hair from the involved portions of the skin (Box 1.7).\n\nThree photographs of darkened and dry patches on the hands and rotting fingernails.\n\nFig. 1.9\nRadiation injury. (Sources: left\u2014Finzi [26], right) https://\u200bwellcomecollecti\u200bon.\u200borg/\u200bworks/\u200bg94c5mtb"}
{"_id": "Radiology$$$a5192f05-88bd-44c6-9c1d-9f37e3d4da64", "text": "Three photographs of darkened and dry patches on the hands and rotting fingernails."}
{"_id": "Radiology$$$2ee6b9a3-5920-4249-b13e-86a13e0b42a6", "text": "Acute radiation effects (radiodermatitis. etc.) were observed almost immediately after the discovery of ionizing radiation.\n\nIn spite of this, the so-called mild radium therapy was extensively misused."}
{"_id": "Radiology$$$2fddbf67-fe8a-4824-97f9-1d57a7a96108", "text": "Acute radiation effects (radiodermatitis. etc.) were observed almost immediately after the discovery of ionizing radiation."}
{"_id": "Radiology$$$e6c794ba-543e-457e-9bf9-48c402eb2dfc", "text": "In spite of this, the so-called mild radium therapy was extensively misused."}
{"_id": "Radiology$$$6e2d5440-64a0-4711-a894-eab8889be69b", "text": "By chance, Roentgen had conducted virtually all his experiments in a zinc box, which gave better definition of the X-ray beam. He had also added a lead plate to the zinc and thus, fortuitously, protected himself from the radiation that he discovered [5]. In 1902, Guido Holzknecht (1872\u20131931) devised a color dosimeter (\u201cchromoradiometer\u201d) based on the discoloration of crystals after exposing them to X-rays. Holzknecht, like a number of other physicians in the early days of radiology, died from the consequences of radiation \u201cpoisoning,\u201d and his name is displayed on the Monument in honor of the X-ray and Radium Martyrs of All Nations erected in Hamburg, Germany [27]."}
{"_id": "Radiology$$$29dea6f7-0fa0-4d90-a880-37597e831d45", "text": "However, these injuries were not initially attributed to X-ray exposures. Nevertheless, formal action to protect from the harmful effects of radiation was required, and in March 1898, a Committee of Inquiry was established by the British Roentgen Society to \u201cinvestigate the alleged injurious effects of Roentgen rays\u201d [28]. The Committee mentioned explicitly the known adverse effects: skin inflammation, loss of hair, and more it urged collecting information on various effects of X-rays."}
{"_id": "Radiology$$$c810d5e1-218b-46e6-a51d-63c1c97f1ce2", "text": "Right from the first days of the use of radiation, the press reported on the death of \u201cradiological\u201d personnel from cancer, and so European countries and the USA established radiation protection Committees [29]. In 1925, the \u201cFirst International Congress of Radiology\u201d was organized in London, and it was decided to establish the \u201cInternational X-ray Unit Committee.\u201d Hence, the ancestor of the \u201cInternational Commission on Radiation Units and Measurements (ICRU)\u201d was born [30, 31]."}
{"_id": "Radiology$$$b0c329d0-73d5-4064-9cab-467799989b45", "text": "Exposure to radium also caused acute injuries. Two incidents are worth mentioning. The first cases of radium \u201cpoisoning\u201d were recorded among girls painting the luminous watch dials in the Radium Luminous Materials Company, New Jersey, USA (\u201cthe radium girls\u201d). The luminous paint was a mixture of radium salts with zinc sulfide. The workers swallowed and inhaled the paint, and this resulted in the death of 18 out of 800 employed workers between 1917 and 1924 [32]. The causes of death were either cancer (probably osteosarcoma of the jaw) or aplastic anemia, necrosis of the jaw, and spontaneous fractures [33, 34]. But it was the death of the wealthy American iron and steel industrialist Eben Byers in 1932 which put an end to the so-called mild radium therapy. His death was attributed to the enormous quantities of Radithor (Fig. 1.10) that he had consumed. Radithor, produced in the Bailey Radium Laboratories in New Jersey and advertised in the newspapers as \u201cScience to cure all the living dead,\u201d was commercially available in the USA. Each bottle contained 1\u00a0\u03bcCi of 226Ra and 1\u00a0\u03bcCi of 228Ra in 16.5\u00a0mL of liquid. Byers started drinking Radithor in 1927 and stopped by 1930 when his teeth started to fall out (it was estimated that he had emptied between 1000 and 1500 bottles). Eventually, he died from sarcoma of the upper and lower jaws [35]. This event was probably the reason why the era of the \u201cmild radium therapy\u201d came to an end [36] (Box 1.8).\n\nA photograph of a bottle of Radithor, certified radioactive water, closed with a cork.\n\nFig. 1.10\nA bottle of Radithor\u2014one of the most famous varieties of radium-infused water commercially available in the USA in the 1920s"}
{"_id": "Radiology$$$b2f8bd3b-c422-48ee-a6f6-d4983085db4a", "text": "A photograph of a bottle of Radithor, certified radioactive water, closed with a cork."}
{"_id": "Radiology$$$d8656580-8928-4989-b5df-0afcf854ef48", "text": "Radium was extensively misused before World War II via consumption of various radium-containing products.\n\nThe first cases of radium \u201cpoisoning\u201d were recorded among the \u201cradium girls\u201d painting the luminous watch dials.\n\nThe death of the American millionaire Eben Byers in 1932 seems to be the event that ultimately led to cessation of radium misuse."}
{"_id": "Radiology$$$a3315df0-b47c-4e12-9df5-83c987b9552b", "text": "Radium was extensively misused before World War II via consumption of various radium-containing products."}
{"_id": "Radiology$$$04784498-cc7e-4b15-a507-67bacaf1044e", "text": "The first cases of radium \u201cpoisoning\u201d were recorded among the \u201cradium girls\u201d painting the luminous watch dials."}
{"_id": "Radiology$$$f5371ecb-5e81-4015-ae95-2fdaa444ab6c", "text": "The death of the American millionaire Eben Byers in 1932 seems to be the event that ultimately led to cessation of radium misuse."}
{"_id": "Radiology$$$696486ec-f75b-4f58-8161-5f65010ea174", "text": "The so-called fundamental Law of Bergoni\u00e9 and Tribondeau put forward in 1906 postulated that normal tissues appear to be more radiosensitive if their cells are less differentiated, have a greater proliferative capacity, and divide more rapidly. Various data suggest that this law applies to tumors as well."}
{"_id": "Radiology$$$d1f6b998-457a-4992-89c4-4f8ebd1d649b", "text": "Heinrich Ernst Albers-Sch\u00f6nberg, Jean Alban Bergoni\u00e9, Claudius Regaud, and Louis Tribondeau made significant contributions to our knowledge of the biological effects of ionizing radiation. Between 1895 and 1908, they studied histological features of irradiated gonads in numerous animal models. Although the law of Bergoni\u00e9 and Tribondeau that links radiosensitivity with proliferation is not generally applicable, the enormous efforts these scientists made to fight cancer by using ionizing radiation should be acknowledged (Box 1.9)."}
{"_id": "Radiology$$$cb82cf06-7699-4e9f-94b8-f91e6922542c", "text": "The \u201claw of Bergoni\u00e9 and Tribondeau\u201d was formulated in 1906 and postulated that normal tissues appear to be more radiosensitive if their cells are less differentiated, have a greater proliferative capacity, and divide more rapidly.\n\nThe law of Bergoni\u00e9 and Tribondeau has not been verified. However, it has facilitated the advances in radiation biology and understanding of the relationship between cell proliferation and tissue radiosensitivity."}
{"_id": "Radiology$$$52140506-09ef-4ccf-b42a-8b1e02a8cbb6", "text": "The \u201claw of Bergoni\u00e9 and Tribondeau\u201d was formulated in 1906 and postulated that normal tissues appear to be more radiosensitive if their cells are less differentiated, have a greater proliferative capacity, and divide more rapidly."}
{"_id": "Radiology$$$bf18a3c0-f988-45df-8321-d0b8a4184e20", "text": "The law of Bergoni\u00e9 and Tribondeau has not been verified. However, it has facilitated the advances in radiation biology and understanding of the relationship between cell proliferation and tissue radiosensitivity."}
{"_id": "Radiology$$$19609e82-df53-43f2-99bf-1b5fd0f9945b", "text": "In 1906, Jean Bergoni\u00e9 and Louis Tribondeau published a communication to the French Academy of Sciences about the link between cellular proliferation and response to radiation. According to Bergoni\u00e9 and Tribondeau [37], \u201cX rays act on cells inasmuch efficiently as cells have a greater reproductive activity, their karyokinetic fate is longer, their morphology and function are at least definitively fixed.\u201d While they never used the term \u201cradiosensitivity,\u201d this article has with time been read as \u201ccells are inasmuch radiosensitive as they grow fastly\u201d and is still considered as a founding law of radiation oncology. Today, however, there is evidence that this \u201claw\u201d can be contradicted by numerous counterexamples. An epistemological analysis of the archives of Claudius Regaud, another pioneer of radiation biology and a contemporary of Bergoni\u00e9 and Tribondeau, sheds new light on this law [38]. Let us now briefly review some important facts about the life and work of these three French scientists."}
{"_id": "Radiology$$$ba21d6f7-5a93-4a2e-b043-2763427db9bb", "text": "Jean Alban Bergoni\u00e9 (1857\u20131925) (Fig. 1.11) was a physicist and a medical doctor. His expertise in the two areas allowed him to use electrical currents in medical therapy and to develop many new devices based on the discovery of X-rays and radium. In 1911, because of his hitherto intense use of X-rays in the therapy of patients, he developed dermatitis on the right index, and in 1922, his hand (and thereafter his arm) was amputated. Ultimately, he died from lung cancer in 1925 [39]. Of note, Bergoni\u00e9 funded the Journal Archives d\u2019\u00c9lectricit\u00e9 M\u00e9dicale where he wrote that X-rays were discovered \u201csimply thanks to the invention of the Crookes tube some 15 years earlier\u201d [39]. In 1906, he expressed the opinion that \u201cthere are two error types that may affect the medical application of X-rays: (1) the uncertainties in the assessment of radiation dose, \u2026 and (2) the differences in the sensitivity of the patients\u201d [23].\n\nThree photographs of Jean Alban Bergoni\u00e9, Louis Tribondeau, and Claudius Regaud.\n\nFig. 1.11\nBergoni\u00e9, Tribondeau, and Regaud"}
{"_id": "Radiology$$$4052211d-cde9-4d0f-b8b7-4901cbdc1dbc", "text": "Three photographs of Jean Alban Bergoni\u00e9, Louis Tribondeau, and Claudius Regaud."}
{"_id": "Radiology$$$ae476a36-5b25-47c3-806b-afd977b186b3", "text": "Louis Tribondeau (1872\u20131918) (Fig. 1.11) was born in S\u00e8te in Southern France and in 1890 joined the Health Corps of the French Navy. Tribondeau was one of the first histologists who described the microscopic features of tuberculous epididymitis. But he became famous thanks to his staining techniques for bacteriology. In 1918, he died from the Spanish flu [39]."}
{"_id": "Radiology$$$b0f776e0-90bf-4843-87b5-20eff004196f", "text": "Born in Lyon, France, Claudius Regaud (1870\u20131940) (Fig. 1.11) studied medicine in Lyon and attended the microbiology lectures at the Pasteur Institute [40]. In 1893, he worked in Lyon in the laboratory of Joseph Renaut, an eminent histologist, known for his staining technique based on mercury. In Renaut\u2019s laboratory, Regaud improved the staining technique of Ehrlich (methylene blue) and developed his own staining method based on ferric hematoxylin, which reveals mitochondria and cytoplasm [40\u201342]. In 1912, Regaud became head of the Biology Section of the new Radium Institute of Paris, where Marie Curie headed the Physics Section. During World War I, he served as head of an Army Hospital. Not only did he organize the emergency services very effectively, but he also managed multidisciplinary meetings between surgeons, radiologists, hygienists, nurses, and other staff. From 1918 until 1939, he treated thousands of cancer patients and developed a method of fractionated radiotherapy. He died of pneumonia in December 1940 [40]."}
{"_id": "Radiology$$$8a3bf39a-560b-437b-8863-0a01d957c5b9", "text": "On August 5, 1895, Regaud presented the new improvements on his staining technique at the Congress of Neurology in Bordeaux [41]. Tribondeau and Bergoni also attended the sessions and had probably read the papers by Regaud in which the histology of the rodent reproductive system was described in detail based on his new staining technique."}
{"_id": "Radiology$$$5e44d561-a43f-4bd7-93d2-1dba3134a673", "text": "After the discovery of X-rays by Roentgen in December 1895, two German scientists, H. E. Albers-Sch\u00f6nberg and H. Frieben, began to study the effects of this type of radiation on spermatogenesis by irradiating testicles of rabbits and guinea pigs [39, 43, 44]. In Bordeaux, Bergoni\u00e9 undertook to reproduce the experiments of the two Germans. As a physicist, he was able to build irradiation devices but, owing to his limited knowledge of histology, he asked Tribondeau for his technical savoir faire [39]. Between 1904 and 1905, Bergoni\u00e9 and Tribondeau published their first observations about irradiated testicles of rats having used Regaud\u2019s staining technique [45]. They emphasized the role of spermatogonia as pluripotent cells and as the most radiosensitive cells of the reproductive system. However, since the experiments involved irradiation with X-rays, interpretation of the data remained ambiguous."}
{"_id": "Radiology$$$c1d194c7-7c97-4524-8da3-dd5f6dca220c", "text": "Regaud realized that there might be misinterpretations of his own technique. Unlike Bergoni\u00e9, Regaud was a histologist and not a physicist and was helped by Thomas Nogier, a specialist in medical physics. Regaud and Nogier replicated the experiments of Bergoni\u00e9 and Tribondeau using rat models, single exposures, and Regaud\u2019s staining technique [46]. In 1908, Regaud claimed that in young rats, spermatogonia are less radiosensitive than in the adult animals although proliferation rates of these cells are similar in the two groups of rats [47]. However, according to Regaud and Lacassagne [48], Bergoni\u00e9 and Tribondeau generalizations were \u201cimprudently\u201d based on the studies of rat testes. In 1925, Regaud did not hesitate to write about the law of Bergoni\u00e9 and the Tribondeau-Bergoni\u00e9\u2019s eulogy that \u201cActual law as so many people believe it? No. But nice formula of the first approximation\u201d [49]."}
{"_id": "Radiology$$$8ae545f5-e44f-4a97-b3f9-ffb829b07f2d", "text": "These days, several oncology lectures still cite Bergoni\u00e9 and Tribondeau\u2019s law as a founding principle of radiotherapy according to which tumors are more radiosensitive than healthy tissues due to the higher proliferation rate of the former. In this erroneous claim, three kinds of errors were made:1.\nTumors are not necessarily more radiosensitive than normal tissues.\n\u00a02.\nProliferation rate is not necessarily correlated with the cellular death rate after irradiation.\n\u00a03.\nRadiosensitivity and cancer susceptibility to irradiation are two different notions [50]."}
{"_id": "Radiology$$$f3c24c0d-95d6-43df-9f6d-a72aeca2aa02", "text": "Proliferation rate is not necessarily correlated with the cellular death rate after irradiation."}
{"_id": "Radiology$$$375c10bf-ba38-4626-9641-6af3601e2f77", "text": "Radiosensitivity and cancer susceptibility to irradiation are two different notions [50]."}
{"_id": "Radiology$$$4ae9a5e8-7258-417e-83e3-6c948cbcc091", "text": "The link between proliferation rate and radiosensitivity is far from obvious, and the law of Bergoni\u00e9 and Tribondeau should have been modified as follows: \u201cthe faster cells proliferate, the faster cell death will appear.\u201d Besides, reviews about the Tpot (the potential doubling time parameter) have shown that the yield of cell death clearly does not correlate with proliferation rate [51, 52]. For example, fibroblasts from ataxia telangiectasia are hyper-radiosensitive, while their proliferation rate is lower than that of fibroblasts from healthy patients [53]. When fibroblasts are transformed by the Simian Virus 40 (SV40), the cells become unstable and their proliferation rate increases while they are less radiosensitive than their non-transformed counterparts [54]. Other counterexamples of the law of Bergoni\u00e9 and Tribondeau are as follows: the Li-Fraumeni syndrome (caused by the p53+/\u2212 mutations) confers radioresistance associated, however, with impaired cell cycle arrests, instability, and cancer proneness. Similarly, some highly proliferating tumors may be very radioresistant [55]."}
{"_id": "Radiology$$$8fb2824e-1f5c-4abd-aaa8-b09fe07bca4b", "text": "To conclude, despite its popularity, the law of Bergoni\u00e9 and Tribondeau has not been fully validated. Yet, it has made a significant contribution to the advances in radiation biology and the relationship between proliferation and radiosensitivity."}
{"_id": "Radiology$$$b51b6978-ed85-4d03-8f44-4ee21e1c026c", "text": "The report of the discovery of \u201cmysterious rays\u201d (X meaning unknown) created a great sensation and spread rapidly in many countries: The first report in the press of Roentgen\u2019s feat appeared in Vienna on January 5, 1896, and days later in Germany, England, and the USA [56]. Of all the properties of X-rays, their ability to make the \u201cinvisible visible\u201d was the most fascinating and remained for several years the principal topic for their use in the imaging of anatomical and technical objects (Fig. 1.12)."}
{"_id": "Radiology$$$e6ba3c96-fb83-4d1c-bd07-8dd1073bea71", "text": "The first X-ray machines were large, loud, sparkling, and smelly devices, prone to causing accidents and injury. Such bizarre and sometimes mind-boggling presentations solidified the current public perception of X-rays as a fantastically powerful and yet controversially useful tool. As one of the symbols of the new scientific medicine, X-rays have largely lived up to the public\u2019s expectations of a technological panacea, which was reinforced by the spectacle of their generation and their undeniable effects on the body. This \u201cdomestication\u201d of X-ray machines highlighted their failure as modern heroic medicine, while reinforcing at the same time the emerging understanding of radiation as a \u201csubtle, cumulative, and insidious threat\u201d [57, 58]  (Box 1.10).\n\nA poster titled The New Roentgen Photography. It features a photographer next to a camera covered with a black cloth. A smiling farmer holding a scythe stands in front of the camera, in front of a rising sun. An inset photograph features a skeleton holding a scythe.\n\nFig. 1.12\nCartoon from \u201cLife,\u201d February 1896. The New Roentgen Photography. \u201cLook pleasant, please\u201d"}
{"_id": "Radiology$$$ca9c50bf-beed-49ab-8d73-4c9585a0162e", "text": "A poster titled The New Roentgen Photography. It features a photographer next to a camera covered with a black cloth. A smiling farmer holding a scythe stands in front of the camera, in front of a rising sun. An inset photograph features a skeleton holding a scythe."}
{"_id": "Radiology$$$90c40dce-e31a-4d9b-9d80-f3729087b659", "text": "The report of the discovery of \u201cmysterious rays\u201d created a great sensation and spread rapidly in many countries.\n\nAs one of the icons of the new scientific medicine, X-rays bore much of the public\u2019s expectations for a technological panacea."}
{"_id": "Radiology$$$13e17cea-fe62-454a-8b33-fb23e82d4f49", "text": "The report of the discovery of \u201cmysterious rays\u201d created a great sensation and spread rapidly in many countries."}
{"_id": "Radiology$$$e767fbfb-122f-4742-997e-316059b4a302", "text": "As one of the icons of the new scientific medicine, X-rays bore much of the public\u2019s expectations for a technological panacea."}
{"_id": "Radiology$$$e53dbb6e-d590-48ff-a926-d30bc66d71dd", "text": "In addition to the discovery of X-rays, the year 1895 also saw the death of Louis Pasteur. After a plethora of controversies, the \u201cmicrobial\u201d theory developed by Pasteur triumphed at the end of the nineteenth century to such an extent that nearly all the diseases were believed to originate from a microbial etiology [59]. This was also the case with cancer, a disease that was already well known, but much less frequent than tuberculosis or diphtheria. The so-called parasitic theory of cancer suggested that tumors arise as a result of infection of tissues by microorganisms. This theory opposed the \u201ccellular\u201d theory, which explained carcinogenesis as due to the transformation of one or more cells. Hence, early after the discovery of X-rays, the first experiments involving both X-rays and microbes revealed the biocidal properties of X-rays [60]."}
{"_id": "Radiology$$$7fcaa200-c8f6-4b42-b57e-e2ac7940f8c1", "text": "In this historical context, Victor Despeignes, a hygienist and physician in a village of Savoy, Les Echelles, France, in February 1896 was visited by a man of 52, who suffered from pain in his abdomen [3, 60] and had been diagnosed with stomach cancer. Convinced by the works of his former colleagues of the Medical Faculty of Lyon, who in March 1896 demonstrated the curative effects of X-rays in patients with tuberculosis [61], in July 1896, Despeignes performed the first anticancer radiotherapeutic trial by irradiating his patient\u2019s tumor with X-rays in two daily sessions. However, although the therapy led to a significant decrease of the tumor volume, the patient died 22\u00a0days after the beginning of the treatment. Despeignes described all these observations in two articles in the Lyon Medical Journal [3, 60, 62\u221264]. The reconstitution of the radiotherapy of Despeignes suggested that his patient did not suffer from a stomach cancer, a rather radioresistant neoplasm, but from gastric lymphoma, possibly the mucosa-associated lymphoid tissue (MALT) lymphoma of a high-grade Burkitt type, which is very radiosensitive. Unfortunately, following the opposition or reservations of his colleagues vis-\u00e0-vis the therapeutic properties of X-rays, Despeignes discontinued further trials with X-rays [3, 60]."}
{"_id": "Radiology$$$134c22af-592e-497e-964a-da7ab3813926", "text": "Emil Grubbe (1875\u20131960), who received his medical degree in 1898, was allegedly the first American to use X-rays as a treatment for cancer. According to his own report, on January 26, 1896, he treated in Chicago a woman with breast cancer and, the following day, a man suffering from ulcerating lupus [65]. However, the validity of these statements remains questionable for many reasons. Firstly, no death certificates or medical records of Grubbe\u2019s patients have been found. Secondly, these treatments were not described in any peer-reviewed publications. Grubbe did not describe any clinical features potentially resulting from these treatments [65]."}
{"_id": "Radiology$$$617b9cea-9314-45f0-94d8-bff171b64f65", "text": "In August 1896, Leonhard Voigt irradiated in Germany a cancer of the nasopharynx, but, as in Grubbe\u2019s case, the records of this treatment cannot be validated [65]. The first radiation treatment considered to be successful was given in 1897 in Germany by Eduard L. Schiff to a patient suffering from erythematous lupus [66, 67]. While the X-rays generated by the Crookes tubes manufactured in the first two decades of the twentieth century were too \u201csoft\u201d to fully permeate the tumorous tissue, the later technological advances permitted Claudius Regaud and Antoine Lacassagne to perform in the 1930s the first series of anticancer radiotherapy at the Curie Institute in Paris, France [2] (Box 1.11)."}
{"_id": "Radiology$$$8dccb388-c6ec-4e8c-83dc-c21c5f255a7d", "text": "Counterintuitively for the modern reader, ionizing radiation was initially used mostly for treatment rather than for diagnosis.\n\nDevelopment of diagnostic radiology remained slow till the outbreak of the Great War (WWI) in 1914."}
{"_id": "Radiology$$$3c7f4807-a782-449a-9ad2-796c423544a0", "text": "Counterintuitively for the modern reader, ionizing radiation was initially used mostly for treatment rather than for diagnosis."}
{"_id": "Radiology$$$adfde31f-e555-416a-90ad-812b68af67a8", "text": "Development of diagnostic radiology remained slow till the outbreak of the Great War (WWI) in 1914."}
{"_id": "Radiology$$$f7fbf5fb-5973-4488-b03a-cc8b9d86fd56", "text": "The development of diagnostic radiology remained slow until about 1914, when two incidents precipitated its growth: the invention in 1913 of a new type of the cathode tube by the American physicist W. D. Coolidge (1873\u20131975) and the beginning of the Great War (World War I) associated with the need for medical assistance to the wounded soldiers."}
{"_id": "Radiology$$$a14017e7-e5e8-4649-ba74-0cf1e39dee32", "text": "Beginning from the 1920s, X-rays were used regularly for the detection of pulmonary tuberculosis. Before that, the \u201cradiologists\u201d were almost no more than \u201cphotographers.\u201d \u201cThanks to\u201d tuberculosis, the \u201cphotographers\u201d became skilled diagnosticians and thus the medical specialty of radiology emerged. Noteworthy, the Roentgen Society founded in London in November 1897 was in 1927 renamed the British Institute of Radiology; in 1931, the section of Radiology was established at the Royal Society of Medicine; and in 1934, the British Association of Radiologists was founded (5\u00a0years later, it was renamed the Faculty of Radiologists)."}
{"_id": "Radiology$$$a5a0f5f6-e1b1-4642-bf57-a3b75c20b1fd", "text": "At that period, radiology was faced with two problems: First, physicians regarded radiology as an intruder in their territory and contrasted the \u201cdead photograph\u201d with the \u201cliving sound\u201d of auscultation, and second, the images obtained were of poor quality because all the anatomical structures were superimposed. To overcome this latter problem, B. G. Ziedses des Plantes (1902\u20131933) built the first machine for planigraphy, in which the X-ray tube and the film moved together around the plane of interest allowing to reconstruct an arbitrary number of planes from a set of projections. He also designed the subtraction method to improve images after the injection of contrast agents [68]."}
{"_id": "Radiology$$$8abd32d9-37de-4529-a764-ea9a06aaeec2", "text": "The history of radiation therapy (radiotherapy) can be traced back to experiments made just after the discovery of X-rays, when it was shown that exposure to ionizing radiation may lead to cutaneous burns. In 1902, several physicians began the systematic use of radiation for the treatment of malignant tumors. The increased use of electrotherapy and escharotics (the medical application of caustic substances) inspired doctors to use radiation for the treatment of nearly any disease\u2014lupus, basal cell carcinoma, epithelioma, tuberculosis, arthritis, pneumonia, and chronic ear infections (https://\u200bwww.\u200bcdc.\u200bgov/\u200bnceh/\u200bradiation/\u200bnri/\u200bpatientinfo.\u200bhtm; [4, 69, 70]). Active use of ionizing radiation for treatment of various diseases continued until the early 1960s. Since then, radiation therapy has been used nearly exclusively in cancer therapy. Two factors contributed to phasing out of radiotherapy for non-oncological purposes: the growing awareness of the radiation-induced carcinogenesis and the development of efficient drugs, primarily, antibiotics (Box 1.12)."}
{"_id": "Radiology$$$260e57dc-cac5-44a7-8145-059224dc8996", "text": "Ionizing radiation was successfully used for the treatment of numerous diseases until the early 1960s.\n\nSince then, radiation therapy has been used almost exclusively in cancer therapy.\n\nTwo factors contributed to phasing out of radiotherapy for non-oncological purposes: the growing awareness of the radiation-associated carcinogenesis and the development of efficient drugs."}
{"_id": "Radiology$$$41a0be41-02df-4595-8855-4b414e619b03", "text": "Ionizing radiation was successfully used for the treatment of numerous diseases until the early 1960s."}
{"_id": "Radiology$$$a40e9251-56b2-4f8f-8820-daeb169d7690", "text": "Since then, radiation therapy has been used almost exclusively in cancer therapy."}
{"_id": "Radiology$$$6c5e6821-64e6-40dc-8f05-40f6cdc07274", "text": "Two factors contributed to phasing out of radiotherapy for non-oncological purposes: the growing awareness of the radiation-associated carcinogenesis and the development of efficient drugs."}
{"_id": "Radiology$$$51735d86-8f10-4f8f-8490-cb9cb2285c7f", "text": "Until 1920, patients with cancer were treated mainly by surgeons who assumed that the mechanism of radioactivity involved a \u201ccaustic effect.\u201d At that time, when the sources of X-rays produced \u201cweak\u201d radiation, capable of only superficial penetration, it was logical that it was dermatologists who strived to use X-rays in therapy. The crucial experiments performed by Robert Kienb\u00f6ck (1871\u20131953) entailed the proof that an X-ray dose, rather than electric phenomena, was the active agent causing biological effects when \u201cilluminating the skin using Roentgen tubes\u201d [71]."}
{"_id": "Radiology$$$4cb7456b-c04e-48a0-9b7d-46987b00c96a", "text": "In the 1910s and 1920s, radiobiology was at its infancy, based mainly on empirical observations of the effects of radiation on the skin. The technical progress made with the Coolidge tubes and the higher voltage that these tubes could be operated with introduced the techniques of the \u201cdeep X-ray treatment.\u201d The first radiotherapy textbook titled \u201cTreatment of Cancer by Radium\u201d was authored by surgeon Sir Stanford Cade and appeared in 1928 [72]."}
{"_id": "Radiology$$$e7f74f2a-3527-4495-8c76-f0bd560f88ec", "text": "At the same time, the Scottish radiotherapist Ralston Paterson (1897\u20131981) who used X-rays for the treatment of lung cancer wrote, \u201cIn cases of true primary carcinoma of the lung, surgery as yet offers little hope of relief \u2026 A group of nineteen patients treated by high-voltage roentgen rays is reported. All died within ten months, all but three within four months. This brief period of survival is the same as that in a group of cases in which there was no treatment. Although life is not prolonged, roentgen-ray treatment in all, but advanced cases give marked temporary palliation\u201d [73]."}
{"_id": "Radiology$$$86931db6-d6c8-4ad8-8e34-de33faefdd5a", "text": "In 1929, the pioneer Swedish radiotherapist G\u00f6sta Forssell (1876\u20131950) delivered the tenth Mackenzie Davidson Memorial Lecture and summarized the current state of radiotherapy [74, 75]. Figure 1.13 shows a table from Forssell\u2019s summary.\n\nA table of the results obtained at Radiumhemmet of the cases cured by only radiotherapy. The table lists the period when the cases were treated, the medical condition, total number of cases, number of cases cured, and their percentage.\n\nFig. 1.13\nSummary of the effects of radiotherapy of cancer performed in Sweden between 1910 and 1923 [75]"}
{"_id": "Radiology$$$fa5f9348-af07-41b9-b470-107336d552bd", "text": "A table of the results obtained at Radiumhemmet of the cases cured by only radiotherapy. The table lists the period when the cases were treated, the medical condition, total number of cases, number of cases cured, and their percentage."}
{"_id": "Radiology$$$e0cd82b7-6031-4c86-86c2-3d47d39f0754", "text": "In 1896, less than a year after the discovery of X-rays, Walter Levitt wrote on modern developments in X-ray therapeutic techniques and stressed that it is Leopold Freund from Vienna to whom \u201cbelongs the credit of having carried out the first X-ray treatment.\u201d Freund had noticed that epilation was one of the most constant effects of the exposure to X-rays, and when a patient with a hairy mole on the face came to him for advice, he conceived the idea of treating it with X-rays [76]."}
{"_id": "Radiology$$$ff0df722-e13b-40e7-b19b-0fb4c1a391f8", "text": "At about the same time, Robert McWhirter from Edinburgh wrote on the radiosensitivity in relation to radiation intensity. Frank Ellis from the Sheffield National Radium Centre during his long life (1905\u20132006) also contributed to the development of radiotherap; in June 1939, he reported on the radiosensitivity of malignant melanoma [77, 78]. Other publications of this period on the use of radium include illustrations of masks holding the radium needles applied to the skin (Fig. 1.14) and tubes containing radium for the internal use in cervical cancer [79].\n\nA sketch of radium needles on a mask layered over a person's nose, upper cheeks, and the side of the face.\n\nFig. 1.14\nMask to hold the radium needles for treatment of skin cancer [79]"}
{"_id": "Radiology$$$63b63f94-fd9b-447a-9979-9b1bc93399b4", "text": "A sketch of radium needles on a mask layered over a person's nose, upper cheeks, and the side of the face."}
{"_id": "Radiology$$$5705bdfb-6ad4-4f13-872a-6cef2675e8aa", "text": "Concurrently, the late effects of radiation on the skin were studied and reported in detail, and plastic surgery was applied to the treatment of radiodermatitis and radionecrosis [26, 80]."}
{"_id": "Radiology$$$70ee840d-cd21-4ff3-99de-7f28e773469d", "text": "At this gestational period, the pioneers of radiotherapy did not really know (a) what doses to use and how to measure them and (b) what are the advantages and disadvantages of using single or fractionated doses of X-rays. The concept of fractionation of the X-ray treatment was introduced by Claudius Regaud from the Foundation Curie in Paris and his brilliant collaborator Henri Coutard at the first International Congress of Radiology held in 1925 in London. Still, well into the 1930s, most radiotherapists were not convinced that fractionated therapy was superior to the single-dose schedule. With the establishment of the fractionation as standard treatment, radiotherapy ceased to rely solely on clinical observation, without rigid, preconceived planning, and began to be based on detailed physical modeling and dosimetry, to avoid as much as possible the irradiation of healthy tissues. This required a very close cooperation between radiotherapist and radiophysicists and led to the birth of two new disciplines, radiobiology and medical physics [81]."}
{"_id": "Radiology$$$4a5ab967-f4e1-430f-93e2-d90976a88a48", "text": "As mentioned above, Victor Despeignes in his historical attempts applied a bi-fractionated radiotherapy based on the hypothesis that the dose should not be too high to spare healthy tissues. Fractionated treatments can be traced back to the first trials performed by Leopold Freund in 1896 in Vienna, Austria. Today, Freund is considered the founder of medical radiology and radiotherapy [3, 82]. During the first decade of the twentieth century, many different anticancer strategies involving ionizing radiation were applied to treat various tumors. However, the energy of X-rays provided by the available tubes was limited to some tens of kilovolts, and therefore the radiation penetration into the body was very limited. Between the 1920s and 1930s, pioneers from the \u201cFrench school\u201d at the Institut Curie in Paris led by Henri Coutard, Claudius Regaud, and Juan A. del Regato showed that hypofractionation might lead to severe tissue reactions and promoted the hyperfractionated regimen by spreading the delivery of the dose over a longer period of time. In 1911, Claudius Regaud showed that a ram\u2019s testes could be sterilized without causing major burns to the scrotal skin if three irradiations were delivered 15\u00a0days apart. This practice was opposed to the \u201cGerman school\u201d led by Holzknecht and Wintz who preferred to apply high doses in a short period of time (intensive radiotherapy) [4]. Particularly, Henri Coutard suggested that high doses per fraction should be avoided due to the damage they caused to the connective tissues [83]. Coutard applied the concept of fractionated radiotherapy with treatment courses protracted over several weeks. With this strategy, Coutard managed to cure patients with various head and neck malignancies that are difficult to treat even today. It should be noted that the French radiotherapist was among the first to recognize that tumors of different histologies vary in their sensitivity to radiation."}
{"_id": "Radiology$$$b557a245-3428-48e5-ab04-f92bc1204ead", "text": "These observations led to the conclusion that radiation oncologists should protract the treatment duration to spare healthy tissues while increasing the dose per fraction to kill a tumor. Obviously, the current standard fractionation scheme of 1.8\u20132 Gy per fraction five times per week originated from individual observations of patients and empirical experience rather than from a purely scientific basis [84]."}
{"_id": "Radiology$$$c93fe6ae-430d-4b1c-9ac7-d5f29d917091", "text": "The technological race to produce the highest X-ray energies permitted the cure of the deepest tumors and helped in extending the application of hyperfractionated treatments to various cancers. For instance, the first electrostatic generator, developed by Robert van de Graaff in 1929, permitted the installation at the Huntington Memorial Hospital Boston, MA, USA, of a 2\u00a0MV irradiator dedicated to radiotherapy, and the first treatments with 60Co source began there in 1951. Two years later, the first 4\u00a0MV double-gantry linear accelerator (linac) was installed at the Newcastle Hospital in the UK [4] (Box 1.13)."}
{"_id": "Radiology$$$d0bab83a-8540-450e-9da8-79e6a2a5899b", "text": "The first fractionated radiation treatment was performed in 1896.\n\nAccelerator-based therapy has been performed since 1929 (with 2\u00a0MV electrostatic accelerator).\n\nTreatments with the 60Co source emerged in 1951."}
{"_id": "Radiology$$$39abdda7-d94b-4e44-a9aa-b411cc866653", "text": "Accelerator-based therapy has been performed since 1929 (with 2\u00a0MV electrostatic accelerator)."}
{"_id": "Radiology$$$77513e43-97ee-44a3-9460-31b2aebed406", "text": "With these technological advances, the early and late post-radiotherapy tissue reactions were more and more accurately documented and standard current hyperfractionated treatments were progressively defined for all types of tumors. In 1967, Frank Ellis developed the so-called Strandqvist\u2019s concept and suggested a formula defining the nominal standard dose (NSD) [85, 86]. Many variant formulas derived from the original one have since been devised [87]. Unfortunately, while the NSD formula has had a significant influence on clinical practice and was successful in predicting isoeffective regimens for the early effects, it dramatically failed in the prediction of severe late effects after the large-dose fractions. Progressively, the use of the parameters of the linear quadratic (LQ) model permitted a better approach to guide clinicians in their choice of the dose fractionation regimen [88]."}
{"_id": "Radiology$$$6b0a34aa-fdff-4d88-bcd6-32dc4a6b37d5", "text": "Today, the generally accepted model explaining both early and late effects consists of four independent processes that are thought to occur between fractions and favor the survival of normal tissues over cancers: (a) repair of sublethal cellular damage, (b) redistribution of tumor cells from radioresistant (late S phase) into radiosensitive (G2-M) portions of the cell cycle, (c) reoxygenation of the hypoxic (and hence radioresistant) portions of tumors, and (d) migration of normal cells into the irradiated healthy tissues close to the tumor to repopulate them with new functional cells."}
{"_id": "Radiology$$$945e85e1-6076-41b5-9ecc-efe24fbc5e3d", "text": "Recently, the debate about dose hypofractionation has been relaunched with the advent of stereotactic technologies that permit targeting the tumor with great precision, limiting therefore the exposure of healthy tissues surrounding the tumor. Particularly, anticancer treatments with stereotactic radiosurgery (SRS) and stereotactic body radiation therapy (SBRT) are based on the combination of a high-precision tumor targeting with hypofractionation [89]. Cyberknife (Accuray Incorporated, Sunnyvale, CA, USA) is one of the most recent and innovative techniques developed for the SBRT. It is a robotic system delivering many (usually a hundred) independent and noncoplanar beams converging onto the tumor with sub-millimetric accuracy under continuous X-ray image guidance [90]. Studies have shown the efficiency and safety of the SRS and SBRT techniques in many instances, including some involving the Cyberknife. Still, however, owing to the lack of a clear radiobiological mechanistic model that will define objective criteria, no consensus about the total dose, dose per fraction, and treatment duration has been achieved [89]."}
{"_id": "Radiology$$$7bf96c5c-70c3-49dc-9d3b-27ec7748181c", "text": "Radiation effects can be divided into early and late outcomes. Another classification is into deterministic and stochastic effects."}
{"_id": "Radiology$$$ed0734ee-2ee0-486b-a8f1-7a1601fe6557", "text": "The most common radiation-induced deterministic injuries include skin burns and cataracts. Since these effects occur after absorption of high doses of radiation, they can be easily avoided by adherence to the rules of radiological protection. The most important stochastic effect of significant irradiation is malignancy. Data suggest an elevated risk from medical radiation [97], especially with the highest exposures [98]."}
{"_id": "Radiology$$$b00c4cdd-dbdf-438c-9097-b02159b55b78", "text": "As mentioned earlier, biological effects caused by X-rays and radium were noted very soon after the discoveries of Roentgen, Becquerel, and the Curies. Early pathologies, such as radiation dermatitis and hair loss (epilation, alopecia), led to the birth of radiobiology and prompted scientists to follow up patients for long periods of time to study late effects of irradiation as well."}
{"_id": "Radiology$$$b053daa5-1fea-4a2e-89c4-cfa2c2b0aa68", "text": "While radiosensitivity reactions require rather high doses, exposure to ionizing radiation may also induce cancer [50]. The first radiation-induced cancer was reported by Frieben in 1902 on his own hand [99]. Cancers, but also leukemia, were mainly diagnosed in the pioneers of radiation. Hence, the incidence of radiation-induced cancers among clinicians manipulating X-ray tubes increased drastically [13]. Before the Second World War, a cohort of hundreds of female workers (\u201cthe radium girls\u201d\u2014see Sect. 1.2.2) in watch factories in New Jersey, Illinois, and Connecticut between 1917 and 1924 contracted some radiation-induced tumors probably due to self-luminous paintings containing radium [32]. This episode had a major societal, ethical, and legal impact in the USA and in the world. This period was contemporary with the organization of the first world congresses of radiology from which the International X-ray and Radium Protection Committee (IXRPC) arose and the first radiation protection recommendations were proposed [13]."}
{"_id": "Radiology$$$94971a39-21da-4064-bd4e-32a6ab84f291", "text": "Regarding epidemiology, radio-induced cancers were observed historically in pioneers of ionizing radiation, later in patients from various medical cohorts [97], and then in the atomic bomb survivors [100]."}
{"_id": "Radiology$$$5b62e598-873d-48b6-a363-e525e646c048", "text": "In the 1920s, the American geneticist, Hermann Joseph Muller, who irradiated fruit flies (Drosophila melanogaster) with large doses of X-rays, discovered radiation-induced mutations [101]. At that time, geneticists were convinced that no mechanism for gene repair existed and therefore that mutagenic damage was cumulative. From their point of view, no tolerant dose could ever be set, and the safety level should only be weighed against the cost of achieving it [102]. In 1946, Muller was awarded the Nobel Prize for his discovery, and in his Nobel Prize Lecture, he argued that the dose-response for radiation-induced mutations was linear and that there was \u201cno escape from the conclusion that there is no threshold dose\u201d [103]. This statement may be ethically questionable since Muller was already aware of counterevidence when he delivered his lecture [104]."}
{"_id": "Radiology$$$220d7291-6e96-4441-8a95-fd378208b5ba", "text": "After the Hiroshima and Nagasaki bombings, geneticists were concerned that exposure to radiation from the nuclear fallout would likely have devastating consequences on the gene pool of the human population. Later (at the end of the 1950s), after no radiation mutagenesis was found in the A-bomb survivors\u2019 descendants [105], carcinogenesis became the main concern."}
{"_id": "Radiology$$$ccbabc5b-1409-4e91-a97e-4473cf940806", "text": "During the next decades, there was considerable controversy and both logical and circular arguments were exchanged. It has been said that among scientists, \u201cthe data to support the linearity at low dose perspective were generally viewed as lacking, but the fear that they may be true was a motivating factor\u201d [102].\nThe linear no-threshold (LNT) model for radiation risk assessment gradually gained ground after Muller\u2019s Nobel lecture. In 1956, the ICRP officially abandoned the tolerance level concept (that was in use since 1931) and substituted LNT for it. The latter model suggests that any radiation exposure presents carcinogenic risk and that the risk is proportional to the absorbed dose of radiation. Formally, LNT has been introduced and remains a practical operational model only for radiation protection. Alas, contrary to the plethora of the existing evidence [106], this hypothesis has acquired de facto the status of a scientific theory and remains the driving force of the prevailing radiophobia in the society (Box 1.15)."}
{"_id": "Radiology$$$5bb70296-afec-4dce-a36d-758cac09c88a", "text": "The linear no-threshold (LNT) model for radiation risk assessment gradually gained ground after Muller\u2019s Nobel lecture. In 1956, the ICRP officially abandoned the tolerance level concept (that was in use since 1931) and substituted LNT for it. The latter model suggests that any radiation exposure presents carcinogenic risk and that the risk is proportional to the absorbed dose of radiation. Formally, LNT has been introduced and remains a practical operational model only for radiation protection. Alas, contrary to the plethora of the existing evidence [106], this hypothesis has acquired de facto the status of a scientific theory and remains the driving force of the prevailing radiophobia in the society (Box 1.15)."}
{"_id": "Radiology$$$27fb766a-9831-4211-93e5-e9900e9a7621", "text": "The linear no-threshold (LNT) model for radiation risk assessment was introduced following Muller\u2019s discovery of radiation-induced mutations in 1927.\n\nEvidence supporting LNT is inconclusive at very low doses."}
{"_id": "Radiology$$$ede6d840-5d90-449a-b0a9-a5189ab14806", "text": "The linear no-threshold (LNT) model for radiation risk assessment was introduced following Muller\u2019s discovery of radiation-induced mutations in 1927."}
{"_id": "Radiology$$$4ecad191-2876-42c0-b9a8-2fdf834f6beb", "text": "Over the last decades, the attitude to risk associated with ionizing radiation has become more sensible. We now know that exposures to low doses of radiation initiate cellular and intercellular changes leading to stress-induced adaptive responses and metabolic alterations. Furthermore, repair mechanisms preventing the accumulation of damage\u2014also of non-radiogenic origin\u2014were also discovered [107]. Consequently, it became obvious that while high doses of ionizing radiation certainly cause harm, low doses can be beneficial for human health; such an effect is called hormesis [108], but the circumstances in which hormesis might occur in humans are not known."}
{"_id": "Radiology$$$0558dbdf-f71d-499e-a9cc-8e01b094b252", "text": "Recently, the so-called secondary neoplasms which appear in patients treated with radiotherapy for a primary tumor have become the focus of interest in the studies of radiation-induced cancer [109]. It is still not clear whether secondary cancers are triggered by radiation or other factors. Characteristic features of these cancers are as follows:\nAs a rule, they appear near the high-dose treatment volume, which supports their radiation origin [110].\n\nCancer patients are at a high risk in general for developing secondary malignancies [111]. It has been estimated that radiotherapy is responsible for only about 8% of the secondary cancers [112].\n\nThe usual confounding factors of carcinogenesis (genetic, lifestyle, environmental, etc.) increase the risk of the secondary and radiation-induced cancer. Individual radiosensitivity may play a major role [3].\n\nThe relative risk of radio-induced cancer is organ dependent, the thyroid being by far the most radiosusceptible organ [113]; however, the recently acknowledged problem of thyroid cancer overdiagnosis [114] demands re-evaluation of the entire field of thyroid cancer epidemiology [115] (Box 1.16)."}
{"_id": "Radiology$$$9a468a34-cee5-490f-9f79-170892ee8664", "text": "As a rule, they appear near the high-dose treatment volume, which supports their radiation origin [110]."}
{"_id": "Radiology$$$fabb58d7-1fcb-4bca-9f59-ae61dcb9c476", "text": "Cancer patients are at a high risk in general for developing secondary malignancies [111]. It has been estimated that radiotherapy is responsible for only about 8% of the secondary cancers [112]."}
{"_id": "Radiology$$$d9e1a916-c0dd-44fa-ae11-6422edd67a00", "text": "The usual confounding factors of carcinogenesis (genetic, lifestyle, environmental, etc.) increase the risk of the secondary and radiation-induced cancer. Individual radiosensitivity may play a major role [3]."}
{"_id": "Radiology$$$fc5ed9ca-215b-4d95-a93f-6e50b945465e", "text": "The relative risk of radio-induced cancer is organ dependent, the thyroid being by far the most radiosusceptible organ [113]; however, the recently acknowledged problem of thyroid cancer overdiagnosis [114] demands re-evaluation of the entire field of thyroid cancer epidemiology [115] (Box 1.16)."}
{"_id": "Radiology$$$48cb18ac-43f6-4b63-a549-d31e57caafac", "text": "As a rule, secondary cancers appear near the high-dose treatment volume; this is a major argument supporting their radiation origin.\n\nCancer patients in general are at a high risk for developing secondary neoplasms. Radiotherapy is probably responsible for only 8% of the secondary cancers.\n\nThe primary carcinogenic factors\u2014genetic, lifestyle, and environmental\u2014increase the risk of the radiation-induced and secondary cancer. Individual radiosensitivity may play a crucial role.\n\nThe relative risk of radio-induced cancer is organ dependent. It has been assumed that the thyroid is by far the most radiosusceptible organ; however, the recently acknowledged problem of thyroid cancer overdiagnosis requires re-evaluation of the entire field of thyroid cancer epidemiology."}
{"_id": "Radiology$$$0326997e-bdc4-42e5-b5cc-9824585eab67", "text": "As a rule, secondary cancers appear near the high-dose treatment volume; this is a major argument supporting their radiation origin."}
{"_id": "Radiology$$$a92578d1-efff-4cb1-b778-bfbbafc5617f", "text": "Cancer patients in general are at a high risk for developing secondary neoplasms. Radiotherapy is probably responsible for only 8% of the secondary cancers."}
{"_id": "Radiology$$$428ed505-7735-4ed5-9e06-b42c9034188b", "text": "The primary carcinogenic factors\u2014genetic, lifestyle, and environmental\u2014increase the risk of the radiation-induced and secondary cancer. Individual radiosensitivity may play a crucial role."}
{"_id": "Radiology$$$de36965c-a2fb-459f-acda-bc63f8847979", "text": "The relative risk of radio-induced cancer is organ dependent. It has been assumed that the thyroid is by far the most radiosusceptible organ; however, the recently acknowledged problem of thyroid cancer overdiagnosis requires re-evaluation of the entire field of thyroid cancer epidemiology."}
{"_id": "Radiology$$$bc94a178-0c74-4764-8745-c8b9c578b1e3", "text": "Various epidemiological studies indicate an association between cancer and previous exposure to ionizing radiation even at rather low doses. Most studies do not consider the potential medical exposures of people, as in the case of the A-bomb survivor studies. Although these studies do not establish a link between exposure to ionizing radiation and cancer, the existence of a dose-effect relationship, when it can be established, is in favor of a possible link. The risk evaluation thus requires that dosimetry should be precisely and accurately monitored. These epidemiological observations give consistency to the linear no-threshold (LNT) relationship, which has been used for regulatory purposes in radiological protection, although, as mentioned above, it has no indisputable scientific basis [116]."}
{"_id": "Radiology$$$2db29c11-2358-44ee-83c7-36e1518509a1", "text": "Radiation-induced carcinogenicity stems from the fact that ionizing radiation is one of the causes of the DNA lesions. Each DNA insult when unrepaired, particularly in persons with an abnormal DNA damage response (DDR), contributes to the overall DNA dysfunction and paves the way to oncogenesis [117]. Abnormal DDR has been reported following low-dose exposures to X-rays [118]. However, multiple repair and defense mechanisms operating at the molecular, cellular, tissue, and organismal levels may assure the effective elimination of potentially carcinogenic cells and may make the LNT model irrelevant to the biological reality [107]."}
{"_id": "Radiology$$$02714319-1d53-402f-b06d-1dd936f96ca2", "text": "To conclude, the responsibility of high-dose ionizing radiation in the stochastic appearance of cancers is certain. However, it is very likely that there are no radio-induced cancers at low doses and low dose rates in the sense that they would be due to the sole ionizing radiation. However, low doses of ionizing radiation and of other genotoxic stressors (exposomes) should not be examined independently from each other (Box 1.17)."}
{"_id": "Radiology$$$ea31fd98-27fa-4527-a915-ba040401bc35", "text": "High-dose ionizing radiation can be associated with the stochastic appearance of cancers.\n\nIt is likely that exposures to low doses of ionizing radiation are not alone responsible for radio-induced cancers.\n\nLow doses of ionizing radiation and other genotoxic stressors should not be examined independently from each other."}
{"_id": "Radiology$$$128d218e-cf07-4c6b-aea0-8906dccfed6f", "text": "High-dose ionizing radiation can be associated with the stochastic appearance of cancers."}
{"_id": "Radiology$$$1ee8cc1d-f949-49c4-abb3-3b8b9eb38505", "text": "It is likely that exposures to low doses of ionizing radiation are not alone responsible for radio-induced cancers."}
{"_id": "Radiology$$$6336d542-01aa-454c-a162-f936362456ae", "text": "Low doses of ionizing radiation and other genotoxic stressors should not be examined independently from each other."}
{"_id": "Radiology$$$203df209-4d96-45cb-b36e-0b5016d715e5", "text": "Q1.\nWho made and when were made the major discoveries in the field of ionizing radiation?\n\u00a0Q2.\nWhat is the basis for conclusion about the carcinogenic effects of ionizing radiation?\n\u00a0Q3.\n(Open question) How was ionizing radiation misused in the first third of the twentieth century? What were the main events that led to cessation of the misuse?\n\u00a0Q4.\n(Open question) What were the main stages in the development of radiation therapy?"}
{"_id": "Radiology$$$69cfc063-e5d7-492d-904d-9473b99767bb", "text": "Who made and when were made the major discoveries in the field of ionizing radiation?"}
{"_id": "Radiology$$$cfc44551-3922-487c-95dd-999828a9e33f", "text": "What is the basis for conclusion about the carcinogenic effects of ionizing radiation?"}
{"_id": "Radiology$$$016b37ec-a11b-4fcb-8773-8bbab4cac15e", "text": "(Open question) How was ionizing radiation misused in the first third of the twentieth century? What were the main events that led to cessation of the misuse?"}
{"_id": "Radiology$$$4a727311-4b18-44e6-90cb-4d2ca03b2459", "text": "(Open question) What were the main stages in the development of radiation therapy?"}
{"_id": "Radiology$$$49189501-85c8-42f6-aa2d-bfb4ecdc5ec9", "text": "QA1.\nWilhelm Roentgen, Henry Becquerel, Pierre and Marie Curie, and Ernest Rutherford laid the foundations of understanding the ionizing radiation from 1895 until the beginning of the Great War (1914).\n\u00a0QA2.\n(a)\nHistorical observations\n\u00a0(b)\nEpidemiologic studies, especially with the cohort of atomic bomb survivors of Hiroshima and Nagasaki\n\u00a0(c)\nBasic understanding of the cellular mechanism regarding DNA insults and DNA damage response"}
{"_id": "Radiology$$$17826ba6-b716-4d5b-b22d-5be3f3904c1a", "text": "Wilhelm Roentgen, Henry Becquerel, Pierre and Marie Curie, and Ernest Rutherford laid the foundations of understanding the ionizing radiation from 1895 until the beginning of the Great War (1914)."}
{"_id": "Radiology$$$7322cbcb-5e92-4abe-bac8-0bac28b53a86", "text": "(a)\nHistorical observations\n\u00a0(b)\nEpidemiologic studies, especially with the cohort of atomic bomb survivors of Hiroshima and Nagasaki\n\u00a0(c)\nBasic understanding of the cellular mechanism regarding DNA insults and DNA damage response"}
{"_id": "Radiology$$$9a4c8084-c4de-4dbf-9532-da996cb93931", "text": "Epidemiologic studies, especially with the cohort of atomic bomb survivors of Hiroshima and Nagasaki"}
{"_id": "Radiology$$$023903f7-0ece-48f9-8624-6ef61a5f808c", "text": "Basic understanding of the cellular mechanism regarding DNA insults and DNA damage response"}
{"_id": "Radiology$$$03543c29-29fd-461b-ae3b-34592591cc05", "text": "There exists a wide variety of different types of particles in nature. These vary across those more commonly known, such as the constituents of atoms like electrons spinning around nuclei and protons and neutrons inside the nuclei. Particles generated through other particles\u2019 decay and those which are the carriers of the fundamental electromagnetic, strong and weak nuclear, and gravitational force are also incredibly important in nature."}
{"_id": "Radiology$$$143398df-e87f-47cb-b85d-ecab13944070", "text": "In physical science, a particle is characterized either as a localized entity which can be described by its own physical characteristics such as volume, density, and mass or as a wave, the latter being a less intuitive concept. Such dual nature of particles is named the wave-particle duality. The de Broglie wavelength associated with a particle is inversely proportional to its momentum, p, through the Planck constant, h:"}
{"_id": "Radiology$$$11e20a50-7b71-47ac-bfa4-844d18ad3803", "text": "(2.1)"}
{"_id": "Radiology$$$5f8a1451-3a94-4124-a35d-2f064be44f23", "text": "When particles interact with objects much larger than the wavelength of the particles themselves, they show negligible interference effects. To get easily observable interference effects in the interaction of particles with matter, the longest wavelength of the particles and hence the smallest mass possible are needed. The wavelengths of high-speed electrons are comparable to the spacings between atomic layers in crystals. Therefore, this effect was first observed with electrons as diffraction, a characteristic wave phenomenon, in 1927 by C.J. Davisson and L.H. Germer [1] and independently by G.P. Thomson [2]. Such experiments established the wavelike nature of electron beams, providing support to the underlying principle of quantum mechanics. Thomson\u2019s experiment of a beam of electrons that can be diffracted just like a beam of light or a water wave is a well-known case taught in basic courses of quantum mechanics [3]."}
{"_id": "Radiology$$$d39b510b-114b-464d-9295-861fc3f57453", "text": "For electromagnetic radiation for energies E\u00a0=\u00a0hc/\u03bb of a few keV, the wavelength \u03bb becomes comparable with the atomic size. At this energy range, photons can be practically considered as particles with zero mass and momentum p\u00a0=\u00a0E/c. Indeed, despite photons having no mass, there has long been evidence that electromagnetic radiation carries momentum. The photon momentum is, however, very small, since p\u00a0=\u00a0h/\u03bb and h is very small [6.62606957\u00a0\u00d7\u00a010\u221234 (m2\u00a0kg/s)], and thus it is generally not observed. Nevertheless, at higher energies, starting from hard X-rays (which have a small wavelength and a relatively large momentum), the effects of photon momentum can eventually be observed. They were observed by Compton, who was studying hard X-rays interacting with the lightest of particles, the electron. On a larger scale, photon momentum can have an effect if the photon flux is considerable and if there is nothing to prevent the slow recoil of matter due to the impinging and conservation of the total momentum. This may occur in deep space (a quasi-vacuum condition), and \u201csolar\u201d sails with low mass mirrors that would gradually recoil because of the impinging electromagnetic radiation are actually being investigated and tested to actually take spacecraft from place to place in the solar system [4\u20136]."}
{"_id": "Radiology$$$8b43b084-4f7b-49a2-b968-f5d1b7a0161c", "text": "While for photons the concept of wavelength is more intuitively directly related to the phenomena and excitations they can trigger in matter, for particles with mass (massive particles), the wavelength is usually too small to have a practical impact on our observation of interaction phenomena. Nevertheless, depending on the phenomenon or on the specific aspect one is looking at, it may be more convenient to consider the particles either as localized entities or in terms of waves."}
{"_id": "Radiology$$$b8d680a9-799b-47da-84bb-5af549c9289b", "text": "Understanding the phenomenon of the passage of charged particles, in particular protons and other hadrons, heavy ions, electrons, and neutral particles, such as neutrons and photons, in matter has been a tempting and fascinating topic since the early development of quantum mechanics. The study of the passage of a particle through matter requires knowledge of the many interactions that govern the response of the target to the incoming (strong or weak) particle in the target itself. The number of these interactions is daunting, especially for the case of high-energy particles. In principle, to understand the types of possible particle-matter interactions and thus the response of the matter to radiation, it is more appropriate to consider the speed of the particle rather than the energy. The energy is less meaningful as the high energy of a heavy ion may be associated mostly to its mass, rather than purely to its speed. It is nevertheless common also to refer to the kinetic energy of the particle when looking at the induced interactions a particle can have when traveling through matter, distinguishing the particles with different mass. The interaction of a massive particle with matter can be understood by looking at Fig. 2.1, where the particle\u2019s kinetic energy is plotted against the de Broglie wavelength, and the relevant dimensions of a nucleon, nucleus, electron orbitals, and water molecule (O\u2013H distance) are reported. At high-projectile kinetic energies in the region of 1\u201310\u00a0GeV (reported are the cases of a proton, a neutron, and a 12C ion), the wavelength of the projectile is similar to the size of the nucleon, and hence the projectile is able to interact directly with the components of the single nucleons (quarks, gluons) in the nucleus of the target atom. At slightly lower kinetic energies (~1\u00a0MeV\u20131\u00a0GeV), the wavelength of the projectile becomes comparable to that of the nucleus of uranium, and thus the projectile can interact with the nucleons, but not with the constituents of the nucleons. This can cause fragmentation of the nucleus and generation of secondary species and decay particles that are emitted in the de-excitation of the nucleus, which is brought in an excited state by the impacting particle. Descending in kinetic energy, the wavelength of the incoming radiation on the order of the entire nucleus means that the impacting particle can interact with the entire nucleus but not with the nucleons. Further lower in energy and at increased wavelength, the incoming radiation has a wavelength of similar size to the electronic orbitals (reported here are lead orbitals), and still further of similar size to a water molecule, thus entering the regime of molecule-dominating behavior. It is thus clear that when spanning large energy windows, many different physical interactions take place with the target, which probe the different units of matter which are considered as elemental for different sub-disciplines of physics.\n\nA profile of projectile kinetic energy versus projectile de Broglie wavelength plots quark-gluon, nucleon, nucleus, and molecule dominating behaviors. The range from 10 powered negative 1 to 1 is the nucleon size, 1 to 10 is the uranium nucleus size, and 10 powered 5 to 10 powered 6 is H 2 O size.\n\nFig. 2.1\nPlot of the projectile kinetic energy vs. the de Broglie wavelength. The sizes of a nucleon, uranium nucleus, lead orbitals and water molecule are also reported. (Courtesy of Dr. Marc Verderi, Laboratoire Leprince-Ringuet, CNRS/IN2P3, Ecole Polytechnique, Institut Polytechnique de Paris, France)"}
{"_id": "Radiology$$$8c6f7bef-4571-4ec0-8123-176f31a5d340", "text": "A profile of projectile kinetic energy versus projectile de Broglie wavelength plots quark-gluon, nucleon, nucleus, and molecule dominating behaviors. The range from 10 powered negative 1 to 1 is the nucleon size, 1 to 10 is the uranium nucleus size, and 10 powered 5 to 10 powered 6 is H 2 O size."}
{"_id": "Radiology$$$9f92dfa3-b190-4448-83fb-d878ce5d8d1a", "text": "It has to be stressed that in its path through matter, the primary particle can generate several secondary particles, such as electrons, by ionization and/or decay particles of excited nuclei in nuclear inelastic collisions. In the latter case, \u201cdaughter nuclei\u201d are generated, which also act as projectiles interacting within the system. In the case of biological targets, primary radiation can generate ions, electrons, excited molecules, and molecular fragments (free radicals) that have lifetimes longer than approximately 10\u221210\u00a0s. The new species in turn travel and diffuse and start chemical reactions, the evolution of which is a main contributor to the effects at biological level."}
{"_id": "Radiology$$$66e45ce4-b34f-43cd-92ba-e9263bd86219", "text": "Nowadays, apart from the well-known fields of the high-energy physics and nuclear science, radiation science is important in numerous sub-disciplines, such as ion beam therapy [7, 8], radiation protection in medicine [9] and nuclear facilities [10], development of risk assessment models for nuclear accidents [11], or radiation protection in deep space manned missions [12\u201314]. Apart from the effects on humans, parallel streams of research exist for the studies on radiation effects induced in plants, seeds, and animals, for the survival and adaptation around the Chernobyl site and even for the effects on small biological molecules of interest in studies on the search of life on other planets or their moons [15\u201319] (Box 2.1)."}
{"_id": "Radiology$$$b42c5f1b-f9ef-4836-bb47-591cf089f645", "text": "The appropriateness of a description of particles as localized entities or as waves depends on the wavelength of the particle, the characteristics of the probed dimension of the target system, and the resulting phenomenon (change in the state of the target) which we are interested in.\n\nThere exists a wide range of interactions that particles can induce in matter, from the interactions with quarks and gluons in high-energy collisions to excitations of electrons and vibrations in molecules which dominate at lower energies."}
{"_id": "Radiology$$$18745cac-1b7d-45fb-99ca-3cb3f1fb2005", "text": "The appropriateness of a description of particles as localized entities or as waves depends on the wavelength of the particle, the characteristics of the probed dimension of the target system, and the resulting phenomenon (change in the state of the target) which we are interested in."}
{"_id": "Radiology$$$1bacc2a5-6555-4cb7-8f28-e8bdea3f081e", "text": "There exists a wide range of interactions that particles can induce in matter, from the interactions with quarks and gluons in high-energy collisions to excitations of electrons and vibrations in molecules which dominate at lower energies."}
{"_id": "Radiology$$$a9e69e48-a41d-456a-a40b-e0a01676adff", "text": "Electromagnetic radiation transfers energy without any atomic or molecular transport medium. According to the wave-particle duality of quantum physics, electromagnetic radiation can be described either as a wave or as a beam of energy quanta called photons."}
{"_id": "Radiology$$$a9535b22-0d2d-4529-b32b-c8d1fe2cded5", "text": "To understand how electromagnetic radiation interacts with matter, we need to think of electromagnetic radiation as photons, and it is the energy of each photon, which determines how it interacts with matter. Figure 2.2 shows the spectrum of electromagnetic radiation. It is divided into radio waves, microwaves, infrared, (visible) light, ultraviolet (UV), and X- and \u03b3-rays depending on the frequency and energy of the individual photons. Depending on the photon energy, the photon interaction with an atom can result in ionization, where an electron gets enough energy to leave the molecule/atom; excitations, where the electron gets the exact energy needed to move from an inner electron shell to an outer shell; or changes in the rotational, vibrational, or electronic valence configurations (Box 2.2).\n\nAn illustration of the electromagnetic spectrum depicts the wavelength, energy of one photon, and frequency of radio waves, microwaves, infrared, visible light, ultraviolet, X-ray, and gamma radiations.\n\nFig. 2.2\nThe electromagnetic spectrum (Created with BioRender)"}
{"_id": "Radiology$$$68a08fc9-8d11-4cd2-b46a-04b9d79310a0", "text": "An illustration of the electromagnetic spectrum depicts the wavelength, energy of one photon, and frequency of radio waves, microwaves, infrared, visible light, ultraviolet, X-ray, and gamma radiations."}
{"_id": "Radiology$$$153300eb-4a29-4744-9b2a-0076ed44f74a", "text": "It is not the total energy but the energy per photon which determines how the radiation interacts with matter.\n\nIonizing radiation is the radiation with enough energy per photon to kick out one atomic electron."}
{"_id": "Radiology$$$b5941fa2-016c-4371-a5a4-972e6fa1cb45", "text": "It is not the total energy but the energy per photon which determines how the radiation interacts with matter."}
{"_id": "Radiology$$$8a65f5c8-917e-474e-b0ce-bae7e9677512", "text": "Ionizing radiation is the radiation with enough energy per photon to kick out one atomic electron."}
{"_id": "Radiology$$$595ffb2e-69cf-48f1-8499-206fd97b5889", "text": "Radiation can be divided into ionizing and nonionizing radiation. Ionizing radiation carries more than 10\u00a0eV, which is enough energy to break chemical bonds. Unlike ionizing radiation, nonionizing radiation does not have enough energy to remove electrons from atoms and molecules."}
{"_id": "Radiology$$$6bf2914b-32f0-4171-adec-c65f19e7d8e2", "text": "The UV spectrum is in the range of 3.1\u2013124\u00a0eV. Even though the high-energy UV (UVC) can be ionizing, this is absorbed in the atmosphere and does not reach the Earth. Only UVA (3.10\u20133.94\u00a0eV) and UVB (3.94\u20134.43\u00a0eV) are transmitted through the atmosphere. UVB radiation has the energy to excite DNA molecules in skin cells. This can result in aberrant covalent bonds forming between adjacent pyrimidine bases, producing pyrimidine dimers. Most UV-induced pyrimidine dimers in DNA are removed by the process known as nucleotide excision repair, but unrepaired pyrimidine dimers have the potential to lead to mutations and cancer. UVA can induce production of reactive oxygen and reactive nitrogen species (ROS, RNS), which happens through interaction with chromophores such as nucleic acid bases, aromatic amino acids, NADH, NADPH, heme, quinones, flavins, porphyrins, carotenoids, 7-dehydrocholesterol, eumelanin, and urocanic acid [20]. ROS can induce ionizations in DNA. In summary, the UV light that reaches the Earth (UVA and UVB) has too low photon energies to induce direct ionization but can cause DNA instability through excitation (Box 2.3)."}
{"_id": "Radiology$$$5bc40bd2-273a-44fd-8642-00dc8fbabbcf", "text": "Ionizing UV radiation (UVC) is absorbed in the atmosphere.\n\nUVB can induce pyrimidine dimers in DNA.\n\nBoth UVA and UVB can induce ROS, which in turn can induce DNA damage."}
{"_id": "Radiology$$$8520fd41-c1df-4166-b222-0715e455a236", "text": "Both UVA and UVB can induce ROS, which in turn can induce DNA damage."}
{"_id": "Radiology$$$47e32339-e136-46b5-93af-3ae8a60c1dd2", "text": "An X-ray photon is emitted from an electron that is either slowed down or moves from one stationary state to another in an atom; a \u03b3-photon is sent out by disintegration of an atomic nucleus. Except for the origin, from the physical perspective, there is no difference between X-ray and \u03b3-photon radiation."}
{"_id": "Radiology$$$9b9432ce-1e4e-4915-a603-4751e7ded22d", "text": "A photon can interact with matter by three different processes depending on its energy and the atomic number of the elements of the matter."}
{"_id": "Radiology$$$0e328452-9936-4bd6-a215-6812fc20133b", "text": "In the photoelectric effect, an atomic electron absorbs all the energy of the incoming photon and is emitted from the atom. Note that the photoelectric effect cannot occur with an electron that does not belong to an atom. This is because both energy and momentum need to be conserved, which cannot be achieved without an atom carrying the rest momentum."}
{"_id": "Radiology$$$392061c5-4eee-4ab4-a000-bfd5d000eeed", "text": "The Compton effect implies, just like the photoelectric effect, that an electron is knocked out from an atom by transfer of energy from the photon. However, for the Compton effect, a secondary photon is also emitted, which preserves the momentum (Fig. 2.3). Therefore, the process may also apply to a nonatomic, or free, electron. The amount of energy transferred from the incident wave to the electron depends on the scatter angle as follows:\n\n (2.2)\n\nA diagram explains the Compton concept. The light source hits the sample and scatters the photons and electrons. The corresponding equations for photons before scattering, electrons before scattering, photons after scattering, and electrons after scattering.\n\nFig. 2.3\nThe Compton process. The incident photon (\u03b3-ray) interacts with an electron initially at rest resulting in a scattered photon (at angle \u03b8) and electron (at angle \u03a6). The energy (E) and momentum (p) of the photon and electron before and after (marked with \u2032) scattering are given in the figure (Created with BioRender)"}
{"_id": "Radiology$$$6dbcd642-2c35-46fd-9ef1-e4024eccfe15", "text": "A diagram explains the Compton concept. The light source hits the sample and scatters the photons and electrons. The corresponding equations for photons before scattering, electrons before scattering, photons after scattering, and electrons after scattering."}
{"_id": "Radiology$$$e4a772c0-59a2-4548-9b87-c120ec990543", "text": "where \n\n is a constant denoted \u201cthe Compton wavelength for electrons\u201d which equals the wavelength of a photon having the same energy as the rest-mass energy of the electron. Notice that maximum energy transfer to the electron is obtained with a scatter angle of 180\u00b0 (backscatter), but it is not possible to transfer all the energy of the incoming photon to the electron (conservation of momentum)."}
{"_id": "Radiology$$$63b61402-aafc-46be-aed6-c285f099d84e", "text": "As seen in Fig. 2.4, depending on the incoming photon energy, there will be a series of Compton processes, each with emission of an electron, followed by a photoelectric process in the end. The result of such a Compton track is an energy distribution of secondary electrons with many low-energy electrons but also a few with high energy. The high-energy electrons are important for the dose distribution in the irradiated material, because they transport energy away from the place of the primary photon interaction and deposit their energy further into the irradiated material.\n\nA series of five gamma rays depicts the points of interaction. Gamma rays 1 to 4 form the tracks of Compton electrons, and gamma ray 5 forms the track of a photoelectron.\n\nFig. 2.4\nA typical example of a sequence of energy deposits. The energy of an original 1.25 MeV photon is deposited in five subsequent Compton processes with a final energy deposition in the form of a photoelectric process. The figure shows the mean range in water (dotted arrows) for the incoming photon and the reduced-energy photons emitted for each Compton process. The scale shown in the bottom left only applies to photons. The electron mean range is much shorter starting at about 2 mm going down to about 36\u00a0\u03bcm in the last Compton scattering (which is still larger than a typical cell diameter) (Created with BioRender)"}
{"_id": "Radiology$$$25d52e0a-913e-43ba-a5ae-559c790f98fb", "text": "A series of five gamma rays depicts the points of interaction. Gamma rays 1 to 4 form the tracks of Compton electrons, and gamma ray 5 forms the track of a photoelectron."}
{"_id": "Radiology$$$21f715f8-f5c1-4324-b1af-d806ee651549", "text": "Pair production occurs by the incoming photon interacting with the nuclear forces in the irradiated material resulting in an electron-positron pair. The rest energy of the two newly formed particles is 1.022\u00a0MeV, so the incoming photon must have higher energy than this for the process to occur. In body tissues and cells, more than 20 MeV in photon energy is required for pair production to dominate over the Compton processes."}
{"_id": "Radiology$$$3dac4c2a-7b3a-4ca4-bb23-fbda69082170", "text": "The Compton process dominates in biological material for energies relevant for medical use of photons. However, the cross section (an expression of the probability of interaction) for each process also depends on the atomic number Z. The cross section is proportional to Z4 for photoelectric effect, Z for Compton effect, and Z2 for pair production. Thus, the higher the effective atomic number, the lesser the importance of the Compton effect (Box 2.4)."}
{"_id": "Radiology$$$7f549d31-757b-4fdc-934a-9465fb5e498d", "text": "Electromagnetic radiation can ionize atoms/molecules through three different processes (photoelectric effect, Compton process, and pair production) depending on the photon energy and atomic number of the elements involved.\n\nThe Compton process dominates in biological material for energies relevant for medical use of photons, but a Compton track ends with the photoelectric effect."}
{"_id": "Radiology$$$70286116-d73c-43cf-9b02-2a14ba07ddf7", "text": "Electromagnetic radiation can ionize atoms/molecules through three different processes (photoelectric effect, Compton process, and pair production) depending on the photon energy and atomic number of the elements involved."}
{"_id": "Radiology$$$863cfb8c-f0bd-4447-ad98-960e4c58e639", "text": "The Compton process dominates in biological material for energies relevant for medical use of photons, but a Compton track ends with the photoelectric effect."}
{"_id": "Radiology$$$04a0e182-1a12-4246-b05d-9dddf5167b12", "text": "As described above, in physics, a particle is considered to be an object, which can be described through its properties including volume, density, and mass. In the context of particle radiation, two types of particles are defined: charged particles, such as electrons, protons, \u03b1-particles, or other ions and uncharged particles such as neutrons. In general, particle radiation can interact with matter through a number of different processes, where the frequency of occurrence depends on the particles\u2019 mass, velocity, and charge. In the first type of the process called electronic interaction, the particle interacts with electrons in the atomic shell, and in the second, called nuclear interaction, the particle interacts with the atomic nuclei. All interactions can be considered as collisions between two masses, which can be either elastic or inelastic."}
{"_id": "Radiology$$$8d79c917-9a13-4198-bd09-310054c8e9ca", "text": "There are three types of electronic or Coulomb interactions, which can occur with or without energy loss from the incident particle. Elastic scattering of the particle in the atomic shell occurs with only neglectable energy transfer, as only the energy which needs to be transferred is that which is necessary to fulfill energy and momentum conservation. In this case, the incident particle is scattered and changes its direction. The two inelastic electronic processes are shown in Fig. 2.5 (left). The particle described through its atomic number z, its mass m, and its energy E is interacting with an atom of the matter characterized by the atomic number Z, the mass number A, and the density of the matter \u03c1. In the inelastic collision, the particle transfers energy to the hit electron. If sufficient energy is transferred, the electron will leave the atom, thus ionizing it. When the transferred energy is higher, the electron gets additional kinetic energy and can then itself act as particle radiation. If the energy is lower and fits the energy difference between two electron shells (the defined energies at which electrons \u201corbit\u201d), the electron is excited, which means lifted to the higher shell. After a certain time, the electron falls back while emitting a photon with the energy corresponding to the energy difference between the shells.\n\nAn illustration of atoms depicts that the bombardment of a particle with electrons causes excitation and ionization, and with nuclei causes scattering. The orbital configurations for the particle during excitation, ionization, and ionization are also provided.\n\nFig. 2.5\nVisualization of the electronic interactions (left) and the nuclear interaction (right) of a particle with atomic number z, mass m, and energy E with matter with atomic number Z, mass number A, and density \u03c1 (Created with BioRender)"}
{"_id": "Radiology$$$355cf08c-272a-4205-9de3-59eb7fed8f6d", "text": "An illustration of atoms depicts that the bombardment of a particle with electrons causes excitation and ionization, and with nuclei causes scattering. The orbital configurations for the particle during excitation, ionization, and ionization are also provided."}
{"_id": "Radiology$$$ab57c4a5-2fe5-4d31-a735-4b2683c85056", "text": "In nuclear interactions, again three types can be defined. Firstly, elastic nuclear scattering, also called nuclear coulomb scattering, describes the elastic collision of a particle with the atomic nucleus. Here, the particle does not lose energy and only a deflection occurs (Fig. 2.5). In inelastic nuclear scattering, the particle is deflected and emits light, the so-called bremsstrahlung. Lastly, an interaction with the target nuclei itself is possible inducing nuclear reactions."}
{"_id": "Radiology$$$5723f6f1-2e06-4116-bef5-4d78c45a0341", "text": "Charged particle radiation describes high-energy massive particles such as electrons, protons , and other ions. These particles interact with matter through the described electronic or nuclear interactions. In each interaction, only a small amount of the total energy is transferred, and although the whole process of interaction is statistical in its nature, one can say that the particles stop more or less uniformly at a certain distance called the range. Furthermore, in each interaction, a certain angular deflection happens, which causes the particle to travel in a crooked path, and which effectively causes the incident particle beam to widen, while traversing a medium. The types of interactions can be described through the occurring energy loss and deflection of particle radiation in matter."}
{"_id": "Radiology$$$b16af1b2-27ad-4530-af8c-fbd8034c398c", "text": "Ionizations and excitations, which occur in the electronic interactions, can be differentiated into soft and hard collisions. Interactions of the charged particle with the electrons in the outer atomic shell are called soft collisions, as the energy transfer is low (a few eV). The electrons, which are ionized, have a low energy and therefore emit all the energy in close proximity to the point of interaction. These soft collisions are responsible for approximately 50% of the total energy transfer of a particle. As the energy transfer of a single collision is very low, the particle velocity decrease is also low. But as a lot of these interactions occur, the slowing is, although of statistical nature, on average happening continuously. For particles which have a very high energy and thus velocity, the Cherenkov effect can occur. This effect describes the emittance of light, when a particle flies through matter with a velocity larger than the speed of light in this corresponding matter. This light is called Cherenkov radiation and can be seen as blue in the cooling water of nuclear reactors. The Cherenkov effect does not play a role in the effects of particle radiation on biological matter."}
{"_id": "Radiology$$$c365ed08-34cf-470b-8665-897ec79b44d5", "text": "Coulomb interactions with the electrons of the inner shells are called hard collisions. Here, the electrons produced in ionizations have a higher energy and larger deflection angles compared to the ones from soft collisions. These electrons are called \u03b4-rays, and they transfer their energy via soft collisions to the matter, thus spreading the energy distribution of an incident particle up to several \u03bcm distance to the incident particle track. This effect plays a major role in the microdosimetry."}
{"_id": "Radiology$$$9af27bda-b45a-4905-957d-27bf94ed8397", "text": "Electronic interactions are the main contributors to the energy loss for high ion energies (see Fig. 2.6) but have a negligible deflection per collision.\n\n4 graphs. a and b of energy loss versus E over A and path length. a. 2 have an increasing trend, and 4 decline. b. 2 lines have a spike pattern. c of stopping power versus energy. 2 follow a declining trend, and 1 follows an increasing trend. d of dose deposition versus depth. 2 right-skewed curves.\n\nFig. 2.6\n(a) Energy loss for protons (purple) and carbon (blue) ions depends on ion type and ion energy. For lower energies, the nuclear energy loss (dotted lines) starts to get an influence. At energies above ~0.0005\u00a0MeV/u for protons and ~0.005\u00a0MeV/u for carbon ions, the electronic energy loss is dominant (dashed lines) and the nuclear energy loss can be even neglected for higher energies. E/A is the energy divided by mass number. (b) Energy loss for a proton with initial energy of Ein\u00a0=\u00a0200 MeV with a range in water of 256 mm on the left and for a carbon ion with initial energy of Ein\u00a0=\u00a0375\u00a0MeV/u with a range in water of 251 mm on the right: at the end of range at a path length, the energy loss is increasing and rapidly goes to zero when the ion stops. The curve shape for the carbon ion is the same as for the proton but with a higher energy loss at all times. Energy losses are calculated via SRIM (SRIM\u2014The Stopping and Range of Ions in Matter, J. Ziegler, http://\u200bwww.\u200bsrim.\u200borg/\u200b). (c) Stopping power of electrons depending on electron energy simulated using estar (https://\u200bphysics.\u200bnist.\u200bgov/\u200bPhysRefData/\u200bStar/\u200bText/\u200bESTAR.\u200bhtml). (d) Energy loss of electrons in adipose tissue with penetration depth (inspired by Hazra et al. 2019) (licensed under CC-BY-4.0) [26]"}
{"_id": "Radiology$$$1e066659-d2c4-4b7a-82e9-9bdacd141370", "text": "4 graphs. a and b of energy loss versus E over A and path length. a. 2 have an increasing trend, and 4 decline. b. 2 lines have a spike pattern. c of stopping power versus energy. 2 follow a declining trend, and 1 follows an increasing trend. d of dose deposition versus depth. 2 right-skewed curves."}
{"_id": "Radiology$$$95b9be98-8a6c-42f5-8dc8-a8f1f6795c00", "text": "Energy loss through elastic nuclear scattering as described above is only an important contribution to the total energy loss for ion energies below approximately 0.01\u00a0MeV/u. Here, the ions are already close to stopping and have a remaining range in the order of nanometers. For high ion energies (E\u00a0>\u00a0several 100\u00a0MeV/u), elastic and inelastic nuclear scattering are again mainly responsible for deflection but also for energy loss through emission of bremsstrahlung. There are also other mechanisms possible, happening quite rarely at the energies used in society, but which should be mentioned here [21, 22]. These are direct interactions with the nuclei, namely transfer reactions like stripping or pickup, where nucleons are transferred from or to the incident particle. Also charge exchange can happen, which is a combination of stripping and pickup, where a neutron of the particle is exchanged with a proton of the atom or vice versa. Also, fragmentation can occur, where the incident particle and/or the atomic nucleus break up into (more than two) fragments. And finally, fusion reactions can occur, where the incident particle is fused into the atomic nucleus and both together form a new nucleus."}
{"_id": "Radiology$$$87c01777-ceb7-4ed9-aff9-69a53ce5a404", "text": "The exact energy loss during an interaction is described through the so-called stopping power S and is made up of the collision Scol and the radiation Srad stopping power [23]:\n\n (2.3)"}
{"_id": "Radiology$$$8d58ac99-4b99-4151-b9ab-0b21d20e4383", "text": "The collision stopping power is the energy loss through collisions along the track in matter. For high energies of the impacting particles, the collisional stopping power can be described by the known Bethe\u2013Bloch formula, which is based on perturbation theory and can also incorporate relativistic corrections."}
{"_id": "Radiology$$$797db36e-e6f2-4b85-a76e-789d505bb3b8", "text": "(2.4)"}
{"_id": "Radiology$$$d4fe0e4c-f320-4e79-a0c8-6bab95de6247", "text": "For electrons or positrons, this is\n\n (2.5)"}
{"_id": "Radiology$$$3cf6d186-e187-428d-8a19-073f4a5516cf", "text": "This formula includes the properties of the particle energy, charge number, and velocity characterized by moc2, z2, and \u03b22 and the properties of the matter density \u03c1, charge number Z, and mass number A. re is the classical electron radius and u the atomic mass unit. The terms Rcol(\u03b2) and \n\n are called rest function for heavier particles or electrons and positrons, respectively. These are dimensionless quantities, which contain the complex energy and matter-dependent cross sections for collision stopping."}
{"_id": "Radiology$$$33321e14-04a9-4500-8d4e-4b4dd7523bee", "text": "In practical use, especially in radiobiology, it is just important to know some proportionalities:\n\n (2.6)"}
{"_id": "Radiology$$$677f1723-5388-4ebe-b7c1-155a2b19f8ae", "text": "The radiation stopping power does not play a role for protons and heavier particles, due to their heavy masses, but for electrons, which are more than three orders of magnitudes lighter."}
{"_id": "Radiology$$$6d5b4356-2099-4ff6-b767-44305db3d17e", "text": "The radiation stopping power for electrons is\n\n (2.7)"}
{"_id": "Radiology$$$a2b12d95-b58b-443e-bf68-bc7348607c8b", "text": "With Etot the total energy of the electron and \u03b1 the fine-structure constant. Again, dimensionless rest functions occur describing the cross sections for interactions with nuclei Rrad, n and electrons in the atomic shell Rrad, e."}
{"_id": "Radiology$$$657c1715-1ac5-41ec-aaff-d285935a103e", "text": "For quantification in radiobiology, the detailed description of the stopping power is not used, as it would be too complicated, and the perturbation parts only contain a small correction. Conventionally, the linear energy transfer \n\n is used instead. The LET only takes electronic interactions into account. The difference between LET and electronic stopping lies in their origin. The electronic stopping is focused on the energy loss of the impacting particle, and it has a negative sign as it acts as a friction force. The LET has a positive sign, and it is the energy that the target sees deposited in itself; this \u201cpositive amount of energy\u201d creates the nonequilibrium dynamics, which are the first radiation-induced effects. The LET and the electronic stopping are equal for big samples, which is the case in radiobiology. Therefore, the LET is the same as the electronic stopping, which can be looked up in programs such as pstar, astar, or SRIM [24, 25]."}
{"_id": "Radiology$$$e0542d69-461f-4a49-aeb1-d37b38980352", "text": "For protons and heavier ions at energies larger than ~0.01\u00a0MeV/u, the electronic energy loss is the dominant process, as can be seen in Fig. 2.6, whereas for low ion energies, the nuclear energy loss becomes dominant, validating the use of LET as the most appropriate measurement quantity for radiobiologically relevant energies of >1 MeV. The energy loss has a peak at"}
{"_id": "Radiology$$$fea9655b-8632-46ba-818a-f189f3d340d0", "text": "(2.8)"}
{"_id": "Radiology$$$ea6ddb9c-eb69-408c-84f2-12babaf1ef6b", "text": "For a single collision, considering a maximum energy \u0394Emax which can be transferred through electronic interactions is"}
{"_id": "Radiology$$$ed9d2d52-ecb4-413d-a109-177d8d024b6d", "text": "(2.9)"}
{"_id": "Radiology$$$442cf164-3951-46d2-ae47-5275d59dabba", "text": "With me being the electron mass, m the ion mass, and E the ion energy. For protons, this maximum energy transfer per collision is \u0394Emax, p\u00a0\u2248\u00a00.2\u00a0%\u00a0Ep. For carbon ions, it is even lower at \u0394Emax, C\u00a0\u2248\u00a00.02\u00a0%\u00a0EC. Therefore, thousands of collisions are necessary before an ion stops, and the more energy it has lost, the slower it gets and therefore the interactions get closer together."}
{"_id": "Radiology$$$357b22f6-d9d9-48c7-88e8-0a4833e2d623", "text": "If one looks at the energy loss of an ion depending on the path length traveled in a target medium, a unique distribution is visible (Fig. 2.6b). The energy loss at the entrance is low and only slightly increasing with depth. Just in the last millimeters or even below, the energy loss sharply increases. After the peak, an even sharper decrease is visible until the ion stops only shortly after reaching the peak energy loss. This distribution is called the Bragg curve. Due to this distribution, a range of the particle can be defined, which is the average distance the ion travels before it stops. Due to the statistical nature of the interactions, the range can only be given as an average quantity. The ion range can be calculated as [23]:\n\n (2.10)"}
{"_id": "Radiology$$$1bfecd01-88e8-4bb0-bc80-95f758a6a9ee", "text": "For example, for protons with therapy-relevant energies between approx. 10 MeV and 200\u00a0MeV, the range can be approximated to\n\n (2.11)"}
{"_id": "Radiology$$$0abd6132-f9ee-4912-9bf5-29583fd92995", "text": "The unique energy loss distribution, with a peak energy loss just at the end of range, gives particles a great advantage in tumor therapy compared to photons, as the tissue behind the tumor will not get irradiated at all, as explained in Chap. 6."}
{"_id": "Radiology$$$10ccdf00-6074-4546-8d65-5ad00ec51f9a", "text": "For low-energy electrons, the collision stopping power is the dominant process, whereas for higher energies, the radiation stopping power gets dominant (Fig. 2.6c). The energy loss distribution with penetration depth is due to the contribution of the radiation stopping power different to protons and heavier ions (Fig. 2.6d). There is no clear range visible, but after a small buildup, the maximum is reached, followed by a decrease, and with higher depth the energy loss will be zero; this is when the electron has stopped. The possible penetration depth and especially the maximum of energy loss are dependent on energy. This is relevant for therapy, where low-energy electrons are used to irradiate skin tumors, whereas for deeper lying tumors, higher energies are necessary (Box 2.5)."}
{"_id": "Radiology$$$d3dddd11-3eb5-4cce-9c17-33a9114430db", "text": "Charged particles transfer their energy mainly through coulomb interactions with electrons and nuclei of the atoms of the matter.\n\nThe energy loss of the particle can be described by the Bethe\u2013Bloch formula of the stopping power.\n\nFor ions, only collision stopping power plays a role, and for electrons also radiation stopping power.\n\nIons have a defined range, where energy loss follows the Bragg curve."}
{"_id": "Radiology$$$d78cf23d-4c74-4651-b9b7-9702a7e2ffdb", "text": "Charged particles transfer their energy mainly through coulomb interactions with electrons and nuclei of the atoms of the matter."}
{"_id": "Radiology$$$c26db3d9-c30a-476c-a197-9e1610300c45", "text": "The energy loss of the particle can be described by the Bethe\u2013Bloch formula of the stopping power."}
{"_id": "Radiology$$$c973f97d-69d9-4ca7-b168-2ba25703ca36", "text": "For ions, only collision stopping power plays a role, and for electrons also radiation stopping power."}
{"_id": "Radiology$$$901a37e5-5dde-4b73-a2c8-8f6625035742", "text": "Ions have a defined range, where energy loss follows the Bragg curve."}
{"_id": "Radiology$$$76f5fd87-1892-4920-ad86-032f4554e659", "text": "The interaction of particles with matter is not only responsible for energy loss but also for a deflection of the incident particle. For the coulomb interactions with electrons, only negligible deflection occurs. The nuclear Coulomb interactions also give small deflections per collision. Furthermore, Rutherford scattering with the atomic nucleus can occur. Taking all the interactions into account, significant deflection of particles is common. This process is called multiple small-angle scattering. Additionally, the Rutherford scattering can lead to single large-angle scattering events, but this effect is very rare. The scattering of single ions leads to widening of the incident beam of particles with penetration depth. Due to the dominance of the multiple small-angle scattering, the lateral profile of the beam can be approximated by a Gaussian distribution. It is important to know that for larger lateral distances, the Gaussian distribution no longer holds, as the large-angle scattered ions are deflected in this region. But as already mentioned, this is a rare process and does not have an influence on the beam size. The lateral spread defined as the \u03c3 of the Gaussian distribution is \n\n, with Ekin the kinetic energy of the particle, z the charge, and x the distance traveled (Box 2.6)."}
{"_id": "Radiology$$$d1a58f5e-479a-4a39-a5a6-3c4fa1e84498", "text": "Coulomb interactions are responsible for scattering of the particle.\n\nMultiple coulomb scattering leads to a deflection of the particle.\n\nSingle Rutherford scattering with the atomic nuclei leads to large deflections, but these are very rare.\n\nAn incident particle beam will have a Gaussian energy distribution profile in the lateral direction due to the statistical nature of scattering."}
{"_id": "Radiology$$$57cac59a-aa08-48b8-8bb5-c3492adced46", "text": "Single Rutherford scattering with the atomic nuclei leads to large deflections, but these are very rare."}
{"_id": "Radiology$$$3bf93958-2970-48c5-80c1-473c8fb99834", "text": "An incident particle beam will have a Gaussian energy distribution profile in the lateral direction due to the statistical nature of scattering."}
{"_id": "Radiology$$$9b6f964a-e88e-4001-aa02-f08cec441bc6", "text": "The existence of the neutron as a component of the atom was first proposed by Rutherford in 1911, though it was Chadwick who in 1932 detected the particle as a result of experiments involving gamma irradiation of paraffin [27]. Advances in particle physics have led to our current understanding of hadronic matter which includes neutrons, such that the quark model of the neutron envisages the particle as consisting of two down quarks and an up quark (udd), as shown in Fig. 2.7.\n\n2 models for the proton and neutron depict triangular structures of u u d and u d d, respectively, connected by coiled gluons. U is an up quark, and D is a down quark.\n\nFig. 2.7\nQuark structure of proton and neutron, with binding gluons shown (Created with BioRender)"}
{"_id": "Radiology$$$e56130e0-1bd2-488f-82e7-4410474a1de6", "text": "2 models for the proton and neutron depict triangular structures of u u d and u d d, respectively, connected by coiled gluons. U is an up quark, and D is a down quark."}
{"_id": "Radiology$$$32220a74-da77-4ca5-8a77-189097cb7015", "text": "The neutron differs from the proton (uud) by a single quark such that it has almost identical mass (mn\u00a0=\u00a0939.6\u00a0MeV/c2, mp\u00a0=\u00a0938\u00a0MeV/c2) though the neutron has zero charge. It also differs further in that, while the proton is thought to be stable (current T1/2 of ~1038\u00a0years), the free neutron is unstable with a mean lifetime of approximately 879.6\u00a0s. While electrically neutral, the neutron does have a magnetic moment of approximately \u22121.93 \u2320N, where that for the proton is approximately 2.79 \u2320N (and where \u2320N is the nuclear magneton). As the neutron is a fermion, it has a spin of \u00bd [28]."}
{"_id": "Radiology$$$2d979d3d-98f1-4131-9fca-29367dc441c1", "text": "Early experiments with neutrons relied upon their production in prototype nuclear reactors. Here, neutrons were classified according to their energies as thermal (E\u00a0~\u00a00.038\u00a0eV, on average associated with a Maxwell\u2013Boltzmann distribution of particles at room temperature), slow (E\u00a0<\u00a00.1\u00a0MeV), fast (E\u00a0>\u00a010\u00a0MeV), or relativistic (with energies producing velocities of 0.1 c or above) [29]."}
{"_id": "Radiology$$$9c20a0c7-c310-458f-b160-08ccf9791ff3", "text": "Exploration of neutron interactions with matter has revealed that they have very complex energy cross sections, which vary substantially with the target material. However, the interactions may be broadly classified as elastic or inelastic interactions, with elastic collisions having a greater cross section at high neutron energies [29]."}
{"_id": "Radiology$$$c30e4ece-e61a-4a92-9a26-4f9be0ce59fe", "text": "In elastic interactions, the neutron collides, typically, with a target nucleus, transferring some of its kinetic energy to the nucleus, which then recoils. It may be demonstrated that the maximum energy Q that a neutron of energy En and mass M may transfer to a recoil nucleus of mass m is given by [29]."}
{"_id": "Radiology$$$60b73806-3779-4334-b79c-bf80efd5f754", "text": "(2.12)"}
{"_id": "Radiology$$$00e59d8f-7d92-43c0-b60a-a90991ea5b4f", "text": "In general, one may observe a cosine-squared spatial distribution of recoil energies for nuclei, Q, from which the original energy of the neutron beam may be estimated [29]:"}
{"_id": "Radiology$$$e6ec3ac0-0c34-40c3-98f3-c5814d604e05", "text": "(2.13)"}
{"_id": "Radiology$$$387e1f08-3de4-432b-8813-31b2c5382942", "text": "In inelastic scattering events, either the neutron can promote the nucleus of element X to an excited state, from which the nucleus itself decays by re-emitting the neutron with different energy and momentum [(n,n\u2032) reactions], or, for neutrons with energy below 0.5\u00a0MeV, the nucleus absorbs (\u201ccaptures\u201d) the incident neutron, causing it to transmute to a new elementary state, Y, generally with the emission of some product projectile, b, such as a proton, alpha particle, or gamma ray. The latter nuclear reactions are written as"}
{"_id": "Radiology$$$4a26de12-0fcd-4001-bcdd-268ae29946e0", "text": "(2.14)"}
{"_id": "Radiology$$$1d7e93f8-e532-4f0e-b833-c3d44fb566ed", "text": "The development of sources of neutrons for industrial purposes has been a highly complex undertaking. Spallation sources of neutrons, where a material is bombarded with a projectile particle and then emits a beam of neutrons, have existed for some time. However, these systems require acceleration of a projectile beam, which renders them costly from an energy-input perspective, though they produce highly intense beams which are useful in the imaging of materials, as well as for both breeding and burning of nuclear fuel. Most neutron beams are produced via collimation and focusing of neutron beams from nuclear reactors, for similar applications to those already highlighted, and importantly for therapeutic applications in medicine. The development of Wolter mirrors and lenses has provided the means to direct and focus beams of neutrons in a highly precise manner allowing for controlled therapeutic applications."}
{"_id": "Radiology$$$6125fb85-bcc9-4440-a292-d6c8588642c4", "text": "Humans are continuously exposed to low levels of ionizing radiation from the surroundings as they carry out their normal daily activities; this is known as background radiation, which is present on Earth at all times [30]. In addition, we are exposed to ionizing radiation from artificial sources during medical examinations and treatments, during processing and using radioactive materials, and during operation of nuclear power plants or accelerators (Figs. 2.8 and 2.9). Below we provide a summary of the possible scenarios of exposure to natural and artificial radiation.\n\nA schematic representation exhibits the pathway of the inhalation or ingestion of cosmic, external, indoor, and terrestrial radiations that form the corresponding radionuclides, which are further inhaled or ingested by plants and animals.\n\nFig. 2.8\nNatural sources of ionizing radiation and their pathways (Figure from European Commission, Joint Research Centre\u2014Cinelli, G., De Cort, M. & Tollefsen, T., European Atlas of Natural Radiation, Publication Office of the European Union [41]) (licensed under CC-BY-4.0)\n\n\nA pie chart provides the proportion of 80% natural and 20% artificial sources. The given data for the natural source are as follows. Radon inhalation, 42%. External terrestrial radiation, 16%. Cosmic radiation, 13%. Ingestion, 10%. The artificial data includes medical diagnosis, 20% and other, 0.4%.\n\nFig. 2.9\nWorldwide average annual human exposure to ionizing radiation (from UNSCEAR (2008) Sources and effects of ionizing radiation) (Created with BioRender)"}
{"_id": "Radiology$$$cb995b97-c4d6-4721-b464-88ecef7f1169", "text": "A schematic representation exhibits the pathway of the inhalation or ingestion of cosmic, external, indoor, and terrestrial radiations that form the corresponding radionuclides, which are further inhaled or ingested by plants and animals."}
{"_id": "Radiology$$$1fc7aab4-7f18-486e-ac4d-3df62f6eed0e", "text": "A pie chart provides the proportion of 80% natural and 20% artificial sources. The given data for the natural source are as follows. Radon inhalation, 42%. External terrestrial radiation, 16%. Cosmic radiation, 13%. Ingestion, 10%. The artificial data includes medical diagnosis, 20% and other, 0.4%."}
{"_id": "Radiology$$$aa840ecb-c175-47d2-81d2-85bd7c4e721a", "text": "Natural radiation is all around us, and we receive it from the atmosphere, rocks, water, plants, as well as the food we eat (Fig. 2.8). Naturally occurring radioactive materials are present in the Earth\u2019s crust; the floors and walls of our homes, schools, or offices; and food. Radioactive gasses are also present in the air we breathe. Our muscles, bones, and other tissues contain naturally occurring radionuclides [31]. Hence, our lives have evolved, and our bodies have adapted to the world containing considerable amounts of ionizing radiation. As per the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR), terrestrial radiation, inhalation, ingestion, and cosmic radiation are the four foremost sources of public exposure to natural radiation.1.\nTerrestrial Radiation: One of the major sources of natural radiation is the Earth\u2019s crust, where the key contributors are the innate deposits of thorium, uranium, and potassium. These minerals are called primordial radionuclides and are the source of terrestrial radiation. These deposits discharge small quantities of ionizing radiation during the process of natural decay, and these minerals are found in building materials. Therefore, humans can get exposed to natural radiation both outdoors and indoors. These radiation levels can fluctuate substantially depending on the location. Traces of radioactive materials can be found in the body where nonradioactive and radioactive forms of potassium and other elements are metabolized in the same way [32].\n\u00a02.\nInhalation: Humans are exposed to inhalation of radioactive gasses that are formed by radioactive minerals found in soil and bedrock. For example, uranium-238, during its decay, produces radon (222Rn) which is an inert gas and thorium produces thoron (220Rn). These gasses get diluted to harmless levels when they traverse the Earth\u2019s atmosphere. However, at times, these gasses escape through cracks in the building foundations, are trapped, and accumulate inside buildings where they are inhaled by the occupants (indoor living) [30].\n\u00a03.\nIngestion: Vegetables and fruits are grown in the soil and groundwater, which usually contain radioactive minerals. We ingest these minerals and subsequently are exposed to internal natural radiation. Carbon-14 and potassium-40 are naturally occurring radioactive isotopes which possess similar biological characteristics as their nonradioactive isotopes. These radioactive and nonradioactive elements are used not only in building our bodies but also in maintaining them. Therefore, such natural radioisotopes recurrently expose us to radiation [30].\n\u00a04.\nCosmic Radiation: Space is permeated by radiation, not only of electromagnetic type but also constituted by ionizing particles with mass. The electromagnetic radiation in space spans all wavelengths, from infrared to visible, from X-ray to gamma rays. In general, however, \u201cspace radiation\u201d mostly refers to corpuscular radiation, which has three main sources:(a)\nGalactic Cosmic Rays (GCRs): The GCRs constitute the slowly varying, low-intensity, and highly energetic radiation flux background in the universe, mostly associated with explosions of distant supernovae. The GCR spectrum consists of approximately 87% hydrogen ions (protons) and 12% helium ions (\u03b1-particles), with the remaining 1\u20132% of particles being HZE (high charge Z and energy) nuclei. The energies are between several tenths and 10 \u00d7 10 GeV/nucleon and more. GCRs directly hit the top of the Earth\u2019s atmosphere, generating secondary particle showers. However, some direct GCRs and generated secondary particles infiltrate the Earth\u2019s atmosphere reaching the ground. Such radiation gets absorbed by humans, and it thus constitutes a source of natural radiation exposure. Since at higher altitude the amount of atmosphere shielding us from incoming radiation is less, the higher we go in altitude, the higher dose we receive. For example, those living in Denver, Colorado (altitude of 5280\u00a0ft\u00a0=\u00a0about 1610\u00a0m), receive a higher annual radiation dose from cosmic radiation than someone living at sea level (altitude of 0\u00a0ft) [32]. GCR ions are a major health threat to astronauts for missions beyond the near-Earth environment and for interplanetary travel [33]. For Mars, the thin atmosphere combined with the absence of a planetary magnetic field essentially offers very little shielding from the incoming GCRs [34, 35]. Also, GCRs directly reach the surface of airless bodies such as the Moon [36].\n\u00a0(b)\nRadiation from the Sun: This consists of both low-energy particles flowing constantly from the Sun (the solar wind) and of solar energetic particles (SEPs), originating from transient intense eruptions on the Sun [37]. The solar wind is stopped by the higher layers of the atmosphere of our planet (and other celestial bodies with an atmosphere). SEPs come as huge injections and are composed predominantly of protons and electrons. Typical proton energies range from 10 to 100 of MeV. They are generally quite efficiently stopped in the Earth\u2019s atmosphere, but some direct SEPs and their high flux of secondaries could eventually be dangerous for high-altitude/latitude flights and their crew [38] and for astronauts of the International Space Station (ISS) in extravehicular activities. Finally, SEPs can be a strong concern also for astronauts during interplanetary travel, such as a trip to Mars, even inside the spacecraft [39], or for humans on the surface of the Moon.\n\u00a0(c)\nTrapped Radiation: This consists of GCRs and SEPs and their secondaries trapped by the Earth\u2019s magnetic field into the Van Allen radiation belts. Such belts comprise a stable inner belt of trapped protons and electrons (energies are between keV and 100\u00a0MeV) and a less stable outer electron belt. The inner Van Allen belt comes closest to the Earth\u2019s surface, down to an altitude of 200\u00a0km, in a region just above Brazil. This area is named the South Atlantic Anomaly [40]. An increased flux of energetic particles exists in this region and exposes orbiting human missions to higher-than-usual levels of radiation (Box 2.7)."}
{"_id": "Radiology$$$b00c64a6-fb15-4bfe-9a58-b2aec24c82b6", "text": "Terrestrial Radiation: One of the major sources of natural radiation is the Earth\u2019s crust, where the key contributors are the innate deposits of thorium, uranium, and potassium. These minerals are called primordial radionuclides and are the source of terrestrial radiation. These deposits discharge small quantities of ionizing radiation during the process of natural decay, and these minerals are found in building materials. Therefore, humans can get exposed to natural radiation both outdoors and indoors. These radiation levels can fluctuate substantially depending on the location. Traces of radioactive materials can be found in the body where nonradioactive and radioactive forms of potassium and other elements are metabolized in the same way [32]."}
{"_id": "Radiology$$$f4eb2bec-78fc-4e09-ac20-58c50dd63998", "text": "Inhalation: Humans are exposed to inhalation of radioactive gasses that are formed by radioactive minerals found in soil and bedrock. For example, uranium-238, during its decay, produces radon (222Rn) which is an inert gas and thorium produces thoron (220Rn). These gasses get diluted to harmless levels when they traverse the Earth\u2019s atmosphere. However, at times, these gasses escape through cracks in the building foundations, are trapped, and accumulate inside buildings where they are inhaled by the occupants (indoor living) [30]."}
{"_id": "Radiology$$$3e81a6da-f6f8-408a-ae36-8009e19da735", "text": "Ingestion: Vegetables and fruits are grown in the soil and groundwater, which usually contain radioactive minerals. We ingest these minerals and subsequently are exposed to internal natural radiation. Carbon-14 and potassium-40 are naturally occurring radioactive isotopes which possess similar biological characteristics as their nonradioactive isotopes. These radioactive and nonradioactive elements are used not only in building our bodies but also in maintaining them. Therefore, such natural radioisotopes recurrently expose us to radiation [30]."}
{"_id": "Radiology$$$e99c42bd-021d-4c6c-9920-dd131b23a2b6", "text": "Cosmic Radiation: Space is permeated by radiation, not only of electromagnetic type but also constituted by ionizing particles with mass. The electromagnetic radiation in space spans all wavelengths, from infrared to visible, from X-ray to gamma rays. In general, however, \u201cspace radiation\u201d mostly refers to corpuscular radiation, which has three main sources:(a)\nGalactic Cosmic Rays (GCRs): The GCRs constitute the slowly varying, low-intensity, and highly energetic radiation flux background in the universe, mostly associated with explosions of distant supernovae. The GCR spectrum consists of approximately 87% hydrogen ions (protons) and 12% helium ions (\u03b1-particles), with the remaining 1\u20132% of particles being HZE (high charge Z and energy) nuclei. The energies are between several tenths and 10 \u00d7 10 GeV/nucleon and more. GCRs directly hit the top of the Earth\u2019s atmosphere, generating secondary particle showers. However, some direct GCRs and generated secondary particles infiltrate the Earth\u2019s atmosphere reaching the ground. Such radiation gets absorbed by humans, and it thus constitutes a source of natural radiation exposure. Since at higher altitude the amount of atmosphere shielding us from incoming radiation is less, the higher we go in altitude, the higher dose we receive. For example, those living in Denver, Colorado (altitude of 5280\u00a0ft\u00a0=\u00a0about 1610\u00a0m), receive a higher annual radiation dose from cosmic radiation than someone living at sea level (altitude of 0\u00a0ft) [32]. GCR ions are a major health threat to astronauts for missions beyond the near-Earth environment and for interplanetary travel [33]. For Mars, the thin atmosphere combined with the absence of a planetary magnetic field essentially offers very little shielding from the incoming GCRs [34, 35]. Also, GCRs directly reach the surface of airless bodies such as the Moon [36].\n\u00a0(b)\nRadiation from the Sun: This consists of both low-energy particles flowing constantly from the Sun (the solar wind) and of solar energetic particles (SEPs), originating from transient intense eruptions on the Sun [37]. The solar wind is stopped by the higher layers of the atmosphere of our planet (and other celestial bodies with an atmosphere). SEPs come as huge injections and are composed predominantly of protons and electrons. Typical proton energies range from 10 to 100 of MeV. They are generally quite efficiently stopped in the Earth\u2019s atmosphere, but some direct SEPs and their high flux of secondaries could eventually be dangerous for high-altitude/latitude flights and their crew [38] and for astronauts of the International Space Station (ISS) in extravehicular activities. Finally, SEPs can be a strong concern also for astronauts during interplanetary travel, such as a trip to Mars, even inside the spacecraft [39], or for humans on the surface of the Moon.\n\u00a0(c)\nTrapped Radiation: This consists of GCRs and SEPs and their secondaries trapped by the Earth\u2019s magnetic field into the Van Allen radiation belts. Such belts comprise a stable inner belt of trapped protons and electrons (energies are between keV and 100\u00a0MeV) and a less stable outer electron belt. The inner Van Allen belt comes closest to the Earth\u2019s surface, down to an altitude of 200\u00a0km, in a region just above Brazil. This area is named the South Atlantic Anomaly [40]. An increased flux of energetic particles exists in this region and exposes orbiting human missions to higher-than-usual levels of radiation (Box 2.7)."}
{"_id": "Radiology$$$80764e1d-df1a-4915-b97d-3d1c336da652", "text": "Galactic Cosmic Rays (GCRs): The GCRs constitute the slowly varying, low-intensity, and highly energetic radiation flux background in the universe, mostly associated with explosions of distant supernovae. The GCR spectrum consists of approximately 87% hydrogen ions (protons) and 12% helium ions (\u03b1-particles), with the remaining 1\u20132% of particles being HZE (high charge Z and energy) nuclei. The energies are between several tenths and 10 \u00d7 10 GeV/nucleon and more. GCRs directly hit the top of the Earth\u2019s atmosphere, generating secondary particle showers. However, some direct GCRs and generated secondary particles infiltrate the Earth\u2019s atmosphere reaching the ground. Such radiation gets absorbed by humans, and it thus constitutes a source of natural radiation exposure. Since at higher altitude the amount of atmosphere shielding us from incoming radiation is less, the higher we go in altitude, the higher dose we receive. For example, those living in Denver, Colorado (altitude of 5280\u00a0ft\u00a0=\u00a0about 1610\u00a0m), receive a higher annual radiation dose from cosmic radiation than someone living at sea level (altitude of 0\u00a0ft) [32]. GCR ions are a major health threat to astronauts for missions beyond the near-Earth environment and for interplanetary travel [33]. For Mars, the thin atmosphere combined with the absence of a planetary magnetic field essentially offers very little shielding from the incoming GCRs [34, 35]. Also, GCRs directly reach the surface of airless bodies such as the Moon [36]."}
{"_id": "Radiology$$$d7cdab2c-5b38-4766-a808-7699e63b96bf", "text": "Radiation from the Sun: This consists of both low-energy particles flowing constantly from the Sun (the solar wind) and of solar energetic particles (SEPs), originating from transient intense eruptions on the Sun [37]. The solar wind is stopped by the higher layers of the atmosphere of our planet (and other celestial bodies with an atmosphere). SEPs come as huge injections and are composed predominantly of protons and electrons. Typical proton energies range from 10 to 100 of MeV. They are generally quite efficiently stopped in the Earth\u2019s atmosphere, but some direct SEPs and their high flux of secondaries could eventually be dangerous for high-altitude/latitude flights and their crew [38] and for astronauts of the International Space Station (ISS) in extravehicular activities. Finally, SEPs can be a strong concern also for astronauts during interplanetary travel, such as a trip to Mars, even inside the spacecraft [39], or for humans on the surface of the Moon."}
{"_id": "Radiology$$$a2deb107-1776-4fe4-a911-71cbd95f9362", "text": "Trapped Radiation: This consists of GCRs and SEPs and their secondaries trapped by the Earth\u2019s magnetic field into the Van Allen radiation belts. Such belts comprise a stable inner belt of trapped protons and electrons (energies are between keV and 100\u00a0MeV) and a less stable outer electron belt. The inner Van Allen belt comes closest to the Earth\u2019s surface, down to an altitude of 200\u00a0km, in a region just above Brazil. This area is named the South Atlantic Anomaly [40]. An increased flux of energetic particles exists in this region and exposes orbiting human missions to higher-than-usual levels of radiation (Box 2.7)."}
{"_id": "Radiology$$$f869e2dc-ef75-49b4-bdb0-0d6d2352e363", "text": "The natural radiation to which we are continually exposed has its sources in:\nCosmic radiation (the portion of it reaching the ground)\n\nRadiation from radioactive elements in rocks\n\nRadioactive gasses, generally at harmless concentration in the air but that can potentially also get trapped in building walls\n\nFood, grown in soil and groundwater, which can contain radioactive minerals"}
{"_id": "Radiology$$$ea471234-a468-4be5-ac0d-752636558a90", "text": "Radioactive gasses, generally at harmless concentration in the air but that can potentially also get trapped in building walls"}
{"_id": "Radiology$$$baa5f1d0-8460-48cf-abcd-4e93345ff453", "text": "Food, grown in soil and groundwater, which can contain radioactive minerals"}
{"_id": "Radiology$$$13db5588-84e1-4aab-9608-ddc6e8420385", "text": "Nuclear power stations/plants use uranium to drive a fission reaction that heats water to produce steam. The latter drives turbines to produce electricity. During their normal activities, nuclear power plants release small amounts of radioactive elements, which can expose people to low doses of radiation. The water that passes through a reactor is processed and filtered to remove these radioactive impurities before being returned to the environment. Nonetheless, minute quantities of radioactive gasses and liquids are ultimately released to the environment. Such releases must be continuously monitored and are under the legislative framework of international organizations dealing with nuclear energy, such as the European Atomic Energy Community (EURATOM), established by one of the Treaties of Rome in 1958. Similarly, uranium mines and fuel fabrication plants release some radioactivity that contributes to the dose of the public [42]. The eventual release of radioactive materials should also be monitored and kept under established levels during the decommissioning of a nuclear power plant, from the shutdown of the reactor to the operation of radioactive waste facilities, and also including the short- and intermediate-term storage of spent nuclear waste to the transport to and storage in long-term geological disposal areas."}
{"_id": "Radiology$$$e752dff1-16b1-4ff9-99f8-ec6336d6ec03", "text": "Technologically enhanced naturally occurring radioactive materials (TENORM): All minerals and raw materials contain radionuclides, commonly denoted as naturally occurring radioactive materials (NORM). When concentrations of radionuclides are increased by technological processes, the term technologically enhanced NORM (TENORM) is applicable. Coal-fired power stations, for example, emit an amount of radioactivity compared to or even higher (especially in the past) than nuclear power plants. Just for example, US coal-fired electricity generation in 2013 gave rise to 1100 tonnes of uranium and 2700 tonnes of thorium in coal ash. Other TENORM industries include oil and gas production, metallurgy, fertilizer (phosphate) manufacturing, building industry, and recycling [43]."}
{"_id": "Radiology$$$bec3d921-3f17-4096-90c5-d8af2d686332", "text": "Accelerators: The operation of accelerators, such as the Large Hadron Collider (LHC) at CERN for fundamental high-energy physics experiments, results in the production of radiation, in particular protons, because of the nuclear interactions between high-energy beams and accelerator components. Thus, the radiation levels around accelerators must be monitored continuously to ensure the protection and safety of the workers and of the public [44]."}
{"_id": "Radiology$$$aab98051-3980-491c-bff6-638947d1b1eb", "text": "Radionuclide production facilities: Radionuclides are used worldwide in (a) medical imaging, fundamental to make correct diagnoses and provide treatments, in which radionuclides are injected into patients at low doses for functional imaging to detect diseases, and (b) therapy, in which radionuclides bound to other molecules or antibodies can be guided to a target tissue, for a local treatment of cancer. Facilities that produce radionuclides and facilities in which radionuclides are processed are reactors and particle accelerators. Radionuclides used in imaging and therapy are often beta or alpha emitters, or both. Thus, the facilities, reactors, and particle accelerators can present radiation hazards to workers and must be properly controlled and monitored, as is the case with the subsequent processing of radioactive material. Among the 238 research reactors in operation in 2017, approximately 83 were considered useful for regular radioisotope production [45]. Approximately 1200 cyclotrons worldwide were used to some extent for radioisotope production in 2015 [46]. The facilities must ensure the application of the requirements of the IAEA [47] (2014) intended to provide for the best possible protection and safety measures."}
{"_id": "Radiology$$$3f3ee9dc-1bbe-4444-8249-24885fbe34f1", "text": "Hospitals: Daily, healthcare workers and patients are exposed to various diagnostic and therapeutic radiation sources [48, 49]. The radiation environment in different hospital departments (nuclear medicine, diagnostic radiology, radiotherapy, \u2026) can be generated by different sources. Hospitals providing radionuclide-based treatments need to protect the staff involved and keep their dose within the acceptable levels. Similarly, the discharged patient must be monitored and measurements for protection purposes must be taken to keep dose to the public within acceptable levels. This may require hospitalization with isolation during the first hours or days of treatment [50, 51]. Waste should be minimized and segregated, and packages labeled and stored for decaying. Measures should also be in place for patients\u2019 household waste related to, for example, urine. In a radiology department, the radiation emitted during fluoroscopic procedures is responsible for the greatest radiation dose to the medical staff. Radiation from diagnostic imaging modalities, such as mammography, computed tomography, and nuclear medical imaging, is a minor contributor to the cumulative dose incurred by healthcare personnel [52]. In radiotherapy departments, photons and electrons are mainly produced by linear accelerators. Rarely, cobalt sources are used to produce radiation. With the current safety regulations, radiotherapy staff will get almost no dose during normal operation. The same is true for modern brachytherapy machines, which are almost all after loading machines avoiding direct contact between the radioactive source and the operator."}
{"_id": "Radiology$$$d7353973-3a13-400a-9307-b22c0b61ab0c", "text": "Ion radiotherapy facilities: Most currently existing ion radiotherapy facilities use protons, with new facilities now being built for the acceleration of other ions, such as carbon. They are mostly cyclotrons or synchrotrons. For such facilities, the major issue is the massive production of neutrons. Ionizing radiation results from the passage of such neutrons through matter and from the radioactivity induced in exposed materials. In accelerator facilities, radioactivity is produced in the very material components, such as their beam delivery/shaping components, as well as in all the structural components and other materials in the facility. Induced radioactivity in treated patients could also reach considerable levels."}
{"_id": "Radiology$$$dd9208f3-6827-4be2-8a90-4b8e6c3b3588", "text": "Nuclear bombs: Nuclear weapons have an explosive power deriving from the uncontrolled fission reaction of plutonium and uranium. This yields a large number of radioactive substances (isotopes) that are blown into the atmosphere. These radioactive isotopes gradually fall back to Earth. If a weapon is exploded near the Earth surface, radioactive fallout is formed in the vicinity of the burst point in a matter of tens of minutes to a couple of days (depending on the burst yield and the distance to the burst point); if a weapon is detonated aboveground (e.g., in Hiroshima and Nagasaki, the bombs exploded about 500 m above the ground level), local fallout is not formed but the radionuclides fall worldwide over a period of many years. Gamma-ray and neutron exposures leading to increased cancer incidence have been studied in the survivors of the atomic bombings in Japan since 1950 (the so-called Life Span Study, LSS, cohort), and currently all potentially suitable risk estimates are built on the excess risk from the LLS study [53]. Interestingly, the numerous tests of nuclear weapons performed by many countries since after World War II and the ensuing fallout have contributed minimally to the overall background radiation exposure (Box 2.8)."}
{"_id": "Radiology$$$14384197-af3b-49ea-a3f1-008ecbed9d3c", "text": "Artificial radiation sources are:\nMedical and radionuclide production facilities, accelerators for ion beam cancer therapy\n\nTechnologically enhanced naturally occurring radioactive materials (TENORM)\n\nNuclear power plants\n\nAccelerators for purely fundamental research in physics"}
{"_id": "Radiology$$$092e527b-2047-43cb-8d32-29361646e4aa", "text": "Medical and radionuclide production facilities, accelerators for ion beam cancer therapy"}
{"_id": "Radiology$$$3c777365-a78c-421c-b861-ffe7f9fc33b5", "text": "The interaction of ionizing radiation (IR) with matter leads to biological damage that can impair cell viability. Biological damage induced by IR arises from either direct or indirect action of radiation. Direct effects occur when IR interacts with critical target molecules such as DNA, lipids, and proteins, leading to ionization or excitation, which causes a chain of events that ultimately leads to the alteration of biomolecules. Indirect effects occur when IR interacts with water molecules, the major constituent of the cell. This reaction, called water radiolysis, generates high-energy species known as reactive oxygen species (ROS) that are highly reactive toward critical targets (cell macromolecules) and, when associated with reactive nitrogen species (RNS), lead to damage to the cell structure. Mechanism and critical targets for ionizing radiation to produce biological damage through direct and indirect effects are shown in Fig. 2.10. Damages to cell macromolecules may be multiple and are detailed in Chap. 3.\n\nA diagram depicts the direct and indirect effects of oxidative stress on the structure and function of D N A, proteins, and lipids. The altered biomolecules affect cell viability.\n\nFig. 2.10\nMechanism and critical targets for ionizing radiation to produce biological damage through direct and indirect effects (Created with BioRender)"}
{"_id": "Radiology$$$6a241c8e-d4ed-4c70-88a6-bc0606beae80", "text": "A diagram depicts the direct and indirect effects of oxidative stress on the structure and function of D N A, proteins, and lipids. The altered biomolecules affect cell viability."}
{"_id": "Radiology$$$59899e61-dcef-40d0-8506-bda9eb3418a3", "text": "Direct effects occur when the ionization takes place within a critical target with relevance to cell functions, such as DNA, lipids, and proteins. These effects are produced by both high and low linear energy transfer (LET) radiation. However, it is the predominant mode of action of high LET radiation such as alpha particles and neutrons, comprising about two-thirds of the radiation effects."}
{"_id": "Radiology$$$7eeabb80-ce07-486c-a525-b88e540c9e89", "text": "When critical molecules in the cell are directly hit by radiation, their molecular structure may be altered resulting in their functional impairment. While molecules from all cell organelles (including mitochondria, endoplasmic reticulum, or Golgi apparatus) may be hit, the nuclear DNA molecule has always been seen as the most critical target (because, unlike proteins, lipids, and carbohydrates, only a single copy of DNA is present in a cell) and was, therefore, the most thoroughly studied. The DNA damage produced by radiation includes base alterations, DNA\u2013DNA cross-links, single- or double-strand breaks (SSB or DSB), or complex damages (described in Chap. 3)."}
{"_id": "Radiology$$$a88e8ff3-4567-408f-b784-ead020cfb11b", "text": "Indirect damages produced by IR in the cell macromolecules are mediated by ROS (resulting from water radiolysis) and by RNS (formed following the reaction of O2 with endogenous nitric oxide). The indirect effects contribute to about two-thirds of the damages induced by low LET radiation (X-rays, gamma-rays, beta particles), which is explained by the fact that they are more sparsely ionizing compared to high LET radiation."}
{"_id": "Radiology$$$a715a29f-735b-4797-96e0-9a9f7e74583c", "text": "When radiation deposits energy in a biological tissue, it takes time until perceiving that an effect has occurred. The succession of the generation of events determines the four sequential stages that translate into the biological effects. These stages, with very different duration, are physical, physicochemical, chemical, and biological [54\u201356]."}
{"_id": "Radiology$$$0b17f25d-3bad-48b3-bcc2-708fe28d438e", "text": "The physical stage is very transient, lasting less than 10\u221216\u201310\u221215\u00a0s, during which energy (kinetic if particles, or electromagnetic if waves) is transferred to the electrons of atoms or molecules, determining the occurrence of ionization and/or excitation. It is at this stage that ions are formed, which will initiate a sequence of chemical reactions that end up in a biological effect. In the case of water radiolysis (decomposition of water molecules due to IR), the ions H2O+ and e\u2212 are formed, as well as the excited water molecule (H2O*) [54\u201356]."}
{"_id": "Radiology$$$fc03814d-5779-4b0a-bbe3-18700fbe1e9c", "text": "Very soon (10\u221212\u00a0s) after the formation of these ions, the physicochemical stage begins, with their diffusion in the medium and consequent intermediate formation of oxygen and nitrogen radical species, i.e., atoms, molecules, or ions that have at least one unrepaired valence electron and hence are very reactive chemically. Following the example of water radiolysis, it is at this stage that \u1e24\u00a0+\u00a0HO\u00b7, H2\u00a0+\u00a02HO, HO\u00b7\u00a0+\u00a0H3O+, HO\u00b7\u00a0+\u00a0H2\u00a0+\u00a0OH\u2212, and e\u2212aq are formed [55, 56], but also superoxide anion (O2\u00b7\u2212) and hydrogen peroxide (H2O2). Peroxynitrite anion (ONOO\u2212) is also formed following the reaction of O2\u00b7\u2212 with endogenous nitric oxide (NO). Together with peroxynitrous acid (ONOOH), nitrogen dioxide (NO2\u00b7), dinitrogen trioxide (N2O3), and others, they are referred to as RNS. The activation of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, the mitochondrial electron transport chain (ETC), or the nitric oxide synthase by IR can also contribute to ROS/RNS generation."}
{"_id": "Radiology$$$496f82c3-26a1-4d0d-8cf2-43b5bd52712e", "text": "In the next chemical stage, the formed radicals and ions recombine and interact with critical cellular organic molecules (DNA, lipids, proteins), inducing structural damages that will translate into disruption of the function of these molecules. Within the DNA molecule, possible chemical reactions with nitrogenous bases, deoxyribose, or phosphate group may result in breaks and recombinations with the consequent formation of abnormal molecules. Among ROS, OH, which has a strong oxidative potential, is a main contributor to cell damages. The chemical stage can last from 10\u221212 s to a few seconds [55, 56]. ROS and RNS have also been largely implicated in the so-called non-targeted effects of IR (further discussed in Sect. 2.8.2)."}
{"_id": "Radiology$$$e2a5cfb5-a6cc-449e-b0a7-151cdcb4ccfe", "text": "Finally, the biological phase occurs, as a consequence of the spreading of chemical reactions involving various biological processes. The existence of more or less effective cellular damage repair mechanisms is responsible for the more or less belated appearance of biological effects and explains the possible long duration of this stage: from a few minutes to decades, depending on the type of radiation, the dose and dose rate, and the radiosensitivity of the irradiated tissue."}
{"_id": "Radiology$$$abe56955-f0e8-415c-9979-ef08909a82d3", "text": "Differences in tissue radiosensitivity can be partially explained by the cellular antioxidant capacity, which may vary between cell types. Indeed, to counteract oxidative insults, cells have evolved several defense mechanisms that consist of enzymatic and nonenzymatic systems. When the amount of ROS/RNS exceeds the antioxidant capacity of the cells, a state of oxidative stress arises, characterized by a decreased pool of antioxidants and modifications in nucleic acids, lipids, and proteins. Oxidative stress can persist for much longer and extend far beyond the primary targets as well as can be transmitted to progeny of the inflicted cells. Responsible for this seems to be the continuous production of ROS and RNS, which can last for months."}
{"_id": "Radiology$$$a40b26b9-d231-4cea-8a1c-d9400973f537", "text": "Virtually all cell molecules and organelles may be damaged by IR, with consequences for the cell function depending on the impact of the damage inflicted."}
{"_id": "Radiology$$$bdc26fd7-d5c9-4f4e-b05a-bb689a89d34a", "text": "According to the radiobiology paradigm, a nucleus is regarded as the main target of IR due to the genetic information contained in the DNA. Therefore, damages to this molecule are considered the most critical ones for cell survival. While efficient repair mechanisms exist to preserve the genome integrity, IR may break bonds in purine and pyrimidine nitrogenous bases in the DNA (which may lead to mutations), SSBs or DSBs, cross-linking, and complex damages. Among these lesions, DSBs and complex damages are the most serious due to the difficulty of their repair. A thorough description of DNA lesions is provided in Chap. 3."}
{"_id": "Radiology$$$662ff4d3-1e0c-4426-a3a7-a7de3a69fac0", "text": "Mitochondria can also be subject to radiation damage, both directly and indirectly. These organelles may represent more than 30% of the total cell volume, and the mitochondrial circular DNA can suffer strand breaks, base mismatches, or even deletions of variable length. In this context, mitochondria constitute a major target of IR [57]. Besides the DNA, changes in mitochondrial morphology have also been observed [58]. Absorption of IR may lead to the enlargement of mitochondria and the increase in length and number of branches of the cristae [58, 59], rupture of the outer and inner membranes, as well as vacuolization and loss of the matrix. These alterations are accompanied by the decreased activity of the respiratory chain, with special emphasis on complexes I, II, and III, which are systematically referred to as especially sensitive to the direct effects of IR. Additionally, there is a decrease in the respiratory capacity driven by succinate and the ATP synthase, with a consequent impact on oxidative phosphorylation. The radiation-induced decrease in the rate of oxidative phosphorylation can recover over time, depending on the cell type [60, 61]. The electrons in the respiratory chain can leak during their transport and reduce oxygen molecules leading to the formation of superoxide anions, which are precursors of most ROS. Upon irradiation, the level of ROS produced in the mitochondria greatly increases, although under physiological conditions, it is already high."}
{"_id": "Radiology$$$c6a369b1-a46d-4f31-9501-f47708a77e8e", "text": "Irradiation may also cause morpho-functional changes in the endoplasmic reticulum (ER). After exposure to IR, ER dilates, vesicles appear, and its cisternae break into fragments. In the case of rough endoplasmic reticulum, irradiation induces degranulation accompanied by transformation of the membrane-bound ribosomes into free organelles [59, 62]."}
{"_id": "Radiology$$$e2d093bd-7385-41a8-bac6-13ecdfed6092", "text": "Likewise, irradiation may also disorganize the structure of the Golgi apparatus due to the induced fragmentation and rearrangement of its cisterns. In view of the effects of IR on the endoplasmic reticulum-Golgi apparatus complex, the ensuing alterations in the synthesis and maturation of proteins in the irradiated cells come as no surprise. Lysosomes may also increase in number and volume in the irradiated cells, which is accompanied by upregulation of the enzymatic activity in these organelles [58, 59] (Box 2.9)."}
{"_id": "Radiology$$$38921c2c-f633-44a2-b4d8-522bd224f2d5", "text": "Direct effects predominate after exposure to high LET radiation (e.g., alpha particles, neutrons).\n\nExposure to low LET radiation (e.g., X-rays, gamma rays, beta particles) induces mostly indirect effects.\n\nIndirect effects are mediated by ROS/RNS produced during and after the radiolysis of water.\n\nApart from nuclear DNA, other cellular molecules and organelles may be altered by IR, including mitochondrial DNA, plasma membrane lipids, endoplasmic reticulum, Golgi apparatus, and lysosomes."}
{"_id": "Radiology$$$454625b2-1d04-424b-94ad-079513f13ed2", "text": "Direct effects predominate after exposure to high LET radiation (e.g., alpha particles, neutrons)."}
{"_id": "Radiology$$$4d63a77e-620b-4953-867d-55ce18889e91", "text": "Exposure to low LET radiation (e.g., X-rays, gamma rays, beta particles) induces mostly indirect effects."}
{"_id": "Radiology$$$1b741f14-d91a-4d10-ae37-503dbcc2ad7c", "text": "Indirect effects are mediated by ROS/RNS produced during and after the radiolysis of water."}
{"_id": "Radiology$$$a0162afd-7145-423f-b12d-f8d1e4c163a9", "text": "Apart from nuclear DNA, other cellular molecules and organelles may be altered by IR, including mitochondrial DNA, plasma membrane lipids, endoplasmic reticulum, Golgi apparatus, and lysosomes."}
{"_id": "Radiology$$$be62ae86-3d41-4aec-b3d8-a0d2dd335782", "text": "Radiation and radioactivity have been existing ever since the Earth was formed and long before life started to evolve. All living organisms on Earth are continuously exposed to both natural and artificial radioactivity, and without it, life in the present form would have not evolved. Since the first experiments with radioactivity, our understanding of this phenomenon has increased, and consequently, today radioactivity has numerous applications important to human life and health."}
{"_id": "Radiology$$$8e4ff391-54d5-4d9a-975a-42ee75528be0", "text": "The rate of decay of a radioactive source is proportional to the amount of the substance that is present at any given instant. Therefore, if the number of radioactive nuclei in a sample is N, then we may say the following:\n\n (2.15)"}
{"_id": "Radiology$$$460e7de5-50c3-429f-a1f4-2d32591d7eec", "text": "where \u03bb is the decay constant, which describes the rate of decay for a particular radioactive isotope."}
{"_id": "Radiology$$$5229500b-b7bd-449a-84c4-71789d243453", "text": "If we integrate both sides of Eq. (2.15), we get the following more familiar equation:\n\n (2.16)"}
{"_id": "Radiology$$$8f95d077-2112-4ced-8224-0b3d90c122c7", "text": "If we let the variable T1/2 be the \u201chalf-life of the substance,\u201d i.e., the time taken for the activity of the substance to reduce from its initial value to half of its initial value, then we may modify Eq. (2.16) as\n\n (2.17)"}
{"_id": "Radiology$$$0826a5ed-88c7-4c4b-b4c4-9f7daec9c94b", "text": "The activity, A, of a given sample of a radioactive substance, i.e., the number of decays per second (in Bq), is given by the following equation:"}
{"_id": "Radiology$$$670373c7-a2d1-4408-81d4-5a15104dd80e", "text": "(2.18)"}
{"_id": "Radiology$$$faaeafb3-f1e9-483b-b502-907483963bc0", "text": "where calculations based on activities may be performed using Eqs. (2.2) and (2.3) above with the values of A inserted instead of N. The radioactivity of a sample is quoted in terms of the units of Curies, Ci (the radioactivity of a gram of 226Ra), where 1 Ci =3.7 \u00d7 1010 decays per second. This is more commonly quoted in terms of the S.I. unit the Becquerel, Bq, where 1\u00a0Bq\u00a0=\u00a01 decay per second. Therefore, 1\u00a0Ci\u00a0=\u00a03.7 \u00d7 1010\u00a0Bq (Box 2.10)."}
{"_id": "Radiology$$$d6f7ae0b-1709-4156-ac67-3846e06624d8", "text": "The activity (A) of a radioactive substance is given in becquerel (1 Bq is the number of decays per second).\n\nThe radioactivity of a sample can also be expressed in curies (Ci), where 1\u00a0Ci\u00a0=\u00a03.7 \u00d7 1010\u00a0Bq."}
{"_id": "Radiology$$$509a353e-0bc6-4704-820f-bba1a3c52cbc", "text": "The activity (A) of a radioactive substance is given in becquerel (1 Bq is the number of decays per second)."}
{"_id": "Radiology$$$eb6d2733-fc98-4eae-a309-bd2d8acd87a6", "text": "The radioactivity of a sample can also be expressed in curies (Ci), where 1\u00a0Ci\u00a0=\u00a03.7 \u00d7 1010\u00a0Bq."}
{"_id": "Radiology$$$44854dbd-571a-47dc-a3f5-77a4072e3c38", "text": "In nature, the abundance of the isotopes of certain radioactive nuclei depends on the abundance of their precursors, and the rate at which these precursors decay. Hence, the rate of production of each daughter nuclide of a certain radioactive isotope depends upon the rate at which its parent nuclide decays. All naturally occurring radioactive nuclides that are located below plutonium, 239Pu, in the periodic table are produced from the decay of just four parent (progenitor) isotopes: thorium (4n series), neptunium (4n\u00a0+\u00a01 series), uranium/radium (4n\u00a0+\u00a02), and actinium (4n\u00a0+\u00a03). Each of these nuclides then has a decay series or chain (see example in Fig. 2.11) with associated rates of decay at each step that determine the abundance of all other radionuclides in the universe.\n\nA graph of the number of neutrons versus the atomic number. It depicts alpha decay or beta decay of U 238, T h 234, P a 234, U 234, T h 230, R a 226, R n 222, P o 218, P b 214, P o 214, P o 210, and P b 206.\n\nFig. 2.11\nUranium, 238U/radium, 226R (4n\u00a0+\u00a02) decay series. Radioactive decay series. (2020, September 8). [Retrieved August 16, 2021, from https://\u200bchem.\u200blibretexts.\u200borg/\u200b@go/\u200bpage/\u200b86256 (open-source CC-BY textbook)]"}
{"_id": "Radiology$$$fedd76f6-3c6b-43c0-9900-3652ade37a04", "text": "A graph of the number of neutrons versus the atomic number. It depicts alpha decay or beta decay of U 238, T h 234, P a 234, U 234, T h 230, R a 226, R n 222, P o 218, P b 214, P o 214, P o 210, and P b 206."}
{"_id": "Radiology$$$6ab8599b-0905-406f-8b25-45a978bfec5b", "text": "The neptunium series is not observed in nature at the present time as 237Np, and all of its daughter nuclides have decayed since the birth of the universe, although the product of the series, bismuth 209Bi, is observed as a stable isotope in nature, pointing to the existence of the series at one time in the past. Each decay series begins with a radioactive isotope and ends with a stable daughter product. The parent isotopes of the isotopes at the beginning of the thorium, neptunium, and actinium series are produced as follows:"}
{"_id": "Radiology$$$99d2c562-a3fb-4a22-a2f6-23a79629d7a3", "text": "Th series: 252Cf \u2192 248Cm \u2192 \u00ae 244Pu \u2192 \u00ae 240U \u2192 \u00ae 240Np \u2192 \u00ae 240Pu \u2192 \u00ae 236U"}
{"_id": "Radiology$$$3b8b3b87-e57e-4d3e-a767-ad8181a0d025", "text": "Np series: 249Cf \u2192 \u00ae 245Cm \u2192 \u00ae 241Pu \u2192 \u00ae 241Am \u2192 \u00ae 237Np"}
{"_id": "Radiology$$$f7d3cefe-299a-4d3c-b275-db3348301f47", "text": "If we consider a hypothetical decay series as in Fig. 2.12, the three daughter isotopes of isotope A (namely isotopes B, C, D) are produced at different rates, each dependent on the decay constants of the isotope that is their parent. Say only N0 atoms of A exist at time t\u00a0=\u00a00; then\n\n (2.19)\n\n (2.20)\n\n (2.21)"}
{"_id": "Radiology$$$0c6894ac-c34a-415d-a620-5bea43487860", "text": "From Eqs. (2.19) and (2.20):"}
{"_id": "Radiology$$$8d74eb02-ab1c-44e2-9175-8401ff02a9fd", "text": "(2.22)"}
{"_id": "Radiology$$$74b9ff28-fdfe-4b1c-b637-c95ee4b869bf", "text": "And multiplying across by \n\n gives\n\n (2.23)"}
{"_id": "Radiology$$$66d9139b-9516-4210-84a1-2aa460aa3daa", "text": "If the parent is very much shorter lived than the daughter, i.e., if \u03bbA\u00a0>\u00a0\u03bbB, we then have radioactive equilibrium (Fig. 2.12a). If the parent is longer lived than the daughter, then \u03bbA\u00a0<\u00a0\u03bbB and a particular case called transient equilibrium arises (Fig. 2.12b). In Fig. 2.12b, the daughter product C is stable and so no further decrease in activity occurs. Finally, secular equilibrium occurs when the parent is much longer lived than its daughter \u03bbA\u00a0<<\u03bbB. In this case, Eq. (2.23) reduces to the following (also see Box 2.11)\n\n (2.24)\n\n A flow diagram and 2 graphs. A diagram depicts the decay of A to B to C to D, with lambda A, lambda B, and lambda C as decay constants. a and b plot N versus t. a. 2 follow an increasing trend. b. Curve A slopes downward, curve B follows a right-skewed trend, and curve C follows an increasing trend. \n\nFig. 2.12\nHypothetical decay series involving four nuclides A, B, C, and D, with various different decay constants \u03bbA, \u03bbB, etc. (a) Radioactive equilibrium. (b) Transient equilibrium"}
{"_id": "Radiology$$$24b3e94a-45bd-4055-a725-de799cf1f8a8", "text": "A flow diagram and 2 graphs. A diagram depicts the decay of A to B to C to D, with lambda A, lambda B, and lambda C as decay constants. a and b plot N versus t. a. 2 follow an increasing trend. b. Curve A slopes downward, curve B follows a right-skewed trend, and curve C follows an increasing trend."}
{"_id": "Radiology$$$969aa128-ce8e-4ed4-9361-2c742d8e4047", "text": "The natural abundance of radionuclides is largely determined by the nuclear decay series of four parent nuclides, thorium, neptunium, uranium/radium, and actinium.\n\nEach decay series starts from an unstable radioactive parent isotope and ends with a stable daughter product.\n\nVarious states of equilibrium can be reached depending on the relationship between the lifetime of the parent and daughter isotopes."}
{"_id": "Radiology$$$6a5fbf80-d6d5-446a-b600-e501ff5e46a9", "text": "The natural abundance of radionuclides is largely determined by the nuclear decay series of four parent nuclides, thorium, neptunium, uranium/radium, and actinium."}
{"_id": "Radiology$$$25b7efdf-7176-4a97-b5af-dd28b525a34d", "text": "Each decay series starts from an unstable radioactive parent isotope and ends with a stable daughter product."}
{"_id": "Radiology$$$8d3c1bb4-4562-47e7-819c-a0899192c5a2", "text": "Various states of equilibrium can be reached depending on the relationship between the lifetime of the parent and daughter isotopes."}
{"_id": "Radiology$$$23aaa90a-931e-43ae-9472-33bd8fcb4779", "text": "Experiments demonstrating the production of radioactive nuclei in the laboratory were performed by Ir\u00e8ne and Fr\u00e9d\u00e9ric Joliot-Curie in 1934 through the bombardment of aluminum and boron atoms with alpha particles. Those scientists observed that positrons were produced long after the bombardment and neutron production had ceased. They postulated that radioactive isotopes of phosphorus and nitrogen had been produced, which decayed to silicon and carbon in the following reactions:"}
{"_id": "Radiology$$$683db5c5-f807-4f06-a0d7-06a68bb11a1e", "text": "Neither of the two radioactive isotopes of phosphorus and nitrogen produced in these reactions occurs in nature. The majority of the artificially produced isotopes are produced via the same bombardment as illustrated here, and most of them decay by the production of \u03b2+/\u03b2b\u2212, the ratio of n/p in the nucleus determining which of the two reactions occurs."}
{"_id": "Radiology$$$a33b0863-cbe5-4615-a833-cc3fd60ef922", "text": "Consider a situation where a nuclear reaction occurs by bombardment of nucleus X with particle a, producing a nucleus Y and another projectile particle b:\n\n (2.25)"}
{"_id": "Radiology$$$40acce47-fd33-4e84-93be-7c8b96db8d91", "text": "Assuming that the rate of production, R, of Y is constant and its decay is also constant, then the infinitesimal change, dN, in the numbers of product atoms of Y over infinitesimal time, dt, is\n\n (2.26)"}
{"_id": "Radiology$$$b1724e6d-d327-4c0d-a422-999d4dec214a", "text": "where Rdt provides the number of nuclides of Y produced per unit time and \u03bbNdt the number decaying over this time period. We can then rearrange to obtain a differential equation for the system:"}
{"_id": "Radiology$$$f4d5f52d-cc2f-4a00-be40-247334e4e93a", "text": "(2.27)"}
{"_id": "Radiology$$$8296b57a-fa55-435e-ad24-492442d009a8", "text": "for which we can obtain a general solution for the number of nuclides of Y at any time t\u00a0>\u00a00:\n\n (2.28)"}
{"_id": "Radiology$$$151e5ed8-af40-4eb4-93b6-39adf7a40e84", "text": "And since activity A\u00a0=\u00a0\u03bbN, we may obtain a relationship for the variation in activity with time as\n\n (2.29)"}
{"_id": "Radiology$$$9ca966e7-3bd7-4608-a13a-456c39b3ac7d", "text": "We may use a Taylor expansion in e-\u03bbt to then obtain\n\n (2.30)"}
{"_id": "Radiology$$$237f0657-8cb5-4118-ae65-ccf7c642abc9", "text": "which allows a solution to be obtained for the special case where t\u00a0<<\u00a0T1/2 for the nuclide Y such that the following is true: (also see Box 2.12)\n\n (2.31)"}
{"_id": "Radiology$$$eb4c90bb-1908-4c84-826c-26f98b43941a", "text": "In 1934, Ir\u00e8ne and Fr\u00e9d\u00e9ric Joliot-Curie demonstrated for the first time that artificial, i.e., not occurring in nature, radioactive nuclei can be produced.\n\nArtificial nuclides are produced by bombarding a nucleus (X) with a particle (a) resulting in the production of a new nucleus (Y) and a projectile particle (b)."}
{"_id": "Radiology$$$ec17ca94-137c-416b-ae0e-ee469641a593", "text": "In 1934, Ir\u00e8ne and Fr\u00e9d\u00e9ric Joliot-Curie demonstrated for the first time that artificial, i.e., not occurring in nature, radioactive nuclei can be produced."}
{"_id": "Radiology$$$01980a92-0574-4b8f-92dd-0723a79ce0ca", "text": "Artificial nuclides are produced by bombarding a nucleus (X) with a particle (a) resulting in the production of a new nucleus (Y) and a projectile particle (b)."}
{"_id": "Radiology$$$ea66b3e1-d3f1-4379-a465-0995a30965b9", "text": "Unstable nuclei will transform spontaneously or artificially into an energetically more stable configuration by the emission of certain particles or electromagnetic radiation. This process, termed nuclear decay, is characterized by a parent nuclide (P) transforming into a daughter nuclide (D), which differs from the former in atomic number (Z), neutron number (N), and/or atomic mass number (A) [63]. The different types of nuclear decay are summarized in Table 2.1 (Box 2.13).Table 2.1\nSummary of the different types of nuclear decay\n\nMode of radioactive decay\n\nReleased particles\n\nGeneral reaction\n\nExample\n\n\u03b1-Decay\n\nHelium nucleus\n\nZAP\u00a0\u2192\u00a0Z\u00a0\u2212\u00a02A\u00a0\u2212\u00a04P\u00a0+\u00a024He\n\n92238U\u00a0\u2192\u00a090234Th\u00a0+\u00a024He\n\n\u03b2-Decay\n\u03b2\u2013\n\u03b2+\n\nElectron\nPositron\n\n\n\na\nZAP\u00a0\u2192\u00a0Z\u00a0\u2212\u00a01AD\u00a0+\u00a0e+\u00a0+\u00a0\u03bdb\n\n\n\na\n611C\u00a0\u2192\u00a0511B\u00a0+\u00a0e+\u00a0+\u00a0\u03bdb\n\n\u03b3-Decay\n\n\u03b3-Emission\n\nGamma ray\n\nZAP\u00a0\u2192\u00a0ZAD\u00a0+\u00a000\u03b3\n\n92238U\u00a0\u2192\u00a024He\u00a0+\u00a090234Th\u00a0+\u00a0200\u03b3\n\nInternal conversion\n\nInternal conversion electron\n\nZAP\u00a0\u2192\u00a0ZAD\u00a0+\u00a0IC\u00a0e\u2212\n\u00a0\nElectron capture (EC)\n\nAtomic X-ray\n\nZAP\u00a0+\u00a0e\u2212\u00a0\u2192\u00a0Z\u00a0\u2212\u00a01AD\u00a0+\u00a0\u03bdb\n\n47Be\u00a0+\u00a0e\u2212\u00a0\u2192\u00a037Li\u00a0+\u00a0\u03bdb\n\nSpontaneous fission (SF)\n\n2 fragment nuclei\n\nZAP\u00a0\u2192\u00a0Z1A1D1\u00a0+\u00a0Z2A2D2\n\n100256Fm\u00a0\u2192\u00a054140Xe\u00a0+\u00a046112Pd\n\nProton emission (PE)\n\nProton\n\nZAP\u00a0\u2192\u00a0Z\u00a0\u2212\u00a01A\u00a0\u2212\u00a01D\u00a0+\u00a011p\n\n711N\u00a0\u2192\u00a0610C\u00a0+\u00a011p\n\nNeutron emission (NE)\n\nNeutron\n\nZAP\u00a0\u2192\u00a0ZA\u00a0\u2212\u00a01D\u00a0+\u00a0n0c\n\n413Be\u00a0\u2192\u00a0412Be\u00a0+\u00a0n0c\n\na\u22bd Antineutrino\nbNeutrino\ncn0 Neutron"}
{"_id": "Radiology$$$80b664ad-974c-4de7-8b30-52d2ecbd5d09", "text": "During nuclear decay, unstable nuclei transform into an energetically more stable configuration by emission of certain particles or energy.\n\nDifferent modes of nuclear decay exist, each with their own mode of reaching this energetically stable configuration (Table 2.1)."}
{"_id": "Radiology$$$57e9467f-1645-4d67-9ee8-6066f303b9cc", "text": "During nuclear decay, unstable nuclei transform into an energetically more stable configuration by emission of certain particles or energy."}
{"_id": "Radiology$$$e87e4d4f-3d45-40b8-ae9e-0d1da3e83d21", "text": "Different modes of nuclear decay exist, each with their own mode of reaching this energetically stable configuration (Table 2.1)."}
{"_id": "Radiology$$$5607fbd0-95ca-46f0-a5b4-c98a6c856d03", "text": "The term nuclide refers to an atom characterized by the number of protons and neutrons present in the nucleus. Nuclides can be sorted according to their number of protons and neutrons in a chart of nuclides. In contrast to the well-known periodic table, a chart of nuclides organizes the currently known radionuclides according to the number of protons and neutrons in their nucleus. Furthermore, it summarizes basic properties of these nuclides, such as atomic weights, decay modes, half-lives, and energies of the emitted radiations [64, 65]."}
{"_id": "Radiology$$$5def2550-dfe2-4562-800d-bed4b4c5de0c", "text": "In 2018, the tenth version of the Karlsruhe chart of radionuclides was published, containing nuclear data on 4040 experimentally observed nuclide ground states and isomers [66]. As mentioned earlier, this chart organizes data of currently known radionuclides according to the number of protons and neutrons present in their nucleus (Fig. 2.13a). Stable nuclides are shown in black, while the colored boxes indicate the decay mode of each nuclide (Fig. 2.13c). Data on individual nuclides can be found in the individual nuclide boxes (Fig. 2.13b). When a single nuclide has different decay modes, it is represented by different sizes of triangles, representing the branching ratios for each decay mode (Fig. 2.13b, 226Ac). A nuclide box can also be subdivided into different sections with a vertical line (Fig. 2.13b, 135Cs). An undivided box refers to the ground state of a nuclide, while when subdivided, the right section corresponds to the ground state and the subsections on the left represent the nuclear isomers (nuclides with the same number of protons and neutrons in the nucleus, but a different energy). Nuclides with a black upper section in the nuclide box represent primordial nuclides, formed during the formation of terrestrial matter and still present on Earth due to their extremely long half-lives. For such nuclides, the upper section provides information on the isotopic abundance, while the lower section indicates decay modes and half-lives (Fig. 2.13b, 232Th) [66]. Radionuclide charts are available in printed or online versions.\n\nA schematic diagram and 2 charts. a plots number of protons versus number of neutrons for nuclides. b. A close-up view depicts certain examples of the nuclide box structure. c. The modes of radioactive decay are color-coded, such as atom, alpha, beta, and neuron particles.\n\nFig. 2.13\n(a) Schematic representation of the complete Karlsruhe radionuclide chart. (b) Detailed representation of different radionuclide boxes. (c) Different colors of boxes representing the different decay modes, from left to right: stable isotope, proton emission (p), alpha decay (\u03b1), electron capture or beta-plus decay (\u03b5 or \u03b2+), isomeric transition (IT), beta-minus decay (\u03b2\u2212), spontaneous fission (SF), cluster decay (CE), and neutron decay (n). [(Figure adapted from Soti et al., 2019) (licensed under CC-BY-4.0)]"}
{"_id": "Radiology$$$865e040e-de92-4e9c-955f-44f7ad6c408b", "text": "A schematic diagram and 2 charts. a plots number of protons versus number of neutrons for nuclides. b. A close-up view depicts certain examples of the nuclide box structure. c. The modes of radioactive decay are color-coded, such as atom, alpha, beta, and neuron particles."}
{"_id": "Radiology$$$6c95edfe-2c52-472f-86d0-f8d4623dce24", "text": "A chart of nuclides can be used to investigate decay chains and nuclear reactions of different radionuclides. By following the specific decay rules of each type of nuclear decay, complete decay chains can be obtained manually. In a similar way, the chart can be used to obtain different activation and reaction products of nuclear reactions [66]. In this way, this chart can be of great assistance to obtain information on nuclear decay chains and isotope stability. It can help with both planning of experiments and interpretation of results [64, 65] (Box 2.14)."}
{"_id": "Radiology$$$4d600ac4-55a1-4137-aab6-ef92dc4fcf67", "text": "A \u201cnuclide\u201d refers to an atom with a certain number of protons and neutrons in the nucleus.\n\nNuclides can be sorted based on their characteristics in a nuclide chart.\n\nA nuclide chart can be used to investigate nuclear decay chains of different radionuclides."}
{"_id": "Radiology$$$e73e69d0-f3ea-43e3-a7db-71b9935a5417", "text": "A \u201cnuclide\u201d refers to an atom with a certain number of protons and neutrons in the nucleus."}
{"_id": "Radiology$$$847fd3d2-8934-4a14-acd2-3d9c51c9003e", "text": "Nuclides can be sorted based on their characteristics in a nuclide chart."}
{"_id": "Radiology$$$58ae3936-f6f2-4153-8190-743c85d933e3", "text": "A nuclide chart can be used to investigate nuclear decay chains of different radionuclides."}
{"_id": "Radiology$$$b6535f7a-8ed6-4f5e-81e8-cefbc0e810b9", "text": "The pioneering experiments performed by Wilhelm Conrad Roentgen (1895), Henri Becquerel (1896), and Marie and Pierre Curie (1898 and 1911) showed the potential of different radioactive elements. Over the decades to follow, radioisotopes have been applied in various fields, including medicine and food industry. In this section, some of the most common applications of radioisotopes will be discussed."}
{"_id": "Radiology$$$b2758fa0-0bcd-4f2a-b416-d9e75a32d153", "text": "Radiometric dating is a technique used to date materials such as rocks or fossils, in which trace radioactive impurities were selectively incorporated when these materials were formed. The method compares the abundance of a naturally occurring \u201cparent\u201d radioactive isotope within the material to the abundance of its decay products (\u201cdaughter isotopes\u201d), arriving at a known constant rate of the decay process."}
{"_id": "Radiology$$$a9e1958d-1483-4758-9897-9ed2f3c6936d", "text": "Today, there are more than 40 different radiometric dating techniques based on different parent-daughter isotope pairs (each with a different half-life) that are useful for dating various geological materials and samples of biological origins. The relative amounts of the parent and daughter isotopes can be measured by different chemical and mass spectrometric techniques. Table 2.2 lists some of the most commonly used isotope pairs in radiometric dating.Table 2.2\nNaturally occurring radioactive isotopes commonly used in radiometric dating [67]\n\nRadioactive isotope (parent)\n\nDecay product (daughter)\n\nHalf-life (years)\n\nSamarium-147\n\nNeodymium-143\n\n106 billion\n\nRubidium-87\n\nStrontium-87\n\n48.8 billion\n\nRhenium-187\n\nOsmium-187\n\n42 billion\n\nLutetium-176\n\nHafnium-176\n\n38 billion\n\nThorium-232\n\nLead-208\n\n14 billion\n\nUranium-238\n\nLead+-206\n\n4.5 billion\n\nPotassium-40\n\nArgon-40\n\n1.26 billion\n\nUranium-235\n\nLead-207\n\n0.7 billion\n\nBeryllium-10\n\nBoron-10\n\n1.52 million\n\nChlorine-36\n\nArgon-36\n\n300,000\n\nCarbon-14\n\nNitrogen-14\n\n5715\n\nUranium-234\n\nThorium-230\n\n248,000\n\nThorium-230\n\nRadium-226\n\n75,400"}
{"_id": "Radiology$$$9c6331a7-c6c4-437a-a76d-057393cf01c1", "text": "One of the most well-known examples is the dating using radioactive 14C (half-life of 5730\u00a0years) formed by nuclear reactions in the atmosphere. The constantly produced 14C reacts with oxygen, leading to the formation of 14CO2. This radioactive form of carbon dioxide is absorbed by plants via photosynthesis and will eventually become incorporated into all living organisms through the food chain. Once an organism dies, its metabolism stops, halting the incorporation of 14C. Therefore, by knowing the characteristic half-life and the ratio of 14C to the total carbon content, the age of the sample can be determined. The same principle applies to dating with the potassium-argon pair, which is commonly used to estimate the age of rocks, volcanic layers around fossils, and artifacts [68]."}
{"_id": "Radiology$$$73573e40-5dad-49f7-ad1b-01d7efab7a84", "text": "Sterilization is the complete killing or removal of all living organisms from a particular location or material. Several methods can be used to achieve sterilization, each with their own benefits and limitations. Irradiation with gamma rays (from a cobalt-60 or cesium-137 source, with a dose of around 15\u201325\u00a0kGy) is often used for the sterilization of medical products and pharmaceuticals, including implants, artificial joints, blood bags, and ointments. Sterilization by radiation has several benefits, the most important of which is that it can be used on heat-sensitive items that cannot be sterilized by other common methods such as autoclaving. It is also safer and cheaper because it can be done after the item is packaged. The sterile shelf life of the item is then practically indefinite provided that the seal is not broken. Indeed, it is estimated that irradiation technologies are used to sterilize almost half of the global supply of single-use medical products."}
{"_id": "Radiology$$$11dda86c-4e01-4bd7-b37e-e5892c027e4b", "text": "The use of gamma rays is, however, not strictly limited to the medical world. By irradiating food, we can significantly reduce their microbial burden, depending on the dose delivered. This prolongs the shelf life of the food in cases where microbial spoilage is the limiting factor. Some foods, e.g., herbs and spices, are irradiated at sufficient doses (5\u00a0kGy) to reduce the microbial counts by several orders of magnitude; such ingredients do not carry over spoilage or pathogenic microorganisms into the final product. It has also been shown that irradiation can delay the ripening of fruits or the sprouting of vegetables. Insect pests can be sterilized (be made incapable of proliferation) using irradiation at relatively low doses. The use of low-level irradiation can also be used as an alternative treatment to pesticides for fruits and vegetables that are considered hosts to a number of insect pests, including fruit flies and seed weevils. Food irradiation is currently permitted by over 50 countries, and the volume of food treated is estimated to exceed 500,000 metric tons annually worldwide [69]."}
{"_id": "Radiology$$$bf90b474-3aec-4a47-89ce-4c5e92626098", "text": "Radioimmunoassays were first developed in the 1960s by Solomon Berson and Rosalyn Sussman Yalow for which they received the Nobel Prize in 1977. It was the first technique being able to determine hormone levels in blood. This type of in vitro assay can be used to measure the concentration of any antigen with very high sensitivity. To date, radioimmunoassays are among the most sensitive and specific laboratory tests employed by immunologists and other specialists. The general principle of an immunoassay is competition for binding to an antibody (Fig. 2.14). More specifically, the unlabeled antigen (sample) is incubated together with a fixed amount of the radiolabeled antigen and the antibody, resulting in competition between the unlabeled and labeled antigens for binding to the antibody. With increasing amounts of an unknown sample (unlabeled antigen), decreasing amounts of labeled antigen (tracer) will bind to the antigen [70]. The antibody\u2013antigen complexes are separated from the free antigen by precipitation using a secondary antibody or chemical solutions. The antibody\u2013antigen complexes are then measured in a scintillation counter. By running a set of standards, a standard curve is generated from which the concentration of the unknown sample can be calculated. The most commonly used radioisotopes for radioimmunoassays are iodine-125, iodine-131, and tritium (3H) [71] (Box 2.15).\n\nAn illustration depicts the mixing and incubating processes of the antibodies, antigens, and radiolabeled antigens. The free fraction has only antigens. The bound fraction has antigen-antibody complexes used to measure radioactivity.\n\nFig. 2.14\nGeneral principle of the radioimmunoassay (Created with BioRender)"}
{"_id": "Radiology$$$0038f368-8b4a-4aa2-8488-9087df7615b6", "text": "An illustration depicts the mixing and incubating processes of the antibodies, antigens, and radiolabeled antigens. The free fraction has only antigens. The bound fraction has antigen-antibody complexes used to measure radioactivity."}
{"_id": "Radiology$$$0aa7d0fd-9c3a-4bb9-a941-f5efdb5ca64a", "text": "Radioactive decay can be used as a natural clock to determine the age of different materials.\n\nThe strong ionizing ability of gamma rays, along with their high penetration range, can be used for the killing or reduction of microorganisms in different items, ranging from medical to food products.\n\nThe use of radioisotopes in immunoassays provides a very high level of sensitivity allowing the measurement of antigens in pictogram quantities."}
{"_id": "Radiology$$$5b9ce16b-3061-4cdf-b465-a6c707b45366", "text": "Radioactive decay can be used as a natural clock to determine the age of different materials."}
{"_id": "Radiology$$$ddddd21c-8d4a-4164-b012-f9e1889b6dc4", "text": "The strong ionizing ability of gamma rays, along with their high penetration range, can be used for the killing or reduction of microorganisms in different items, ranging from medical to food products."}
{"_id": "Radiology$$$6da4dec3-b6ee-477a-879a-9b5a089ec4b1", "text": "The use of radioisotopes in immunoassays provides a very high level of sensitivity allowing the measurement of antigens in pictogram quantities."}
{"_id": "Radiology$$$e20510a6-9c6f-4a21-9889-f8823dd26a72", "text": "In radionuclide therapy (RNT), radioisotopes are administered to patients with cancer or other medical conditions. Particles emitted from the isotopes will deliver cytotoxic levels of radiation to target sites within the human body, resulting in destruction of the targeted tissue (Fig. 2.15).\n\nA diagram depicts radiolabeled antigen as a key and cancer cells as lock. The radioactive substance enters the cell via a surface receptor and alters the nucleus and other cellular components.\n\nFig. 2.15\nSchematic representation of the mechanism of action of radionuclide therapy. The blue line represents the path of ionizing radiation (Created with BioRender)"}
{"_id": "Radiology$$$a6ea8ced-e771-4288-b97a-3635c1496053", "text": "A diagram depicts radiolabeled antigen as a key and cancer cells as lock. The radioactive substance enters the cell via a surface receptor and alters the nucleus and other cellular components."}
{"_id": "Radiology$$$8cc8b6ec-9a2b-4269-9146-755bddf72813", "text": "Three types of ionizing radiation can be used for radionuclide therapy (RTN), namely alpha and beta particles and Auger electrons (their most important characteristics are summarized in Fig. 2.16). The linear energy transfer (LET) and tissue particle range are the most important parameters to be considered for this type of therapy. Ideal therapeutic radionuclides have a short particle range so it only damages targeted tissue and a high LET so it deposits as much radiation as possible on its short path length. All of the above-listed particles fulfill these criteria to ensure lesion-specific damage.\n\nA schematic diagram presents the range and linear energy transfer of beta-emitting radionuclides, alpha-emitting radionuclides, and Auger electron-emitting radionuclides.\n\nFig. 2.16\nSchematic representation of the energy deposition of the ionizing radiation and tissue range of the different emission types used for targeted radionuclide therapy, being \u03b2\u2212, \u03b1, and Auger electron emitters (Created with BioRender)"}
{"_id": "Radiology$$$4ba2370b-a076-4830-9ce7-dfa051c32d0e", "text": "A schematic diagram presents the range and linear energy transfer of beta-emitting radionuclides, alpha-emitting radionuclides, and Auger electron-emitting radionuclides."}
{"_id": "Radiology$$$de14c767-296c-48bd-b3d7-e1591a5491cb", "text": "The major breakthrough for RNT was in 1946, when iodine-131 was first used for the treatment of thyroid cancer. In the following years, a large variety of other radionuclides were introduced for the treatment of different cancer types, palliation of bone pain due to metastases, and treatment of inflammatory processes such as rheumatoid arthritis [72]. This was followed by the development of the peptide receptor radionuclide therapy (PRRNT), utilizing low-molecular-weight radiolabeled peptides targeted at specific cell surface receptors which are very often upregulated on cancer cells. Lutathera\u00ae (177Lu-DOTA-TATE) was the first-in-class PRRNT drug to be formally approved (by the EMA in 2017 and the FDA in 2018) for the treatment of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). The initial success of Lutathera\u00ae led to the development of new radiopharmaceutical-based strategies for treating other cancer types. These include the PSMA-targeted radionuclide therapy for prostate cancer and radioimmunotherapy with nanobodies for glioblastoma (Table 2.3) (Box 2.16).Table 2.3\nExamples of radionuclides used for therapy (World Nuclear Association)\n\nRadioisotope\n\nHalf-life\n\nTherapeutic applications\n\nActinium-225\n\n10 days\n\nTargeted alpha therapy (TAT)\nProstate cancer\n\nBismuth-213\n\n46 min\n\nTAT\nLeukemia, cystic glioma, and melanoma\n\nErbium-169\n\n9.4 days\n\nArthritis pain relief in synovial joints\n\nHolmium-166\n\n26\u00a0h\n\nDiagnosis and treatment of liver tumors\n\nIodine-131\n\n8 days\n\nThyroid cancer treatment\nNonmalignant thyroid disorders\n\nIridium-192\n\n74 days\n\nHigh-dose-rate brachytherapy\nProstate, head, and breast cancer\n\nLead-212\n\n10.6\u00a0h\n\nTAT, alpha radioimmunotherapy, or PRRT\nMelanoma, breast, pancreatic, and ovarian cancer\n\nLutetium-177\n\n6.7 days\n\nImaging and therapy of multiple tumor types (e.g., endocrine, prostate)\n\nPhosphorus-32\n\n14 days\n\nPolycythemia vera treatment (excess red blood cells)\n\nRadium-223\n\n11.4 days\n\nTAT brachytherapy in the bone\n\nSamarium-153\n\n47\u00a0h\n\nPain relief of bone metastases from, e.g., prostate and breast cancer"}
{"_id": "Radiology$$$d8a10fe1-f85d-4bff-9c02-c521395d2e77", "text": "In radionuclide therapy (RNT), radioisotopes are used to treat cancer or other medical conditions by administration of radiation sources to patients.\n\nThree types of radioisotopes can be used for RNT, namely alpha and beta particles and Auger electrons.\n\nThe most important applications to date of RNT are iodine-131 for thyroid cancer, Lutathera\u00ae for neuroendocrine tumors, and PSMA-targeted RNT for prostate cancer."}
{"_id": "Radiology$$$958f9f9f-2a4b-4107-9cef-02ac0a31357d", "text": "In radionuclide therapy (RNT), radioisotopes are used to treat cancer or other medical conditions by administration of radiation sources to patients."}
{"_id": "Radiology$$$eb0e1d78-99d4-4fb7-bcce-f6a7a6889d58", "text": "Three types of radioisotopes can be used for RNT, namely alpha and beta particles and Auger electrons."}
{"_id": "Radiology$$$28436ba4-a9c4-4b01-b7bf-b40f443c2190", "text": "The most important applications to date of RNT are iodine-131 for thyroid cancer, Lutathera\u00ae for neuroendocrine tumors, and PSMA-targeted RNT for prostate cancer."}
{"_id": "Radiology$$$be6d34b7-ef7a-4842-a768-3c7d47e72d40", "text": "Nuclear imaging techniques such as positron-emission tomography (PET) and single photon emission tomography (SPECT) are noninvasive procedures, which make use of radiolabeled probes to examine biological processes on the cellular or molecular levels in vivo. These techniques enable 3D visualization, quantification, and characterization of the target (enzyme, receptor, transporter, protein aggregates, etc.) under investigation [73]. For these purposes, the compounds are labeled with a radioisotope, with a fairly short half-life (T1/2, min to days). Both PET and SPECT allow visualization and quantification of targets expressed in very low quantities (nano-to-femtomoles per milligram tissue) or detection of molecular aberrancies before phenotypical or morphological changes have occurred [74] (Fig. 2.17).\n\n2 models explain the SPECT and PET concepts for diagnostic purposes. a. SPECT uses a detector and collimator made of photons and crystals. PET uses coincidence detectors based on the annihilation reaction of orbital electrons and positrons in the nucleus.\n\nFig. 2.17\nComparison of the SPECT (a) and PET (b) imaging techniques used for clinical diagnostic (adapted with permission of Hicks and Hofman, 2012) [75]"}
{"_id": "Radiology$$$b99f4a34-59c5-486f-a48f-92dcd99b3126", "text": "2 models explain the SPECT and PET concepts for diagnostic purposes. a. SPECT uses a detector and collimator made of photons and crystals. PET uses coincidence detectors based on the annihilation reaction of orbital electrons and positrons in the nucleus."}
{"_id": "Radiology$$$d58be697-cc7c-4878-91cb-fbebbc6b15ff", "text": "SPECT makes use of the inherent decay properties of specific radionuclides, which decay with the emission of a photon (X-ray) (Hutton 2014)."}
{"_id": "Radiology$$$e2cb6283-1983-4c34-881a-cdfd8a8599c9", "text": "The nuclides of choice are those which emit electromagnetic rays in the energy range of 100\u2013200\u00a0keV. This is determined based on the absorption of the electromagnetic rays by the subject and the designated detector and is a trade-off between sensitivity and resolution. Low-energy rays are more easily absorbed by surrounding tissue (tissue not under investigation), leading to higher patient doses and less efficient detection. However, higher energy levels are not optimally detected (stopped) by the scintillation NaI crystals. Additionally, the half-life (T1/2) of the radionuclide should be tailored to the conducted experiment."}
{"_id": "Radiology$$$1e099396-0189-400e-b00b-16adf9497d92", "text": "A SPECT apparatus typically contains two cameras which rotate around the body of the patient and are focused on an area under investigation. The cameras contain a lead collimator to directionalize the incoming radiation. As such, only rays parallel to the holes of the collimator will reach the detector, and radiation coming from scatter or other tissues not under investigation will be absorbed less by the scintillation detector, leading to less interference in image reconstruction and in turn increase in the contrast and hence the resolution but decrease in the sensitivity significantly."}
{"_id": "Radiology$$$7ab77ec8-5e85-434a-b31e-503a099a2075", "text": "Compared to planar (2D) X-ray imaging, where the electromagnetic rays are projected on an imaging detector leading to reduced contrast of the tissue under investigation compared to the background, SPECT imaging provides a noninvasive 3D method to determine the accumulation of administered diagnostic radiopharmaceuticals [73]. The term tomography indicates the use of a combination of individual \u201cslices\u201d to generate a 3D image."}
{"_id": "Radiology$$$84af6de7-77d2-445e-ad7d-6aa676946a2a", "text": "The most widely used SPECT radioisotope, 99mTc, is metastable and decays via isomeric transition with emission of \u03b3-rays of approximately 140\u00a0keV with a T1/2\u00a0=\u00a06\u00a0h. Further, 99mTc is a radiometal that can be complexed by various chelators and can be incorporated into different ligands used in different investigations of a plethora of diseases (bone, heart, cancer, brain, liver). Another benefit of 99mTc is the cost and the ease of acquirement via a 99Mo/99mTc generator."}
{"_id": "Radiology$$$6f970055-1c51-45df-bccf-d27165562c9e", "text": "Frequently clinically used radionuclides are depicted in Table 2.4.Table 2.4\nSPECT radionuclides [73, 76]\n\nRadionuclide\n\nT1/2\n\nNuclear reaction\n\nMode of decay\n\nEnergy (keV)\n\n67Ga\n\n3.26 days\n\n67Zn(p,n)67Ga\n68Zn(p, 2n)67Ga\n\nEC (100%)\n\n93\n\n67Cu\n\n3 days\n\n68Zn(\u03b3,p)67Cu\n\n\u03b2\u2212 (100%)\n\u03b3 (52%)\n\n185\n\n299mTc\n\n6.06\u00a0h\n\n99Mo/99mTc-generator\n\nIT (89%)\n\n140\n\n111In\n\n2.83 days\n\n111Cd(p,n)111In\n112Cd(p,2n)111In\n\nEC (100%)\n\n245\n\n123I\n\n13.2\u00a0h\n\n123Xe/123I generator\n124Xe(p,pn)123I\n\nEC (100%)\n\n159\n\n201Ti\n\n73\u00a0h\n\n203Ti (p,3n) 201Ti\n\nEC (100%)\n\n69\u201380 (Hg X-rays)\n135 (9%)\n167 (27%)\n\nEC electron capture, IT internal transition, thermal neutron bombardment"}
{"_id": "Radiology$$$c1bb4bc0-1b77-4dc2-95c6-5f5bdf115494", "text": "PET probes generally consist of a pharmaceutical vector molecule, which carries a coupled radionuclide to the target. Because of the radioactive decay, only a low mass amount of the tracer needs to be administered to the subject. As such, pharmaceutical or toxicological effects are avoided. The radioactive decay further enables highly sensitive detection of emitted \u03b3-rays by a dedicated ring of detectors. PET allows to detect early molecular changes and follow-up of disease progression [74]. Typically, low atomic mass radioisotopes (C, N, O, F), with a rather short T1/2 of minutes to hours, are coupled to the pharmaceutical vector. Additionally, these radioisotopes are commonly found in different small molecules and biomolecules, so they can be incorporated without changing the chemical structure of the compounds. Advances in radiolabeling techniques are continuously increasing the radiochemical and -pharmaceutical space, which allows for a more robust and quicker radiolabeling [77]. PET is increasingly used in the drug development stream, as it enables examination of pharmacodynamics, drug-target interaction, and dose occupancy [78]."}
{"_id": "Radiology$$$fd43754d-32d4-42c9-a057-91c15f363459", "text": "Radionuclides with an excess of protons in their core will decay by conversion of a proton to a neutron with emission of a positron (\u03b2+, a positively charged electron) and a neutrino (\u03bd, a quasi-massless particle) over which the decay energy is distributed to fulfill the quantum mechanical rule of conservation of energy and angular momentum. Based on the kinetic energy obtained from the decay, the \u03b2+ particle will travel a short distance (positron range, up to 0.5 cm for 18F, 1\u20132 cm for 11C) and collides with an electron in the environment after which the masses of both are converted into energy in an annihilation event. Two \u03b3-ray photons of 511\u00a0keV are emitted back-to-back over an angle of approximately 180\u00b0. These two \u03b3-rays travel through the body and can be coincidentally detected by a ring of detectors (within a time interval of 10\u00a0ns), allowing to localize the imaginary \u201cline of response\u201d along which the annihilation event occurred. Many response lines can then be combined to determine the position of the PET radionuclide of which tissue concentrations can be derived. Compared to SPECT, thicker scintillation crystals are necessary to detect the higher \u03b3-ray energy of 511\u00a0keV. These detectors typically consist of bismuth germanate (BGO) or lutetium oxyorthosilicate (LSO) and are more expensive compared to NaI crystals used in conventional SPECT and gamma counting. Hybrid imaging techniques such as PET/MRI and PET/CT allow a combination of morphological and functional imaging, where molecular and anatomical changes can be detected simultaneously with high accuracy. State-of-the-art PET technology research is investigating total-body PET with increased sensitivity (up to 40-fold) compared to normal PET scanners [79]. The worldwide workhorse of PET imaging is a radiolabeled glucose derivative, 2-[18F]fluoro-2-deoxy-d-glucose ([18F]FDG), which visualizes the glucose metabolism and is hence taken up and trapped in organs with extensive glucose metabolism such as brain and heart and aberrant growth. Because of this, [18F]FDG can be applied in the diagnostic imaging of cancer, inflammation, cardiology, and neurology [80]. [18F]FDG differs from glucose by the replacement of the hydroxyl moiety by 18F at C-2. This has consequences for the metabolization process of [18F]FDG and is depicted in Fig. 2.18. Both glucose and [18F]FDG are taken up by glucose transporters (Glut) and processed by glycolysis. Hexokinase will phosphorylate the C-6 OH-moiety of both molecules. As this brings a negative charge to the molecules, they will remain trapped inside the cell. Glucose is then further processed to fructose-6-phosphate by glucose-6-phosphate isomerase on the C-2 OH-moiety, and further metabolization will yield pyruvate. As [18F]FDG lacks the C-2 OH-moiety, further metabolization will not take place and the molecule will remain trapped in the cell until decay (T1/2\u00a0=\u00a0109.7\u00a0min) of 18F to 18O, after which metabolization can resume.\n\nA set of reactions in a cell depicts the conversion of glucose to pyruvate and also F D G to F D G 6 phosphate, which inhibits the synthesis of glucose-6-phosphate isomerase.\n\nFig. 2.18\nMetabolization of glucose and its radioactive analogue [18F]FDG (Created with BioRender)"}
{"_id": "Radiology$$$bc993d27-538a-48a0-8a0a-739c07d9618b", "text": "A set of reactions in a cell depicts the conversion of glucose to pyruvate and also F D G to F D G 6 phosphate, which inhibits the synthesis of glucose-6-phosphate isomerase."}
{"_id": "Radiology$$$8a7b8074-cbe4-4f5d-aa49-e562f373b863", "text": "PET radiopharmaceutical development has been favored over investigation into SPECT tracers over the last years. PET omits the use of mechanical collimation, replacing it with electronic collimation, increasing detector efficiency 100-fold compared to SPECT. The spatial resolution of PET is also higher with less influence of scattered photons. Attenuation correction is more efficient, and the imaging contrast is also better compared to SPECT [81]. A disadvantage of PET is the cost and the availability of PET radioisotopes, which need to be generated in a cyclotron (except for 68Ga, which is generator based). Furthermore, the short T1/2 of routinely used PET isotopes (carbon-11, fluorine-18, nitrogen-13, oxygen-15) requires production by an in-house cyclotron [82, 83]."}
{"_id": "Radiology$$$21341380-7758-441a-b9b7-7b7635883471", "text": "Typical radionuclides, used for PET imaging, are listed in Table 2.5 (Box 2.17).Table 2.5\nPET radionuclides (Vermeulen et al. 2019)\n\nRadionuclide\n\nT1/2\n\nNuclear reaction\n\nMode of decay\n\nEnergy (MeV)\n\n11C\n\n20.4 min\n\n14N(p,\u03b1)11C\n\n\u03b2+ (100%)\n\n0.960 (\u03b2+ Emax)\n\n13N\n\n10.0 min\n\n16O(p,\u03b1)13N\n\n\u03b2+ (100%)\n\n1.199 (\u03b2+ Emax)\n\n15O\n\n2.0 min\n\n14N(d,n)15O\n\n\u03b2+ (100%)\n\n1.732 (\u03b2+ Emax)\n\n18F\n\n109.7 min\n\n18O(p,n)18F\n20Ne(d,\u03b1)18F\n\n\u03b2+ (97%)\nEC (3%)\n\n0.634 (\u03b2+ Emax)\n\n64Cu\n\n12.7\u00a0h\n\n64Ni(p,n)64Cu\n\n\u03b2+ (18%)\nEC (24%)\n\u03b2\u2212 (37%)\n\n0.653 (\u03b2+ Emax)\n0.3293\u20131.675\n0.5794\n\n68Ga\n\n67.6 min\n\n68Ge/68Ga-generator\n\n\u03b2+ (89%)\nEC (11%)\n\n1.899 (\u03b2+ Emax)\n0.227\u20132.821\n\n76Br\n\n16.0\u00a0h\n\n76Se(p,n)76Br\n\n\u03b2+ (55%)\nEC (45%)\n\n3.382 (\u03b2+ Emax)\n0.599\n\n82Rb\n\n1.3 min\n\n82Sr/82Rb-generator\n\n\u03b2+ (100%)\n\n3.378 (\u03b2+ Emax)\n\n86Y\n\n14.7\n\n86Sr(p,n)86Y\n\n\u03b2+ (32%)\nIT (68%)\n\n1.221, 1.545, 1.988 (\u03b2+1,2,3 Emax)\n0.433\u20131.920\n\n89Zr\n\n78.4\u00a0h\n\n89Y(p,n)89Zr\n\n\u03b2+ (23%)\nEC (77%)\n\n0.902 (\u03b2+ Emax)\n0.909\n\n124I\n\n4.2\u00a0days\n\n124Te(p,n)124I\n\n\u03b2+ (26%)\nEC (74%)\n\n2.138, 1.535 (\u03b2+1,2 Emax)\n602\n\nEC electron capture, IT isomeric transition"}
{"_id": "Radiology$$$e9a2fcb1-5cad-447f-a88a-133a741865fc", "text": "SPECT and PET are noninvasive imaging techniques that allow to functionally diagnose different pathologies, including cancer, neurodegenerative diseases, and cardiovascular aberrations.\n\nSPECT and PET make use of radiolabeled drugs to specifically target aberrantly expressed receptors, enzymes, etc.\n\nSPECT makes use of the inherent \u03b3- or X-ray decay of the used radioisotope, whereas the PET principle is based on the coincidental detection of the emission of 511\u00a0keV \u03b3-rays, resulting from the annihilation of a \u03b2+ and an electron.\n\nThe most frequently used SPECT radioisotope is 99mTc, which can be incorporated in a plethora of vector molecules.\n\nThe most widely used PET radiotracer is [18F]FDG, a radioactive glucose analogue."}
{"_id": "Radiology$$$d17c4eaf-b02a-46ae-8dc7-a86505468ab2", "text": "SPECT and PET are noninvasive imaging techniques that allow to functionally diagnose different pathologies, including cancer, neurodegenerative diseases, and cardiovascular aberrations."}
{"_id": "Radiology$$$fc5fd37c-a62e-4715-87e8-323c042a4d2c", "text": "SPECT and PET make use of radiolabeled drugs to specifically target aberrantly expressed receptors, enzymes, etc."}
{"_id": "Radiology$$$e713ee19-866b-437f-9e01-4b3889807220", "text": "SPECT makes use of the inherent \u03b3- or X-ray decay of the used radioisotope, whereas the PET principle is based on the coincidental detection of the emission of 511\u00a0keV \u03b3-rays, resulting from the annihilation of a \u03b2+ and an electron."}
{"_id": "Radiology$$$2333db2f-0a47-4566-9501-f53dfa1a08a8", "text": "The most frequently used SPECT radioisotope is 99mTc, which can be incorporated in a plethora of vector molecules."}
{"_id": "Radiology$$$a6a5b780-6cee-42da-898b-e6ec5e030935", "text": "The most widely used PET radiotracer is [18F]FDG, a radioactive glucose analogue."}
{"_id": "Radiology$$$2aa9b004-860f-419f-951e-67380a165575", "text": "Dose or absorbed dose is the mean energy imparted by ionizing radiation to a material."}
{"_id": "Radiology$$$16b18765-fd6c-4ad2-b702-7f5997c251b4", "text": "where dE is the mean energy imparted by ionizing radiation and dm is the mass of the material."}
{"_id": "Radiology$$$e1ffa455-390b-413a-a072-b874f073faec", "text": "The SI unit of dose is gray (Gy) and is defined as absorbed energy per unit of mass of tissue, given by one joule per kg. The old unit is rad, and the conversion is defined as 1\u00a0Gy\u00a0=\u00a0100\u00a0rad [84]."}
{"_id": "Radiology$$$2e674e7f-a3ad-4ef5-ad60-3700e224ff20", "text": "Dose rate is defined as the dose of ionizing radiation absorbed or delivered per unit time. It is measured in gray per hour."}
{"_id": "Radiology$$$51e144c1-a958-4eef-b220-aa0172cbe62e", "text": "The biological effect of a certain dose is dependent on its dose rate, known as the dose rate effect. The biologic effect of a given dose is reduced if the exposure time is extended, and so if the dose rate is lowered. This is due to repair of sublethal damage that occurs during long radiation exposure. It is also due to redistribution of cells in cell cycle and cell proliferation (see Chap. 5 for details)."}
{"_id": "Radiology$$$1a9d9a8a-cfa1-4d0f-af07-4debcbc29f15", "text": "On the contrary, inverse dose rate effect is observed when increased biologic effects of a given dose at lowering the dose rate occur. This only happens at a limited range of dose rates. This is attributed to progression of cells through the cell cycle and accumulation in the G2 cell cycle phase, which is a radiosensitive phase. Further lowering of the dose rate below this critical level leads to lowering of biologic effects as cells cross the G2 block and divide, leading to cell proliferation."}
{"_id": "Radiology$$$6415ce6a-5f29-4920-b9f9-db15aec044c4", "text": "Importantly, dose rate reduction has a differential effect between most tumors or early-responding normal tissues and late-responding normal tissues. Late-responding normal tissues are more sensitive to dose rate changes, like changes in fraction size in external beam radiotherapy [85]."}
{"_id": "Radiology$$$5411d3fe-87f9-4fb0-91d0-b6d5f65da5b5", "text": "The dose rate of environmental exposure is low (around 0.1\u00a0\u03bcGy/min). Clinically, the concept of dose rate is utilized in brachytherapy. Accordingly, there are different categories such as1.\nUltralow dose rate (ULDR)\u2014less than 0.4\u00a0Gy/h\n\u00a02.\nLow dose rate (LDR)\u20140.4\u20132Gy/h\n\u00a03.\nMedium dose rate (MDR)\u20142\u201312\u00a0Gy/h\n\u00a04.\nHigh dose rate (HDR)\u2014more than 12\u00a0Gy/h"}
{"_id": "Radiology$$$b864c50a-2235-46c7-9225-6bb85694392e", "text": "Ultralow dose rate (ULDR)\u2014less than 0.4\u00a0Gy/h"}
{"_id": "Radiology$$$cc5acf15-4817-488e-8e97-6dcf02fdd529", "text": "Low dose rate (LDR)\u20140.4\u20132Gy/h"}
{"_id": "Radiology$$$0319c4bd-b38a-4735-87ad-2c3d2b5a8c10", "text": "Low-dose-rate irradiation can be considered as an extreme form of fractionation."}
{"_id": "Radiology$$$d525e6ba-1546-460b-8f85-b205c3cae615", "text": "There is another entity called pulsed dose rate (PDR), which is used in brachytherapy. Dose and treatment time are prescribed for LDR, but radiation is delivered in a pulsed manner every 1\u20134\u00a0h in many small fractions. Contrastingly, in FLASH radiotherapy, an ultrahigh dose rate of more than 1,44,000\u00a0Gy/h is administered [86]."}
{"_id": "Radiology$$$8fd40e24-bf21-46dc-8b40-5cb50cdbe0e6", "text": "The biological effect will be explained in Chaps. 5 and 6 (Box 2.18)."}
{"_id": "Radiology$$$005b740b-41cb-495c-ac44-9131101a8db1", "text": "Dose or absorbed dose is the mean energy imparted by ionizing radiation to a material. The SI unit of dose is gray (Gy).\n\nDose rate is defined as a dose of ionizing radiation absorbed or delivered per unit time. The SI unit of dose rate is gray/hour."}
{"_id": "Radiology$$$572f2e6b-e123-4197-8670-e1b3def1dd9c", "text": "Dose or absorbed dose is the mean energy imparted by ionizing radiation to a material. The SI unit of dose is gray (Gy)."}
{"_id": "Radiology$$$5a535ea0-6830-4f3d-a238-6a3cad57c75b", "text": "Dose rate is defined as a dose of ionizing radiation absorbed or delivered per unit time. The SI unit of dose rate is gray/hour."}
{"_id": "Radiology$$$cb6e4331-0837-4eff-a78a-00ad598b471f", "text": "The interaction of radiation with matter or tissue is also influenced by the type of radiation. Some types of radiation produce different effects than others for the same amount of energy. This is because the pattern of dose distribution and the density of ionization events will be different. To account for these variations when describing human biological harm from radiation exposure, the \u201cequivalent dose\u201d is used. For example, for equal absorbed doses, neutrons may be 20 times as damaging as X-rays. The equivalent dose is the product of the absorbed dose averaged over the tissue or organ and the radiation weighting factor WR particular for the type and energy of radiation involved. It is based on the absorbed dose to an organ, adjusted to account for the effectiveness of the type of radiation [85, 87]:"}
{"_id": "Radiology$$$4fd19fe9-9d91-480a-923d-b4b39ed31a8a", "text": "(2.32)"}
{"_id": "Radiology$$$f03d577f-7647-45ed-a939-a5b424c02476", "text": "The SI unit of equivalent dose is sievert (Sv). The unit \u201crem\u201d (roentgen equivalent in man) is also still used. One rem is equivalent to 0.01\u00a0Sv."}
{"_id": "Radiology$$$fdc46b3f-f2b7-44df-b791-148dbfc77a04", "text": "The radiation weighting factors recommended by the ICRP are shown in Table 2.6.Table 2.6\nRadiation weighting factors (ICRP 103)\n\u00a0\nWR\n\nX-\u03b3-rays\n\n1\n\n\u03b2+\u2013\u03b2\u2212\n\n1\n\nProtons and charged particles\n\n2\n\nNeutrons\n\n5\u201320\n\n\u03b1-Particles\n\n20"}
{"_id": "Radiology$$$356aedf1-1d70-4ca2-bcf3-e5579588ca07", "text": "If a mixture of radiation types is used, the equivalent dose is the sum of the individual doses of the various types of radiation, each multiplied by the corresponding weighting factor:"}
{"_id": "Radiology$$$4551ff73-96e7-40f3-b3ae-1167f1a002b2", "text": "(2.33)"}
{"_id": "Radiology$$$bf98fcbd-705d-4cf7-a772-16d3828a539e", "text": "The effective dose is the addition of equivalent doses to all organs, each adjusted to account for the sensitivity of the organ to radiation. If a body is uniformly exposed to radiation, the probability of biological effects is assumed to be proportional to the equivalent dose. However, various tissues react to ionizing radiation in different ways and have different sensitivity to radiation. The ICRP has introduced the tissue weighting factor (WT), which represents the relative contribution of each tissue or organ to the total damage or \u201ceffect\u201d resulting from uniform irradiation of the whole body [85, 87, 88] (Table 2.7).Table 2.7\nTissue weighting factors (ICRP 103)\n\nTissue/organ\n\n2007 WT\n\nBone marrow\n\n0.12\n\nBreast\n\n0.12\n\nColon\n\n0.12\n\nLung\n\n0.12\n\nStomach\n\n0.12\n\nBladder\n\n0.04\n\nEsophagus\n\n0.04\n\nGonads\n\n0.08\n\nLiver\n\n0.04\n\nThyroid\n\n0.04\n\nBone surface\n\n0.01\n\nBrain\n\n0.01\n\nSalivary glands\n\n0.01\n\nSkin\n\n0.01\n\nRemainder tissues\n\n0.12"}
{"_id": "Radiology$$$fa9d4f19-0372-4295-90f3-60f338b2ec85", "text": "The effective dose is the product of the equivalent dose and the tissue weighting factor:\n\n (2.34)"}
{"_id": "Radiology$$$e3ac028e-7007-44bb-aa9e-97258bfbe4dd", "text": "Despite differences in the sensitivity of tissue due to age and sex of the person, for the purpose of radiation protection, the values for tissue weighting factors are taken as constants and are applicable to the average population. The effective dose is a calculated quantity and not a physical, measurable quantity."}
{"_id": "Radiology$$$5342fdd4-fde5-4215-b063-e882c335fe71", "text": "The effective dose is used to compare radiation exposure and risks between different radiation types and exposure modes and a total body exposure. According to the ICRP Publication 103, effective dose is to be used for \u201cprospective dose assessment for planning and optimization in radiological protection, and retrospective demonstration of compliance for regulatory purposes.\u201d"}
{"_id": "Radiology$$$8381066d-0afa-4658-81df-7ee4613867fa", "text": "Annual dose limits for occupational and public exposure are given in terms of the annual effective dose."}
{"_id": "Radiology$$$c0b562ae-2fe3-4a76-8964-a6608757c559", "text": "In case of external irradiation, the absorbed dose is delivered at the time of exposure. In the case of internal irradiation, when radionuclides are taken into the body, the total absorbed dose is distributed over time as well as to different tissues in the body. The dose rate falls depending on the half-lives of the radionuclides. The committed equivalent dose considers the varying time distributions of dose delivery. The committed equivalent dose is calculated as the integral over 50\u00a0years of the equivalent dose in each tissue after intake of a radionuclide [85, 87]."}
{"_id": "Radiology$$$4c66ca56-5aea-4808-b358-358947080e61", "text": "This is the sum of the committed equivalent dose to the individual tissues or organs multiplied by their respective WT."}
{"_id": "Radiology$$$0bc561b9-9f3e-4bd8-8ff5-b7a4cef1a858", "text": "The radiation doses discussed above relate to exposures of individuals. The collective equivalent dose is used to measure the total impact of a radiation exposure to a group or population. The collective equivalent dose is the product of the average equivalent dose to a population and the number of persons exposed. It is measured in man-sievert (man-Sv)."}
{"_id": "Radiology$$$5ca9c25f-e76e-4308-8611-dd00cc108d49", "text": "The collective effective dose allows a rough estimation of the potential health risks to a population after exposure to radiation. It is the product of the average effective dose to a population and the number of persons exposed. It is measured in man-sievert (man-Sv)."}
{"_id": "Radiology$$$9fb222d5-b256-458c-93a3-7ed245bbff7b", "text": "If a population is exposed to internal exposure by radionuclides, the integral of the effective dose over 50\u00a0years is called the collective committed effective dose. It is measured in man-sievert (man-Sv) (Box 2.19)."}
{"_id": "Radiology$$$32005074-ba31-4bfb-a345-9cfe12e9b665", "text": "The effective dose is the product of the equivalent dose and the tissue weighting factor. The SI unit of effective dose is sievert (Sv).\n\nThe equivalent dose is the product of the absorbed dose averaged over the tissue or organ and the radiation weighting factor WR. The SI unit of equivalent dose is sievert (Sv)."}
{"_id": "Radiology$$$fa35f854-b06a-4c34-a706-1cd253a96709", "text": "The effective dose is the product of the equivalent dose and the tissue weighting factor. The SI unit of effective dose is sievert (Sv)."}
{"_id": "Radiology$$$880be399-488a-4731-abd8-12a452918313", "text": "The equivalent dose is the product of the absorbed dose averaged over the tissue or organ and the radiation weighting factor WR. The SI unit of equivalent dose is sievert (Sv)."}
{"_id": "Radiology$$$c1ad06cf-8160-43ea-a9e9-27b352168c5a", "text": "Ionizing radiation causes significant physical and chemical modifications, which eventually lead to biological effects in the exposed tissue. The amount of energy absorbed by the tissue (absorbed dose) and the rate at which such energy is deposited (dose rate and fractionation for clinical applications) play a critical role in determining the type and extent of the effects. However, other physical parameters can also affect the biological response. It is therefore necessary to introduce a radiation quality term to discriminate between different radiation types. Radiobiological data and models clearly point to the spatial distribution of energy deposition as a key radiation quality parameter. However, the stochastic nature of the interaction of radiation with matter prevents a comprehensive and unique description and measurements of the ionization patterns produced by the pathway of charged particles in matter. The alternative is, therefore, to define a suitable but inevitably incomplete characterization of radiation quality that will enable radiobiological predictions with sufficient accuracy."}
{"_id": "Radiology$$$b8ab555e-fbe9-4072-b56d-77ffa7a6de3e", "text": "The concept of linear energy transfer (LET), the amount of energy transferred per unit length, was introduced by Zirkle et al. [89] to account for the density of energy transfer occurring along the track of charged particles, including excitations and ionizations, until the particles reach the end of their range. LET values are generally reported in keV/\u03bcm. The symbol LET\u221e (unrestricted LET) is used when all possible energy transfers are included, and also the energy deposition by particles that in principle exit the volume of interest. The LET\u221e is numerically equivalent to electronic stopping power, i.e., the energy loss by the incoming particle (which may be a primary or a secondary particle) without any restrictions in energy and range. The formula for the electronic stopping power contains a negative sign as it is seen as the slowing force acting on charged particles, due to interaction with matter, resulting in loss of particle energy:"}
{"_id": "Radiology$$$e4b23b0f-8cd6-4bc6-9a1a-c3aa87deeb9b", "text": "(2.35)"}
{"_id": "Radiology$$$406ef9ba-2d5d-461d-8603-f8e43a5c4ccf", "text": "where S(E) is the stopping power, dl is the distance traversed by the particle, and dE is the mean energy loss due to collisions with energy transfers."}
{"_id": "Radiology$$$5c4ca404-dc3f-4c12-a56a-600eb8b51f8c", "text": "There is however a conceptual difference: the stopping power deals with the energy loss of the particle, while the LET\u221e focuses on the energy deposition in the medium, and thus, the LET generally has an opposite sign. For large volumes, the electronic stopping and the LET\u221e coincide (same absolute value), as for large volumes all the energy loss by the impacting particles is well likely deposited in the sample."}
{"_id": "Radiology$$$c08bb4e2-11ce-439c-aed1-6e940ebcfa83", "text": "In radiobiology, the concept of \u201crestricted LET\u201d is mostly used. This is the locally transferred energy per unit length, with \u201clocally\u201d restricting to only the energy fraction, which leads to ionizations and/or excitations within the considered site. The remaining kinetic energy of particles leaving the site is excluded. This is particularly relevant for electrons since they may possess considerably long ranges. For example, for ions with E\u00a0>\u00a01000\u00a0MeV/\u03bc, these electrons can have energies higher than 1 MeV. The lateral spread of the track is usually 100\u00a0s of nm, but for higher energies of the ions such as 1000\u00a0MeV/\u03bc, this lateral spread can even be 1 cm."}
{"_id": "Radiology$$$c5f35964-367e-4439-885c-90cc85a96caf", "text": "According to the ICRU 1970, the linear energy transfer of charged particles in a medium is the quotient of dE by dl. Here, dE is less than some specified value \u0394. The definition includes an energy cutoff rather than a range cutoff as this is of more practical use:\n\n (2.36)"}
{"_id": "Radiology$$$8bc7fc7b-c5e8-4ef1-bf67-65ac568b51dc", "text": "It has become customary to specify a limit of energy deposition below which the deposition is considered to be local (energy restriction); 100\u00a0eV has been widely accepted, which corresponds to an electron range of about 5 nm. Electrons of longer ranges are called \u201c\u03b4 electrons\u201d or \u201c\u03b4 rays.\u201d"}
{"_id": "Radiology$$$60c5a161-4dba-4b9f-902c-e34e83df6d32", "text": "X-rays and gamma rays are considered low LET (sparsely ionizing) radiation types, while high-energetic protons, neutrons, and heavy charged particles are considered as high LET (densely ionizing) radiation. A proton can have high or low LET, depending on its energy. Although commonly high-energy protons have been considered low LET radiation, recently this has been questioned, starting a new \u201cparadigm in radiation biology\u201d [90]. For indirectly ionizing neutrons, LET refers to that of the secondary charged particles they produce. The value which is generally considered to mark the distinction between low and high LET is about 10\u00a0keV/\u03bcm."}
{"_id": "Radiology$$$159c1432-3b88-4061-9fa0-1c768914ad89", "text": "As ionizing particles decelerate along their track, the LET decreases, leading to a LET distribution, and consequently two different LET average concepts can be defined. The \u201ctrack average LET\u201d is calculated by performing a weighted average considering the proportion of the total track length that is within specified LET intervals and assigning equal statistical weight to each unit of the track length. On the other hand, the \u201cdose average LET\u201d is a weighted average of the LET values taking into account the proportion of the energy that is deposited for each LET interval so equal statistical weight is assigned to each unit of the energy deposition. In the first approximation, the dose-averaged LET is more suitable as the radiation quality factors are based on such quantity."}
{"_id": "Radiology$$$5356beea-aad5-415d-8bef-c1a304d8cdde", "text": "Apart from ionizations and excitations, among which ionizations bring the highest contribution to electronic stopping over a wide range of energies [91], other mechanisms cause energy loss of the impinging particle and thus induce deposited energy. At energies below some few keV/\u03bcm of the traveling ion, also nuclear collisions can occur. Such elastic nuclear collisions (described by the concept of nuclear stopping), which cause displacement of atoms, can induce alteration and breaking of bonds, and thus also contribute to biological damage. For particles with high energy, inelastic nuclear collisions, where the impacting particle causes fragmentation of the nuclei generating daughter nuclei with emission of several secondary particles, can also occur. These loss mechanisms are not described by the concept of stopping. A significant loss of primary beam fluence is caused by such nuclear reactions. The inelastic nuclear cross section determines the number of particles left at a certain depth. For instance, for protons hitting a water target with an energy of 160\u00a0MeV, at the Bragg peak position, approximately 20% of the incident protons will be lost [92]."}
{"_id": "Radiology$$$4a261583-941d-4380-ac04-e487479ae96c", "text": "The Bragg curve represents the energy loss, in this case electronic stopping or LET, as a function of the distance through a stopping medium. The energy loss is characterized primarily by the square of the nuclear charge, Z, and the inverse square of the projectile velocity, \u03b2. This gives the Bragg curve its familiar shape, peaking at very low energies (Bragg peak), just before the projectile stops (Fig. 2.19). The stopping of charged particles increases with decreasing ion energy; in particular, around the Bragg peak, the stopping (or the LET) is maximum, near the very end of the particle\u2019s range. Ions of the same specific energy (energy per nucleon) have a similar range, typically on the order of 10\u00a0\u03bcm at ~1\u00a0MeV/\u03bc up to 1 mm at ~100\u00a0MeV/\u03bc [25].\n\nA line graph plots dose in arbitrary units and linear energy transfer in kiloelectron volts per micrometer versus depth. 5 lines follow a left-skewed trend, with the peaks at 50, 100, 150, 200, and 250 mega-electron volts, respectively. 5 dashed lines follow an increasing trend along the peaks.\n\nFig. 2.19\nDose and LET distribution for proton beams of various energy in water (simulated using TOPAS MC)"}
{"_id": "Radiology$$$26dbdcef-077e-452d-8a09-1888faec6ebc", "text": "A line graph plots dose in arbitrary units and linear energy transfer in kiloelectron volts per micrometer versus depth. 5 lines follow a left-skewed trend, with the peaks at 50, 100, 150, 200, and 250 mega-electron volts, respectively. 5 dashed lines follow an increasing trend along the peaks."}
{"_id": "Radiology$$$46f48704-9813-42fa-944e-9d99f371f3f5", "text": "Sparse energy deposition events along the track of a particle per unit of energy deposited appear to be less biologically damaging than \u201cdense\u201d deposition. The value of the LET that seems \u201coptimal\u201d for cell killing is in the range of 100\u00a0keV/\u03bcm. This is linked to the fact that the average separation of ionization events at this LET is about the same as the diameter (2\u00a0nm) of the DNA double helix, implying a higher probability of DSB, from the passage of a single particle. Clusters of lesions in the DNA molecule play a key role in biological damage [93] (Box 2.20)."}
{"_id": "Radiology$$$64ad3f38-3a74-4f22-bfd7-00350b7d2d6c", "text": "LET is a parameter that quantifies the amount of transferred energy per unit length.\n\nLET is reported in units of keV/\u03bcm.\n\nLET increases with the ion mass and with decreasing ion energy."}
{"_id": "Radiology$$$78a17d78-361b-47f6-82d8-5d52a0fd0740", "text": "LET is a parameter that quantifies the amount of transferred energy per unit length."}
{"_id": "Radiology$$$41124fbb-5da8-4ffd-b5d6-b5389c5c388d", "text": "LET increases with the ion mass and with decreasing ion energy."}
{"_id": "Radiology$$$ec6eb0cb-1873-4fda-a7a8-fd926365e7fd", "text": "There is an intrinsic relationship between the quantities in dosimetry, e.g., absorbed dose (see Sect. 2.5), linked to the electronic stopping power, and quantities at the microscale and down to the nanoscale."}
{"_id": "Radiology$$$28545ab6-1c27-4e5b-b5af-bebc54e6ae33", "text": "The study of the pattern of energy deposition at micrometer length scale is called microdosimetry [94]. In particular, microdosimetry studies the fluctuations and pattern of energy deposition in a micrometer-sized target, providing a comprehensive view of the energy deposition more detailed than the one given just by the LET alone. The measured spectra are distributions of energy depositions in the microscopic volume, which are a combination of several stochastic processes including the LET distribution, the track length distribution, the energy loss straggling (statistical fluctuation of energy loss along the particle track) of the primary particles, and the transport of energy by \u03b4-rays [95]. Microdosimetric quantities are stochastic and therefore given in terms of particle interaction probabilities [95, 96]. The relevant quantities in microdosimetry are as follows:\ny: the lineal energy, which is defined as the energy imparted to matter in the microscopic volume by a single event divided by the mean chord length in that volume and the mean length of randomly oriented chords in a given convex volume\n\nf (y): the probability distribution of linear energy\n\n\n\n: the first moment of f (y), also called the frequency mean lineal energy\n\ndy\u00a0=\u00a0yf (y)/\n\n: the dose distribution, which is important for obtaining the dose components of the microdosimetric spectrum\n\n\u2022 \n\n: the first moment of d (y), also called the dose mean lineal energy"}
{"_id": "Radiology$$$f1104da6-d4d4-4cd9-a03c-39a8edabf0d5", "text": "y: the lineal energy, which is defined as the energy imparted to matter in the microscopic volume by a single event divided by the mean chord length in that volume and the mean length of randomly oriented chords in a given convex volume"}
{"_id": "Radiology$$$7a6ee243-c234-423e-aa89-36c76dd0fad6", "text": ": the first moment of f (y), also called the frequency mean lineal energy"}
{"_id": "Radiology$$$8f853bc0-68a1-44f0-9f7b-748969924cf8", "text": "dy\u00a0=\u00a0yf (y)/\n\n: the dose distribution, which is important for obtaining the dose components of the microdosimetric spectrum"}
{"_id": "Radiology$$$b7ce53d0-90f5-4834-b308-ba1a125904dc", "text": "\u2022 \n\n: the first moment of d (y), also called the dose mean lineal energy"}
{"_id": "Radiology$$$6dac3aa0-80fa-439f-86b9-7939d6f0c744", "text": "Relative biological effectiveness (RBE) is a method to quantify and compare the biological damage of different types of radiation [97]. The RBE is a dimensionless quantity and can be described as a radiation quality index with regard to biological damage. Quantitatively, RBE is the ratio between the absorbed dose of a reference radiation type and the absorbed dose of the radiation type of interest, such that both the absorbed doses compared produce the same amount of a biological effect, known as isoeffect. The reference radiation is defined as a low LET radiation. Previously, the standard radiation used was 250\u00a0keV of X-ray; however, nowadays, it is more common to use as standard 1 MeV photons (from a cobalt-60 source). This means that RBE is 1, when cobalt-60 biological effect is compared with itself."}
{"_id": "Radiology$$$17699e61-c957-42a1-bf87-f3f10c7dee18", "text": "RBE guides in the selection of the weighting factors, which are required to define the effective dose (E) (Sect. 2.5). RBE varies with several factors described in detail later, namely LET, radiation dose, fractionation, dose rate, biological system, endpoint measured, and radiation quality."}
{"_id": "Radiology$$$f02d2428-df17-4c15-b300-6ddc1f5ee1f5", "text": "(2.37)"}
{"_id": "Radiology$$$34b52e95-278c-4ea0-9f76-c2bbc834ff21", "text": "Over the past decades, radiobiology and nanodosimetry studies have pointed out that the characteristic spatial distribution of energy deposition at the subcellular scale induced by different particles at different speed is a key aspect at the origin of the RBE of different radiation qualities [91]. Localized clusters of energy deposition within the DNA molecule play a critical role. The frequency and topological distribution of clustered lesions determine the effectiveness of the DNA repair mechanisms. Isolated lesions are more efficiently repaired, while for complex lesions, errors are more likely to occur in the repair, often leading to permanent damage [98]. One of the main aims of the radiation community is to develop models for the radiation quality factors, the RBE and cell survival, which are consistent with nanodosimetry. Several efforts have been done recently to (a) develop biologically relevant quantities based on nanodosimetry [99], in order to overcome the simplistic description of the quality factor as a (continuous) function of the sole LET; (b) develop new quality factors incorporating a formula that relates to densely and sparsely ionizing components of the radiation tracks and core track contributions and penumbra contributions [13]; (c) develop an RBE based on a radiation quality descriptor depending on energy deposition clustering [100]; (d) develop a cell damage/survival model based on the interactions between lesions at both the nanometer and micrometer scale [101]; and (e) perform a detailed analysis of the radial distribution of ionization cluster size distribution [102]."}
{"_id": "Radiology$$$b8d396ba-1d9d-4353-aa99-edfec9bb041b", "text": "Prediction of radiobiological response is a major challenge in radiotherapy. Survival curves allow to determine the radiosensitivity of a cell line to different types of radiation, as well as to compare the response of one different cell type to one type of radiation. The linear-quadratic (LQ) model has been best validated by experimental and clinical data and describes the surviving fraction (SF) of cells as a function of radiation dose D: SF (D)\u00a0=\u00a0e\u2212\u03b1.D\u00a0\u2212\u00a0\u03b2D2. It allows determining important biological parameters such as the survival fraction or the ratio \u03b1/\u03b2, which represents the intrinsic radiosensitivity. Cells with a higher \u03b1 and \u03b2 are more sensitive to radiation. The shape of the curves depends on the LET. Indeed, cells irradiated with the same dose of different LET induce different biological effects translated into different cell survivals. As the LET increases, the slope of the curve becomes steeper and straighter with less shoulder. This indicates a higher ratio of lethal to potentially lethal lesions or a less efficient repair of the high LET radiation damage. For the LQ representation, this is shown by a higher \u03b1/\u03b2 ratio for high LET radiation. However, the lower the \u03b1/\u03b2 ratio is (high \u03b2 relative to \u03b1), the more curved the clonogenic curve is."}
{"_id": "Radiology$$$19ada5d4-754a-4e37-8578-4d1bae216453", "text": "Although the LET is a common and useful parameter to quantify the distribution of absorbed radiation energy, there are considerable limitations, which need to be considered. The limitations in terms of using the LET for predicting biological effects are strongly related to the RBE models and have been discussed in previous sections. There are also caveats of more physical nature. In particular, LET measurements are complex, difficult to relate to clinical or radiobiological setups, and affected by several constraints particularly if LET distributions are to be reported rather than single LET values. Direct measurements of dE/dl can be attempted with very thin particle detectors (such that multiple interactions within the active volume rarely occur) with high-energy resolution and able to discriminate between secondary particles and photons. In this case, the energy loss (\u0394E) by a particle passing through is related to the thickness of the detector (\u0394l). Ideally, detectors with different thickness would be employed and the energy detected plotted against the detector thickness from which the slope at the origin is extrapolated. The density of the sensitive material of the detector should also be considered to convert the measurements into water. This provides an estimation of the stopping power and therefore the LET\u221e. The development of several Monte Carlo-based codes has offered the possibility to quickly calculate LET values taking also into consideration the specific experimental settings."}
{"_id": "Radiology$$$70b05f34-629b-4020-be20-76c0f2775fef", "text": "The definition of the LET concept also implies that an average LET value may not always be adequate to describe the radiation quality to which biological samples are exposed. As mentioned, the LET changes significantly along the path of an individual charged particle and it is affected by the specific irradiation setup including any scattering conditions. Single LET values are suitable for \u201ctrack segment\u201d experiments where thin biological samples are exposed to mono-energetic charged particle beams. Even under such conditions, however, the energy loss by a charged particle over a cellular distance fluctuates and it can occasionally reach extreme high or low values, which are not well accounted for in an averaging process. Also, the angular deflection and the lateral extension of the particle tracks due to the finite range of \u03b4-rays are in principle not taken into account in the LET concept. The restricted LET, which only includes energy transfer below a specified cutoff, can actually partially take into account the second point. However, a set of LET distributions that belong to different cutoff values would be needed, but still little information about the actual structure of particle tracks would be gained [103]. A quantitative evaluation has shown that the LET concept is quite inadequate for electrons; there are no sites sufficiently small to disregard the finite range of the electrons and simultaneously sufficiently large to disregard the lateral escape of \u03b4-rays and the energy loss straggling [103]."}
{"_id": "Radiology$$$bf428058-6fc5-45bb-b1d6-477892442d5b", "text": "Contrarily, for heavy ions, there are site sizes and particle energies for which the LET predicts adequately the energy deposition. LET increases approximately as the square of the ion charge, Z, and the inverse square of its velocity, v. On the other hand, the maximum range of the \u03b4-ray electrons depends on the velocity of the particle but not its charge. Thus, the consideration of the sole LET of a particle is not sufficient for a description of the particle\u2019s track structure, as two particles of identical LET but very different velocity and charge will have very different track structures [104]."}
{"_id": "Radiology$$$1d8f298f-35af-4877-8620-f934fbae6a9c", "text": "RBE increases as LET increases, up to a maximum LET value of about 100\u00a0keV/\u03bcm, and then decreases as LET increases (Fig. 2.20\u2014RBE and LET) [97]. In general, high LET radiations allow the deposition of a given amount of energy over a shorter distance, being more efficient in producing biological effects than low LET radiations. In other words, low LET radiation creates sparse ionization, requiring more than one radiation track to pass through the cell and induce lethal biological damage, while high LET radiation is more effective, since one radiation track through the cell is enough to induce lethal biological damage. However, over 100\u00a0keV/\u03bcm, there are many \u201cwasted\u201d ionizations due to the very high ionization densities (number of ions per unit of path length). This phenomenon is the so-called overkilling and reflects the RBE declining for further increases in LET, for which biological effect is reduced since most of the energy is wasted.\n\nA line graph of R B E versus L E T plots a curve of low L E T, high L E T, and overkill. A line begins near the origin, increases gradually at the low L E T region, reaches a peak at 100 kiloelectron volts per micrometer at the high L E T region, and declines at the overkill region.\n\nFig. 2.20\nRBE variation with LET. RBE increases as LET increases, up to a maximum LET value of about 100\u00a0keV/\u03bcm. An \u201coverkilling\u201d effect is observed for higher LET values (Created with BioRender)"}
{"_id": "Radiology$$$20845506-3aa8-4732-8c88-ba87e6a05016", "text": "A line graph of R B E versus L E T plots a curve of low L E T, high L E T, and overkill. A line begins near the origin, increases gradually at the low L E T region, reaches a peak at 100 kiloelectron volts per micrometer at the high L E T region, and declines at the overkill region."}
{"_id": "Radiology$$$669983b3-ba11-42f6-bbfd-9b6dce3572dd", "text": "When determining RBE, it is important to understand that RBE values also depend on the radiation dose and, consequently, on the isoeffect level chosen for the comparison between radiation types [97]. For small radiation doses, RBE is particularly variable tending to increase. This is explained by the fact that at low doses, the difference in the biological damage induced by low and high LET radiation is huge; that is, high LET radiation is very effective in killing cells, while low LET radiation is ineffective in doing so. For high radiation doses, the difference between the effects induced by low and high LET radiation becomes smaller, considering that low LET radiation becomes more lethal. At very high doses, the RBE no longer depends on the dose."}
{"_id": "Radiology$$$b9025329-48cf-451b-9842-237a1f50bb93", "text": "The shape of the cell survival curve determines the presence or absence of a fractionation effect. With repeated daily low-dose X-ray fractions, the shoulder curvature is repeated, and cell survival is increased relative to a single high-dose radiation fraction at equal total dose. As mentioned previously, the bending of the cell survival curve is described by the \u03b1/\u03b2 ratio parameter of the LQ model equation. The principle of fractionation is the repeat of the shoulder of the cell survival curve. The broader the shoulder, the lower the \u03b1/\u03b2 ratio and the higher the cell survival in fractionated irradiation, i.e., the higher the sparing effect. In other words, the straighter the curve is, the less the fractionation effect is. The cell survival curve of high LET irradiation such as alpha particles is a straight line (e.g., Fig. 2.22); hence, the effect of fractionation is lost. Fractionation of carbon ions does not influence its biological effectiveness."}
{"_id": "Radiology$$$e7a007ed-aa4d-4703-ba70-4dbe0ae3c499", "text": "The same effect is seen when the dose per fraction is reduced in vivo. While low LET X-ray irradiation shows\u2014related to the \u03b1/\u03b2 ratio of the LQ model\u2014sparing effect with multiple low dose fractions, high LET irradiation does not show such typical fractionation sparing effect, as illustrated in Fig. 2.21 [105]. Figure 2.21 (left) shows large sparing, and thus an increased tolerance to low LET irradiation, for late-responding normal tissues (with a low \u03b1/\u03b2 ratio such as the spinal cord and kidney) with decreasing dose per fraction, while early-responding normal tissues (e.g., jejunum) and tumors (e.g., fibrosarcoma), both characterized with a high \u03b1/\u03b2 ratio in the LQ model, are marginally spared. With high LET neutron irradiation, very little normal tissue sparing of fractionation has been demonstrated (Fig. 2.21, right), neither for early-responding normal tissues and tumors nor for late-responding normal tissues. The current view is to use at least two high LET fractions to obtain some sparing and benefit from reoxygenation, but multiple fractions would not be further beneficial [106] (Box 2.21).\n\n2 multi-line graphs plot total dose for several isoeffects versus dose per fraction for low L E T and high L E T. The values are plotted for late and acute responding tissue in various organs. 1. The late line for skin has the highest value. 2. The acute line for skin necrosis has the highest value.\n\nFig. 2.21\nIsoeffect curves as a function of total dose and the number of fractions for low LET X-rays or gamma rays (left) and high LET neutrons (right). See insert for explanation of symbols and curves. [Redrawn from Withers et al. [105] with permission]"}
{"_id": "Radiology$$$9186b89a-18f8-4c5c-9cc3-aa57d7553de8", "text": "2 multi-line graphs plot total dose for several isoeffects versus dose per fraction for low L E T and high L E T. The values are plotted for late and acute responding tissue in various organs. 1. The late line for skin has the highest value. 2. The acute line for skin necrosis has the highest value."}
{"_id": "Radiology$$$bdaef29b-16bc-407c-9806-441d332366cc", "text": "The higher the LET, the straighter the radiation\u2013cell survival relationship, and the lower the sensitivity to dose fractionation.\n\nThe RBE of high LET irradiation decreases with increasing dose or dose per fraction for both cells and tissues.\n\nLittle normal tissue sparing after fractionated high LET irradiation: Few fractions are sufficient."}
{"_id": "Radiology$$$ebc62e2a-7dda-4b7e-8f46-7396ac95a87c", "text": "The higher the LET, the straighter the radiation\u2013cell survival relationship, and the lower the sensitivity to dose fractionation."}
{"_id": "Radiology$$$0640672f-c5fb-4e18-ac62-90580e6dc4f9", "text": "The RBE of high LET irradiation decreases with increasing dose or dose per fraction for both cells and tissues."}
{"_id": "Radiology$$$23f110e6-662c-4217-9c50-ff8d614e8136", "text": "Little normal tissue sparing after fractionated high LET irradiation: Few fractions are sufficient."}
{"_id": "Radiology$$$1edd82c5-9bf6-4ac4-891f-364a7feaffab", "text": "The dose rate is defined as the ratio of the radiation dose [Gy] to the duration of the radiation exposure [hour]. The spectrum of dose rates used in radiation oncology is broad: from low dose rate (LDR\u00a0<\u00a02\u00a0Gy/h) to ultrahigh dose rate (FLASH, >144.000\u00a0Gy/h). The dose rate of radiation exposure largely determines its RBE. Lowering the dose rate reduces the effectiveness of radiation in many ways. In terms of the 6 Rs of radiobiology, the dose rate affects the induction and repair of DNA damage and related clonogenic cell survival, cell cycle (re-)distribution and activation of cell cycle checkpoints, and cell repopulation and reoxygenation and likely influences the immune response as well. For a particular equal biological effect, a biological endpoint, lowering the dose rate relative to a reference radiation quality (usually high-dose-rate 250\u00a0keV X-rays), the RBE decreases (Fig. 2.22). The dose rate effect could also be defined with the dose reduction factor (DRF), also termed the dose recovery factor. The DRF indicates the ratio of the radiation dose to achieve an equal biological effect at specified dose rate and the dose at high dose rate. The term DRF is used by analogy with the dose enhancement factor or sensitizer enhancement ratio, to quantify a change toward steeper cell survival curves. With increasing dose rate, the DRF value is >1.\n\nA multi-line graph of surviving fraction versus dose plots the curves for no repair, 150 centigray per minute, 7.6 centigray per minute, 1.6 centigray per minute, and full repair. 5 lines begin at (0, 1) and follow decreasing trend.\n\nFig. 2.22\nEffects of the dose rate on clonogenic cell survival for a human melanoma cell line irradiated at dose rates of 1.6, 7.6, and 150\u00a0cGy/min. At equal biological effectiveness, e.g., 0.01 cell survival (broken line), high-dose-rate irradiation has larger relative biological effect than low-dose irradiation, resulting in a dose reduction of approximately 5\u00a0Gy, i.e., a DRF of 1.6 (12.8/7.7). Dotted lines: (A) no repair; (B) condition of full repair at infinitely low dose rate. (Figure adapted from Steel [107], with permission)"}
{"_id": "Radiology$$$9f7f4c98-af6d-4091-a074-6d635e99f517", "text": "A multi-line graph of surviving fraction versus dose plots the curves for no repair, 150 centigray per minute, 7.6 centigray per minute, 1.6 centigray per minute, and full repair. 5 lines begin at (0, 1) and follow decreasing trend."}
{"_id": "Radiology$$$99fef41e-41e4-4199-9bd7-c708ae94a5dc", "text": "The increase in biological effectiveness with increasing dose rate applies to all tissues and organs and, importantly, discriminates between early-responding tumors and normal tissues and late-responding normal tissues. In late-responding normal tissues, characterized by a low \u03b1/\u03b2 ratio of the LQ model, the increase of dose rate is more detrimental than for tumors and early-responding normal tissues with a high \u03b1/\u03b2 ratio. Literature data show that, at ultrahigh dose rate in FLASH radiotherapy, this differential effect could be inverted [108]. This inverse effect could be explained by the oxygen depletion hypothesis, the DNA damage hypothesis, and the immune response hypothesis."}
{"_id": "Radiology$$$a2a4b008-9bc4-41cf-ba34-84c62c7329dd", "text": "Dose rate: radiation dose delivery per unit time (e.g., Gy/hour)\n\nDose rate effect: decrease in biological effectiveness with decreasing dose rate"}
{"_id": "Radiology$$$5fdf9513-70f6-4355-a0b7-f67a2d3eeaef", "text": "Dose rate: radiation dose delivery per unit time (e.g., Gy/hour)"}
{"_id": "Radiology$$$8c51b235-d59d-4303-b955-a1953bb7b9d7", "text": "Dose rate effect: decrease in biological effectiveness with decreasing dose rate"}
{"_id": "Radiology$$$392f76cd-0101-44db-9f6a-14b7328ab37d", "text": "During the last decades, many tissues and cells were characterized by survival curves in response to different types of radiation, especially X-rays. They underlined a great variation of the RBE for all the biological systems studied. Indeed, large variable shoulder regions were observed in response to X-rays, whereas less variation was observed with neutrons, explaining that the RBE is different for each cell line. In response to heavy ions, the depth of the irradiation has also to be considered and explains in part the different RBE calculated for one cell line compared with X-rays."}
{"_id": "Radiology$$$37845aa2-42f2-4c5c-bcf5-e4cc5acf4e2e", "text": "While the physical and dosimetric aspects of radiobiology are well understood, the biological aspects such as the complex biological endpoints induced need further attention. The current estimates of RBE listed above depend on the biological system, but also depend on the detection methods used as it has been demonstrated that DNA damage and the resulting apoptotic responses vary greatly depending on the radiation quality in a tissue- and dose-dependent manner. Experimental data emerging from recent studies suggest that, for several endpoints of clinical relevance, the biological response is differentially modulated by particles compared to photons. However, up to date, only few studies have been performed to understand the differential response on the molecular and cellular levels between different radiation qualities."}
{"_id": "Radiology$$$e95bb288-982d-42d1-851e-7db2e99835ae", "text": "The biological effects of ionizing radiation relate strongly to the dose, dose rate, and quality of the radiation. To distinguish the different types of radiation, from low LET to high LET particle radiation, the quality factor Q (L) has been introduced. This factor reflects all cumulative knowledge on the dependence of the detrimental effects of radiation on physical characteristics and mainly LET (ionization density). Therefore, this factor can be used to multiply the absorbed dose (rad or gray) to obtain a quantity that expresses, on a common scale for all ionizing radiations, the biological damage (rem or sievert) to the exposed tissue. Although Q (L) has been superseded by the radiation weighting factor WR in the definition of equivalent dose, it is still being used in calculating the operational dose equivalent quantities used for example in monitoring [109]."}
{"_id": "Radiology$$$28a334ea-c5b2-4b14-a9c4-d2058547755b", "text": "In order to encompass the dependence of biological effects to LET, many studies have been performed in order to measure RBE for a specific biological endpoint (usually reproductive cell death) for radiations of different LET [110]. In most cases, survival curves are evaluated assuming a linear-quadratic dose dependence of the induction of reproductive death of cells. The linear term accounts for damage from single particle tracks and the quadratic term for damage due to interaction of lesions from independent tracks. Although for many years 250\u00a0kVp X-ray was considered the standard reference radiation for the determination of RBE, the International Commission on Radiation Protection (ICRP) recommended in their 92nd report to use gamma rays of 60Co as the reference radiation [111]. In both cases of low LET radiation, RBE is assumed to be equal to 1.0. When specific biological effects of high LET radiation (such as fast neutrons) on human cells are measured, the RBE ranges from about 3 to greater than 100 for various biological effects."}
{"_id": "Radiology$$$601b1e7d-5b82-43c2-9c01-168b021b1ef1", "text": "The oxygen effect is an important parameter in radiation therapy. Its influence on the tissue\u2019s biological response (typically survival curves) will differ according to the radiation type used. This concept is represented by the oxygen enhancement ratio (OER)."}
{"_id": "Radiology$$$9e86540f-08f7-4b13-9cca-f7a473c888d4", "text": "The OER is a measure of the influence of the oxygen effect. It is defined as the ratio of radiation doses that produce the same biological effect in hypoxic compared to aerobic (well-oxygenated) conditions:"}
{"_id": "Radiology$$$2bbd0c52-9a75-4d04-b788-535af9b3469e", "text": "The OER varies with the LET (ionization density) (Fig. 2.23). The OER decreases as the LET increases and approaches OER\u00a0=\u00a01 at LET \u2248 150\u00a0keV/\u03bcm, meaning that the level of oxygenation has little or no influence on the cell survival in case of high LET radiation (\u03b1 particles, neutrons, and heavily charged particles). This is explained by the fact that high LET radiation mostly induces direct damage, which is not oxygen dependent. Therefore, high LET radiation is expected to lead to a better tumor control of hypoxic tumors compared to low LET radiation.\n\nA line graph of log surviving fraction versus absorbed dose plots the curves for normoxia and hypoxia. 2 lines follow a decreasing trend. O E R equals a dose of normoxia overdosed of hypoxia.\n\nFig. 2.23\nOER as a function of LET (Created with BioRender)"}
{"_id": "Radiology$$$caa648c8-ed5e-454c-9942-62f47b309b18", "text": "A line graph of log surviving fraction versus absorbed dose plots the curves for normoxia and hypoxia. 2 lines follow a decreasing trend. O E R equals a dose of normoxia overdosed of hypoxia."}
{"_id": "Radiology$$$c37a7604-384f-458c-a2cb-fe4b1d0fa3ef", "text": "It should be noted that these OER values were originally derived from in vitro experiments. Recently, the oxygen effect during carbon ion therapy was questioned due to low LET values in the spread-out Bragg peak, giving rise to a possible impact of oxygen on carbon ion treatment outcome [112]. In case of low LET radiation (X- and \u03b3-rays, electrons), the OER increases and is in the range of 2.5\u20133.5, meaning that a 2.5\u20133.5 times higher dose is needed to achieve the same killing effect in hypoxic cells compared to normoxic cells. Indirect effects, relying on reactive oxygen species (ROS) production, are the dominant process associated with low LET radiation and explain the importance of oxygen for low LET radiation. Hypoxic regions within a tumor may therefore show radioresistance to low LET radiation. The OER has an intermediate value for neutrons. Based on this concept, a massive work on oxygen-based radiosensitization is being done and is discussed in Chap. 5."}
{"_id": "Radiology$$$45540481-ef4e-407b-a40d-1483e1fdf63d", "text": "The damage caused by ionizing radiation in the body can become clinically apparent as a number of different health effects. The type and severity of the effect are strongly dependent on dose and exposure conditions, but also on the health status of the exposed individual. For radiation protection purposes, and to ensure the safe use of radiation in society, the health effects of ionizing radiation exposure are classified into two types [113]:"}
{"_id": "Radiology$$$ddfd4984-d2e5-49a2-a9ca-98112e571475", "text": "Deterministic effects, which are also called tissue reactions, are those for which there is a defined threshold below which the effect is not expected to occur. In addition, the severity of the effect increases with dose. The acute radiation syndromes are examples of early effects following high doses. However, deterministic effects are not a synonym for acute effects, as some, e.g., fibrosis, can occur much later."}
{"_id": "Radiology$$$258b6ab2-57ac-4a07-9a0d-27c92505cbfd", "text": "Stochastic effects have no threshold, and the occurrence of the effect is probabilistic, such that any exposure to ionizing radiation increases the risk of these effects. The severity of the effect is not related to the dose. Stochastic effects tend to manifest many years postexposure and include cancer and heritable effects."}
{"_id": "Radiology$$$72eaae09-7c56-41be-82e1-9d5ffcf452de", "text": "High-dose penetrating radiation causes damage both to functional tissues and to stem cell compartments. In general, maintenance of health depends on a balance between loss and replacement of cells in many, but not all, organs and tissues of the body, reflecting physiological \u201cwear and tear.\u201d"}
{"_id": "Radiology$$$83d9c2c7-3fdf-47ed-a15d-4794a42ac0aa", "text": "Cellular damage is known to occur after exposing tissues to ionizing radiation. If the number of cells damaged is small relative to the total number of stem cells in the tissue, then the remaining stem cells can repopulate adequate numbers of functional cells. Consequently, there will be no obvious loss of tissue function. Conversely, if the stem cell population is reduced below a critical size, the tissue will cease to function efficiently, either transiently or permanently."}
{"_id": "Radiology$$$0e23c409-cd66-4d03-aeea-e2febedaf9a0", "text": "Organs and tissues differ in their sensitivity to radiation (Chap. 7), and the damage from radiation particularly affects the more radiosensitive cells, for example the lymphocytes in the lymphatic tissue, red bone marrow precursor cells, and crypt cells in the mucosal lining of the gastrointestinal tract."}
{"_id": "Radiology$$$a88b3b10-8aa8-44b3-9635-7d3b958c46ea", "text": "Whether or not recovery will be possible will strongly depend upon the rate at which viable stem cells (that is, those cells undamaged or repaired) can repopulate the depleted stem cell population by self-renewal. The whole process of recovery is dependent upon feedback mechanisms stimulated by the body\u2019s recognition of depleted functional cell numbers. Following exposure of a large proportion of or all of the body, the normal steady state of cellular regeneration for tissues throughout the body is interrupted: cells and tissues break down and cannot be replaced. This is the basis for the observed threshold for such deterministic effects or tissue reactions."}
{"_id": "Radiology$$$e630fced-0a4f-4b25-b1e3-8a5c4037455b", "text": "It is, however, very important to note that there is a variation in sensitivity among individuals in an exposed population with any particular dose and exposure scenario. This variation reflects differences in the ability of individuals to cope with radiation-induced cellular damage, which is influenced by the age and state of health of the individual at the time of irradiation [85]."}
{"_id": "Radiology$$$056862f3-9ab9-4605-b985-b2695c52e585", "text": "When individuals are exposed to sufficiently high doses of acute, penetrating ionizing radiation, the acute radiation syndrome begins with the prodromal phase [114, 115]. Following this, there will be a latent period, which represents the time period between initial exposure and manifestation of full acute radiation syndrome (ARS) due to a lack of cell renewal, as described above. The severity of the initial prodromal effects, the time for their development, the timing and any symptoms experienced during the latent period, and the type and severity of the full manifestation of ARS are all dependent on the dose and exposure scenario. This is described in more detail in Fig. 2.24 (Box 2.23).\n\nA graph of radiation exposure versus time after radiation exposure plots the zones of initial prodromal phase, latent phase, and acute manifestation phase.\n\nFig. 2.24\nRadiation syndrome phases (Created with BioRender)"}
{"_id": "Radiology$$$dbd0a8f1-716d-48bb-b335-d8467fbe6097", "text": "A graph of radiation exposure versus time after radiation exposure plots the zones of initial prodromal phase, latent phase, and acute manifestation phase."}
{"_id": "Radiology$$$64868148-612a-42ae-8685-99f5d60705ea", "text": "The clinical signs and symptoms of high-dose radiation exposure are observed up to ~6\u00a0days after exposure (with a high degree of uncertainty). These come as soon as a few minutes after a very high dose.\n\nThe symptoms of deterministic effects are dependent on dose (deterministic), with increased symptoms associated with higher doses.\n\nIn general, individuals exhibit flu-like symptoms, vomiting, diarrhea, and headache. For doses in the region of:\n1\u20132\u00a0Gy, these are classified as \u201cmild,\u201d and we would expect 10\u201350% people vomiting, and others experiencing fatigue and weakness.\n\n2\u20134\u00a0Gy, these are classified as \u201cmoderate,\u201d following which 70\u201390% people would be constantly vomiting, 2\u20136\u00a0h after exposure; 50% people would have a headache; 10\u201380% people would have a slight increase in body temperature.\n\n4\u20138\u00a0Gy, these are \u201csevere,\u201d following which ~100% of people would be vomiting <1\u00a0h after exposure; 50\u201380% people would have a headache; most others would have a constant fever <1\u00a0h after exposure; some people might lose consciousness or feel confused; 10% of individuals would have diarrhea 1\u20138\u00a0h after exposure.\n\n8\u00a0Gy, these are \u201cvery severe/lethal\u201d (depending on the medical resources available); most people lose consciousness fairly quickly; temperature peak at about 41\u00a0\u00b0C is usually observed, and many patients would present with skin burns at these doses."}
{"_id": "Radiology$$$6bd6240b-707c-49c4-aa53-72f9d331ba6d", "text": "The clinical signs and symptoms of high-dose radiation exposure are observed up to ~6\u00a0days after exposure (with a high degree of uncertainty). These come as soon as a few minutes after a very high dose."}
{"_id": "Radiology$$$bf36ac1a-817e-475c-b5d8-552a7054e1b7", "text": "The symptoms of deterministic effects are dependent on dose (deterministic), with increased symptoms associated with higher doses."}
{"_id": "Radiology$$$ed687110-ab0e-418c-afcb-1216113c5348", "text": "In general, individuals exhibit flu-like symptoms, vomiting, diarrhea, and headache. For doses in the region of:\n1\u20132\u00a0Gy, these are classified as \u201cmild,\u201d and we would expect 10\u201350% people vomiting, and others experiencing fatigue and weakness.\n\n2\u20134\u00a0Gy, these are classified as \u201cmoderate,\u201d following which 70\u201390% people would be constantly vomiting, 2\u20136\u00a0h after exposure; 50% people would have a headache; 10\u201380% people would have a slight increase in body temperature.\n\n4\u20138\u00a0Gy, these are \u201csevere,\u201d following which ~100% of people would be vomiting <1\u00a0h after exposure; 50\u201380% people would have a headache; most others would have a constant fever <1\u00a0h after exposure; some people might lose consciousness or feel confused; 10% of individuals would have diarrhea 1\u20138\u00a0h after exposure.\n\n8\u00a0Gy, these are \u201cvery severe/lethal\u201d (depending on the medical resources available); most people lose consciousness fairly quickly; temperature peak at about 41\u00a0\u00b0C is usually observed, and many patients would present with skin burns at these doses."}
{"_id": "Radiology$$$2ce9e241-9dce-4c0e-aec5-ebc0fee3951f", "text": "1\u20132\u00a0Gy, these are classified as \u201cmild,\u201d and we would expect 10\u201350% people vomiting, and others experiencing fatigue and weakness."}
{"_id": "Radiology$$$a0db087f-0155-4027-93fd-bb53768520b6", "text": "2\u20134\u00a0Gy, these are classified as \u201cmoderate,\u201d following which 70\u201390% people would be constantly vomiting, 2\u20136\u00a0h after exposure; 50% people would have a headache; 10\u201380% people would have a slight increase in body temperature."}
{"_id": "Radiology$$$c3f1a30b-956e-479f-9d29-593fd4a58505", "text": "4\u20138\u00a0Gy, these are \u201csevere,\u201d following which ~100% of people would be vomiting <1\u00a0h after exposure; 50\u201380% people would have a headache; most others would have a constant fever <1\u00a0h after exposure; some people might lose consciousness or feel confused; 10% of individuals would have diarrhea 1\u20138\u00a0h after exposure."}
{"_id": "Radiology$$$49793108-78de-473a-a178-14d29ac4c7e7", "text": "8\u00a0Gy, these are \u201cvery severe/lethal\u201d (depending on the medical resources available); most people lose consciousness fairly quickly; temperature peak at about 41\u00a0\u00b0C is usually observed, and many patients would present with skin burns at these doses."}
{"_id": "Radiology$$$715bda0c-0572-4889-bfcc-4bab60390367", "text": "Following these initial signs and symptoms, for doses less than approximately 6\u00a0Gy, the latency period is generally fairly asymptomatic, and individuals usually start to feel a little better. Then, unless radiation has been identified as the cause of the observed prodromal symptoms, often nothing is done, because the symptoms can be mistaken for those of many other non-radiation-related illnesses. However, if ionizing radiation has been identified as a potential cause, differential white blood cell counts should be taken as a marker of the potential severity of the effects. A summary of the different types of ARS is given in Fig. 2.25.\n\nA line graph of dose versus time plots a baseline for therapy. A declining curve with phases of cerebral death, gastrointestinal death, and hematopoietic death. \n\nFig. 2.25\nThe dominant syndromes leading to death vary with dose and time postexposure. Therapy is possible for doses lower than approximately 8\u201310 Gy (depending on medical resources) (Created with BioRender)"}
{"_id": "Radiology$$$139feef7-5dbb-4963-b8b9-a97f94292e36", "text": "A line graph of dose versus time plots a baseline for therapy. A declining curve with phases of cerebral death, gastrointestinal death, and hematopoietic death."}
{"_id": "Radiology$$$7e0b2cae-0a6f-4763-82df-24c4bc8b436c", "text": "Following exposures greater than around 2\u00a0Gy, and with this syndrome dominating up to around 10\u00a0Gy, the fall in blood cell counts may result in death from septicemia or hemorrhage, due to bone marrow failure, unless the symptoms can be treated. When the bone marrow is acutely exposed to radiation, this causes hypoplasia, aplasia, and/or hemolysis of cells. This leads to a sudden and dose-dependent reduction in the stem cell population, and ultimately atrophy of the lymph nodes and spleen. Differentiating and maturing cells may initially be only marginally affected. Depletion of cellular components of blood leads to infection and hemorrhage."}
{"_id": "Radiology$$$f1378e92-35c5-4653-ad3f-65cc72dd227b", "text": "The stem cell population may attempt to recover and, if successful, increasing numbers of granulocytes will appear in the blood about 3\u00a0weeks after exposure. Loss and recovery of blood platelet cell numbers follow a similar dose- and time-related pattern."}
{"_id": "Radiology$$$27207c4b-330d-43d5-94c4-aecf1d5ca282", "text": "The severity of the radiation effect can be estimated based on differential white blood cell counts (neutrophils and lymphocytes). If neutrophil and lymphocyte levels are measured repeatedly following initial exposure (the half-life of circulating neutrophils is only about 6\u20138\u00a0h), this can give an indication of the likely severity of the ARS or other tissue effects: A large initial peak of neutrophils and a rapid drop-off could indicate a dose ~>5 Gy."}
{"_id": "Radiology$$$1b3ab01a-4399-4836-bf90-5f8f1269e339", "text": "The mucosal crypt stem cells provide the protective mucosal cell lining of the intestinal tract wall. Due to the high turnover of these cells, particularly in the small intestine, damage to these cells results in a denudation of the gut surface as the epithelial cells are not replenished, within 5\u201310\u00a0days after exposure of the gastrointestinal tract to doses of radiation >1 Gy. Leakage of blood from damaged blood vessels into the gut then occurs, and blood appears in the feces. Simultaneously, translocation of normally harmless intestinal bacteria from the gut through the damaged blood vessels occurs, leading to infection. Once in the blood, these bacteria become pathogenic. Symptoms include severe bloody diarrhea, anemia, severe electrolyte disturbances, malnutrition, and sepsis."}
{"_id": "Radiology$$$fb49b063-b479-41da-b808-f94453be5d02", "text": "This gastrointestinal syndrome is seen in individuals who have received acute doses to the gastrointestinal tract in excess of about 8\u201310 Gy."}
{"_id": "Radiology$$$a92c0e8f-56bb-417d-85c9-e5f6568f245b", "text": "With the traditional paradigm of the dependence of severity of response on cell turnover, it was thought for a long time that the effects in the brain, beyond direct cell killing, were minimal. However, we now know that ionizing radiation can otherwise affect the way the brain functions, e.g., through changes in mediation of substance release."}
{"_id": "Radiology$$$52380473-d423-44cd-b7d4-a1a7fb14c6f4", "text": "For doses to the brain >~15\u00a0Gy, swelling (edema) of the brain, cerebral death (breakdown of the nerve impulse pathways), and generalized shock lead to coma and death. At such high doses, this happens very quickly, with loss of consciousness followed by death within a few hours or days at most, before the wider systemic prodromal reaction can start."}
{"_id": "Radiology$$$e52a0dde-7031-4ee4-ad6c-a80b82df0c0a", "text": "At lower doses, the regulatory functions of the central nervous system (CNS) within the body are affected\u2014either through vascular injury or through changes in how various neurotransmitters are released or by affecting the functioning of the brain itself. After whole-body exposure, the prodromal symptoms in the case of brain effects can also be detected as abnormalities on an electroencephalogram (EEG). This \u201cneurovascular syndrome\u201d tends to manifest around 10\u00a0Gy, and the vascular changes lead to hypertension, dizziness, confusion, impaired cognitive function, and neurological deficit later on. For cerebrovascular (and cardiovascular) effects, the assumed threshold is approximately 0.5 Gy."}
{"_id": "Radiology$$$9578c80c-bf00-4dbe-b7ab-845dae6ac272", "text": "It should be noted that multiple-organ dysfunction syndrome (MODS) can also occur\u2014this is a clinical syndrome with the development of progressive and potentially reversible physiological dysfunction in two or more organs or organ systems induced by a variety of acute insults, like ionizing radiation."}
{"_id": "Radiology$$$68e42f78-2d66-47d3-9e2a-5350b3d2e12e", "text": "Cell proliferation is generally slower in the lung than in the hematopoietic or gastrointestinal systems; however, in the weeks and months following initial exposure, pulmonary effects may lead to death due to massive respiratory failure. Damage to the cells lining the alveoli may result in acute inflammation of the lungs (pneumonitis) at doses in the range of 5\u201315 Gy. This leads to pulmonary edema, which can result in adult respiratory distress syndrome and secondary bacterial and viral pneumonia. Pulmonary failure then occurs due to fibrosis as a direct result of the radiation itself or as a result of infection, between around 6\u00a0months and 2\u00a0years or more postexposure."}
{"_id": "Radiology$$$0d1dc4f0-65fa-476a-83b8-a22b241aa118", "text": "Local radiation injury (LRI) may be defined as a setting of signs and symptoms following local overexposure to ionizing radiation of the skin. Although sometimes called cutaneous radiation syndrome, this term applies better to skin manifestations in the context of ARS."}
{"_id": "Radiology$$$bd9c69e3-8929-4a61-b52c-78255fe8a31a", "text": "Skin injuries caused by the high initial dose occur initially as burning, itching, and acute pain coupled with very painful primary erythema (reddening of the skin). This is usually followed by edema, accumulation of fluid in the skin as a result of tissue damage. Cutaneous syndrome is usually characterized by a fairly short latency phase, but if edema occurs within a few hours, this will usually result in very severe ARS. After a few days, hair loss occurs and the skin starts to break down leading to ulceration and necrosis\u2014tissue death occurs. Bacteria may use this as an entrance to the body ultimately followed by sepsis. Skin transplantation or amputation may be needed. As a late effect, telangiectasia and secondary erythema (and associated pain) can be very long lasting."}
{"_id": "Radiology$$$e0240bcb-8af9-422d-a395-433fc22db2f3", "text": "Evidence of the deterministic effects of radiation on the embryo and fetus is derived almost entirely from animal experiments. Extrapolation of the results of these studies can be used to predict the consequences of radiation exposure in humans."}
{"_id": "Radiology$$$7376b20d-7c85-4c46-9f37-d21b799ad28f", "text": "The effects on the embryo depend on the time of exposure relative to its development. When the number of cells in the embryo is small (i.e., in the first 6\u00a0days of pregnancy) and the cells are not yet specialized, damage is frequently seen in animals as failure of the embryo to implant in the wall of the uterus. In humans, the only manifestation of this would be a late or missed menstrual period. However, evidence from in vitro human embryo research has shown that the survival of even one cell in the early embryo before implantation can allow normal development, since all the necessary genetic components are present in each cell of the embryo at this stage of development. The consequences of any of these cells carrying a point mutation are unknown, but the possibility of stochastic (genetic, heritable) effects occurring cannot be excluded."}
{"_id": "Radiology$$$41708d1c-bd10-438f-b871-a8a17d6b5d06", "text": "Because of the lack of direct human evidence, it is useful to look in brief at the animal data. The data taken from animal experiments suggest that threshold doses in humans for radiological protection purposes are in the order of 0.05 Gy for reabsorption of preimplantation embryos; 0.05 Gy for minor skeletal abnormalities; 0.20 Gy for impaired fertility in the female; 0.2 Gy for functional disorders of the central nervous system; and between 0.20 and 0.50 Gy for serious skeletal abnormalities and growth retardation. Such information provides a basis for guidelines to ensure that pregnant women are adequately protected."}
{"_id": "Radiology$$$e7d5da9c-9df4-48c0-81c7-11075a995f66", "text": "Brain development has been particularly well studied in animals. It is when neurons (the information-conducting cells in the brain) are developing and when they are migrating to their predetermined sites in the cerebral cortex that irradiation is most damaging. In humans, this corresponds to between 8 and 25\u00a0weeks postconception. Only a very small amount of human data exists. For example, data were published in 1984 from a relatively small study on intellectual disability in children exposed in utero following the atomic bombs dropped on Hiroshima and Nagasaki in 1945."}
{"_id": "Radiology$$$d92f2ead-252f-473c-bbee-4d3e3cbf5da3", "text": "Intellectual disability is associated particularly with irradiation between the 8th and 15th weeks following conception. From these data, it has been estimated that the excess probability is about 40% per Gy; that is, at a dose of 1\u00a0Gy, 40 out of every 100 children exposed would be expected to experience severe intellectual disability. This compares with a background frequency of 0.8%. It is less marked between the 16th and 25th weeks, and no effect has been seen at other times of pregnancy."}
{"_id": "Radiology$$$6cf58a0e-5077-4152-9671-d09e71ce849d", "text": "The uncertainties at each measured dose point are extremely wide, because of the small numbers. Thus, the presence or absence of a threshold for developmental effects remains highly uncertain. However, school performance and IQ scores have been measured for children irradiated in utero, with a decrease of approximately 30 points at 1 Gy for children irradiated in the 8th to 15th week of pregnancy (but not before or after) [116]."}
{"_id": "Radiology$$$deb6afe8-9586-4f4e-85bb-5b5391d21be7", "text": "A variety of additional effects can occur, but of particular note, ionizing radiation can also cause nephropathy, which is reduced renal function, leading to progressive scarring kidneys and ultimately failure months to years following exposure."}
{"_id": "Radiology$$$e19bf1bc-9f8b-4d2f-83a5-d066930ac7fc", "text": "Other tissue effects may be seen many years postradiation exposure, for example cataract, which has an assumed threshold of approximately 0.5 Gy but which for low dose likely has a very long latency period. This topic is further considered in Chap. 8."}
{"_id": "Radiology$$$efada3ee-281c-47c1-9aa5-b8f8e367f21c", "text": "The probability of detecting tissue reactions, characterized by loss of tissue function, in healthy individuals following exposure to radiation is non-existing in some tissues at doses of up to a few hundred mGy. In other tissues, the threshold of detection is above a few thousands of mGy. Above the threshold, the probability of a tissue reaction increases steeply in a sigmoid manner, with the severity of effect increasing linearly with dose. It is important to note that protracting the dose will result in a lower frequency of effects and less severe symptoms at a given dose compared with acute exposure [113, 117]."}
{"_id": "Radiology$$$ac0f794e-de5a-4bfb-a6cc-b0aa90c43808", "text": "The range of doses associated with death from these syndromes after acute exposure to low linear energy transfer (LET) radiations is given in Table 2.8.Table 2.8\nRange of doses associated with death after exposure to low LET radiations\n\nWhole-body absorbed dose\n\nPrincipal effect contributing to illness or death\n\nTime of death after exposure\n\n1\u20136 Gy\n\nDamage to bone marrowa\n\n30\u201360\u00a0days\n\n5\u201315 Gy\n\nDamage to gastrointestinal tract and lungsb\n\n10\u201320\u00a0days\n\n>15 Gy\n\nDamage to nervous system and shock to cardiovascular system\n\n1\u20135\u00a0days\n\naDose range considered to result in 50% of an exposed population dying (LD50) without medical treatment is LD50\u00a0=\u00a03\u20134 Gy\nbDamage to vasculature and cell membranes, especially at high doses, is an important factor in causing death"}
{"_id": "Radiology$$$b0c50fab-5c36-40f6-ac73-7029207c8cb5", "text": "In an exposed population, there is a chance of death of approximately 5% of the population (5 persons dying in a population of 100) exposed to about 2 Gy or of about 50% without medical treatment (lethal dose, LD50) within the dose range of 3\u20134 Gy. Most individuals would be expected to die at doses between about 6 Gy and 10\u00a0Gy, unless they receive treatment to prevent infection and bleeding. Above about 10\u00a0Gy, death is very likely, even after attempts to stimulate the bone marrow or bone marrow transfusion from a suitable donor. The risk of death thus also depends on the number of exposed individuals, and the available expertise and facilities for appropriate treatment, as discussed further in Chap. 7."}
{"_id": "Radiology$$$b2c17ef3-e813-4eac-bc32-e8ebcb40fa21", "text": "High exposures do not always prove fatal, especially if the irradiation is nonuniform so that sufficient vital bone marrow stem cells are spared. Recent advances in immunology and in the administration of growth factors or cytokines to accidentally irradiated persons may rescue the bone marrow so that the hematopoietic syndrome might no longer be the limiting lethal condition. Matched stem cell transplantation is an alternative, provided that such stem cells are available at short notice. Death would then depend on whether damage to the lungs or intestine was sufficient to cause fatal pneumonitis or breakdown of the gut wall."}
{"_id": "Radiology$$$64f793e2-cb14-4f99-9cfe-54419bfcc239", "text": "Table 2.9 shows proposed values of the LD50 and/or ED50 and 1% thresholds for a selection of the most important conditions of ARS (Table 2.10).Table 2.9\nParameters for acute mortality (various sources including ICRP, 2007)\n\nThreshold (Gy)\n\nLD50 (Gy)\n\n1%\n\nBone marrow syndrome\n\nFirst aid only\n\n3.0\n\n1.5\n\nSupportive treatment\n\n4.5\n\n2.2\n\nPneumonitis\n\n10.0\n\n5.5\n\nGut syndrome\n\n15.0\n\n10.0\nTable 2.10\nParameters for acute morbidity (various sources including ICRP, 2007)\n\nThreshold (Gy)\n\nED50 (Gy)\n\n1%\n\nProdromal\n\nVomiting\n\n2\n\n0.5\n\nDiarrhea\n\n3\n\n0.5\n\nLung fibrosis\n\n5\n\n2.7\n\nSkin burns\n\n20\n\n8.6\n\nHypothyroidism\n\n60\n\n2.3\n\nCataract\n\n3\n\n1.3\n\nTemporary sterility\n\nMales\n\n0.7\n\n0.5\n\nFemales\n\n3.5\n\n0.8"}
{"_id": "Radiology$$$b748513d-cd1c-48cf-b75a-7d1e5c5a8f30", "text": "Cancer develops in tissues through the accumulation of various mutations over several conceptual stages [118]. Initiation of the process can occur following exposure to various environmental agents including radiation, but further changes in neoplastic development require a complex interaction between various factors in the host and environment. For this reason, it is not possible to attribute causal relationships between a particular environmental agent (in this case, radiation exposure) and cancer in individuals [119]. Instead, attribution is made for increased cancer incidence in an exposed population over a known baseline rate either pre-exposure or in a nonexposed population. This attribution is expressed through risk estimates."}
{"_id": "Radiology$$$190519ba-2d42-45a4-8b6c-a066cd25a38e", "text": "Present risk estimates for cancer following radiation exposure are based on a number of epidemiological studies, most notably the Life Span Study (LSS) of the Japanese atomic bomb survivors. The study is a gold standard against which the results of other studies on long-term radiation effect on humans are evaluated. In the latest analysis of mortality patterns between 1950 and 2003 [120] of the 50,234 deceased cohort members with dosimetric measurement data, there were 10,929 deaths from solid cancers and 695 deaths from hematological malignancies. Of these, 527 (4.8%) solid cancer deaths can be attributed to radiation exposure from the bomb in 1945. A dose-dependent increase in the rate of solid cancer deaths can be observed (Table 2.11).Table 2.11\nObserved and excess death from solid cancer and non-cancer diseases (adapted from Ozasa et al. 2012)\n\nColon dose (Gy)\n\nNumber of subjects\n\nNumber of deaths\n\nNumber of excess cases\n\nAttributable fraction (%)\n\n<0.005\n\n38,509\n\n4621\n\n2\n\n0\n\n0.005\u2212\n\n29,961\n\n3653\n\n49\n\n1.3\n\n0.1\u2212\n\n5974\n\n789\n\n46\n\n5.8\n\n0.2\u2212\n\n6536\n\n870\n\n109\n\n12.5\n\n0.5\u2212\n\n3424\n\n519\n\n128\n\n24.7\n\n1\u2212\n\n1763\n\n353\n\n123\n\n34.8\n\n2+\n\n624\n\n124\n\n70\n\n56.5\n\nTotal\n\n86,611\n\n10,929\n\n527\n\n4.8"}
{"_id": "Radiology$$$77daec6e-730d-4dee-a6ad-6e2055cc5786", "text": "In the analysis of solid cancer incidence among the LSS population between 1958 and 2009 [53], the latest follow-up data of a cohort of 105,444 people who were alive without known history of cancer was presented. For a person exposed at age 30, the excess relative risk (ERR) for any cancer by the age of 70 was estimated to be 0.50 per Gy without adjusting for smoking. The dose-response was linear with an estimated ERR of 0.64 per Gy for females, but for males, a linear quadratic fit was observed instead, with ERR of 0.20 per Gy at 1 Gy and 0.010 per Gy at 0.1 Gy (Fig. 2.26).\n\n2 line graphs. a plots excess relative risk versus attained age for smoking E R R. 4 lines, 2 follow an increasing trend, and 2 remain stable along the increasing lines. b plots cases per 10,000 person-year versus attained age for the solid cancer rate. 6 lines follow an increasing trend.\n\nFig. 2.26\nSmoking effects on solid cancer baseline rates. (a) Smoking ERR as a function of attained age for males (black curves) and females (gray curves). The solid curves represent lifelong smokers, while the dashed curves represent past smokers from the age at which they quit (shown are male past smokers quitting at age 50\u00a0years and female past smokers quitting at age 55\u00a0years). (b) Total smoking risk for current smokers, past smokers, and those who never smoked (thin solid curves) for males and females. The curves represent typical smoking histories. Male smokers started at age 20\u00a0years and smoked 20 cigarettes per day, while female smokers started at 30\u00a0years and smoked 10 cigarettes per day (reproduced with permission from Grant et al. \u00a9 2017 Radiation Research Society) [53]"}
{"_id": "Radiology$$$0c4e5c46-5ad4-416d-8f15-4507b926ce90", "text": "2 line graphs. a plots excess relative risk versus attained age for smoking E R R. 4 lines, 2 follow an increasing trend, and 2 remain stable along the increasing lines. b plots cases per 10,000 person-year versus attained age for the solid cancer rate. 6 lines follow an increasing trend."}
{"_id": "Radiology$$$ebdc1547-499d-45e1-a571-384da69725fd", "text": "At the moment, 0.1 Gy is the lowest dose for which the overall cancer risk from radiation exposure can be reliably estimated. Uncertainties from various factors such as limited statistical power, dosimetric uncertainties, and confounders begin to grow increasingly large and mask any possible effects in lower dose ranges or site-specific risk estimation. Unless properly addressed, these uncertainties distort the results and lead to erroneous estimation of risk [119]."}
{"_id": "Radiology$$$093feb42-62f1-4f14-86c1-9e63ebb92883", "text": "Together with radiation-induced cancers, the hereditary effects of radiation are stochastic effects. By comparison with cancer, induced hereditary diseases are considered to be a minor component of the total stochastic disease risk due to radiation exposure of an individual or of the population generally."}
{"_id": "Radiology$$$081ae7ec-e329-4eaa-8532-7dd5655e164e", "text": "There is little direct human evidence of hereditary effects; however, it is clear that ionizing radiation can cause mutations of the types seen in hereditary effects."}
{"_id": "Radiology$$$8a650f77-dde8-41f2-a6ec-1466b21f4efe", "text": "Multifactorial diseases are an additional class of effect, which combine heritable aspects in addition to influence from environmental factors. These include congenital abnormalities present at birth or chronic conditions, which appear later in life (Box 2.24)."}
{"_id": "Radiology$$$ef2a7cf6-1526-4379-ac24-47a3919d868e", "text": "There are three classes of Mendelian-type gene mutations, where genes are inherited from each parent:(a)\nDominant conditions, where even in the heterozygote (a person inheriting one mutant and one normal gene), the abnormality is seen in the individual. Their effects in the homozygote (double dose of the mutant gene) are usually more severe, if not lethal. An example of a dominant gene condition is Huntington\u2019s chorea (HC), which is characterized by nerve cell damage and changes in physical, emotional, and mental state. HC is caused by a faulty gene on chromosome 4.\n\u00a0(b)\nRecessive conditions, which have an effect only when present in the homozygote (two genes with the same, disease-linked, mutation). Recessive disorders are usually rare, as the mutation would need to be inherited from both parents. However, some recessive genes even when present in a single dose, i.e., heterozygote accompanied by a dominant normal gene, do still confer slight deleterious effects. An example of a recessive gene disorder is cystic fibrosis, which is caused by mutations on a gene located on chromosome 7.\n\u00a0(c)\nSex-linked conditions, which involve genes located on the X chromosome. A large proportion of mutations that are inherited are related to the X chromosome. Since there is only one X chromosome in males, mutant genes here act as dominant genes in males who suffer, whereas they are masked in the female with two X chromosomes who act as carriers. Mutations in these genes will exert their effect in females only when present in homozygotes and therefore appear as a recessive condition. Half the male offspring of a carrier mother will suffer and half her female offspring will be carriers. Examples of sex-linked conditions are color-blindness and hemophilia."}
{"_id": "Radiology$$$387f996b-99d2-4c72-a526-c2597c48e0f8", "text": "Dominant conditions, where even in the heterozygote (a person inheriting one mutant and one normal gene), the abnormality is seen in the individual. Their effects in the homozygote (double dose of the mutant gene) are usually more severe, if not lethal. An example of a dominant gene condition is Huntington\u2019s chorea (HC), which is characterized by nerve cell damage and changes in physical, emotional, and mental state. HC is caused by a faulty gene on chromosome 4."}
{"_id": "Radiology$$$8a801e88-ab57-4e73-a2b0-a5920fa2ab98", "text": "Recessive conditions, which have an effect only when present in the homozygote (two genes with the same, disease-linked, mutation). Recessive disorders are usually rare, as the mutation would need to be inherited from both parents. However, some recessive genes even when present in a single dose, i.e., heterozygote accompanied by a dominant normal gene, do still confer slight deleterious effects. An example of a recessive gene disorder is cystic fibrosis, which is caused by mutations on a gene located on chromosome 7."}
{"_id": "Radiology$$$6636b3d7-de11-4166-b379-5ca924f59772", "text": "Sex-linked conditions, which involve genes located on the X chromosome. A large proportion of mutations that are inherited are related to the X chromosome. Since there is only one X chromosome in males, mutant genes here act as dominant genes in males who suffer, whereas they are masked in the female with two X chromosomes who act as carriers. Mutations in these genes will exert their effect in females only when present in homozygotes and therefore appear as a recessive condition. Half the male offspring of a carrier mother will suffer and half her female offspring will be carriers. Examples of sex-linked conditions are color-blindness and hemophilia."}
{"_id": "Radiology$$$9f674c9e-fc5f-4acf-a346-d0f38f7e49f8", "text": "A low dose of irradiation can be defined as acute and chronic. An acute low dose is defined as less than 0.1 Gy (100\u00a0mGy), while a chronic low dose is defined as less than 6\u00a0mGy/h (or Sv equivalent). In this low-dose range, there are a variety of phenomena that dominate the dose-response relationship and lead to nonlinear and unpredictable outcomes."}
{"_id": "Radiology$$$5ff45121-ae4c-46fd-8551-13a9087b70ef", "text": "A key finding in low-dose radiobiology is that the effects seen are not directly proportional to the dose received. Rather, there are a number of factors such as genetic background, age, gender, and lifestyle, which can modify the outcome. After higher doses, DNA strand breaks are the predominant cause of radiation effects, and these are more directly related to dose deposited in the tissue or cells. Figure 2.27 depicts the usual dose-response relationship with the low-dose region shown as of uncertain outcome. The expanded section shows the variety of factors and outcomes which can be expected.\n\nA graph of stochastic effect versus effective dose plots low dose extrapolations and deterministic effects. A magnified graph of the low dose extrapolations plots adverse effects versus dose for uncertainty, transitional, and hormetic zones.\n\nFig. 2.27\nUsual dose-response relationship with the low-dose region shown as of uncertain outcome. (Figure from Kugathasan and Mothersill, 2022 [121])"}
{"_id": "Radiology$$$923cc22c-19cf-4be5-8627-fa27b8250af4", "text": "A graph of stochastic effect versus effective dose plots low dose extrapolations and deterministic effects. A magnified graph of the low dose extrapolations plots adverse effects versus dose for uncertainty, transitional, and hormetic zones."}
{"_id": "Radiology$$$7aa07fe6-b6c9-46cc-97de-15e9365cb844", "text": "Mechanisms involved in non-targeted effects are described in Sect. 2.8.2, and low-dose hypersensitivity, hormesis, and adaptive response mechanisms are described in Chap. 3. Global mechanisms underlying LDR are mentioned here and include production of oxidative stress, mitochondrial and membrane channel changes, signaling to neighboring cells, release of exosomes carrying modified cargos, and changes in the proteome. It is important to recognize that these changes may be proactive damage responses and not harmful per se. Change does not necessarily equate with harm."}
{"_id": "Radiology$$$4dd68f5a-4280-4c4c-808a-97765b18d61b", "text": "It is quite common that while a high dose/amount/rate of some medication or procedure is detrimental, a low dose is beneficial. Classical well-known examples include physical exercise (as opposed to forced labor), immunization (as opposed to virulent infection), and\u2014directly related to biologically active radiation\u2014controlled sun tanning (as opposed to sunburns and skin cancer caused by overexposure). Therefore, low-dose radiation effects may well be different from the effects of high doses. Actually, people have been using ionizing radiation for centuries: already, Herodotus and Hippocrates described healing properties of what we now know as radon springs. Radon treatment is considered to be a legitimate tool by mainstream medicine in Europe, especially for treating arthritis and other inflammatory diseases [122]. During the past four decades approximately, there has been a growing body of biological evidence regarding low-dose radiation effects. This evidence is concurrent with the shift in radiobiology from a DNA-centric view on radiation damage to a more systemic view that incorporates multi-level protection and nonlinear systems\u2014adaptive response [123]."}
{"_id": "Radiology$$$bf533c2c-6915-4e8e-9b3a-b7773b71789f", "text": "There is emerging evidence that low doses induce cellular and intercellular changes, which can lead to adaptive metabolic alterations. Adaptive responses against accumulation of damage\u2014also of non-radiogenic origin\u2014were also discovered [124]. Many studies demonstrated that radiation effects are far from linear [125]. Moreover, experimental, epidemiological, and ecological studies have shown that low doses of ionizing radiation can be beneficial to health [126, 127]."}
{"_id": "Radiology$$$4dec6a42-69c3-4951-b477-7729213a9db4", "text": "Beneficial low-dose effects of an agent that is harmful in high doses are called hormesis. Back in 1884, Hugo Schulz observed that low doses of many toxic agents, mercury and formaldehyde for example, enhanced the vitality of yeast cells. The term \u201chormesis\u201d was introduced by John Ehrlich (also in the context of chemical toxicity) in 1942 [128]. The term \u201chormesis\u201d is applied now to any kind of biphasic dose-response, i.e., when low doses of some agent are beneficial while higher doses are detrimental [128]. Physical exercise (as opposed to hard labor) is a typical example of hormetic response. According to the present knowledge, \u201chormetins\u201d\u2014agents inducing hormesis\u2014include but are not limited to heat and oxidative stress, various food components, micronutrients, intermittent fasting, calorie restriction, etc. [129]. Radiation hormesis is the most thoroughly investigated among all hormesis-like phenomena."}
{"_id": "Radiology$$$c32b842b-abf2-401c-9022-a1aee8d80db4", "text": "Speaking about radiation hormesis, we should point out two somewhat different uses of the terms \u201chormesis\u201d and \u201clow dose.\u201d Since radiation carcinogenesis is often considered as the single most important health hazard of ionizing radiation, radiation hormesis is usually understood in the narrow sense that low radiation doses may suppress cancer. In this narrow sense, curing arthritis or pneumonia is not viewed as a hormetic effect. Accordingly, there are two quite different meanings of the term \u201clow dose.\u201d In the context of radiation protection and many fields of radiobiology, \u201clow dose\u201d is understood to be 100\u00a0mGy or less as defined above. However, in the field of radiation therapy, the daily dose fraction is typically 2000\u00a0mGy and 6\u00a0weeks of therapy amounts to a total dose of 60,000\u00a0mGy\u2014hence a single 1000\u00a0mGy dose to treat pneumonia may be regarded as a low dose [130]."}
{"_id": "Radiology$$$7ee13323-8ebb-447d-be38-b70b0eb0861d", "text": "Low-dose hyper-radiosensitivity (HRS) and induced radioresistance (IRR) describe a type of survival curve which has a dose range usually below 500\u00a0mGy acute dose, where the dose-response is significantly more radiosensitive than the overall fit to the higher dose points would suggest (see Fig. 2.28). The phenomenon is seen in a large variety of both tumor and normal cell lines and has been detected in human skin from patients [131]. It is seen following acute and fractionated irradiation meaning that it is likely to be relevant for radiotherapy and diagnostic radiology/medical imaging. It was first described by Lambin et al. (1993) and Marples and Joiner (1993) [132, 133]. The HRS phenomenon results in a significant reduction of clonogenic cell survival, increase in chromosome breaks, micronuclei, unrepaired DSB, or gene mutations after a single low dose in the range of 100\u2013800\u00a0mGy. The maximal HRS effect is generally obtained at 200\u00a0mGy and corresponds to a biological effect equivalent to a dose 5\u201310 times higher. The mechanism of HRS/IRR is discussed in Chap. 3 (Box 2.25).\n\nA line graph plots survival versus dose. The H R S line begins (0, 1), reaches a peak at (0.4, 0.82), follows a decreasing trend, and ends at (2.5, 0.3). The L Q line begins at (0, 1) and ends at (2.5, 0.3). Values are estimated.\n\nFig. 2.28\nLow-dose hyper-radiosensitivity (HRS) can be observed in a typical survival curve. The dashed line represents the linear-quadratic (LQ) model, while the solid line shows the induced repair (IR) model"}
{"_id": "Radiology$$$e67be627-5e99-43e5-a92a-dea34ca94c62", "text": "A line graph plots survival versus dose. The H R S line begins (0, 1), reaches a peak at (0.4, 0.82), follows a decreasing trend, and ends at (2.5, 0.3). The L Q line begins at (0, 1) and ends at (2.5, 0.3). Values are estimated."}
{"_id": "Radiology$$$029335b6-6382-49f4-ac50-3c3e6f8e30f9", "text": "Low-dose hypersensitivity: Increased sensitivity to low-dose radiation which is not apparent at doses above 0.5 Gy."}
{"_id": "Radiology$$$631ab9e7-cdcf-4423-b118-8bbbf40f8c85", "text": "Adaptive response: The ability of a low first dose of radiation to \u201cprotect\u201d against the effects of a subsequent high dose."}
{"_id": "Radiology$$$5ad8bdcf-e5a6-46f4-bdcf-e8742f77f97d", "text": "Hormesis: Beneficial effects seen after low-dose exposure compared to unirradiated controls."}
{"_id": "Radiology$$$015feeae-b4c6-4ff6-9cca-a4c6bf4286fb", "text": "Bystander effects: One of the non-targeted effects defined as radiation-like effects seen in cells which did not get any energy deposition but which received signals from irradiated cells."}
{"_id": "Radiology$$$b552865c-d319-46d5-bd5c-9189dbc9c065", "text": "Genomic instability: Detection of non-clonal chromosomal damage or other DNA changes in distant progeny of cells which are genetically normal in the first postirradiation mitosis."}
{"_id": "Radiology$$$d44c1401-0861-4ebd-a4a9-9dc21245282e", "text": "Lethal mutations: A form of genomic instability, detected as a permanently reduced plating efficiency of progeny cells which survived irradiation."}
{"_id": "Radiology$$$c446e963-554b-4cbe-ba63-5107a01aa5ba", "text": "Non-DNA-targeted effects (NTE) refer to effects in cells, tissues, organs, or individuals which have not themselves received any radiation energy deposition but are in receipt of signals from irradiated entities. They include bystander effects, abscopal effects, clastogenic effects, genomic instability, and lethal mutations. Sometimes, adaptive responses and low-dose hypersensitivity are included as NTE, but although they can be induced by signaling in bystander cells, they are not strictly speaking NTE as they occur in directly exposed cells. Box 2.25 defines the terms. Box 2.25 shows the different effects observed in bystander cells and progeny cells compared to those seen in directly irradiated cells. The lists are the same showing that signaling can induce in bystanders most of the effects associated with low-dose direct radiation exposure. An NTE dose-response saturates in the low-dose region (Fig. 2.28). In general, increasing the dose beyond 0.5 Gy produces no additional NTE."}
{"_id": "Radiology$$$f2a11390-7f82-4a77-b49c-6600c8979794", "text": "The United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) defines bystander effect as a radiobiological effect that is transmitted from irradiated cells to neighboring unirradiated cells, generating biological alterations in the receiver cells that can influence the radiation-associated cancer risk [134]. As a communicative effect, bystander effects occur mainly at the primary site over a few millimeters or cellular diameters. This effect is mediated by the secretion of soluble factors or by signaling through gap junctions as well as through networks involving inflammatory cells of the microenvironment [135]."}
{"_id": "Radiology$$$13a48f58-f4d7-453c-9141-05304dee7131", "text": "The term radiation-induced bystander effect (RIBE) is described as the ability of irradiated cells to transport manifestations of damage to other cells which were not directly targeted by irradiation. An irradiated cell sends out signals and induces response in nonirradiated neighboring cells. The intensity of the bystander response in nonirradiated cells is not necessarily proportional to the dose delivered to the irradiated cells and can occur even at low doses. The RIBE is highly dependent on the cell tissues concerned and the irradiation sources (such as radiation doses, LET, dose rates) and can influence the nature of the bystander factors secreted by irradiated cells, the intensity of the bystander response in nonirradiated cells, and the timing of the events in the bystander signaling [136]. This amplification can cause similar radiation-induced effects in cells not directly exposed to radiation and exhibit the heritable changes that include cellular damage, DNA damage, mutations, chromosomal aberrations, chromosomal instability, senescence, apoptosis, genomic instability, micronucleation, oncogenic transformations, etc. [137\u2013139]."}
{"_id": "Radiology$$$890cbb30-7e9a-4985-b598-fca085f5db94", "text": "Some RIBEs can have deleterious effects, which involve the type of cell inducing the bystander signal after irradiation and the type of cells receiving these signals. Such effects can be determined by intercellular communication and level of amplification of original consequences of the event. Knowledge of the mechanism(s) by which non-targeted bystander effects are activated is still in its infancy and not well understood; however, it is believed that multiple pathways are involved in this phenomenon and also different cell types respond differently to bystander signaling."}
{"_id": "Radiology$$$d2ff857b-5a79-4124-a0aa-bcca688f3104", "text": "RIBE is believed to be an incredibly complex phenomenon considering the involvement of sheer number of proteins, inorganic molecules, and cofactors. This effect encompasses a number of distinct signal-mediated effects (Figs. 2.29 and 2.30). Lately, communication of bystander signals between adjacent cells connected by gap junctions has been studied extensively. Signaling molecules are propagated through direct intercellular communication via gap junctions or through diffusible secretion in the surrounding environment of irradiated and bystander cells. Exosomes and signaling mRNAs also play a potential role in mediating bystander effect [140]. Exosomes can be released by bystander cells exposed to radiation-induced UV biophoton signals [141, 142], while miRNAs have a pivotal role in intercellular signaling between irradiated and bystander cells [143]. ROS and secondary messengers (such as nitric oxide), protein kinase, as well as cytokines (such as TGF-\u03b2 and TNF-\ud835\udefc) are also considered to be involved in RIBE. Additionally, irradiated dying cells (predominantly from apoptotic rather than necrotic cells) release cell-free chromatin (cfCh) particles, which can integrate into genomes of surrounding healthy cells to induce extensive genomic instability (DNA damage) and inflammation [144]. In the absence of macrophages, cfCh shows direct involvement in the activation of H2AX by bystander cells. The bystander effect can be observed in different cell types with different endpoints.\n\nA diagram of gap junctions, calcium flux, and binding of exosomes, bystander factor molecules, and ultraviolet photons to receptors activating p 53, R O S, and nitric oxide and leading to their propagation.\n\nFig. 2.29\nProbable players driving the non-targeted effects of radiation\n\n\nAn illustration describes the examples and roles of the immune system, free radicals, modified gene expression, and epigenetic modulators in radiation-induced bystander effects.\n\nFig. 2.30\nFactors involved in RIBE (created with BioRender)"}
{"_id": "Radiology$$$852b93ba-39d6-4e2a-a890-9cedfe754410", "text": "A diagram of gap junctions, calcium flux, and binding of exosomes, bystander factor molecules, and ultraviolet photons to receptors activating p 53, R O S, and nitric oxide and leading to their propagation."}
{"_id": "Radiology$$$a1f4faf8-0eaf-4d03-88b1-af3703631dc7", "text": "An illustration describes the examples and roles of the immune system, free radicals, modified gene expression, and epigenetic modulators in radiation-induced bystander effects."}
{"_id": "Radiology$$$d308b091-ee04-4a2a-a2fb-5b8bafe11407", "text": "The term abscopal or out-of-field effect is an in vivo phenomenon in normal tissue that describes the occurrence of radiation-like damage in organs that have never been irritated. In other words, abscopal effects are bystander effects in vivo. Abscopal effects are known to occur after exposure to high or low doses of ionizing radiation in vivo and are often observed after high doses of targeted partial-body radiotherapy [145, 146]. The mediation of the effect is attributed to systemic factors such as the blood or the endocrine system [136, 147\u2013149]. The immune system is also thought to play an important role. Experiments show that high levels of macrophage activation and neutrophil infiltration in mice are a consequence of radiation-triggered recognition and elimination of apoptotic cells [150]. The abscopal effect on normal tissue differs conceptually from the abscopal effect on tumors, which is often described in radiation oncology. The abscopal effect on tumors refers exclusively to systemic antitumor immune responses induced by radiotherapy alone or in combination with immunotherapy to only part of the tumor load. These antitumor immune responses are capable of completely eliminating primary tumors and unirradiated metastases in patients. For more information about the abscopal effect on tumors, see Chap. 5."}
{"_id": "Radiology$$$c79a9f41-2c80-425d-926e-bb0d18c3367e", "text": "Clastogenic factors (CFs), potential biomarkers of a prooxidant state, are composed of endogenous lipid peroxidation products, cytokines such as necrosis factor alpha, unusual nucleotides, and other oxidants with chromosome-damaging properties. They are frequently noticed in the plasma of patients exposed to radiation [151]. Subsequently, it has been shown that CFs are not specific for irradiated subjects (Table 2.12), but are found in a variety of pathological conditions accompanied by oxidative stress. In both conditions, they can be considered as biomarkers of oxidative stress [152] as well as risk factors for carcinogenesis.Table 2.12\nClastogenic factors (irradiation)\n\nClastogenic factors (irradiation)\n\nTherapeutic and accidental exposure\n\n(Goh and Summer, 1968; Hollowell and Littlefield, 1968)\n\nExposure at Chernobyl\n\n(Emerit et al., 1994; Emerit et al., 1997)\n\nA-bomb survivors\n\n(Pant and Kamada, 1977)\n\nPUVA treatment for psoriasis\n\n(Alaoui-Youssefi et al., 1994; Emerit et al., 2011)"}
{"_id": "Radiology$$$415f4459-959c-40df-ae7b-fe5987e95b07", "text": "The non-targeted effect is a dynamic complex response of epigenetic dysfunctions, DNA damage, and cell death in nonirradiated tissues as consequences of secretion of clastogenic factors\u2014\u201cchromosome breakage factors\u201d from irradiated cells. The formation of these breakage factors (CF) with their chromosome-damaging actions is mediated by the superoxide anion radicals, which are regularly inhibited by exogenous superoxide dismutase (SOD). These free radicals are an initiator of a series of events leading to formation of clastogenic materials. In vitro experiments provide strong evidence for the role of O2 in those cells exposed to superoxide-generating systems, such as the xanthine\u2013xanthine oxidase reaction, a phorbol 12-myristate-13 acetate (PMA)-stimulated photodynamic reaction. The supernatant of these cells contains CF, while cell-free systems do not lead to CF formation. Studies of CFs originating from observations on the plasma from irradiated persons were shown to induce chromosomal aberrations when co-cultured with cells from unexposed persons (Fig. 2.31). However, this phenomenon is common in a large number of health defects as well [153].\n\n2 flow diagrams depict the assays to screen for clastogenic factors, components of clastogenic factors, and possible mechanisms of action of clastogenic factors.\n\nFig. 2.31\nClastogenic factors (created with BioRender)"}
{"_id": "Radiology$$$2e4c8cb3-7594-4a05-9e88-a5407ada17ff", "text": "2 flow diagrams depict the assays to screen for clastogenic factors, components of clastogenic factors, and possible mechanisms of action of clastogenic factors."}
{"_id": "Radiology$$$449b4a56-c6fe-4348-8941-103d381896d6", "text": "TNF-\ud835\udefc and inosine triphosphate (ITP) stimulate the production of superoxide by monocytes and neutrophils. The lipid peroxidation product, 4-hydroxynonenal, inhibits superoxide production; however, it has the capacity to decrease the activity of DNA polymerases by inactivating their sulfhydryl groups leading to genotoxic effects. Formation of CF often damages/changes the chromatid structure; which indicates that they are not immediate and occur late in the S phase or in the G2 phase of cell cycle where they have duplicated their chromatids. These chromosome-damaging effects can be detected by classical cytogenetic techniques."}
{"_id": "Radiology$$$01613b76-4495-43fb-8043-0ef31bfbb483", "text": "Ionizing irradiation is known to have mutagenic and carcinogenic potential for the exposed host as it induces chromosomal aberrations in directly exposed cells."}
{"_id": "Radiology$$$1caf7c33-f1e9-4210-a9d6-984d10401dd1", "text": "Genomic instability (GI) is a hallmark of cancer cells, which includes variations of increased frequencies of base pair mutation, microsatellite instability (MSI), and chromosome instability (CIN) [154]. GI is a complex multiple-gene event marked during the development of some but not all cancers and also induced effectively by ionizing radiation. Radiation can provoke cellular communications eliciting a cascade of cellular events, which results in the destabilized genome in irradiated as well as unirradiated (bystander) cells. Radiation-induced genomic instability (RIGI) is observed in the progeny of irradiated cells as a delayed and elevated stochastic appearance of de novo chromosomal aberrations, gene mutations, and reproductive cell death [137, 155]. The effects of instability occur at a stable rate and are persistent in the postirradiation survivors for many generations."}
{"_id": "Radiology$$$bbfe1af1-88fe-4fda-af38-ba051c041520", "text": "Radiation-induced bystander effects are also involved in RIGI [156] due to contribution of indirect (by stimulating the reactive intermediates over many generations) and delayed effects (delayed DNA breakage, delayed reactivation of p53, delayed induction of various phenotypes) to cellular outcomes after radiation exposure. More detailed molecular studies on RIGI can provide deep insights into radiation-induced carcinogenesis (Box 2.26)."}
{"_id": "Radiology$$$74c5c293-eb9c-466a-a1c0-ae6986de9815", "text": "Genomic instability (GI), a characteristic of most cancers, is a complex multigene event and is often expressed by the appearance of chromosome aberrations many generations later.\n\nMicrosatellite instability or chromosomal instability due to mutations in DNA repair genes or mitotic checkpoint genes is the underlying basis for GI in hereditary cancers.\n\nIn sporadic (non-hereditary) cancers, GI occurs at least at the early stages of cancer development."}
{"_id": "Radiology$$$85b90c01-3bf5-4e0b-9efa-9d17fca9f6c0", "text": "Genomic instability (GI), a characteristic of most cancers, is a complex multigene event and is often expressed by the appearance of chromosome aberrations many generations later."}
{"_id": "Radiology$$$2278aea9-6884-4e8c-b87f-a519e4fb67bc", "text": "Microsatellite instability or chromosomal instability due to mutations in DNA repair genes or mitotic checkpoint genes is the underlying basis for GI in hereditary cancers."}
{"_id": "Radiology$$$0afd9506-a78a-410c-ae24-fe10ef6645da", "text": "In sporadic (non-hereditary) cancers, GI occurs at least at the early stages of cancer development."}
{"_id": "Radiology$$$2171b137-7e2f-46c8-a19a-b599a8e86514", "text": "Biological effects of IR-induced GI are transmitted over several generations after irradiation via the progeny of surviving cells with delayed phenotypic expression, but not uniformly. Delayed manifestations of induced GI include delayed cell death, chromosomal instability, and mutagenesis."}
{"_id": "Radiology$$$b5f3047a-1246-48f2-9ca9-331dc1df4ab2", "text": "The incidence of GI is significantly higher than that of conventional gene mutation, which eventually induces delayed reproductive death or delayed lethal mutations and increases the frequency of giant cells, micronuclei, senescence-like growth arrest, apoptosis, or necrosis in the progeny of surviving cells [157], suggesting that one of the potential initiators of RIGI is delayed cell death."}
{"_id": "Radiology$$$2848a408-4ed7-46fb-9804-5b052b170420", "text": "Exposure to sparse LET or dense LET radiation produces non-clonal chromosome aberrations (NCCAs), a highly significant feature for delayed chromosomal instability, genome heterogeneity, and complexity, in clonal descendants or stem cells that result in transmission of chromosome-type and chromatid-type aberrations to their progeny after irradiation [158]."}
{"_id": "Radiology$$$85393036-fc47-478a-8da9-571badcd4e85", "text": "Radiation may induce a type of GI in cells which results in an increased rate of spontaneous mutation that persists for many generations of cells. Clonal populations of cells surviving radiation exposure indicate such instability in a fraction of irradiated cells, which can persist longer over generations. Subpopulation of genetically unstable cells may arise from irradiated cells with a high frequency of even featureless minisatellite mutations [159], signifying the delayed appearance of certain mutational events in the progeny of irradiated cells."}
{"_id": "Radiology$$$925a77ba-e68f-4b56-86a3-4b078f306fbf", "text": "The mechanism of perpetuation in progeny populations is thought not only to be epigenetic but also to involve an excess generation of ROS over the course of time, cell-to-cell gap junction communication, dead and dying cells in the unstable population, and/or secreted factors from unstable cells (Fig. 2.32).\n\nAn illustration describes several factors and their corresponding effects during the initiation, perpetuation, and induction of delayed effects in RIGI.\n\nFig. 2.32\nMechanisms involved in radiation-induced genomic instability (Created with BioRender)"}
{"_id": "Radiology$$$fb8195ef-38d3-4fc2-a3a6-fb00fcfcbb7a", "text": "An illustration describes several factors and their corresponding effects during the initiation, perpetuation, and induction of delayed effects in RIGI."}
{"_id": "Radiology$$$ef3329ef-cfd4-46cd-85f1-4d0e07b0320f", "text": "DNA-damaging agents (such as X-rays, IR, restriction endonuclease Hinfl), radiomimetic drugs (bleomycin and neocarzinostatin), DNA DSBs, and DNA damage at the site of their decay are considered as effective initiators of RIGI. In some cases, sufficiently small or powerful environmental cues can directly exert their impact upon a cell\u2019s DNA, which is a critical target for RIGI. DNA strand breaks, the most lethal lesions induced by IR, activate a number of cellular DDR signaling cascades such as the activation of DNA damage-sensing and early transduction pathways, cell cycle arrest, and DNA repair. To a certain degree, it could convert the initial sites of DNA DSBs to unforeseen structures and results in reorganized chromatin domains and a disrupted genome structure, evident as a mutation induction. Generation of gross chromosomal rearrangements, or multiple intrachromosomal aberrations, or DNA damage signatures is accountable for the initiation of GI."}
{"_id": "Radiology$$$8f2b32d2-76af-4c14-a157-7bf4fbeb48b2", "text": "RIGI is transmitted through many generations after irradiation, suggesting that the memory of unrepaired DNA damage can be perpetuated over time by a number of processes involving ROS, communication through cell-to-cell gap junction, unstable dying cell population, and/or secreted factors from unbalanced cells. RIGI appears to be independent of the p53 status of the irradiated cells, but a number of genetic factors influence the expression of the unstable phenotype."}
{"_id": "Radiology$$$7c9de07e-d73c-4cc9-86c4-bc2c1da1941a", "text": "Radiation-induced DNA DSBs could cause nonlethal, \u201cpotentially unstable chromosome regions (PUCR)\u201d and altered chromatin architecture within the nucleus through DNA repair, which are transmissible through the progeny of surviving cells for many generations after irradiation [160]. Indeed, though PUCRs are potentially unstable, they are capable of persisting for prolonged periods through bridge-breakage-fusion (BBF) cycle [161] and thus could be the regions susceptible for causing delayed DNA breakages [162], inducing telomere instability and delayed cell death."}
{"_id": "Radiology$$$94514581-544d-4d88-974f-577c3e5f32b6", "text": "PUCRs can possibly be reactivated by large deletions or abnormal positioning of telomeres, loss of nuclear matrix-attachment regions (MARs), translocations of the chromosomes, distorted nucleosome, and altered nuclear architecture, leading to upregulating or silencing gene transcription, delayed p53 reactivation, and delayed manifestation of GI in the progeny of surviving cells (Table 2.13).Table 2.13\nPUCR effects\n\nPUCRs near the telomeres\n\nPUCRs in the interstitial regions\n\nCould cause telomere instability, chromosomal aberrations involving telomeric sequences\n\nInterstitial telomeric sequences are potentially more unstable than non-telomeric sequences\n\nLess detrimental to the cell, as it would result in loss of less genetic material\n\nMore destructive as it may lose chromosome fragments or large deletions\n\nLead to genomic instability across many generations\n\nLead to different consequences in the long-term progeny"}
{"_id": "Radiology$$$5c3136f5-b196-46fc-adca-a799c1fa0a3b", "text": "IR-induced DSB repair defects predominantly persuade various delayed phenotypes, indicating that delayed DNA damage is associated with delayed phenotypes. It is expected that delayed DNA damage arising in the progeny of surviving cells activates the uniquely sensitive tumor suppressor p53 protein, a multifunctional, highly regulated, and promoter-specific transcription factor. It is known to depend on the kinase ATM, which acts via the downstream kinases Chk2/hCds1 and mediates phosphorylation of various nuclear proteins, including p53. Stabilized and activated p53 protein transactivates a variety of downstream gene products, which direct either a prolonged cell cycle arrest in G1, senescence-like growth arrest or an apoptotic pathway."}
{"_id": "Radiology$$$2b149310-4da2-409b-86c4-c80d6a9a013d", "text": "RIGI enhances the accumulation of genomic alterations, resultant of delayed unscheduled DNA breakage, which triggers deferred activation of p53 in the progeny of irradiated cells; however, RIGI can be induced in all cell types regardless of the presence and status of a p53 function. Reactivated PUCRs and delayed DNA breakage are directly or indirectly involved in the delayed expression of instability phenotypes (Box 2.27)."}
{"_id": "Radiology$$$e6043514-7ece-4da1-abd8-71a302275bc7", "text": "Radiation-induced genomic instability (RIGI) is characterized by an elevated and persistent rate in the accumulation of de novo genetic alterations in the progeny of irradiated cells after the initial insult.\n\nDelayed manifestations, e.g., chromosomal instability, mutational events, and cell death, are the potential initiators of RIGI for multiple generations following irradiation or exposure to DNA-damaging agents.\n\nUnirradiated progeny cells display phenotypic changes due to RIGI at delayed times after radiation of the parental cells.\n\nAlong with changes in DNA, epigenetic aberrations may be involved in RIGI, suggesting that epigenetics may also be the link to understand the initiation and perpetuation of GI."}
{"_id": "Radiology$$$4a584970-4b7f-489d-8bb9-2ac62c730995", "text": "Radiation-induced genomic instability (RIGI) is characterized by an elevated and persistent rate in the accumulation of de novo genetic alterations in the progeny of irradiated cells after the initial insult."}
{"_id": "Radiology$$$b0a8d3e5-8eae-41fe-b869-5daccc34597b", "text": "Delayed manifestations, e.g., chromosomal instability, mutational events, and cell death, are the potential initiators of RIGI for multiple generations following irradiation or exposure to DNA-damaging agents."}
{"_id": "Radiology$$$e4ce972d-9149-445e-b7bd-d43c8fccfc07", "text": "Unirradiated progeny cells display phenotypic changes due to RIGI at delayed times after radiation of the parental cells."}
{"_id": "Radiology$$$859fd697-c9ea-4ff0-97ca-283e4e4bdcf7", "text": "Along with changes in DNA, epigenetic aberrations may be involved in RIGI, suggesting that epigenetics may also be the link to understand the initiation and perpetuation of GI."}
{"_id": "Radiology$$$4083aa78-b142-4dde-8367-22f22d6fe117", "text": "Q1.\nAs seen in the figure below, the difference between the attenuated radiation, i.e., the radiation lost from the beam, and the absorbed dose is much larger for the energies where the Compton process dominates. Can you explain this?\n\nA graph of mass absorption in centimeters squared per gram versus energy in mega-electron volts The values are plotted for photon, pair, Compton, absorption, and attenuation. The lines for attenuation and photon have the highest values.\n\n\nAbsorption and attenuation in water for photons with different energies [Figure from Kiefer, J. (1990). Biological radiation effects. Germany: Springer.]\n\n\u00a0Q2.\nCan you tell why people living at high altitudes are more exposed to cosmic radiation? Can you tell which is the treatment at hospitals which is of most concern for radiation exposure?\n\u00a0Q3.\nWhich of the following is the most harmful to cells?(a)\nH2O2\n\u00a0(b)\nH\u22c5\n\u00a0(c)\nO\u1e24\n\u00a0(d)\ne\u2212aq\n\u00a0\n\u00a0Q4.\nName the four stages of indirect effects of ionizing radiation.\n\u00a0Q5.\nLow LET radiation mostly induces direct effects: true or false?\n\u00a0Q6.\nFill in the missing items in the table (modes of radioactive decay).\nMode of radioactive decay\n\nReleased particles\n\nGeneral reaction\n\nExample\n\n\u03b1-Decay\n\u00a0\u00a0\n92238U\u00a0\u2192\u00a090234Th\u00a0+\u00a024He\n\u00a0\nTwo fragment nuclei\n\u00a0\n100256Fm\u00a0\u2192\u00a054140Xe\u00a0+\u00a046112Pd\n\u00a0\u00a0\nZAP\u00a0\u2192\u00a0ZA\u00a0\u2212\u00a01D\u00a0+\u00a0n0***\n\n413Be\u00a0\u2192\u00a0412Be\u00a0+\u00a0n0***\n\n\u00a0Q7.\nDescribe the difference between the well-known periodic table and a chart of nuclides (chart of nuclides).\n\u00a0Q8.\nThe unit of effective dose is:(a)\nGy\n\u00a0(b)\nSv\n\u00a0(c)\nBq\n\u00a0(d)\nJ\n\u00a0\n\u00a0Q9.\nThe dose that takes into account both the quality of the radiation and the radiosensitivity of the tissue, and is thus a direct measure of the likelihood of developing cancer, is called:(a)\nAbsorbed dose\n\u00a0(b)\nEquivalent dose\n\u00a0(c)\nEffective dose\n\u00a0(d)\nDose rate\n\u00a0\n\u00a0Q10.\nX-rays and beta particles have been given a radiation weighting factor of 1 because they produce:(a)\nVirtually the same biological effect in tissue for equal absorbed doses\n\u00a0(b)\nNo biological effect in tissues for equal absorbed doses\n\u00a0(c)\nVarying degrees of biological effect in body tissue for equal absorbed doses\n\u00a0(d)\nNone of the answers above\n\u00a0\n\u00a0Q11.\nDuring flash radiotherapy, an ultralow dose rate is used. True or false?\n\u00a0Q12.\nArrange the following radiations in order of increasing LET in water:(a)\n5 MeV alpha particle\n\u00a0(b)\n100 MeV carbon ion\n\u00a0(c)\n10 MeV proton\n\u00a0(d)\nCobalt-60 \u03b3-rays\n\u00a0(e)\n200 MeV iron ion\n\u00a0\n\u00a0Q13.\nExplain why high LET irradiation exerts a relatively larger RBE in the low-dose range.\n\u00a0Q14.\nWith decreasing dose rate, a discriminative biological effect can be obtained between late-responding normal tissues and tumors. Please explain.\n\u00a0Q15.\nThe consequences for human exposure to ionizing radiation can be classified into two categories\u2014stochastic or deterministic effects/tissue reactions. Explain the reasoning behind this classification and describe the main features of these effects, giving examples."}
{"_id": "Radiology$$$8d8ea215-f5ea-4275-b9f2-9d7825e55743", "text": "As seen in the figure below, the difference between the attenuated radiation, i.e., the radiation lost from the beam, and the absorbed dose is much larger for the energies where the Compton process dominates. Can you explain this?\n\nA graph of mass absorption in centimeters squared per gram versus energy in mega-electron volts The values are plotted for photon, pair, Compton, absorption, and attenuation. The lines for attenuation and photon have the highest values.\n\n\nAbsorption and attenuation in water for photons with different energies [Figure from Kiefer, J. (1990). Biological radiation effects. Germany: Springer.]"}
{"_id": "Radiology$$$84648978-36fc-40c5-8900-37543ddd35a3", "text": "A graph of mass absorption in centimeters squared per gram versus energy in mega-electron volts The values are plotted for photon, pair, Compton, absorption, and attenuation. The lines for attenuation and photon have the highest values."}
{"_id": "Radiology$$$d5d6aaac-a284-4433-b1a8-efc6ddf545e5", "text": "Can you tell why people living at high altitudes are more exposed to cosmic radiation? Can you tell which is the treatment at hospitals which is of most concern for radiation exposure?"}
{"_id": "Radiology$$$eda3ee9e-2647-4c55-bb24-c79a3700a5c4", "text": "Which of the following is the most harmful to cells?(a)\nH2O2\n\u00a0(b)\nH\u22c5\n\u00a0(c)\nO\u1e24\n\u00a0(d)\ne\u2212aq"}
{"_id": "Radiology$$$bbb56fc0-c5ca-48b9-b5bd-8c0b6bdfa453", "text": "Fill in the missing items in the table (modes of radioactive decay).\nMode of radioactive decay\n\nReleased particles\n\nGeneral reaction\n\nExample\n\n\u03b1-Decay\n\u00a0\u00a0\n92238U\u00a0\u2192\u00a090234Th\u00a0+\u00a024He\n\u00a0\nTwo fragment nuclei\n\u00a0\n100256Fm\u00a0\u2192\u00a054140Xe\u00a0+\u00a046112Pd\n\u00a0\u00a0\nZAP\u00a0\u2192\u00a0ZA\u00a0\u2212\u00a01D\u00a0+\u00a0n0***\n\n413Be\u00a0\u2192\u00a0412Be\u00a0+\u00a0n0***"}
{"_id": "Radiology$$$cf8013e5-75b9-48b3-a881-eb9933daaea9", "text": "Describe the difference between the well-known periodic table and a chart of nuclides (chart of nuclides)."}
{"_id": "Radiology$$$ec21c9e3-8fb1-427c-92ef-9ecdc1f6fbed", "text": "The unit of effective dose is:(a)\nGy\n\u00a0(b)\nSv\n\u00a0(c)\nBq\n\u00a0(d)\nJ"}
{"_id": "Radiology$$$d235f20e-691a-4cec-a519-a9484d479a2b", "text": "The dose that takes into account both the quality of the radiation and the radiosensitivity of the tissue, and is thus a direct measure of the likelihood of developing cancer, is called:(a)\nAbsorbed dose\n\u00a0(b)\nEquivalent dose\n\u00a0(c)\nEffective dose\n\u00a0(d)\nDose rate"}
{"_id": "Radiology$$$5000153b-5836-4bbf-9810-ee8dec6d9e8d", "text": "X-rays and beta particles have been given a radiation weighting factor of 1 because they produce:(a)\nVirtually the same biological effect in tissue for equal absorbed doses\n\u00a0(b)\nNo biological effect in tissues for equal absorbed doses\n\u00a0(c)\nVarying degrees of biological effect in body tissue for equal absorbed doses\n\u00a0(d)\nNone of the answers above"}
{"_id": "Radiology$$$0ecaae1e-e166-44f0-b4fc-14ee45c60a00", "text": "Virtually the same biological effect in tissue for equal absorbed doses"}
{"_id": "Radiology$$$2587fdde-329f-4c38-94a8-63531f12c6b9", "text": "Varying degrees of biological effect in body tissue for equal absorbed doses"}
{"_id": "Radiology$$$f29e8f21-fbde-45a1-b7d5-46ceb5ee131f", "text": "During flash radiotherapy, an ultralow dose rate is used. True or false?"}
{"_id": "Radiology$$$ad20800f-4548-4a0e-89c3-85f9345deedb", "text": "Arrange the following radiations in order of increasing LET in water:(a)\n5 MeV alpha particle\n\u00a0(b)\n100 MeV carbon ion\n\u00a0(c)\n10 MeV proton\n\u00a0(d)\nCobalt-60 \u03b3-rays\n\u00a0(e)\n200 MeV iron ion"}
{"_id": "Radiology$$$040760bd-0e83-45b1-be02-792f486f724b", "text": "Explain why high LET irradiation exerts a relatively larger RBE in the low-dose range."}
{"_id": "Radiology$$$b07fe4ad-7c2e-4e61-ba80-136588ea1cb0", "text": "With decreasing dose rate, a discriminative biological effect can be obtained between late-responding normal tissues and tumors. Please explain."}
{"_id": "Radiology$$$0ed2286b-3768-431b-9e91-080000ef78c8", "text": "The consequences for human exposure to ionizing radiation can be classified into two categories\u2014stochastic or deterministic effects/tissue reactions. Explain the reasoning behind this classification and describe the main features of these effects, giving examples."}
{"_id": "Radiology$$$ef1c98ce-ad3b-4bdd-b910-f5291ba561fa", "text": "SQ1.\nThe Compton process results in a secondary photon, which has its own track, and an electron, which may also have enough energy to move away from where the primary ionization took place. In both cases, some of the dose is deposited in a different position than where the energy was lost from the beam.\n\u00a0SQ2.\nWhen going higher in altitude, the amount of atmosphere shielding us from incoming radiation is smaller than at the Earth\u2019s surface. Thus, at higher altitudes, the \u201cshielding\u201d provided by the atmosphere against the incoming radiation from space is less efficient. Radionuclide-based treatments are the main concern in terms of radiation exposure at hospitals. There is the need to protect healthcare staff and to keep dose to caregivers and the public within the acceptable levels.\n\u00a0SQ3.\nO\u1e24.\n\u00a0SQ4.\nPhysical, physicochemical, chemical, biological.\n\u00a0SQ5.\nFalse.\nMode of radioactive decay\n\nReleased particles\n\nGeneral reaction\n\nExample\n\n\u03b1-Decay\n\nHelium nucleus\n\nZAP\u00a0\u2192\u00a0Z\u00a0\u2212\u00a02A\u00a0\u2212\u00a04P\u00a0+\u00a024He\n\n92238U\u00a0\u2192\u00a090234Th\u00a0+\u00a024He\n\nSpontaneous fission (SF)\n\nTwo fragment nuclei\n\nZAP\u00a0\u2192\u00a0Z1A1D1\u00a0+\u00a0Z2A2D2\n\n100256Fm\u00a0\u2192\u00a054140Xe\u00a0+\u00a046112Pd\n\nNeutron emission (NE)\n\nNeutron\n\nZAP\u00a0\u2192\u00a0ZA\u00a0\u2212\u00a01D\u00a0+\u00a0n0***\n\n413Be\u00a0\u2192\u00a0412Be\u00a0+\u00a0n0***\n\n\u00a0SQ6.\nThe periodic table organizes chemical elements by their respective atomic number, while a chart of nuclides organizes nuclides according to the number of protons (Y-axis) and neutrons (X-axis) present in the nucleus.\n\u00a0SQ7.\nB.\n\u00a0SQ8.\nC.\n\u00a0SQ9.\nA.\n\u00a0SQ10.\nFalse.\n\u00a0SQ11.\nCobalt-60 \u03b3-rays (0.2\u00a0keV/\u03bcm)\u00a0<\u00a010 MeV proton (~5\u00a0keV/\u03bcm)\u00a0<\u00a05 MeV alpha particle (~100\u00a0keV/\u03bcm)\u00a0<\u00a0100 MeV carbon ion (~200\u00a0keV/\u03bcm)\u00a0<\u00a0200 MeV iron ion (>300\u00a0keV/\u03bcm).\n\u00a0SQ12.\nThe RBE is defined as the ratio of the high LET dose and the low LET reference dose (generally 250\u00a0kV X-rays) at isoeffect. The high LET dose-effect cell survival relation is a straight line over the full dose range. The low LET cell survival curve is however characterized by a broad shoulder in the low-dose range, followed by a straight, parallel steep downward curve in the higher dose range. Hence, the RBE in the low-dose range is higher than in the high-dose range.\n\u00a0SQ13.\nLate-responding normal tissues (low alpha/beta ratio) are better spared than tumors and early-responding normal tissues (high alpha/beta ratio) by decreasing the dose rate. Lowering the dose rate can be considered as decreasing the \u201cfraction size,\u201d with larger sparing of late-responding normal tissues than of tumors, hence a therapeutic beneficial effect.\n\u00a0SQ14.\nDeterministic effects or tissue reactions are those for which there is a threshold (varying between different effects), below which the effect is not seen. Above the threshold, the severity of the effect increases with dose. The syndromes of ARS are examples of deterministic effects.\nStochastic effects are the probabilistic ones, for which there is no threshold\u2014any increase in dose slightly increases the risk of the effect, and severity does not increase with increasing dose. Radiation cancers and genetic/hereditary effects are classified as stochastic effects."}
{"_id": "Radiology$$$9cedd9cd-21c8-4596-be4a-cea240e2f028", "text": "The Compton process results in a secondary photon, which has its own track, and an electron, which may also have enough energy to move away from where the primary ionization took place. In both cases, some of the dose is deposited in a different position than where the energy was lost from the beam."}
{"_id": "Radiology$$$d6d4b563-7ca4-4acf-87fe-63dbc19c00c0", "text": "When going higher in altitude, the amount of atmosphere shielding us from incoming radiation is smaller than at the Earth\u2019s surface. Thus, at higher altitudes, the \u201cshielding\u201d provided by the atmosphere against the incoming radiation from space is less efficient. Radionuclide-based treatments are the main concern in terms of radiation exposure at hospitals. There is the need to protect healthcare staff and to keep dose to caregivers and the public within the acceptable levels."}
{"_id": "Radiology$$$3c406a23-99a6-4ad4-9c98-38b2948d9653", "text": "False.\nMode of radioactive decay\n\nReleased particles\n\nGeneral reaction\n\nExample\n\n\u03b1-Decay\n\nHelium nucleus\n\nZAP\u00a0\u2192\u00a0Z\u00a0\u2212\u00a02A\u00a0\u2212\u00a04P\u00a0+\u00a024He\n\n92238U\u00a0\u2192\u00a090234Th\u00a0+\u00a024He\n\nSpontaneous fission (SF)\n\nTwo fragment nuclei\n\nZAP\u00a0\u2192\u00a0Z1A1D1\u00a0+\u00a0Z2A2D2\n\n100256Fm\u00a0\u2192\u00a054140Xe\u00a0+\u00a046112Pd\n\nNeutron emission (NE)\n\nNeutron\n\nZAP\u00a0\u2192\u00a0ZA\u00a0\u2212\u00a01D\u00a0+\u00a0n0***\n\n413Be\u00a0\u2192\u00a0412Be\u00a0+\u00a0n0***"}
{"_id": "Radiology$$$6625013c-31f3-483a-a959-fc31fa691892", "text": "The periodic table organizes chemical elements by their respective atomic number, while a chart of nuclides organizes nuclides according to the number of protons (Y-axis) and neutrons (X-axis) present in the nucleus."}
{"_id": "Radiology$$$46d3873c-2073-42c2-89aa-952ecc65f0bb", "text": "Cobalt-60 \u03b3-rays (0.2\u00a0keV/\u03bcm)\u00a0<\u00a010 MeV proton (~5\u00a0keV/\u03bcm)\u00a0<\u00a05 MeV alpha particle (~100\u00a0keV/\u03bcm)\u00a0<\u00a0100 MeV carbon ion (~200\u00a0keV/\u03bcm)\u00a0<\u00a0200 MeV iron ion (>300\u00a0keV/\u03bcm)."}
{"_id": "Radiology$$$4c7f5933-5e75-4a75-a594-b92909a18da2", "text": "The RBE is defined as the ratio of the high LET dose and the low LET reference dose (generally 250\u00a0kV X-rays) at isoeffect. The high LET dose-effect cell survival relation is a straight line over the full dose range. The low LET cell survival curve is however characterized by a broad shoulder in the low-dose range, followed by a straight, parallel steep downward curve in the higher dose range. Hence, the RBE in the low-dose range is higher than in the high-dose range."}
{"_id": "Radiology$$$f37ed955-799b-4793-95db-5b3a6e440b6e", "text": "Late-responding normal tissues (low alpha/beta ratio) are better spared than tumors and early-responding normal tissues (high alpha/beta ratio) by decreasing the dose rate. Lowering the dose rate can be considered as decreasing the \u201cfraction size,\u201d with larger sparing of late-responding normal tissues than of tumors, hence a therapeutic beneficial effect."}
{"_id": "Radiology$$$cb2a215f-7b98-4e46-ab95-af860ac67c3b", "text": "Deterministic effects or tissue reactions are those for which there is a threshold (varying between different effects), below which the effect is not seen. Above the threshold, the severity of the effect increases with dose. The syndromes of ARS are examples of deterministic effects."}
{"_id": "Radiology$$$a98573f6-2f02-4673-a628-f5b65944bc01", "text": "Stochastic effects are the probabilistic ones, for which there is no threshold\u2014any increase in dose slightly increases the risk of the effect, and severity does not increase with increasing dose. Radiation cancers and genetic/hereditary effects are classified as stochastic effects."}
{"_id": "Radiology$$$7c3f3518-c231-40a4-8047-8e93323d24ea", "text": "As described in Chap. 2, ionizing radiation (IR) can interact with matter directly, via molecule ionization, or indirectly, via the radiolysis of water. The result of this interaction is highly reactive ionized molecules that undergo a rapid cascade of chemical reactions, which leads to the breaking of chemical bonds. The radiolytic damage of biomolecules, such as carbohydrates, lipids, and proteins, is described as an indirect effect following water radiolysis and depends on biomolecule concentration in the irradiated medium. The products of water radiolysis\u2014radicals\u2014are often found in clusters and react with the biomolecules present within cells before they have a chance to diffuse and form a homogeneous distribution of products. To date, the studies on radiation-induced damage of these biomolecules are mainly based on the radical analysis of model molecules or on the molecular analysis of cellular mixtures after irradiation. Figure 3.1 shows an overview of the radiolysis products described in this chapter. The description of radiolysis products of the different biomolecules clearly demonstrates possible interactions and reactions between radicals and subcellular targets [1].\n\nA diagram of the membrane bilayer has the carbohydrate, protein, lipid, gated channel, and glycoprotein processes. Radioactive material causes lipid peroxidation, protein radical formation, and carbohydrate rearrangement.\n\nFig. 3.1\nSummary of the radicals produced with proteins, lipids, and carbohydrates following external IR exposure. Cellular exposure to IR leads to dissociation of biological macromolecules. Radiolysis of carbohydrates, proteins, and lipids is explained in their respective blue boxes. PO protein radicals, CO carbohydrate radicals, LO lipid radicals, OOH hydroxyl radicals, POOO protein peroxyl radicals, Trp tryptophan, Tyr tyrosine, His histidine, Met methionine, Cys cysteine, Gly glycine, ROH alcohol\u2014an analog of water where R is alkyl group, O is oxygen atom, and H is hydrogen atom"}
{"_id": "Radiology$$$09581332-fdcd-42d9-91ec-1a245bdbdd89", "text": "A diagram of the membrane bilayer has the carbohydrate, protein, lipid, gated channel, and glycoprotein processes. Radioactive material causes lipid peroxidation, protein radical formation, and carbohydrate rearrangement."}
{"_id": "Radiology$$$5b43ced2-cad0-4033-a597-f8435a40a3f2", "text": "Carbohydrates are hydrated organic molecules consisting of carbon (C), hydrogen (H), and oxygen (O), characterized by the formula Cx(H2O)y, where x and y denote the numbers of carbon or water in the molecule. Chemically, most carbohydrates are polyhydroxy aldehydes, ketones, alcohols, and acids, which can polymerize, form connected chains of molecules, and, therefore, become more complex [2]. In biological media, such as cells, some carbohydrates are a major energy source for all non-photosynthetic organisms (e.g., glycogen), and others have vital structural functions (e.g., chitin, cellulose) or are essential components of RNA, DNA, and biochemical cofactor synthesis (e.g., adenosine mono/di/triphosphate)."}
{"_id": "Radiology$$$24a033f0-9cbe-4991-9232-a85a08dd4b6d", "text": "Investigations of ionization damage to carbohydrates were done mainly in the fields of food and DNA [3]. Food irradiation can be used to extend shelf life (0.5\u20133.0\u00a0kGy), to inhibit sprouting (0.03\u20130.12\u00a0kGy), for insect disinfestation (0.2\u20130.8\u00a0kGy) and parasite disinfestation (0.1\u20133.0\u00a0kGy), and to eliminate pathogenic bacteria that do not form spores (1.5\u20137.0\u00a0kGy). In this context, it is important to know the chemical transformations occurring at a molecular level, including carbohydrates, that might have an adverse impact on the nutritional, sensory, or functional state of food [4]. In DNA, the sugar moiety plays an important role in the radiation-induced strand breaking process, even if not all the carbohydrate alterations are implied [3]."}
{"_id": "Radiology$$$a2283db3-f67a-4736-9736-a6089755d182", "text": "Model molecules of carbohydrates, such as ethylene glycol, glycerol, and glucose, were used to understand radiation products yielded from carbohydrates. Furthermore, they were used to study the formation of radicals via electron spin resonance (ESR) and electron paramagnetic resonance (EPR) or molecular products via high-performance liquid chromatography-mass spectrometry (HPLC-MS2) [4]."}
{"_id": "Radiology$$$09430e7a-7cd9-4193-9f88-183fb7968938", "text": "The radiolysis of carbohydrates in aqueous system is pH dependent and occurs mainly by an indirect interaction of hydroxyl radical (\u00b0OH) with C\u2013H bonds producing carbohydrate radicals. In contrast, carbohydrates react slowly with superoxide radicals (coming from solvated electrons) and scarcely with \u00b0H radicals [3, 4]. The carbohydrate radicals readily react with molecular oxygen or experience dismutation, dimerization, and elimination of alcohol or water (the most ubiquitous). Thus, radiolysis of carbohydrate inside the DNA molecule can lead to a degradation of the sugar structure and a loss of the base."}
{"_id": "Radiology$$$2666d31b-970d-4aff-9813-8b61cf465d0d", "text": "Lipids are small organic molecules, representing 21% of the eukaryotic cell content. Biochemically, they originate entirely or in part from carbanion-based condensations of thioesters, forming fatty acids, which are components of triacylglycerols (TAGs), phospholipids, and sphingolipids, or by carbocation-based condensation of isoprene units, forming isoprenol derivatives including sterols [2]. Lipids perform many essential functions in the cell including signaling and energy storage (due to their highly reduced state) and are the hydrophobic units of bilayers that form cellular and organellar membranes, which contribute to their function and topology."}
{"_id": "Radiology$$$c4d2f322-bd11-4075-bccc-78566d267d26", "text": "In aqueous biological media, during IR, lipids (mostly polyunsaturated acids) are likely to undergo lipid peroxidation. This is initiated by some water radiolysis species and presence of endogenous transition metals [5] and propagates the chain reaction and produces several other organic reactive radicals. These primary and secondary radicals, being able to penetrate the membrane interior, may react either with the lipid matrix or with integral membrane proteins."}
{"_id": "Radiology$$$1794c585-d2c3-4989-b3d9-0fd751701992", "text": "This radio-induced lipid peroxidation can thus contribute to the loss of cellular function through the inactivation of membrane enzymes and even of cytoplasmic (i.e., water soluble) proteins. Moreover, consequences include also perturbation of membrane function itself (thinning, change of structure or charge distribution, polarity) and consequently some carrier ion complexes and ion channels: efficiency can increase due to accumulation of polar oxidation products, but also be inhibited due to depolarization following conductance leakage [6]."}
{"_id": "Radiology$$$21e38d63-be8b-45fb-b82c-89f5cfe414d2", "text": "Proteins are biomolecules made of many linear chains of amino acid residues arranged in a three-dimensional structure, with various binding types (covalent or weak electrostatic bonds). Proteins constitute about 74% of the eukaryotic cell organic content. Amino acids, peptides, and proteins undergo a variety of reactions with radio-induced radicals which in most cases are pH dependent. These reactions involve mostly hydrogen abstraction at the \u03b1 position of the amino acid, electron transfer, addition, fragmentation and rearrangement, dimerization, disproportionation, and substitution [7]. Many studies showed that the most reactive amino acids are the aromatic (Trp, Tyr, His) and sulfur-containing (Met, Cys) amino acids, whereas the least reactive is glycine (Gly) [7, 8]. Once generated, the formed protein radicals can interact with oxygen, yielding a peroxyl radical, and with other biological components for instance yielding other reactive radicals or initiating lipid peroxidation."}
{"_id": "Radiology$$$8c674156-fa46-4661-ac4a-a35e2dc6a208", "text": "Some of the most commonly measured oxidative protein modifications are protein carbonyl groups originating from the oxidation of the amino acid residues or their side chains [9]. This leads to the formation of carbonyl derivatives, protein backbone cleavage, or beta scission of side-chain alkoxyl radicals of aliphatic residues (e.g., Ala, Val). In addition, oxidation of the sulfur of cysteine residues can lead to disulfur bond rearrangement."}
{"_id": "Radiology$$$672500b3-7ff2-4060-a788-a68a467649ac", "text": "Studies performed in biological media, e.g., cells, tend to show that in case of hydroxyl radicals coming from external irradiation, damage to DNA and lipids is a secondary process and proteins are more likely the initial targets, due to their relative amount and reactivity [7, 8] (Box 3.1)."}
{"_id": "Radiology$$$b84136c2-9cab-4538-a8e0-8dd8b50a0657", "text": "Radiolysis of carbohydrates and proteins occurs mostly via OH, begins with an abstraction of one hydrogen atom, and is pH dependent.\n\nRadiolysis of the carbohydrates within DNA may result in the loss of the base and thus DNA damage.\n\nLipids are likely to undergo peroxidation following IR processes, initiating a chain reaction leading to the production of organic reactive radicals.\n\nLipid peroxidation may lead to the loss of cellular functions including those associated with membranes.\n\nIn proteins, the most reactive amino acids are the aromatic (Trp, Tyr, His) and sulfur-containing (Met, Cys) ones, whereas the least reactive is glycine (Gly).\n\nProtein radicals may react with oxygen-yielding peroxyl radicals or with other biological compounds such as lipids, leading to lipid peroxidation or formation of other reactive radicals.\n\nSome of the most measured oxidative protein modifications are protein carbonyl groups.\n\nIn cells, proteins are the initial targets, due to their relative amount and reactivity."}
{"_id": "Radiology$$$05ebdefe-3144-4bbd-b970-850e825d894c", "text": "Radiolysis of carbohydrates and proteins occurs mostly via OH, begins with an abstraction of one hydrogen atom, and is pH dependent."}
{"_id": "Radiology$$$608b72dc-7884-45ce-a965-3a587a555fe9", "text": "Radiolysis of the carbohydrates within DNA may result in the loss of the base and thus DNA damage."}
{"_id": "Radiology$$$7028bfc0-1fd3-4e3b-8d34-a45a0c370b7f", "text": "Lipids are likely to undergo peroxidation following IR processes, initiating a chain reaction leading to the production of organic reactive radicals."}
{"_id": "Radiology$$$2c1b5e82-0027-49d6-9cf8-33a6923a499a", "text": "Lipid peroxidation may lead to the loss of cellular functions including those associated with membranes."}
{"_id": "Radiology$$$bc6ecb97-9e1d-4544-912e-a4b71b44360b", "text": "In proteins, the most reactive amino acids are the aromatic (Trp, Tyr, His) and sulfur-containing (Met, Cys) ones, whereas the least reactive is glycine (Gly)."}
{"_id": "Radiology$$$371cd839-09d7-4fb8-a707-1d15fb9c87de", "text": "Protein radicals may react with oxygen-yielding peroxyl radicals or with other biological compounds such as lipids, leading to lipid peroxidation or formation of other reactive radicals."}
{"_id": "Radiology$$$0653e602-d426-4982-b5cb-fabfc7cf0ddd", "text": "Some of the most measured oxidative protein modifications are protein carbonyl groups."}
{"_id": "Radiology$$$2fa9f424-fa6c-4626-ae4e-70a666a8e20c", "text": "In cells, proteins are the initial targets, due to their relative amount and reactivity."}
{"_id": "Radiology$$$90ca0dd8-f8a4-4df8-bb28-09cbed0f840c", "text": "In contrast to the above-described effects of IR in carbohydrates, lipids, and proteins, DNA radiolytic lesions occur both directly and indirectly, with the proportion being dependent on radiation type (\u03b1, \u03b2, \u03b3, heavier ions). Deoxyribonucleic acid (DNA) molecules are, unlike other biomolecules within a cell, unique, and if they get damaged and stay unrepaired, this may lead to serious and often lethal consequences."}
{"_id": "Radiology$$$3cdcb353-000e-49fd-aa90-6b6af349a713", "text": "Due to the importance of DNA, cells have a complex DNA damage response system, consisting of several interrelated signaling pathways, which can recognize the damage and initiate its repair. DNA can be damaged by different mutagens, such as oxidizing agents and alkylating agents, as well as by IR or UV light. However, the type of DNA damage depends on the type of mutagen, as well as the type, dose, and energy of radiation."}
{"_id": "Radiology$$$078e33fc-cce9-443b-92bf-1cb83b50df8b", "text": "DNA is a large molecule composed of two polynucleotide chains that coil around each other to constitute a double-stranded helix structure. DNA molecules carry the genetic information for most biological processes. The two antiparallel DNA strands are connected by hydrogen bonds, and the backbone of each strand is composed of nucleotides. Each nucleotide consists of an alternating sugar (2-deoxyribose), a phosphate group, and one of the four nitrogen-containing nucleobases [adenine (A), cytosine (C), guanine (G), or thymine (T)]. The structure of the bases is shown in Fig. 3.2. Two of the bases, thymine and cytosine, are single-ring groups (pyrimidines), whereas two other bases, adenine and guanine, are double-ring groups (purines).\n\nChemical structures of guanine-cytosine and adenine-thymine base pairs. The G-C base pair has three hydrogen bonds and the A-T base pair has two hydrogen bonds.\n\nFig. 3.2\nThe four DNA bases with respective hydrogen bonds (dashed lines). G guanine, C cytosine, A adenine, T thymine"}
{"_id": "Radiology$$$767f3f9f-5f5c-4725-85a2-1ea7eca1238f", "text": "Chemical structures of guanine-cytosine and adenine-thymine base pairs. The G-C base pair has three hydrogen bonds and the A-T base pair has two hydrogen bonds."}
{"_id": "Radiology$$$7778b164-c3ec-40ec-8013-6f61f9bc45c8", "text": "On one strand, nucleotides are joined to another by covalent bonds between the sugar of one nucleotide and the phosphate group of the next one (phosphodiester bond). The bases on the opposite strands are complementary, adenine pairs with thymine and guanine pairs with cytosine through hydrogen bonds [10]."}
{"_id": "Radiology$$$c5fce100-cf95-4918-9e39-ff15a49a6b93", "text": "A base lesion is defined as a modification (oxidation, alkylation, and deamination) of the chemical structure of one of the four DNA bases. Modification can occur through the loss of an electron, called oxidation, the transfer of an alkyl group, called alkylation, or the removal of an amino group, called deamination. After the break of the N-glycosidic bond between the DNA base and the 2-deoxyribose, a base can get lost and an abasic site can be created [11]. A representation of base lesion and abasic site is shown in Fig. 3.3. Sugar and base damages are quite easy for the cell to repair, as will be shown in Sect. 3.4.\n\nTwo chemical structures of double-stranded D N A depict a base lesion indicated by an alteration of the base and abasic site indicated by the gap between the bond of the D N A base and the 2-deoxyribose.\n\nFig. 3.3\nExamples of DNA base damages. In base lesions, the chemical structure of any DNA base is modified (highlighted with yellow and red), whereas in abasic sites, the N-glycosidic bond between the DNA base and the 2-deoxyribose is broken (as shown with red arrow). G guanine, C cytosine, A adenine, T thymine, H-bond hydrogen bond, P phosphate"}
{"_id": "Radiology$$$59cd4ca4-dc5d-4f1e-a92a-17e833a2eb0b", "text": "Two chemical structures of double-stranded D N A depict a base lesion indicated by an alteration of the base and abasic site indicated by the gap between the bond of the D N A base and the 2-deoxyribose."}
{"_id": "Radiology$$$eb80d5ff-c41c-4f9f-bff3-901cf77cecf2", "text": "Most of the sugar and base modifications are due to the hydroxyl radical (OH\u00b0). This radical reacts with the bases by addition to double bonds and by abstraction of hydrogen from the methyl group of thymine or from any C\u2013H bond, but more likely from the C4 and C5 positions of the deoxyribose [12]. Pyrimidine base modifications are more readily formed after radiation compared with purines. The main radiation-induced base degradation products can be found in the work of Cadet and Wagner [13]."}
{"_id": "Radiology$$$0c401dca-970d-46cc-8a8a-af21ce1615d7", "text": "A DNA\u2013DNA intrastrand cross-link (intra CL) is formed when chemical bonds are created between two DNA bases of the same DNA strand, while a DNA\u2013DNA interstrand cross-link (inter CL) is created when the chemical bonds are between bases of opposing strands. A chemical cross-link can also be generated with another endo- or exogenous molecule such as surrounding proteins to produce a DNA-protein cross-link (DPC). A DPC is formed as a covalent linkage between the protein and DNA after radiation-induced generation of DNA base radicals and amino acid radicals, mostly via hydroxyl radicals, which interact with each other [12]. A representation of the cross-links is given in Fig. 3.4.\n\nThree chemical structures of double-stranded D N A depict intra crosslink within a strand, inter crosslink between two strands, and D N A protein crosslink in a strand.\n\nFig. 3.4\nExamples of DNA cross-links. Chemical bonds (yellow) are created between two DNA bases within the same DNA strand (intra cross-link) or opposite strands of double-stranded DNA (inter cross-link). Proteins (blue) can become cross-linked to DNA to form DNA-protein cross-link (DPC). G guanine, C cytosine, A adenine, T thymine, H-bond hydrogen bond, P phosphate"}
{"_id": "Radiology$$$6a39675c-1112-4f36-bd29-33321f3c29e8", "text": "Three chemical structures of double-stranded D N A depict intra crosslink within a strand, inter crosslink between two strands, and D N A protein crosslink in a strand."}
{"_id": "Radiology$$$5c695d1d-638f-4617-bd26-5f9d02426462", "text": "They are problematic since replication and transcription mechanisms require a separation of the DNA strands. The most frequent cross-links observed are between tyrosine and thymine, tyrosine and cytosine, or lysine and thymine."}
{"_id": "Radiology$$$0f4f8f8d-e018-4edf-bd99-8c4164d11312", "text": "Single-strand breaks (SSBs) result from endogenous processes and exposure to exogenous agents such as radiation and chemicals. A representation of this process is given in Fig. 3.5. More frequently, IR creates free highly reactive radicals, especially hydroxyl radicals (OH\u00b0), which may react with nearby DNA and produce an SSB. The repair of SSB is rather simple, as it will be discussed in Sect. 3.4, and thus most of the time, an SSB does not cause any serious problems to the cell. The quantity of SSBs increases linearly with the IR dose applied, and their formation decreases when the linear energy transfer (LET) increases [14].\n\nA chemical structure of double-stranded D N A depicts a single-strand break or S S B, which is indicated by the absence of a phosphate group in a strand. G and C are linked by the H bond.\n\nFig. 3.5\nSingle-strand breaks (SSB): an illustration of a single-strand break in DNA. G guanine, C cytosine, A adenine, T thymine, H-bond hydrogen bond, P phosphate"}
{"_id": "Radiology$$$845c6971-41dd-4a89-be08-15ce17a302f4", "text": "A chemical structure of double-stranded D N A depicts a single-strand break or S S B, which is indicated by the absence of a phosphate group in a strand. G and C are linked by the H bond."}
{"_id": "Radiology$$$ff0e64dc-3233-4407-8332-f3616480e8f6", "text": "Double-strand breaks (DSBs) are produced when two SSBs on the two opposite DNA strands appear in close vicinity (one or two helix turns, thus about 15\u201320 DNA base pairs apart) [11]. Since DSBs are considered as the most important cause of cell death after IR, understanding their mechanisms of formation is essential. Radiation-induced DSBs increase linearly with radiation doses up to several hundred Gray (Gy) and have been detected at as low as 1\u00a0mGy [15]. As explained in Chap. 2, low linear energy transfer (LET) IR consists of electrons and photons that liberate secondary electrons and produce reactive oxygen species (ROS). However, even if they can create closely spaced lesions, the collision between particles and atoms in tissues is infrequent, thus leading to less, randomly distributed DSBs. On the contrary, the damages induced by high-LET particles are distributed along the particle tracks, which exhibit higher rates of collision and lead to nonrandom DSB distributions. Furthermore, there is a complexity of the nature of the DSBs formed according to the dose and the type of radiations, which influence the DNA damage response (DDR) and its efficacy. One can talk about \u201cclean DSBs,\u201d produced by hydrolysis of the phosphodiester bonds, which are easier to repair compared to \u201cdirty DSBs,\u201d which contain residual modified sugar residues produced by reaction of the 2-deoxyribose with hydroxyl radicals [11] (see Fig. 3.6). \u201cDirty\u201d DSBs are more frequently created by high-LET heavy ions or \u03b1 particles.\n\nTwo chemical structures of double-stranded D N A depict clean and dirty double-strand breaks or D S B, indicated by the absence of the phosphate group in both strands and the sugar-phosphate bond in both strands.\n\nFig. 3.6\nDouble-strand breaks (DSB): an illustration depicting different types of double-strand breaks in DNA. G guanine, C cytosine, A adenine, T thymine, H-bond hydrogen bond, P phosphate"}
{"_id": "Radiology$$$1e77212d-4e86-4d6c-b798-0f86eb849a3b", "text": "Two chemical structures of double-stranded D N A depict clean and dirty double-strand breaks or D S B, indicated by the absence of the phosphate group in both strands and the sugar-phosphate bond in both strands."}
{"_id": "Radiology$$$e2eff82e-9b53-4eb2-aedc-8c02c424c85c", "text": "Induction of DSB lesions by radiation is reviewed by Sage and Shikazono [16]. The ROS produced by the water radiolysis mediated by irradiation induces oxidized bases and loss of bases. Both lesions are repaired by base excision repair (BER, see Sect. 3.4), which can lead to DSB formation. Usually, DNA gaps of 1 or 2 nucleotides are filled by DNA polymerase and sealed by DNA ligase III\u03b1. During this process, SSBs can be generated in both DNA strands, and when they are close enough lead to a DSB. Moreover, the repair of a cluster lesion, e.g., an SSB opposite to an oxidative DNA lesion, could also result in the formation of a DSB as a result of irradiation. Additionally, through replication, if a damage is complex, e.g., effect on DNA secondary structures, formation of abasic sites, cross-links, and effect on DNA-binding proteins, the replication fork can stall and a DSB might occur. Moreover, conformational variables of the chromatin, which is a dynamic entity, and nuclear factors might affect DSB formation caused by radiation-induced radicals across the genome and according to the different points of the cell cycle."}
{"_id": "Radiology$$$fd3db9e4-47eb-4368-8aa5-7a15f492fade", "text": "Complex DNA damages, described as clustered DNA damages, are also named \u201clocally multiple damaged sites\u201d (LMDSs). LMDSs consist of closely spaced DNA lesions within a short DNA segment and are responsible for an increased cellular lethality since they are more difficult to repair. Two or more DNA lesions of the same or different type may be induced by IR within one or two helical turns of the DNA molecule, on the opposite strand. This clustered bistranded damage can be SSBs, DSBs, oxidized bases, and abasic sites. For example, at a dose of 1 Gy of IR, all this damage can be generated isolated or up to 10\u00a0bp apart [17]. Furthermore, the number of lesions per cluster depends on the radiation type and dose [18]. Experimental and theoretical studies have evidenced an increased complexity of the DNA damage induced by high-LET IR due to clustered ionizations, making complex DNA damage the signature of high-LET IR. Indeed, such lesions are considered the most important ones in terms of biological effects since they are the most challenging for the DNA repair machinery."}
{"_id": "Radiology$$$6b75f361-7ffb-4dfa-b83c-4bd456ea08cb", "text": "Not all cellular DNA damage is caused by exogenous factors; it can also be the result of cell metabolism as well as other normal cell processes. An overview of the average yield of DNA damage by endogenous factors per day and by low- and high-LET IR by 1 Gy is given in Table 3.1. One can see that even though the number of particles in the nucleus for high-LET radiation is much lower compared to low-LET radiation, the number of ionizations is the same. The dose deposition profile of high-LET IR induces more localized, complex, and clustered damages, which are more difficult to repair.Table 3.1\nComparison of DNA damage for endogenous factors and low- or high-LET radiations\n\u00a0\nEndogenous/cell/day\n\nLow-LET IR/Gy\n\nHigh-LET IR/Gy\n\nTracks in nucleus\n\n\u2013\n\n1000\n\nA few <1\n\nIonizations in nucleus\n\n\u2013\n\n100,000\n\n100,000\n\nIonizations in DNA\n\n\u2013\n\n1500\n\n1500\n\nBase damage\n\n16,000\n\n10,000\n\n10,000\n\nDNA single-strand breaks\n\n10,000\u201355,000\n\n700\u20131000\n\n300\u2013600\n\nDNA double-strand breaks\n\n8\n\n40\n\n>40\n\nCross-link DNA/DNA\n\n8\n\n30\n\n\u2013\n\nCross-link DNA/protein\n\nA few\n\n150\n\n\u2013\n\nLocally multiple damaged sites\n\nA few\n\nIncreased with LET\n\nThe number of tracks in the cell nucleus as well as the number of induced damages for high-LET IR depends on the particle type and energy; therefore, the given values represent only an estimate"}
{"_id": "Radiology$$$346c3166-e422-46ef-801e-ea70c6de1848", "text": "Ultraviolet (UV) light (100\u2013400\u00a0nm) is a natural genotoxic agent able to induce deleterious effects affecting biological processes and structures, but also DNA structure, leading to a genomic instability [19]. DNA damage induced by UV is mainly pyrimidine dimers, oxidized bases, as well as SSBs and DSBs. Nucleotides absorb UV radiations, which raise the DNA base to a highly reactive singlet or triplet state, leading therefore to photochemical reactions. The chemical nature and the amount of DNA damage strongly depend on the wavelength of the incident photons. Three main types of DNA lesions are formed involving two successive pyrimidine bases (CC, TT, TC, and CT) and leading to a DNA double-helix distortion: cyclobutane pyrimidine dimers (CPDs), pyrimidine 6-4 pyrimidone photoproducts (6-4PPs), and their Dewar isomers. The most energetic part of the solar spectrum corresponding to UVB (290\u2013320\u00a0nm) leads to the formation of CPDs and 6-4PPs, whereas less energetic but 20 times more intense UVA (320\u2013400\u00a0nm) also induces the formation of CPDs associated with a wide variety of lesions such as single-strand breaks and oxidized bases. Furthermore, in addition of the direct photolesions induced, some indirect DNA damage can occur through the production of ROS, especially hydroxyl radicals (OH\u00b0) and RNS. ROS can induce the oxidation of pyrimidine and purine bases, and also the deoxyribose backbone of DNA, such as the induction of the most frequent, i.e., the 8-hydroxyguanine (8-oxo-G) and in a smaller extent SSBs and DSBs. Moreover, the ROS induced by UV can lead to the alkylation of bases and to cross-linking of DNA\u2013DNA or DNA-protein. CPDs and 6-4PPs are mostly formed between TT and TC, and in less proportion for CT and CC sequences. Additionally, the chromatin structure, as well as the composition of the neighboring nucleotide sequence of pyrimidine dimers, also influences the formation of UV-induced DNA damage. More recently, some studies discussed the influence of the epigenetic markers (DNA methylation, histone posttranslational modifications) in the induction of UV-induced lesions at a particular locus. Indeed, the methylation of DNA at C5 of cytosine (5-mC) was associated with an increase by 80% of the CPD yield and a decrease by 3 of the 6-4PP [20] (Box 3.2)."}
{"_id": "Radiology$$$d1503c31-7e3d-460a-8c75-fa7562837eaa", "text": "Deoxyribonucleic acid (DNA) is a large molecule composed of two polynucleotide chains that coil around each other to constitute a double-stranded helix structure.\n\nIR can cause DNA base or sugar damage, single- or double-strand breaks, DNA interstrand, intrastrand, or protein cross-links.\n\nDSBs are considered to be one of the most serious DNA lesions.\n\nHigh-LET IR induces more localized, complex, as well as clustered damage, which has the most serious potential biological consequences."}
{"_id": "Radiology$$$8652480f-e222-42e5-b8c0-35775a401170", "text": "Deoxyribonucleic acid (DNA) is a large molecule composed of two polynucleotide chains that coil around each other to constitute a double-stranded helix structure."}
{"_id": "Radiology$$$6e26b497-0ae9-4bea-9e30-0ec45c83dfbb", "text": "IR can cause DNA base or sugar damage, single- or double-strand breaks, DNA interstrand, intrastrand, or protein cross-links."}
{"_id": "Radiology$$$0360ec6d-4e83-407c-911a-ddfda405a94c", "text": "DSBs are considered to be one of the most serious DNA lesions."}
{"_id": "Radiology$$$f6bbc4c2-c9ad-459f-a3ea-47502fcf8d0d", "text": "High-LET IR induces more localized, complex, as well as clustered damage, which has the most serious potential biological consequences."}
{"_id": "Radiology$$$33941164-06e0-4fbc-a66e-7b70dc287c22", "text": "As described above, various types of DNA lesions occur through endogenous and exogeneous factors frequently in a human cell. Depending on the complexity, these lesions challenge cellular genomic integrity. At the time of cell division, many cellular processes are coordinated to ensure the maintenance of the stable genome and ascertain the preservation of the nuclear material [21]. These processes are known as the DNA damage response (DDR). The types of DNA damage and their primary repair pathway are listed in Table 3.2. The DDR signaling capacity can, if not sufficient, cause problems for the cell to maintain genome stable, which may result in a mutation. This may, as a last consequence, trigger transformation into a tumor or cancer cell. As DNA damage occurs physically, it can be repaired; however, when the mutation is established, the alterations that took place in the base sequence cannot be repaired. Accordingly, it is essential for normal cells to maintain DDR function to avoid such process.Table 3.2\nDNA damage repair mechanisms\n\nDNA repair mechanism\n\nDNA damaging/genotoxic agents\n\nDNA lesion feature\n\nDNA damage example\n\nDNA repair features\n\nBase excision repair (BER)\n\nReactive oxygen species, X-rays, alkylating agents\n\nOxidative lesion\n\nOxidation (8-oxo-G) uracil, single-strand break\n\nRemoval of base by N-glycosylase abasic sugar removal, replacement\n\nNucleotide excision repair (NER)\n\nUV lights and polycyclic aromatic hydrocarbons\n\nHelix-distortion lesion\n\nBulky adducts, intrastrand cross-link\n\nRemoval of DNA fragment and replacement\n\nMismatch repair (MMR)\n\nReplication\n\nReplication error\n\nA\u2013G mismatch, T\u2013C mismatch, insertion, deletion\n\nRemoval of strand by exonuclease, digestion, and replacement\n\nDouble-strand break repair (DSBR)\n\nX-rays, ionizing radiations, reactive oxygen species, anti-tumor agents\n\nDouble-strand DNA breaks\n\nDouble-strand break, interstrand cross-link\n\nUnwinding, alignment, ligation"}
{"_id": "Radiology$$$cb41af91-e46f-490f-b0cd-4f06f9108a72", "text": "Base excision repair (BER) is the most common and important DNA repair process involved in removing minor DNA base defects. Many BER genes are extremely maintained from bacteria to humans demonstrating that BER is a fundamental repair process [22]. BER is a well-studied pathway for damage repair caused by respiration, spontaneous hydrolysis, and alkylation events, such as single-nucleotide bases (small, non-helix-distorting base lesions), that occur hundreds of times every day in each cell [23]. Thus, the BER system is critical to eliminate damaged bases that could otherwise produce mispair mutations or DNA replication breakdowns. In BER, SSBs are formed and repaired in an organized chain of events involving multiple proteins. Within BER, two pathways are simultaneously active: short patch repair (SP-BER), which is used to eliminate a broken base which has a non-bulky character, and long patch repair (LP-BER), which can replace the area in which the damaged DNA base is found. A schematical view of SP- and LP-BER can be found in Fig. 3.7.\n\nA flow diagram depicts short and long patch repair carried out by the activities of glycosylase, A P lyase, polymerase, and standard displacement. The hemieacetal and aldehyde formations lead to short and long patch repairs, respectively.\n\nFig. 3.7\nShort and long patch base excision repair: recognition of the DNA lesion occurs by a specific DNA glycosylase which removes the damaged base by hydrolyzing the N-glycosidic bond. The remaining AP site is processed by APE. Depending on the cleavability of the resulting 5\u2032dRP by Pol\u03b2, repair is performed via the short or long patch BER pathway. Reproduced with permission from [24]. AP-endonuclease apurinic/apyrimidinic endonuclease, AP-lyase apurinic/apyrimidinic lyase, OH hydroxide, P phosphate, 5\u2019dRP 5\u2032 deoxyribose phosphate, Lig III ligase III, XRCC1 X-ray repair cross-complementing 1, RF-C replication factor C, Fen1 flap structure-specific endonuclease 1, PCNA proliferating cell nuclear antigen, Lig I ligase I"}
{"_id": "Radiology$$$aab5c727-701f-4a92-9538-ba84b184845c", "text": "A flow diagram depicts short and long patch repair carried out by the activities of glycosylase, A P lyase, polymerase, and standard displacement. The hemieacetal and aldehyde formations lead to short and long patch repairs, respectively."}
{"_id": "Radiology$$$7af5e1bb-514e-42d4-8cc3-a4f531ad1cec", "text": "In BER, specialized proteins called glycosylases recognize and remove the majority of the damaged DNA bases. There are multiple glycosylases, each of which is unique to a certain form of base damage. All these enzymes have, as their primary function, to cut out the base which got damaged yet without impacting the DNA backbone, causing further damage in an abasic place in the DNA (either apurinic or apyrimidinic site) [25]. Although each DNA glycosylase is specialized to a certain substrate and works in a distinct manner, they all have a single principal way of action: first, taking the damaged base outside the DNA helix, thus assisting the detection of bases with minute alterations, and, second, triggering the cutting of an N-glycosidic bond, which in turn enables the formation of an abasic site [22]. Humans have 11 DNA glycosylases, which are classified as monofunctional (removing a base which results in formation of an AP site), bifunctional (removing a base and cutting the DNA backbone close to the damaged base), or Nei-like (which removes the base but also cuts each side of it)."}
{"_id": "Radiology$$$fc5ffcfe-5cfc-4937-a00d-cdc0abc6d2e5", "text": "Once the monofunctional DNA glycosylase has created the AP site, another repair enzyme, AP endonuclease 1 (APE1), incises and hydrolyzes the AP site, removing the base followed by the sugar residue, cutting the DNA backbone, and as a result an SSB is formed. APE1 also operates on bifunctional glycosylase products, creating a one-nucleotide gap product after hydrolysis. Polynucleotide kinase phosphatase (PNKP), whose product is suitable for DNA polymerase action, is required for the repair of oxidized DNA bases. When there is a gap or SSB is formed, poly(ADP-ribose) polymerase 1 is activated (PARP1) [23]. In this way, the integrity of the break can be maintained. PARP1 also orchestrates, via its poly(ADP-ribosyl)ation activity, a cascade of proteins binding to the SSBs with the main aim to detect and promote its further repair."}
{"_id": "Radiology$$$2e4cafdd-d6b1-4354-ac17-7f4626554a83", "text": "The most common polymerase used in BER is DNA polymerase (Pol), which fills the gap with the proper nucleotide and catalyzes a lyase reaction. SP-BER is linked by the DNA ligase III-XRCC1-mediated mechanism to complete the process [25]. In contrast to SP-BER, LP-BER occurs when a lesion is resistant to Pol cleavage, and polymerases such as PCNA, flap endonuclease 1 (FEN1), and PARP are recruited. While displacing the broken strand, the polymerase synthesizes DNA and inserts a repair patch consisting of 2\u201312 of the correct nucleotides into the gap. The repair synthesis is carried out by the T complex of the replication factor C (RFC)/proliferating cell nuclear antigen (PCNA)/DNA polymerase \u03b4/\u03b5. Here, the lap endonuclease 1 (FEN1) acts by taking out the flap structure that is overhanging the damaged base site, and the nick that is formed is ligated by DNA ligase I [14]. SP-BER and LP-BER primarily differ in how many of the DNA bases are cut out during the repair (see Fig. 3.8). SP-BER only replaces the bases which are damaged, whereas LP-BER cuts out and replaces up to ten nucleotides.\n\nTwo flow diagrams compare G G R or global genomic repair and T R or transcription-coupled repair. The common steps are incision, excision, polymerization, and ligation.\n\nFig. 3.8\nNucleotide excision repair (NER) pathway: during global genomic repair (GGR), recognition of the DNA lesion occurs by XPC\u2013HR23B, RPA\u2013XPA, or DDB1\u2013DDB2. DNA unwinding is performed by the transcription factor TFIIH and excision of the lesion by XPG and XPF\u2013ERCC1. Finally, resynthesis occurs by Pol\u03b4 or Pol\u03b5 and ligation by DNA ligase I. During transcription-coupled repair (TCR), the induction of the lesion results in blockage of RNAPII. This leads to assembly of CSA, CSB, and/or TFIIS at the site of the lesion, by which RNAPII is removed from the DNA or displaced from the lesion, making it accessible to the exonucleases XPF\u2013Ercc1 and XPG cleaving the lesion-containing DNA strand. Resynthesis again occurs by Pol\u03b4 or Pol\u03b5 and ligation by DNA ligase I. 23B: Reproduced with permission from Christmann et al. [24]. DDB1 DNA damage-binding protein 1, DDB2 DNA damage-binding protein 2, RPA replication protein A, TFIIH transcription factor IIH, ERCC1 excision repair cross-complementing group 1 protein, Poly\u03b4/\u03b5 DNA polymerase delta/epsilon, PCNA proliferating cell nuclear antigen, Lig1 DNA ligase 1, RNAPII RNA polymerase II, CSA and CSB Cockayne syndrome factors A and B, TFIIS transcription initiation factor IIS, HR23B homologous recombinational repair group 23B"}
{"_id": "Radiology$$$fbc6d942-8d92-413b-aa85-4dbab68af9b9", "text": "Two flow diagrams compare G G R or global genomic repair and T R or transcription-coupled repair. The common steps are incision, excision, polymerization, and ligation."}
{"_id": "Radiology$$$180efb57-0609-4582-8f7b-4db651f8367e", "text": "IR-induced base damage is effectively repaired by BER. BER deficiencies can result in a higher mutation rate but seldom cause cellular radiosensitivity [26]. The X-ray cross-complementing factor 1 (XRCC1) gene mutation, which causes a 1.7-fold increase in radiation sensitivity, is an exception. The radiation sensitivity of XRCC1-deficient cells, on the other hand, could be due to XRCC1\u2019s involvement in other repair processes, such as SSB repair. Reduced repair and radiosensitization can be caused by mutations, deletions, or inhibition of either of these genes."}
{"_id": "Radiology$$$cc6cb14e-2a19-48de-b296-3124e84956bc", "text": "In both BER and SSB repair, DNA polymerase beta (pol) is a key enzyme. Under some situations, cells lacking pol or expressing a dominant negative construct to pol, which inhibits its function, have been demonstrated to be more vulnerable to ionizing radiation in vitro [27]. Small-molecule medicines that block PARP1 have also been produced. The PARP inhibitors are a medication that targets BER and SSB repair and are now being tested in clinical trials for cancer treatment, as described in Chap. 6 (Box 3.3)."}
{"_id": "Radiology$$$ed152078-118b-488c-b229-ccd2bcdbb7d3", "text": "BER is a specific repair mechanism that is used to handle DNA base damage.\n\nBER removes single-nucleotide base lesions (small, non-helix-distorting base lesions) from the genome.\n\nSP-BER and LP-BER are two complementary BER systems essential for removing base damage and fixing SSB in DNA, minimizing mutagenesis but differing in what base damages they can handle.\n\nBER inhibitors have showed potential as radio/chemosensitizers in a variety of malignancies, or they can create synthetic deadly alliances with common cancer mutations."}
{"_id": "Radiology$$$9e5a365f-d3e0-449e-b814-ed92044a4c2d", "text": "BER is a specific repair mechanism that is used to handle DNA base damage."}
{"_id": "Radiology$$$1f57f29a-b7c8-443e-844b-21ef3e2d8764", "text": "BER removes single-nucleotide base lesions (small, non-helix-distorting base lesions) from the genome."}
{"_id": "Radiology$$$bc859b7e-fe17-426a-85ac-3756ba9f4bf8", "text": "SP-BER and LP-BER are two complementary BER systems essential for removing base damage and fixing SSB in DNA, minimizing mutagenesis but differing in what base damages they can handle."}
{"_id": "Radiology$$$ca502eb2-a5cd-4809-a804-4c48ee0bf6ba", "text": "BER inhibitors have showed potential as radio/chemosensitizers in a variety of malignancies, or they can create synthetic deadly alliances with common cancer mutations."}
{"_id": "Radiology$$$63e880af-b6b5-4c80-9eb8-f1d7eb62d87f", "text": "From unicellular bacteria to complex humans and plants, nucleotide excision repair (NER) works in a similar way. In humans, NER is known for its one-of-a-kind repair process to remove photolesions caused by UV radiation. However, there is one circumstance in which NER genes can influence the IR response. More DNA cross-links are formed when cells are irradiated under hypoxia than when irradiated under normoxic circumstances. Excision activity of two NER genes, DNA excision repair protein (ERCC1) and DNA repair endonuclease (XPF), is required for such cross-links, among other things. Defects in either of these genes may cause hypoxic cells to become more radiosensitive. As a result, the status of the NER pathway is relevant to radiotherapy in combination with specific chemotherapeutic drugs, as well as hypoxic tumors treated only with radiotherapy [28]."}
{"_id": "Radiology$$$e63044c5-2f46-447e-9b60-b4fec89848de", "text": "The principle of NER is shown in Fig. 3.8. The lesion-recognizing NER factors look for unpaired single-stranded DNA on the other side of the damaged strand [22]. The oligonucleotide that contains the lesion is eliminated, and to restore the DNA to its original form, a repair patch is created using the opposite undamaged complementary strand as a template. With varied degrees of success, NER eliminates lesions from the entire genome and can be separated into two paths [24]:1.\nGlobal Genome Repair (GGR or GG-NER): GG-NER is a genome-wide process, i.e., lesions can be eliminated from DNA that encodes, or not, for genes.\n\u00a02.\nTranscription-Coupled Repair (TCR or TC-NER): TC-NER exclusively eliminates lesions in the DNA strands of genes that are actively transcribed. If a DNA strand that is actively transcribed is broken, the RNA polymerase could inhibit DNA repair by blocking access to damage sites. TC-NER has evolved to overcome RNA polymerase\u2019s barrier by essentially eliminating it from the damage site, allowing repair proteins access."}
{"_id": "Radiology$$$3e7bc18a-9b59-4c27-84d4-4ff80bcd4875", "text": "Global Genome Repair (GGR or GG-NER): GG-NER is a genome-wide process, i.e., lesions can be eliminated from DNA that encodes, or not, for genes."}
{"_id": "Radiology$$$f0376337-5684-45d6-8058-30341d447b5c", "text": "Transcription-Coupled Repair (TCR or TC-NER): TC-NER exclusively eliminates lesions in the DNA strands of genes that are actively transcribed. If a DNA strand that is actively transcribed is broken, the RNA polymerase could inhibit DNA repair by blocking access to damage sites. TC-NER has evolved to overcome RNA polymerase\u2019s barrier by essentially eliminating it from the damage site, allowing repair proteins access."}
{"_id": "Radiology$$$b942c6f7-2e6c-4f0f-be7e-8808f678f116", "text": "In the early damage recognition phase, the two NER subpathways vary. In GGR, the NER proteins are recruited by the stalled RNA polymerase in collaboration with Cockayne syndrome protein B and A (CSB and CSA). In TCR, the NER proteins are engaged by the stalled RNA polymerase in collaboration with CSB and CSA [14]."}
{"_id": "Radiology$$$3eb6c830-499b-463c-b2ca-36ac80b517e6", "text": "Mutations in the NER genes do not cause IR sensitivity. However, defective NER increases sensitivity to UV-induced DNA damage and anticancer drugs that create bulky adducts, such as alkylating agents. Human DNA repair deficiency such as xeroderma pigmentosum, in which individuals are hypersensitive to UV radiation, is caused by germline mutations in the NER genes [14] (Box 3.4)."}
{"_id": "Radiology$$$5a89d365-baa0-4de2-af69-df9a7c8fc5ae", "text": "Nucleotide excision repair (NER) is a technique for removing bulky adducts from DNA, chiefly those caused by UV.\n\nDefects in certain NER proteins may result in enhanced radiosensitivity of hypoxic cells.\n\nLarge DNA lesions like thymine dimers and cisplatin adducts are repaired using a DNA repair pathway.\n\nThe two types of NER pathways are global genome repair (GGR or GG-NER) and transcription-coupled repair (TCR) (TCR or TC-NER)."}
{"_id": "Radiology$$$cc8af1ae-c763-4eed-924a-d8dc33dd4705", "text": "Nucleotide excision repair (NER) is a technique for removing bulky adducts from DNA, chiefly those caused by UV."}
{"_id": "Radiology$$$529ecc2f-33c1-47df-8273-8ecb35b8ed50", "text": "Defects in certain NER proteins may result in enhanced radiosensitivity of hypoxic cells."}
{"_id": "Radiology$$$41e28159-aa2b-4572-8644-9bc58799b08d", "text": "Large DNA lesions like thymine dimers and cisplatin adducts are repaired using a DNA repair pathway."}
{"_id": "Radiology$$$12099a17-480a-4589-92c7-73f2a131ed82", "text": "The two types of NER pathways are global genome repair (GGR or GG-NER) and transcription-coupled repair (TCR) (TCR or TC-NER)."}
{"_id": "Radiology$$$d85b6388-e8f9-4c64-951e-695839781853", "text": "The mismatch repair (MMR) system has a role after the cellul replication process, where sometimes incorrect bases pair with each other (which is called a mismatch). Therefore, MMR aids in keeping DNA homeostasis and plays a major role in evolutionary genomic stability [29]. Its basic purpose is to rectify the small insertion-deletion loops (indels) and the base-base mispairs that are spontaneously generated at the time of DNA replication. These mis-incorporated bases have escaped the proofreading action of replication polymerase. Usually, the polymerase that carries out the DNA synthesis process is not completely error-free. The DNA polymerase on average makes one mistake for every 105 nucleotides [29], which implies that ~100,000 errors arise through each S phase of the cell. Even though the DNA polymerase is there to ascertain that such mistakes do not occur, a few mutations can go unnoticed by it and hence the MMR-associated genes act as the second line of defense. However, if the cell is deficient in the MMR process, these errors remain uncorrected. Therefore, the mutational rate and sequence length modification in the microsatellites, which is a known trait of tumor cells, increase. The relevance of MMR in radiation-induced damage and cellular radiosensitivity is a matter of controversy. The mismatch repair (MMR) pathway was first discovered in E. coli cells [30]. Researchers have explored and understood that the MMR pathways and its associated proteins are evolutionarily conserved in almost all organisms including humans [31]. MMR works by inserting or deleting the mispaired bases by recognizing the mispaired lesion; excision, i.e., removal of the erroneous strand; and DNA resynthesis and gap repair by filling it with the correct resynthesized DNA."}
{"_id": "Radiology$$$eb90c6bd-851f-491d-8d04-6a24ca3e6ead", "text": "The parent strand, which includes a palindrome DNA sequence \u201cGATC\u201d and adenine, is methylated by the enzyme deoxy-adenine-methylase. However, after replication when there are two new incorrect strands, methylation in the newly formed daughter strand is not seen [32] (Fig. 3.9). Such alterations are recognized and repaired by the methyl mismatch repair. The specific region of mispairing is recognized by the Mut S protein, which is coupled by the MutL. The activity of MutS is stimulated by the heterodimer MSH2\u2013MSH6, along with MutS\u03b1. The MutS\u03b1 recognizes small IDLS comprising 1\u20132 nucleotides, whereas the MSH2\u2013MSH6 identifies longer insertion-deletion loop-type mismatches. After the binding of MutS to the DNA, it is followed by the ATP-dependent prerequisite of MutL homolog (MSH) complex. The parent strand is recognized by the MutL, which brings the misrepaired region nearer and leads to a loop formation around the area. Another protein, MutH, an endonuclease enzyme, performs the activity of cleaving. Next, UVr-D, a helicase, releases the cut strand leading to the formation of a gap where the new error-free or accurate nucleotide sequence is included by the polymerase 1 and joined by ligase. Cells that are deficient in the MMR proteins exhibit a high frequency of mutations and also irreversible microsatellite instability. Accordingly, individuals with germline mutations in MMR genes are more susceptible to various types of cancers [33] (Box 3.5).\n\nA flow diagram depicts the steps of mismatch detection in double-stranded D N A, nicking A T P to A D P plus P i. excision, re-synthesis, and ligation.\n\nFig. 3.9\nOverview of eukaryotic mismatch repair system. In the human cell, the predominantly found MutS\u03b1 (MSH2\u2013MSH6) or the MutS\u03b2 recognizes the DNA mismatch repair and initiates its repair. Some of the crucial molecules which participate in the repair are the MutL\u03b1 (MLH1-PMS2), the proliferating cell nuclear antigen (PCNA), and the replication factor (RCF). EXO1 catalyzes the repair, and ligase finally ligates the repaired DNA"}
{"_id": "Radiology$$$921b6471-1379-419f-8d56-e1071c296497", "text": "A flow diagram depicts the steps of mismatch detection in double-stranded D N A, nicking A T P to A D P plus P i. excision, re-synthesis, and ligation."}
{"_id": "Radiology$$$ff60e472-2102-4a5d-8fdd-b766a51a3abf", "text": "MMR targets DNA mismatches that arise mainly during replication, as well as repairing mismatches that occur in DNA following treatment with alkylating agents.\n\nThe MMR pathway detects and repairs erroneous insertions, deletions, and base substitutions that have not been detected by the proofreading function of DNA polymerase during DNA replication, thus maintaining the genome stability.\n\nIt works by recognition of mispair, excision of the affected strand, and filling of the gap."}
{"_id": "Radiology$$$dcd4568d-c2de-4488-a608-6d8769cfa6c4", "text": "MMR targets DNA mismatches that arise mainly during replication, as well as repairing mismatches that occur in DNA following treatment with alkylating agents."}
{"_id": "Radiology$$$4030063e-0c30-4480-b9b0-aee1853dbd7e", "text": "The MMR pathway detects and repairs erroneous insertions, deletions, and base substitutions that have not been detected by the proofreading function of DNA polymerase during DNA replication, thus maintaining the genome stability."}
{"_id": "Radiology$$$2955eabe-5fe9-4a32-ac91-fa048b963d68", "text": "It works by recognition of mispair, excision of the affected strand, and filling of the gap."}
{"_id": "Radiology$$$ae656c2c-07f3-463a-950a-6dac7100c70a", "text": "Double-strand breaks (DSBs) are the most lethal kind of DNA damage because even one uncorrected DSB can result in loss of genetic information and finally lead to cell death. Moreover, such unrepaired or misrepaired DSBs can lead to augmented genomic instability and eventually tumorigenesis [21]. Accordingly, for a cell to pursue its genetic information, a functional DSB repair system is of major importance. As a result, cells have evolved a dedicated response to identify and mend DSBs. For repair of DNA DSBs, two principal pathways are used, namely homologous recombination (HR) and Non-homologous end joining (NHEJ)."}
{"_id": "Radiology$$$920bebc5-cfa1-4193-8d7c-20a4781d0b97", "text": "These pathways differ with respect to the use of homologous template DNA as well as in DNA repair fidelity. HR utilizes undamaged sister chromatid as its template to repair the damage, and therefore it is error-free. However, NHEJ works by eliminating the damaged DNA followed by direct ligation and hence is error-prone. As HR needs an undamaged template, it only operates in late S and G2, in contrast to NHEJ, which has the capacity for DSB repair regardless of the cell\u2019s position in the cell cycle phase [33]."}
{"_id": "Radiology$$$51e4fe9f-6c47-40fd-aa2f-12d4fb35066e", "text": "The homologous recombination (HR) molecular pathway is associated with a large number of cellular processes, from imparting genetic diversity to DNA repair or replication. HR is evolutionarily conserved from bacteria to mammalian cells. This pathway is essential for fixing DNA damages with high accuracy by using the genomic code of the chromosomal copy which was not damaged [34]. HR works by precisely repairing the DSB, shielding cells from any chromosomal abnormalities such as those observed in many cancers. Throughout the process of DNA replication, HR-associated proteins endorse the faithfulness and restoring of distressed DNA replication forks. This adds sturdiness, serving the replication machinery to circumvent under replication and succeeding segregation tribulations of the chromosome. Inherent HR insufficiency in cells can persuade instability in the genome and further lead to cancer. Conversely, discrepancy in the HR pathway also sensitizes tumors not only to DNA damage treatment but also to other potential DNA repair inhibitors for remedial repair pathways."}
{"_id": "Radiology$$$ab8714c7-d783-4486-95f3-374b4dc8b75c", "text": "For the commencement of the HR pathway, the break site 5\u2032\u20133\u2032 end resection is a requirement, which not only exposes the single-stranded DNA (ssDNA) overhangs but also averts the NHEJ pathway to repair the DNA breaks (Fig. 3.10) [36]. The repair proteins MRE11 (meiotic recombination 11), RAD50 (RAD50 double-strand break repair protein), and NBS1 (nibrin) form the MRN complex, and together with the ataxia-telangiectasia mutated (ATM) kinase, they are the first to recognize the DNA damage. By attaching to the DNA ends, the MRN complex instigates the process of DNA end resection. Next C-terminal binding protein 1 interacting protein (CtIP) is employed so as to produce the overhangs at the 3\u2032 end of the single-stranded DNA [36]. The preference of the choice of repair pathway is governed by the p53-binding protein 1 (53BP1) and breast cancer-associated protein 1 (BRCA1) contrasting activity in addition to the MRE11 resection activity. Whenever a DNA break is identified, both BRCA1 and 53BP1 compete to govern the commitment of the cell to undergo NHEJ or HR, respectively. By hindering the DNA end resection and concurrently securing two double-stranded DNA (dsDNA) ends, facilitating their successive ligation, 53BP1 supports the NHEJ pathway [37]. The mechanism by which BRCA1 suppresses 53BP1 still remains uncertain. Ubiquitination of CtIP occurs when BRCA1 interacts with BRCA1-associated RING domain protein 1 (BARD1). This subsequently enhances the affinity of CtIP for DNA and as a consequence promotes resection [37]. At this time, the DNA ends are protected and prevented from resection by replication timing regulatory factor 1 (RIF1), which is a 53BP1-interacting partner and a Shieldin complex. The increased HR activity can be attributed to either the loss of 53BP1 or the Shieldin complex that weakens the NHEJ pathway. Blocking wide-ranging end resection is central, meant for preventing the hyper-recombination by HR and stopping the loss of genetic material. Some other lethal repairing pathways like break-induced replication (BIR) or single-strand annealing (SSA) can lead to wide-ranging resection whose outcome is loss of heterozygosity [35].\n\nA flow diagram depicts the following steps. Pathway selection, resection, formation of RAD 51 filament, homology search and strand invasion, synthesis, S D S A, heteroduplex extension, resolution, and dissolution.\n\nFig. 3.10\nOverview of homologous recombination (HR) pathways in double-strand break repair. When cells suffer a DSB (purple lines), they can repair them either by HR, with the help of a template that is homologous (turquoise lines), or by the NHEJ pathway. (a) BRCA1 promotes the HR pathways, whereas the Shieldin complex, RIF1, and 53BP1 promote the NHEJ pathway. (b) The resection process is performed by the MRN complex along with CtIP, EXO1, BLM, and DNA2 that form the 3\u2032 ssDNA overhangs. These overhangs are then coated with the RPA (green boxes), which is later shifted by the RAD51 (brown circles). On the other hand, single-strand annealing occurs in case of the RAD-independent repair process, where annealing of the complementary DNA sequences takes place followed by overhangs cleaved by the flap endonuclease and finally the ends of the DNA are ligated. (c) Positive regulators of RAD51 such as RAD51 paralogs, BRCA2, and PALB2 aid in the formation of the RAD51 filament, whereas RECQL5 and FBH2 negatively regulate RAD51. (d) The RAD51 paralogs and RAD54A-B support the RAD51-mediated homology searching and strand invasion. At the same time, FANCM and RTEL negatively govern the RAD51-mediated D loops. (e) The homologous template in the form of sister chromatid or a homologous chromosome is used by the DNA polymerases to copy the missing sequence. (f) The DNA is resolved into a noncrossover product when SDSA dislodges the D loop. (g) In case there is an extension of the heteroduplex and development of Holliday junction created by the second-end capture, the intermediate states can be resolved by either resolution or dissolution. (h) The outcome of resolution is both the crossover and noncrossover products. (i) The outcome of dissolution is a noncrossover product. Adapted with permission (CCBY) from Sullivan and Bernstein [35]. Abbreviations: DSB double-strand DNA break, HR homologous recombination, NHEJ Non-homologous end joining, BRCA1 breast cancer gene 1, RIF1 Rap1-interacting factor 1, 53BP1 p53-binding protein 1, MRN MRE11\u2013RAD51\u2013NBS1 complex, CtIP CtBP-interacting protein, EXO1 exonuclease 1, BLM Bloom\u2019s syndrome helicase, RecQ helicase-like gene, DNA2 DNA replication helicase/nuclease 2, ssDNA single-stranded DNA, RPA replication protein A, RAD51 RAD51 recombinase, PALB2 partner and localizer of BRCA2, RECQL5 RecQ-like helicase 5, FBH2 also GNA11, G protein subunit alpha 11, FANCM FA complementation group M, RTEL regulator of telomere elongation helicase 1, SDSA synthesis-dependent strand annealing"}
{"_id": "Radiology$$$c186c1ac-fd65-4d0d-8598-1450a05649ac", "text": "A flow diagram depicts the following steps. Pathway selection, resection, formation of RAD 51 filament, homology search and strand invasion, synthesis, S D S A, heteroduplex extension, resolution, and dissolution."}
{"_id": "Radiology$$$b63ce86e-4a3d-4ee9-9d6a-1b9a4ca6c703", "text": "A full functional HR pathway can be utilized after the DNA end resection. A detailed review of this process can be found in the work of Ranjha et al. [38]. The canonical HR pathway not only restores a direct DSB, but also repairs damage created by stalled or collapsed replication forks [21]. As soon as an extensive resection is executed by the action of several nucleases, cells are obligated to follow a homology-governed mode of repair. The DSB goes through a nuclease-driven progression known as DNA end resection in order to produce 3\u2032-end ssDNA segments all through HR. This is crucial for the searching and strand invasion that occurs later during the recombination process. Along with the CtIP nuclease, DNA end resection is instigated by the MRE11 nuclease within the MRN complex. MRN/CtIP in combination with Bloom syndrome protein (BLM) or exonuclease 1 (EXO1) and DNA replication helicase/nuclease (DNA2) arbitrates the short- as well as long-term resections. During this resection, the 3\u2032 ends of ssDNA get exposed that are rapidly covered by replication protein A (RPA) complex. The ssDNA region covered by RPA further recruits and stimulates the ataxia-telangiectasia and Rad3-related (ATR) kinase. This in turn triggers the checkpoint kinase 1 (Chk1) kinase. The RPA coating not only ascertains the nondegradation of ssDNA overhangs but also avoids the formation of secondary structures. To form the presynaptic filament, RAD51 dislocates RPA, which is then involved in the action of several RAD51 mediator proteins. To construct a displacement loop (D-loop), the RAD51 nucleoprotein filament explores a homologous sequence to occupy and dislocate one strand of the homologous template. This structure aids in the formation of a heteroduplex by pairing the broken strand with the displaced strand, and DNA synthesis at the break site repairs for any missing nucleotides. The outcome of the second end capture leads to the configuration of a double-Holliday junction (dHJ). The resolution of such an intermediate occurs either by a resolution mechanism or by a dissolution, which makes it susceptible to crossover (CO) or noncrossover (NCO). On the other hand, at the time of synthesis-dependent strand annealing (SDSA), no more than one-end invasion takes place, therefore leading to the formation of a single-Holliday junction. This transitional structure is suspended into an NCO. The HR repair pathway is known to also involve chromatin modifiers, remodelers, and even integration of histone variant so as to deal with the obstructions that the nucleosomes produce to the resection machinery. HR is active during the late S phase and the G2 phase and therefore is able to utilize the sister chromatid as a guiding template to repair the DSBs. Hence, this pathway is error-free [38]."}
{"_id": "Radiology$$$7d92a933-99e8-42c3-926e-924570fc6afe", "text": "The Nonhomologous end joining pathway (NHEJ) pathway (Fig. 3.11) has long been demonstrated to be central in repairing DNA DSBs, and cells deficient in some of these signaling components are known to be very IR sensitive [39]. Moreover, NHEJ has a critical role in V(D)J-recombination when B and T lymphocytes are developed in the immune system. This is also illustrated by severe combined immunodeficiency (SCID) patients who, due to lack or alteration in some of the NHEJ components including the catalytical subunit of DNA-PK (DNA-PKcs) as well as others, have T and B lymphocytes that do not have proper function [39]. Importantly, cells from such patients also display high IR sensitivity.\n\nA 7-step flow diagram depicts that the repair of I R induced D-N-A D-S-B starts with I R indued D N A D S B and ends with the association of the ligase four complex to seal the break.\n\nFig. 3.11\nSchematic of the principal steps of NHEJ. (I) IR triggers the formation of DNA DSB in the cell nucleus. (II) To act on these, the NHEJ pathway commences with the movement of Ku (Ku70/Ku80) proteins towards the loose ends in the DNA DSB. (III) Ku70/Ku80 forms a complex embracing the ends protecting DNA integrity. DNA DSBs with noncomplex termini can be ligated directly after this step as end processing is not required. (IV) When the ends in the DSB require end trimming, the DNA-PKcs is recruited onto DNA via association to the Ku70/Ku80 complex forming a platform for subsequent steps. (V) Once associated to Ku proteins and DNA, DNA-PKcs undergoes autophosphorylation which changes its conformation. (VI) In this way, DNA-PKcs is active as a kinase and regulates the association of multiple DNA end-trimming proteins (e.g., Artemis, WRN, Pol\u03bc/\u03bb, PNK), which restores the nucleotides at the termini allowing ligation to take place. (VII) The ligation step is controlled by the DNA ligase IV complexes, which apart from ligase IV also include XRCC4, XLF, and PAXX. At the end of the trimming and ligation step, some bases may be lost causing loss of genomic information which may cause mutations. Abbreviations: DNA DSB DNA double-strand break, NHEJ Non-homologous end joining, Ku dimeric Ku70/Ku80 protein complex, DNA-PKcs DNA-dependent protein kinase catalytic subunit, WRN protein deleted in Werner syndrome, Pol\u03bc/\u03bb DNA polymerase \u03bc/\u03bb, PNK polynucleotide kinase, XRCC4 X-ray repair cross-complementing protein 4, XLF XRCC4-like factor, PAXX paralog of XRCC4 and XLF"}
{"_id": "Radiology$$$92f96207-2bb1-4096-b84a-c9d13e5ad42a", "text": "A 7-step flow diagram depicts that the repair of I R induced D-N-A D-S-B starts with I R indued D N A D S B and ends with the association of the ligase four complex to seal the break."}
{"_id": "Radiology$$$fde174fa-8ca9-4455-b24b-707ca8761fca", "text": "The NHEJ process starts at the DNA end termini, also known as the break synapsis, where a heteromeric complex of the Ku proteins, Ku70/Ku80, forms a ringlike structure around the DNA. The Ku70/Ku80 complex then moves towards the break to bring the free DNA ends together and protect them from nuclease digestion (Fig. 3.11). This is critical for NHEJ function and for IR sensitivity as cells deficient in either Ku subunits have impaired NHEJ and also are IR sensitive [41].\n\nA flow diagram depicts D N A double helix, nucleosomes, 30-nanometer fiber, and higher-order chromatin fiber, divided into chromosome territory in the interphase and condensed chromosome in the metaphase.\n\nFig. 3.12\nStructure of DNA organization. The DNA forms a double-helix structure, which is wrapped around histones forming so-called nucleosomes. The nucleosomes form complex fibers of 30 nm size, which themselves form the higher order chromatin fibers, which are in the range of 300 nm. In the interphase, these fibers build the chromatin territories, where territories from different chromosomes can overlap, forming so-called networks. In the metaphase, the higher order chromatin fibers are condensed to form chromosomes. (Adapted with permission (CCBY) from Liu et al. [40])"}
{"_id": "Radiology$$$7472a015-9c11-4f5b-8773-ab13f4569e14", "text": "A flow diagram depicts D N A double helix, nucleosomes, 30-nanometer fiber, and higher-order chromatin fiber, divided into chromosome territory in the interphase and condensed chromosome in the metaphase."}
{"_id": "Radiology$$$2f2ceaab-b9db-4ff1-b061-e11ad9ccf0d5", "text": "The end structures within the DNA DSB which are sensed and protected by the Ku protein complexes are 3\u2032 or 5\u2032 overhangs, blunt ends, closed hairpin, and complex structures including those found in IR-induced DSBs [41]. The current understanding is that the Ku complex heterodimer slides along the DNA strand and multiple subunits align onto DNA to form a protein scaffold. The end structure in the DSB, i.e., the blunt ends, 3\u2032 or 5\u2032 overhangs, thereafter dictates what route the NHEJ takes as some proteins are required for certain end termini to be processed prior to ligation while others are not [41, 42]. For example, when the end termini have some regions with certain nucleotides that overlap, the ends are ligated by the DNA ligase IV and X-ray repair cross-complementing 4 (XRCC4) complex alone. However, in the majority of the cases, the DNA protein kinase catalytic subunit (DNA-PKcs) orchestrates the reactions forming a holocomplex with the Ku proteins on the DNA [42] (Fig. 3.11)."}
{"_id": "Radiology$$$919d0da2-bf83-4639-9d49-9f585c9364d3", "text": "DNA-PKcs is a kinase with the capacity to phosphorylate proteins on serine or threonine resides. It belongs to a protein family also named the PIK kinases to which also ATM and ATR belong. DNA-PKcs requires DNA binding for its kinase activity to control the end-processing activity within NHEJ as well as inactivation of its own function [42]. Thus, when the Ku complex binds DNA-PKcs, it causes autophosphorylation of multiple residues in the kinase domain and thereafter DNA-PKcs can phosphorylate its downstream substrates."}
{"_id": "Radiology$$$853af5b6-14cd-4972-88c5-da7ad375cfa7", "text": "Multiple studies in rodent and human cells using various genetic approaches have shown that a defective DNA-PKcs activity impairs the repair of some but not all IR-induced DNA DSBs, but nevertheless causes increased radiation sensitivity [39]. To further study the function of DNA-PKcs for repair of IR or chemotherapy-induced DNA damage, inhibitors towards the kinase pocket have been developed, some of which have also been demonstrated to function as IR sensitizers of tumor cells and in tumor-bearing mice (reviewed in the work of Myers et al. [43]). All in all, it is clear that DNA-PKcs orchestrates the NHEJ pathway, but despite decades of research, the understanding of the entire molecular mechanisms is still not complete."}
{"_id": "Radiology$$$21915afc-353a-48f4-8bef-0dc43a21fb6e", "text": "The end processing of the nucleotides is required as a DNA DSB seldom has the 3\u2032OH and 5\u2032P termini that are required for ligation. Therefore, the ends in the DNA DSB need to be processed by exonucleases such as Artemis, which has intrinsic 5\u2032 exonuclease function and 5\u2032 exonuclease acquired once in complex with DNA-PKcs [44]. The critical role for Artemis in the NHEJ processing has been shown as cells deficient in Artemis are sensitive to IR. However, Artemis is only required for repair of a subset of ~10\u201320% of the DNA DSBs, while the others are rejoined efficiently in the absence of Artemis. Therefore, it has been suggested that Artemis is responsible for repair of DNA DSBs that display slow repair kinetics. Apart from Artemis, there are also other proteins involved in the end-processing activity including Werner syndrome ATP-dependent helicase (WRN). It exhibits helicase and exonuclease function and suppresses 5\u2032 end resection as well as HR by blocking MRE11 and CtlP association. Other examples are the polynucleotide phosphatase/kinase (PNKP) and tyrosyl-DNA phosphodiesterase 1 (TDP1) that modify the phosphorylation of the nucleotides and trim the ends to a state allowing ligation to take place. As some nucleotides may be lost in the end termini, the DNA polymerase \u03bc and DNA polymerase \u03bb are also part of the end-trimming activity in NHEJ."}
{"_id": "Radiology$$$60b4ebc8-3a22-4833-aca2-f308c60a86f8", "text": "Ligation of broken ends by NHEJ is carried out in a protein complex, which bridges around the DNA end in the DSB. The complex contains, among other proteins, XRCC4, DNA ligase IV, and XRCC4-like factor (XLF). Out of all the proteins involved in NHEJ, DNA ligase IV stands out when it comes to repair of DNA DSBs because mice, in which this gene is disrupted, experience lethality as embryos and dissection of such embryos have revealed extensive apoptosis, in particular in the nervous system [45]. Both ligase IV and XLF mutations, that impair their function, are reported in humans in different tumor types, e.g., leukemias and lymphomas, with the patients showing various degrees of deficiency in B and T lymphocyte function [46] (Box 3.6)."}
{"_id": "Radiology$$$605dd35e-fe47-4420-9b6d-67a3cda64ee6", "text": "The NHEJ pathway plays a crucial role in the repair of DNA DSBs generated endogenously and by IR.\n\nNHEJ has less fidelity in repair than HR and may therefore in certain circumstances cause mutations.\n\nNHEJ deficiency results in increased radiation sensitivity.\n\nSome of the NHEJ pathway components, e.g., DNA ligase IV, are essential for NHEJ repair, while others are required for efficient repair of certain subsets of DNA DSBs.\n\nNHEJ components, e.g., DNA-PKcs, offer a target that can be used for radiation sensitization purposes in various tumor types."}
{"_id": "Radiology$$$c923fbb6-279d-471f-acf7-f395612d0349", "text": "The NHEJ pathway plays a crucial role in the repair of DNA DSBs generated endogenously and by IR."}
{"_id": "Radiology$$$3e64d624-85ef-4784-94b2-275e26577bf7", "text": "NHEJ has less fidelity in repair than HR and may therefore in certain circumstances cause mutations."}
{"_id": "Radiology$$$bfa60863-382d-4cd6-91f2-455deb95c1a5", "text": "Some of the NHEJ pathway components, e.g., DNA ligase IV, are essential for NHEJ repair, while others are required for efficient repair of certain subsets of DNA DSBs."}
{"_id": "Radiology$$$435a4abc-f1c7-4f6c-a736-f7a4b497274d", "text": "NHEJ components, e.g., DNA-PKcs, offer a target that can be used for radiation sensitization purposes in various tumor types."}
{"_id": "Radiology$$$16874605-78ba-450a-9537-821c3edd0e85", "text": "Cells fundamentally utilize two conventional mechanisms to repair their DSBs, i.e., the HR and the NHEJ pathways. However, in recent times, a third pathway is discovered which is known as the alternative NHEJ (alt-NHEJ or aNHEJ), microhomology-mediated end joining (MMEJ), and B (backup)-NHEJ. This is an extremely error-prone pathway that operates in NHEJ-proficient as well as -deficient cells. Unlike HR, this pathway does not require any long homologous DNA templates and is therefore called as \u201calternative end-joining\u201d pathways. This mechanism typically but not always depends on the microhomologies that exist at or near the DNA DSB ends, which implicates that it might not be completely divergent from the mechanism of HR. The junctions of this repair pathway demonstrated overlapping microhomologies of 3\u201316 nucleotides as well as nucleotide deletions. Earlier, it was known that the NHEJ pathway could recover short microhomologous region of up to five nucleotides in mammalian cells. However, the alt- NHEJ can operate even in the NHEJ-deficient cells [47]. It is a unique pathway that is seen to be ongoing throughout the cell cycle but found to be augmented in the G2 phase when compared to the G1 phase. Although it is arguable if there are other alt-NHEJ overlapping pathways, there is evidence of a microhomology-mediated end joining (MMEJ) that involves the arrangement of microhomologous series on the inner side of the broken ends prior to fusion and is linked with deletion adjoining the original DSB. This is also an error-prone pathway leading to chromosomal translocations."}
{"_id": "Radiology$$$0c5019c3-f2e7-4699-96bc-310ebdbbd3f1", "text": "One of the characteristics of alt-NHEJ is the excessive deletions and frequent microhomologies at the junction, while such microhomologies are not always present. The exclusivity of alt-NHEJ products implicates the usage of end resection-promoting enzymes, their association of proteins that get benefitted from the microhomologies that can support the intermediates to stabilize, nucleases competent of eliminating the noncompatible 5\u2032 and 3\u2032 overhangs, and finally ligation. The MRE11 complex and CtIP in end resection are known to facilitate the alt-NHEJ, and DNA ligase III emerges to uphold the ligation step."}
{"_id": "Radiology$$$fa98a1d5-7f7a-4255-b0e6-b36ab4789673", "text": "It is observed that the microhomology-mediated DNA repair proceedings take place via RAD52-dependent single-strand annealing (SSA)-type machinery where the minimum SSA-dependent DSB repair lies between 5 and 29 base pairs of homology. In this mechanism, it is mandatory to have direct repeats on both the sides of the DNA break. Since SSA does not involve any strand invasion events, it is independent of RAD51. As MMEJ depends on the already existing microhomologies around the break, its probable mode of action is associated with SSA. Finally, for the sealing event, MMEJ depends on ligase III [47]."}
{"_id": "Radiology$$$86b46842-af93-42f7-9ab1-7e3ccba24040", "text": "Although repair processes have been intensively investigated for decades, many principal questions concerning the mechanisms of radiation DNA damage induction and repair remain open [reviewed in the work of Falk and Hausmann [48]]. Chromatin in the cell nucleus is arranged into numerous hierarchical levels (Fig. 3.12) from micrometer to nanometer, which leads to the formation of a three-dimensional (3D) architectural chromatin network."}
{"_id": "Radiology$$$98f9788d-41fd-403e-8ca8-27724067a45f", "text": "This network is dynamic and influenced by the cellular status and ongoing processes in the cell nucleus. Chromatin architecture is precisely regulated by physical and biochemical regulation systems and, in turn, regulates global and local genome functions. Local chromatin arrangement thus both reflects and determines the functions of the particular genetic locus, such as its transcriptional activity. Importantly in the context of radiobiology, nonrandom chromatin architecture seems to co-determine the response of cells to irradiation in numerous ways: First, in a tight interplay with physical characteristics of the radiation, functional chromatin structure states increase or decrease DNA susceptibility to DNA damage induction. Second, the chromatin architecture acts as an additional level of DSB repair regulation, cooperating with \u201cstandard\u201d biochemical genetic and epigenetic regulation systems. Chromatin architecture may regulate DSB repair at individual DSB sites and also globally, via tuning the transcription intensity of genes involved in DNA repair and other processes related to the complex response of cells to radiation DNA damage (e.g., cell cycle progression or apoptosis). Theoretically, chromatin architecture might collect and unify signals of other different signaling networks (biochemical, epigenetic) and transfer these heterogeneous signals into single integrated output signal represented by a specific architectural status of the chromatin network that can be easily interpreted by the cell. Chromatin architecture might thus impersonate a \u201croofing\u201d regulatory system based on simple physical laws, which allows for a sufficiently fast decision-making process for the optimal repair mechanism at each individual DNA damage site."}
{"_id": "Radiology$$$40289999-4b29-4302-a01d-694b069353bc", "text": "Different types (low LET vs. high LET) of IR interact with chromatin in specific ways. Therefore, the relationship between the radiation quality, architecture of structurally and functionally distinct chromatin domains, and DSB induction, repair, and misrepair play a role in the cellular radiation response. Genetically active, decondensed euchromatin and mostly inactive, condensed heterochromatin are the two traditionally recognized structurally and functionally distinct chromatin domains, which affect radiation response. However, it should be noted that radiation response differences may be even more prominent for other chromatin architectural and functional counterparts [49], such as RIDGE (regions of increased gene expression) and anti-RIDGE domains [50], which have even more precisely defined function and more homogenous architecture as compared to euchromatin and heterochromatin (Box 3.7)."}
{"_id": "Radiology$$$921155bf-d831-4b27-a932-0d19263b9089", "text": "DNA is organized in structural units ranging from micrometers to nanometers, forming 3D chromatin architecture.\n\nChromatin architecture is a key factor determining local damage induction by radiation.\n\nChromatin architecture operates with genetic and epigenetic regulatory factors orchestrating DNA damage response."}
{"_id": "Radiology$$$2fc7b79f-4fb9-427f-ba54-499d2fe5d154", "text": "DNA is organized in structural units ranging from micrometers to nanometers, forming 3D chromatin architecture."}
{"_id": "Radiology$$$e3efc37e-faad-4091-8020-dcf8d06dfac8", "text": "Chromatin architecture is a key factor determining local damage induction by radiation."}
{"_id": "Radiology$$$bb659f3d-0682-404b-a346-ce167ce70d97", "text": "Chromatin architecture operates with genetic and epigenetic regulatory factors orchestrating DNA damage response."}
{"_id": "Radiology$$$99dbe76e-f63e-4d6b-bd46-8e880588d9fa", "text": "DNA damage and repair processes can be related to specific cell states and chromatin architectures. The spatiotemporal sequence of repair protein binding to DSB and surrounding phosphorylated and thus activated H2AX histone (called \u03b3H2AX) sites can be analyzed using microscopy (Fig. 3.13). The analysis of the formation and subsequent dissociation of repair complexes, and the structure of these complexes, brought deep insights into the mechanisms of the two main DSB repair pathways in human cells, nonhomologous end-joining (NHEJ) and homologous recombination (HR)\u2014as discussed above.\n\nThree micrographs with two fluorescent dyes depict the presence of gamma H 2 A X, chromatin, and gamma H 2 A X with chromatin, respectively, at 5-micrometer scales.\n\nFig. 3.13\nLocalization of DNA damage on chromatin: radiation damage induced by high-LET alpha particle radiation microscopically visualized by \u03b3H2AX as a biomarker for double-strand breaks (left, magenta), chromatin labeling (middle, green), and merge of the two (right)"}
{"_id": "Radiology$$$b56a4ec9-0851-42fb-b549-0aae13d2f9a3", "text": "Three micrographs with two fluorescent dyes depict the presence of gamma H 2 A X, chromatin, and gamma H 2 A X with chromatin, respectively, at 5-micrometer scales."}
{"_id": "Radiology$$$42bd0a89-5f4f-4924-92e8-e74ed54762f5", "text": "The most obvious architectonical chromatin types are condensed (hetero)chromatin with only a low number of active genes and decondensed (eu)chromatin, which is generally considered as genetically (transcriptionally) active. It has been shown that condensed chromatin protects DNA from free radicals generated by ionizing radiation [51], but, at the same time, it is this condensed architecture and a high content of repetitive sequences that complicate and slow down the repair of DSBs located in heterochromatic domains. The protective function against free radicals of the heterochromatic status does not seem to simply result from high condensation of heterochromatin domains but rather from a high amount of proteins that specifically bind to heterochromatin and interact with radiation-induced free radicals before they can damage DNA [51]. However, if a DSB occurs in heterochromatin, its condensed architecture must decondense first in order to allow the formation of huge repair complexes and continuation of repair processes [52]. Moreover, numerous studies indicate that the slower repair of heterochromatic DSBs not only reflects this necessity for the decondensation of a damaged chromatin domain but also points to a slower repair mechanism, specifically homologous recombination (HR) [48]. HR in heterochromatin could be superior over NHEJ for numerous structural reasons and therefore preferred by the architecture of heterochromatin domain; however, at the same time, repetitive sequences present in heterochromatin are a clear contraindication for this repair mechanism. This paradox can be again explained and overcome by the already described heterochromatin decondensation at the beginning of repair. The RAD51 recombinase, which is responsible for complementary DNA strand search and exchange, can bind to heterochromatic DSB sites only upon heterochromatin decondensation and protrusion of a DSB to the domain surface, which ensures spatial separation of the damaged DNA ends from repeats remaining embedded within the heterochromatin domain. HR is thus evidently regulated by chromatin architecture changes, which also ensure the fidelity of this repair mechanism [48]. It remains unknown whether NHEJ or other repair pathways are also associated with some specific chromatin architecture requirements and rearrangements, similar to HR. However, some recent studies suggest that epigenetic and structural regulations are involved in repair pathway selection at individual DSB sites, as it is discussed later. The key properties of hetero- and euchromatin as mentioned here are summarized in Table 3.3.Table 3.3\nProperties of hetero- and euchromatin\n\nHeterochromatin\n\nEuchromatin\n\nCondensed DNA\nLow amount of active genes\nProtection of DNA from radicals through condensed structure and high amount of radical catching proteins clustering around DNA\nSlow repair due to necessary decondensation\nHomologous recombination superior to nonhomologous end joining\n\nDecondensed DNA\nTranscriptionally active\nNo radical protection\nNo decondensation necessary and therefore fast repair\nNo preference of repair mechanisms defined by chromatin architecture"}
{"_id": "Radiology$$$46d487f3-8960-4855-ad8d-48d5fbbdec10", "text": "A serious consequence of irradiation is the formation of chromosomal aberrations, and the chromatin architecture significantly participates in this process. The severity and complexity of the genetic damage are related to the complexity of the underlying DNA damage. The connection between damage complexity and radiation type was discussed in Sect. 3.2. An additional factor defining the complexity is the chromatin state, and radiation interacts with this. These interactions can be illustrated on the example of chromosomal translocation formation upon irradiation of euchromatin and heterochromatin with low-LET and high-LET radiation, respectively. The type of radiation, chromatin architecture, and consequently initiated DSB repair processes participate in a specific way in free DNA-end misrejoining (review [53, 54])."}
{"_id": "Radiology$$$6a6d1d1c-138a-492c-9731-131b1a57597a", "text": "The probability of a chromosomal translocation formation between two specific genetic loci, i.e., the linking of the ends of different chromosomes after induction of DSB in both chromosomes at the same time, depends on spatial (3D) separation of these loci in the cell nucleus. Chromatin is nonrandomly organized in the cell nucleus, though on the probabilistic basis, this means that chromosomal translocations between some genetic locus pairs appear more frequently than translocations between other pairs. This expectation was confirmed by experiments with interphase cells exposed to neutrons or high-LET particles where translocations appeared most frequently between the neighboring chromosomal territories or even genetic loci statistically located in close proximity [55]. Overall, there are two hypotheses used to explain the processes related to repair of DSB in the context of chromatin organization:1.\nPosition-first hypothesis: It considers DSBs as immobile structures and emphasizes the role of (preset) chromatin architecture in determining the probability of a chromatin exchange between two specific genetic loci.\n\u00a02.\nBreakage-first hypothesis: It considers DSBs as mobile and gives the chromatin architecture a subsidiary role."}
{"_id": "Radiology$$$dd2c27fe-7d6f-4213-bdf9-e6d7353e329c", "text": "Position-first hypothesis: It considers DSBs as immobile structures and emphasizes the role of (preset) chromatin architecture in determining the probability of a chromatin exchange between two specific genetic loci."}
{"_id": "Radiology$$$7b7055be-87ac-4f0e-b596-9c0372091bb4", "text": "Breakage-first hypothesis: It considers DSBs as mobile and gives the chromatin architecture a subsidiary role."}
{"_id": "Radiology$$$b72ae511-e88f-4bf8-8b34-7322ce17e84d", "text": "Both hypotheses explain different phenomena occurring. While the position-first hypothesis works well in explaining the enhanced probability of translocations to be formed by neighboring chromosomes, it does not allow chromatin exchanges between spatially more distant genetic loci, though such translocations were experimentally observed. Furthermore, although complex chromosomal translocations are only occasional events upon cell exposure to photonic (low-LET) radiation, they do occur. As DSBs are dispersed through the cell nucleus and thus spatially separated in cells irradiated with low-LET radiation, formation of complex translocation between three or more DSBs can hardly be explained without involving DSB movement. Both observations can be explained by the breakage-first hypothesis. However, the idea of highly mobile chromatin at DSB sites in cells exposed to low-LET radiation, where chromatin is not locally fragmented as in cells exposed to high-LET particle radiation, has not been generally confirmed. The explanation of this paradox came with the spatiotemporal tracking of individual radiation-induced protein accumulations (foci) [52], showing the majority of \u201cimmobile\u201d DSBs accompanied with a small proportion of highly mobile DSB lesions or by subdiffusive nature of DSB loci [56]. The increased mobility correlated with DSB localization in heterochromatin and can thus be attributed to chromatin decondensation at the beginning of heterochromatin repair process, leading to the protrusion of DSBs onto the surface of heterochromatin domains. Numerous DSBs thus accumulate in nuclear subcompartments of a limited volume, which increases the probability of their mutual interactions and consequently chromatin exchanges even among multiple DSBs."}
{"_id": "Radiology$$$67d528b3-a688-4537-ad2b-55ae857ebbb0", "text": "After irradiation with high-LET particles, on the other hand, locally concentrated energy deposition causes serious chromatin fragmentation and mobilization within cell nucleus micro-volumes along the particle tracks. This situation allows mutual contacts of many short chromatin fragments from one or several neighboring chromosomes and thus easy formation of complex chromatin translocations, irrespectively of the original chromatin architecture and chromatin architecture changes during repair. Chromosomal translocations in cells exposed to high-LET radiation thus occur due to physical rather than biological (repair) processes. We have already mentioned that heterochromatin architecture protects DNA from low-LET radiation as heterochromatin-binding proteins prevent DNA interaction with free radicals, mostly mediating harmful effects of low-LET radiation. With high-LET radiation, however, most damage to DNA is caused by the direct effect of radiation particles or emitted secondary electrons. In this case, heterochromatin represents a more dangerous chromatin architecture, as particles cannot be stopped by any chromatin architecture and heterochromatin provides more DNA targets per a volume unit compared to euchromatin. Hence, in cells exposed to high-LET radiation, translocations in heterochromatin tend to be more complex than in euchromatin (Box 3.8)."}
{"_id": "Radiology$$$285c2067-8379-493a-ba98-b88fb373557d", "text": "Hetero- and euchromatin form different chromatin architectural regions within a cell nucleus resulting in different consequences of radiation damage induction.\n\nChromosomal aberrations after low-LET radiation can be explained through the \u201cposition-first hypothesis\u201d in combination with chromatin decondensation in heterochromatic regions.\n\nChromosomal aberrations after high-LET radiation occur due to physical fragmentation of DNA rather due to biological processes.\n\nHeterochromatin protects DNA from indirect damage (mainly induced by low-LET radiation) but is more sensitive to direct damage (mainly induced by high-LET radiation)."}
{"_id": "Radiology$$$8dcbe4ed-1f1c-468f-82c4-5420bed5f4e7", "text": "Hetero- and euchromatin form different chromatin architectural regions within a cell nucleus resulting in different consequences of radiation damage induction."}
{"_id": "Radiology$$$40726756-aa92-4a27-bb2b-4161edc6e825", "text": "Chromosomal aberrations after low-LET radiation can be explained through the \u201cposition-first hypothesis\u201d in combination with chromatin decondensation in heterochromatic regions."}
{"_id": "Radiology$$$14c2ac7d-e491-4ba7-9a3f-38690e053076", "text": "Chromosomal aberrations after high-LET radiation occur due to physical fragmentation of DNA rather due to biological processes."}
{"_id": "Radiology$$$3b567d8a-243e-4afb-ae9e-dbd0dd3a574d", "text": "Heterochromatin protects DNA from indirect damage (mainly induced by low-LET radiation) but is more sensitive to direct damage (mainly induced by high-LET radiation)."}
{"_id": "Radiology$$$560fd7fa-c3d9-4c15-8b29-384239973d0c", "text": "Using a variety of tools of super-resolution microscopy and image data computing has revealed that \u03b3H2AX foci in cell nuclei exposed to low-LET X-rays are subdivided into several equally sized, functionally relevant clusters. The number of clusters increased with the radiation dose according to the well-known linear-quadratic dependence and decreased at later time periods postirradiation. Calculations of the persistence of homology revealed a highly similar topology of \u03b3H2AX and other repair protein clusters, especially when these clusters were closely associated with heterochromatin regions. During the repair period, size and topology of these clusters seem to be maintained as long as they are attached to chromatin at actively repairing DSB sites. These findings suggest a functional relevance of the focus/cluster topology [57]."}
{"_id": "Radiology$$$8d14658c-6698-4930-847c-56d4b16af2f6", "text": "For instance, while the \u03b3H2AX clusters had a typical diameter of about 400\u00a0nm\u2013600\u00a0m, the MRE11 clusters were smaller (about 200\u00a0nm) and usually completely embedded within \u03b3H2AX clusters [58]. The sizes of clusters were independent of repair time and cell type. On the other hand, the topological similarity of clusters followed the dynamics of the repair protein interaction with chromatin; that is, binding to damage sites was accompanied by ordering while detachments caused the relaxation of topological arrangements. In contrast, \u03b3H2AX and MRE11 clusters spontaneously occurring in the nonirradiated cells (e.g., due to replication defects) did not show this topological similarity."}
{"_id": "Radiology$$$c90c983c-e6c1-4568-b7fb-d2638da1bcbe", "text": "Recent studies discovered spatial distribution changes of tri-methylated H3K9 histone (H3K9me3), ALU repeat sequences (ALU), or long interspersed nuclear element (LINE)-like L1 sequences, indicating chromatin reorganization or movement and DNA strand relaxation after radiation exposure, followed by recovery during repair [59]. Altogether, described results suggest a functional relevance of chromatin and repair focus nano-architecture in DSB repair process and their regulation (Box 3.9)."}
{"_id": "Radiology$$$fab4e8da-ff88-453b-88bd-dda21b7fbaa6", "text": "DNA repair locations marked by \u03b3H2AX and 53BP1 are subdivided into functional clusters at the nanoscale, in a manner which is cell type and radiation type specific.\n\nOther repair protein clusters are smaller and are embedded in the \u03b3H2AX and 53BP1 clusters.\n\nAfter damage induction, chromatin is reorganized accompanied by DNA movement.\n\nChromatin reorganization is recovered during DNA repair."}
{"_id": "Radiology$$$2f899b51-d4b0-41b8-b8d4-554d8bbe1801", "text": "DNA repair locations marked by \u03b3H2AX and 53BP1 are subdivided into functional clusters at the nanoscale, in a manner which is cell type and radiation type specific."}
{"_id": "Radiology$$$8c9145d1-caec-451e-aff4-fd13d1f5b5a8", "text": "Other repair protein clusters are smaller and are embedded in the \u03b3H2AX and 53BP1 clusters."}
{"_id": "Radiology$$$e989e024-36bd-4833-8596-ae52bebd4cbf", "text": "Lack of repair (unrepair) and misrepair of DNA damage can lead to increased chromosome breaks or rearrangements and mutations usually referred to as a status of genomic or genetic instability (GI). GI is usually associated with loss of cell cycle control, senescence, and cell death and in humans with pathological disorders including premature aging and predisposition to various types of cancer and inherited diseases [60]. On the other hand, GI is also fundamental for evolution and induction of genetic diversity. It is known that genomic integrity is carefully supervised by specific surveillance mechanisms like DNA damage checkpoint, DNA repair, or mitotic checkpoint. A deficiency in the regulation of any of these mechanisms often leads to GI, which can predispose a cell to malignant transformation [61]."}
{"_id": "Radiology$$$7af6c823-34d8-4d78-9efb-f38958e74b0f", "text": "In huge DNA molecules in the cell, nucleus genes are present. These genes are responsible for the development and function of the cell and the whole organism, because they code proteins. Due to this fact, unrepaired or misrepaired DNA lesions, which can lead to gene mutations, can promote changes in the structure of the encoded protein or lead to the decrease or complete loss of its expression. The types of DNA lesions occurring were already discussed in Sect. 3.3. Based on the current experimental and theoretical evidence, the most repair-resistant lesions are not the single ones but a combination of them in a short DNA segment of 10\u201320\u00a0bp called clustered damage. Clustered DNA lesions are considered the signature of ionizing radiations especially for particle radiation [45]. Various studies suggest that the probability for a break or other DNA lesion to be incorrectly processed and amended is fairly low when damage is spatially separated but increases drastically when multiple breaks and/or non-break lesions coincide. For an analytical description of DNA repair pathways, the reader can refer to Sect. 3.4. As was already mentioned in Sect. 3.3, the DNA molecule consists of nucleotides (deoxyribose + phosphate group + base), which can be for simplicity named based on the four bases [adenine (A), cytosine (C), guanine (G), thymine (T)]. Thus, the DNA alphabet is a very easy one; it only consists of four letters. These four letters are then combined to give rise to groups of three, which define the amino acids that are then the new alphabet for the translation to proteins. For more details on DNA-to-RNA transcription and RNA-to-protein translation, see for example [62]. Even if the cells have a very sophisticated DNA damage response and repair system, it may happen that not all the damage is removed. A mutation is when a permanent change in the DNA sequence occurs. Mutations can be divided into somatic or germline mutation in terms of what kind of cell is affected. A germline mutation occurs in a sperm or in an egg and can be passed to offspring. Somatic mutations occur in cells of the body and cannot be passed to next generations. Mutations can also be grouped as point or chromosomal mutations. Point mutations are when a single nucleotide is replaced with another single nucleotide, or deleted, or inserted in a place that it should not be. Point mutations do not always have significant consequences on the encoded protein. For example, as is shown in Table 3.4, the mutation can be silent. This means that even if there is a change in the original DNA sequence, the final product of the transcription will be the same, because there are several combinations of the DNA alphabet that lead to the same amino acid. In other cases, the mutation can lead to the change of the final amino acid (missense mutation) or to the creation of a stop codon (nonsense mutation), which then affects the final protein.Table 3.4\nPoint mutations and their consequences\n\u00a0\nPoint mutations\n\u00a0\nNo mutation\n\nSilent\n\nMissense\n\nNonsense\n\nDNA\n\nTTC\n\nTTT\n\nTCC\n\nATC\n\nmRNA\n\nAAG\n\nAAA\n\nAGG\n\nUAG\n\nAmino acid\n\nLysine (Lys)\n\nLysine (Lys)\n\nArginine (Arg)\n\nStop"}
{"_id": "Radiology$$$34a49840-1359-496b-a2fd-880c236a06b8", "text": "Mitotic cell death, also called mitotic catastrophe (MC), is the process when a cell dies during or right after mitosis [63]. It can be triggered by DNA damage and its mis- and unrepair and therefore through radiation. MC can be both a caspase-dependent, regulated and caspase-independent, unregulated pathway of cell death. Some characteristic morphologies can be found in Fig. 3.14a.\n\n8 micrographs. a. A set of 5 micrographs of cells with alpha-tub and D A P I depict control, P D T, T x, and N c. b. A set of 3 micrographs depicts non-senescent and senescent cells.\n\nFig. 3.14\nMorphologies of mitotic catastrophe (a) and senescence (b). (a) Fluorescence image of cancer cells undergoing mitosis. The DNA is labeled with DAPI and mitotic spindles using \u03b1-tubulin staining. The cells exhibiting mitotic catastrophe are treated with photodynamic therapy (PDT), Taxol (Tx), or nocodazole (Nc). The control shows normal mitotic spindles. The treated cells show various types of altered spindles and mitosis. Scale bar: 10\u00a0\u03bcm. Reproduced with permission (CCBY) from Mascaraque et al. [64]. (b) Phase-contrast images of Chang cells. Senescence was induced using 1\u00a0mM of deferoxamine. (Reproduced with permission (CCBY) from Kwon et al. [65])"}
{"_id": "Radiology$$$04ff0c06-5aee-478a-9dde-a1bdd76fa387", "text": "8 micrographs. a. A set of 5 micrographs of cells with alpha-tub and D A P I depict control, P D T, T x, and N c. b. A set of 3 micrographs depicts non-senescent and senescent cells."}
{"_id": "Radiology$$$5939835d-619e-4086-a6b3-8c6fe222c36d", "text": "Senescence in biology refers to a process by which a cell ages and permanently and irreversibly stops dividing but does not die [63]. The number of senescent cells increases with age, but senescence also plays an important role during development as well as during wound healing and can be triggered by radiation. In culture, senescent cells exhibit a different morphology compared to non-senescent cells, called \u201cfried egg\u201d appearance (see Fig. 3.14b). It was shown that among other features, the radiation dose plays a major role in the induction of either senescence or apoptosis and necrosis. In some cell lines, senescence is the major response to low doses of radiation, whereas higher doses lead to apoptosis or necrosis. In IR-treated tissue, enhanced senescence may lead to pathogenic onsets, such as loss of organ function."}
{"_id": "Radiology$$$1160fca1-12b1-4ae9-a628-81328ddc5ea3", "text": "Recent advances in the field indicate that a further consequence of DNA damage misrepair or unrepair can be the release of cytoplasmic DNA that can also trigger immune responses. In general, it is widely accepted that immune signaling can be activated by the presence of DNA in unusual locations, such as the cytoplasm or the endosomes, as DNA is normally located in the nucleus of eukaryotic cells. Emerging evidence indicates a cross talk between DNA repair machinery and the immune system, and more specifically it has been discovered that DDR factors like DNA repair proteins can enhance innate immune signaling [66]. Defects in DDR and proper processing of DNA damage can therefore trigger a multitude of cellular phenotypes, including autoinflammatory disease, cellular senescence, and cancer. Genotoxic agents such as radiations or high oxidative stress can act as the primary instigators for immune signaling activation through the release of a wide range of biological and chemical factors often referred to as \u201cdanger signals\u201d or damage-associated molecular patterns (DAMPs) [67] (Box 3.10)."}
{"_id": "Radiology$$$1edb2fbb-7c39-483a-98cc-3a2e0918fe22", "text": "Genomic instability (GI) collectively refers to a status of increased DNA changes, chromosomal rearrangements, and enhanced tendency for genetic alterations occurring during cell division.\n\nUnrepaired or misrepaired DNA lesions can lead to chromosomal mutations, which can lead to cell death or loss of genetic material, thus promoting GI.\n\nMitotic cell death is the process of a cell dying in relation to mitosis and can be triggered by radiation-induced damages.\n\nSenescence is the status of irreversible cell cycle arrest, which occurs naturally during aging but can be triggered by radiation, which can lead to pathological onsets.\n\nCytoplasmic DNA and DNA repair defects can trigger immune response."}
{"_id": "Radiology$$$3c794a59-9567-48d6-97ca-ad069c213067", "text": "Genomic instability (GI) collectively refers to a status of increased DNA changes, chromosomal rearrangements, and enhanced tendency for genetic alterations occurring during cell division."}
{"_id": "Radiology$$$c7e992fe-3c10-4755-81a5-375297ab6496", "text": "Unrepaired or misrepaired DNA lesions can lead to chromosomal mutations, which can lead to cell death or loss of genetic material, thus promoting GI."}
{"_id": "Radiology$$$acd2d42b-8f2f-434b-8eb9-a2f57c6ebec1", "text": "Mitotic cell death is the process of a cell dying in relation to mitosis and can be triggered by radiation-induced damages."}
{"_id": "Radiology$$$85a629a0-90b8-4fbc-a49b-7dac02a379a7", "text": "Senescence is the status of irreversible cell cycle arrest, which occurs naturally during aging but can be triggered by radiation, which can lead to pathological onsets."}
{"_id": "Radiology$$$edced7d9-a9cb-435c-8735-24d0ad688f02", "text": "Cytogenetic techniques can be used to analyze chromosomal aberrations in metaphase and morphological abnormalities of DNA content in interphase nuclei. The applicability of these aberrations in the fields of biological dosimetry, clinical cytogenetics, and environmental monitoring is based on a large number of radiobiological and DNA-repair theories."}
{"_id": "Radiology$$$fceb3824-8afb-4c6a-8b70-419c19ef6727", "text": "As described before, when cells are exposed to a variety of genotoxic agents (chemical/physical/radiation/DNA-damaging agents), they cause defects in DNA, chromosomes, and other cellular components. Radiation induces extensive DNA damage such as DSBs that, if misrepaired or unrepaired, ordinarily result in asymmetrical chromosome rearrangements and exchanges, which may lead to formation of small chromatinic bodies also known as micronuclei (MN) (see Fig. 3.15). MN are tiny extranuclear bodies that contain damaged chromosome fragments and/or whole chromosomes that were not incorporated into the nucleus after cell division and are surrounded by a membrane. As a variety of genotoxic agents may damage DNA and the mitotic machinery by multiple mechanisms, leading to MN formation, MN are not IR specific.\n\nA chart lists several genotoxic agents and describes genotoxic damages that result in micronuclei, nuclear bud, and nucleoplasmic bridge with their respective symptoms.\n\nFig. 3.15\nMechanisms by which genotoxic agents cause micronuclei and other nuclear anomalies. Micronuclei (MN) can originate from lagging acentric chromosomes or chromatid fragments or whole chromosomes at anaphase in mitosis. Nuclear bud (NBUD) formation represents the process of extrusion of the amplified/surplus DNA, DNA repair-recombinational protein complexes, and possibly excess chromosomes from aneuploidic cells. Nucleoplasmic bridges (NPBs) originate from dicentric chromosomes. This arises because the centromeres of dicentric chromosomes are often pulled in opposite directions and defective separation of sister chromatids occurs during anaphase leading to bridge formation, which can be observed as an NPB in telophase"}
{"_id": "Radiology$$$c55d9b8e-e9b9-4c6f-b3f3-1a3b1bdc88a1", "text": "A chart lists several genotoxic agents and describes genotoxic damages that result in micronuclei, nuclear bud, and nucleoplasmic bridge with their respective symptoms."}
{"_id": "Radiology$$$22081e48-107d-42e6-97c2-bf25abb01850", "text": "It is now well established that MN are formed from acentric chromatid fragments caused by misrepaired or unrepaired DNA breaks or lagging acentric chromosomes due to mitotic spindle failure at an anaphase. Additionally, the formation of DNA DSBs and MN is sometimes the result of simultaneous excision repair of damages (e.g., 8-oxo-deoxyguanosine) and inappropriate bases\u2019 (e.g., uracil) incorporation in proximity on opposite complementary DNA strands."}
{"_id": "Radiology$$$5ef40d96-d9cb-49ba-8737-daa759d1e6d9", "text": "A whole chromosome lagging behind (chromosome mal-segregation) during anaphase also results in MN formation. Mal-segregation usually happens due to absence or inappropriate attachment of spindle microtubules to chromosome kinetochore. However, the potential mechanisms behind the formation of MN are hypomethylation repeat sequences in centromeric and pericentromeric DNA, defects in kinetochore proteins or assembly, dysfunctional spindle, defective anaphase checkpoint genes, and malfunctioning in cell cycle control system. Sometimes, mis-segregation events occur when the centromeres of the dicentric chromosomes are pulled towards opposite poles of cells with sufficient forces to detach the chromosome from spindle during anaphase, thus resulting in micronucleus formation from whole chromosome loss."}
{"_id": "Radiology$$$058cdbc6-a592-458a-8620-8e253ac1158c", "text": "Furthermore, multiple extrachromosomal acentric double minutes (DMs), cytogenetic hallmarks of genomic amplification, can aggregate after DNA damage and generate cytoplasmic MN that are subsequently eliminated from the cell."}
{"_id": "Radiology$$$03df4f84-4d51-437f-a8d9-a41aaead4300", "text": "Other nuclear anomalies such as nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) (see Fig. 3.15) are sensitive and reliable biomarkers for early genotoxic instability and chromosomal breakages and rearrangements. NPBs originate as an aftereffect of misrepair of DNA strand breaks or failure of complete chromatid separation to opposite poles of the cell during anaphase. It can also originate from telomere end-to-end fusion mechanism, a fundamental indication of and a marker for loss of telomere function, which is caused by (a) excessively short telomeres, (b) dysfunctional telomeres due to loss of telomere-binding proteins without telomere erosion, (c) inappropriate assembly of telomere-capping protein structure, (d) defects in recombinational repair proteins, or (e) lack of telomeres. Another distinctive nuclear anomaly, NBUDs, is one of the precursors of MN and is associated with chromosomal instability events. Most NBUDs originate from interstitial or terminal acentric fragments and represent the expulsion of undesirable amplified extrachromosomal DNA content, which localizes to specific sites at the periphery of the nucleus and is eventually eliminated via nuclear budding during the S phase of cell cycle. It is also plausible that NBUDs might occur after elimination of DNA repair-protein complexes in the cytoplasm (Box 3.11)."}
{"_id": "Radiology$$$58763ef8-773e-48b0-91bc-c08753982e4e", "text": "Micronuclei are small extranuclear bodies surrounded by a membrane that contain damaged chromosome fragments or even whole chromosomes. The genetic information encoded in the MN DNA will get lost and lead to large genomic consequences.\n\nChromosome segregation errors and/or fragment loss at anaphase (\u201cinter-cell bridges\u201d) and exclusion of acentric fragments from daughter nuclei lead to formation of MN in the cytoplasm.\n\nMicronuclei occur outside the main cellular nucleus and are prone to rupturing, which leads to changes in DNA that can drive cancer development.\n\nExtensive DNA damage may cause dicentric/concatenated ring chromosomes and acentric chromatid/chromosome fragments, which can result in the formation of a nucleoplasmic bridge (NPB) at anaphase and micronuclei, respectively.\n\nNuclear buds (NBUDs) are the result of elimination of amplified extrachromosomal DNA, which adheres to the nucleus by a thin nucleoplasmic connection, and are observed as double minute-type micronucleus bodies."}
{"_id": "Radiology$$$d53a0b34-2152-4e32-b19d-2b4a1e557f9b", "text": "Micronuclei are small extranuclear bodies surrounded by a membrane that contain damaged chromosome fragments or even whole chromosomes. The genetic information encoded in the MN DNA will get lost and lead to large genomic consequences."}
{"_id": "Radiology$$$cd20a513-a5a0-4043-8ac8-bab5dbfa5992", "text": "Chromosome segregation errors and/or fragment loss at anaphase (\u201cinter-cell bridges\u201d) and exclusion of acentric fragments from daughter nuclei lead to formation of MN in the cytoplasm."}
{"_id": "Radiology$$$d9d7b496-3066-4225-89f7-24e6f02501ea", "text": "Micronuclei occur outside the main cellular nucleus and are prone to rupturing, which leads to changes in DNA that can drive cancer development."}
{"_id": "Radiology$$$14b2f549-9a63-4967-9ee4-c5b299a03fb1", "text": "Extensive DNA damage may cause dicentric/concatenated ring chromosomes and acentric chromatid/chromosome fragments, which can result in the formation of a nucleoplasmic bridge (NPB) at anaphase and micronuclei, respectively."}
{"_id": "Radiology$$$b5129067-ba73-4125-9064-517025e3c7c6", "text": "Nuclear buds (NBUDs) are the result of elimination of amplified extrachromosomal DNA, which adheres to the nucleus by a thin nucleoplasmic connection, and are observed as double minute-type micronucleus bodies."}
{"_id": "Radiology$$$60500de1-2ec7-4e55-afa0-426dd1ee8d3d", "text": "Micronucleus assays are frequently used to assess genotoxicity and cytotoxicity of different chemical and physical factors, including IR-induced DNA damage. The cytokinesis-block micronucleus assay can measure MN, NPBs, and NBUDs. A diverse range of reliable micronucleus tests (Fig. 3.16) are executed with different cell types, eventually reflecting chromosomal aberrations, ongoing DNA injury, initial stage in the development of genomic instability, and tumorigenesis. In the widely used cytokinesis-blocked MN assay, MN are scored in once-divided binucleated cells, where cytokinesis is blocked with addition of cytochalasin B, an inhibitor of microfilament ring assembly necessary for the completion of cytokinesis. In order to get statistically solid results, a huge amount of cells need to be scored. Therefore, automatic analysis of MN boosts the reliability of the assays. Concomitantly, it increases the statistical validity after analyzing a large number of cells in one go. Additionally, the existing automatic/semiautomatic micronucleus scoring by microscopic systems, by flow cytometry and imaging flow cytometry, gives high accuracy and sensitivity and leads to rapid analysis (Box 3.12).\n\nAn illustration lists the different factors of the cytokinesis-blocked micronucleus cytome assay, the mammalian erythrocyte micronucleus assay, the buccal micronucleus cytome assay, and the micronucleus assay in other cell types.\n\nFig. 3.16\nDepending on the cell type, different micronucleus assays can be employed to assess and determine the genotoxicity and cytotoxicity of different chemical and physical factors. Applications of each assay are outlined in their respective boxes. The most popular CBMN assay can be applied to cultured human lymphocytes or cell lines to measure MN and other chromosomal instability biomarkers such as NPBs and NBUD. The mammalian erythrocyte micronucleus assay is performed on immature erythrocytes from bone marrow to determine cytogenetic damage after radiation exposure. The buccal micronucleus cytome assay is done in rapidly dividing buccal epithelial exfoliated cells (oral cavity) to analyze MN and other cytogenetic biomarkers (source of DNA damage, cytotoxicity, etc.). Occasionally, MN assay is performed on nasal mucosa cells or urine-derived cells for detection of chromosomal damage caused by environmental and lifestyle factors, occupational exposures, prognosis of cancer, and certain diseases. Although the objective and method of performance are similar to CBMN or bone marrow MN assays, these tests have not gained much popularity so far"}
{"_id": "Radiology$$$ac39ae0d-8fd9-4480-9ac9-7f0f6dcecb74", "text": "An illustration lists the different factors of the cytokinesis-blocked micronucleus cytome assay, the mammalian erythrocyte micronucleus assay, the buccal micronucleus cytome assay, and the micronucleus assay in other cell types."}
{"_id": "Radiology$$$cd9d9f9d-8cef-43b0-9e5e-f56e799d8e13", "text": "Micronucleus assays are used to assess genotoxicity and cytotoxicity of radiation.\n\nDepending on cell type, different MN assays are used.\n\nAutomated analysis of MN boosts the reliability and statistical validity."}
{"_id": "Radiology$$$c4e92187-a94e-4ff2-9fee-b921d1966281", "text": "Micronucleus assays are used to assess genotoxicity and cytotoxicity of radiation."}
{"_id": "Radiology$$$2ec36fe5-0b76-4cf0-bb0e-557c3ca49a70", "text": "Chromosomal mutations, also called chromosomal aberrations (CA), are observed at the first mitosis after irradiation and are those that incorporate chromosomal changes, such as deletions, inversions, insertions, substitutions, duplications, or translocations of parts of chromosomes. For better understanding, some types of mutations are shown in Fig. 3.17.\n\nA schematic diagram depicts 5 different kinds of mutations in chromosomes. These are duplication, inversion with flip, deletion, translocation with the exchange of chromosomes, and insertion.\n\nFig. 3.17\nTypes of chromosomal mutations. Nonlethal aberrations are observed at the first mitosis after irradiation. Duplication: one or more copies of a DNA segment/a region of a chromosome are formed. Inversion: A segment of a chromosome breaks off and reinserts in reverse orientation within the same chromosome. Deletion: A part of a chromosome/one or more nucleotides from a segment of DNA are missing or deleted. Translocation: It involves two chromosomes in which a piece of one chromosome breaks off and rejoins to another chromosome. Insertion: A segment of one chromosome is removed and inserted to another chromosome or the same chromosome"}
{"_id": "Radiology$$$9f0d6b1c-2631-401b-8fec-feb556135583", "text": "A schematic diagram depicts 5 different kinds of mutations in chromosomes. These are duplication, inversion with flip, deletion, translocation with the exchange of chromosomes, and insertion."}
{"_id": "Radiology$$$6dda17ea-c4d8-4246-97b7-08f9af647c54", "text": "The mutations shown can also lead to other aberrations. Three which should be mentioned are dicentric and ring chromosomes as well as acentric fragments as shown in Fig. 3.18. A dicentric chromosome is created when two chromosomes with two centromeres are fused. In metaphase, they are visible as one chromosome with two centromeres. This aberration will most likely die during mitosis. Acentric fragments are either fragments of a single chromosome or fused parts of different chromosomes containing no centromere. A ring chromosome is a chromosome which has two breaks on the opposing ends and is fused to form a ring. Both aberrations cannot be pulled into a daughter cell and most likely will, together with the encoded genetic information, be lost during mitosis [68]. According to the severity of the chromosomal aberration, the cell will more likely die; in some cases, it can get transformed to a cancer cell or, in case of germ line cell or a cell in early embryogenesis, several genetic disorders can occur [69]. For a more detailed view on this, refer to Chaps. 2 and 7.\n\nA set of chromosomes at the metaphase stage and exposed to gamma radiation depicts abnormal dicentric, fragmented, and ring chromosomes.\n\nFig. 3.18\nHuman metaphase cell irradiated with 5 Gy gamma rays. Two dicentric chromosomes, three acentric fragments, and a ring chromosome could be found. From https://\u200bwww.\u200bqst.\u200bgo.\u200bjp/\u200bsite/\u200bnirs-english/\u200b1369.\u200bhtml (accessed 05/2022)"}
{"_id": "Radiology$$$07794073-b424-43a4-b84e-c4bb428f63d3", "text": "A set of chromosomes at the metaphase stage and exposed to gamma radiation depicts abnormal dicentric, fragmented, and ring chromosomes."}
{"_id": "Radiology$$$f3af131f-2094-4ead-9dbc-f1d953e6774a", "text": "The frequency of radiation-induced CAs rises with increasing radiation dose to the cells. Different types of CAs depend on the phase of cell cycle at which the nucleus is exposed to irradiation. Chromosome-type aberrations (Table 3.5) occur when pre-synthetic phase (G1) is exposed to irradiation, while chromatid-type aberrations (Table 3.6) appear if irradiation occurs during post-synthetic phase (G2). In chromosome-type aberrations, more than one break is unable to rejoin at the correct ends that often results in abnormal chromosomes. There is much hidden damage present, some of which is transmitted to future cell generations. In contrast, radiation can induce chromatid aberrations during late S and G2 phases, when sister chromatids are being duplicated and the DNA DSBs may result in chromatid breaks (deletions), interchanges, or triradials. Mostly, sister chromatids or non-sister chromatids of homologous chromosomes are affected by all the breaks and rejoins. The chromosomal aberrations serve as a biological dosimeter\u2014an indicator of radiation exposure. Furthermore, radiation-induced CAs delineate an early marker of late effects, including cell killing and transformation.Table 3.5\nChromosome-type aberrations\n\nDicentrics\n\nWhen G1 phase is exposed to irradiation, it causes chromatid breaks in two different chromosomes, which rejoin during S phase and can be seen as dicentric at M phase. Two centromeres in one chromosome appear in dicentrics via breakage-fusion-bridge cycle. These are relatively easy to detect and the main aberration used for biodosimetry\n\nChromosomal gap\n\nRandom achromatic lesions can occur at both the chromatids of a metaphase chromosome, which can be visible as non-stained/lightly stained thinner region. The width of this region is less than the width of chromatid arm\n\nAcentric chromosomal fragments\n\nWhen single or double breaks occur in the same chromosome arm, either at the end of a chromosome or between centromere and telomere region, it will produce terminal or interstitial acentric fragments, respectively. These acentric chromosomal fragments (without centromere) are lost during anaphase. These are generally associated with dicentric chromosomes\n\nRing chromosome (centric ring/acentric ring)\n\nUsually, they result from two terminal breaks in both chromosome arms (chromatids), followed by fusion of the broken ends together to form a circular (centric ring) chromosome, leading to the loss of genetic material. Alternatively, the subtelomeric sequences or telomere-telomere fusion with no deletion also results in complete acentric ring chromosomes\n\nTerminal and interstitial deletion (excess acentrics)\n\nA terminal deletion is the loss of the end of a chromosome (telomere), leaving longer acentric fragment than the width of the chromatid. Interstitial deletion occurs when two breaks are induced in interstitial region and the terminal part rejoins the main body of the chromosome, generating double minutes as acentric fragments\n\nReciprocal translocation\n\nReciprocal (complete or two-way) translocations involve non-acrocentric chromosomes, and it occurs when two different (nonhomologous) chromosomes have exchanged segments with each other\n\nMarker chromosome\n\nMarker chromosomes are often referred to as mysterious supernumerary piece of chromosomal material. In addition to normal chromosomes, these are small additional structurally abnormal metacentric/centric chromosome fragments whose genetic origin is unknown; however, it can be determined by FISH analysis using specific probes\nTable 3.6\nChromatid-type aberrations\n\nChromatid gaps (achromatic lesions)\n\nChromatid gap is a non-staining or very lightly stained region (achromatic lesion) of a single chromatid in which there is a minimal misalignment of the chromatid. The width of this region is less than the width of chromatid arm\n\nIsochromatid deletions\n\nThe double breaks (often called isochromatid breaks) at the same position on both chromatids are an apparent exception to the definition of chromatid aberrations. They may be induced upon irradiation in the S and G2 phases of the cell cycle\nIsochromatid deletions with complete and incomplete sister union (SU): The side-by-side ends of isochromatid breaks usually undergo a cross union to produce U-shaped fragments\nIsochromatid deletion without unions (NU: nonunions): Occasionally, the sister union does not occur and such sister nonunions may be in either the proximal (centric) or the distal (acentric) fragments. They are cited as NUp (nonunion proximal) and NUd (nonunion distal), respectively\n\nTerminal and interstitial deletion\n\nLoss of terminal end of one of the chromatids of a chromosome\n\nSymmetric interchanges\n\nSymmetrical chromatid exchanges are equivalents of chromosome-type reciprocal translocation. Exchanges that yield a balanced interchange of genetic material between two identical sister chromatids (i.e., SCE) with no loss of genetic material and no mechanical problems at mitosis\n\nAsymmetric interchanges\n\nInter-arm interchanges and asymmetrical chromatid exchanges are equivalents of chromosome-type dicentrics. The segments of chromatids are differently joined up, yielding an acentric and dicentric chromatid\n\nIntra-chromatid exchanges/intra-arm interchanges\n\nChromatid exchanges may occur between non-sister chromatids of paired homologous chromosomes or between sister chromatids of a homologous chromosome. These exchanges may result in symmetrical or asymmetrical interchanged forms such as intra-chromatid exchange with centric ring, inter-chromatid exchange with dicentric, pericentric inversion, and duplication/deletion\n\nTriradials\n\nA three-armed configuration occurs when there is an interaction between one chromosome with an isochromatid deletion and a second having a chromatid deletion"}
{"_id": "Radiology$$$bc026553-dd95-4227-aa52-1afa5d2df067", "text": "A series of methods and techniques (Fig. 3.19) have been developing to assess stable or unstable type of CAs in order to evaluate the potential of a test compound (chemical/mutagen/radiation exposure). Human peripheral blood lymphocytes offer unique possibilities to study somatic cell division (in vitro) and thus have been utilized for detection of CAs (Box 3.13).\n\nAn illustration describes standard cytogenetic techniques such as chromosome banding, karyotyping, and flow cytometry on the left and 4 advanced cytogenetic techniques on the right, which are based on I S H, C G H, P C R, and southern blot.\n\nFig. 3.19\nTechniques to assess constitutional or acquired chromosomal abnormalities using standard banding techniques (left) or advanced molecular cytogenetic techniques (right). Standard cytogenetic techniques are traditionally performed by karyotyping of stained metaphase chromosomes or by flow cytometry. Chromosome banding is used to produce alternating light and dark regions, also referred to as \u201ccytogenetic bands,\u201d along a chromosome with the use of special stains (abbreviations are listed below). Chromosome banding patterns are essential in pairing and ordering all the chromosomes, known as karyotyping. Flow cytometry-based procedures have been developed to assess numerical (ploidy) and structural (telomere length) chromosomal aberrations in mitotic cells largely based on DNA content. To overcome the limitations of the banding analysis, advanced cytogenetic techniques are introduced. In techniques based on ISH, fluorescently labeled \u201cpainting\u201d probes are used to localize nucleic acid sequences. FISH identifies chromosomal rearrangements and mapping-specific genes on individual mitotic chromosomes. GISH determines the origin of genomes or chromatins in hybrids. RISH reveals cellular patterns of mRNA expression in cells. CGH-based techniques provide an overview of chromosome ploidy level (gain and loss) throughout the whole genome. CGH with the use of microarrays\u2014aCGH\u2014detects aneuploidies, deletions, duplications, and amplifications based on DNA content. Southern blotting and PCR-based molecular cytogenetic techniques have good potential to detect chromosomal abnormalities from trace amounts of specific regions of DNA/RNA. G-banding Giemsa banding, Q-banding quinacrine fluorescence banding, R-banding reverse banding, C-banding centromere banding, ISH in situ hybridization, FISH fluorescence in situ hybridization, GISH genomic in situ hybridization, RISH RNA in situ hybridization, CGH comparative genomic hybridization, aCGH array comparative genomic hybridization, QF-PCR quantitative fluorescence polymerase chain reaction, qPCR quantitative polymerase chain reaction, MAPH multiplex amplifiable probe hybridization, MLPA multiplex ligation-dependent probe amplification"}
{"_id": "Radiology$$$4cbfb82a-ab4c-41c0-8ab8-3bcf389c9427", "text": "An illustration describes standard cytogenetic techniques such as chromosome banding, karyotyping, and flow cytometry on the left and 4 advanced cytogenetic techniques on the right, which are based on I S H, C G H, P C R, and southern blot."}
{"_id": "Radiology$$$0a3cb5f3-0100-4fd2-a2e9-10a6df4a60b4", "text": "Radiation-induced breakage and improper rejoining in pre-replication (G1) chromosomes may lead to chromosome-type aberrations.\n\nRadiation-induced breakage and inappropriate rejoining in post-replication (late S or G2) chromosomes may lead to chromatid-type aberrations.\n\nSince the radiation-induced aberrations in G0 lymphocytes are of the chromosome type, all paired acentric fragments are to be classified as chromosome-type terminal deletions and not isochromatid deletions.\n\nUnstable aberrations like dicentrics, rings, and anaphase bridges are lethal to cells and not passed on to the progeny. Small deletions and stable symmetric translocations are nonlethal and are passed on to the progeny; thus, they may have genetic consequences."}
{"_id": "Radiology$$$21d5136d-a8a7-4fb5-9d2a-820c6ed1f729", "text": "Radiation-induced breakage and improper rejoining in pre-replication (G1) chromosomes may lead to chromosome-type aberrations."}
{"_id": "Radiology$$$8ccce3ec-b973-406b-867f-dfe9820bd737", "text": "Radiation-induced breakage and inappropriate rejoining in post-replication (late S or G2) chromosomes may lead to chromatid-type aberrations."}
{"_id": "Radiology$$$3713bb5f-e50a-443f-a9c6-38736c3b900d", "text": "Since the radiation-induced aberrations in G0 lymphocytes are of the chromosome type, all paired acentric fragments are to be classified as chromosome-type terminal deletions and not isochromatid deletions."}
{"_id": "Radiology$$$966bb2f0-3fb2-46ae-90fd-20e72cdfb4ff", "text": "Unstable aberrations like dicentrics, rings, and anaphase bridges are lethal to cells and not passed on to the progeny. Small deletions and stable symmetric translocations are nonlethal and are passed on to the progeny; thus, they may have genetic consequences."}
{"_id": "Radiology$$$c76db725-7b7d-4fa8-9cc3-1c3ad7b9ec2d", "text": "From the mentioned chromosomal mutations, the translocations are especially dangerous as, in contrast to many other types of chromosomal aberrations, they can be tolerated by the cells. They usually neither cause loss of genetic material nor mitotic cell death and are thus transmitted to the next cell generations. At the same time, translocations are highly oncogenic or affect cell physiology in other ways. Translocations may be simple; reciprocal; i.e., if chromatin fragments are exchanged between two chromosomes; or even complex [70]. Translocations mostly arise due to erroneous DNA end joining by classical NHEJ or mutagenic alternative repair pathways. Although homologous recombination is generally considered a highly precise repair mechanism, recombination between repetitive sequences especially in heterochromatin may also lead to chromatin exchanges [48]. In addition, HR can trigger chromosomal translocations when its intermediates are resolved by crossover between allelic or nonhomologous chromosomes [70]. Although translocations are not associated with extensive losses of the genetic material, they can generate fusion genes (and proteins) with aberrant, often oncogenic, functions. An example could be the reciprocal translocation t(9;22)(q34;q11) between genes BCR and ABL [71], which is responsible for the development of the well-known chronic myeloid leukemia (for terminology and categorization of translocation types, the reader is referred to specialized books on medical genetics or cytogenetics, e.g., Griffiths et al. [70]). In addition to formation of fusion genes, translocations may activate proto-oncogenes by repositioning them along or between the DNA molecules into a close proximity of a strong promoter of some other gene. If the reading frame of the translocated gene is shifted, its function may be lost. However, the gene activity can be changed also epigenetically, if a gene is moved into an incorrect chromatin environment. This is often a cause of the tumor suppressor silencing, after a tumor suppressor is translocated close to a genetically inactive heterochromatin domain. In the context of radiobiology, it is important to emphasize that cell exposures to different radiation types lead to different types of translocations. Cells irradiated with photonic radiation with low LET mostly contain interchromosomal translocations where one chromatin fragment is translocated to another chromosome or two fragments are reciprocally exchanged between two chromosomes. These lesions are usually simple, but the proportion of complex translocations increases with the radiation dose. Cells exposed to a particle high-LET radiation, on the other hand, mostly suffer from complex chromosomal translocations arising as the consequence of extensive chromatin fragmentation by highly localized energy deposition along the particle tracks [72]. For the same reason, high-LET radiation preferential generates intrachromosomal translocations affecting a single chromosome at multiple sites. To explain this phenomenon, it should be emphasized that chromosomes in the interphase cells occur in the form of chromosomal territories with only a limited extent of mutual intermingling along their borders, as explained in Sect. 3.5. Hence, the areas of chromosome territory borders where translocations between the neighboring chromosomes can be formed represent only a small proportion of the nuclear volume along the radiation particle track [53, 54]. With increasing doses and more particles transversing a single nucleus, however, extensive rearrangements of the genome affecting high numbers of chromosomes can be detected (Box 3.14)."}
{"_id": "Radiology$$$2707ae65-3033-4b54-b5b3-3ae62933889d", "text": "Chromosomal translocations are the consequence of illegitimate rejoining of DNA double-strand breaks generated by radiation.\n\nChromosomal translocations pose a risk of formation of a fusion gene/protein with oncogenic functions; even single translocation may be a sufficient genetic defect to initiate leukemia.\n\nWhile low-LET radiation generates mostly simple translocations, exposure to high-LET radiation leads to complex genotype rearrangements.\n\nDue to the character of energy deposition, low-LET radiation produces predominantly interchromosomal translocations; higher occurrence of intrachromosomal translocations is then a sign of a high-LET exposure."}
{"_id": "Radiology$$$f748ef02-b125-4f3b-bba0-fe458afcf42c", "text": "Chromosomal translocations are the consequence of illegitimate rejoining of DNA double-strand breaks generated by radiation."}
{"_id": "Radiology$$$c8249c02-4899-4f15-bfb1-dda96fbeba6c", "text": "Chromosomal translocations pose a risk of formation of a fusion gene/protein with oncogenic functions; even single translocation may be a sufficient genetic defect to initiate leukemia."}
{"_id": "Radiology$$$738eb22d-366a-4677-860c-0acb1a9145ad", "text": "While low-LET radiation generates mostly simple translocations, exposure to high-LET radiation leads to complex genotype rearrangements."}
{"_id": "Radiology$$$f5b872aa-abb7-48e4-972a-8f910dba3f2e", "text": "Due to the character of energy deposition, low-LET radiation produces predominantly interchromosomal translocations; higher occurrence of intrachromosomal translocations is then a sign of a high-LET exposure."}
{"_id": "Radiology$$$30a16a0a-5189-462c-8bf3-3eb3194a4f60", "text": "Chromosome condensation, the landmark event at the onset of prophase, is the dramatic reorganization of the isolated patches of long thin chromatin strands at the nuclear periphery into compact short chromosomes that can be visualized at metaphase during mitosis or meiosis in eukaryotic cells. Maturation-promoting factor (also called mitosis-promoting factor or M phase-promoting factor, abbreviated MPF), the p34cdc2/cyclin B complex, serves as a master cell cycle regulator for the M-phase transition and chromatin condensation by phosphorylated condensins (Fig. 3.20). MPF activity mainly depends on the cellular concentration of cyclin B, which usually oscillates through cell cycle. During cell division, chromatin condenses and individualizes to discrete chromosomes, which are further segregated by mitotic spindle fibers. Once divided, chromatin decondenses to re-establish its interphase structure component facilitating DNA replication and protein-making processes.\n\nA graphical representation of the relative concentration of cyclin and M P F expression during different phases of the cell cycle, namely, G 1, S, G 2, and M. It points to the M phase and S phase thresholds.\n\nFig. 3.20\nThe presence and action of MPF protein in the cell control premature chromosome condensation induction. Cyclin B oscillates through the cell cycle being undetectable during interphase, very low in G1, gradually increasing from S, reaching maximum in G2, and decreasing abruptly at G2/M transition. This corresponds to the MPF activity during cell cycle. MPF maturation/mitosis-promoting factor"}
{"_id": "Radiology$$$4dde9355-d463-44a8-bcb6-6660b57485c5", "text": "A graphical representation of the relative concentration of cyclin and M P F expression during different phases of the cell cycle, namely, G 1, S, G 2, and M. It points to the M phase and S phase thresholds."}
{"_id": "Radiology$$$de86cf23-65b6-4d0d-86bc-381769c243af", "text": "Chromosome condensation may also occur prematurely in interphase test cells when they are fused to mitotic cells or chemically using specific phosphatase inhibitors. The most common approach is the use of Chinese hamster ovary (CHO) cells as mitotic inducer cells. Following cell fusion, the MPF present in a mitotic cell interacts with the interphase nucleus causing dissolution of its nuclear membrane and premature chromosome condensation of interphase chromosomes. This phenomenon is known as premature chromosome condensation (PCC). The morphology of prematurely condensed chromosomes (PCCs) depends on the stage of the interphase cell in the cell cycle (i.e., G0, G1, S, and G2) (Fig. 3.21). PCCs in G0-phase cells exhibit single chromatids, highly condensed and distinct. During the G1 phase, G1-PCCs are despiralized single chromatid chromosomes, while chromosomes condensed during the S phase (S-PCCs) have a \u201cpulverized\u201d appearance because of less condensed chromatin at the sites of replication [73]. Condensation during the G2 phase (G2-PCCs) yields distinct elongated double-chromatid chromosomes. Consequently, cell fusion-mediated or chemical induction of PCCs has been proven a powerful cytogenetic tool in radiobiology to study the conversion of radiation-induced DNA lesions into chromosomal aberrations at various cell cycle stages since it enables visualization and quantification of radiation-induced numerical and structural chromosomal alterations directly in interphase cells.\n\nFour sets of chromosomes depict different types of premature chromosome condensations during the G 0, G 1, S, and G 2 phases of the cell cycle. Centromeres are largely absent in the S and G 2 phases.\n\nFig. 3.21\nPremature chromosome condensations (PCCs) at various stages of the cell cycle: darkly stained metaphase chromosomes belong to mitotic CHO cells, whereas the lighter stained to the interphase CHO cells. (a) G0-PCCs, (b) G1-PCCs, (c) S-PCCs (reproduced with permission (CCBY) from Pantelias et al. [73]), (d) G2-PCCs. CHO Chinese hamster ovary"}
{"_id": "Radiology$$$ede5846b-60f8-468c-bc52-36ca18db53e2", "text": "Four sets of chromosomes depict different types of premature chromosome condensations during the G 0, G 1, S, and G 2 phases of the cell cycle. Centromeres are largely absent in the S and G 2 phases."}
{"_id": "Radiology$$$7fe89627-ec9e-4e44-8815-7b96af368fa0", "text": "PCC can be induced either by fusion of human lymphocytes with mitotic cells (fusion-mediated PCC) or with the use of specific chemicals (chemical-induced PCC)."}
{"_id": "Radiology$$$46be6857-36ca-4e12-bf22-032670990f23", "text": "In the case of fusion-mediated PCC, the condensation was at first achieved with the use of fusogenic viruses (such as Sendai virus or its equivalent). However, an important disadvantage of this method is that the fusion efficiency depends on various notable factors [74]. These difficulties were overcome by using cell-fusing chemical agents (e.g., polyethylene glycol\u2014PEG). PEG overcomes these difficulties and can be widely used for radiation cytogenetic studies."}
{"_id": "Radiology$$$3c49b75c-21a4-4ded-be8f-082166755fd9", "text": "Chemical-induced PCC exploits specific inhibitors for serine/threonine protein phosphatase, which can activate endogenous intracellular MPF, which is much simpler and easier than fusion-induced PCC. Chemicals that can be used for the achievement of drug-induced PCC are okadaic acid, calyculin A, 2-aminopurine, staurosporine, wortmannin, and sodium vanadate. A limitation of this method is that no PCC can be induced in G0 resting-phase cells (Box 3.15)."}
{"_id": "Radiology$$$bfa3ba12-8d57-4000-b6c1-a4df5ea03dbd", "text": "The appearance of a prematurely condensed interphase chromosome depends on the stage of cell cycle.\n\nPCC can be done in two main ways either by the fusion of human lymphocytes with mitotic cells (fusion-mediated PCC) or by the use of chemicals (chemical-induced PCC).\n\nG1-PCC displays very long single chromatids; PCC in an early, middle, and late S-phase cell shows crushed and pulverized appearance of both single and sister chromatids; G2-PCC demonstrates still long separated sister chromatids with no clearly visible centromere.\n\nThe dephosphorylated active form of MPF, a p34cdc2/cyclin B complex, promotes chromosome condensation in meiotic and mitotic cells.\n\nUpon inhibition of protein phosphatase enzymes, cdc25 and cyclin B/cdc2 complex is activated which promotes condensation of chromosomes prematurely."}
{"_id": "Radiology$$$70bddf18-6f87-4541-b7fd-be4ddc9e9e56", "text": "The appearance of a prematurely condensed interphase chromosome depends on the stage of cell cycle."}
{"_id": "Radiology$$$faffa637-e845-4f93-be9e-4ce6a50bff87", "text": "PCC can be done in two main ways either by the fusion of human lymphocytes with mitotic cells (fusion-mediated PCC) or by the use of chemicals (chemical-induced PCC)."}
{"_id": "Radiology$$$74f7dcad-ac48-4618-b6c0-ac6e956640e2", "text": "G1-PCC displays very long single chromatids; PCC in an early, middle, and late S-phase cell shows crushed and pulverized appearance of both single and sister chromatids; G2-PCC demonstrates still long separated sister chromatids with no clearly visible centromere."}
{"_id": "Radiology$$$b3e11dba-3cda-4af7-9e37-8aa3673178b5", "text": "The dephosphorylated active form of MPF, a p34cdc2/cyclin B complex, promotes chromosome condensation in meiotic and mitotic cells."}
{"_id": "Radiology$$$2b473e5a-38d3-412a-8155-fb4b491f5a57", "text": "Upon inhibition of protein phosphatase enzymes, cdc25 and cyclin B/cdc2 complex is activated which promotes condensation of chromosomes prematurely."}
{"_id": "Radiology$$$6a6e1cfa-be93-41d9-aeb7-b5078ab59c8c", "text": "Because of its unique properties, PCC is used for visualizing and scoring chromosomal damage induced by radiation or other clastogenic agents, measuring the induction yield and repair kinetics of chromosome damage in cells at various cell cycle stages immediately after irradiation. It can also be used for the study of condensation dynamics and conformational changes that occur during the cell cycle. The data obtained using the PCC assay can correlate radiation-induced DNA damage and CAs observable at metaphase [75]."}
{"_id": "Radiology$$$cdb9d547-484f-485a-879a-b50a01b25ec6", "text": "Mitotic cell fusion-induced PCC in human lymphocytes (G0-PCC) allows early detection of cytogenetic damage in interphase, the stage of human lymphocytes in peripheral blood, and is the most suitable technique especially for biodosimetry applications in radiation emergency accidents as well as for triage biodosimetry [76]. A later ring PCC (rPCC) assay is an alternative biodosimetry method to the \u201cgold standard\u201d cytogenetic approach (dicentric analysis in metaphase) for high-dose exposure to radiation and can be applied in a simulated mass casualty accident either after chemical induction of PCC [77] or by means of cell fusion providing a much faster assessment of dose [78]."}
{"_id": "Radiology$$$9fd6c36b-3c5f-4d99-a310-cba7719c0cd5", "text": "During the last decade, it has been reported that high-LET radiation induces chromothripsis-like complex chromosomal alterations, resembling the phenomenon of chromothripsis appearing in tumors [79]. The term chromothripsis arises from the Greek dialect (chromo for chromosome and thripsis for shattering into pieces), and it was initially described in 2011 by Stephens et al. [80]. Rather than a progressive accumulation of sequential alterations induced in the genome, chromothripsis is a process where chromosome segments undergo tremendous but localized shattering and random rearrangements in a single catastrophic event. Inaccurate rejoining of the induced chromosome fragments results in a new genomic arrangement and the formation of complex chromosomal aberrations that may trigger carcinogenesis (Fig. 3.22)."}
{"_id": "Radiology$$$1d700af8-7e02-4dc1-9ecc-6f8d970f3806", "text": "The mechanisms responsible for chromothripsis are still under debate. However, studies have shown several situations that could be catastrophic for the cell and result in chromothripsis. One possible mechanism proposed is that DNA damage such as DSBs and chromosomal aberrations may cause aberrant mitosis and formation of MN including one or more chromosomes that may undergo localized shattering and chromothripsis. Chromosome shuttering and chromothripsis may emerge in MN when the main nucleus enters mitosis while DNA is still being replicated within micronuclei. Additionally, PCC induces a mechanical stress in the asynchronous micronucleated cells leading to chromosome shattering [73]. Random genomic rearrangements in micronuclei can then be integrated into the cell\u2019s genome, triggering amplification of oncogenes and cancer development [81]. Other additional mechanisms have also been proposed, such as dicentric chromosome formation, telomere erosion, and abortive apoptosis [82]."}
{"_id": "Radiology$$$b3c67c4b-c06c-4b1e-bb77-d54ce45e698e", "text": "Regarding radiation-induced chromothripsis-like chromosomal alterations, it was tested recently whether clustered DNA lesions and chromatin decompaction induced by high-LET irradiation can subsequently evolve in localized chromosome shattering in chromosome domains along the particle tracks. This is a critical risk for chromothripsis to occur, and the results obtained provided experimental evidence that high-LET particle radiation is effective in inducing chromothripsis-like aberrations, which can be used as a fingerprint of high-LET exposure [83]. These discoveries are valuable in the fields of radiation oncology and space radiation protection, since chromothripsis-like aberrations can be responsible for adverse effects and increase the hazard for secondary induced cancer.\n\nA flow diagram depicts a chromosome with a centromere in the middle and telomeres leading to chromosomal shattering and abnormal re-ligation events, or random genomic rearrangements. In the end, the centromere shifts to the left.\n\nFig. 3.22\nSchematic illustration of chromothripsis. It is a phenomenon where one single catastrophic event leads to a massive and localized shattering of one or few chromosomes. Shattered chromosome fragments are not properly rejoined resulting in a new genome configuration and a large number of complicated chromosomal aberrations"}
{"_id": "Radiology$$$ca4c57c2-351b-4560-b5cd-1aab7c1def19", "text": "A flow diagram depicts a chromosome with a centromere in the middle and telomeres leading to chromosomal shattering and abnormal re-ligation events, or random genomic rearrangements. In the end, the centromere shifts to the left."}
{"_id": "Radiology$$$d67e4920-75a0-4da5-8a0f-ad7bbd47eb1e", "text": "This chapter is dedicated to the importance of ionizing radiation-induced foci (IRIF) (Fig. 3.23) in DNA damage measurements. Traditional biomarkers of radiation exposures are chromosomal aberrations and micronuclei. In contrast to quantification of these biomarkers, which emerge due to repair errors in some cells only, IRIF of certain proteins and posttranslational modifications are formed in all cells on all DSB damages, almost immediately after irradiation. Hence, these IRIF can be considered specific biomarkers of DSB lesions [84]. This allows easier and faster victim triage. Moreover, naturally occurring amplification of the DSB damage signal, associated with extensive focal accumulation of \u03b3H2AX and numerous repair proteins at DSB sites (for detailed description on DNA repair, see Sect. 3.4), offers the unprecedented sensitivity of radiation dose estimation via the pure counting of IRIF on immunofluorescence microscopy images [84]. The radiation dose absorbed by the cells can be estimated by simple counting of such IRIF or, more automatically, by measuring the integrated intensity of the IRIF signal for high numbers of individual cells by flow cytometry [85]. Under the optimal conditions, especially the time range around 30 min after irradiation, the reported minimal detectable values lie in the range of mGy [86].\n\nThree micrographs with two fluorescent dyes depict the presence of 53 B P 1, gamma H 2 A X, and 53 B P 1 plus gamma H 2 A X, respectively, at 5-micrometer scales.\n\nFig. 3.23\nRadiation-induced DNA damage foci. 53BP1 (left, cyan) and \u03b3\u03972\u0391\u03a7 (middle, magenta) foci in HeLa cells irradiated with 1.2 Gy alpha particles and spatially fixed at 60 min postirradiation. Colocalization of \u03b3\u03972\u0391\u03a7 and 53BP1 foci is shown (right). Yellow line indicates the cell nucleus"}
{"_id": "Radiology$$$d8f5a804-5fec-4eac-a6fe-20656708455f", "text": "Three micrographs with two fluorescent dyes depict the presence of 53 B P 1, gamma H 2 A X, and 53 B P 1 plus gamma H 2 A X, respectively, at 5-micrometer scales."}
{"_id": "Radiology$$$12872d83-827e-43ab-aaf5-8f5bf17102d2", "text": "Furthermore, DNA damage induction and repair processes can be studied in individual cells using the IRIF assay. In practice, this is important in situations where individual cells can be differentially affected by irradiation, such as in the cases of a partial-body exposure. The ability to study individual cells is critically important also for radiobiological research as individual cells, even if irradiated homogeneously, appear in different phases of the cell cycle, belong to specific (cancer) cell clones, may be to a various extent affected by the bystander effect, etc."}
{"_id": "Radiology$$$828ec7e0-73d0-4c94-a412-6aeaaaf822de", "text": "On the other hand, the biochemical nature of IRIF means that their formation potentially depends on various factors, which may introduce some variability to DSB quantification. It remains a subject of discussion whether all DSBs necessarily require IRIF formation for successful repair. Additionally, some foci may persist at DSB sites even after the break rejoining. A real obstacle could follow from the fact that IRIF occur, to some extent, in nonirradiated cells. However, recent results have proved that the spontaneously forming foci differ in size and topology from the radiation-induced ones. So, staining patterns corresponding, for instance, to replication-stressed or apoptotic cells can be distinguished from IRIF related to DNA repair [87]. Importantly, this phenomenon is more prominent only in cancer cells, which are not relevant for biodosimetry. In any case, \u201cthe second \u03b3H2AX assay intercomparison exercise\u201d carried out in the framework of the European biodosimetry network (RENEB) confirmed a high fidelity of irradiated victims\u2019 triage (dose categorization, rather than dosimetry) based on IRIF detection of the postradiation modification of histone variant H2AX, called \u03b3H2AX [84]."}
{"_id": "Radiology$$$086bab98-971f-49e1-91f5-bb86fe904ed6", "text": "\u03b3H2AX is formed by the phosphorylation of histone H2AX at ser139 [57]. This process is mediated by ATM, ATR, and DNA-PK kinases, appears in minutes after DNA breakage, and spreads over ~2\u00a0Mbps of DSB-surrounding chromatin. Due to this extent of chromatin modification, \u03b3H2AX can be microscopically visualized as compact IRIF at DSB sites of 400\u2013600 nm size as described in Sect. 3.5."}
{"_id": "Radiology$$$92427773-b8ae-48f8-9721-cdab897f88f4", "text": "The number of \u03b3H2AX foci at a particular time postirradiation corresponds to a dynamic equilibrium between the IRIF formation and disassembly as shown in Fig. 3.24. This is the reason why the maximum \u03b3H2AX numbers per cell are detected with a short delay after irradiation and the numbers of counted \u03b3H2AX are slightly lower compared to physically detected DNA breaks (PFGE, comet assay) [49].\n\nA line graph with error plots depicts the number of foci versus time after irradiation for 1 and 2 gray units. Both lines exhibit a downward trend. A set of 6 microscopic images compares the foci at one hour and two hours of 1, 1, and 3 G y. 2 G y depicts a large cluster of foci.\n\nFig. 3.24\nDNA repair kinetics. (a) Formation and disassembly of \u03b3H2AX foci in human cancer cells irradiated with 1 Gy or 2 Gy X-rays. (b) Representative microscopic images for \u03b3H2AX foci 1\u00a0h and 2\u00a0h after X-ray irradiation. (Reproduced with permission (CCBY) from Mariotti et al. [88])"}
{"_id": "Radiology$$$6f611e74-c300-42d5-abd1-d59dc2c4a4a9", "text": "A line graph with error plots depicts the number of foci versus time after irradiation for 1 and 2 gray units. Both lines exhibit a downward trend. A set of 6 microscopic images compares the foci at one hour and two hours of 1, 1, and 3 G y. 2 G y depicts a large cluster of foci."}
{"_id": "Radiology$$$e8e98f35-81ab-422b-bb75-11e0a317d80b", "text": "For most cell types, the peak number of \u03b3H2AX is detected in the time window between 30 min and 1\u00a0h postirradiation on average, and some shift to later postirradiation times may appear in cancer cells as they often suffer from DSB repair defects. If the integrated \u03b3H2AX signal is measured by flow cytometry, the maximal values are measured later than with focus counting, at about 1\u00a0h postirradiation, as the size of \u03b3H2AX foci grows longer than their number [49]. After reaching the peak value, the number of \u03b3H2AX foci rapidly reduces (Fig. 3.24) and, at 24\u00a0h postirradiation, only few DSBs that are repaired only with difficulty persist in cells irradiated with medium doses (in order of Gy) of low-LET radiation. However, a substantial proportion of DSBs may still be detected at this late period of time or even after several days postirradiation in cells exposed to high-LET radiation or high doses of low-LET radiation. From the perspective of biodosimetry, this means that the highest precision of the absorbed dose estimation can be achieved in a few-hour window immediately after irradiation. This requirement can be fulfilled during planned medical care, where, in addition, the monitoring of \u03b3H2AX foci formation and disassembly (DSB repair kinetics) may be used to identify patients hypersensitive to radiotherapy or radioresistant tumors. However, in the case of unpredicted accidents with mass screening, IRIF-based biodosimetry must rely on the persistent foci due to the necessary reaction time. This requires suitable mathematical models for the absorbed dose estimation and restricts the method applicability to the acute photon dose range of ~0.5 to ~8.5 Gy and days after exposure (i.e., 1\u00a0day after 1 Gy and 14\u00a0days after 8.5\u00a0Gy) [89]. For military countermeasures, it should also be kept in mind that some chemical warfare agents, such as mustard gas, also generate \u03b3H2AX foci. Furthermore, background levels may vary due to non-irradiation-induced IRIF, which are also counted and vary individually, so this assay is best suited for triage rather for accurate dosimetry."}
{"_id": "Radiology$$$adfc60fc-25f7-493c-adb6-e6c241f5590b", "text": "In addition to the analysis of \u03b3H2AX IRIF numbers, the spatial distribution of \u03b3H2AX foci can be determined by microscopy. This is an important advantage of microscopy over flow cytometry as low-LET and high-LET exposures can be distinguished according to nuclear topology of \u03b3H2AX foci [90] as described in Sect. 3.5. On the other hand, flow cytometry offers more room for automation than microscopy and can analyze much higher cell numbers, making it the more suitable method for routine biodosimetry in most circumstances (Box 3.16)."}
{"_id": "Radiology$$$1febda37-0fee-4472-a195-dcb720e5077b", "text": "\u03b3H2AX IRIF form as the histone H2AX is phosphorylated after DSB induction.\n\n\u03b3H2AX IRIF formation starts a few minutes after irradiation and peaks at 30\u00a0min\u20131\u00a0h postirradiation.\n\nEspecially after high-dose irradiation or irradiation with high-LET particles, persistent \u03b3H2AX IRIF are left after repair.\n\n\u03b3H2AX IRIF can be used for triage-level biodosimetry by counting foci either in the first hours or persistent foci in microscopic images."}
{"_id": "Radiology$$$425de38e-4ad6-4092-8996-11ceb2bc7ebc", "text": "\u03b3H2AX IRIF form as the histone H2AX is phosphorylated after DSB induction."}
{"_id": "Radiology$$$608e0c6c-b747-4e29-9ea2-2aa533d2ebd1", "text": "\u03b3H2AX IRIF formation starts a few minutes after irradiation and peaks at 30\u00a0min\u20131\u00a0h postirradiation."}
{"_id": "Radiology$$$2c0274fb-8741-449c-ac63-0833ee9d2ae0", "text": "Especially after high-dose irradiation or irradiation with high-LET particles, persistent \u03b3H2AX IRIF are left after repair."}
{"_id": "Radiology$$$153c81cb-2e21-401f-a415-aba5951d6c9f", "text": "\u03b3H2AX IRIF can be used for triage-level biodosimetry by counting foci either in the first hours or persistent foci in microscopic images."}
{"_id": "Radiology$$$84fbfdc9-d2cf-4b11-8e69-9b823d9be3cb", "text": "\u03b3H2AX attracts numerous proteins with specific signaling and/or repair functions to DSB sites. These proteins, in turn, form IRIF with protein-specific time occurrence and extent of colocalization with \u03b3H2AX. Hence, IRIF formed by numerous repair proteins can be used to quantify DSBs and estimate the absorbed dose in the same way as it was described above for \u03b3H2AX. Alternatively, repair protein and \u03b3H2AX foci can be detected simultaneously to enhance the fidelity of DSB evaluation. Furthermore, the protein composition and structure of IRIF protein complexes (e.g., their specific persistent homology at the nanoscale), and differences of these parameters in specific chromatin domains and after exposure to different types of ionizing radiation, help to understand the mechanisms of DNA repair."}
{"_id": "Radiology$$$3d3ae7c7-0ffd-4541-9ca2-abbc7bd77d97", "text": "Some proteins like 53BP1 form IRIF morphologically comparable to \u03b3H2AX foci. Others, which are required in only a few copies (Ku70 and Ku80), are too tiny and can be visualized only with electron microscopy or super-resolution optical microscopy [91]. Other proteins [such as MRE11, NBS1, or ATM (Fig. 3.25)] create small, but large enough, IRIF to be recognized by standard immunofluorescence microscopy. However, these proteins are, in addition to their IRIF location, also dispersed over the cell nucleus. As IRIF and free aggregates of these proteins may be similar in size, and cannot be discriminated by antibody staining, it is often difficult to reliably distinguish these IRIF from the background [52]. Depending on the function of a particular protein in the repair process, IRIF appear immediately (e.g., MRE11, NBS1, 53BP1) or only later after irradiation (BRCA1, BRCA2, RAD51, etc.). This timing may correspond with repair pathway specificity of a given protein. Some proteins, such as 53BP1 [57], are involved in the regulation of both major DSB repair pathways (NHEJ and HR), while other proteins are selective either for NHEJ or for HR (BRCA1, BRCA2, RAD51).\n\nTwo sets of micrographs with 2 B N of X-L-F and 2 hours of 1 gray unit depict, at the top, D A P I, RAD 51, p A T M, and merge and at the bottom, D A P I, RAD 51, gamma H 2 A X, and merge.\n\nFig. 3.25\nDNA repair protein markers forming small foci. 2BN hTert (XLF-deficient) human fibroblasts were analyzed 2\u00a0h post-IR with 1 Gy. Cells were stained against DAPI, pATM, and RAD51, or DAPI, \u03b3H2AX, and RAD51. RAD51 is present in a subset of pATM and \u03b3H2AX foci. Reproduced with permission (CCBY) from Geuting et al. [92]. DAPI 4\u2032,6-diamidino-2-phenylindole used for staining nuclei, XLF XRCC4-like factor"}
{"_id": "Radiology$$$2460d76c-47ab-45b7-b939-e57cfe9d1aa8", "text": "Two sets of micrographs with 2 B N of X-L-F and 2 hours of 1 gray unit depict, at the top, D A P I, RAD 51, p A T M, and merge and at the bottom, D A P I, RAD 51, gamma H 2 A X, and merge."}
{"_id": "Radiology$$$3f303218-83a6-426c-bad1-497efd941972", "text": "IRIF of repair pathway nonselective proteins, such as 53BP1, occur in all cells and colocalize with most \u03b3H2AX foci [57]. 53BP1 is thus a good DSB marker for biodosimetry, in addition to \u03b3H2AX. Moreover, 53BP1 foci have similar size and shape as \u03b3H2AX foci so that 53BP1 and \u03b3H2AX foci extensively colocalize (Fig. 3.23). This fact improves DSB detection in cells where both types of foci are labeled simultaneously. Co-labeling of \u03b3H2AX and 53BP1 foci may be especially useful when cells were exposed to low radiation doses generating only few DSBs or if cancer cells with a strong background signal are analyzed. A significant improvement of DSB number estimation due to \u03b3H2AX and 53BP1 co-detection is experienced also in cells exposed to high-LET radiation, where DSBs are extensively clustered and can be thus discriminated only with limitation. However, super-resolution microscopy methods, such as single-molecule localization microscopy (SMLM) or STED microscopy, are necessary for more precise analysis of IRIF foci or even their internal composition and arrangement [48, 57]."}
{"_id": "Radiology$$$a21f12c0-89a5-4d44-b7e4-0e1abd8346cc", "text": "It should be noted that not all \u03b3H2AX foci necessarily colocalize with 53BP1 (or other repair proteins) at early time periods postirradiation. This includes also the period of 30 min postirradiation when the maximum \u03b3H2AX focus numbers are detected. On the other hand, at late time periods after irradiation, 53BP1 foci may persist in cells without being accompanied by \u03b3H2AX. These non-colocalizing 53BP1 foci probably label and protect incompletely repaired chromatin [93]."}
{"_id": "Radiology$$$34de0267-06df-462e-ab43-31634b1d4333", "text": "Moreover, as IRIF form also at sites of single-stranded DNA breaks (SSB) or oxidative base damages, co-labeling of \u03b3H2AX with suitable markers of these lesions (e.g., XRCC1 or OGG1) [94] can provide information on the complexity of individual DNA damage sites. This information may be correlated to various factors, such as the LET of the incidental radiation or chromatin density and genetic activity at DSB sites [16]. Table 3.7 shows a summary of the IRIF markers mentioned in this section and their occurrence (Box 3.17).Table 3.7\nDNA repair proteins and occurrence\n\nProtein/IRIF\n\nOccurrence\n\n\u03b3H2AX\n53BP1\nNBS1\nMRE11\nKu70/80\nRAD51\nBrca1\nBrca2\n\nAll DSB\nAll DSB\nPart of MRN complex\nPart of MRN complex\nAll DSB\nPredominantly HR\nTransition between NHEJ and HR\nPredominantly HR"}
{"_id": "Radiology$$$2b653c47-70f1-4f87-9dae-3c60408ea438", "text": "Repair protein IRIF, depending on the protein\u2019s role throughout repair, can also be used for biodosimetry.\n\nRepair protein IRIF can be used to understand repair mechanisms and pathways of individual DSB sites.\n\nIRIF can be used to understand the effect of radiation of different LET."}
{"_id": "Radiology$$$0004c036-2a2e-4bc3-b72f-a9621d271a5f", "text": "Repair protein IRIF, depending on the protein\u2019s role throughout repair, can also be used for biodosimetry."}
{"_id": "Radiology$$$914ef1d6-c1fb-4dc8-adb7-9e83a4d029f4", "text": "Repair protein IRIF can be used to understand repair mechanisms and pathways of individual DSB sites."}
{"_id": "Radiology$$$636ad242-378d-4201-aeee-064fbb3320b6", "text": "IRIF can be used to understand the effect of radiation of different LET."}
{"_id": "Radiology$$$93da825b-9a4e-447f-8e26-74755c8d68c4", "text": "Exposure to IR induces oxidative damage to cellular molecules such as proteins, lipids, and DNA as a result of oxidative stress (OS), a consequence of the indirect effects of IR (see Chap. 2 and Sect. 3.2), as shown in Fig. 3.26. OS refers to a state of imbalance between oxidants and antioxidants, in favor of oxidants, due to either antioxidant depletion or oxidant accumulation. Oxidants include reactive oxygen (ROS) and nitrogen (RNS) species that comprise free radicals, which are characterized by oneself or more unpaired electrons in the outer shell, and non-radical reactive species. A list of radicals and non-radicals can be found in Table 3.8. Some of these species, e.g., superoxide and hydroxyl radical, are short-lived due to their high reactivity towards other molecules, while others, like hydrogen peroxide, are more stable. Among the ROS, the hydroxyl radical is particularly toxic and involved in the mediation of IR-induced lesions to cell biomolecules. By analogy to OS, nitrosative stress is mentioned when referring to RNS.\n\nA flow diagram depicts the following steps. Plasma membrane damage, mitochondrion disruption with apoptosis, lipid peroxidation, nuclear and D N A damage, and oxidative stress that leads to protein denaturation.\n\nFig. 3.26\nPossible ROS-mediated oxidative stress. Upon exposure to IR, oxidative stress can induce collateral damage, such as lipid peroxidation, protein denaturation, nuclear and DNA damage, mitochondrial damage, and apoptotic death by releasing cytochrome c. Oxidative stress owing to excess ROS generation induces overexpression of antioxidant enzymes in an attempt to control ROS levels. At high levels of oxidative stress, antioxidant defenses are overwhelmed, which leads to inflammatory and cytotoxic responses. (Reproduced with permission from Sanvicens and Marco [95]). NP nanoparticles, ROS reactive oxygen species\nTable 3.8\nList of free radicals and non-radicals\n\nFree radicals\n\nNon-radicals\n\nReactive oxygen species (ROS)\n\nSuperoxide \u00b0O2\u2212\n\nHydrogen peroxide H2O2\n\nHydroxyl \u00b0OH\n\nSinglet oxygen 1O2\n\nPeroxyl \u00b0ROO\n\nOzone O3\n\nLipid peroxyl LO\u00b0O\n\nHypochlorous acid HOCl\n\u00a0\nLipid peroxide LOOH\n\nReactive nitrogen species (RNS)\n\nNitric oxide \u00b0NO\n\nNitrous acid HNO2\n\nNitrogen dioxide \u00b0NO2\n\nPeroxynitrite ONOO\u2212\n\u00a0\nDinitrogen trioxide N2O3"}
{"_id": "Radiology$$$b9d0ee09-9e96-4261-88e1-c1a50b14c06d", "text": "A flow diagram depicts the following steps. Plasma membrane damage, mitochondrion disruption with apoptosis, lipid peroxidation, nuclear and D N A damage, and oxidative stress that leads to protein denaturation."}
{"_id": "Radiology$$$2f8a8c8a-ba2c-4fe0-a9f1-a87bfc0fe5f6", "text": "Oxidants are produced from exogenous, such as air pollutants, xenobiotics, and IR, and endogenous sources as normal cellular metabolism by-products. Examples are the mitochondrial electron transport chain (ETC), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, xanthine oxidase, and peroxidases. Low to moderate ROS levels are crucial in physiological function of cell to avoid oxidative stress involved in aging and several neurodegenerative diseases, diabetes, cancer, atherosclerosis, etc. ROS are also signaling molecules involved in the IR non-targeted effects (see Chap. 2)."}
{"_id": "Radiology$$$bec33318-7544-40ff-95f0-5d9435a7f34f", "text": "OS occurs in pathologic conditions, when the cellular antioxidant defenses are overwhelmed by free radicals and oxidants. Their great oxidative ability leads to oxidative damages to cellular biomolecules (DNA, proteins, and lipids) resulting in multiple damage affecting cell membrane, cellular signaling, and genome integrity. The accepted radiation biology paradigm considered DNA for a long time as the critical IR target and the primary cause for the harmful effects of IR, due to its content of genetic information, with nucleic acid damage being extensively characterized, without consideration that damaged lipids and proteins may also have detrimental effects on cellular function."}
{"_id": "Radiology$$$815aea37-59ed-4a1c-9279-78c558ac0d2f", "text": "Further targets of radiation-generated ROS are lipids, major constituents of the cell membrane, because of their molecular structure containing abundant reactive double bonds [96]. Upon ROS reaction with polyunsaturated fatty acids (PUFA), chain reactions occur, leading to lipid peroxidation (LP) and generation of toxic decomposition products such as malondialdehyde (MDA), 4-hydroxy-2-nonenal (4-HNE), and isoprostanes (IsoPs), which are quantifiable markers of LP reactions. Biological LP consequences include changes in the permeability and fluidity of the membrane lipid bilayer, ion gradient disruption across membrane, and alterations in membrane-associated protein activity [96]."}
{"_id": "Radiology$$$257167ae-cece-4d23-8e49-326331408914", "text": "Potential oxidative damage to proteins is multiple, cysteine, methionine, and tyrosine residues. Chemical modifications include oxidation, carbonylation, and nitration and lead to posttranslational modifications inducing conformational changes affecting protein structure and function, i.e., loss of enzyme activity."}
{"_id": "Radiology$$$a2821c81-c1bd-4cc1-ab6e-073ac96d7e97", "text": "While the physical and chemical reactions initiated by radiation occur in less than a millisecond, the resulting biological effects may take hours, days, months, or years to be expressed and may differ among individuals due to varying intrinsic radiosensitivity. In particular, since the oxidative damage extent depends on the antioxidant availability, increased expression of antioxidant defense systems has been linked to decreased radiosensitivity [97]."}
{"_id": "Radiology$$$0f9d4bf4-c00f-4864-af67-d07e789ddaa6", "text": "OS also has a central role within the inflammatory process. ROS such as superoxide can rapidly combine with NO to form other RNS, such as peroxynitrite, and is 3\u20134 times faster than the dismutation of superoxide by the SOD. The RNS, in turn, induces nitrosative stress, which adds to the pro-inflammatory burden of ROS. Injured cells release chemoattractant molecules, and NO increases vascular permeability and vasodilation that trigger local inflammation. Neutrophils are the first inflammatory cells to arrive at the site of injury, and the increased expression of intercellular adhesion molecule 1 (ICAM-1) and platelet endothelial cell adhesion molecule 1 (PECAM-1) on disrupted endothelial surfaces contributes to neutrophil extravasation. When leukocytes come into contact with collagen fragments and fibronectin, they release pro-inflammatory cytokines like tumor necrosis factor alpha (TNF-\u03b1), IL-1, and IL-6 that increase ROS production and lead to even greater local inflammation that can perpetuate inducing chronic radiation injury, which in some cases develop into fibrosis [98] (Box 3.18)."}
{"_id": "Radiology$$$d31bfe8f-078a-4e3a-a96d-cb10131497c6", "text": "Oxidative stress is characterized by an imbalance between prooxidant molecules and antioxidants.\n\nOxidative stress participates in the oxidative damage of cellular components.\n\nAntioxidants play a key role in stopping the oxidative chain reactions by scavenging the free radical intermediates.\n\nExcessive generation of ROS, that provokes mitochondrial DNA mutations, impairs the mitochondrial respiratory chain and modifies membrane permeability and mitochondria-associated defense systems.\n\nSeveral biomarkers of oxidative stress exist and comprise direct ROS measurement, indirect measure of oxidative stress by quantifying oxidation products, and measure of antioxidant defenses."}
{"_id": "Radiology$$$9357e4f2-49e5-4845-9daa-0c430055fbf3", "text": "Oxidative stress is characterized by an imbalance between prooxidant molecules and antioxidants."}
{"_id": "Radiology$$$0181b669-78fd-4167-849f-09dad34cd50c", "text": "Antioxidants play a key role in stopping the oxidative chain reactions by scavenging the free radical intermediates."}
{"_id": "Radiology$$$dcc199ab-1655-4cb9-92fd-a5544f98a3d2", "text": "Excessive generation of ROS, that provokes mitochondrial DNA mutations, impairs the mitochondrial respiratory chain and modifies membrane permeability and mitochondria-associated defense systems."}
{"_id": "Radiology$$$a88510eb-7888-422c-ac9c-9ae9273447fe", "text": "Several biomarkers of oxidative stress exist and comprise direct ROS measurement, indirect measure of oxidative stress by quantifying oxidation products, and measure of antioxidant defenses."}
{"_id": "Radiology$$$ee59ee41-381f-4f51-bdab-53dbbfc67b22", "text": "In order to cope with ROS and RNS, living organisms have evolved essential antioxidant defense mechanisms (Fig. 3.27). These are classified as enzymatic and nonenzymatic systems or as high-molecular-weight and low-molecular-weight compounds. The first line of antioxidant defenses includes the highly abundant glutathione (GSH), catalase, glutathione peroxidase (GPx), and superoxide dismutase (SOD). GSH acts directly as an oxidant scavenger or indirectly as a cofactor of several enzymes such as the GPx. SOD exists in three isoforms using different metals as cofactors: SOD1, which is predominantly cytoplasmic; SOD2, which is mitochondrial; and SOD3, which is extracellular. SOD1 and SOD3 contain copper (Cu) and zinc (Zn), whereas SOD2 has manganese (Mn) in its active site. They catalyze the dismutation of \u00b0O2\u2013 to H2O2 afterwards converted to water by catalase, GPx, or peroxiredoxin (Prx). GPx transforms reduced GSH to its oxidized form (GSSG). GSH pool regenerates by de novo synthesis and glutathione reductase using NADPH as a reducing equivalent. GPx is also involved in hydroperoxide detoxification. Prx is involved in hydroperoxides and peroxynitrite detoxification, using thioredoxin (Trx) as a source of reducing equivalents. The most reactive and highly toxic \u00b0OH is produced from H2O2 in the presence of reduced transition metal, a reaction known as the Fenton reaction. Apart from GSH, nonenzymatic antioxidants include endogenous compounds which are produced in organism (uric acid, lipoic acid, l-arginine \u2026) and exogenous compounds which are supplemented through the diet, i.e., carotenoids, ascorbic acid (vitamin C), vitamin E and derivatives (tocopherols and tocotrienols), polyphenols (curcumin, resveratrol, quercetin \u2026), and others.\n\nA flow diagram depicts the action of G S H reductase on G S H and G S S G, G S H peroxidase on R O O H, S O D 1 and 2 on O 2, catalase on H 2 O 2, p r x red on R O O H, t r x R 1 and 2 on t r x red and t r x o x.\n\nFig. 3.27\nAntioxidant defense mechanisms"}
{"_id": "Radiology$$$e53d748d-d776-4be2-9e0e-f9c97b8f08c1", "text": "A flow diagram depicts the action of G S H reductase on G S H and G S S G, G S H peroxidase on R O O H, S O D 1 and 2 on O 2, catalase on H 2 O 2, p r x red on R O O H, t r x R 1 and 2 on t r x red and t r x o x."}
{"_id": "Radiology$$$b1f93952-5e05-4315-9d00-7aa9453569d5", "text": "Glutathione is the major low-molecular-weight thiol in mammals. It plays a key role in cell resistance against oxidative and nitrosative damage by providing reducing equivalents to enzymes involved in the metabolism of ROS, by eliminating potentially toxic oxidation products, and by reducing oxidized or nitrosated protein thiols. In its reduced form (GSH), glutathione is the principal intracellular antioxidant. The conversion of the oxidized form (GSSG) into GSH is done by glutathione reductase (GR) in the presence of NADPH, which is generated by glucose-6-phosphate dehydrogenase in the pentose phosphate pathway (Fig. 3.27). Hence, any damages to these enzymes can compromise GSH functions. The processes of glutathione synthesis, transport, utilization, and metabolism are tightly controlled to maintain intracellular glutathione homeostasis and redox balance. Glutathione is exclusively synthesized in the cytosol and about 85% of it remains there, mainly in the reduced form. The ratio of GSH:GSSG in the cytosol is conservatively estimated at about 10,000:1\u201350,000:1, and the concentration of the cytosolic GSH is as high as 10\u00a0mM, while GSSG in the cytosol is as low as nanomolar concentration [99]. Directly and indirectly, GSH effectively scavenges free radicals and other reactive species (e.g., hydroxyl radical, lipid peroxyl radical, peroxynitrite, and H2O2) through enzymatic reactions, such as those catalyzed by GPxs, glutathione-S-transferases (GST), formaldehyde dehydrogenase, maleylacetoacetate isomerase, and glyoxalase I (Fig. 3.27). GSH also helps to recover other important antioxidants as vitamin C."}
{"_id": "Radiology$$$f5f1afa7-5b88-4e05-81e1-716d9d6a5624", "text": "OS was shown to promote the activation of redox-sensitive transcription factors such as the nuclear factor erythroid 2-related factor 2 (NRF2) and the nuclear factor kappa B (NF-\u03baB). The NRF2 transcription factor plays a central role in the maintenance of cellular redox homeostasis via the coordinated transcriptional upregulation of numerous antioxidant proteins (Fig. 3.28). These include more than 500 genes that are crucial to metabolize electrophilic attack and protect against OS and inflammatory damage. Kelch-like ECH-associated protein 1 (KEAP1) is a key cytoplasmic repressor of NRF2. KEAP1 interaction with NRF2 leads to NRF2 proteasomal degradation. In the presence of OS or inducers, key \u201csensor\u201d cysteine thiol groups on KEAP1 are modified, disrupting the degradation process and allowing NRF2 to directly translocate into the nucleus. NRF2 then upregulates the expression of enzymes involved in the synthesis and recycling of GSH, such as the catalytic and modulator subunits of glutamate\u2013cysteine ligase (GCLC and GCLM), GR, GPx, SOD, and several GST. Moreover, several proteins within the redoxin family, such as Trx, TrxRs, Prxs, and sulfiredoxins, are also upregulated by NRF2 [100] as shown in Fig. 3.29. NRF2 stimulates the mitochondrial biogenesis program through activation of nuclear respiratory factor 1 and indirectly prevents/attenuates inflammation, because NRF2 activation results in the expression of previously mentioned antioxidant enzymes, which detoxify ROS, and in turn this reduces the expression of NLRP3 inflammasome and NFK\u03b2 (the main regulator of pro-inflammatory response). Moreover, NRF2 upregulates heme oxygenase activity (HO-1) and increases CO production, which in turn reduces NFK\u03b2 activity. In response to this, pro-inflammatory cytokine (IL6 and TNFa) production is reduced, and at the same time the production of anti-inflammatory cytokines (such as IL10) increases. As a consequence of these changes, NRF2 facilitates cells to survive oxidative stress and the inflammatory response that aggravates their cytotoxic effects (Fig. 3.29).\n\n A flowchart depicts that the reduced R O S levels lead to anti-inflammatory effects due to the decreased production of pro-inflammatory factors and increased production of anti-inflammatory cytokines. \n\nFig. 3.28\nNRF2 protection against oxidative stress and excessive inflammatory responses involved in IR injury. NRF2 induces antioxidant response genes, like SOD, CAT, GPX, and GST that enhance ROS elimination. In addition, expression of enzymes such as GR and GS increases GSH cellular content and antioxidant capacity of the cell. Reduction in ROS levels decreases the expression of NFK\u03b2, the main contributor to the inflammatory response. Moreover, NRF2 enhances the expression of HO-1 and its activity in the production of CO that reduces NFK\u03b2 activity, pro-inflammatory cytokine secretion (IL-6, TNF\u03b1, and IL-1\u03b2), and pro-inflammatory enzyme activity (COX-2 and iNOS). ARE antioxidant-responsive element, NRF2 NF-E2-related factor 2, SOD superoxide dismutase, CAT catalase, GPx glutathione peroxidase, GST glutathione S-transferase, GS glutathione synthetase, GR glutathione reductase, GSH glutathione, ROS reactive oxygen species, NFK\u03b2 nuclear factor kappa \u03b2, IL-6 and 10 interleukin 6 and 10, IL-1\u03b2 interleukin 1 beta, TNF\u03b1 tumor necrosis factor alpha, COX-2 cyclooxygenase 2, iNOS inducible nitric oxide synthase, HO-1 heme oxygenase 1\n\n\nA flow diagram depicts that radiation generates R O S causing oxidative stress that weakens the mitochondrial membrane potential and leads to cytochrome c release and apoptosis.\n\nFig. 3.29\nMitochondria as the key player in radiation-induced oxidative stress-mediated apoptosis. Various stimuli like radiation or improper functioning of the oxidative phosphorylation induce oxidative stress via ROS production. This causes the mitochondria to dysfunction and subsequently leads to cell death by apoptosis. NAD+ nicotinamide adenine dinucleotide, NADH nicotinamide adenine dinucleotide hydrogen, H+ hydrogen, FAD flavin adenine dinucleotide, FADH2 flavin adenine dinucleotide hydrogen, ATP adenosine triphosphate, ADP adenosine diphosphate, Mn-SOD manganese superoxide dismutase, GPx glutathione peroxidase, H2O2 hydrogen peroxide, CuZn-SOD copper zinc superoxide dismutase, ROS reactive oxygen species, Bcl-2 B-cell lymphoma 2, Bax Bcl2-associated X, APAF1 apoptotic protease-activating factor 1"}
{"_id": "Radiology$$$e5212386-8ef2-4bd5-8629-77bf92b6afc6", "text": "A flowchart depicts that the reduced R O S levels lead to anti-inflammatory effects due to the decreased production of pro-inflammatory factors and increased production of anti-inflammatory cytokines."}
{"_id": "Radiology$$$10043393-17af-41df-b291-4864d5b7faeb", "text": "A flow diagram depicts that radiation generates R O S causing oxidative stress that weakens the mitochondrial membrane potential and leads to cytochrome c release and apoptosis."}
{"_id": "Radiology$$$d1e3b40f-f00d-46e2-9fff-5b0d52bd0549", "text": "Mts are double-membrane multifunctional organelles associated with biosynthesis, metabolism, cell survival, signaling of ROS, etc. In the late 1960s, it was found that radiation could significantly modify the structural form of mts and also the mitochondrial DNA. Human mtDNA is a 16,569 base pair (bp) double-strand circular DNA molecule containing 37 genes, encoding 13 polypeptides for the mt electron transport chain, 2 ribosomal RNA, and 22 transfer RNA for mt protein synthesis. Somatic cells have an average of 100\u2013500 mts with 1\u201315 mtDNA molecules per mitochondrion."}
{"_id": "Radiology$$$8986abb7-8d8d-40f7-a3ca-50054ec50a6d", "text": "Although nuclear DNA (nDNA) is the main IR target, mts are constantly removing excess ROS created during energy production and mtDNA is much more vulnerable to IR effects than nDNA. mtDNA is generally repaired less efficiently than nDNA [101], although it uses the same repair mechanisms such as BER, MMR, and HR but not NER and classical NHEJ. Furthermore, the histones for better exposure protection are lacking. Together, this leads to a mutation rate which is 10\u20131000 times higher than nDNA [102]. Both direct IR exposure and irradiated cell-conditioned medium induce mtDNA damage and alter directed protein synthesis. As a consequence, IR exposure can cause the loss of mt membrane potential, leading to mt undergoing either fission, division of one mitochondrion, or fusion, combination of several mitochondria, autophagy (mitophagy), apoptosis, modification in the mtDNA copy number per cell (mtDNAcn), and cause DNA damage and mutations, like point mutations or deletions. A common deletion mutation of 4977 base pair deletion in mtDNA genes coding for subunits of the mitochondrial ATPase, NADH dehydrogenase complex I, and cytochrome c oxidase is known as a marker for oxidative damage [101]."}
{"_id": "Radiology$$$fb18fec0-8f97-4ed2-9330-f6447d9515fb", "text": "Changes in mtDNAcn or mutations in mtDNA both caused by high intra-mtROS control mt-dependent methylation potential of nDNA by decreasing methyltransferase activity and thus causing global DNA hypomethylation or changes in the expression of specific genes [103]. Global DNA methylation levels depend on human mtDNA variants and are also tissue specific and, therefore, may be connected with the differences in susceptibility to the pathogenic processes resulting from IR exposure and OS in different tissues [103]."}
{"_id": "Radiology$$$fccf5d43-fcb8-41b3-9951-ba4ef50dd032", "text": "OS also appears to target the mitochondrial DNA polymerase-\u03b3 activity required for replication and repair of mtDNA, thereby reducing the overall repair capacity. Therefore, subsequent to radiation exposure, mtDNA might be damaged, with an ensuing decrease in respiratory chain activity and decrease of mitochondrial function, giving rise to an increased ROS production. Moreover, mutations in mtDNA could lead to an increase in accessibility of reduced components of the ETCs to O2, which may result in an increase in prooxidant formation. The functional disablement can be weighed by the limitations of the complexes I and III of the mitochondria, reduction of succinate-induced respiratory competence, augmented ROS levels, and increased mitochondrial protein oxidation. The net consequence is persistent metabolic OS that continues to cause de novo oxidative damage to critical biological structures. Such mitochondrial dysfunction can lead to stress signals, which lead to reduced electron transport chain (ETC), and oxidative phosphorylation can cause imbalance in the mitochondrial ROS production, decrease in the mitochondrial membrane potential, and lesser cellular ATP or energy. Although mts are the main producer of ROS, mts themselves can be susceptible to the pathological outcomes once targeted by ROS. By triggering the mitochondrial stress and downstream signaling, the increased levels of free radicals linked to the mtDNA oxidative damage lead to apoptosis."}
{"_id": "Radiology$$$932f12cd-6668-46f6-8a34-c1f4d74786c2", "text": "One of the crucial steps in the process of apoptosis is the permeability transition pore opening (mPTP), followed by drop in the mitochondrial membrane potential. Opening of the pore increases the permeability of the mitochondrial membrane to molecules, leading to mitochondrial swelling and necrosis. NO produced at the basal level (e.g., 5\u00a0\u03bcM) could S-nitrosylate cyclophilin D (CypD), a critical mPTP regulatory component. This prevents the association of CypD with mPTP that is required for opening the pore and confers a protection to the cell under a stress. On the other hand, NO produced at a high concentration (e.g., 500\u00a0\u03bcM) could produce peroxynitrite in the presence of large amounts of ROS. Peroxynitrite could oxidize mPTP leading to its opening, which would lead to the opening of mPTP, loss of ATP production, and necrosis. The damaged mitochondria generated excessive ROS like hydrogen peroxide and superoxide anion, which provokes the mitochondrion-driven ROS propagation. ROS themselves accelerate the production of mitochondrial ROS. This process is also called as ROS-instigated ROS release (RIRR) by initiating as inter-mitochondria signaling network [104] (Fig. 3.28). Oxidative insult by radiation to the mt alters the mitochondrial membrane potential and causes the leakage of cytochrome c from the inner membrane compartment, which elicits a sequence of signal transduction progression, the outcome of which is apoptotic cell death. Once the mitochondria are severely stressed, the pro-apoptotic factors like Bax create pores on the mitochondrial membrane, which lets the release of cytochrome c in the cell cytoplasm. It interacts with Apaf-1 to form a complex called apoptosome (Apaf-1, cytochrome c, and ATP). Caspase-9 then gets activated and commences the action of other caspases like caspase-3, -6, and -7. These lead to DNA fragmentation and cell degradation, thereby pushing the cells towards apoptosis. This kind of cell death is known as mitochondrial mediated cell death or intrinsic pathway of apoptosis (Fig. 3.29). However, in this case, apoptosis plays a role in abashing cells that induce excessive ROS."}
{"_id": "Radiology$$$1cfd54b9-91bf-4a10-8a7d-922ba71c2950", "text": "Biomarkers of OS can be classified as molecules that are modified by interactions with ROS or molecules of the antioxidant system that change in response to increased OS. ROS levels can also be monitored using fluorescent probes of commercial kits, which specifically detect intracellular ROS such as H2O2, NO, or \u00b0O2\u2212. However, assays that monitor ROS levels are unlikely to be useful for biomonitoring purposes due to the short half-life of ROS and the fact that the response is not specific to radiation exposure."}
{"_id": "Radiology$$$7c1225ae-cdbd-4c57-af13-8ae7975e907b", "text": "S-Glutathionylation is the posttranslational modification of protein cysteine residues by the addition of glutathione. This modification can prevent proteolysis caused by the excessive oxidation of protein cysteine residues under oxidative or nitrosative stress conditions. Measuring S-glutathionylation of the proteins as biomarkers (Fig. 3.30) is hampered by difficulty in accessing the tissue in which these modifications occur. Nevertheless, S-glutathionylation of hemoglobin has been proposed as a biomarker of OS strengthened by finding that it occurs in the circulating erythrocytes in parallel with S-glutathionylation of molecules in the vasculature or myocardium [105].\n\nA flow diagram lists the oxidative products of proteins, polyunsaturated fatty acids, and deoxyribonucleic acid that are created by R N S or R O S.\n\nFig. 3.30\nMain oxidative products of DNA, lipids, and proteins. Oxidative products (listed in gray boxes) are formed depending on the free radicals (RNS/ROS) and the biomolecule target (amino acids, proteins, phospholipids, nucleic acids). These products can be used as oxidative stress biomarkers. RNS reactive nitrogen species, ROS reactive oxygen species"}
{"_id": "Radiology$$$78aa91a8-b283-4bcf-ba6c-76b4169f18c7", "text": "A flow diagram lists the oxidative products of proteins, polyunsaturated fatty acids, and deoxyribonucleic acid that are created by R N S or R O S."}
{"_id": "Radiology$$$2f3364a3-ba34-423a-a088-86c5dde23240", "text": "The participation of GSH in antioxidant reactions, either chemically or enzymatically via GPx, results in its own oxidation to GSSG. Decrease in intracellular GSH/GSSG ratio is one of the most used biomarkers of OS. In these conditions, GSSG is preferentially secreted out of the cell, and therefore, blood levels of GSH and GSSG may reflect changes in glutathione status in other less accessible tissues. 6\u00a0h after a single dose of irradiation (equivalent to 5\u00a0Gy), GSH/GSSG ratio decreases in blood. The decrease in GSH/GSSG is mainly due to an increase in the concentration of GSSG, because GSH levels do not change significantly [106]."}
{"_id": "Radiology$$$bfe50270-538f-4553-8cec-2b9581325c76", "text": "Antioxidants protect the body from the harmful effects of free radical damage. Thus, measurement of antioxidant levels in target tissues or biofluids has been widely used to assess the extent of oxidant exposure and, in turn, OS. TAC is the measure of the free radical amount scavenged by a test solution, being used to evaluate the antioxidant capacity of biological samples (tissues or biofluids). The TAC system involves enzymes (SOD, CAT, GPxs, and other enzymes), endogenous antioxidants, and dietary antioxidants (mentioned before), which are generally decreased when OS increases. TAC can be easily measured in cells, tissue lysates, and biological fluids by commercial colorimetric kits and represents a global approach (integrated parameter considered as the cumulative effect of all antioxidants of the biological sample) if no specific antioxidant molecule is to be investigated. One of the critical points is that the results obtained with different methods are not always comparable, depending on the different technologies used for their assessment. Moreover, as mentioned by Dr. Sies (who coined the concept of oxidative stress): \u201cneither the term \u2018total\u2019 nor the term \u2018capacity\u2019 are applicable to the in vivo assays using an arbitrarily selected oxidant generator assaying a sample removed from its biological context, which is characterized by enzymatic maintenance of steady state\u201d [107]. For that reason, we agree with him \u201cthat investigators should measure individually parameters associated with oxidative stress (GSH, urate, ascorbate, tocopherol, etc.) and antioxidant enzymes activities (in tissues samples and lymphocytes (in the case of blood samples) if their want to have an idea of the exposure of the entire organism to oxidative stress\u201d [108]."}
{"_id": "Radiology$$$c6eb2d64-7ffe-4570-88eb-c81b99e56a17", "text": "The \u201ccomet assay\u201d and newer techniques [e.g., gas chromatography, high-pressure liquid chromatography (HPLC), immunoassays] can distinguish gross DNA damage produced by IR and damage from oxidation (for a detailed description, see Chap. 7). For low doses of radiation, the total number of induced DNA alterations is probably small when compared with the total number of equivalent alterations from endogenous sources. At DNA level, guanine is the most susceptible base to OS, and its oxidation at the C8 of the imidazole ring of deoxyguanosine generates 7,8-dihydro-8-oxo-2\u2032deoxyguanosine (8-oxodG), which is the most predominant and stable DNA oxidative lesion in the genome (Fig. 3.30). A failure to repair oxidized bases creates a risk of mutation during DNA replication. For example, 8-oxodG mispairs with deoxyadenosine (dA) rather than deoxycytosine (dC) resulting in a C-A point mutation, thus increasing the risk of carcinogenesis. Besides the impact of confounding factors like age, sex, and smoking habits, with the help of correction factors, 8-oxodG levels are good and sensitive biological indicators of OS, which can be quantified in serum or urine samples, using HPLC coupled with mass spectrometry [109]. 8-OxodG can be removed by NER or BER with the action of 8-oxodG DNA glycosylase 1 (OGG1), a base excision DNA repair enzyme that cleaves the N-glycosidic bond between the base and the deoxyribose, generating an apurinic/apyrimidinic site (AP) and triggering the BER mechanism. DNA strand breaks and AP sites are effective substrates to activate DNA damage sensor PARP1. Overactivation of PARP1 is associated with apoptosis-inducing factor (AIF)-mediated and caspase-independent cell death. OGG1 seems to guard genome integrity through lesion repair or cell death depending on the magnitude of guanine oxidation. OGG1 may also be measured as an OS marker."}
{"_id": "Radiology$$$6a33001a-e665-42e8-8f62-9db41c213bd6", "text": "As previously mentioned, lipid peroxidation products include MDA, 4-HNE, or IsoPs and can be used as oxidative stress biomarkers (Fig. 3.30). The latter are prostaglandin-like molecules formed by the nonenzymatic peroxidation of arachidonic acid (AA). MDA may be formed as a result of enzymatic and free radical peroxidation of PUFAs containing at least three double bonds and is also formed during prostaglandin synthesis. MDA can also react with DNA bases to form deoxyguanosine, deoxyadenosine, and deoxycytidine adducts, and these DNA-MDA adducts have mutagenic effects. Phospholipids containing linoleic acid and AA are considered the main source for 4-HNE production. Many different analytical methods are available for the measurement of MDA, 4-HNE, or IsoPs in biological samples and are reviewed by Tsikas [96]."}
{"_id": "Radiology$$$16f0715d-669c-4cf3-a62d-79df9b183f61", "text": "It has been estimated that proteins scavenge a majority (50\u201375%) of generated reactive species. To function as biomarkers, protein oxidation products must be stable, accumulate in detectable concentrations, and correlate with OS exposition. Protein carbonylation is an irreversible protein modification, associated with alterations in functional and structural integrity of proteins, contributing to cellular dysfunction and tissue damages. Due to relatively early formation during OS, higher stability in comparison to other oxidation products, and simple analysis methods, protein carbonyls are one of the most OS biomarkers. Protein carbonyls can be easily quantified in plasma, serum, tissue samples, and also saliva by enzyme-linked immunosorbent assay (ELISA) [110]."}
{"_id": "Radiology$$$4c5eb4c2-0d63-431e-8721-2fe0778927c3", "text": "The reaction between \u00b0NO and \u00b0O2\u2212 forms peroxynitrite, which can nitrate tyrosine residues in proteins. This process is in competition with the enzymatic dismutation of \u00b0O2\u2212 and the diffusion of \u00b0NO across cells and tissues. Peroxynitrite-mediated damage has been implicated in a wide range of disease pathologies, and 3-nitrotyrosine (3-NT) and nitrated proteins have been established as a footprint of nitro/oxidative biomarker of progression and severity in conditions. The measurement of 3-NT can be performed in plasma, serum, as well as tissue samples by special mass spectrometry. Commercially available ELISAs are usually used in clinical studies due to standardization and easy sample preparation. In turn, several limitations have been highlighted in the literature, such as low sensitivity and minor specificity. This and other protein oxidation biomarkers in human diseases are extensively reviewed by Kehm et al. [110]. The advancement of proteomics will allow us to assess changes in proteins (including the assessment of carbonylated, S-glutathionylation, S-nitrated, and/or N-nitrated derivatives) that serve as biomarkers of exposure to IR. An overview of the oxidation products of DNA, lipids, and proteins formed can be found in Fig. 3.30."}
{"_id": "Radiology$$$8399a9fd-9c7a-4332-b623-0044dd37aed1", "text": "The cell cycle is a fundamental process through which the cell grows and accurately duplicates the genetic material before it divides to give rise to two daughter cells. The cell cycle is divided into two phases: interphase in which the cell spends most of its time, followed by mitosis during which the cell divides into two daughter cells. The interphase has three distinct phases. The first phase is the G1 phase in which the cell grows and prepares itself for DNA synthesis. Second is the S phase, when the cell actually duplicate its DNA. The third phase is the G2 phase, where it prepares itself for mitosis. The duration of G1 varies considerably from cell to cell, while S, G2, and mitosis show less variation. Quiescence is a reversible state of a cell in which it does not divide but retains the ability to reenter cell cycle. This state is also called G0 phase."}
{"_id": "Radiology$$$be9d612c-9039-4b6f-bd4b-973fd092d96b", "text": "The transition from one cell cycle phase to another is controlled by a variety of proteins, cyclins, and cyclin-dependent kinases. If the system identifies any inaccuracies, the transition from one phase to the next will be delayed and the cells arrested in the so-called cell cycle checkpoints [111]. Cells, which enter mitosis with unrepaired DNA damage, will most likely fail to divide properly resulting in cell death. In order to provide time for DNA damage repair or, if repair is not the best solution for inducing cell death, e.g. apoptosis, before DNA synthesis (S phase) and in particular mitosis is initiated, radiation induces arrest in checkpoints at the end of the G1 and G2 phases. Since the process that kills the cells after radiation damage is related to cell division, cells in G0 or cells which are differentiated or in senescence and have lost the ability to proliferate are very resistant to radiation [112]."}
{"_id": "Radiology$$$bb23fd76-579a-4d2d-8205-e08f3cff3a1e", "text": "Cell division is a highly regulated progression allowing cells to divide and to generate daughter cells. The regulation is necessary for the recognition and restoration of genetic injury along with the prevention of uninhibited cell division. It is regulated by cyclins and cyclin-dependent kinases (CDKs). CDKs are serine or threonine kinases, which unite with a separate subunit of functional cyclins, which presents domains essential for enzymatic activity. CDKs are known to have a crucial function not only in cell division but also in amending the transcription responses. Hence, the deregulation of CDKs is a characteristic of cancers and utilized for anticancer therapy purposes. On the other hand, cyclins establish the activity of CDKs as their levels keep changing during the cell cycle. Depending on their participation and function during the cell cycle, cyclins are divided into four categories: G1 cyclins, i.e., D cyclins; G1/S cyclin, i.e., cyclin E; S-phase cyclins, i.e., cyclins E and A; and M-phase cyclins, i.e., B cyclins. Researchers have discovered around 20 CDK-associated proteins, which makes the cell cycle a complex process that involves the combination of CDKs (Cdk1, Cdk2, Cdk3, Cdk5, Cdk4, Cdk6, Cdk7, Cdk8, etc.) and cyclins (A1, A2, B1, B2, B3, C, D1, D2, D3, E1, E2, F, etc.) in distinct phases of the cell cycle endowing extra governance to the cell cycle apparatus (Table 3.9 and Fig. 3.31). Cyclins impart the specificity for substrates and normal cell cycle regulation, which includes the subunit binding, localization, activation/deactivation, etc. to the Cdk/cyclin complexes [113].Table 3.9\nCyclins, CDKs, and their function throughout cell cycle\n\nCell cycle phase\n\nCyclins\n\nCDKs\n\nFunctions\n\nG1\n\nCyclin D\n\nCDK 4, CDK6\n\nCan act in response to external cues, e.g., growth factors and/or mitogens\n\nG1/S\n\nCyclins E\n\nCDK2\n\nControl the centrosome duplication\n\nS\n\nCyclins A and E\n\nCDK2\n\nThe main targets are helicases and polymerases\n\nM\n\nCyclins B\n\nCDK1\n\nControl G2/M checkpoint. The cyclins are produced in S phase but are inactive until the synthesis is entirely completed. Phosphorylate several downstream targets\n\n\nA cyclic diagram of the cell cycle depicts the action of C D K 4 by 6 and cyclin D in the G 1 phase, C D K 2 and cyclin A in the S phase, C D K 1 and cyclin A in the G 2 phase, and C D K 1 and cyclin B in the M phase.\n\nFig. 3.31\nOverview of cell cycle: functions of different phases, cyclins and CDKS, and CDIs"}
{"_id": "Radiology$$$7c1008aa-a7a1-4341-91c8-690982d2865f", "text": "A cyclic diagram of the cell cycle depicts the action of C D K 4 by 6 and cyclin D in the G 1 phase, C D K 2 and cyclin A in the S phase, C D K 1 and cyclin A in the G 2 phase, and C D K 1 and cyclin B in the M phase."}
{"_id": "Radiology$$$2bf03825-c490-4941-a797-9442aa7b4f71", "text": "CDKs have a very limited activity without the presence of a cyclin. To be an active kinase, it should be bound to its cyclin partner and its activity can be further altered by phosphorylation and association of additional proteins like p27. Every CDK/cyclin complex possesses a distinct function that is restricted to a specific cell cycle phase (Table 3.9). Cdk4 and/or Cdk6 are activated by D-type cyclins in the beginning of the G1 phase, and it commences phosphorylation of the retinoblastoma protein (Rb) family (Rb, p107, and p130). This releases the E2F transcription factor and causes the activation and transcription of the E2F-responsive genes that are necessary for the cell cycle progression. The cyclin A and E types are the early E2F-responsive genes. During the later G1 phase, cyclin E binds to Cdk2 to activate it and executes the phosphorylation of Rb (pocket proteins), provoking the further activation of the E2F intervened transcription. This assists in the crossing over of the cell cycle checkpoints at the periphery of the G1/S phase, and to S-phase commencement. Cdk2 unites with cyclin A and aids the progression of the S phase. During the inception of the S phase, A-type cyclins are synthesized, which phosphorylates proteins associated with DNA replication. Going further, at the time of G2/M transition, the activity of Cdk1/cyclin A is necessary for the induction of the prophase. Lastly, Cdk1/cyclin B complexes dynamically contribute to the completion of the mitosis process. Cdk1 activity fluctuates throughout cell cycle succession and is proficient of governing varied cell cycle adaptations (G1/S, S, and G2/M phases) by connecting with diverse cell cycle phase-associated specific cyclins, and several processes like action of CDK-activating kinase (CAK) and inhibitory phosphorylation on CDK. Regulating the cyclin levels and action of CDK inhibitors during the cell cycle assures that CDKs are active in the precise stage of the cell cycle. Cells exploit many processes such as transcriptional control of cyclin genes and breakdown of cyclins; the transcriptional control of the cyclin subunits is one way that ensures appropriate temporal expression of the cyclins and degradation of cyclins, to confine cyclins to the proper cell cycle phase and to keep them at the accurate concentration [114]. Ubiquitin-mediated protein degradation is one of the most crucial regulatory controls that confine the cyclins to the proper cell cycle phase. However, SCF (Skp1, Cullin, and F-box proteins) and APC/C (anaphase-promoting complex or cydosome) are two ubiquitin proteins involved in the degradation of cyclins. During the G1-S-phase transition, SCF controls degrading G1 cyclins (cyclin D), while APC/C degrades the cyclins of the S phase and mitosis, thus advancing the exit from mitosis. To control the CDK activity, the regulation of cyclin levels is not the only mechanism. Other mechanisms like activation and inhibition of phosphorylation actions on the CDK subunit and existence of inhibitors are critical in controlling cyclin-CDK activity [114]."}
{"_id": "Radiology$$$84a5f60d-7b96-4145-8786-6ac57d29559a", "text": "CDK inhibitors are a family of proteins that can bind directly to the cyclin-CDK complex and hinder its activity. In the transition of the G1-S phases, these proteins play a very crucial role. CKIs implicated in controlling the S phase and mitotic CKIs are indispensable to avoid early commencement of the S- and M-phase CDKs. However, in human cancers, genes coding these CKIs are often mutated leading to aberrant cell cycle regulation. During normal or extreme conditions (DNA damage, telomere dysfunction, and stress), the functions and activities of the CDK/cyclin complexes are governed and controlled by two families of CKIs. The INK4 family comprises the p16INK4a, p15INK4b, p18INK4c, and p19INK4d which can specifically bind to Cdk4 and Cdk6 and hinder the activity of the D-type cyclin. The other Cip/Kip family (p21Cip1/Waf1/Sdi1, p27Kip1, p57Kip2) obstructs Cdk2/cyclin E, Cdk2/cyclin A, Cdk1/cyclin A, as well as Cdk1/cyclin B activity. The p21 protein hinders the formation of cyclin/CDK protein complexes that are required for the progression from the G1 phase to the S phase of the cell cycle (Box 3.19)."}
{"_id": "Radiology$$$6ab50c96-ab95-47cd-b219-1418b4b5f87c", "text": "Irradiated cells display a complex set of responses that can include either progression or arrest of the cell cycle.\n\nEvery phase of the cell cycle has a very specific set of cyclins and cyclin-dependent kinases to perform functions associated with that particular cell cycle phase."}
{"_id": "Radiology$$$9f74cb2f-8282-49a2-9855-ac8109607597", "text": "Irradiated cells display a complex set of responses that can include either progression or arrest of the cell cycle."}
{"_id": "Radiology$$$105191f3-3cc1-4627-8f2f-73f43df1c0ca", "text": "Every phase of the cell cycle has a very specific set of cyclins and cyclin-dependent kinases to perform functions associated with that particular cell cycle phase."}
{"_id": "Radiology$$$90310ddf-5b84-40c7-87a8-39a341f2f170", "text": "To study the variation of radiosensitivity with position in the cell cycle, it is necessary to synchronize the cells to get a population of cells that are all in the same cell cycle phase."}
{"_id": "Radiology$$$62e641ce-2377-4b03-82b0-4a2889ec3afe", "text": "For cells in culture, there are three main techniques.1.\nIn fluorescence-activated cell sorting (FACS), a flow cytometer is used to sort cells based on fluorescence from a DNA-binding dye, such as Hoechst 33342, which can be used for live cells.\n\u00a02.\nChemically induced cell cycle arrest collects over time all the cells at a cell cycle checkpoint. When the drug is removed, the cells will go through the cell cycle synchronously for some time before they become more and more asynchronous. The most used drug is hydroxyl urea, which arrests cells at the border between G1 and S. The advantage of this method is that it can also be used in vivo.\n\u00a03.\nMitotic selection was introduced by Terasima and Tolmach [115] and is the most used synchronization method in cell culture in vitro. As cells enter mitosis, they round up and become less attached to the flask bottom. By then shaking the flask, the mitotic cells will detach and can be collected with the medium. The cells can then be irradiated at different time points as they go through cell cycle."}
{"_id": "Radiology$$$c914f72d-b977-4e03-9f28-8442f9654df6", "text": "In fluorescence-activated cell sorting (FACS), a flow cytometer is used to sort cells based on fluorescence from a DNA-binding dye, such as Hoechst 33342, which can be used for live cells."}
{"_id": "Radiology$$$4da8467f-5e1f-4d83-85d2-445c11ee4ac7", "text": "Chemically induced cell cycle arrest collects over time all the cells at a cell cycle checkpoint. When the drug is removed, the cells will go through the cell cycle synchronously for some time before they become more and more asynchronous. The most used drug is hydroxyl urea, which arrests cells at the border between G1 and S. The advantage of this method is that it can also be used in vivo."}
{"_id": "Radiology$$$eb5adf77-82d9-483e-89ef-53b647c97ac1", "text": "Mitotic selection was introduced by Terasima and Tolmach [115] and is the most used synchronization method in cell culture in vitro. As cells enter mitosis, they round up and become less attached to the flask bottom. By then shaking the flask, the mitotic cells will detach and can be collected with the medium. The cells can then be irradiated at different time points as they go through cell cycle."}
{"_id": "Radiology$$$555da609-4a2a-4ef8-97ac-1428a681f49c", "text": "The first age-response curve by Terasima and Tolmach [115] using 3 Gy irradiation of HeLa cells is shown in Fig. 3.32, left panel, together with a curve showing the fraction of labeled cells after pulsed incorporation of [3H]-thymidine during S phase. Cell survival was measured as the ability to form a macroscopic colony. The data indicate four times higher survival if the dose is delivered during early G1 compared to at the start of S phase. Furthermore, there is an increase in cell survival with age during S phase; that is, the radioresistance increases as more and more of the DNA is synthesized. HeLa cells are HPV infected and do not have functional p53, which normally would give the cells time for repair before entering S phase. The cells irradiated early in G1 will have time for repair, which is reflected in a high survival, while the cells in late G1 are more sensitive, because they may enter S phase with unrepaired DNA damages. Cell lines with short G1 are sensitive throughout G1. Terasima and Tolmach also irradiated the synchronized cells with various radiation doses and thereby recorded complete dose-response curves for HeLa cells irradiated in different phases of the cell cycle (see Fig. 3.32, right panel). These curves confirmed the variation in radiosensitivity through the cell cycle, as was demonstrated by the age-response curves. In addition, they also showed that cells irradiated while in mitosis are far more radiosensitive than cells irradiated in any part of interphase.\n\n2 line graphs. Graph 1 plots the relative number of cells and percentage of mitoses versus the hour after collection. Graph 2 plots the fraction surviving versus dose for random population, 0, 5, 14, and 19 hours.\n\nFig. 3.32\nAge-response of cells after radiation. Left: Age-response curves for HeLa-S3 cells (open circles: synchronized cells, triangles: asynchronous cells) irradiated with 3 Gy X-rays (= 300\u00a0rad) at different time points after selection in mitosis and the fraction of cells with incorporated [3H]-thymidine in DNA after a 20-min pulse (black circles, right y-axis). Right: Dose-response curves for HeLa-S3 cells synchronized by mitotic selection and X-irradiated at different times after selection. 0\u00a0h: mitosis, 5\u00a0h: early G1 phase, 14\u00a0h: S phase, 19\u00a0h: late S/G2 phase. [Reproduced with permission from Terasima and Tolmach [115]]"}
{"_id": "Radiology$$$7d5f43c9-6fec-42e6-9b75-f4ee3be77d7e", "text": "2 line graphs. Graph 1 plots the relative number of cells and percentage of mitoses versus the hour after collection. Graph 2 plots the fraction surviving versus dose for random population, 0, 5, 14, and 19 hours."}
{"_id": "Radiology$$$2aa2ca0a-eb4a-4a09-bc0d-084be67998d4", "text": "Measurements of the radiosensitivity of cells in G2 are technically difficult, and it has become customary to suppose that cells are radiosensitive if irradiated in G2. However, the radiosensitivity of cells in G2 has been shown to be dose dependent to a quite different degree than in any other phase of the cell cycle. Cells are hyper-radiosensitive for small radiation doses because the mechanism for early radiation-induced G2 arrest by ATM is not activated by radiation doses in the range below about 0.3\u20130.5 Gy (Box 3.20)."}
{"_id": "Radiology$$$864e2b54-8e96-4f6a-a3ed-6873c60ff4cf", "text": "Cells increase radioresistance throughout S phase.\n\nCell radiosensitivity is highest during mitosis."}
{"_id": "Radiology$$$a5189ca2-1cb3-4aa3-9dfa-1f8a15e7fad0", "text": "Telomeres are nucleoprotein structures located at the end of each linear chromosome in the cell nucleus. They are composed by tandem repeats of the G-rich hexanucleotide TTAGGG and are typically 10\u201315\u00a0kb long [116]. These structures are organized into heterochromatin domains, and they play a significant role in maintaining genome stability. There are at least two very important functions of telomeres in eukaryotes. The first one is the protection of the linear DNA molecules from the DNA repair mechanisms, which may recognize these sites as double-strand breaks. Secondly, they define the maximum number of cell cycles that a cell may undergo [116]. At each cell cycle division, telomeres shorten by 50\u2013200\u00a0bp due to the DNA end-replication problem [117]. This problem results from the inefficient copying of the last base pairs of the linear DNA molecule by DNA polymerase. After several cell divisions, the length of telomeres reaches a critical threshold, which means that the cell can no longer divide. The cell has then reached its Hayflick limit, and it proceeds to senescence. Telomere shortening is thus a very-well-known hallmark of cellular senescence and aging. A good example of the telomere shortening is the deficiency of the adaptive immune system in older individuals caused by T cells reaching their Hayflick limit [118]."}
{"_id": "Radiology$$$42f819a9-2b40-48d2-ba56-4a971cce038a", "text": "The telomere attrition can be opposed by an RNA-dependent DNA polymerase known as telomerase. This enzyme can elongate the telomeres by adding 5\u2032-TTAGGG-3\u2032 repeats to the chromosomes 3\u2032 terminal ends. Telomerase is connected with cells\u2019 immortality; thus, it is present in germline and malignant cells. There is only little or no telomerase in most somatic cells [118]. This information is summarized in Fig. 3.33. An inverse correlation between the telomere length and the radiation-induced cytogenetic damage was found for lymphocytes, fibroblasts, epithelial cells, and many cancer cell lines. It was shown that telomere shortening leads to chromosome fusion, chromosome bridges, or higher frequencies of micronuclei. Thus, telomere shortening is closely linked to the cell radiosensitivity. Therefore, targeting the telomeres could be a very good radiosensitizing method in our fight with cancer during radiotherapy [116].\n\nAn illustration depicts the varying length of telomeres in the chromosome of an adult cell with a short telomere after multiple replications and of an immortal cell with telomerase and a telomere at senescence.\n\nFig. 3.33\nTelomeres, their shortening, the senescence state, and immortal cells. An adult cell chromosome with telomeres and the enzyme telomerase, which plays a crucial role in telomere end lengthening (left). Telomere characteristics in an adult cell\u2019s chromosome, after multiple replications, at cell senescence, and when the cell is immortal (left to right, blue box). (Adapted with permission from Aunan et al. [119])"}
{"_id": "Radiology$$$54200623-3f3e-4eae-a051-2987d647a57c", "text": "An illustration depicts the varying length of telomeres in the chromosome of an adult cell with a short telomere after multiple replications and of an immortal cell with telomerase and a telomere at senescence."}
{"_id": "Radiology$$$4dfca531-52c8-4226-a11e-0ef21e03de60", "text": "As described in Sect. 3.7, cellular senescence is a cell state triggered by extrinsic (cellular stressors) and intrinsic (physiological processes) factors. It is characterized by a prolonged and generally irreversible cell cycle arrest, associated with secretory features, macromolecular damage, and altered metabolism, with its function to remove potentially harmful cells from the proliferative pool [120]. Senescent cells are detected at any life stage from embryogenesis (contributes to tissue development) to adulthood (to prevent the proliferation of damaged cells). Yet, senescent cells can also potentiate various aspects of tumorigenesis, including proliferation, metastasis, and immunosuppression by secreting a collection of pro-inflammatory factors collectively termed as senescence-associated secretory phenotype (SASP) [121]. It is important to clarify that senescence is a distinct form of cell cycle arrest and distinct from quiescence, where cells can reenter the cell cycle when favorable growth conditions are restored; terminal differentiation, where cells exhibit functional and morphological changes resulting in loss of original cellular identity; and cell death, where cells are being eliminated and are thus nonfunctional. The existence of multiple senescence programs and the nonspecificity of current senescence markers make it difficult to fully unveil the complex mechanism behind senescence (current understanding presented in Fig. 3.34). It is therefore recommended to apply a multi-marker approach when investigating cellular senescence [120]. Yet, it is currently accepted that two main signaling pathways initiate and maintain the cell cycle arrest: p53\u2013p21\u2013retinoblastoma protein (RB) and p16INK4A\u2013RB. As a consequence, depending on the senescence program, senescent cells express a multitude of hallmarks such as morphological alterations, senescence-associated beta-galactosidase (SA-\u03b2-gal), and SASP among others [122].\n\nA flow diagram depicts the conversion of a healthy cell into a senescent cell by senescence inducers and senescence signals. Senescent cells cause S A S P which leads to senescence programs.\n\nFig. 3.34\nOverview of cellular senescence processes. ROS reactive oxygen species, ATM ataxia-telangiectasia mutated, ATR ATM and Rad3-related protein, Cdk2/4/6 cyclin-dependent kinase 2/4/6, RB retinoblastoma tumor suppressor gene, SASP senescence-associated secretory phenotype, SA-\u03b2-gal senescence-associated beta-galactosidase"}
{"_id": "Radiology$$$f196bd6c-4701-4d6c-8487-1262a6d35d8b", "text": "A flow diagram depicts the conversion of a healthy cell into a senescent cell by senescence inducers and senescence signals. Senescent cells cause S A S P which leads to senescence programs."}
{"_id": "Radiology$$$c87c845f-47c8-46ec-a71c-fe6affc335ab", "text": "Senescence in developmental processes, i.e., in embryogenesis and organogenesis, is induced by paracrine signaling and is mediated by the expression of the cell cycle inhibitor p21. Although SA-\u03b2-gal is highly expressed, developmental senescence is not associated with DNA damage, does not secrete the typical range of SASP cytokines, and is independent of p53 and p16INK4a. Senescence in wound healing prevents excessive fibrosis by secreting PDGFA-enriched SASP to stimulate appropriate skin repair. Senescence causes, or at least contributes to, organismal aging through the shortening of telomeres followed by the induction of p16INK4a and resulting in an accumulation of senescent cells over time. Studies by Baker et al. [123], first in BubR1-mutant mice (Cdkn2ap16 knockout mice) and then later in naturally aged mice, demonstrated that in the absence of p16INK4a, it is possible to inhibit the production of senescent cells and improve health span [123]. Also, SASP triggers multiple intercellular communication paths that also promote aging. Finally, the elimination of senescent cells improved several age-associated conditions. Senescence in cancer has shown a dual role as tumor suppressor and tumor promoter. Senescence is a key mechanism of tumor suppression via the inhibition of proliferation of cancer cells or by stimulating immune surveillance. Yet, cells induced to senescence by oncogenes or chemotherapy exhibit stemlike properties that promote cancer. Several stressors can induce cellular senescence and radiation in one of them. Thus, IR may cause cell cycle arrest resulting in a prematurely induced senescence phenotype (including SA-\u03b2-gal, p16INK4a, p21, and SASP), which is p53 dependent [121]. Unfortunately, the accumulation of these senescent cells can have a negative impact by promoting tumorigenesis. Thus, eliminating senescent cells from tumors and surrounding healthy tissues may be a successful and beneficial adjuvant strategy (Box 3.21)."}
{"_id": "Radiology$$$4a0c5951-bf62-453f-b465-6dd321ff8643", "text": "Telomeres are part the ending parts of chromosomes, which protect the genome integrity\n\nTelomeres shorten in each cell division by 50\u2013200\u00a0bp due to the DNA end-replication problem.\n\nTelomere shortening is closely linked to cellular radiosensitivity.\n\nAfter several cell divisions, the length of telomeres reaches a critical threshold, the Hayflick limit, and the cell proceeds to senescence.\n\nSenescence is sometimes addressed as a type of cell death. A cell in senescence cannot proliferate anymore, it lives only metabolically.\n\nCellular senescence is characterized by a prolonged and generally irreversible cell cycle arrest, and it functions as a process to remove potentially harmful cells from the proliferative cell pool.\n\nSenescence is a key mechanism of tumor suppression via the inhibition of proliferation of cancer cells or by stimulating immune surveillance in cancers treated with radiotherapy."}
{"_id": "Radiology$$$c62a0543-11a4-462a-a8cb-0e50a4b2d58b", "text": "Telomeres are part the ending parts of chromosomes, which protect the genome integrity"}
{"_id": "Radiology$$$c4c7fe91-2672-4d9a-bf4b-2547ea81e469", "text": "Telomeres shorten in each cell division by 50\u2013200\u00a0bp due to the DNA end-replication problem."}
{"_id": "Radiology$$$5f83d1cd-81eb-4468-b8a9-dfd3f887a07e", "text": "After several cell divisions, the length of telomeres reaches a critical threshold, the Hayflick limit, and the cell proceeds to senescence."}
{"_id": "Radiology$$$1c88d8b2-9640-4166-a4fd-09a664f77c41", "text": "Senescence is sometimes addressed as a type of cell death. A cell in senescence cannot proliferate anymore, it lives only metabolically."}
{"_id": "Radiology$$$d7ac6f92-1667-417a-b4fc-8c796866677b", "text": "Cellular senescence is characterized by a prolonged and generally irreversible cell cycle arrest, and it functions as a process to remove potentially harmful cells from the proliferative cell pool."}
{"_id": "Radiology$$$7cf4f59f-334b-407e-9c92-d757bf67357d", "text": "Senescence is a key mechanism of tumor suppression via the inhibition of proliferation of cancer cells or by stimulating immune surveillance in cancers treated with radiotherapy."}
{"_id": "Radiology$$$b082939a-5308-44e7-9857-59aee627a65a", "text": "In response to IR, multiple, molecularly distinct forms of cell\u00a0death may be initiated. Although the decision points of their initiation are not completely clear, it is known that the level of the DNA damage but also the individual signaling status of different cell death pathways in different cell types, e.g., hematological vs. epithelial cells, influence the decision regarding the cell death route."}
{"_id": "Radiology$$$3671ed26-9f74-41cc-860b-6684565d3df8", "text": "The cellular factors that influence include cell type, position in cell cycle when irradiated, DNA repair capacity, as well as functionality of TP53 and similar DNA-damaging sensors [124]. The dose and radiation quality also contribute to the cellular IR response to cell death, and in the tissue, the oxygen levels may impact the cell death route taken [124]. In this section, an overview of four cell death mechanisms are given: (I) mitotic cell death/mitotic catastrophe, (II) apoptosis, (III) necrosis, and (IV) autophagy (Fig. 3.35), some of which are also interconnected in the cell. Furthermore, the underlying molecular mechanisms and importance of these forms of cell death following IR are also described alongside methods of assessment.\n\nA flow diagram depicts the factors influencing the cell death response. Cell fate is divided into damage repair and cell survival and cell death. The principle cell death pathways are mitotic cell death, apoptosis, necrosis, and autophagy.\n\nFig. 3.35\nOverview of cell death and cell death-protective mechanisms in response to radiation. Radiation-induced cell death is influenced by different factors, such as radiation factors, cell intrinsic factors, and cellular microenvironment factors (left). Cell death pathways are listed to the right. The mechanisms and importance of these principal cell death forms are described in detail in the text"}
{"_id": "Radiology$$$81b48cec-dc14-4c27-9302-eb28ca2b5a4e", "text": "A flow diagram depicts the factors influencing the cell death response. Cell fate is divided into damage repair and cell survival and cell death. The principle cell death pathways are mitotic cell death, apoptosis, necrosis, and autophagy."}
{"_id": "Radiology$$$f9217ca4-0f8e-4200-a3f6-2bf9a11765d0", "text": "Mitotic catastrophe (MC) is an important type of IR-induced cell death mechanism, which is triggered when cells enter into the mitotic phase without appropriately completing the S and G2 cell cycle phases [125]. Hence, MC controls cells that are often incapable of successfully completing mitosis. MC works by activating mitotic arrest, and later it may lead to a controlled or a regulated cell death mechanism or senescence. Therefore, MC is a controled cell death that usually follows the intrinsic apoptotic pathway route [124] (Fig. 3.37). MC is also promoted when the proteins that regulate the G2 phase like the p21CDKN1A, checkpoint kinases 1 and 2 (CHK1/2), ataxia-telangiectasia mutated (ATM) and ataxia-telangiectasia, and Rad3-related protein (ATR) are inhibited. MC basically commences with the irregular condensation of the chromatin around the nucleoli, which looks similar to early chromosome condensation. Cells may die in the same cell cycle or in the successive cell cycle progression or division after IR. The anomalous mitosis in such cases leads to unusual segregation of the chromosomes and cell division. As a consequence, this causes formation of giant cells which exhibit the uncharacteristic nuclear morphology and numerous micronuclei and nuclei. Also, it is noteworthy that MC induced by IR is accompanied with excess duplication of chromosomes and hyper-amplification, which results in a mitosis that is multipolar and later development of micronuclei. DNA damage and flaws in the DNA repair processes lead to centrosome hyper-amplification. Cyclin-dependent kinase 2 (CDK2) and cyclin A or E initiate the amplification of the centrosomes at the boundary of G1/S phase. This is often observed in cells that lack a functional TP53; however, in cells with a functional TP53 and p21CDKN1A, which is known as an inhibitor of CDK2, cellular senescence is promoted."}
{"_id": "Radiology$$$0126aa27-daac-4535-b8d9-d82c7a29c87d", "text": "The outcome of MC in the form of cell death can be elicited in the mitotic phase or in the successive interphase. Some cells activate apoptotic pathways in the metaphase that results in delayed apoptosis, i.e., it can take up to 6\u00a0days after IR. Cells that get away with the mitotic arrest of the mitotic cell death are frequently observed to have an unsuccessful cytokinesis consequentially exhibiting tetraploid anomalous nuclei developing into giant cells. Giant cells that possess a functional TP53 will eventually undergo apoptosis following the mitochondrial pathway of apoptosis in the subsequent G1 phase. However, cells with mutant TP53 or deficient TP53 function go on with a few number of cell cycles and attain a growing amount of chromosomal anomalies before they finally succumb to either delayed apoptosis or necrotic form of cell death [125]. As the cells that undergo MC are usually the ones who have lost the potential to carry out any further replication, MC is frequently referred to as a genuine type of cell death. One of the most common properties exhibited by cancer cells is that of defects in cell cycle checkpoints. This lets the cells enduring IR-induced damage to hastily inscribe in the mitotic process even with the misrepaired DNA that eventually leads to MC. More than a few cell division attempts can take place before adequate genetic injuries mount up to activate mitotic death, emphasizing why solid tumors frequently display deferred reactions to IR [124]. MC is triggered after IR exhibits diverse mechanisms of action (Table 3.10) [126].Table 3.10\nExamples of IR-induced MC in different tumor cell lines\n\nInducer of MC\n\nCell line\n\nFeatures/signaling components of MC\n\nIonizing radiation\n\nHeLa (cervical adenocarcinoma)\n\nIncreased levels of cyclin B\n\nU2OS (osteosarcoma)\n\nCheckpoint adaptation\n\nHT0180 (fibrosarcoma)\n\nMicronucleation\n\nMOLT4 (leukemia)\n\nCheckpoint adaptation"}
{"_id": "Radiology$$$ec708c43-fea5-4516-987c-873ab75ca8cd", "text": "During MC, the mitotic damage is recognized and guides the cell into one of the three potential antiproliferative fates (Fig. 3.36). In one of them, when cyclin B levels are elevated, the malfunctioning mitotic cells recruit the cell death machinery and die during mitosis. Another cell death pathway that cells can take is by mitotic slippage. Here, cells go out from mitosis and cell death is triggered in the next G1 cell cycle transition. Lastly, cells with a MC character can also undergo senescence after exiting mitosis.\n\nA flow diagram depicts that the D N A damage response leads to interphase cell death that leads to apoptosis and necrosis and mitotic cell death that is further divided into caspase-independent and caspase-dependent, leading to mitotic catastrophe.\n\nFig. 3.36\nCell death pathways operative in mitotic catastrophe. Different signaling events triggered in response to a nonfunctional mitosis are shown. Upon DNA damage, cells which lack functional p53 can go out from mitosis without commencing cytokines or initiate cell death even in mitosis. Apoptosis and necrosis signaling in the context of mitotic catastrophe are depicted"}
{"_id": "Radiology$$$04207df1-be31-45fb-9937-7b6f199e5fbc", "text": "A flow diagram depicts that the D N A damage response leads to interphase cell death that leads to apoptosis and necrosis and mitotic cell death that is further divided into caspase-independent and caspase-dependent, leading to mitotic catastrophe."}
{"_id": "Radiology$$$9ebbae22-739a-4ad7-99f5-c1eef0441818", "text": "MC may not at all time be accompanied by mitotic arrest. Nevertheless, the mechanism of action that dictates cell fate of subsequent MC continues to remain unclear [127]. When mitotic arrest is extended, the amount of cyclin B is decreased albeit the spindle assembly checkpoint (SAC) is functional. As a result, if cyclin B levels drop below the verge that determines mitotic exit, slippage occurs (Box 3.22)."}
{"_id": "Radiology$$$40e52bfb-6615-4efb-929f-726613781019", "text": "IR-induced cell death depends on radiation quality, dose as well as cell type, cell cycle position, and functionality in DNA damage signaling.\n\nMitotic catastrophe is one of the principal forms of IR-induced cell death that results from early/untimely entry into mitosis, even before the fulfillment of S and G2 phases of the cell cycle.\n\nThe characteristic features of IR-induced mitotic catastrophe are altered nuclear morphology, micronucleation, and formation of multinucleated cells."}
{"_id": "Radiology$$$30228e26-c188-4b73-8f4d-a84f1a6d0ea1", "text": "IR-induced cell death depends on radiation quality, dose as well as cell type, cell cycle position, and functionality in DNA damage signaling."}
{"_id": "Radiology$$$205e4866-e77c-43c9-a11b-10a083b51663", "text": "Mitotic catastrophe is one of the principal forms of IR-induced cell death that results from early/untimely entry into mitosis, even before the fulfillment of S and G2 phases of the cell cycle."}
{"_id": "Radiology$$$b171ba9b-1a4c-4d35-b7b2-e4ba83693989", "text": "The characteristic features of IR-induced mitotic catastrophe are altered nuclear morphology, micronucleation, and formation of multinucleated cells."}
{"_id": "Radiology$$$e40757d7-57a6-475d-ada5-6e2f54f8ec2c", "text": "Apoptosis (originally from Greek language translated \u201cfalling off\u201d) is also known as \u201ccellular suicide.\u201d It is a cell death process which may be executed under normal physiology, e.g., organism development, but also in the context of disease. Apoptosis is a highly controlled pathway with distinct molecular features. Thus, some of the rapidly proliferating cells undergo apoptosis, which is an essential part of neurogenesis and tissue development in humans as well as in other mammalians. During apoptosis, cells are disposed in a complex but well-ordered fashion which involves energy-requiring molecularly defined effector mechanisms [128]. To simplify, apoptosis allows the cells to self-destruct with limited tissue damage when they are exposed to different triggers/signals which can be endogenous, e.g., formed DNA damages, telomere shortening, or encountered from the outside of the cell, e.g., cytotoxic or DNA-damaging agents, IR exposure, loss of growth factors, cytokine or glucocorticoid hormone level alterations, or hypoxia [128]."}
{"_id": "Radiology$$$33abe0ca-702f-4ab3-ac28-e7b6365b5529", "text": "Apoptosis results in the production of apoptotic bodies, which are cell fragments, e.g., collapsed cytoskeleton, disassembled nuclear envelope, and fragments of nuclear DNA. An apoptotic cell is also marked by certain \u201cfind-me\u201d and \u201ceat-me\u201d signals at the cell surface, which allow the dying cell to be recognized and rapidly engulfed by different macrophage subtypes in the near or distant tissue, thereby avoiding inflammation. A well-recognized potential \u201ceat-me\u201d signal is the expression of phosphatidylserine (PS) on the outer side of plasma membrane, which in turn is being used for assessing early apoptotic cells [129]."}
{"_id": "Radiology$$$bcf2a484-c964-4c1e-9194-e30271cc3fce", "text": "In the 1990s, studies which resulted in authors being awarded a Nobel Prize revealed that core machinery components of some apoptotic pathways are highly conserved from nematodes to humans [130]. Subsequently, research on the molecular mechanisms regulating apoptosis has established two major routes of this cell death type, namely intrinsic and extrinsic apoptosis, respectively (Fig. 3.37).\n\nA flow diagram depicts the intrinsic and 2 extrinsic pathways leading to apoptotic membrane blebbing, the formation of apoptotic membrane protrusion, and cell fragmentation via different steps.\n\nFig. 3.37\nThe intrinsic and extrinsic route to apoptosis. Intrinsic stress signals (e.g., DNA damage, hypoxia, metabolic stress) or lethal stimuli (e.g., IR exposure) can induce intrinsic mitochondrial apoptosis (middle). Cleaved or truncated Bid (tBid) can also connect the extrinsic pathway to the intrinsic route. In the extrinsic pathway, ligands for death receptors (left) can trigger caspase activation, but the pathway can also be activated when some dependence receptors are inactivated (right). Abbreviations: FasL Fas ligand, TRAIL TNF-related apoptosis-inducing ligand, TNF tumor necrosis factor, Fas Fas cell surface death receptor, TRAILR TNF-related apoptosis-inducing ligand receptor, TNFR tumor necrosis factor receptor, TRADD TNFR1-associated death domain protein, FADD Fas-associated protein with death domain, caspase cysteine-aspartic proteases, BID BH3-interacting domain death agonist, tBID truncated BID, Bcl-2 B-cell lymphoma 2 (an apoptotic inhibitor), BCL2L1 Bcl-2-like 1, MOMP mitochondrial outer membrane permeabilization, BH3 Bcl-2 homology 3, DIABLO direct inhibitor of apoptosis-binding protein with low pI, APAF-1 apoptotic peptidase-activating factor 1, Bax Bcl2-associated X (an apoptotic regulator), Bak Bcl-2 homologous antagonist/killer, XIAP X-linked inhibitor of apoptosis protein, SMAC second mitochondria-derived activator of caspase, UNC5B Unc-5 netrin receptor B"}
{"_id": "Radiology$$$5119950f-f9b9-465c-ba84-5d1eb7da1baf", "text": "A flow diagram depicts the intrinsic and 2 extrinsic pathways leading to apoptotic membrane blebbing, the formation of apoptotic membrane protrusion, and cell fragmentation via different steps."}
{"_id": "Radiology$$$93a09344-36eb-465f-8d1b-718d5e6670ce", "text": "Multiple perturbations may trigger intrinsic apoptotic cell death, e.g., growth factor withdrawal, cytokine alterations, endoplasmic reticulum stress, replication stress, formation of reactive oxygen species (ROS), microtubular alterations or mitotic defects, and IR-induced DNA damage. In the context of DNA damage, mitochondrial release of apoptogenic proteins is central. This commences in part via mitochondrial outer membrane permeabilization (MOMP) that allows cytochrome C and other proteins to be released to cytosol. Once there, cytochrome forms the apoptosome complex together with apoptotic peptidase-activating factor 1 (APAF-1), where pro-caspase-9 is cleaved to active caspase-9 (CASP9). Subsequently, CASP9 cleaves the effector caspases (e.g., caspase-3, caspase-6, and caspase-7), which then causes degradation of cell signaling and structural proteins resulting in an apoptotic morphology. The BCL-2 proteins are regulators of MOMP. These can either promote, e.g., BCL-2-associated X apoptosis regulator (BAX) or BCL-2 antagonist/killer (BAK) or block MOMP, e.g., BCL-2 or BCL-XL members [131]. Another set of BCL-2 members, which only have a BH3 domain, can also promote MOMP, but they act via alleviation of BCL-2 or BCL-XL function or via promotion of BAX/BAK activity. Examples thereof are BCL2-associated agonist of cell death (BAD), BH3-interacting domain death agonist (BID), BCL2-interacting mediator of cell death (BIM), NOXA, and TP53-upregulated modulator of apoptosis (PUMA)."}
{"_id": "Radiology$$$cbb2d419-28e9-4d4b-86fa-d596bf238acc", "text": "In DNA damage-induced apoptosis, TP53 and BAX/BAK proteins are important. The BCL-2 family members also sense other cellular clues to elicit intrinsic apoptosis including alterations in growth factor receptor/PI3K signaling or microtubule disruption, both of which may have impact in the context of IR-induced cell death. In addition, the mitogen-activated protein kinases 8 and 9 (MAPK8 and MAPK9), more commonly referred to as c-jun N-terminal kinase 1/2 (JNK1/JNK2), are known to regulate the BCL-2 rheostat by phosphorylation of BCL-2 and BAD, via induction of NOXA and PUMA by TP53 transcriptional regulation as well as by association of BIM to microtubuli [132]."}
{"_id": "Radiology$$$98fc6c51-00bb-47b8-aa73-8d5219276308", "text": "The extrinsic pathway starts by the activation of membrane receptors, so-called death receptors (DRs), e.g., FAS/CD95 cell surface death receptor and TNF receptor superfamily member 1A (TNFRSF1A)/TNFR1, and is driven by initiator caspases, e.g., caspase-8 (CASP8) and caspase-10 (CASP10). The extrinsic pathway is also used by various immune cells to trigger apoptotic cell death in tumor cells including TRAIL [133]. In addition, the inflammatory cytokine TNF-\u03b1 produced by activated macrophages, which binds to the TNFR1 and TNFR2 receptors in most human cells, can elicit apoptotic response. Moreover, cytotoxic lymphocytes carry the FasL, which binds and activates the FAS receptor on the surface of the target cell that is followed by death-inducing signaling complex (DISC) formation. Subsequently, adapter proteins bind to the intracellular region of aggregated DISC complex, causing the accumulation of procaspase-8 molecules, which via proteolytic cleavage initiate a proteolytic cascade leading to effector caspase activation. There is also an amplification step where further release of mitochondria-localized pro-apoptotic factors takes place to amplify the initial CASP-3 activation (Box 3.23)."}
{"_id": "Radiology$$$f69921c5-4c85-4105-96eb-20ccc1ae4bc3", "text": "Apoptosis is a distinctive and highly controlled form of programmed cell death, which requires energy to hit the self-destruct button of an affected cell.\n\nApoptosis which can be triggered in response to endogenous or exogenous signals is a chain of sequential morphological events during which the early apoptotic cell shrinks and chromatin is irreversibly condensed and cleaved culminating into formation of apoptotic bodies.\n\nIn the mitochondria-mediated or intrinsic route to caspase activation, induction of mitochondrial outer membrane permeabilization (MOMP) is a central event that sets free pro-apoptotic factors such as cytochrome c.\n\nThe BCL-2 proteins can positively and negatively control MOMP.\n\nThe extrinsic pathway is mediated by a death ligand/signal binding to a membrane death receptor and downstream activation of CASP8."}
{"_id": "Radiology$$$2b66711c-bf10-4dbe-944b-1fa6157a3ede", "text": "Apoptosis is a distinctive and highly controlled form of programmed cell death, which requires energy to hit the self-destruct button of an affected cell."}
{"_id": "Radiology$$$60fb0766-8775-4c7e-abf9-45323e532eab", "text": "Apoptosis which can be triggered in response to endogenous or exogenous signals is a chain of sequential morphological events during which the early apoptotic cell shrinks and chromatin is irreversibly condensed and cleaved culminating into formation of apoptotic bodies."}
{"_id": "Radiology$$$99a4f5c4-507d-41cd-8f85-4eafa4473f53", "text": "In the mitochondria-mediated or intrinsic route to caspase activation, induction of mitochondrial outer membrane permeabilization (MOMP) is a central event that sets free pro-apoptotic factors such as cytochrome c."}
{"_id": "Radiology$$$0f5f1d73-cd99-42e3-9013-31d6571ee0f5", "text": "The extrinsic pathway is mediated by a death ligand/signal binding to a membrane death receptor and downstream activation of CASP8."}
{"_id": "Radiology$$$92b45ec7-fd01-448b-88f2-24b156e0dc11", "text": "IR-induced DNA damages, e.g., unrepaired DNA SSBs or DSBs, primarily trigger apoptosis via the intrinsic pathway [134]; however, at certain IR doses and in certain cell types, the extrinsic apoptotic pathway may also be executed. IR can also initiate mitochondria-mediated signaling in response to ceramide production/formation at the plasma membrane. Moreover, IR can trigger the production of O2\u2212 and ROS (like H2O2 or OH\u2212 radicals), which via release of Ca2+ and cytochrome c from mitochondria can cause apoptosis [135]."}
{"_id": "Radiology$$$b02a5aba-4418-4fc7-b82a-7432ef9d5e15", "text": "One important signaling regulator of apoptosis in response to IR is TP53 [136] (Fig. 3.38). Thus, TP53 is phosphorylated in response to DDR signaling, accumulates in the nucleus, and binds to promoters of target genes, e.g., BAX, PUMA, NOXA, p53AIP1, and APAF-1. This results in an alteration in their transcription and hence expression levels, which is followed by mitochondria-mediated apoptosis.\n\nA flow diagram depicts that stress or stimuli activate p 53 which binds to pro-apoptotic genes, resulting in cytochrome c release, apoptosome formation, and effector caspases with apoptosis.\n\nFig. 3.38\nTP53-mediated intrinsic route to apoptosis. The mechanisms of TP53-induced apoptosis through the Bcl-2-regulated pathways in cells undergoing stress are shown. DNA damage triggers stress signaling, which in turn causes stabilization of the TP53 protein in the nucleus. Subsequently, TP53 as a nuclear transcription factor increases the expression of BH3-only proteins such as PUMA and NOXA and downregulation of BCL-2 or BCL-XL expression. The BH3-only proteins bind and inhibit the anti-apoptotic or pro-survival BCL-2 family proteins, so as to unleash the cell death effectors (BAX/BAK) which are often held as hallmarks of apoptosis in affected cells. Oligomerization of BAX/BAK causes MOMP, with subsequent release of cytochrome c, formation of the apoptosome complex, and activation of CASP9 and subsequently effector caspases, which causes apoptotic features of the dying cells. Abbreviations: ROS reactive oxygen species, MOMP mitochondrial outer membrane permeabilization, BH3 Bcl-2 homology 3, PUMA p53 upregulated modulator of apoptosis, BAD Bcl-2-associated agonist of cell death, CHOP CCAAT/enhancer-binding protein homologous protein, Bcl-2 B-cell lymphoma 2 (an apoptotic inhibitor), Bcl-xL B-cell lymphoma-extra-large, Bax Bcl2-associated X (an apoptotic regulator), Bak Bcl2 antagonist killer 1, APAF-1 apoptotic peptidase-activating factor 1, caspase cascade of aspartate-specific cysteine proteases"}
{"_id": "Radiology$$$c9a99be8-01aa-4b0c-8865-35e75527b176", "text": "A flow diagram depicts that stress or stimuli activate p 53 which binds to pro-apoptotic genes, resulting in cytochrome c release, apoptosome formation, and effector caspases with apoptosis."}
{"_id": "Radiology$$$883a34c0-99a1-444e-80e8-0fabefe946a8", "text": "The extrinsic pathway may also play a role in IR-induced apoptosis in which TP53 may upregulate the expression of the FAS receptor and its ligands, which subsequently causes downstream transactivation of initiator CASP8 and apoptosis."}
{"_id": "Radiology$$$741482e5-b33b-4bcd-a662-bc822dadee1e", "text": "IR may moreover activate the ceramide pathway at the plasma membrane, wherein formation of ROS inflicts lipid oxidative damage in the membrane (Fig. 3.39). Subsequently, acid sphingomyelinase is activated, and second messenger ceramide is released as a result of sphingomyelin hydrolysis. IR-induced DNA damage may also trigger mitochondrial ceramide synthase resulting in the accumulation of ceramide which subsequently can induce apoptosis [137].\n\n A flow diagram depicts many stress factors that cause E R, Golgi, and mitochondrial stress. They cause the accumulation of misfolded proteins, altered B c l 2, and A T P depletion that leads to apoptosis. \n\nFig. 3.39\nOverview of ceramide signaling and connection to the apoptotic machinery. IR-induced lipid oxidative damage causes sphingomyelinase activation at the plasma membrane, followed by hydrolysis of sphingomyelin and release of ceramide. High dose of IR-induced DNA DSBs can also trigger the mitochondrial ceramide synthase for de novo synthesis of ceramide. Inhibition of SERCA and calcium depletion in ER promote ER stress. Expression of downstream pro-apoptotic factor, e.g., CHOP, increases. The UPR activator proteins, ATF6, IRE1, and PERK, alter ER stress. The PERK pathway via ATF4-dependent NRF2 expression triggers the CHOP-mediated apoptotic pathway. CHOP can also be induced by spliced ATF-6 (in Golgi), which regulates the Bcl-2 protein family. CAPPs can alter the BCL-2 protein family, which determines the commitment of cells to apoptosis. Abbreviations: Cer ceramide, CerS1\u20136 a family of six ceramide synthases, SMase sphingomyelinase, SERCA sarco-endoplasmic reticulum calcium transport ATPase, ER endoplasmic reticulum, ATF6 activating transcription factor 6, IRE1 inositol-requiring enzyme 1, PERK protein kinase R-like ER kinase, NRF2 nuclear factor erythroid 2-related factor-2, ATF4 activating transcription factor 4, CHOP CCAAT/enhancer-binding protein homologous protein, Mt mitochondria, CAPPs ceramide-activated protein phosphatase, Bcl-2 B-cell lymphoma 2 (an apoptotic inhibitor), Bcl-xL B-cell lymphoma-extra-large, Bax Bcl-2-associated X (an apoptotic regulator), RNS reactive nitrogen species, ATP adenosine triphosphate"}
{"_id": "Radiology$$$91da2a63-5f0e-4053-876e-100869536b13", "text": "A flow diagram depicts many stress factors that cause E R, Golgi, and mitochondrial stress. They cause the accumulation of misfolded proteins, altered B c l 2, and A T P depletion that leads to apoptosis."}
{"_id": "Radiology$$$7822c9e8-e3a5-447a-a685-ff204e8d790d", "text": "Ceramide may also activate the RAC1/mitogen-activated protein kinase kinase kinase-1 (MAP3K1) pathway by which MAPK8 and the effector CASP-1, -3, and -6 are induced and which also stimulate the DR pathway. MAPK8/JNK1 is known to be triggered in response to IR as well as other apoptotic stimuli, and depending on the duration of activity, it may induce apoptotic signaling. In summary, the rate of apoptotic events after IR may be executed via different routes and is influenced by cell type, cell cycle phase, dosage number, as well as radiation quality (Box 3.24)."}
{"_id": "Radiology$$$375a3460-85d5-458f-99df-753ae20bbaa6", "text": "IR-induced apoptosis can be executed through intrinsic, extrinsic, or membrane stress (ceramide) pathways.\n\nIR may trigger apoptosis via mitochondria where TP53 regulation of the BCL-2 family proteins is of major importance."}
{"_id": "Radiology$$$0b88797c-692b-4dee-aa50-744afbaf0a77", "text": "IR-induced apoptosis can be executed through intrinsic, extrinsic, or membrane stress (ceramide) pathways."}
{"_id": "Radiology$$$bcf867b3-a985-40fa-93d9-711629f4be53", "text": "IR may trigger apoptosis via mitochondria where TP53 regulation of the BCL-2 family proteins is of major importance."}
{"_id": "Radiology$$$70df69cb-f538-4d89-9e05-ad6db6e852a1", "text": "The apoptotic cell features, i.e., cell morphology, and the activation of different apoptotic signaling routes giving rise to distinguishable phenotypes have been extensively studied with multiple methods at hand. The detection of apoptosis includes methods (Fig. 3.40) related to membrane alterations, e.g., PS exposure monitored by annexin V association [129]; DNA fragmentation assessment; cytotoxicity and cell proliferation assays; analyses of mitochondrial effects, i.e., cell permeabilization; loss of mitochondrial potential; BCL-2 family protein complex formation; association of the apoptosome or DISC complex in cytosol; and pro-caspase cleavage later via different antibody-based, enzymatic assays or by flow cytometry [138]. Moreover, less frequently used technologies such as light-scattering flow cytometry and time-lapse microscopy perfusion platform can be performed to avoid underestimating the extent and timing of apoptosis, temporal aspects of death, cell surface area assessment, cellular adhesion analysis, and genotoxicity-specific chromatin changes.\n\nAn illustration describes different assays to evaluate cell death based on membrane integrity assay, functional assay, D N A labeling assay, morphological mechanism-based assay, reproductive assay, and colony forming assay.\n\nFig. 3.40\nMethods to detect cell death, in particular apoptotic cell death. The schematic diagram outlines various biological assays used to determine apoptotic cell death. Some of these assays can also be used to assess other types of cell death. These assays are based on the morphological criteria and distinguishing features of apoptotic pathways, e.g., staining for PS exposure on the outer plasma membrane (by annexin V assay) and caspase-3 activation or PARP cleavage (by, e.g., western blotting). Cell viability assays such as membrane integrity assays and reproductive assays are performed to monitor live cells in culture and measure an enzymatic activity as a marker of viable cells by using different classes of colorimetric reagents and substrates generating a fluorescent signal. Results from these assays do not always indicate apoptosis, but more about cell death in general. DNA labeling assay, functional assays, and morphological mechanism-based assays detect and quantify the cellular events, some of which are specifically associated with apoptotic cell death, such as formation of apoptotic antibodies, expression of apoptotic inhibitors, caspase activation in either intrinsic or extrinsic pathways, and DNA fragmentation. The principles for each assay are given in the respective yellow boxes. Abbreviations: MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide), LDH lactate dehydrogenase, BrdU bromodeoxyuridine, PARP polyadenosine diphosphate-ribose polymerase, PS phosphatidylserine"}
{"_id": "Radiology$$$0a8fafb0-269e-4f25-ae09-48e6fbd54615", "text": "An illustration describes different assays to evaluate cell death based on membrane integrity assay, functional assay, D N A labeling assay, morphological mechanism-based assay, reproductive assay, and colony forming assay."}
{"_id": "Radiology$$$fe6bab85-484b-4a84-bfba-7feaef0aec26", "text": "Necrosis (from the Greek \u201cnekros\u201d designating \u201cto kill\u201d) has for long been seen upon as an uncontrolled, irreversible mode of cell death, while recent work suggests that necrosis is a tightly genetically regulated pathway yet triggering inflammatory and/or reparative reactions in the tissue [139]. Necrotic cell death can be classified into accidental cell death (ACD) and regulated necrotic cell death (RNCD). RNCD can be further classified into necroptosis, pyroptosis, ferroptosis, NETosis, and methuosis given their molecular routes [139] (Table 3.11).Table 3.11\nAccidental and regulated necrosis, key features, and methods of detection\n\nType of cell death\n\nMorphology\n\nDetection methods\n\nAccidental necrosis\n\nMembrane disruption, mitochondria swelling (loss of organelle), cell swelling\n\nLDH quantification, cell-impermeable DNA-binding dye, membrane integrity loss\n\nNecroptosis\n\nMembrane disruption, moderate chromatin condensation, cell swelling\n\nFlow cytometry, western blot, immunohistochemistry\u2014levels of biomarker proteins, mitochondrial depolarization detection, fluorescence microscopy for membrane loss, electron microscopy for morphology\n\nPyroptosis\n\nMembrane disruption, bubbling, moderate chromatin condensation\n\nLDH quantification, fluorescence microscopy for membrane integrity loss, western blot for GSDM D, IL-1\u03b2\n\nFerroptosis\n\nMembrane disruption, iron accumulation, lipid peroxidation, diminutive mitochondria\n\nLipid peroxide quantification\u2014flow cytometry and BODIPY-C11 probe\n\nMethuosis\n\nMembrane disruption, accumulation of large fluid-filled vacuoles, cell swelling\n\nElectron microscopy, time-lapse fluorescence microscopy for morphology, metabolic flux analysis\n\nNETosis\n\nMembrane disruption, chromatin condensation\n\nFluorescence microscopy for morphology, flow cytometry, ELISA, western blot"}
{"_id": "Radiology$$$4bccf526-9e6e-4249-9b57-5dc9fb5446b8", "text": "Necroptosis, pyroptosis, methuosis, and ferroptosis are all triggered in response to IR [124, 140]. In the context of RT of cancer, necrosis can be induced either directly following DNA damage or indirectly by ROS formation that reacts with lipids generating lipid peroxides. IR has also been linked to lipid peroxidation and ferroptosis, and necroptosis together with ferroptosis was postulated to occur via ATM signaling."}
{"_id": "Radiology$$$832f5744-ed94-474d-b38d-d28b5b602450", "text": "Both ACD and RNCD trigger immunogenic cell death (ICD). In turn, ICD can stimulate an adaptive immune response after antigen is exposed by cells after RT or chemotherapeutics [141]. In case of immunogenic cell death, damage-associated molecular patterns (DAMPs) are delivered and identified by pathogen recognition receptors (PRRs) exhibited by intrinsic components of the immune system, conducting to the stimulation of an immune response [141]. ACD is an uncontrolled type of cell death which is activated by, e.g., physical damage, hypoxia, inflammatory toxins, and high doses of IR. The cells respond by morphological alterations, such as cytoplasmic swelling of the cell organelles, i.e., oncosis [142], which is a result of disturbance of ionic pumps causing Ca+ influx, plasma membrane disruption followed by the leakage of intracellular organelles with accidental deteriorated DNA, and absence of clear chromatin condensation [142]. RNCD comprises upregulation of diverse pro-inflammatory proteins and molecules such as nuclear factor-\u03baB, leading to the rupture of the cell membrane causing leakage of the cellular debris, e.g., ATP, DNA, nuclear proteins, heat-shock proteins, and uric acid, into surrounding zones, provoking a cascade of inflammation and tissue injury. Thus, the release of proteins/molecules promotes inflammasome activation and production of pro-inflammatory cytokine interleukin-1 beta (IL1). The methods used to detect necrosis are lactate dehydrogenase (LDH) activity measurement and cell-impermeable DNA-binding dye. These techniques are based on the morphological characteristics proving the cellular release and membrane porosity (Table 3.12).Table 3.12\nExamples of some oncogenes in cancer from Weinberg [143] and Gillies et al. [144]\n\nOncogene\n\nGeneral function\n\nMajor tumor type with deregulation\n\nK-ras\n\nGuanine nucleotide-binding protein\n\nLung, ovarian, colorectal, bladder carcinomas\n\nN-ras\n\nGuanine nucleotide-binding protein\n\nHead and neck cancers\n\nH-ras\n\nGuanine nucleotide-binding protein\n\nColorectal carcinomas\n\nc-myc\n\nTranscription factor\n\nVarious leukemias, carcinomas\n\nL-myc\n\nTranscription factor\n\nLung carcinomas\n\nEGFR/HER2\n\nReceptor tyrosine kinase\n\nGlioblastomas, lung cancer, breast cancer\n\nSrc\n\nCytoplasmic tyrosine kinase\n\nColon cancer, head and neck cancers, chronic myelogenous leukemia\n\nSis/PDGF\n\nGrowth factor\n\nSimian sarcoma"}
{"_id": "Radiology$$$fafd561c-79de-481b-9fa9-d801eb8b4edb", "text": "Necroptosis, also known as a regulated necrosis, which works in a caspase-independent fashion, exhibits a necrotic morphology with membrane disruption and leakage of organelles (reviewed by Weinlich et al. (2017)). Different stimuli can elicit necroptosis: DRs, e.g., members of the TNFR superfamily, pattern recognition receptors (PRRs), Toll-like receptors (TLRs), T-cell receptors (TCRs), multiple chemotherapeutic drugs, and hypoxia. The process of necroptosis commences by the stimulation of receptor-interacting protein kinases (RIPKs) (Fig. 3.41).\n\nFive flow diagrams depict the cellular pathways of necroptosis, pyroptosis, ferroptosis, netotic cell death, and methuosis. Cell death occurs for many reasons, such as membrane rupture and lipid peroxidation.\n\nFig. 3.41\nSummary of regulated necrotic cell death. (a) Necroptosis elicited by DR, TLR, and viruses stimulates RIPK3 and then MLKL, which is required for membrane disruption. (b) Pyroptosis induced by GSDMD following its cleavage by CASP1 and CASP11. The main elicitors: PAMPs and DAMPs, or cytosolic LPS. (c) Ferroptosis is dependent on the balance between ROS production due to iron accumulation and antioxidant defense mechanisms that inhibit lipid peroxidation. The ACSL4\u2013LPCAT3\u2013ALOX15 pathway mediates lipid peroxidation, while system xc- (comprising SLC7A11, GPX4, and NFE2L2) impeded this process. (d) NETosis is triggered by NET leakage, which is mediated by ROS generation and histone citrullination. (e) Methuosis is associated with macropinocytosis. Nascent micropinosomes fused forming large vacuoles that contain late endosomal markers (LAMP1 and Rab7). These do not recycle or unify with lysosomes causing cell death. Reproduced with permission (CCBY) from Tang et al. [145]. DR death receptor, TLR Toll-like receptor, RIPK3 receptor-interacting protein kinases 3, MLKL mixed-lineage kinase domain-like protein, GSDMD gasdermin D, CASP1 caspase 1, CASP11 caspase 11, PAMPs pathogen-associated molecular patterns, DAMPs damage-associated molecular patterns, or cytosolic, LPS lipopolysaccharide, ACSL4 acyl-CoA synthetase long-chain family member 4, LPCAT3 lysophosphatidylcholine acyltransferase 3, ALOX15 arachidonate lipoxygenases (ALOXs, specifically ALOX15), SLC7A11 the catalytic subunit solute carrier family 7 member 11, GPX4 glutathione peroxidase 4, NFE2L2 nuclear factor erythroid 2-like 2, NET NETosis extracellular trap, ROS reactive oxygen species, LAMP1 lysosomal associated membrane protein 1, Rab7 lysosomal Rab protein 7. (Adapted from Tang et al. [145])"}
{"_id": "Radiology$$$32d22d13-84ac-45a9-a205-130bfe749916", "text": "Five flow diagrams depict the cellular pathways of necroptosis, pyroptosis, ferroptosis, netotic cell death, and methuosis. Cell death occurs for many reasons, such as membrane rupture and lipid peroxidation."}
{"_id": "Radiology$$$f7dfbba0-92a1-4b81-a966-eed3062ccf2c", "text": "RIPKs are stimulated to go into macromolecular complexes from the membrane receptors with the necrosome with RIPK1 and RIPK3 being the main components. RIPK3 subsequently stimulates mixed-lineage kinase domain-like protein (MLKL) through phosphorylation causing its oligomerization and relocalization, resulting in cell membrane permeabilization and subsequent cell death."}
{"_id": "Radiology$$$db0385c1-fc67-487e-9f69-c708acf48dac", "text": "Different techniques can be used to identify necroptosis, e.g., flow cytometry, western blotting, and immunohistochemistry. Through these techniques, the expression levels of MLKL, RIPK3, and RIPK1 are evaluated as well as cell by electron microscopy (Table 3.11)."}
{"_id": "Radiology$$$9c59360e-e5d4-4a1b-bf73-5a1149c021c3", "text": "Pyroptosis, which is stimulated by IR as well as intracellular pathogenic factors in immune cells, follows a series of caspase-dependent events and is pro-inflammatory (reviewed by Yu et al. [146]). Thus, the NOD-like receptors (NLRs) of irradiated/infected macrophages/monocytes recognize cytoplasmic pathogen-associated molecular patterns (PAMPs) as well as DAMPs and trigger inflammasome complex production, which activates CASP1. CASP1 in turn activates gasdermin D, which mediates the plasma membrane rupture (Fig. 3.42) as well as the inflammatory cytokines interleukin 1\u03b2 (IL-1\u03b2) and IL-18, which further regulate inflammation. Pyroptosis also involves cell swelling followed by disintegration of the plasma membrane and leakage of the pro-inflammatory contents, e.g., DAMPs, IL-1\u03b2, and IL-18, contributing to elimination of the immunologic challenges locally or systemically. Pyroptosis can be detected by LDH assay, fluorescence microscopy, western blot analysis (for identification of gasdermin D, IL-1\u03b2), and measurement of the cell intake of propidium iodide (Table 3.11).\n\nA flow diagram depicts those monolayer cells in trypsin form cell suspension, which is 2 D and 3 D. Seeding, incubation, and staining give colony count, plating efficiency, and survival fraction.\n\nFig. 3.42\nMethodology for 2D (Puck) and 3D clonogenic curves. The clonogenic assay measures the ability of single cells to form colonies. A cancer cell that is not able to form a colony can be regarded as inactivated. Cellular monolayers are dissociated into single cells and counted and diluted to the required concentration, depending on the dose. The cells are then seeded in cell flasks/dishes for colony formation or in a 3D matrix for spheroid formation. After irradiation, the cells are incubated for 1\u20133\u00a0weeks depending on the cell doubling time of that particular cell line, before they are fixed, stained, and counted. The surviving fraction is calculated as the number of colonies in irradiated samples relative to the plating efficiency of unirradiated control dishes"}
{"_id": "Radiology$$$0ff42be3-9f24-4570-819c-afe6b6db0408", "text": "A flow diagram depicts those monolayer cells in trypsin form cell suspension, which is 2 D and 3 D. Seeding, incubation, and staining give colony count, plating efficiency, and survival fraction."}
{"_id": "Radiology$$$69b38158-e2b3-4c84-8938-ba7e81586113", "text": "Ferroptosis is a form of caspase-independent regulated necrosis and is distinguished by excessive iron-dependent lipid peroxidation. It presents a necrotic morphology with altered mitochondria, i.e., small mitochondria, fewer cristae, rupture of outer membrane, and an electron-dense ultrastructure. Execution of ferroptosis is decided by the equilibrium between ROS production due to iron increase and antioxidant protection mechanisms that impede lipid peroxidation. Thus, ferroptosis is activated after lipid peroxidation in a process catalyzed by iron, either in a Fenton-like manner or through lipoxygenases (Fig. 3.41). Accordingly, the oxidation of polyunsaturated fatty acids (PUFAs), like arachidonic acid (AA), is necessary for lipotoxicity in ferroptosis, which takes place via a catalytic pathway comprising acyl-CoA synthetase long-chain family member 4 (ACSL4), lysophosphatidylcholine acyltransferase 3 (LPCAT3), and arachidonate lipoxygenases (ALOXs, specifically ALOX15) [147]. In addition, lipid peroxidation can be hindered by the various antioxidant systems such as the cystine/glutamate antiporter system, which consists of the catalytic subunit solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), and pro-survival proteins, like nuclear factor erythroid 2-like 2 (NFE2L2). System xc- facilitates the exchange of cystine and glutamate in and out of the cell. The cystine which is taken up is reduced to cysteine in cells, which is needed for the synthesis of glutathione GSH. GSH is used by GPX4 to stop the generation of phospholipid hydroperoxides (PLOOH), the key mediator of chain reactions in lipoxygenases. The induction of ferroptosis can be determined by measuring lipid peroxides coupled with flow cytometry (Table 3.11)."}
{"_id": "Radiology$$$ef5b3167-c1e6-4aaa-93eb-d04ab93c58f3", "text": "NETosis is stimulated by various pathogens or other stimuli, which release neutrophil extracellular traps of mainly DNA-protein structures [148] in a process dependent on NADPH oxidase 4 (NOX4), the principal source of ROS (Fig. 3.41). NETosis also comes along with important increase of ROS conducting to the stimulation of protein-arginine deiminase 4 (PAD4). Then, PAD4 citrullinates (converts arginine to citrulline via deamination) the histones, promoting the nuclear chromatin decondensation. Further, the NET is released into the cytosol leading to the disruption of the neutrophil membrane. Then, neutrophil breaks up and the NETs are released into the environment. NETs can be generated by other forms of immune cells, e.g., eosinophils, mast cells, basophils, macrophages, and also epithelial cells and cancer cells as a response to various injuries [145]. NETosis can be studied using various techniques: immunofluorescence, transmission electron microscopy, scanning electron microscopy, ELISA tests, flow cytometry, as well as western blot analyses of NETosis markers (Table 3.11)."}
{"_id": "Radiology$$$6c0c7107-49e7-406a-9c48-65c735670aa8", "text": "Methuosis (from Greek methuo\u2014\u201cdrink to intoxification\u201d) is another type of caspase-independent regulated necrotic cell death that is induced by exposure to heat, trauma, and infection and which lead to cell swelling, lysis of plasma membrane, as well as inflammation. Methuosis is correlated to macropinocytosis (referred to as \u201ccell drinking\u201d) and is associated with the extensive accumulation of fluid-filled cytoplasmic vacuoles stemmed from macropinosomes, which for example is observed in cancer cells driven by the oncoprotein Ras [149] (Fig. 3.41). Methuosis can be detected by electron microscopy, time-lapse fluorescence microscopy, visualization of vacuoles using fluorescent dyes, and metabolic flux analyses (Table 3.11) (Box 3.25)."}
{"_id": "Radiology$$$922796af-8d78-440b-8424-2ff3e7be7413", "text": "Necrotic cell death is classified into accidental cell death and regulated necrotic cell death with different subtypes: necroptosis, pyroptosis, ferroptosis, NETosis, methuosis, etc.\n\nIR may stimulate necrosis via direct DNA damage response and via radical oxygen species.\n\nAll types of necrosis are immunogenic cell death types."}
{"_id": "Radiology$$$9d6c8974-eb02-47a9-8db9-be0d20c26761", "text": "Necrotic cell death is classified into accidental cell death and regulated necrotic cell death with different subtypes: necroptosis, pyroptosis, ferroptosis, NETosis, methuosis, etc."}
{"_id": "Radiology$$$4873e289-a914-4eb4-997e-147a29dc6830", "text": "IR may stimulate necrosis via direct DNA damage response and via radical oxygen species."}
{"_id": "Radiology$$$42d01a33-c6e6-47d1-9095-e895ad95d202", "text": "Autophagy is an adaptive and catabolic process induced by various forms of cellular stress, intended to mitigate the impact of cell damage to avoid cell death, by recycling biomolecules and damaged organelles. This mechanism occurs via a self-digestion process involving the formation of double-membrane vesicles, called autophagosomes, that merge with lysosomes. Autophagy can be induced by nutrient deprivation (amino acids, in particular leucine and glutamine, and glucose) and cytotoxic insults such as IR or chemotherapy. The main function of autophagy is to provide nutrients and building blocks for vital cellular functions during different forms of stress. Therefore, this pathway is generally considered as a cytoprotective mechanism [150]. Autophagy is a complex mechanism involving several steps. First, the recruitment of autophagy-related proteins (ATG) to a specific subcellular location called the phagophore assembly site (PAS) allows phagophore nucleation (initiation and phagophore nucleation). During phagophore elongation, a portion of the cytoplasm is engulfed (cargo sequestration) and the autophagosome, a double-membrane vesicle, is being formed (autophagosome maturation). Fusion of the autophagosome with lysosome allows the degradation of the autophagic cargo."}
{"_id": "Radiology$$$d389da3f-03f2-47a5-baa3-a6b6646b88fd", "text": "A key regulator of autophagy is the mammalian target of rapamycin (mTOR) that exists in two distinct protein complexes, mTORC1 and mTORC2. In its active conformation, mTORC1 prevents autophagy by inhibiting the UNC51-like kinase 1 (ULK1) complex, composed of ULK1, the autophagy-related gene 13 (ATG13), ATG101, and the FAK family-interacting protein of 200\u00a0kDa (FIP200). Upon autophagic stimuli, mTORC1 is inhibited, leading to the activation of ULK1. Active ULK1 phosphorylates ATG13 and FIP200, which leads to the activation of the class III phosphoinositide 3-kinase (PI3K) complex, allowing phagophore nucleation. This triggers the production of phosphatidylinositol-3-phosphate (PIP3) at a characteristic ER structure called omegasome. PIP3 recruits WD repeat domain phosphoinositide-interacting proteins (WIPI2) and zinc finger FYVE domain-containing protein 1 (DFCP1) to the omegasome. By binding ATG16L1, WIPI2 recruits the ATG12-ATG5-ATG16L1 complex that allows the conjugation of ATG8 family proteins (including microtubule-associated protein light-chain 3 (LC3) and \u03b3-aminobutyric acid receptor-associated proteins (GABARAPs)) to membrane-resident phosphatidylethanolamine (PE). By this process, LC3-I (diffuse form) is converted into LC3-II (membrane-anchored, lipidated form), a marker of autophagic membranes. The recruitment of ATG9-containing vesicles (coming from the plasma membrane, mitochondria, recycling endosomes, and Golgi complex), delivering additional lipids and proteins, further contributes to autophagosomal membrane expansion. Once the membrane is sealed, the autophagosome is formed and undergoes maturation. Then it can merge with the lysosome, where the autophagic cargo will be degraded by acidic hydrolases. For the molecular details, see Dikic et al. [151]."}
{"_id": "Radiology$$$9ecc260b-d788-4ae9-a9ac-42bb6e371808", "text": "Beyond apoptosis, the commonly studied IR-induced cell death mechanism, autophagy was shown to be frequently induced in response to IR. For example, autophagy can be triggered following DNA damage inflicted by IR or other agents. Indeed, DNA damage repair (DDR) is an energy-demanding process that consumes ATP but also NAD+ via the action of polyADP-ribose polymerase 1 (PARP1). Autophagy induction allows the recycling of metabolic precursors for ATP and provides energy for the DDR. ROS was also shown to trigger and regulate autophagy [152]. The function of IR-induced autophagy is still being debated. Results of in vitro and in vivo studies provided conflicting notions whether autophagy acts as a cytoprotective mechanism, promoting cell survival responsible for radioresistance. In that respect, radiosensitization strategies based on genetic or pharmacological autophagy inhibition led to different outcomes. Several studies also pointed out the non-cytoprotective function of IR-induced autophagy where autophagy inhibition failed to alter radiosensitivity. Although autophagic functions may vary depending on both cell type and treatment regimen applied, specific characteristics able to distinguish cytotoxic, cytoprotective, or non-cytoprotective forms of IR-induced autophagy have not yet been identified. There are assumptions that autophagy duration may play a role in radiosensitivity, with radioresistance occurring in case of prolonged autophagy, while a transient form of autophagy will ultimately lead to apoptosis [150]."}
{"_id": "Radiology$$$c790c8aa-7609-4749-a7df-e8f46739ea9e", "text": "Outcomes of clinical trials conducted with approved autophagy inhibitors (e.g., chloroquine and hydroxychloroquine) were mitigated due to toxicity issues and unsatisfactory autophagy inhibition. Concerns were raised regarding the most probable non-tumor selectivity of autophagy inhibitors, off-target effects, effects on immune response, and difficulty to monitor autophagy inhibition in patients\u2019 tumors [153]. Further studies on the molecular mechanisms governing IR-induced autophagy may bring additional evidence on how to optimally modulate autophagy to produce favorable outcomes (Box 3.26)."}
{"_id": "Radiology$$$c661067d-82f4-4f35-ab58-d5b6c06e2dca", "text": "Autophagy is triggered by IR and often considered as a cytoprotective mechanism.\n\nAutophagy inhibition as a radiosensitization strategy led to inconsistent results, suggesting an intricate role of autophagy, being regulated by many factors."}
{"_id": "Radiology$$$96a81f3d-64e9-4a78-bdbc-98cf5433d267", "text": "Autophagy is triggered by IR and often considered as a cytoprotective mechanism."}
{"_id": "Radiology$$$c573bd71-3cb5-4423-8026-66c15c6b251a", "text": "Autophagy inhibition as a radiosensitization strategy led to inconsistent results, suggesting an intricate role of autophagy, being regulated by many factors."}
{"_id": "Radiology$$$f44e84b6-4ee9-4db0-990b-45743bf1daf6", "text": "As described in the sections before, cells damaged by radiation might suffer from genetic instability and/or die through, e.g., apoptosis or other types of cell death. These consequences of radiation exposure can be used to qualify and quantify the damage and draw conclusions on its severity. In this context, it is possible to look at not only the fatal outcome of radiation damage but also the capability of cells to survive IR. It is important to distinguish between cell survival and cell viability. In radiobiology, the term cell death is used also for cells that are inactivated, i.e., have lost their proliferation ability. Cancer cells and stem cells are characterized by their capacity for sustained proliferation. A cancer cell that has lost the ability to divide is by definition dead as a cancer cell even though it may still have an intact cell membrane and retained metabolic function. While non-proliferating cells retain their function even after radiation doses as high as 50\u2013100\u00a0Gy, cancer cells may lose the capacity for uncontrolled cell division after doses in the order of 2 Gy."}
{"_id": "Radiology$$$5806c9fc-c2df-49d2-9cea-d2823d36a7e2", "text": "There are several assays available to measure cell viability. Some use dye exclusion, such as trypan blue, to measure the proportion of cells with intact cell membrane. Others measure metabolic function through the activity of mitochondrial enzymes, such as the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium) assay, cellular reducing conditions such as the Alamar Blue assay, or ATP production. Even though viability measurements over time can give an indication of cell proliferation, the only direct measurement of clonogenic function is the clonogenic assay, the gold standard for cell survival measurements. These assays can be performed in vitro with cultured cells or in vivo from biopsies."}
{"_id": "Radiology$$$c06ee230-bdde-4f66-8207-6c68d15fd738", "text": "The first survival curve, i.e., the relation between survival and delivered doses, was established with HeLa cells cultivated in vitro and irradiated with X-rays by Puck and Marcus in 1956 [154]. A surviving cell is defined as a cell able to divide and form a colony composed of at least 50 cells. To find the surviving fraction, the capacity of nonirradiated and irradiated cells to form colonies is compared. Typically, in vitro cell survival is measured in adherent cells in monolayer culture. The day before the experiment, cells are trypsinized. Viable cells are counted with a hematocytometer or a cell counter. A determined number of cells in suspension is seeded in Petri dishes (or flasks) destined to be a control or irradiated before their first doubling time. Depending on the design of the experiments, the medium can be changed after irradiation. Then cells are incubated at 37\u00a0\u00b0C for 1\u20133\u00a0weeks according to the cell types (\u22658 divisions). When the colonies grow to exceed 50 cells, observable by microscopy or visually detectable, they are fixated with methanol or ethanol and then stained with Giemsa, methylene blue, or crystal violet before several washes with water and drying [155]. After that, the clones formed are counted manually or with an automatic counter (Fig. 3.42)."}
{"_id": "Radiology$$$9e9e0ee6-ec5e-4d07-bec9-ccf63e9b3bc2", "text": "All cells comprising each colony are the progeny of a single initial cell seeded, which survived irradiation. If we consider 100 untreated cells, the ideal number of colonies formed should be 100. However, this is never the case, depending on diverse factors (medium change, errors and uncertainties in counting the cell suspension, trauma of the detachment \u2026), and in fact 50\u201390 colonies might be expected. Considering the outcome of the control conditions (nonirradiated), the term plating efficiency (PE) can be defined. This corresponds to the percentage of cells seeded, which grew into colonies. If 75 colonies are counted after seeding 100 cells, we talk about a PE of 75%. It must be noted that the PE may differ according to the number of cells seeded: this is the \u201cfeeder effect.\u201d This effect is attributed to the need of some cell types to be able to cooperate with neighboring cells [156]. If this communication is missing, the cells are not able to start proliferation. Therefore, the cell density seeded might play a role in the fraction of cells able to form colonies. This might limit the robustness of the classical analysis of the colony-forming assay. In future, a different way of performing and analyzing this assay might be necessary [156]."}
{"_id": "Radiology$$$37813b42-55b9-4691-8316-c0ab614c4580", "text": "In classical colony-forming assay parallel to the control samples, cells are irradiated, then incubated, fixed, and stained at the same time point as control cells. Different cases can therefore be observed: (1) some of the seeded cells being still single and not divided; (2) cells that managed one or two divisions to form a tiny abortive clone; and (3) cells able to form large colonies of at least 50 cells, corresponding to 5\u20136 cell divisions, but which can look like a little bit different from the untreated cells in terms of aspect and size. These latter cells, able to form colonies, are qualified of \u201csurvivors\u201d and counted since they have retained their reproductive integrity. For example, if we seed 3000 cells followed by irradiation of 5\u00a0Gy, and if the PE previously determined is 0.75, then we can expect the attachment of 2250 cells (0.75 \u00d7 3000). If at 5 Gy 42 colonies grew up after incubation, the surviving fraction can be calculated at 1.9%: 42/(3000 \u00d7 0.75)\u00a0=\u00a00.019. In general, the plating efficiency (PE) and the surviving fraction (SF) are given by\n\n (3.1)"}
{"_id": "Radiology$$$c6d09431-1cc5-4d4e-9708-a39d10f23cb8", "text": "Survival curves for mammalian cells are usually presented in a form with dose plotted on a linear scale and surviving fraction on a logarithmic scale and can be fitted by several models, as for example the linear-quadratic model (see Chap. 1). The form of the curves, as seen in Chap. 1, depends on the linear energy transfer and allows determining important biological parameters such as the surviving fraction, the ratio \u03b1/\u03b2, or the relative biological efficiency (RBE) for example (see Chap. 1 for details). The surviving fraction at 2 Gy (SF2) is often used to approximate cell radiosensitivity."}
{"_id": "Radiology$$$f7dfb09c-cd8f-4e52-8745-3ebde97208eb", "text": "To obtain a survival curve, several doses of irradiation have to be applied. The number of cells seeded per dish needs to be accurate and often adjusted after preliminary experiments to count a significant number of colonies since these parameters are dependent on doses, cell lines, and type of radiation. At least a triplicate of different dilutions is realized for each condition tested (here each dose delivered). If colonies are few, the statistical significance is reduced. On the opposite, if the colonies are too many, some colonies can be merged with another one, and the counting is inaccurate. In some cases, cells could be irradiated first (one flask for one dose) and then detached to be seeded at different dilutions [157]. However, precautions need to be considered since some cells are sensitive to detachment after irradiation, which affects cell survival. In addition, colony-forming assays require very accurate cell counting, since the controls come from a separate trypsinization. Clonogenic curves cannot discriminate the type of cell death, but they give information about the radiosensitivity of the cells."}
{"_id": "Radiology$$$3b13abbe-9be7-4f36-94c1-ebaf6c9d2d30", "text": "More recently, the literature showed that survival curves obtained with three-dimensional (3D) cell models more reliably reflect the cell response in vivo than the results obtained with 2D cell monolayer culture [158]. 3D cell models for cell survival can be obtained by embedding single cells in an extracellular matrix, put in 96-well plates pre-coated with agarose, covered with medium, and then exposed to radiations. Cells are grown for a few days until cell clusters reach 50 cells, and the number of colonies is microscopically counted (Fig. 3.42)."}
{"_id": "Radiology$$$9956afc3-594c-4e49-b876-0b0b4bcb7bda", "text": "An in vivo clonogenic assay allows measuring cell survival in an animal model, allowing the study of radiosensitivity of normal or tumor cells treated in vivo. These systems depend on the reproductive integrity of individual cells and allow the observation of a clone of cells regenerated in the irradiated tissue. There are assays developed for early-responding tissues, which divide rapidly and respond early to the effects of radiation, like bone marrow cells, skin, and intestinal epithelium, and assays for late-responding tissues, like lung, kidney, and spinal cord (Fig. 3.43).\n\nAn illustration depicts the approximate number of days taken for the jejunum crypt assay, skin clone assay, spleen colony assay, bone marrow assay, and kidney assay carried out in an irradiated mouse.\n\nFig. 3.43\nIn vivo assays. Four in vivo animal assays to assess clonogenic capacity after irradiation have been important for radiobiology. (1) The jejunum crypt assay measures the regenerative ability of jejunal crypts after high doses of irradiation. The animals are sacrificed 3.5\u00a0days after irradiation, and the numbers of regenerating crypts per circumference are measured. One regenerating crypt corresponds to one surviving clonogenic cell. (2) The skin clone assay used pre-irradiation with a high dose in a ring (moat) around the test skin area to avoid migration of neighboring cells into the test area. The test area is then irradiated, and the number of regrowing skin nodules per cm2 is counted. (3) The spleen colony assay uses transplants of bone marrow cells from an irradiated donor animal. These cells are transferred to recipient animals who have previously been irradiated with a high dose to kill all their own bone marrow cells. After 10\u201311\u00a0days, the recipient animals are sacrificed and their spleens are analyzed for colony-forming units arising from the implanted single cells. (4) The kidney assay uses the same animal for irradiation and control. One kidney of each animal is irradiated, and 60\u00a0weeks later, the animals are sacrificed. The number of intact kidney tubules is then counted in both kidneys, and the irradiated kidney can be compared to the unirradiated one"}
{"_id": "Radiology$$$30d41fa6-15ff-452b-b3e9-4c4134fb3354", "text": "An illustration depicts the approximate number of days taken for the jejunum crypt assay, skin clone assay, spleen colony assay, bone marrow assay, and kidney assay carried out in an irradiated mouse."}
{"_id": "Radiology$$$91c76c92-f5fd-42ae-9626-7eef164e11ac", "text": "The spleen colony assay, also called bone marrow stem cell assay, was first described by Till and McCulloch [159]. The basis of this assay relies on the use of one donor mouse and a group of recipient mice. Recipient mice are previously exposed to whole-body irradiation (9\u00a0Gy) to sterilize the spleen and suppress endogenous hematopoiesis. Then, from a donor mouse irradiated with a test dose, a cell suspension of bone marrow cells is taken and injected intravenously into the recipient donors. Some of these cells will lodge in the spleen, and after 10\u201311\u00a0days, single cell-derived clones will appear in the surface of the spleen. These colonies are usually called colony-forming units (CFUs). At this point of the experiment, the spleen of the recipient mouse is removed and the CFUs are counted. The surviving fraction is given by Eq. (3.2), similar to the one used for the in vitro assay. The experiment is then repeated for different radiation doses, enabling to trace a survival curve:\n\n (3.2)"}
{"_id": "Radiology$$$c717834c-fab2-40de-88a2-7f7c93069a7b", "text": "The skin clone assay is based on the formation of nodules of mouse skin regrowing from a single surviving cell. In a practical way, after shaving a small area on the back of one mouse, a ring of skin is irradiated with a massive dose of 30 Gy to create a \u201cmoat\u201d of dead cells. A small metal sphere is put in the central area to protect it from the radiation and create an isolated island of intact skin. This skin island is then irradiated with a test dose. Some days later, nodules of regrowing skin will be observed. The survival curve is obtained after repeating the experiment in different skin areas and by plotting the number of surviving cells per cm2 of skin as a function of the radiation dose (Gy)."}
{"_id": "Radiology$$$308b0708-8fba-4a56-b53b-f6cc2f9bcfd7", "text": "The jejunal crypt stem cell assay is based on the self-renewal system of the jejunum. Within this system, the stem cells in the crypts divide rapidly and move up to the villi where they undergo differentiation in functioning cells. For the assay, groups of animals are subjected to increasing doses of whole-body irradiation. The jejunal crypts will begin to regenerate after 3.5\u00a0days, time at each animal is sacrificed, and sections of the jejunum are imaged. One regenerating crypt corresponds to one surviving clonogenic cell. The survival curve is obtained by plotting the number of regenerating crypts per circumference of the sectioned jejunum as a function of the radiation dose (Gy)."}
{"_id": "Radiology$$$47ca4413-cf07-4241-997a-9fa8b678fa99", "text": "The kidney tubule assay includes the irradiation of one kidney per mouse with a small field. As the kidney is a late-responding tissue, the assay is finished 60\u00a0weeks later, when unirradiated and irradiated kidneys are removed, and histologic sections are imaged. The number of intact kidney tubules is compared between the unirradiated and irradiated sides. The survival curve is obtained by plotting the number of tubule-regenerating cells in a defined number of tubule cross sections counted as a function of the radiation dose (Gy)."}
{"_id": "Radiology$$$6d803976-c1b9-4326-ba45-d69e2a0b7e3c", "text": "In addition, the tumor control dose assays (TCD50) relate with tumor survival. During these assays, small parts of tumors (xenografts), which can be derived from tumor cell lines or from patient tumors, are implanted to nude mice. After they reach a desirable size, the tumors are irradiated by several doses and then the local control or recurrence is observed. A plot between the percentage of the controlled tumors versus the dose is made. TCD50 is then the dose to control 50% of the tumors [160] (Box 3.27)."}
{"_id": "Radiology$$$eb0e5097-313a-4fb4-9ccf-bda8175c88cb", "text": "A surviving cell corresponds to a cell able to divide and form a colony.\n\nClonogenic assay is based on the ability of a single cell to grow into a colony.\n\nThe only direct measurement of clonogenic function is the clonogenic assay, the gold standard for cell survival measurements.\n\nCell survival measurements allow to trace a cell dose-response curve, usually presented with dose plotted on a linear scale and surviving fraction on a logarithmic scale, and can be fitted by several models.\n\nAn in vivo clonogenic assay allows measuring cell survival in an animal model, allowing the study of radiosensitivity of normal or tumor cells treated in vivo."}
{"_id": "Radiology$$$5c331c4d-7052-4947-a4e7-af44c80c2786", "text": "A surviving cell corresponds to a cell able to divide and form a colony."}
{"_id": "Radiology$$$23939b01-d968-45bc-848a-0501120b21ea", "text": "Clonogenic assay is based on the ability of a single cell to grow into a colony."}
{"_id": "Radiology$$$6e3d7c57-fe04-466c-9d14-04132f55ce90", "text": "The only direct measurement of clonogenic function is the clonogenic assay, the gold standard for cell survival measurements."}
{"_id": "Radiology$$$c3f199db-d5d0-49db-b929-0717c281f718", "text": "Cell survival measurements allow to trace a cell dose-response curve, usually presented with dose plotted on a linear scale and surviving fraction on a logarithmic scale, and can be fitted by several models."}
{"_id": "Radiology$$$f44974f2-47be-465f-8969-a185fad2278d", "text": "An in vivo clonogenic assay allows measuring cell survival in an animal model, allowing the study of radiosensitivity of normal or tumor cells treated in vivo."}
{"_id": "Radiology$$$b59294f3-ac08-432e-940d-ff359b834585", "text": "Transformation of a normal cell into a cancer cell is a multistep process where mutations or other genomic alterations, e.g., copy number alterations, deletions, and gene fusions, alter the normal gene coding sequence. These alterations can occur due to mis- or unrepaired IR damage. Not all alterations lead to the transformation of a normal cell to a cancer cell, called oncogenesis, as it is associated with alterations of specific places on DNA [143]. Cell transformation is mostly related to the activation of proto-oncogenes, which are then named oncogenes and the deactivation of tumor suppressor genes [143]. Proto-oncogenes are genes associated with the activation of cell proliferation and differentiation. When they mutate or are somehow pressed to overexpression, cells proliferate out of control [143]. On the other hand, tumor suppressor genes are genes that control cell proliferation, play significant roles during DNA repair, or activate cell death pathways, when it is needed. Mutations of tumor suppressor genes cause loss of control upon important pathways, which may again lead to unregulated cell proliferation [143]. Oncogenes and tumor suppressor genes can be affected genetically by mutations on the DNA or also switched on or off epigenetically. An overview is given in Fig. 3.44.\n\n A flowchart depicts that proto-oncogenes and tumor suppressor genes cause cancer due to their activation and control of cell proliferation, followed by oncogene upregulation and tumor suppressor gene downregulation, respectively. \n\nFig. 3.44\nOverview of oncogenes and tumor suppressor genes\u2019 function and regulation"}
{"_id": "Radiology$$$c6e407d7-a6fe-41b3-8e46-2d6014074ea4", "text": "A flowchart depicts that proto-oncogenes and tumor suppressor genes cause cancer due to their activation and control of cell proliferation, followed by oncogene upregulation and tumor suppressor gene downregulation, respectively."}
{"_id": "Radiology$$$9efdf2b4-6285-4083-ac09-d92f264ddd90", "text": "The discovery of proto-oncogenes came with investigation of the Rous sarcoma virus (RSV). This virus is able to transform normal chicken cells to cancer cells, and in its structure, the src gene was found, which as it was shown later was responsible for this transformation. The src gene was later also found in the normal chicken genome, but it was inactivated. These findings meant that the genomes of normal cells carry genes (proto-oncogenes) that have, under certain circumstances, the potential to induce cell transformation when activated [143]. For some time, biologists were convinced that cancer is caused by viruses which present into cells\u2019 genes (oncogenes) that activate uncontrolled cell proliferation. It was thus strange that people around these \u201cinfected\u201d people do not suffer from the same cancer type as well, due to the fact that viruses are infectious. Indeed, viruses can include oncogenes into a cell\u2019s DNA, but viruses are not the main cancer cause. Viruses are responsible only for a minority of all cancers [143]. All this information led to new questions about proto-oncogenes and oncogenes. To find out if oncogenes exist in chemically or physically transformed cells, DNA from cancer cells was introduced to normal cells to see if they will be transformed. This gene transfer procedure is named transfection. Indeed, many other oncogenes were revealed using this method [143]. Another very important issue is that it is sufficient to activate only one of the alleles of a proto-oncogene to get oncogene upregulation [161]. Some of the most common oncogenes in human cancer are given in Table 3.12."}
{"_id": "Radiology$$$829f4646-1d5e-4b91-9bba-72b7ef491af8", "text": "In general, when a system has an activation \u201cbutton,\u201d there has to be somewhere a deactivation \u201cbutton\u201d as well. Oncogenes are the genes activating uncontrolled cell proliferation, and on the other hand the deactivation/control of cell proliferation is associated with tumor suppressor genes. Tumor suppressor genes were discovered much later than proto-oncogenes and oncogenes. Some of the tumor suppressor genes are listed in Table 3.13. One of the most important and known tumor suppressor genes is the TP53. A mutation of TP53 is associated with various tumor types. This gene codes the p53 protein, which is also sometimes called the \u201cMaster Guardian.\u201d p53 is responsible for activation of DNA repair as well as activation of cell cycle arrest, to enable DNA repair.Table 3.13\nExamples of some tumor suppressor genes and familial cancer syndromes from Macleod [162] and Weinberg [143]\n\nTumor suppressor gene\n\nGeneral function\n\nTypes of cancer\n\nFamilial syndrome\n\nTP53\n\nChromosome stability, transcriptional regulator, growth arrest, apoptosis\n\nMany\n\nLi\u2013Fraumeni syndrome\n\np16\n\nCyclin-dependent kinase inhibitor\n\nMany\n\nFamilial melanoma\n\nBRCA1\n\nTranscriptional regulator, DNA repair\n\nMany, mostly breast and ovarian cancer\n\nFamilial breast cancer\n\nBRCA2\n\nTranscriptional regulator, DNA repair\n\nMany, mostly breast and ovarian cancer\n\nFamilial breast cancer\n\nRB1\n\nTranscriptional regulator of cell cycle\n\nRetinoblastoma, osteosarcoma\n\nFamilial retinoblastoma\n\nE-cadherin\n\nCell adhesion regulator\n\nBreast, colon, lung, skin carcinoma\n\nFamilial gastric cancer\n\nAPC\n\n\u03b2-Catenin degradation\n\nColorectal, pancreatic, stomach, prostate cancer\n\nFamilial adenomatous polyposis coli\n\nNF2\n\nCytoskeleton-membrane linkage\n\nSchwannoma, meningioma, ependymoma\n\nNeurofibroma-predisposition syndrome"}
{"_id": "Radiology$$$bb79d3b5-914a-45fe-8c24-73f7c8e8826c", "text": "To deactivate a tumor suppressor gene, both alleles have to be damaged or switched off, because only one allele is enough for the production of a specific protein. Anyhow, if one allele of a tumor suppressor gene of a germ line cell is defective, then there is much higher probability of the born individual to suffer from cancer. This is because for this person, it becomes much more probable that the second allele will be damaged during life as well [143, 161, 162]. Since the defective allele in this case is genetically transferred to offspring, many familial syndromes were identified (Box 3.28)."}
{"_id": "Radiology$$$ccc346d5-6843-4d6e-8061-1e4f2d0d404e", "text": "DNA alterations in genomic or epigenetic level may cause proto-oncogenes to become oncogenes, disrupting normal cell division and causing cancers to form.\n\nCell transformation is mostly related to the activation of proto-oncogenes, which are then named oncogenes, and deactivation of tumor suppressor genes.\n\nProto-oncogenes are genes associated with the activation of cell proliferation and differentiation.\n\nTumor suppressor genes are genes that control cell proliferation, play significant roles during DNA repair, or activate cell death pathways.\n\nMutations of tumor suppressor genes cause loss of control upon important pathways, which may again lead to unregulated cell proliferation.\n\nOncogenes and tumor suppressor genes can be affected genetically by mutations on the DNA or also switched on or off epigenetically.\n\nTP53 is one of the most important tumor suppressor genes."}
{"_id": "Radiology$$$7f66a3ee-bcfd-4e58-bd8b-fe001aca3359", "text": "DNA alterations in genomic or epigenetic level may cause proto-oncogenes to become oncogenes, disrupting normal cell division and causing cancers to form."}
{"_id": "Radiology$$$140ef5b9-f5c6-4814-8630-ddd3b9fe60b9", "text": "Cell transformation is mostly related to the activation of proto-oncogenes, which are then named oncogenes, and deactivation of tumor suppressor genes."}
{"_id": "Radiology$$$1dbb04a4-724d-44c5-9a4b-83d5421dabae", "text": "Proto-oncogenes are genes associated with the activation of cell proliferation and differentiation."}
{"_id": "Radiology$$$15ef933e-d2b3-4da2-ab4b-f2fc0ffdeecd", "text": "Tumor suppressor genes are genes that control cell proliferation, play significant roles during DNA repair, or activate cell death pathways."}
{"_id": "Radiology$$$9e6db3bf-1652-4915-9dc6-29b03c7669e5", "text": "Mutations of tumor suppressor genes cause loss of control upon important pathways, which may again lead to unregulated cell proliferation."}
{"_id": "Radiology$$$c5c84852-54f4-4bf3-8292-94ba640e9611", "text": "Oncogenes and tumor suppressor genes can be affected genetically by mutations on the DNA or also switched on or off epigenetically."}
{"_id": "Radiology$$$9725066b-409e-493c-a947-19fed4571e4c", "text": "Cells are organized in complex cellular systems such as tissues or organs; therefore, it is crucial that they are able to communicate with each other. The most rapid way of communication is directly through cell-to-cell contact. There are various ways of direct interconnectivity of cells as shown in Table 3.14.Table 3.14\nSummary of the size properties of the three main direct cell connections\n\nType of connection\n\nDiameter\n\nLength\n\nGap junctions\nTunneling nanotubes\nEpithelial bridges\n\n2\u20133 nm\n50\u20131500 nm\n1\u201320\u00a0\u03bcm\n\n2\u20134 nm\nFew to >100\u00a0\u03bcm\n25\u20131000\u00a0\u03bcm"}
{"_id": "Radiology$$$b2d5c663-64b7-47dd-8424-85f7a784dfa2", "text": "The most famous type of cell-to-cell connection is gap junction, which is the most direct manner of cell interconnectivity and forms the fastest communication channel. Gap junctions have a pore diameter of 2\u20133 nm and a length of 2\u20134 nm and are involved in the exchange of nutrients, ions, second messengers, and small metabolites up to ~1\u00a0kDa, allowing ionic and biochemical coupling between neighboring cells. These specialized structure membranes have a short half-life of a few hours (~1\u20134\u00a0h), and their biosynthesis and assembly are firmly regulated [163]. These transmembrane structures are composed of connexons (Fig. 3.45) constituted of six connexin (Cx) subunits around a central pore, which allow communication between adjacent cells. These connexons could be made up of six similar Cx isoforms (homomeric) or a combination of six different Cx isoforms (heteromeric). To date, 21 Cx isoforms have been identified in human proteosome, each named according to its approximate molecular weight (in kDa), with Cx43 being the most studied till now [163]. According to electron microscopy analyses, all Cx share a common topology composed of four transmembrane proteins, with a cytoplasmatic C- and N-terminal domains, two extracellular loops, and an intracellular loop. In contrast to the transmembrane proteins and the extracellular loop which are highly conserved among the Cx family members, the intracellular loop and the C- and N-terminal showed high variability in terms of the length and amino acid sequence of each Cx. Thus, these regions play an important role in the modulation of the gap junction channel gating and in the intracellular trafficking of connexins, and consequently a variety in their biological roles and interactions [163].\n\nA schematic representation depicts the structural organization of connexin, homomeric connexon, heteromeric connexon, homotypic, and heterotypic gap junction channels in cells.\n\nFig. 3.45\nConnexins and gap junctions. Each connexin (a) consists of four transmembrane domains. Six connexins form a hexameric torus called connexon (b). Depending on the composition, connexons are called homomeric (six equal connexins) or heteromeric (up to six different connexins). (c) When the cells form direct contact, the connexons stick together forming gap junctions. Here, the differentiation is made between homotypic channels (both connexons are the same) and heterotypic channels (different connexons). (Reproduced with permission (CCBY) from Totland et al. [163])"}
{"_id": "Radiology$$$00a02336-03b4-45cf-bf6f-6a775e3ffa6e", "text": "A schematic representation depicts the structural organization of connexin, homomeric connexon, heteromeric connexon, homotypic, and heterotypic gap junction channels in cells."}
{"_id": "Radiology$$$8b71a401-a8c0-43ac-9e14-cd5fa1e735f0", "text": "The spatial arrangements of Cx43 in breast cancer cells, fibroblasts, and internal mammary artery endothelial cells were studied by CLSM and super-resolution localization microscopy [164]. After radiation treatment (50 min postirradiation with a dose of 4\u00a0Gy), these cells behaved differently concerning the trafficking and response of Cx43. In breast cancer cells, high accumulations of Cx43 were found in the cytosol and along the membrane. The results did not significantly differ between non-treated and irradiated cells. In contrast to that, normal fibroblasts and endothelial cells revealed differences at the membrane and in the perinuclear cytosol after radiation exposure. In endothelial cells, a significant Cx43 accumulation and condensation were observed in the perinuclear region, whereas at the membrane, a signal reduction was found. In fibroblasts, Cx43 accumulations were found in the perinuclear region but also at the membrane."}
{"_id": "Radiology$$$1a74ed09-48d0-460c-956f-60b97e32b3e3", "text": "Furthermore, as the Cx are phosphoproteins, they also play an important role in modulating the physiological properties and regulation responses of the channels, such as differentiation process, neuronal activity, development, cell synchronization, and immune response. Therefore, the presence of mutation in these structures is associated with several human diseases, such as neurodegenerative and skin diseases, deafness, and developmental abnormalities [165]. Also, gap junctions have been described as having a selective permeability, dependent on the combination of Cx isoforms that are made, conferring a single gating, conductance, and permeability to specific molecules, which could allow the association of each channel to a specific disease."}
{"_id": "Radiology$$$a469e80f-fa69-4636-88f9-cd607ea9aade", "text": "Another type of intercellular communication is via membrane connections such as tunneling nanotubes (TNTs) and epithelial (EP) bridges, which can be distinguished through their structural composition. These connections serve as direct signaling path when cells are separated by greater distances, than necessary for gap junctions. A microscopic image of both connection types can be found in Fig. 3.47."}
{"_id": "Radiology$$$24b85836-3dfe-4c9a-8416-45b0db0b3f6c", "text": "TNTs are thin cytoplasmic membrane bridges, which appear in straight lines in vitro but also with a curved shape in tissue or in vitro cultures in a three-dimensional extracellular matrix found in various mammalian cells [166]. Their diameter ranges from 50 nm up to 1.5\u00a0\u03bcm, and they can contact cells over long distances up to several cell diameter length. Even if an obstacle blocks the direct distance between two cells, TNTs, due to their flexible structure, can form a connection. The length of the TNTs dynamically varies when cells migrate up to a certain distance of several 100\u00a0\u03bcm, which is too large to keep the structure, and the tube disappears. The detailed structure of TNTs is very complex and not yet known in detail. Most TNTs consist of F-actin, and the thicker ones additionally contain microtubules and cytokeratin filaments. Further compounds are sequentially identified as more and more information about the responsibility of TNTs is gathered. TNTs are proven to serve as a highway for exchange of cellular compounds such as mitochondria, vesicles, and many more. Larger compounds are mainly transported along TNTs in so-called gondolas (see Fig. 3.46). Furthermore, TNTs play a key role in direct and active signal transduction including calcium and electric signals, which are known to occur in cells due to radiation stress. Overall, it can be said that the frequency of occurrence and also the complexity of TNT networks within a cell composite are connected to the stress this composite is exposed to. Under stress conditions, the networks are intensified, so that signal and compound exchange is enhanced and fastened. Furthermore, the TNT networks were identified to play a role in the bystander and also the rescue effect and other effects related to radiotherapy [166].\n\nA micrograph highlights a thin intercellular membrane connected by a T N T with a gondola at its end and a thick epithelial bridge.\n\nFig. 3.46\nMembrane connections. Microscopic image of membrane label of cells connected by a tunneling nanotube transporting a gondola and an epithelial bridge containing vesicles and cytoplasmic material. Scale bar: 10\u00a0\u03bcm. EP epithelial, TNT tunneling nanotube"}
{"_id": "Radiology$$$0bcc8722-d022-41fa-898d-73aedde172d1", "text": "A micrograph highlights a thin intercellular membrane connected by a T N T with a gondola at its end and a thick epithelial bridge."}
{"_id": "Radiology$$$b0825168-51fb-4d47-a56b-983e228e6bd1", "text": "In contrast to TNTs, EP bridges could, as also the name suggests, only be found in normal as well as cancerous human epithelial cells. They also differ from TNTs structurally, as they show a larger diameter of 1\u201320\u00a0\u03bcm and also a larger range from 25\u00a0\u03bcm to over a millimeter [166]. EP bridges consist of F-actin as well as microtubules, which promotes the structural stability allowing these connections to bridge such large distances. As TNTs, the EP bridges play a major role in cellular compound and signal transduction (Box 3.29)."}
{"_id": "Radiology$$$25a5bd97-294e-495d-8883-bcc88a377ecd", "text": "Cells communicate through direct cell-to-cell contact and for interconnectivity networks.\n\nGap junctions, constituted by connexins, allow short-range ionic and biochemical coupling.\n\nTNTs and EP bridges are responsible for long-range signal and molecule transduction.\n\nDirect cellular communication plays a role in various diseases, spreading of pathogen and health signals, as well as stress and radiation response of cell composites."}
{"_id": "Radiology$$$7ad64963-7648-4f81-9fcb-a6a20f9ca469", "text": "Gap junctions, constituted by connexins, allow short-range ionic and biochemical coupling."}
{"_id": "Radiology$$$1e676ce8-9f25-4533-bd94-0c7766d5efa1", "text": "TNTs and EP bridges are responsible for long-range signal and molecule transduction."}
{"_id": "Radiology$$$a51f6a68-8fcc-4134-a5f4-5717cf2f7e89", "text": "Direct cellular communication plays a role in various diseases, spreading of pathogen and health signals, as well as stress and radiation response of cell composites."}
{"_id": "Radiology$$$6a063386-42de-4352-9aad-be93cea4548d", "text": "Since inflammation that can be induced by microbial infections and tissue damage is an essential mechanism of innate immune response, the terms \u201cinflammation and immunity\u201d are intrinsically linked [167]. The process of inflammation includes several biochemical events and multi-level cellular interrelationships. In a concerted action, inflammation is initiated, propagated, matured (effector phase), and finally resolved. This implies that radiation exposure under inflamed conditions affects several cell types including many immune cell (sub)types. Macroscopically, vasodilatation and extravasation of immune cells into the inflamed tissue occur that in sum results in the key characteristics of inflammation, namely swelling, redness, pain, loss of function, and increased temperature. The major immune cells involved in the inflammatory process are polymorphonuclear neutrophils (PMNs), which are the most abundant leukocytes in peripheral blood and are very quickly recruited to sites of inflammation, mononuclear monocytes that can differentiate into dendritic cells (DCs) and macrophages, and different subtypes of B and T lymphocytes mediating an antigen-specific adaptive immune response."}
{"_id": "Radiology$$$cb5cd2fc-292a-4c62-a2c1-9b42075e00a0", "text": "The response of the key immune cells involved in inflammation is strongly dependent on the basal inflammatory status of these cells and the systemic inflammatory (micro)-environment. Further, the monocytic cells are central in all phases of the inflammatory process from initiation to termination and are characterized by an initial high plasticity that is weakened by prolonged tissue residency. Their phenotype is strongly influenced by the microenvironment, and radiation responses are therefore manifold and dose dependent [168]. Regarding inflammatory cytokine expression by macrophages, particularly TNF-alpha and IL1-beta, secretion is reduced following a single radiation exposure of 0.3\u20130.7 Gy without affecting the immune cell\u2019s viability. Further, decreased expression of the inducible nitric oxide synthase (iNOS) protein and, as a consequence, nitric oxide (NO) production in inflammatory macrophages after radiation exposure are observed in inflamed joints. Radiation exposure causes stress in cells via the production of reactive oxygen species (ROS), and a dose of 0.5\u00a0Gy, being routinely applied for low-dose radiotherapy of benign chronic inflammatory and destructive diseases, resulted in the strongest reduction of ROS by activated endothelial cells. Besides affecting immune cells and endothelial cells, low/intermediate-dose radiation exposure has osteoimmunological modes of action by reducing the activation of bone-resorbing osteoclasts and by fostering bone construction by osteoblasts [169]. Epidemiological, clinical, and experimental data regarding the effects of low-dose radiation on the homeostasis and functional integrity of immune cells was just recently comprehensively summarized [170]. Finally, particularly in the interactions of radiation with immune cells and cells of the inflammatory process, nonlinear dose relationships are prominent and may reflect a nonlinearity and complexity of immune responses. Figure 3.47 summarizes the key immune cells that are involved in inflammation and are modulated together with the endothelium by radiation in a dose range of 0.1\u20131.0 Gy. Finally, in polymorphonuclear leukocytes (PMN), irradiation with doses between 0.5 and 1.0 Gy resulted in a discontinuous reduction of chemokine CCL20 secretion that parallels a hampered PMN adhesion to endothelial cells [171].\n\nA diagram depicts the adverse effects of low-dose irradiation of 0.1 to 1.0 gray units on macrophages, lymphocytes, polymorphonuclear cells, and endothelial cells.\n\nFig. 3.47\nRadiation affects key cells involved in initiation and maintenance of inflammation"}
{"_id": "Radiology$$$188912fe-715f-4c1d-b85f-d85f87b79ca1", "text": "A diagram depicts the adverse effects of low-dose irradiation of 0.1 to 1.0 gray units on macrophages, lymphocytes, polymorphonuclear cells, and endothelial cells."}
{"_id": "Radiology$$$9c0a4690-af6e-4720-8e63-ea150462479d", "text": "Ionizing radiation causes phenotypic changes in endothelial cells, resulting in endothelial activation and ultimately endothelial dysfunction [172]. In vitro, this activation triggers an increase in the expression of the adhesion molecules vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), platelet endothelial cell adhesion molecule (PECAM-1), and E- and P-selectins involved in the recruitment of circulating lymphocytes. In vivo, increased expression of endothelial ICAM-1 and VCAM-1 was demonstrated in a model of radiation-induced intestinal inflammation. ICAM-1 knockout mice showed less severe pulmonary and intestinal inflammation than wild-type mice, suggesting that cellular infiltration may be deleterious in this situation. In humans, the endothelium may be activated by RT via the transcription factor nuclear factor kappa B (NF-kB) pathway, which is likely critical in the development of RT-induced cardiovascular diseases [173]. Overall, these studies demonstrated that radiation-induced increase in adhesion molecule expression by endothelial cells plays a crucial role in circulating cell recruitment and radiation-induced inflammation of the tissue and/or tumor, with a potential deleterious effect on normal tissues. Therefore, the vascular endothelium can be considered as a main control point of radiation-induced inflammatory and immune processes in normal tissues and tumors and may thus cover an ideal target to improve the therapeutic efficacy of radiotherapy of malign diseases. Furthermore, low-dose irradiation was demonstrated to result in a nonlinear expression and activity of major compounds of the antioxidative system in endothelial cells. This might contribute to anti-inflammatory effects in these stimulated cells and be beneficial in low-dose radiotherapy for benign diseases [174]. The effects of higher doses on the immune system in healthy tissue and tumors differ from those of low and intermediate doses and are covered in Chap. 4 (Box 3.30)."}
{"_id": "Radiology$$$f1be5f7f-fa38-46c7-87fa-26f1965613ac", "text": "Inflammation is intrinsincally linked to the immune response.\n\nMonocytes/macrophages are key immune cells in the initiation and resolution of inflammation.\n\nRadiation in a dose range of 0.1\u20131.0 Gy ameliorates inflammation by mainly affecting macrophages, PMN, lymphocytes, and endothelial cells.\n\nIonizing radiation causes several phenotypic changes in endothelial cells\n\nVascular endothelium can be considered as a main control point of radiation-induced inflammatory and immune processes."}
{"_id": "Radiology$$$6f329779-68be-4500-bb72-fc174c7455a6", "text": "Monocytes/macrophages are key immune cells in the initiation and resolution of inflammation."}
{"_id": "Radiology$$$d0723835-b721-464c-8018-5a850bdc697d", "text": "Radiation in a dose range of 0.1\u20131.0 Gy ameliorates inflammation by mainly affecting macrophages, PMN, lymphocytes, and endothelial cells."}
{"_id": "Radiology$$$4d1bc1fa-66ae-42ab-8693-2d98aa15fb86", "text": "Vascular endothelium can be considered as a main control point of radiation-induced inflammatory and immune processes."}
{"_id": "Radiology$$$8f3015cb-8bc8-454b-85f3-8252cd751111", "text": "Clustered regularly interspaced palindromic repeats (CRISPR)-CAS (CRISPR-associated protein) system is a defense mechanism that has been identified in prokaryotes that effectively acts to fight viruses. The five homologous sequences of 29 nucleotides separated by spacers of 32 nucleotides were observed initially in 1987 by a Japanese research group. The group identified a gene responsible for the conversion of alkaline phosphatase isozyme in Escherichia coli [175]. In 2002, another grouping of genes adjacent to the CRISPR locus was revealed which was termed CRISPR-associated system, or Cas. The system has been found in diverse species of bacteria and archaea, however with slightly different composition and mechanism of action. Since this time, new forms of CRISPR systems have been discovered that can be classified into six types and grouped into two classes [176]. Types I\u2013III are well studied, while other types IV\u2013VI, which have more recently been discovered, need further research to fully understand their mechanism of action. These systems have now been realized to be important breakthroughs for modern genetic engineering and are revolutionizing science."}
{"_id": "Radiology$$$7eba09e2-56b9-45d2-85be-e537e5834696", "text": "CRISPR are fragments of RNA that are cloned from the DNA of viruses that have infected a bacterium. Together with other sequences, it forms an adaptive immune system that stores memory of viral DNA within the bacterial host chromosomes. It is comprised of three main components: an RNA sequence made from the relevant CRISPR gene (crRNA) that contains within it a 20-base pair-long sequence complementary to the target DNA sequence; a DNA endonuclease that can edit genes and is referred to as Cas9; and a tracrRNA that acts to help bind the crRNA and Cas9 together. All three components are well studied [177]. In concert, the CRISPR-Cas9 system works to fight virus invasion in prokaryotes. When a bacterium comes across a virus that it was previously exposed to, it produces an RNA copy of the CRISPR that contains that virus\u2019 genetic information. The crRNA then binds with the tracrRNA to form a single-guide RNA (sgRNA) that leads the enzyme Cas9 to the correct DNA sequence. The sgRNA binds to the target site in the genome that matches the viral sequence on the crRNA and directs the Cas9 protein to create a double-stranded break. Next to the viral sequence is a protospacer adjacent motif (PAM), which also helps to align the enzyme. Once broken, the strand will experience a change in the viral DNA sequence through the activation of a DNA repair method, either nonhomologous end joining or homology-directed repair [177, 178]. The process shown in Fig. 3.48 is very efficient and effective and shown to be a valuable tool for researchers to study gene function and uncover biological mechanisms.\n\nA flow diagram depicts that t r a c r R N A and c r R N A form s g R N A. The s g R N A and Cas 9 form the C R I S P R Cas 9 forward slash s g R N A complex, which binds to D N A and causes D S B, or double-stranded break.\n\nFig. 3.48\nMechanism of CRISPR-Cas9 to produce a DNA double-strand break. The CRISPR-Cas9/single-guide RNA (sgRNA) complex consists of the Cas9 protein, which is coupled to the sgRNA, consisting of the transactivating crRNA (tracrRNA), responsible for binding of the RNA complex to Cas9 and the CRISPR RNA (crRNA) which encodes the target sequence. The CRISPR-Cas9/sgRNA complex binds to the specifically targeted DNA sequence and induces a DSB. (Adapted with permission (CCBY) from Zhao et al. [178])"}
{"_id": "Radiology$$$83250dc8-beb1-4033-98e2-e7ed4647a95c", "text": "A flow diagram depicts that t r a c r R N A and c r R N A form s g R N A. The s g R N A and Cas 9 form the C R I S P R Cas 9 forward slash s g R N A complex, which binds to D N A and causes D S B, or double-stranded break."}
{"_id": "Radiology$$$179c09a2-27c0-49d1-879e-a91ea6c7fe9e", "text": "The CRISPR-Cas9 system is unique due to its ability to induce double-strand breaks in almost any type of organism or cell type. The system is more accurate, providing an alternative to previous genome editing tools, such as zinc finger nucleases (ZFNs) and transcriptional activator-like effector nucleases (TALENs) [178]. The technology is an efficient genome editing system that can detect, manipulate, and annotate from diverse species-specific DNA sequences. The system is mainly used for studying DNA because manipulating RNA is difficult due to the lack of a PAM sequence, requiring efficient RNA targeting tools. The most widespread application of the CRISPR-CAS system has been in the context of genome editing of DNA, achieved through three mechanisms: (1) nonhomologous end joining, (2) single-base editing enzymes, and (3) homology-directed repair for DNA repair. The system can be delivered virally (adenovirus or lentivirus) or through nonviral mechanisms (hydrodynamic injection, electroporation, nanoparticles, and transposon carriers) and combined [178]."}
{"_id": "Radiology$$$35fbbe81-e857-4079-9fa2-5d2ec1f8a56c", "text": "The technology can be applied to develop a better understanding of a specific gene function or the manipulation of genetic material, as genetic sequences can be removed or edited. For example, a select tissue type can undergo multiplex mutagenesis for high-throughput analysis to identify cancer drivers or correction of a loss-of-function mutation; likewise, gene knockout could be used to enhance a specific cell type. Beyond gene editing, researchers have also used the Cas9 unit for targeting purposes instead of catalytically, known as the dead Cas9 (dCas9) [179]. For instance, epigenetic editing involves the alteration of the chromatin structure without modifying the individual\u2019s genomic sequence. The dCas9 is fused to a functional DNA methylation or demethylation enzymes or DNA modifiers [179]. The same idea follows CRISPRi and CRISPRa, which repress and inhibit gene expression. The CRISPRi uses the dCas9 to bind to the DNA-blocking RNA polymerase and transcription factor binding, while CRISPRa combines the dCas9 unit and selects transcription factors targeting activating sequences."}
{"_id": "Radiology$$$60cb0f09-cfb5-4ece-a20d-cfe7fcd9c269", "text": "Overall, these advancements provide new avenues to study genetic mechanisms and demonstrate the applicational value of CRISPR-Cas-based tools. It is being used with success in the field of agriculture, therapeutics, food industries, and more. The success of CRISPR has inspired efforts to discover new systems for targeting nucleic acids, including those from Cas9, Cas12, and Cas13 orthologues. The approach is gaining traction for use across multiple fields of research."}
{"_id": "Radiology$$$d1ecf7bd-76e3-426a-bb56-e269354ea8c5", "text": "As the field of CRISPR-Cas rapidly evolves, challenges have emerged which have also been the focus of much research. This is particularly in the context of development of treatment modalities for cancer. Some hurdles that have been identified are in relation to methods for effectively delivering the technology into the host that ensures suppression of the innate immune responses. Injection methods are traditionally used to deliver CRISPR-Cas9 components to cells via delivery vectors; however, the efficiencies of these injection methods are dependent on the target cells and tissues. Traditional delivery methods targeting cancer cells are not yet efficient enough to be applied clinically. For CRISPR-Cas9 to be applied as a therapeutic tool in cancer treatment, delivery must be more efficient and accurate which may require novel delivery methods [180]."}
{"_id": "Radiology$$$c1aa3ce7-89b1-4a58-9e64-7a06a88e52f8", "text": "Apart from limitations with delivery methods, the delivery vehicle itself also prevents a challenge, as delivery vectors hold a limited amount of genomic material. The most used delivery vehicle is adeno-associated virus (AAV) as it is relatively safe and effective; however, this method has a limited packaging capacity due to its size, which restricts the amount of genetic information that can be transferred to the target cell or tissue. AAVs can contain roughly 5\u00a0kB of information, while information for the Cas9 protein and the sgRNA which must be included on the plasmid is roughly 4.2\u00a0kB in size. To offset this, current research is being done to find smaller Cas9 orthologues, which in the future may allow for more helpful elements to be added such as reporter genes or fluorescent tags to support more successful gene editing [179]."}
{"_id": "Radiology$$$01b88eec-8b5f-4304-aea5-ad7085636562", "text": "Immune responses to the Cas9 protein have also been well documented in animal models, which presents an added challenge to the clinical application of the CRISPR-Cas system. A high prevalence of the human population has been exposed to the bacteria from which the Cas9 protein originates, meaning that there is likely a large population with preexisting immunity. While the implications of this are not yet entirely clear, testing of Cas9 orthologues may be required before CRISPR-Cas technology can be applied as a therapeutic to prevent T-cell responses. Alternatively, immunosuppressant drugs could potentially be used during treatment [179]. Off-target effects of the CRISPR-Cas system, such as mutations at undesired sites, also present a challenge. Extensive research has been done to minimize these effects; however, further investigation on increasing precision is required to improve safety [181]. As these hurdles become addressed, CRISPR-Cas9 will play a crucial role in medical treatments, including the treatment of cancers, and will effectively support gene therapy modalities (Box 3.31)."}
{"_id": "Radiology$$$1110e8b6-2a9a-4c42-a1c1-a4544647bc0c", "text": "CRISPR-Cas system is a defense mechanism that has been identified in prokaryotes that effectively acts to fight viruses.\n\nCRISPR are fragments of RNA that are cloned from the DNA of viruses that have infected a bacteria.\n\nCas9 is a DNA endonuclease that can edit genes.\n\nTogether, CRISPR-Cas9 is an efficient genome editing system that can detect, manipulate, and annotate from diverse species-specific DNA sequences.\n\nIt can be applied to develop a better understanding of a specific gene function or the manipulation of genetic material, as genetic sequences can be removed or edited."}
{"_id": "Radiology$$$7f8e24b0-2405-4ee0-b760-7af52204ab3a", "text": "CRISPR-Cas system is a defense mechanism that has been identified in prokaryotes that effectively acts to fight viruses."}
{"_id": "Radiology$$$c338a1b0-ec87-4eff-9bae-40d8d961142c", "text": "CRISPR are fragments of RNA that are cloned from the DNA of viruses that have infected a bacteria."}
{"_id": "Radiology$$$2b6f9cec-2bbe-4b93-8a46-f603d880f11d", "text": "Together, CRISPR-Cas9 is an efficient genome editing system that can detect, manipulate, and annotate from diverse species-specific DNA sequences."}
{"_id": "Radiology$$$96af8f91-9dbd-4a54-8f8a-fc796384edc3", "text": "It can be applied to develop a better understanding of a specific gene function or the manipulation of genetic material, as genetic sequences can be removed or edited."}
{"_id": "Radiology$$$758bb2b9-e8d5-4f75-b0e5-5449326f7133", "text": "DNA methylation, histone modifications, and incorporation of histone variants are chemical alterations of the cellular DNA. Such changes are not necessarily permanent and can be influenced by endogenous and exogenous stressors. One of these stressors is radiation. Radiation induces various alterations in these epigenetic modifications, mainly affecting gene expression and DNA repair."}
{"_id": "Radiology$$$f0ece090-6528-4ddf-90dd-b95523af74c2", "text": "MicroRNAs are small, highly conserved noncoding RNA molecules that regulate gene expression. They are single-stranded RNA transcripts with a length of 21\u201325 nucleotides that are derived from hairpin loop precursors. miRNAs affect the cellular radiation response via regulation of vital genes involved in DNA damage repair, cell cycle checkpoints, autophagy, and apoptosis."}
{"_id": "Radiology$$$af1b85b8-2d9b-49be-af67-1de02239f6d2", "text": "Long noncoding RNAs (lncRNAs) are defined as RNA transcripts with a length of more than 200 nucleotides missing a distinct protein-coding region. lncRNAs regulate gene expression on multiple levels, including transcription, RNA stability, and translation. Radiation exposure deregulates lncRNA expression, which affects radiosensitivity by interfering with canonical radiation response pathways, such as cell cycle control, DNA repair, and cell death induction."}
{"_id": "Radiology$$$c64442d2-d998-4cdb-a527-63fc6a1a59b7", "text": "Circular RNAs (circRNAs) are a recently described class of RNA molecules that are derived from precursor mRNA (pre-mRNA) in a process called backsplicing. Despite increasing attention, the number of studies investigating the direct effect of ionizing radiation on circRNA expression is still very limited. However, it is now evident that circRNAs are affected by irradiation and that they are important players in the cellular radiation response and sensitivity."}
{"_id": "Radiology$$$e28d0cc4-dedb-43f1-8567-a03cc30764bf", "text": "Extracellular vesicles (EVs) are generated by all cells within our body and are important communicators in normal and cancer cells. EVs have different sizes ranging from 40 nm up to several \u03bcm and are produced via different biogenesis routes. EVs\u2019 cargo contains various RNA species, DNA fragments, proteins, and lipids partly reflecting their cell of origin. EVs may influence neighboring cells via their cargo but also act in distant tissue as illustrated in cancer, where they play a role in both carcinogenesis and metastasis. Exosomes are a particular type of EVs formed by viable cells via the endosomal system, and there are specific cellular mechanisms that determine their cargo. Upon radiation, EVs are generated by both normal and cancer cells and transmit effects in irradiated and nonirradiated cells (e.g., bystander or non-targeted effects). EVs may constitute a source of biomarkers for diseases and stress conditions, including radiation."}
{"_id": "Radiology$$$fdb4269d-8b90-4de9-9e73-25f33414c388", "text": "Modifications of DNA bases and histone proteins, including the incorporation of histone variants, have important functions in the epigenetic control of gene expression. Both types of alterations add further information to the DNA molecule in addition to the genetic code, which contribute to phenotypic changes without altering the DNA sequence. Importantly, such changes are not necessarily permanent and can be influenced by endogenous and exogenous stressors. Enzymes that add, recognize, and dislodge DNA and histone modifications are called writers, erasers, and readers. The generation of modifications is facilitated by writers. Erasers modify and/or remove labels. Readers recognize and associate to modifications [182]."}
{"_id": "Radiology$$$aabfd27c-f2be-4f2a-a964-60cd2f4d8527", "text": "The methylation of DNA is a heritable epigenetic label in dividing cells. Methylation of DNA segments typically induces its silencing, while demethylation is characteristic for actively transcribed regions. Possible mechanisms for these effects are the binding of methyl-DNA-binding proteins, which affect gene activity or alterations of the chromatin structure. In mammals, DNA methylation patterns are retained or established by DNA methyltransferases (DNMTs) that catalyze the addition of methyl groups to nucleotides. S-Adenyl methionine (SAM) acts as a methyl group donor. DNMT1 function is the maintenance of methylation, and DNMT3a/b is responsible for de novo methylation. On the other hand, DNA demethylases can catalyze active demethylation. Most of DNA methylation takes place at cytosines, which are succeeded by a guanine nucleotide (CpG sites). Regions (>200 nucleotides and CG content >50%) with a high frequency of CpG sites are called CpG islands. Promotor sequences are often located within such CpG islands. Methylation of CpG islands silences gene expression, for example by impeding the binding of transcription factors or by recruitment of repressive methyl-binding proteins. The most common modification of DNA bases is the methylation of cytosine on carbon position 5, leading to 5-methylcytosine (5-mC). This modification accounts for approximately 1% of all bases and is therefore sometimes designated as the fifth base of the DNA. Further less abundant modifications are for example 5-hydroxymethylcytosine, 5-carboxycytosine, and 6-methyladenine."}
{"_id": "Radiology$$$2275d07c-4fc3-4833-a1c1-eb27c331c9c9", "text": "Histone modifications are covalent modifications joined to histone proteins. These modifications impair DNA-histone interactions, thereby changing chromatin architecture and gene expression. Some reduce DNA-histone interactions leading to nucleosome unwinding, chromatin opening, and increased accessibility for the transcription machinery leading to the activation of gene expression (euchromatin). Others increase DNA-histone interactions, leading to tightly packed chromatin followed by reduced access of the transcription machinery and thus gene silencing (heterochromatin). Currently, acetylation, methylation, phosphorylation, and ubiquitination are the most well understood, while others, like GlcNAcylation, citrullination, crotonylation, and isomerization, are more recent discoveries. All of these modifications are highly dynamic and added to or removed from histone amino acid residues by specific sets of enzymes. A well-described posttranslational histone modification is the trimethylation of histone H3 on the lysine located at position 4 of the protruding N-terminal tail (H3K4me3), which is correlated with promoters of actively transcribed genes. In contrast, the trimethylation of lysine on positions 9 (H3K9me3) and 27 (H3K27me3) is a heterochromatin mark, associated with repressed genes."}
{"_id": "Radiology$$$8e39c901-dc44-4374-b656-e1c220500283", "text": "In addition to posttranslational modifications, the histone structure of the chromatin can also be influenced by the incorporation of histone variants. Histone variants are low abundant and differ only in one or a few amino acids with their canonical counterparts. They are produced throughout the cell cycle and can be deposited into chromatin independent of replication by rapid exchange processes. Histone variants seem to be especially important for protecting genome integrity by the regulation of damaged chromatin accessibility and restoration."}
{"_id": "Radiology$$$24323c47-61c3-49f6-bd90-06c3a85918fe", "text": "Both DNA methylation and histone modifications are essential components in the cellular stress response. Therefore, it is not surprising that various alterations are reported after radiation exposure. On a molecular level, radiation-induced alterations in histone and DNA modifications either are required for the efficient detection and repair of DNA damage to avoid chromosomal instability or lead to changes in transcriptional activity and thereby alter a variety of cellular processes, including cell cycle regulation, DNA repair, and cell death induction. At organism level, epigenomic alterations were reported in various radiation-induced cancer and non-cancer diseases. As epigenomic alterations can be transferred to the offspring also, the contribution to radiation-induced transgenerational effects was recently suggested [183, 184]."}
{"_id": "Radiology$$$fa609b1c-2169-4ba6-bacf-c48c2c0e7b08", "text": "Altered DNA methylation patterns were found in in vitro and in vivo studies in response to irradiation. The majority of studies showed global hypomethylation, which was often linked with a reduced expression of enzymes involved in DNA methylation. As global hypomethylation is connected to malignant transformations, radiation-impaired DNA methylation may contribute to cancer development. However, hypomethylation is not always evenly dispersed across the genome and also radiation-induced hypermethylation was reported for specific loci. Interestingly, new studies imply that low- and high-LET radiations affect methylation differentially."}
{"_id": "Radiology$$$b57fbb65-3b93-405e-9cd7-711056d6fa63", "text": "A variety of radiation-induced histone modifications affecting transcriptional regulation and particularly DNA repair are described. In regard to DNA repair, an intensively studied histone modification is the phosphorylation of the histone H2A variant H2AX at serin-139 (phosphorylated H2AX is designated as \u03b3-H2AX) at sites of DNA double-strand breaks (DSBs). Formation of \u03b3-H2AX is an initial response after exposure and facilitates a cascade of further histone modifications, including ubiquitination of H2A/H2B as well as changes in the acetylation of H3 and H4. Together, these posttranslational histone modifications contribute to chromatin relaxation that enables the accession of DNA repair factors and influences the repair pathway choice. Moreover, the \u03b3-H2AX modification is widely used as a biomarker for DSBs, and a lot of methods were developed to use \u03b3-H2AX counting for DSB quantification."}
{"_id": "Radiology$$$3db5120a-cff1-4ec1-8144-6b84e9be4bdc", "text": "With the knowledge about DNA methylation and histone modification in radiation response, the targeted modulation of these features is investigated as a novel strategy to radiosensitize tumor cells during radiotherapy. For example, radiosensitizing activity was shown for DNA demethylation agents, like cytidine analogs. In addition, small-molecule inhibitors of histone deacetylases changing histone acetylation showed the potential to alter radiosensitivity."}
{"_id": "Radiology$$$fafca7d7-099b-4928-816b-557d73e8b619", "text": "The first studies in this field also demonstrated an exchange of histone variants in response to radiation exposure. For example, it was shown that the histone variant H2A-Z.2 is incorporated into chromatin immediately after DSB induction, where it contributes to recombinational repair by assisting RAD51 foci formation. In line, H2A-Z.2 U2OS tumor cells were shown to be more radiosensitive than controls. H2A.J, another histone variant, accumulates during radiation-triggered senescence processes in the vicinity of 53BP1 foci and affects the expression of inflammatory genes (Box 3.32)."}
{"_id": "Radiology$$$257dd6fe-f56a-42a2-b658-7a93beb5689b", "text": "DNA methylation, histone modifications, and incorporation of histone variants are chemical alterations of the cellular DNA.\n\nRadiation induces various alterations in these epigenetic modifications, mainly affecting gene expression and DNA repair.\n\nPhosphorylation of histone H2AX (\u03b3-H2AX) is the most prominent radiation-induced epigenetic alteration with significant impact on DNA repair."}
{"_id": "Radiology$$$89606a4d-4cc5-491d-863e-1958fbc69940", "text": "DNA methylation, histone modifications, and incorporation of histone variants are chemical alterations of the cellular DNA."}
{"_id": "Radiology$$$d52f8451-9e58-4df3-b95b-681d090957d6", "text": "Radiation induces various alterations in these epigenetic modifications, mainly affecting gene expression and DNA repair."}
{"_id": "Radiology$$$d76df320-f714-4547-a121-0b7690b02fbd", "text": "Phosphorylation of histone H2AX (\u03b3-H2AX) is the most prominent radiation-induced epigenetic alteration with significant impact on DNA repair."}
{"_id": "Radiology$$$606ceeac-ff12-4366-a4b1-e72090141ad9", "text": "MicroRNAs are small, highly conserved noncoding RNA molecules that regulate gene expression. They are single-stranded RNA transcripts with a length of 21\u201325 nucleotides that are derived from hairpin loop precursors. The basic mode of action of miRNAs is competitive partial binding with the 3\u2032 UTR of the target mRNA, which inhibits translation and/or leads to mRNA destruction. MiRNAs have also been shown to interact with the 5\u2032 UTR, coding regions, and gene promoters via binding complementary sequences [185]. Because each miRNA can act on multiple different target genes, and one target gene can be regulated by many different miRNAs, the miRNA-mediated regulation of cellular phenotype is highly complex. miRNA-mediated regulation is thought to affect roughly 60% of all protein-coding genes, according to estimations. To regulate miRNA abundance at the levels of transcription, maturation, and stability, cells have evolved various sophisticated methods to govern such extensive miRNA-mediated functions. miRNA actions have been linked to the regulation of a variety of cellular processes, including cellular homeostasis and stress responses. Furthermore, they have been linked to a variety of diseases. miRNAs, in addition to their intracellular roles, are also found in the extracellular environment. miRNAs can be identified in physiological fluids such as plasma, saliva, and urine. This extracellular miRNA population is varied and heterogeneous. Although the activities of extracellular miRNAs are not completely understood, it has been demonstrated that extracellular microvesicle-embedded miRNAs can be transferred and incorporated into destination cells [186]."}
{"_id": "Radiology$$$582467af-9af3-40dd-8ffb-b0ddb3f3cbdc", "text": "Ionizing radiation (IR) disturbs cellular equilibrium in a variety of ways. Cellular stress pathways shield cells from the harmful consequences of genotoxic assault. Cells respond to ionizing radiation-induced stress by activating several pathways ranging from DNA damage processing, signal transmission, altered gene expression, cell cycle arrest, genomic instability, and cell death. The available evidence implies that radiation exposure causes cellular responses that are influenced in part by gene expression networks. miRNAs govern several intracellular processes involved in the response to cellular stress and have been demonstrated to regulate gene expression [187]."}
{"_id": "Radiology$$$22c48842-7c73-4106-8055-10eecdbed043", "text": "Radiation exposure, whether accidental or intentional, is a serious public health issue that demands immediate attention for correct diagnosis and clinical planning. Exposure to large doses of ionizing radiation in a short time causes acute radiation syndrome (ARS), often known as radiation sickness or radiation poisoning. ARS involves a total dose of over 0.7 Gy (70\u00a0rad) from an external source, administered in a few minutes. Radiation sources might be accidental or deliberate. Several animal species were used to study the effects of radiation on miRNA expression. For ARS, miRNA analysis has been done in murine and nonhuman primate (NHP) models. Several studies employing different mouse strains (CD2F1, C57BL/6J, C57BL/6, and CBA/J) have identified miRNAs as biomarkers for radiation injury and countermeasure efficacy."}
{"_id": "Radiology$$$9db7cbaa-7625-40eb-8bbd-23de1b167934", "text": "While several miRNAs have been proven to be modulated by radiation, not all studies have showed the same miRNAs. However, most studies have shown downregulation of miR-150 and overexpression of miR-30 and miR-126. Exposure to 60Co \u03b3-radiation, high LET, and high-energy particles reduced miR-150 expression (56Fe, iron-56) [188]. In addition to total-body irradiation, miR-150 downregulation was observed in the lung and blood of female WAG/RijCmcr rats irradiated (15 Gy at 1.43\u00a0Gy/min), indicating the potential of employing miRNAs for partial-body exposure and the impact on miRNA expression in organs and biofluids [189]. A profile of seven significantly changed miRNAs (miR-150-5p, miR-215-5p, miR-30a-5p, miR-126-5p, miR-133a-3p, miR-133b-3p, and miR-375-3p) was discovered in rhesus macaques 24\u00a0h after exposure to ionizing radiation. Differences in the expression of three miRNAs (miR-133b, miR-215, and miR-375) were used to accurately discriminate between irradiated and nonirradiated NHPs. Two miRNAs (miR-30a and miR-126) were able to predict radiation-induced mortality in NHPs in this study. Another study utilizing rhesus macaques found miR-126-3p upregulated and miR-150-5p downregulated. Unlike rhesus macaques, miR-342-3p was shown to be most affected (tenfold persistent downregulation) at 24 and 48\u00a0h postirradiation in baboons [190]."}
{"_id": "Radiology$$$9730373d-8fb4-4cf8-b548-dba8492412b4", "text": "miRNAs strongly affect the cellular radiation response via regulation of vital genes involved in DNA damage repair [187], cell cycle checkpoints [191], and apoptosis [187]. Several important miRNAs, as well as their mRNA targets and signaling pathways implicated in radioresistance and radiosensitivity, are depicted in Fig. 3.49a, b, respectively.\n\nTwo diagrams depict the cellular pathways related to molecules and the clinical manifestations caused by the adverse effects of radio resistance and radiosensitivity.\n\n\nFig. 3.49\n(a) miRNAs and cellular radioresistance: a summary representation of miRNAs in different cancers (outer circle) that regulate various mRNA targets (middle circle). These mRNA targets in turn influence various crucial biological pathways (inner circle) responsible for cellular radioresistance. Data for the figure acquired and modified from Ebahimzadeh et al. [192] (data taken with permission); [193] (CCBY). Gene names: P21 cyclin-dependent kinase inhibitor 1, AIFM3 apoptosis-inducing factor mitochondria-associated 3, APAF1 apoptotic peptidase-activating factor 1, BRCA1 breast cancer gene 1, p53 TP53 gene and tumor protein p53 gene, RB retinoblastoma protein, TCEAL7 transcription elongation factor A-like 7, PTEN phosphatase and tensin homolog, APAF1 apoptotic peptidase-activating factor 1, MTOR mechanistic target of rapamycin kinase. miR microRNA, NSCLC non-small cell lung cancer, GBM glioblastoma, CRC colorectal cancer, HCC hepatocellular carcinoma, NPC nasopharyngeal carcinoma, OSCC oral squamous cell carcinoma. (b) miRNAs and cellular radiosensitivity. A summary representation of miRNAs in different cancers (outer circle) that regulate various mRNA targets (middle circle). These mRNA targets in turn influence various crucial biological pathways (inner circle) responsible for cellular radiosensitivity. Data for the figure acquired and modified from Ebahimzadeh et al. [192] (data taken with permission); [193] (CCBY). Gene names: STAT3 signal transducer and activator of transcription 3, CDK4 cyclin-dependent kinase 4, MCL1 MCL1 apoptosis regulator, BCL2 family member, SIRT1 sirtuin 1, E2F1 E2F transcription factor 1, P21 cyclin-dependent kinase inhibitor 1, EGFR epidermal growth factor receptor, BCL2 BCL2 apoptosis regulator, LDHA lactate dehydrogenase A, ATM ataxia-telangiectasia mutated, AKT AKT serine/threonine kinase 1, H2AX H2A histone family, member X, Beclin-1 coiled-coil, moesin-like BCL2-interacting protein, ATG12 autophagy-related protein 12, TP53INP1 tumor protein p53 inducible nuclear protein 1, DRAM1 DNA damage-regulated autophagy modulator 1, UBQLN1 ubiquilin 1, DUSP10 dual-specificity phosphatase 10, STMN1, stathmin 1, c-MYC Myc-related translation/localization regulatory factor, WNT2B wingless-type MMTV integration site family, member 2B, WNT wingless-type MMTV integration site family, member, PKM2 pyruvate kinase isozymes M1/M2, LDHA lactate dehydrogenase A, MTOR mechanistic target of rapamycin kinase. miR microRNA, NSCLC non-small cell lung cancer, NK/T-cell lymphoma natural killer/T-cell lymphoma, SCC squamous cell carcinoma, ESCC esophageal cancer, GBM glioblastoma; CRC colorectal cancer, HCC hepatocellular carcinoma, NPC nasopharyngeal carcinoma, OSCC oral squamous cell carcinoma, DSB double-strand breaks"}
{"_id": "Radiology$$$2c66f3ff-717b-4944-ab74-a193e0985dc5", "text": "Two diagrams depict the cellular pathways related to molecules and the clinical manifestations caused by the adverse effects of radio resistance and radiosensitivity."}
{"_id": "Radiology$$$5e0cb005-252f-4881-a32c-62ba0d84b4a8", "text": "The expression of RAD51 and the subsequent formation of RAD51 foci in response to IR are a critical stage in HR. Following IR, RAD51 was revealed to be a direct target of miR-34a, miR-107, miR-155, and miR-222. Overexpression of miR-34a in lung cancer cells prevented the formation of radiation-induced RAD51 foci. Greater miR-155 levels were associated with lower RAD51 expression and better overall survival in a large dataset of triple-negative breast cancer patients. IR-induced damaged DNA is sensed by ataxia-telangiectasia mutated (ATM), which can initiate the signaling pathway, leading to checkpoint activation and DNA repair. ATM was shown to be downregulated by miR-18a in breast cancer, miR-26a in glioma, and miR-421 in squamous cell carcinoma (SCC), making the cells more sensitive to radiation."}
{"_id": "Radiology$$$fa7ae3e4-bb81-488e-86a0-6988c121a98b", "text": "Additionally, in response to IR, two miRNAs, miR-24 and miR-138, have been discovered to directly control H2AX. miR-182 suppressed BRCA1, another important protein in HR, in breast cancer cells. miR-875 also hampered the HR pathway by directly targeting the epidermal growth factor receptor (EGFR) and disrupting the EGFR-ZEB1-CHK1 axis."}
{"_id": "Radiology$$$1f5cb517-2566-47eb-99e7-db66a9b6a127", "text": "PI3K/AKT is one of the key downstream targets of EGFR. The PI3-K/AKT pathway is crucial for establishing radiation resistance and intrinsic radiosensitivity of the cell. It is a critical regulator of normal and malignant development and cell fate decisions via activities such as proliferation, invasion, apoptosis, and activation of hypoxia-related proteins in cell signaling cascades. Several miRNAs are known to target and regulate key components of this pathway and help elicit the cellular response to radiation. AKT, an immediate downstream effector of the PI3K cascade, has been found to be directly targeted by miR-150 in natural killer (NK) and T-cell lymphoma cells. In a xenograft mouse model, miR-150 overexpression increased IR-induced apoptosis by decreasing PI3K/AKT signaling and sensitized NK/T-cell lymphoma cells to radiation. Furthermore, through blocking the AKT/GSK3/Snail signaling pathway, miR-203a-mediated ATM downregulation promoted apoptosis and cell cycle arrest in G1 phase in ovarian cancer cells. The tumor suppressor protein phosphatase and TENsin homolog (PTEN) is the central negative regulator of the PI3K/AKT pathway by dephosphorylation of PIP3 at the plasma membrane."}
{"_id": "Radiology$$$82d01b98-10f5-406a-b2f8-0834549c1649", "text": "Several miRNAs generate pro-survival signals in response to IR by targeting PTEN. Activation of the PI3K/AKT pathway, suppression of apoptosis, and improved radioresistance were seen when miR-17, miR-20a, miR-106b, miR-205, miR-221, miR-222, and miR-498 were overexpressed. Regulation of PTEN expression is crucial for cell cycle maintenance. In colorectal cancer cells, miR-106b is known to target the CDK inhibitor p21 as well as PTEN. Overexpression of miR-106b promoted the G1-to-S transition in CRC cells, which was blocked by overexpression of either PTEN or p21. miR-17-mediated PTEN inhibition, like miR-106b, boosted G2-to-M progression and increased NPC cell proliferation through its effects on AKT signaling."}
{"_id": "Radiology$$$8aa20f95-ffbc-44cd-a575-176f4a13b7d1", "text": "After IR exposure, apoptotic regulatory pathways are activated to remove cells with a high burden of DNA damage. Several miRNAs, including miR-133a, miR-125b, miR-124, miR-320a, and miR-634, are known to exert their effects on IR response via targeting components of crucial survival pathways, i.e., extracellular signal-regulated kinase (ERK), Janus kinase/signal transducer, and activator of transcription (JAK/STAT) as well as PI3K/AKT pathway. These pathways are initiated in response to IR-dependent activation of EGFR. In the JAK/STAT pathway, STAT3 is a direct target of miR-124, 320a, and 634, and the regulatory effect of these miRNAs on STAT3 upon IR is known to promote radiosensitivity. p53 is a critical tumor suppressor that is activated in response to IR to cause cell cycle arrest or apoptosis. Apoptosis mediated by p53 was abolished in IR-treated gastric cancer cells when miR-375 was overexpressed. In lung cancer cells, miR-300 directly regulates Apaf-1, the structural core of the apoptosome. Ectopic miR-300 expression caused radioresistance via reduced Apaf-1-induced apoptosis. P21 (Waf1/Cip1) is a p53 transcription target implicated in both major functions of the tumor suppressor, apoptosis, as well as cell cycle arrest. In oral squamous cell carcinoma (OSCC) cells, miR-17 has been shown to inhibit p21. In xenograft tumors, suppressing miR-17 boosted p21 expression, apoptotic rate, and radiosensitivity. miR-210 improved radioresistance in hypoxic hepatoma cells by targeting AIFM3. The retinoblastoma (Rb) tumor suppressor protein is an important component in the protection of cells from apoptosis. miR-622 was shown to prevent apoptosis by inhibiting the Rb gene in colorectal cancer cells. Another miRNA that reduced IR-induced apoptosis was miR-212, which directly targeted BRCA1 in glioma cells."}
{"_id": "Radiology$$$b6458cae-4e8a-4096-8d1f-72f660c85e26", "text": "IR-induced autophagy is important in defining cell fate and determining whether cells survive or die, and it also impacts radiosensitivity. A multitude of proteins, including Beclin-1, LC3B-II, mTOR, and other autophagy-related proteins, are crucial for the regulation of this multistep process. Beclin-1 is an autophagy central regulator that regulates autophagosome nucleation and maturation. Beclin-1 is known to be directly regulated by miR-216a and miR-199a, which inhibit autophagy and promote radiosensitivity in response to radiation. mir-199 has also been shown to regulate the DNA damage-regulated autophagy modulator protein 1 (DRAM1) in response to IR. In breast cancer cells, miR-26b also targets DRAM1. miR-23b reduced IR-induced autophagy by targeting ATG12, a ubiquitin-like protein involved in the production of autophagy vesicles. miR-214 also targets ATG12, which enhances radiosensitivity while blocking IR-induced autophagy in CRC both in vitro and in vivo. Several additional miRNAs that target autophagy activators have been demonstrated to suppress IR-induced autophagy. These include miR-200c, which targets ubiquilin-1 (UBQLN1), an autophagosome formation promoter; miR-101, which targets autophagy activator stathmin 1 (STMN1) in NPC cells; miR-30a and miR-205 in prostate cancer cells; and miR-450, which targets DUSP10. miR-1246 was one of the miRNAs that enhanced autophagy in NSCLC cells. In vitro and in vivo, ectopic expression of miR-1246 reduced mTOR activity and radiosensitivity in lung cancer cells."}
{"_id": "Radiology$$$e56c7783-a645-4223-8956-23b0dfde9140", "text": "miRNAs have been proven to be valuable diagnostic and prognostic biomarkers in the clinic for over three decades. miRNAs are found in plasma, serum, blood, and urine and even retrieved from formalin-fixed tissues. These benefits make it a biomarker that is persistent after IR exposure and allow for less invasive testing. Two miRNAs (miR-30a and miR-126) were found as predictors of radiation-induced death in nonhuman primates. Another study suggested that serum miRNAs could be utilized as functional dosimeters to detect early hematopoietic radiation harm. After 2 Gy total-body irradiation, miR-130a-3p expression increased, but miR-150-5p, -142-5p, -706, and -342-3p expression dropped. Determining the sublethal dose of 6.5 Gy required five miRNAs (miR-136-5p, -173p, -126-3p, -322-3p, and -34b-3p), while miR-30a-3p/30c-5p discriminated the lethal (8\u00a0Gy) and sublethal (6.5\u00a0Gy) groups. miRNAs can be used as clinical biomarkers to predict prognostic irradiation effects, in addition to radiation harm biomarkers. Some miRNAs show sensitivity or resistance to IR in cancer patients who have already received radiotherapy (Fig. 3.47). These miRNAs may be utilized as radiosensitivity or radioresistance biomarkers. miRNAs may soon be acknowledged as biomarkers at the level of proteins, which will be utilized to promptly classify harm from radiation exposure, as well as treatment responses, adverse reactions, and personalized radiotherapies."}
{"_id": "Radiology$$$812252f1-8fbf-4a73-aa1f-18a5b062194c", "text": "Research conducted thus far shows a relevant role for miRNAs in the future of radiation oncology, which may offer the basis for predicting patient response to radiotherapy and aid in developing miRNA-based individualized treatments to improve radiosensitivity. Early research indicated that the use of miRNAs as a biomarker for therapeutic monitoring and prognosis, and hence for more precise and individualized patient treatment, is feasible. Applications of miRNA for treatment as radiosensitizers are currently limited to cell culture or xenograft model systems and will need to be expanded into in vivo applications in the future. The role of extracellular miRNAs is still unknown. A thorough examination of radiation-induced mechanisms for secretion, transfer, and activity in recipient cells may aid in the understanding of major RT issues such as abscopal effects and radiation-induced secondary cancers (Box 3.33)."}
{"_id": "Radiology$$$211344b3-3582-47c3-bf5d-c5585621b787", "text": "miRNAs are small, highly conserved noncoding RNA molecules that regulate gene expression.\n\nmiRNAs can be identified in physiological fluids such as plasma, saliva, and urine.\n\nmiRNAs have been identified as biomarkers for radiation injury and countermeasure efficacy.\n\nmiRNAs affect the cellular radiation response via regulation of vital genes involved in DNA damage repair, cell cycle checkpoints, autophagy, and apoptosis."}
{"_id": "Radiology$$$54f18303-78c3-4077-aada-bf14300a4aa4", "text": "miRNAs are small, highly conserved noncoding RNA molecules that regulate gene expression."}
{"_id": "Radiology$$$53a208d7-2837-456f-a3ea-c77aeb6cfb0b", "text": "miRNAs can be identified in physiological fluids such as plasma, saliva, and urine."}
{"_id": "Radiology$$$b651e0c9-8c87-4106-9ea7-4df7adf1b374", "text": "miRNAs have been identified as biomarkers for radiation injury and countermeasure efficacy."}
{"_id": "Radiology$$$1ea93d38-a135-497f-aef2-a06662fa7aa5", "text": "miRNAs affect the cellular radiation response via regulation of vital genes involved in DNA damage repair, cell cycle checkpoints, autophagy, and apoptosis."}
{"_id": "Radiology$$$55ff4ea5-33ec-40b0-a073-e21f10c863f3", "text": "Long noncoding RNAs (lncRNAs) are defined as RNA transcripts with a length of more than 200 nucleotides missing a distinct protein-coding region. In the genome, they are located in intergenic, intronic, and exonic regions as well as sense, antisense, and bidirectional with transcripts overlapping sometimes genes [194]. In humans, 30,000\u201360,000 long noncoding transcripts are estimated compared to 20,000\u201325,000 protein-coding mRNA transcripts. Details about the biogenesis and functions of lncRNAs are very well summarized by Statello and colleagues [195]. In principle, the biogenesis of most lncRNAs corresponds to the production of mRNAs with transcription by RNA polymerase II and subsequent 5\u2032-end capping and 3\u2032 poly-A-tailing. In comparison to mRNAs, lncRNAs are less efficiently processed and often remain in the nucleus. As mechanisms for nuclear retention, tethering, or degradation on chromatin, weak splicing signals and cis- and trans-acting motifs are suggested. However, a substantial proportion of lncRNAs is distributed to the cytoplasm, where they can be sorted to specific organelles (e.g., mitochondria and exosomes) or they associate with diverse RNA-binding proteins. A considerable amount of lncRNAs assembles with ribosomes."}
{"_id": "Radiology$$$d4f4d00e-0819-4dd3-bd3b-75037c69eadb", "text": "Initially, lncRNAs were considered as transcription by-products, but meanwhile important cellular functions are described for an accumulating number of lncRNAs. In general, lncRNAs are regulators of gene expression, which interact with DNA, RNA, and proteins on various levels. There are examples for both lncRNAs acting locally at the site of transcription (cis-acting) and lncRNAs leaving the site of transcription (trans-acting). To activate or suppress gene transcription, lncRNAs can regulate chromatin structure to change their accessibility or sequester chromatin-modifying proteins from or to the promoters of target genes. In addition to their roles in transcription regulation and nuclear organization, lncRNAs are involved in posttranscriptional regulation. This can occur by the association between lncRNAs and RNA processing proteins, resulting in altered mRNA splicing and turnover. Other lncRNAs can directly base pair with RNAs and subsequently recruit proteins involved in mRNA degradation or they support translation by promoting polysome association. Also, the binding between lncRNAs and microRNAs can regulate gene expression as miRNAs are sequestered from their target mRNAs by binding to an lncRNA [=sponge or competitive endogenous (ce) RNA] and thus abolish the inhibitory effect of miRNAs on mRNAs."}
{"_id": "Radiology$$$a8b6dbea-38c2-4c7f-9634-df5e3aa64e98", "text": "Through their manifold impacts on the regulation of gene expression, lncRNAs affect widespread aspects of physiology, including differentiation, growth, and responses to diverse stimuli and stresses."}
{"_id": "Radiology$$$d8962ddf-03e5-4604-8981-148b1cdc2255", "text": "lncRNAs are involved in many aspects of cellular response to radiation. For a detailed overview, see May et al. [196] and Podralska et al. [193]. Firstly, radiation affects the expression levels of a plethora of lncRNAs in cancer and non-cancer tissues and both up- and downregulation are reported. Radiation-triggered changes are also reported for a wide dose range including low doses (below 100\u00a0mGy) as well as therapeutically relevant doses and for single and chronic treatments. The functional relevance in radiation response was shown for a considerable number of lncRNAs, where some enhance radiosensitivity and others increase radioresistance. The affected pathways cover crucial pathways of cellular radiation response, such as cell cycle control, DNA damage repair, and apoptosis. As the mechanism during radiation response of action, frequently, the sponging of microRNAs by lncRNAs and thereby promoting of the expression of target genes are described."}
{"_id": "Radiology$$$8a99a94d-5201-45e0-aa30-4ff46774a70c", "text": "The broad effects of irradiation on lncRNAs suggest valuable applications of this class of RNAs. Applications of biomarkers for radiation exposure may be important for biodosimetry or markers for normal tissue effects and radiotherapy response. Moreover, in vitro and in vivo studies demonstrated that modulation of the levels of lncRNAs can significantly enhance radiosensitivity of tumor cells. This suggests that lncRNAs may be used as targets to improve the outcome of radiotherapy in the future."}
{"_id": "Radiology$$$8eba31bb-de16-43a3-8ae0-92a96a330301", "text": "Prominent examples for lncRNAs with multiple roles in radiation response are HOTAIR, PVT1, and MALAT1. In breast cancer models, HOTAIR has been shown to increase radioresistance through interfering with DNA damage repair by targeting miR-218 and miR-449b-5p. In pancreatic ductal adenocarcinoma (PDAC), HOTAIR was induced by radiation, while a knockdown increased radiosensitivity. The knockdown increased the expression of Wnt inhibitory factor 1 (WIF-1), which was shown to enhance radiosensitivity. HOTAIR also promoted radiosensitivity of PDAC by increasing autophagosome formation through increasing LC3-II and ATG7A proteins. In cervical cancer, knockdown of HOTAIR increased radiosensitivity by the induction of a G1 cell cycle-phase arrest."}
{"_id": "Radiology$$$b2e664ba-dd76-48d7-96af-f29d2740c661", "text": "PVT1 contributes to NF90 transcription and HIF-1\u03b1 stabilization in nasopharyngeal cancer, resulting in enhanced radioresistance. On the other hand, the knockdown of PVT1 resulted in reduced phosphorylation of ATM, p53, and CHk2 leading to increased radiosensitivity by decreased DNA damage signaling and increased apoptosis. In non-small cell lung cancer, PVT knockdown increases radiosensitivity by sponging miR-195."}
{"_id": "Radiology$$$c7a87f8d-944c-45b7-b33d-e26a0f647aa1", "text": "lncRNA MALAT1 was downregulated after radiation in esophageal squamous cell carcinoma, and its overexpression enhanced radioresistance. It was shown that MALAT1 inhibited the downregulation of cyclin-dependent kinase subunit (Cks1), which resulted in a decrease in irradiation-induced apoptosis. MALAT1 also affected IR-induced apoptosis by interacting with miRNAs. In nasopharyngeal cancer cells, MALAT1 associated to miR-1, which led to increased levels of the anti-apoptotic protein SLUG. In cervical cancer cells, MALAT1 directly interacted with miR-145 to affect radiation-induced apoptosis (Box 3.34)."}
{"_id": "Radiology$$$713dc5a2-91ac-41b4-af09-2c5a545eb556", "text": "Long noncoding RNAs (lncRNAs) are transcripts >200\u00a0bp, which are not translated into proteins.\n\nlncRNAs regulate gene expression on multiple levels, including transcription, RNA stability, and translation.\n\nlncRNA expression is deregulated after radiation exposure, and they affect radiosensitivity by interfering with canonical radiation response pathways, such as cell cycle control, DNA repair, and cell death induction."}
{"_id": "Radiology$$$341cc3ba-8485-4bf7-8920-350ec85fc9c1", "text": "Long noncoding RNAs (lncRNAs) are transcripts >200\u00a0bp, which are not translated into proteins."}
{"_id": "Radiology$$$6653b406-e76b-4f53-9982-a49f137fd68b", "text": "lncRNAs regulate gene expression on multiple levels, including transcription, RNA stability, and translation."}
{"_id": "Radiology$$$4cefd3ba-1648-4b85-984c-bf2e6127f193", "text": "lncRNA expression is deregulated after radiation exposure, and they affect radiosensitivity by interfering with canonical radiation response pathways, such as cell cycle control, DNA repair, and cell death induction."}
{"_id": "Radiology$$$48983178-7eac-4e2a-b3ec-8b06a47f1166", "text": "Circular RNAs (circRNAs) are a recently described class of RNA molecules that are derived from precursor mRNA (pre-mRNA) in a process called backsplicing. During this process, which is regulated by the spliceosome, a splice donor is joined to an upstream splice acceptor. This generates a covalently closed RNA molecule, which is typically resistant to degradation by exonucleases, and therefore circRNAs are in general biologically more stable compared to their linear counterparts. Although most circRNAs are expressed in relatively low levels, their increased stability can result in accumulation to levels far exceeding those of their cognate linear mRNAs [197]. This is for instance observed during aging, which led to the hypothesis that certain circRNAs may represent biomarkers for aging tissues (such as the brain) and aging-associated diseases. Recent studies even implicate circRNAs as causative factors in aging and cellular senescence [198]. Since irradiation and excessive DNA damage are often proposed as inducers of senescence and accelerated aging, radiation-responsive circRNAs may contribute to these longer term effects of radiation exposure."}
{"_id": "Radiology$$$ae32a9b5-3d66-4354-8f0d-828902b735df", "text": "A detailed description of the biogenesis and function of circRNAs is beyond the scope of this chapter; we therefore refer the readers to some excellent reviews about these subjects [198] and will only briefly discuss matters that may directly relate to DNA damage and radiation."}
{"_id": "Radiology$$$bf29ea31-8aeb-4d7b-b35b-f20d535bbde4", "text": "Unlike original views that circRNAs are no more than aberrant by-products of normal splicing, it has become increasingly clear that they are often generated and function independently from their linear cognates. One important mechanism of circRNA biogenesis acts via the RNA-binding protein quaking (QKI). QKI is an alternative splicing factor that belongs to the STAR family of KH domain containing RNA-binding proteins and binds to specific sequences (QKI-binding motifs) in pre-mRNA [199]. The proposed mechanism for the role of QKI in circRNA biogenesis is that it binds motifs in introns adjacent to the circle-forming exons and subsequently forms a dimer to bring these exons into close proximity for further processing by the splicing machinery [200]. Importantly, QKI is expressed at low levels in epithelial cells but is increased during epithelial-to-mesenchymal transition (EMT), when cells reprogram their gene expression profiles resulting in the loss of intracellular junctions, polarity, and cytoskeletal organization, ultimately leading to a more migratory and invasive mesenchymal phenotype. The increase of QKI during EMT triggers the expression of hundreds of circRNAs [200]. EMT is a process which can be induced by irradiation, and very often the mesenchymal cells display a more radiation-resistant phenotype, highlighting the relevance of EMT, and therefore QKI-regulated circRNAs, for radiation and cancer biology."}
{"_id": "Radiology$$$8219e67a-c286-43ad-8225-034dd9e828e2", "text": "Different functions for circRNAs have been identified, including (1) binding and transportation of RNA-binding proteins; (2) generation of protein isoforms; and (3) regulators of transcription and alternative splicing (e.g., Xiao et al. [198]). However, the most established and investigated function of circRNAs is the regulation of microRNA expression and subcellular localization via a sponging mechanism (competing endogenous RNA, ceRNA). However, since most circRNAs are expressed at only low levels, and they usually contain only a limited number of microRNA-binding sites, it is now clear that the function of microRNA sponges or ceRNAs to regulate the expression of microRNA targets cannot be generalized for many circRNAs [198]."}
{"_id": "Radiology$$$74784f0b-5d45-4784-bfc7-d36ee41be63a", "text": "An important consideration here is that studies often perform gene ontology enrichment analyses based on the functions of the host genes of differentially expressed circRNAs. However, since there is currently little evidence that circRNAs in general function in the same pathways as their hosts, such analyses should be critically interpreted."}
{"_id": "Radiology$$$b3cdc6e5-1958-486c-b538-6ef640bd6f30", "text": "Despite increasing attention, the number of studies investigating the direct effect of ionizing radiation on circRNA expression is still very limited. On the other hand, there have been quite some studies in which the differential expression of circRNAs between radiation-sensitive and radiation-resistant cancer cell lines and patients was compared."}
{"_id": "Radiology$$$6a61160a-8dd1-490f-a262-aa73183d9398", "text": "In HEK293-T cells, gamma irradiation (8\u00a0Gy, single dose) resulted in very big differences in the expression of circRNAs between control and irradiated cells. Here, the authors focused only on circRNAs detected under both experimental conditions and identified a total of 158 differentially expressed circRNAs. However, among 5592 detected circRNAs in total, 2205 were detected uniquely in control cells while 1026 circRNAs were uniquely found in irradiated cells. This indicates that the differences were actually larger than was reflected by the 158 that were considered to be differentially expressed."}
{"_id": "Radiology$$$8e023a01-5201-426e-85b3-d34ee63b8016", "text": "A study by O\u2019Leary and co-workers investigated differential circRNA expression at 4\u00a0h and 24\u00a0h after exposure of endothelial HUVECs to a medium (0.25\u00a0Gy) and high dose (2.5\u00a0Gy) of g-rays [202]. Radiation-responsive circRNAs were predominantly produced from genes involved in the p53 pathway, as is in general the case for the early transcriptional response to radiation. The authors furthermore focused on two circRNAs derived from the WWOX gene, showing that they are differently regulated by QKI in response to radiation depending on the cell type and that they are enriched in exosomes [202]."}
{"_id": "Radiology$$$ce839498-01c6-47eb-8812-8d47ec5b2352", "text": "Another study focused on specific p53-dependent genes and their circRNA abundance in the embryonic mouse brain and primary neurons [203]. This study showed that the temporal induction of circRNA expression follows that of their linear mRNA hosts and that they remained more abundant for a longer time after irradiation compared to mRNA. This may have important implications for the use of circRNAs as long-term biomarkers of radiation exposure [203]. Indeed, gene expression changes at the level of mRNA are usually short-lived. Therefore, the increased stability of circRNAs may result in prolonged radiation-induced expression as was shown by Mfossa and co-workers [203]."}
{"_id": "Radiology$$$fe2b30c6-906a-4359-ab00-34bed30497d5", "text": "One of the most extensively studied circRNA host genes related to radiation and cellular radiosensitivity is PVT1, a long noncoding RNA (lncRNA) gene from which different circRNAs can be generated. One of these, termed circPVT1 (CircBase ID: hsa_circ_0001821, consisting of the exon 2 of the PVT1 mRNA), is downregulated during both multiplicative and radiation-induced senescence in human diploid WI-38 fibroblasts. This leads to reduced sponging of the hsa-let-7 microRNA and a subsequent reduction of proliferative proteins encoded by let-7 targets (e.g., IGF2BP1, KRAS, and HMGA2) that prevent senescence. Thus, circPVT1 is a suppressor of (radiation-induced) senescence by acting as a decoy for let-7. Interestingly, linear PVT1 lncRNA was not decreased in senescent cells, indicating that the observed effects were exclusively regulated by circPVT1 [204]."}
{"_id": "Radiology$$$5e4a31b4-5060-420f-a925-3f7b84bdc9a8", "text": "Pvt1 was one of the p53 target genes investigated in the aforementioned study of Mfossa et al. [203]. Also, in human head and neck squamous cell carcinoma cells, circPVT1 expression was found to be dependent on p53 as it was enriched in tumors with p53 mutations and silencing of p53 resulted in a downregulation of circPVT1, but not linear PVT1 [205]. Several other studies have implicated circPVT1 as an oncogene in different cancers, and it enhances to chemotherapy resistance in gastric cancer cells and lung adenocarcinoma by acting as a ceRNA for miR-124-3p and miR-145-5p, respectively [201, 205]. In non-small cell lung cancer, circPVT1 expression is induced after irradiation, while it enhances radiosensitivity via inhibition of the PI3K/AKT/mTOR pathway through sponging of miR-1208 [206]."}
{"_id": "Radiology$$$307a01aa-d485-464f-934b-e3660b89f84f", "text": "The PI3K/AKT/mTOR pathway plays a central role in cancer cell radioresistance in part via activation of EMT [207]. Inhibitors are currently being investigated as therapeutics to improve radiotherapy outcome. AKT is a serine-threonine kinase that exists in three isoforms, AK1, AKT2, and AKT3. The AKT3 gene hosts different circRNAs. Of these, circ-AKT3 (hsa_circ_0017250) is a protein-coding circRNA that competes with AKT phosphorylation, thereby reducing radiation resistance of different GBM cell lines. In contrast, another circ-AKT3 transcript (hsa_circ_0000199) increases chemoresistance of gastric cancer to cisplatin by upregulation of PIK3R1 (Huang et al. 2019). This suggests that different circRNAs originating from the same host gene can have opposite biological functions, as is sometimes also observed with linear splice variants. This furthermore highlights the importance of functional characterization of individual circRNAs. Several other circRNAs have been demonstrated to affect PI3K/AKT/mTOR signaling. Some of these have been described in the review papers by Cui et al. [201] and Jeyaraman et al. [208]."}
{"_id": "Radiology$$$908b8cb1-6f77-47cf-9eed-4b515a5d6011", "text": "Altogether, it is now evident that circRNAs are affected by irradiation and that they are important players in the cellular radiation response and sensitivity. However, their exact functions in these processes, which furthermore may be cell type dependent, need to be investigated in a case-by-case manner. Novel methods for the genome-wide identification and functional characterization of circRNAs may prove to be useful tools for these future investigations [209]."}
{"_id": "Radiology$$$6f48c785-5c48-43cc-8115-fe529880823d", "text": "Extracellular vesicles (EVs) are particles generated by all cells in our body by different routes and differ in diameter from <50 nm up to several \u03bcm [210]. EVs can based on their physical and molecular characteristics be divided into exosomes, ectosomes, microvesicles, microparticles, oncosomes, and apoptotic bodies. Size and expression of certain proteins reflecting their biogenesis and cellular origin are used for their classification (Table 3.15) [211]. Physical properties, e.g., size, density, and solubility of EVs, are often used for the isolation by differential high-speed centrifugation, size-exclusion chromatography, and precipitation. However, due to overlapping characteristics, pure preparations of individual EV species are challenging.Table 3.15\nCharacteristics of different extracellular vesicles (EVs)\n\nType of vesicle [size (nm)]\n\nDescription of characteristics\n\nMicrovesicles\n100\u20131000 nm\n\nA subgroup of EVs generated at the cell membrane. Found in both body fluids and tissues\n\nApoptotic bodies\n500\u20132000 nm\n\nA subgroup of EVs composed of cellular organelles and cytoplasm. Formed during apoptotic cell death by budding after the plasma membrane has undergone blebbing\n\nEctosomes\n100\u20131000 nm\n\nMembrane microvesicles produced by neutrophils or monocytes formed by direct budding from cell membrane. Vesicles larger than 350\u2013400 nm are not always considered as true ectosomes\n\nOncosomes\n100\u2013500 nm\nLarge oncosomes\n1\u201310\u00a0\u03bcm\n\nEVs of different sizes generated by tumor cells which function as transmitters of oncogenic signals (RNA, protein complexes) between cells\n\nExosomes\n40\u2013150 nm\n\nMembrane-bound EVs formed by the endocytic pathway. These EVs are first formed at the plasma membrane and subsequently transformed into early endosomes. These subsequently mature into late endosomes where they bud off to the ER intracytoplasmic lumen. The formed multivesicular bodies thereafter are unified with the cell membrane, and exosomes are released to the extracellular surroundings of the cell. Exosomal markers include CD63, CD9, CD81, and TSG101 among others"}
{"_id": "Radiology$$$e68bdb9d-538a-474a-b13d-09d5ccaf290e", "text": "EVs are enclosed by a lipid-bilayer membrane, and their cargo includes coding and noncoding RNAs, genomic and mitochondrial DNA fragments, proteins, metabolites, and lipids. Initially, EVs were discovered as \u201cgarbage bins\u201d to remove unwanted materials. Now, it is clear that most of the cells in our bodies utilize EV secretion into its close or distant microenvironment as a way of communication [212]. Thus, EVs can transfer functional biological molecules to recipient cells either by direct fusion with the plasma membrane or by internalization but also via interaction with cell surface receptors triggering downstream signaling (Box 3.35)."}
{"_id": "Radiology$$$09c2b3e4-8e50-4f44-bf73-cd19adf6f061", "text": "Extracellular vesicles (EVs) can be of different sizes and are generated via different biogenesis routes from all cells within our body.\n\nEVs cargo RNA, DNA fragments, lipids, and proteins partly reflecting their cell of origin.\n\nEVs are important communicators in health and disease.\n\nEVs regulate carcinogenesis and metastasis.\n\nExosomes are generated via the endosomal system and are released from viable cells."}
{"_id": "Radiology$$$9a02393e-71d7-4a63-ade5-b7f5cbf6a5cc", "text": "Extracellular vesicles (EVs) can be of different sizes and are generated via different biogenesis routes from all cells within our body."}
{"_id": "Radiology$$$0bb91f5e-b39b-4a93-9d66-60259d6d7beb", "text": "EVs cargo RNA, DNA fragments, lipids, and proteins partly reflecting their cell of origin."}
{"_id": "Radiology$$$d8bdd8b2-6bec-4f71-887b-e0f379e7a79c", "text": "Exosomes are generated via the endosomal system and are released from viable cells."}
{"_id": "Radiology$$$1aec5afd-071f-4edb-adb0-7bd695b65b33", "text": "EVs are found to be an integrated part of cell-to-cell communication, thereby contributing to regulation of the immune as well as the nervous system but also to tissue regeneration after damage [213]. Also, in the carcinogenesis and cancer metastasis fields, EVs have been demonstrated to be important communicators. Thus, EVs regulate the tumor and the tumor microenvironment signaling including angiogenic promotion, conversion of fibroblast into cancer-associated fibroblasts, and interplay with the immune system, thereby providing a good milieu for disseminated tumor cells to grow as well as establish themselves as metastases."}
{"_id": "Radiology$$$be77aaac-9df2-4943-bf74-7a51bccbf8d6", "text": "Given that EVs can influence a multitude of cell and tissue processes, it is not surprising that EVs today are considered an important source of biomarkers of different diseases including cancer. Thus, analyses of EVs and their cargo have been able to gain the US Food and Drug Administration (FDA) and international approvals to some extent [214]. With such diverse and varied roles of EVs in assisting cancer progression, it is essential that one can understand how IR, given its essential place in cancer therapy, can alter EVs cargo and/or function."}
{"_id": "Radiology$$$ba31f4c9-dc04-425c-b6fe-ba30c0c352a8", "text": "Exosomes are generated in the endosomal system of almost all cells (Fig. 3.50). These vesicles of nano size have membranes with parts from their cell of origin but also cargo membrane and cytosolic lipids, proteins, as well as various RNA species and DNA fragments [215].\n\nA schematic diagram of a cell depicts that receptors form an early endosome that leads to a late endosome, which has I L Vs, R N A, D N A, and proteins that cause exocytosis. The exosomes released enter the recipient cell.\n\nFig. 3.50\nPrincipal steps in exosome biogenesis. The early endosomes, which are generated at the plasma membrane (1), later undergo maturation, called late endosomes or multivesicular bodies (MVBs) (2). The MVBs\u2019 membrane invagination results in the formation of intraluminal vesicles (ILVs). During the invaginating process, particular proteins are incorporated into the invaginating membrane. Other cytosolic biomolecules, i.e., nucleic acids and proteins, are engulfed and enclosed within ILVs. The release of exosomes into the extracellular environment happens after fusion of the MVB with plasma membrane (3)"}
{"_id": "Radiology$$$b12075c2-de3a-4540-ad00-b8dd566e41d0", "text": "A schematic diagram of a cell depicts that receptors form an early endosome that leads to a late endosome, which has I L Vs, R N A, D N A, and proteins that cause exocytosis. The exosomes released enter the recipient cell."}
{"_id": "Radiology$$$caef8ed6-2cdf-4f76-be27-f895c79bdaeb", "text": "When exosomes were identified in the 1980s, they were seen upon as \u201cgarbage bins,\u201d but later it was reported that exosomes generated from B lymphocytes could trigger a T-cell response. From that time, exosomes have been shown to participate in a multitude of cell\u2013cell communication routes by carrying cargoes which are taken up by recipient cells close by or in a multicellular organism, in another tissue as exemplified in the cancer metastasis process [216]. The scientific community have gathered data on the exosome cargo, e.g., protein, lipid, and mRNA or miRNAs, into large databases, e.g., ExoCarta (http://\u200bwww.\u200bexocarta.\u200borg/\u200b) and Vesiclepedia (http://\u200bwww.\u200bmicrovesicles.\u200borg/\u200b), which are growing as more exosomes from cells of different origin and in different contexts are being deciphered and reported (Box 3.36)."}
{"_id": "Radiology$$$ad59a979-ccf0-4f53-9804-1496f2be3f51", "text": "Exosomes are EVs of endosomal origin, which contain nucleic acids, membrane and cytosolic proteins, metabolites, and lipids.\n\nOnce released, exosomes may act on cells in close vicinity or in a distant tissue.\n\nExosomes are involved in a multitude of human diseases including cancer where they regulate carcinogenesis, tumor-immune cell interplay, angiogenesis, and metastasis."}
{"_id": "Radiology$$$2a18e664-39a9-4ccb-a2aa-048bf98a04e0", "text": "Exosomes are EVs of endosomal origin, which contain nucleic acids, membrane and cytosolic proteins, metabolites, and lipids."}
{"_id": "Radiology$$$8ea590bc-86c0-4e97-b607-eee7520c51c9", "text": "Once released, exosomes may act on cells in close vicinity or in a distant tissue."}
{"_id": "Radiology$$$84eaa150-2377-409e-b00e-a69700d33218", "text": "Exosomes are involved in a multitude of human diseases including cancer where they regulate carcinogenesis, tumor-immune cell interplay, angiogenesis, and metastasis."}
{"_id": "Radiology$$$9b604142-df74-4486-a7c2-bb4ae5f2731a", "text": "It is still to some extent difficult to sort out plasma membrane-derived EVs from exosomes as their sizes are similar and given that there is a cell heterogeneity in the expression of the protein markers that define exosomes [210]. However, there are certain proteins that characterize exosomes including Rab GTPases, flotillin, heat-shock proteins (HSP70 and -90), tetraspanins (CD63, CD9, CD81, and CD82), Alix, flotillin, and TSG101. These markers are also suggested by the International Society for Extracellular Vesicles (ISEV) to be used to define exosomes [210]."}
{"_id": "Radiology$$$416771fc-0417-4eaf-9cb4-05f5237dd1fa", "text": "The lipid membrane of EVs has a different composition relative to plasma membranes. Thus, EV membrane has higher level of sphingomyelin, cholesterol, ceramide, and phosphatidylserine while less expression of phosphatidylcholine. These lipids have been shown to have a profound effect on carcinogenesis and cancer progression including enhancing invasiveness, angiogenesis, and chemoresistance via transport of oncogenic elements."}
{"_id": "Radiology$$$19371e5d-9540-4916-88e4-6065860a8695", "text": "There is clear evidence that cancer cells may have another rate of exosome release than non-transformed cells [217] while it is still a controversy as to what extent that is reflected in human liquid biopsies, e.g., plasma, and if it can be linked to therapy response. Also, it has been recognized that cancer and normal cells differ with respect to exosome cargo, e.g., miRNA, mRNA protein, and lipids. Exosomes have been found in plasma, serum, lymph fluid, bronchial fluid, cerebral spinal fluid (CSF), urine, saliva, tears, bile and gastric acid, amniotic fluid, breast milk, semen, and synovial fluid [218]. This has spurred an interest in their role as a source of biomarkers."}
{"_id": "Radiology$$$7832d6a7-e2a8-4c5d-b8e3-2fc459380016", "text": "As indicated above, in human tissues, exosome can act near its cell of release or be transported in the blood to a distant tissue, e.g., site of metastasis in the context of cancer. It has been demonstrated in a large number of publications that once the exosome cargo reaches its target cell, several mechanisms cooperate for uptake as well as for altering signaling in the recipient cells [219]. Similar to EVs, exosomes participate in different processes of the immune system as well as in neurological signaling processes. Exosomes also have a clear function in cancer signaling. Exosomes are described to regulate tumor internal signaling but also tumor\u2013tumor microenvironment interplay. For example, exosomes may promote angiogenesis as well as metastatic spread, and they are important communicators between tumor and different infiltrating immune cells."}
{"_id": "Radiology$$$4733ea28-0ebb-43c5-856b-e6399c1ef7e8", "text": "Exosomes may exert these events by modulating paracrine, autocrine, and endocrine pathways in different cell types via their cargo. The exosome surface proteins are reported to resemble those of plasma membrane and endosome of a given cell yet with minor contribution of proteins from nucleus or Golgi. It has also been reported that EV membrane composition differs from plasma membrane concerning their lipids. Thus, EV membrane has higher level of sphingomyelin, cholesterol, ceramide, and phosphatidylserine while less expression of phosphatidylcholine."}
{"_id": "Radiology$$$de1adf77-f361-4121-9e8a-650570ffaaed", "text": "Exosomes carry a wide range of cargoes, and it is currently thought that such cargoes, e.g., RNA species, are selectively loaded into exosomes and that loading is not a random process. This is supported by observed differences in miRNA abundances in cells compared to exosomes, which have been linked to 3\u2032 uridylation in miRNAs of exosomes, while 3\u2032 adenylated miRNAs are enriched in cellular fractions [220]. Moreover, certain sequence motifs are recognized by the nuclear ribonucleoprotein A2B1 (hnRNPA2B1), which then dictates the miRNA loading process into exosomes, possibly via interaction with cytoskeletal components. The protein AGO2 has also been shown to selectively package exosomes with miRNAs specifically miR-451. In addition, overexpression of the protein neutral sphingomyelinase 2 has been associated with an increase in exosome-associated miRNA. It has also been demonstrated that 3\u2032 mRNA fragments are enriched in exosomes. The conserved 25-nucleotide sequence (also known as a zip code-like 25 nucleotide) is usually incorporated into mRNA\u2019s 3\u2032-untranslated region and expressed in many types of cells, leading to mRNA enrichment in the MVs/exosomes. It has been suggested that miR-1289 plays a crucial role in MV enrichment of the mRNA via binding to zip code sequence directly."}
{"_id": "Radiology$$$6a57cb5d-dde0-45e7-ae94-46e075c430b7", "text": "The release of exosomes requires the movement of late endosomes/multivesicular bodies (MVBs) to the cell surface, where they fuse with the cell membrane (Fig. 3.50). The actin cytoskeleton and microtubule network have been shown to be important in facilitating MVB movement towards the cell surface, while Rab GTPases facilitate the release of exosomes into the extracellular space. Interestingly, certain Rabs have been demonstrated to preferentially export exosomes with certain phenotypes; for example, Rab27A/B have been shown to release exosomes positive for CD63-, TSG101-, and Alix expression [221]."}
{"_id": "Radiology$$$085e7185-49f4-4e1a-8f39-d7d97c6c2d1d", "text": "Exosomes may, via their cargo, induce both pro-survival and pro-death signaling in recipient cells. Thus, exosomes may promote tumor growth as well as induce inflammation through activation of mesenchymal stem cells (MSCs) and the subsequent secretion of IL-6 as well as IL-8. There is also evidence that exosomes carry inhibitors of apoptosis proteins (IAPs), e.g., survivin, XIAP, cIAP1, and cIAP2, the delivery of which is postulated to offer protection from a continually changing microenvironment, thereby helping tumor progression."}
{"_id": "Radiology$$$63402ee9-5555-4cfb-bfdf-5426526ad6f9", "text": "In the context of tumor and immune cell interplay, there is growing substantiation that tumor cells of different origin can via their exosome cargo impair infiltrating T-cell function as illustrated by PD-L1-expressing exosomes [222]. Similarly, CD73, an ecto-5\u2032-nucleotidase and a master regulator in the tumor-immune microenvironment, has been reported in exosomes and also to have functional activity in this context, e.g., impairing T-cell function [222]. The effect exosomes have on tissue poses a number of interesting questions when it comes to radiation biology as radiation has tumor growth-inhibiting effects yet may negatively influence certain normal tissue in the radiation therapy field. Exosomes are also thought to offer some beneficial properties against different tissue damages. Thus, exosomes from MSCs have been reported to offer protection against diabetic nephropathy in the renal system by blocking apoptosis as well as promote vascular regeneration. Moreover, acute kidney injury caused by the DNA-damaging agent cisplatin was found to be blocked by microvesicles as a result of inhibition of apoptosis. Exosomes have moreover been shown to enhance recovery from ischemic brain injury through promoting angiogenesis and providing an extracellular milieu for appropriate brain remodeling."}
{"_id": "Radiology$$$3d33cce6-8c16-45af-be19-dbaf2fdf2154", "text": "As EVs are important regulators of multiple cellular signaling events, it is not surprising that EVs are also important communicators in the context of IR [223]. EVs are affected by IR on multiple levels, including alterations in subtype/size, release, cargo, uptake, and function. These changes facilitate the dissemination of IR signals to neighboring cells and to distant sites, which contributes to systemic effects in irradiated and nonirradiated areas. Therefore, EVs are potential mediators of IR-targeted and non-targeted effects, e.g., bystander and abscopal effects."}
{"_id": "Radiology$$$aab38ef0-2b75-4b80-8b87-bf4896c2c8f7", "text": "Several studies suggest increased EV release after irradiation in in\u00a0vitro and in\u00a0vivo models. As an example, it has been shown that IR may increase EV release in different tumor models including head and neck cancer and glioblastoma. Moreover, also in normal tissue after partial-body irradiation of mice, it has been reported that the EV content is altered in different tissues including the liver, brain, and heart. As the potential mechanism for the IR-increased EV release, p53-mediated induction of genes involved in the EV biogenesis and altered MAPK signaling were suggested. It was also shown that the cellular uptake of EVs is affected by radiation exposure. In mesenchymal stem cells, irradiation induced changes in the formation of cell surface CD29/CD81 complexes, which increased the cellular uptake of EVs [224]."}
{"_id": "Radiology$$$722adaa1-a326-4d70-a54b-1cde2350af08", "text": "IR also induces changes in the composition of EVs released from cancer and non-cancer cells. Alterations seem to be highly related to cell type, radiation dose, and also time postradiation exposure where both microRNA and protein changes have been described. Additionally, changes in lipids and metabolites in EVs from irradiated donor cells are reported. EV cargo changes were also shown for EVs isolated from blood during or after tumor RT. For example, differential expression of serum EV miRNAs was monitored in prostate cancer or glioma patients after RT. In the serum of HNC patients, it was shown that tumor-derived exosome (TDE) amount relative to total exosomes increased in patients that were refractory to a combination of radio-, targeted, and immune therapy while the opposite was found in the patients that responded. Moreover, in the same study, results demonstrated an increase in regulatory T-cell (Treg)-derived exosomes as well as in CD3(\u2212)PD-L1+ exosomes in serum after treatment if the patients were refractory. Such alterations in EV cargo open up for potential applications of EVs/exosomes as a source of biomarkers for radiation exposure as well as for prognostic or predictive biomarkers of RT response in the context of cancer."}
{"_id": "Radiology$$$fd139ef0-3a46-4791-8ce7-4f0e0d5dd684", "text": "A substantial amount of studies suggest that EVs play a role in the progression, RT resistance, and metastasis of cancer cells. In glioblastoma, Mrowczynski et al. demonstrated a pro-survival function of EVs derived after IR, which may be triggered by elevated cargo levels of oncogenic miRNAs and mRNAs, while tumor-suppressive RNAs were reduced [225]. In the same cancer type, a pro-migratory role of radiation-related EVs was reported. Likewise, EVs from irradiated HNC and neuroblastoma cells were shown to stimulate survival, migration, and invasiveness. However, there are also studies reporting on an induction of harmful effects of EVs from irradiated cancer cells into recipient cells, like chromosomal damage and increased ROS levels."}
{"_id": "Radiology$$$be88598d-0f34-4d95-bc98-8f6e53ab1d96", "text": "EVs are also involved in the communication of radiation signals among normal cells. Early work by Jella et al. showed the transmission of cytotoxic effects between irradiated and nonirradiated keratinocytes in an in\u00a0vitro model system. Thus, EVs from irradiated mice were able to increase DNA damage and reduce viability in co-cultivated mouse embryonic fibroblasts. On the other hand, several reports found beneficial effects of EVs released from irradiated human PBMCs. For example, EVs from irradiated blood cells were shown to reduce radiation-induced apoptosis in endothelial cells [226]. Accordingly, pro-angiogenic and tissue-regenerative capacities were attributed to EVs from irradiated PBMC. In this regard, it was shown that EVs (especially from mesenchymal cells) could be used for the treatment of radiation injury [227]."}
{"_id": "Radiology$$$35f0ad18-af1d-4d54-83c5-f153d486bf71", "text": "In summary, current knowledge indicates a vital role of EVs in the IR response of cancer and non-cancer cells. IR not only affects the production and the composition of EVs, but also alters the phenotypes of recipient cells. Therefore, these mechanisms can contribute to the communication between irradiated cells as well as to the systemic distribution of local radiation effects throughout an organism. Moreover, EVs may offer a source of biomarkers for monitoring RT responses in cancer patients (Box 3.37)."}
{"_id": "Radiology$$$7d5a6231-1dc6-430d-8358-dfe0b56b3571", "text": "EVs, including exosomes, act as intercellular signaling components in response to IR.\n\nIR may influence the EV release/uptake as well as cargo in normal as well as tumor cells contributing to both direct and bystander effects of IR.\n\nEVs/exosomes may contribute to the distribution of systemic IR effects and offer a source of IR response biomarkers."}
{"_id": "Radiology$$$e48e5217-4335-4ba1-9a7f-c0575e6c5bf1", "text": "EVs, including exosomes, act as intercellular signaling components in response to IR."}
{"_id": "Radiology$$$40d8acaa-3bdb-44fa-8d9a-d403fc7087ff", "text": "IR may influence the EV release/uptake as well as cargo in normal as well as tumor cells contributing to both direct and bystander effects of IR."}
{"_id": "Radiology$$$d0d3c7c1-0a24-4f0b-862a-94238ac88891", "text": "EVs/exosomes may contribute to the distribution of systemic IR effects and offer a source of IR response biomarkers."}
{"_id": "Radiology$$$431e9463-7eae-416e-bd1a-a51a6f6af910", "text": "The term proteome was created to describe the set of proteins expressed by the genome [228]. Proteomics analyzes the proteome at a specific time and in a specific state. Proteome profiling provides information not only about the protein expression, but also about the function, structure, and interactions of proteins."}
{"_id": "Radiology$$$c4c4f206-54c9-4f54-b613-ff22b9ec6b2e", "text": "In the well-established paradigm of proteomics, protein mixture will be separated before digestion either by gel electrophoresis (gel-based approaches) or using liquid chromatography (gel-free approaches) to resolve the complexity of the protein mixture [228]. In the next step, proteins were fragmented into smaller units called peptides during digestion. The generated peptides were further separated and sorted in the mass spectrometry system based on the mass and charge, where the abundance of each peptide is translated into numerical values called intensity. To identify a protein, a certain number of good-quality peptides must be detected. Quantitative proteomics compares the peptide intensities for each protein between treated (e.g., irradiated) and non-treated (e.g., nonirradiated) samples. The alterations in peptide intensities represent the changes in the expression level of corresponding protein."}
{"_id": "Radiology$$$d5b4b34e-529f-442f-a5b0-148b65324b73", "text": "Protein quantification can be performed in two ways: either label based or label free. In label-free methods, protein expression in several samples is compared by measuring the intensity of the corresponding peptides or counting the number of correlated spectra for each protein. Label-based quantification is performed by labeling peptides or proteins with fluorescent dyes, chemical isotopes, radioisotopes, or affinity tags before mass spectrometry. Label-based proteomic approaches are classified into chemical labeling (ICPL, iTRAQ, and iCAT) and metabolic labeling techniques (SILAC)."}
{"_id": "Radiology$$$4d70c56b-32d3-4606-9523-b5fb9af4486b", "text": "Advanced proteomics approaches also offer an accurate platform to identify and quantify the posttranslational modifications (PTMs) such as phosphorylation, acetylation, methylation, or ubiquitination [229]. These modifications are crucial for the stability, localization, and conformation and functions of proteins. The analysis of phosphoproteome, acetylome, or ubiquitinome has revealed the regulatory role of these PTMs in cellular function and homeostasis [229]."}
{"_id": "Radiology$$$0ed94c1d-8b33-48d5-af55-fff69a7775e9", "text": "A comprehensive combination of proteomics and advanced bioinformatics makes the complex biological processes in cells understandable. The bioinformatics tools provide a broad spectrum of information on protein functions, protein-protein interactions, protein interactions with other biomolecules (genes and metabolites), contribution to the signaling pathways, and predictions of diseases [230]."}
{"_id": "Radiology$$$4e726815-1650-4d92-89f8-97de017755ec", "text": "Different proteomics approaches were applied to investigate the biological effects of radiation exposure on normal and tumor tissues, cancer radiotherapy outcome, individual sensitivity, risk assessment, biodosimetry, and biomarker discovery; an extensive review can be found in the work of Azimzadeh et al. [231]."}
{"_id": "Radiology$$$9c15782c-c16e-4fe3-aab7-90af77d686da", "text": "One of the main goals of cancer proteome profiling in radiation research has been to identify biomarkers that predict the tumor\u2019s response to radiation exposure. The proteomes of different cancer cell lines such as nasopharyngeal carcinoma, head and neck cancer, oral squamous cell carcinoma, laryngeal cancer, breast cancer, and lung cancer have been analyzed in radiobiological studies to identify signatures of cancer radioresistance and potential prognostic markers for radiotherapy. Although the results of these studies are not uniform, the proteins identified and quantified belong mainly to the family of antioxidant proteins, heat shocks, and structural proteins."}
{"_id": "Radiology$$$2da0365d-2767-4804-8ff7-3e6b70b7022a", "text": "The most challenging aspect of radiotherapy for cancer is to select the radiation dose so that the tumor is killed but the surrounding normal tissue is harmed as little as possible. The effect of radiation on normal tissue has also been analyzed by proteomics approaches. A number of studies have been carried out on in vitro and in vivo models to simulate the effects of radiation on normal tissue such as the heart, brain, and liver. These studies underlined the adverse effects of irradiation on tissue structure and function. The mitochondrial proteins, the metabolic enzymes, and the oxidative stress response proteins are the main groups of proteins affected in the irradiated heart. The structural proteins, proteins involved in cognition and learning function, and inflammatory response were impaired in the irradiated brain."}
{"_id": "Radiology$$$51cb81d9-741c-4cb0-ae8c-d11e4862ed80", "text": "Biofluids such as serum, plasma, and urine are optimal biomaterials for biomarker discovery, mainly because of the relatively noninvasive collection methods. However, proteomic profiling in biofluids is still an analytical challenge due to the complexity and variable spectrum of protein abundance. Several studies have compared the biofluid proteome before and after radiation exposure. These studies provide a panel of proteins that serve as biomarkers of radiation exposure, radiation damage, cancer radiosensitivity and radiotherapy outcome, and biodosimetry."}
{"_id": "Radiology$$$1d06fad4-39dd-421b-b2e1-a56aba557dea", "text": "Since cellular responses to irradiation are tightly regulated by PTMs, the analysis of these changes is becoming increasingly important in radiation research. PTM profiling is still a young field in radiation research, and only a few studies have analyzed the change in protein phosphorylation, acetylation, and ubiquitination in the context of cancer and normal tissue response to irradiation."}
{"_id": "Radiology$$$eaf2fc84-1bb9-43bb-80db-815c1394e918", "text": "Archival formalin-fixed, paraffin-embedded (FFPE) tissues are the invaluable alternative of fresh frozen biomaterial in radiation research. Proteomic analysis of these samples is challenging, mainly due to the harsh conditions of tissue fixation and, in particular, biomolecule extraction method. The proteomics studies conducted on FFPE tissues from radiobiology archives have mainly investigated the predictive marker for radiotherapy resistance of cancer or adverse effect on normal tissue. They demonstrated the compatibility and applicability of FFPE tissues for proteomics studies [231]."}
{"_id": "Radiology$$$9dce9b86-0269-4e07-b8a6-dfc05b79527d", "text": "The study of cellular lipid pathways and networks in biological systems is known as lipidomics [232]. Lipids are a necessary component of biological membranes and play essential roles in biological systems, such as the plasma membrane bilayer structure that separates the cell cytoplasm from the extracellular microenvironment, the provision of a hydrophobic medium for the functional performance and interactions of membrane proteins, and the generation of second messengers through enzyme reactions [233]. Lipidomics refers to the analysis of all lipids present in a sample using liquid chromatography (LC) and mass spectrometry (MS) techniques."}
{"_id": "Radiology$$$a8a28c93-de72-4133-8631-09564f487d5a", "text": "Glycerolipids, saccharolipids, sphingolipids, glycerophospholipids, sterols, polyketides, fatty acyls, and prenols are the eight types of lipids that can be classified based on their chemical structures and hydrophobic and hydrophilic aspects [233]. The most prevalent phospholipids (PLs) are glycerophospholipids, found in biological membranes and essential for numerous cellular activities. PCs and other related phospholipid derivatives like lysophosphatidylcholines (LPCs) are signaling molecules that play a role in regulating cellular death and proliferation. Triacylglycerides (TGs), sphingomyelins (SMs), phosphatidylinositols (PIs), diacylglycerides (DGs), and cholesteryl esters are also among lipids with key roles in cell physiology [234]."}
{"_id": "Radiology$$$8a65af49-8b99-4319-8a59-c1352d6fc88d", "text": "Reactive oxygen/nitrogen species (ROS/RNS) react extensively with lipid molecules following irradiation, causing lipid breakdown and eliciting both direct and indirect inflammatory responses. Lipid peroxidation and pro-inflammatory lipid intermediates can have immediate impacts on physiology and can lead to long-term consequences like CVD, lung damages, and even carcinogenesis. Apoptosis can also be triggered by the direct action of radiation or by lipid intermediates, such as the activation of sphingomyelinase, which produces ceramide from the hydrolysis of sphingomyelin. Ceramide is a direct apoptotic cell death [234]. Post-ionizing irradiation (IR) changes affecting lipids have been proven in preclinical investigations and may have biological consequences such as the acute radiation sickness (ARS) or lead to delayed effects of acute radiation exposure (DEARE)."}
{"_id": "Radiology$$$e5c0ea11-732a-4c71-a98a-a2dff123f69c", "text": "When comparing sham or pre- and post-IR specimens, lipids examined in blood, such as PCs, LPCs, TGs, SMs, and CEs, exhibit modifications."}
{"_id": "Radiology$$$4aa4886e-b611-4fbe-85aa-af78e9e30b61", "text": "The link between lipid levels in serum/plasma and radiation has been studied in animal models in several publications. Phosphatidylethanolamine (PE) and phosphatidylserine (PS) levels in rat plasma following gamma irradiation exposure increased dramatically, thus indicating that IR may disrupt phospholipid metabolism [233]. Fatty acids, such as linoleic acid and palmitic acid, were found to be present at reduced levels in the blood following 137Cs exposure in mice, while phosphatidylcholines were among the most disturbed molecules in 137Cs-exposed mouse serum. A total of 67 biomarkers were discovered in some tissues and biofluids of mice exposed to radiation (6\u00a0Gy) (serum and urine). Among these, 3-methylglutarylcarnitine was found to be a unique metabolite seen in the liver, serum, and urine that might be employed as a marker of early radiation response."}
{"_id": "Radiology$$$36a209bc-33c3-42da-ae14-c865db708e31", "text": "Changes in lipid metabolism, including key lipid species such as free fatty acids, glycerolipids, glycerophospholipids, and esterified sterols, have also been observed in nonhuman primates exposed to IR. The results show that diacylglycerides decreased 1\u00a0day after IR, but triacylglycerides and lysophosphatidylcholines increased from 2 to 7\u00a0days after IR. At 7\u00a0days, after 10 Gy irradiation, the amount of polyunsaturated fatty acids, such as arachidonic acid and docosahexaenoic acid, increased significantly in the nonhuman primate model. Between 2 and 3\u00a0days after irradiation, an increase in LysoPCs and a decrease in SMs could be regarded as viable indicators (6.5\u00a0Gy). Compared to nonirradiated controls, recent research in nonhuman primates has discovered plasma-derived exosomal indicators of IR exposure related to the enrichment of N-acyl-amino acids, fatty acid esters of hydroxyl fatty acids, glycolipids, and triglycerides."}
{"_id": "Radiology$$$dd67e4c2-43d4-46ea-9618-f4488e6202dd", "text": "Radiation therapy caused blood lipidome disturbances, which were corrected within 1\u20132\u00a0months after IR treatment, according to lipid species quantification in individuals receiving radiation therapy. As a result, radiation-induced lipidome modifications could indicate changes in early time points and, perhaps, alternative damage pathways. Patients undergoing a complete body irradiation at the MSK Cancer Center (NYC), before hematopoietic stem cell transplantation, showed seven urine indicators with changes between pre- and postexposure at 4\u20136\u00a0h (1.25\u00a0Gy) and 24\u00a0h (three fractions of 1.25 Gy each) postirradiation, which involved trimethyl-l-lysine, acetylcarnitine, decanoylcarnitine, and octanoylcarnitine (carnitine conjugates involved in fatty acid transport), as well as hypoxanthine, xanthine, and uric acid (purine catabolism pathway end products)."}
{"_id": "Radiology$$$bfc63b8c-0f8e-4512-9bb7-760d1e95c734", "text": "During the period 2015\u20132019, the National Cancer Institute\u2019s Radiation Research Program, in partnership with the Small Business Innovation Research Development Center, financed four small firms. This led to the development of a metabolomic/lipidomic assay for predicting late effects that have a negative impact on the quality of life in prostate cancer patients treated with radiation. Shuttle Pharmaceuticals (Rockville, MD) intended to move forward by developing and validating a metabolomic/lipidomic biomarker panel that could predict radiation toxicity. In a phase I experiment, metabolites in plasma from 100 patients were examined in order to develop a kit that could support metabolomic analysis and act as a biomarker panel to predict sensitivity to radiation late effects. A phase II SBIR project was set up for the multi-site analytic validation of the metabolite panel kit created in the phase I SBIR project [235]."}
{"_id": "Radiology$$$15bd20b9-1155-499c-abf6-530f9cf41c46", "text": "Lipidomics has then emerged as a reliable technique for lipid identification and quantification and the search for biomarkers that can be used in radiation-related incidents such as nuclear and radiological hazardous occurrences. In this sense, easily available biofluids are critical, especially in the case of irradiated victims, as well as the use of biodosimetry techniques that are both quick and accurate. Huang et al. [233] discovered seven radiation-responsive lipids in the serum of mice and showed their utility in dose calculation. Lipid changes after whole-body exposures have been thoroughly documented in a variety of animals, including atomic bomb survivors [234]. Indeed, estimating the radiation dose has always been a priority in the medical treatment of these events."}
{"_id": "Radiology$$$f881432e-13f8-49e2-b727-caec4a3da7ef", "text": "Because of the combined effects of neutrons and photons, shielding from structures, and closeness to the epicenter, among other factors, radiation exposures from an IND can be complicated. Using lipidomics, Laiakis et al. [234] evaluated serum samples from mice exposed to varying percentages of neutrons and X-rays to a total dosage of 3 Gy. Several lipids including triacylglycerides, phosphatidylserines, lysophosphatidylethanolamines, lysophosphatidylcholines, sphingolipids, and cholesteryl esters exhibited a delayed increase in mixed exposures, while diacylglycerides declined and phosphatidylcholines (PCs) remained virtually unaltered."}
{"_id": "Radiology$$$bcc885a2-5934-4f2a-86a6-a62d20bedcf6", "text": "The mammalian lipidome\u2019s structural variety is so great that it necessitates a systematic nomenclature for precise categorization (identifying lipid subclasses, or the total number of carbons in the fatty acid chain and the number of double bonds). Because numerous lipid classes showed differences when comparing sham or pre- to post-IR samples, the variable sums and ratios within each metabolite class can increase and must be carefully considered."}
{"_id": "Radiology$$$ff426738-d737-472d-b809-7d24bc8b195c", "text": "Radiation exposure can cause a complex molecular and cellular response having an impact in metabolic processes and consequently change metabolite levels [236]. This approach aims to detect small molecules (<1000\u00a0Da) in biological samples, which occur downstream of genomic, transcriptomic, and proteomic processes, constituting a more complete picture of the system\u2019s response to insult even prior to the onset of clinical symptoms [237]. The first use of metabolomics concerning radiation exposure studies was reported in the 1960s according to the experiences developed in human and animal samples; however, the understanding of cellular and molecular effects of ionizing radiation and the identification of radiation exposure biomarkers remain a challenge [236]. To obtain metabolic information, different methodologies can be used as nuclear magnetic resonance (NMR) or mass spectrometry (MS), including gas chromatography (GC) and liquid chromatography (LC). After sample collection, processing, and data acquisition, data analysis is the second step using principal component analysis (PCA) to have an initial perception about patterns and outliers, and if there are any easily discernible biomarkers. After, complex statistical data analysis should be employed in order to at the end perform biomarkers data interpretation and validation [236]. However, it is important to consider that there exist multiple analytical and clinical challenges that constitute an impediment for the successful translation of these biomarkers for clinical use [237]."}
{"_id": "Radiology$$$b5d5caba-b769-47a5-beab-82d76542f48e", "text": "Despite the few existing studies, some metabolite changes in small-molecule metabolites remain underexplored and underexploited concerning ionizing radiation effects [236]. The role of polyamine metabolism has been studied related to ionizing radiation effects. Present in all cells, polyamines, as putrescine, spermidine, and spermine, are aliphatic polycations with multiple functions related to cell metabolism, cell proliferation, and cell differentiation. These molecules have pleiotropic effects that allow their linkage to DNA, RNA, and proteins, identifying a regulatory role in cell metabolism [236]. Besides this, increased levels of these molecules are reported as healthy cell protectors against oxidative stress. Different studies using animal and patient samples have been performed reporting altered metabolites in response to ionizing radiation, namely creatine, creatinine, carnitine, hypoxanthine, citric acid, taurine, xanthine, threonine, uric acid, and citrulline. Besides these metabolites with high alterations, 2\u2032-deoxyuridine, arginine, glycine, glutamine, hippuric acid, inositol, palmitic acid, uridine, lactic acid, leucine, linoleic acid, methionine, tyrosine, and sebacic acid are described as metabolites with moderate alterations in consequence of ionizing radiation. Therefore, and considering experimental data, among them exist strong candidates for diagnostic biomarkers being considered time- and dose-dependent measures [232]. Data obtained using T cells demonstrated that different metabolic pathways related to amino acid, nucleotide, fatty acid, and glutathione metabolism can be affected by in vivo radiation. Related with cancer and ionizing radiation response, metabolic profiling may help identify metabolites responsible for response to therapy, being the alteration of metabolite production, a feature that can influence tumor microenvironment and consequently cancer progression [237]. The complete characterization of the metabolome can be an opportunity to influence prognostic, predictive, and even pharmacodynamic biomarkers contributing to an individualized and targeted treatment [232]. Notwithstanding the capacity of metabolomics to detect alterations, it is necessary to be aware of the tumor-related responses, namely to the therapy, as inflammation and altered energy metabolism. Besides that, and considering cancer as a syndrome, there are also other cancer-associated conditions such as weight loss that can influence metabolism [238]. Having in consideration that ionizing radiation triggers a complex response influencing molecular and cellular processes and alteration of the metabolic processes and metabolite levels, more research work is necessary to identify biomarkers related to specific type and dose of radiation, genotypic differences, pathological conditions, and specific organs or tissues (Box 3.38)."}
{"_id": "Radiology$$$b5aac0c6-4297-4fd2-9dd6-8f4ba6364d20", "text": "Omics might provide biomarkers of high sensitivity and specificity for radiation research.\n\nOmics can provide a qualitative and quantitative overview of the global perturbations induced by IR in cells and biological fluids.\n\nProteomics provides a comprehensive analytical platform to study the molecular mechanisms of the biological effects of radiation on normal tissues and tumours.\n\nProteomic profiling is used to identify biomarkers of radiation exposure, radiation-induced damage, individual sensitivity, and biodosimetry.\n\nProteome analyses of cancers deliver information on the outcomes of cancer radiotherapy.\n\nMetabolomics is used to detect small molecules (<1000\u00a0Da) in biological samples.\n\nTo obtain metabolic information, different methodologies can be used as nuclear magnetic resonance (NMR) or mass spectrometry (MS).\n\nIonizing radiation triggers a complex response influencing molecular and cellular processes that can be characterized using metabolomics."}
{"_id": "Radiology$$$294fda59-e35a-411c-a22c-e0b8d890c40c", "text": "Omics might provide biomarkers of high sensitivity and specificity for radiation research."}
{"_id": "Radiology$$$393a2b53-3921-458d-9b76-08642c136be3", "text": "Omics can provide a qualitative and quantitative overview of the global perturbations induced by IR in cells and biological fluids."}
{"_id": "Radiology$$$5e57c11c-3cb3-4390-a1e2-7c351c69fa81", "text": "Proteomics provides a comprehensive analytical platform to study the molecular mechanisms of the biological effects of radiation on normal tissues and tumours."}
{"_id": "Radiology$$$d50b9ae3-a5c3-4598-9f47-3de735e278af", "text": "Proteomic profiling is used to identify biomarkers of radiation exposure, radiation-induced damage, individual sensitivity, and biodosimetry."}
{"_id": "Radiology$$$dd0bd5d0-65f9-4690-bfaa-8017c1b87a3f", "text": "Proteome analyses of cancers deliver information on the outcomes of cancer radiotherapy."}
{"_id": "Radiology$$$fc8ca23e-7456-4902-98b2-04441943b79f", "text": "Metabolomics is used to detect small molecules (<1000\u00a0Da) in biological samples."}
{"_id": "Radiology$$$969236f5-2d9c-4ef1-b0e8-26cddbc34ba8", "text": "To obtain metabolic information, different methodologies can be used as nuclear magnetic resonance (NMR) or mass spectrometry (MS)."}
{"_id": "Radiology$$$7fd510f0-7c73-4112-84ea-a4a96f414b59", "text": "Ionizing radiation triggers a complex response influencing molecular and cellular processes that can be characterized using metabolomics."}
{"_id": "Radiology$$$d8c951f0-c662-4064-8398-d7a155fbc2c2", "text": "Molecular signatures provide a composite inventory of radiation-specific responses as changes in the composition of these molecules and their abundance. Transcript levels of signature genes in various tissues, notably blood, saliva, skin, and tumor samples, can discriminate and, in some instances, quantify irradiated from unexposed samples [239]. Expression of coding genes and noncoding miRNAs, and lncRNAs, has been implicated in radiation responses, in some cases, which can be precisely calibrated to dose. For individual genes, e.g., FDXR, alternative splice isoforms have also been demonstrated to arise in a radiation-specific manner."}
{"_id": "Radiology$$$04947553-0d4b-43a4-b9cf-8b7a1fd7a35e", "text": "Transcriptomic approaches to classify radiation response can be based on the evaluation of many known genes, which minimizes technical bias in the selection of optimal combinations of gene subsets. Detection and quantification of ionizing radiation have been based on changes in the expression of a set of genes, primarily in blood from multiple individuals. Generally, signatures selected genes with largest average differences and combined changes in gene expression levels, to predict ionizing radiation exposure in humans and mice [240]. Genes previously implicated or established from genetic evidence and biochemical pathways that are altered in response to these exposures can be used to predict radiation exposure by supervised machine learning (ML) [241] (Fig. 3.51). Termed biochemically inspired ML, diagnostic gene signatures for radiation and chemotherapy have been proven accurate on clinical samples. However, typical sample sizes of typical datasets have limited the effective ML methods for deriving gene signatures.\n\nA flow diagram depicts the gene in models and not in models that enhance or inhibit D N A damage, apoptosis, actin nucleation, keratinocyte differentiation, regulation of proliferation, survival, and differentiation.\n\nFig. 3.51\nGraphical depiction of major cellular functions containing the most frequently appearing genes of the highest performing human signatures adapted with permission (CCBY) from Zhao et al. [241]. Genes common among these signatures (white lettering) are indicated in pathways which contain products that these genes interact with (black lettering)"}
{"_id": "Radiology$$$392cd6e3-d6e1-4a41-8834-274ad2e81861", "text": "A flow diagram depicts the gene in models and not in models that enhance or inhibit D N A damage, apoptosis, actin nucleation, keratinocyte differentiation, regulation of proliferation, survival, and differentiation."}
{"_id": "Radiology$$$7b40e99e-835b-44dd-acad-900f26dc07fa", "text": "To establish the reproducibility of these signatures, radiation exposures are predicted with data from independently exposed individuals. Consistent performance on independent dataset depends on the composition of the genes, how genes are ranked, how they validate the response, and how they account for the amplitude of the radiation response. Other important variables include how well signatures differentiate irradiated from unirradiated samples, or even different levels of absorbed radiation from each, or different radiation qualities (energy levels and source, particle types). Transcriptomics can integrate different genes/transcripts in the induced and repressed biochemical pathways that constitute these responses. There is an enormous range of accurate gene signatures that can be derived in many independently derived datasets. Interestingly, there are some core sets of genes and pathways that are present from different studies."}
{"_id": "Radiology$$$112c7ca0-1fae-42f2-8687-ad310ec99859", "text": "Many radiation response genes were frequently selected for multiple blood signatures, which include genes with roles in DNA damage response (CDKN1A, DDB2, GADD45A, LIG1, PCNA), apoptosis (AEN, CCNG1, LY9, PPM1D, TNFRSF10B), metabolism (FDXR), cell proliferation (PTP4A1), and immune system (LY9 and TRIM22). While biochemical pathways comprising the best performing radiation gene signatures are often shared between human and other species, there are some distinctive differences, notably genes associated with immune cell communication (mice) and redox response (humans)."}
{"_id": "Radiology$$$6c914453-ea70-462b-92f7-c82e3839f408", "text": "Expression of gene combinations that detect radiation exposure can also exhibit similar expression patterns in infectious diseases and other blood disorders [242]. Underlying pathways activated by radiation effects, for example DNA damage response and apoptosis, appear to be activated in some individuals affected with other conditions The genes involved are commonly present in multiple published radiation gene signatures and assays. For example, a 74-gene radiation signature comprised of 16 genes present in the human signatures was developed as reported in Zhao et al. [241], including CDKN1A, DDB2, and PCNA. Misclassification of radiation exposures in unexposed individuals with other blood disorders might be mitigated by reevaluating false-positive predictions with signatures containing radiation-responsive genes explicitly derived from other unrelated biochemical pathways, including those encoding secreted proteins."}
{"_id": "Radiology$$$4ed08efe-0d96-4d09-8de9-3a7664decaa5", "text": "An important factor in the cellular response to radiation is the ability to repair DNA damage. In some individuals, hereditary mutations in genes involved in DNA repair result in a high sensitivity to irradiation [243]. The A-T syndrome is an example of one such mutation and is described in detail below. However, even with intact DNA repair pathways, it turns out that for small doses, cells refrain from the cell cycle arrest that would give time for repair. This results in a much higher cell kill per unit dose for small doses than higher doses, a phenomenon called low-dose hyper-radiosensitivity (HRS). An explanation to the presence of HRS could be that sacrificing a few cells may be advantageous to the risk of misrepair."}
{"_id": "Radiology$$$cb21420c-1964-4128-af7d-f1d5bfd4dca8", "text": "Ataxia-telangiectasia mutated (ATM) is a serine/threonine protein kinase with a key role in repairing double-strand DNA breaks (DSBs) and is also involved in the regulation of oxidative stress, metabolic syndrome, and neurodegeneration, among others reported [244]."}
{"_id": "Radiology$$$7136b6d6-22cd-4829-808f-761633362590", "text": "The human ATM gene is located at 11q22-23, contains 66 exons, covers 160\u00a0kb of genomic DNA, and encodes the 370\u00a0kDa ATM protein. Germline mutation in ATM gene, either loss or inactivation of both copies, leads to the autosomal recessive ataxia-telangiectasia (A-T) syndrome, a devastating childhood condition characterized by chromosomal instability, neurological degeneration, immune dysfunction, premature aging, and high cancer risk. In fact, ATM has a critical role in the activation of the cell cycle progression and checkpoint activation in response to DSBs, as well as in the repair of these lesions through homologous recombination (HR) and nonhomologous end joining (NHEJ) pathway [245]. Thus, these mechanisms need to be active during DNA replication to maintain genome integrity in cells. When disruptions occur in these mechanisms, the cells are more susceptible to damage induced by the exposure to endogenous or exogenous agents, such as radiation exposure. Considering the well-known fact that exposure to IR activates ATM kinases to mediate the cellular response, individuals with these defective mechanisms, like A-T patients, will be more sensitive to the same IR exposure than non-A-T patients. Several published studies have corroborated these hypotheses, showing that failures in cell cycle checkpoints lead to a failure in the arrest in G1/S, S, or G2/M allowing the cells to escape from the proper DSB repair, among other signaling pathways including apoptosis and chromatin remodeling process [243]. Therefore, these non-repaired or misrepaired DBSs are responsible for chromosomal instability also in daughter cells, increasing the radiation sensitivity in these individuals as well as the carcinogenesis risk. It is important to elucidate that this cellular radiosensitivity is not unique for A-T syndrome being also observed in other individuals carrying mutations in other genes related to DNA damage repair and response pathways, namely in FANC, BRCA 1/2, MRE11, and DNA Lig4 genes, among others (Box 3.39)."}
{"_id": "Radiology$$$bc9c2003-10f6-4b03-b29f-c35659b0a002", "text": "Individuals carrying mutations in genes related to DNA damage repair are hypersensitive to radiation.\n\nA-T syndrome is connected to mutations in ATM, which has a critical role in checkpoint activation and DNA damage recognition and repair.\n\nHRS/IRR has been attributed to the early G2 checkpoint, which is only activated at a certain level of phosphorylated ATM."}
{"_id": "Radiology$$$467235ab-bffa-432c-a8fb-fb28bc0d18e9", "text": "Individuals carrying mutations in genes related to DNA damage repair are hypersensitive to radiation."}
{"_id": "Radiology$$$ae5b1cd2-d485-468d-bd3f-9920199fffc6", "text": "A-T syndrome is connected to mutations in ATM, which has a critical role in checkpoint activation and DNA damage recognition and repair."}
{"_id": "Radiology$$$873ef77a-8867-419d-99ea-ad79ee7fcabb", "text": "HRS/IRR has been attributed to the early G2 checkpoint, which is only activated at a certain level of phosphorylated ATM."}
{"_id": "Radiology$$$a898bb70-6426-401e-9ed2-5ea02e7bf471", "text": "As described in Sect. 3.19.1, cells with defects in DNA DSB repair pathways are very sensitive to radiation. However, even repair-competent cell lines can be hypersensitive to radiation within a certain low-dose range. This is called low-dose hyper-radiosensitivity (HRS) and is characterized by a high sensitivity to radiation doses below about 0.5 Gy (depending on the cell line and radiation quality) [246], which is followed by a more radioresistant response per unit dose in the dose range of ~0.5\u20131 Gy. This transition towards radioresistance is described by the term induced radioresistance (IRR) (Fig. 3.52) and occurs at doses corresponding to about ten double-strand breaks.\n\nTwo line graphs of surviving fraction versus dose in gray units plot the falling curves for I R R and H R S. The H R S indicates about 10 D S B per cell on the right graph.\n\nFig. 3.52\nLow-dose hyper-radiosensitivity (HRS) and increased radioresistance (IRR) in T-47D breast cancer cells. The left panel shows a full dose-response curve. The right panel shows the low-dose region. Below about 0.3\u00a0Gy, the cells appear to proceed from G2 to mitosis without repair of DNA damage, leading to a steep decrease in survival with dose. For doses above a threshold around 0.3\u00a0Gy, the damage is repaired increasingly with dose until the surviving fraction follows the linear-quadratic response curve. The transition dose corresponds to approximately 8\u201310 double-strand breaks. The dashed line shows a curve fit by the linear-quadratic model, and the solid line by the induced repair model (see Chap. 4)"}
{"_id": "Radiology$$$59116a08-8bdb-4ffa-a06a-448dc0254f59", "text": "Two line graphs of surviving fraction versus dose in gray units plot the falling curves for I R R and H R S. The H R S indicates about 10 D S B per cell on the right graph."}
{"_id": "Radiology$$$92895934-d162-4073-aa41-5036e46d669c", "text": "HRS [247] was first identified in vitro in 1993 after having been observed in mouse skin in 1986 and in mouse kidney in 1988. HRS has been observed in cells given acute proton and pi-meson irradiation as well as in cells given high-LET neutrons at a low dose rate and appears to be the default response for all radiation qualities in both tumor and normal cell lines. IRR, on the other hand, is only observed after low-LET irradiation and only in repair-competent cell lines [247]."}
{"_id": "Radiology$$$e448fa3f-d314-4212-b5ab-2ee85ea1c356", "text": "In 2003, a mechanism explaining the basis for the HRS effect was proposed [248]. A second radiation-induced G2 checkpoint was discovered to be associated with HRS/IRR [249]. The radiation-induced G2 checkpoint that was known earlier, often denoted the Sinclair checkpoint, does not arrest cells irradiated while in G2, because it takes some time for the checkpoint to be activated. Only cells irradiated while in G1 or S phase are accumulated in G2 by the Sinclair mechanism. The newly discovered G2 checkpoint, also called the early G2 checkpoint, is induced immediately after irradiation and therefore arrests cells that were irradiated while in G2."}
{"_id": "Radiology$$$3d1d017c-fc4d-44f8-a122-d2b308546bdd", "text": "Contrary to the dose-dependent mechanisms by which cells irradiated in G1 or S phase accumulate in the Sinclair checkpoint, the \u201cearly\u201d G2 checkpoint is ATM dependent [249] and independent of dose over the range of 1\u201310 Gy. Activation of the critical damage sensor molecule ATM by an autophosphorylation event at serine 1981 is detectable at doses of 0.1 Gy with a gradual increase until phosphorylation of more than 50% of the ATM molecules in the cell after a dose of about 0.5 Gy and saturated expression at larger doses. Thus, the HRS/IRR transition appears to be coincident with both the induction of the early G2-phase checkpoint and activation of ATM."}
{"_id": "Radiology$$$a944c001-0162-4688-a005-19f697720c15", "text": "The hyper-radiosensitivity is thus a result of the progress into mitosis with repairable but unrepaired DNA damages for cells that were irradiated while in G2 but received doses below the threshold for checkpoint activation (see Fig. 3.53).\n\nA flowchart starts with 0 to 1 gray that leads to dose-dependent activation of A T M and is divided into 2 paths. Path 1 includes 0 to 0.3 gray, no arrest, mitosis with unrepaired damage, cell death, H R S. Path 2 includes 0.3 to 1 gray, early G 2 arrest, repair before mitosis, cell survival, I R R.\n\nFig. 3.53\nPath to \u201cincreased radioresistance\u201d or \u201chyper-radiosensitivity.\u201d Cells irradiated with doses below about 0.3 Gy while in G2 will not have enough ATM activated by serine 1981-phosphorylation to reach the threshold level for activation of the early G2 checkpoint. They therefore follow the alternative in the left column, which does not give extra time for repair before mitosis resulting in \u201chyper-radiosensitivity\u201d (HRS). Cells irradiated with doses above 0.3 Gy while in G2 follow the alternative in the right column and thereby are given more time for repair before mitosis resulting in \u201cincreased radioresistance\u201d (IRR)"}
{"_id": "Radiology$$$cbcc6765-b10c-4d95-bad2-75418f8cfbe0", "text": "A flowchart starts with 0 to 1 gray that leads to dose-dependent activation of A T M and is divided into 2 paths. Path 1 includes 0 to 0.3 gray, no arrest, mitosis with unrepaired damage, cell death, H R S. Path 2 includes 0.3 to 1 gray, early G 2 arrest, repair before mitosis, cell survival, I R R."}
{"_id": "Radiology$$$47ff8cb9-7f67-454d-a252-977ff20b681a", "text": "It has been demonstrated that HRS-negative cell lines have the same ATM activation pattern as cells with HRS, whereas they show an early G2 arrest even after low radiation doses that produce insufficient damage to induce full ATM activation. It has therefore been suggested that the dose-dependent ATM regulatory control is evaded by aberrant early G2-checkpoint response in HRS-negative cell lines caused by dissociation between ATM activity and early G2-checkpoint function [250]."}
{"_id": "Radiology$$$b22c72cd-7ee7-483d-ad84-24817ac4fdf8", "text": "The existence of HRS appears in some cell lines to be associated with an elevated level of caspase-3-mediated apoptosis after low-dose exposures [250], suggesting that the radiation-damaged G2-phase cells that evade the early G2 checkpoint are disposed of by this mechanism when entering mitosis. However, also cell lines deficient in TP53 induction after irradiation or with mutated TP53 have been shown to display HRS/IRR, and no increase in apoptosis in response to HRS-inducing doses was observed in BMG-1 cells with wild-type TP53. In addition, no connection between HRS and apoptosis in the six HRS-competent cell lines investigated measured by DNA-PKcs as early apoptosis marker was found. This corroborates the hypothesis that the transition from HRS to IRR primarily is related to induction of the \u201cearly\u201d G2 checkpoint and that the death process of the cells entering mitosis with damages is cell line dependent."}
{"_id": "Radiology$$$3082a4dd-6d73-4e89-b549-17e91874658d", "text": "Early G2-checkpoint activation as the underlying mechanism for HRS/IRR is supported by priming experiments where a dose of 0.2\u20130.5 Gy removes the HRS response to subsequent irradiation given within 6\u20138\u00a0h after the priming. This timing corresponds to the duration of the early G2-checkpoint activation. Surprisingly, the HRS/IRR response can be permanently eliminated by priming irradiation if it is given with a low dose rate of 0.1\u20130.3\u00a0Gy/h for 1\u00a0h (shown in T98G glioblastoma and T-47D breast cancer cells). The low dose rate primed cells activated the early G2 checkpoint for all doses. The response was shown to involve transforming growth factor beta 3 (TGF-\u03b23) and inducible nitric oxide synthase (iNOS) activation. The HRS phenotype could be reinstated by inhibition of iNOS [251]."}
{"_id": "Radiology$$$ef4cd04a-f733-4bf8-94d1-05d596ecb3d6", "text": "It has been suggested that HRS is a protective mechanism and that it is advantageous to sacrifice a small fraction of cells rather than risking the development of genomic instability and mutations. While cells without the IRR are deficient in DNA repair or checkpoint activation, cells without HRS may have been \u201cturned off\u201d by mechanisms similar to the ones induced by low dose rate priming (Box 3.40)."}
{"_id": "Radiology$$$b61fb1de-a0c0-4e4e-a5b7-09935c254295", "text": "Cells with HRS are very sensitive to doses below about 0.5 Gy.\n\nAbove 0.5\u00a0Gy, the survival per dose increases until it reaches the LQ curve.\n\nHRS/IRR has been attributed to the early G2 checkpoint, which is only activated at a certain level of phosphorylated ATM."}
{"_id": "Radiology$$$e0185d6c-c2f5-4d6f-859b-3ff41d1a915f", "text": "Cells with HRS are very sensitive to doses below about 0.5 Gy."}
{"_id": "Radiology$$$4d88ac91-d9cc-460a-9737-bcf58be3cc8e", "text": "Above 0.5\u00a0Gy, the survival per dose increases until it reaches the LQ curve."}
{"_id": "Radiology$$$bfa20790-261c-4135-bfea-4f03fc370b2c", "text": "As described in Chap. 2, irradiated (donor) cells can secrete signals which, when transferred to unirradiated (reporter) cells, make these respond as if they had been irradiated themselves. This is called the bystander effect. For a while, it was believed that HRS and cell kill by the bystander effect were mutually exclusive, but when doses in the HRS dose range were tested on HRS-proficient cells, these were able to induce strong bystander signals. However, when doses reached the level where IRR was dominating, there was no bystander signaling."}
{"_id": "Radiology$$$4bf5b3cc-2a74-4e3d-b317-e354f6a5b9e7", "text": "Bystander signals may also be protective. Transfer of medium from HRS-deficient HaCaT normal human epithelial cells to HRS-proficient T98G glioblastoma cells increased the survival above the normal plating efficiency for these cells [252]. In addition to the effect on cell survival, bystander signals can also moderate the HRS/IRR response to subsequent irradiation. Medium transferred from cells, in which the HRS/IRR response was permanently eliminated by priming with 0.1\u20130.3 Gy for 1\u00a0h, has been seen to remove the HRS response in recipient cells for 8\u201312\u00a0h [251] (Box 3.41)."}
{"_id": "Radiology$$$b7801962-210e-47d5-88d0-d02d3bd9dc7c", "text": "HRS-proficient cells irradiated with doses in the HRS range produce bystander signals that reduce the survival of reporter cells.\n\nHRS-proficient cells, in which the HRS response has been removed by low dose rate priming, produce bystander signals that remove the HRS response to subsequent irradiation in recipient cells."}
{"_id": "Radiology$$$d5d3817e-f8b7-4a37-bc64-c47b359aa209", "text": "HRS-proficient cells irradiated with doses in the HRS range produce bystander signals that reduce the survival of reporter cells."}
{"_id": "Radiology$$$3091c409-bdb4-4cc3-8a0d-5516da489eab", "text": "HRS-proficient cells, in which the HRS response has been removed by low dose rate priming, produce bystander signals that remove the HRS response to subsequent irradiation in recipient cells."}
{"_id": "Radiology$$$6a7e9988-f200-4a1d-8ede-941588662645", "text": "The presence of HRS may have implications for cancer radiotherapy in which the aim is to control the eradication of tumor tissue while minimizing the damage to normal tissue. The introduction of intensity-modulated radiation therapy (IMRT) in cancer treatment results in irradiation of a larger proportion of normal tissue but at lower doses when compared to conventional treatment. In some situations, one could fear that HRS will tend to increase the effect of low doses in normal tissue and thus negate the benefits of using IMRT, in particular in tissues with a pronounced volume effect [253]."}
{"_id": "Radiology$$$3e0009df-3d5c-4705-a61e-e172a20ed755", "text": "Since HRS is related to the fraction of cells in G2 phase, it may be of more consequence for early-responding proliferating tissues, such as skin, than for slowly proliferating normal tissues with a small fraction of cells in G2. In support, evidence of HRS has been demonstrated in studies with human skin using basal cell density or skin erythema as endpoint. On the other hand, with the HRS effect being more pronounced in fast-dividing tumor cells than slowly or nondividing normal tissues, it may be possible to exploit HRS clinically using dose fractions within the HRS dose range. However, to obtain the same cell kill as with 2 Gy fractions, more fractions are needed. Increasing treatment time would give the tumor more time to grow; therefore, the time between fractions has to be decreased, but that could be a problem: Experiments with ultrafractionation of 0.4 Gy per fraction, three fractions per day in murine DDL1 lymphoma or in human A7 glioblastoma xenografts, did not show evidence of HRS. This could be because with three fractions per day, the timing between fractions would have been too short for the cell to be released from the early G2-checkpoint arrest induced by the previous dose. Since HRS affects cells in G2, another approach is to synchronize the cells to improve the therapeutic potential of ultrafractionation. A protocol using a taxane (paclitaxel), which synchronizes cells in G2 phase, in combination with carboplatin and low-dose fractionated radiation, was extremely well tolerated by the patients and showed a synergistic effect in patients with squamous cell cancer of the head and neck [254] (Box 3.42)."}
{"_id": "Radiology$$$8eb26d6f-72c2-4337-ad76-77b19a48150f", "text": "Attempts to exploit HRS in the clinic using hyperfractionation have not been successful.\n\nCombination of low radiation doses with chemotherapeutics synchronizing cells in G2 phase has shown promise."}
{"_id": "Radiology$$$49c92572-9e0d-442b-9257-98c408239ed8", "text": "Attempts to exploit HRS in the clinic using hyperfractionation have not been successful."}
{"_id": "Radiology$$$191fdd1e-eef1-4fd3-b455-7caef6f7ffcb", "text": "Combination of low radiation doses with chemotherapeutics synchronizing cells in G2 phase has shown promise."}
{"_id": "Radiology$$$a8df02c8-c770-44ee-8951-f07475da0d16", "text": "By the term radiation resistance, we refer to the inherent ability of specific types of cells and tissues (usually of malignant origin) to show a differential response to ionizing radiation overcoming its damaging effects like cell killing or inactivation. The amount of energy (for example level of dose in Gy) and consecutive damage that each organism can withstand is a characteristic of the organism\u2019s ability to respond to radiation by a variety of mechanisms often called as DNA damage response (DDR) mechanisms. At the organism level, usually humans are more sensitive compared to other primates or mammals. In nature, there is a great variety of resistance to radiation with the extreme case of certain extremophiles, such as the bacteria Deinococcus radiodurans and the tardigrades, to be able to withstand large doses of ionizing radiation on the order of 5000 Gy. Although none of the strategies discussed in various studies on extreme radioresistance appear to be universal against ionizing radiation, a general trend was found. There are two cellular mechanisms by which radioresistance is accomplished: (a) protection of the proteome and DNA from damage by scavenging and regeneration strategies and (b) recruitment of advanced and highly sophisticated DNA repair mechanisms, in order to reconstruct a fully functional genome [255]."}
{"_id": "Radiology$$$cbab7e14-1436-419c-b898-6ef44b86ec9d", "text": "While normal (nonmalignant) mammalian cells compared to tumor ones are usually less radioresistant, one cannot exclude the opposite possibility. Elucidation of the molecular mechanisms and pathways related to radioresistance of tumor cells is of major importance in order to develop strategies maximizing tumor control during chemo- or radiation therapies. Many studies using a wide range of in\u00a0vitro, ex\u00a0vivo, and in\u00a0vivo models as well as bioinformatics have fingerprinted the main pathways leading to cellular radioresistance, and these are primarily implicated in DNA damage repair, oxidative stress, cell pro-survival, hypoxia, cell cycle control, and apoptotic pathways [231]."}
{"_id": "Radiology$$$77652acd-06d1-49a8-ba4e-a7f77df22bc4", "text": "Another important factor contributing to resistance of tumors is the existence of cancer stem cells (CSCs) as a distinct subpopulation within a tumor. CSCs are able to self-renew and differentiate while showing a high proficiency to repair DNA damage, reveal low levels of reactive oxygen species (ROS), and proliferate at a slower rate compared to other tumor cell populations. These features render CSCs resistant to various therapies, including radiation therapy (RT) [256]. The results of such studies can serve as potential diagnostic/prognostic markers of cancer cell resistance to radiation treatment, as well as for therapy outcome and increase of cancer patient survival."}
{"_id": "Radiology$$$7c3992f0-c37f-46a7-94ac-fedd4caff08e", "text": "The radiation-induced adaptive response was first described by Olivieri et al. in 1984 [257] as the reduced sensitivity to a challenge irradiation induced by a previous small priming dose. Radio-adaptive responses have been observed in vitro and in vivo using various endpoints, such as cell lethality, chromosomal aberrations, mutation induction, radiosensitivity, and DNA repair [258]. Adaptation is most efficiently induced by doses of 0.01\u20130.5 Gy at dose rates from 0.01 to 1.0\u00a0Gy/min (Tapio und Jacob 2007) with challenge doses in the range of 0.5\u20132 Gy. The protective effect has been reported to last for about three generations following the priming irradiation. The molecular mechanisms underlying the adaptive response are not well understood, but data indicate involvement of DNA damage repair, antioxidant production (NRF2 pathway), NF-\u03baB inflammatory pathway, MAPK pathway, autophagy, cell cycle regulation, apoptosis, and bystander signaling [258] (Box 3.43)."}
{"_id": "Radiology$$$5b320409-c238-4b8c-92a7-0ab61f5db22d", "text": "Cellular radioresistance can be modulated either through protection against DNA damage or through DNA repair.\n\nPre-exposure to a low dose can induce protection against a subsequent high dose."}
{"_id": "Radiology$$$58ebf574-0c13-42d3-8c1d-4d1c86477614", "text": "Cellular radioresistance can be modulated either through protection against DNA damage or through DNA repair."}
{"_id": "Radiology$$$9757f70e-0998-46a3-b847-416c5155f73a", "text": "Pre-exposure to a low dose can induce protection against a subsequent high dose."}
{"_id": "Radiology$$$1f7c3d06-04e6-4eb3-8332-67097551322f", "text": "The continuous advances and improvements in anticancer therapies using IR has significantly increased the treatment efficacy and quality. However, radioresistance is still one of the major problems of radiation oncology, since it leads to tumor locoregional recurrence and disease progression. One plausible cause of tumor radioresistance is the failure of the current treatments in eradicating a subpopulation of cells intrinsically more resistant to multiples therapies, the cancer stem cells (CSCs). The biological characteristics and radioresistance mechanisms of CSCs are shown in Table 3.16. Targeting CSCs and controlling their behavior is an approach to overcome radioresistance and to improve on the efficacy of cancer treatments (Box 3.44).Table 3.16\nBiological characteristics and radioresistance mechanisms of cancer stem cells\n\nBiological characteristics\n\nRadioresistance mechanisms\n\nAre long-lived and have tumorigenic abilities\n\nTo activate pro-survival pathways\n\nAre able to proliferate, maintain their growth indefinitely\n\nTo improve DNA repair ability through the activation of DNA damage checkpoint proteins, such as ATM, Chk1, Chk2, SMC1, and TP53\n\nDifferentiate, generating different cell populations inside the tumor\n\nTo defend against oxidative stress, since CSCs present lower levels of ROS and overexpress ROS scavengers that protect them from ROS produced in response to radiation\n\nHave long-term repopulation potential\n\nTo indefinitely self-renew, through the activation of cell signaling pathways, such as Wnt/\u03b2-catenin, notch, TGF-\u03b2, and PI3K/AKT/mTOR\n\nHave a flexible phenotype (plasticity), since a conversion of a CSC into a non-CSC phenotype can be reversed, a process highly dependent on the epithelial-mesenchymal transition (EMT)\n\nTo overcome the cell cycle control by the abnormal expression of cell cycle-related proteins\n\nCan adapt to the tumor microenvironment\n\nTo inhibit cell death pathways after radiation exposure, through the upregulation of anti-apoptotic proteins (like BCL-2 and survivin) and the inhibition of autophagy-related proteins (like Beclin-1 and ATG-5)"}
{"_id": "Radiology$$$e9dad3c1-cb14-4278-bf77-d81406b46da4", "text": "Cancer stem cells are a radioresistant tumor subpopulation due to high DNA repair proficiency, low ROS generation and high ROS scavenging, and slow proliferation (giving time for repair)."}
{"_id": "Radiology$$$0d01cf90-f587-4d91-9dc8-206926c3aea1", "text": "Hypoxia refers to conditions with low oxygen. Hypoxia induces radiation resistance by preventing the sensitizing effect of the presence of oxygen during or within microseconds of radiation exposure. Oxygen has high affinity for electrons. It may therefore react with radiation-damaged biomolecules as well as with radiation-induced water radicals (see Chap. 1)."}
{"_id": "Radiology$$$902044a9-a6bf-4fab-bfd4-497375c48147", "text": "Radiation creates radicals either directly in a biomolecule (e.g., DNA) or indirectly through water radicals: MH\u00a0+\u00a0radiation \u2192 M\u00b0\u00a0+\u00a0H\u00b0, where MH is an intact biomolecule while M\u00b0 is the radical after loss of one hydrogen atom. Oxygen can sensitize by a direct interference with the primary radiation process. This can take place because deposit of radiation energy not always completes the dissociation. Often, the large biomolecule is just polarized as follows: MH\u00a0+\u00a0radiation \u2192+MH\u2212"}
{"_id": "Radiology$$$bc580f30-0061-41a2-8d4e-dc22af4d30da", "text": "This process is however reversible. Thus, a spontaneous restitution can take place by the electron falling back to its normal position in the molecule and losing the excitation energy. Due to its great affinity for electrons, oxygen may however \u201csteal\u201d the excited electron before it gives away the excitation energy:"}
{"_id": "Radiology$$$052d69e4-d125-4b3e-a15f-80d19a4a293d", "text": "By this process, oxygen creates a biomolecule radical after the following dissociation:"}
{"_id": "Radiology$$$c7c9cdb4-37b3-4b30-a4f8-7b0a795543d3", "text": "Due to its great affinity for electrons, oxygen will easily react with both radiation-damaged biomolecules and radiation-induced water radicals. When oxygen reacts with the biomolecule radical, it forms a stable bond as follows:"}
{"_id": "Radiology$$$a3db4193-2f66-48cf-9d56-415ad437475b", "text": "Thereby, oxygen fixates the damage and prevents restitution by hydrogen donors (antioxidants), which is a natural protective means of the cells:"}
{"_id": "Radiology$$$65edde23-c890-4557-a28e-4e214dea125f", "text": "where RSH represents hydrogen donors, of which glutathione is one example."}
{"_id": "Radiology$$$336ed57c-5d2f-440c-aa22-05fdfc008205", "text": "In cells, the concentration of SH compounds is normally high, and they represent a fundamental protective means against harmful radicals if not outcompeted by oxygen. Hypoxia thus protects against radiation damage through restitution by hydrogen donors because oxygen is not present to outcompete restitution and fixate the damage (Box 3.45)."}
{"_id": "Radiology$$$0e36d416-9742-4515-b2b8-5ee656b4025c", "text": "Hypoxia induces radioresistance by preventing the radiosensitizing effect of oxygen.\n\nOxygen radiosensitizes by fixating DNA damage and thus preventing restitution by hydrogen donors.\n\nOxygen can also increase the amount of radicals through the direct effect."}
{"_id": "Radiology$$$8ebab014-2144-42c4-bcc6-78d313e6c732", "text": "Oxygen radiosensitizes by fixating DNA damage and thus preventing restitution by hydrogen donors."}
{"_id": "Radiology$$$64e0764b-c15d-4e50-9616-37cf22c6d6c5", "text": "Oxygen can also increase the amount of radicals through the direct effect."}
{"_id": "Radiology$$$b726e7c2-d1c4-4d2e-81ac-fa17404c7ec0", "text": "Q1.\nWhich of the following effects of IR produce free radicals within the cell, which can damage the cellular macromolecules?(a)\nDouble ionization\n\u00a0(b)\nDirect action\n\u00a0(c)\nIndirect action\n\u00a0(d)\nSingle ionization\n\u00a0\n\u00a0Q2.\nWhat are the most significant differences between the two repair patterns of the base excision repair (BER) repair mechanism?\n\u00a0Q3.\nWhich repair pathway provides a \u201cbackup\u201d to the replicative proofreading carried out by most (but not all) DNA polymerases during DNA replication?(a)\nBase excision repair\n\u00a0(b)\nNucleotide excision repair\n\u00a0(c)\nNonhomologous end joining\n\u00a0(d)\nMismatch repair\n\u00a0\n\u00a0Q4.\nCompare the two principal DNA DSB pathways. What is similar and what is different in these?\n\u00a0Q5.\nComplex translocation to some extent depends on the radiation quality. Please indicate when they most often occur. Complex translocation types are characteristic especially for cellular exposure to:(a)\nLow-LET radiation\n\u00a0(b)\nHigh-LET radiation\n\u00a0(c)\nPhotonic radiation\n\u00a0(d)\nLET of radiation has no effect on the character of chromosomal translocation\n\u00a0\n\u00a0Q6.\nPick one incorrect statement for completing the sentence \u201cThe superoxide anion is \u2026\u201d(a)\nProduced by mitochondria\n\u00a0(b)\nA free radical reactive oxygen species\n\u00a0(c)\nConverted to water by superoxide dismutase\n\u00a0(d)\nAble to react with hydrogen peroxide producing hydroxyl radicals\n\u00a0(e)\nLess lipid soluble than hydrogen peroxide\n\u00a0\n\u00a0Q7.\nFor cell transition in the cell cycle, in which phase do the CDK1/cyclin B complex plays a significant role?(a)\nG2 into M\n\u00a0(b)\nG1 into S\n\u00a0(c)\nS into G2\n\u00a0(d)\nG0 into G1\n\u00a0(e)\nM into G1\n\u00a0\n\u00a0Q8.\nWhat will the cycling cells do when They get a \u201cgo-ahead\u201d indication at the checkpoint?(a)\nDirectly progress into the telophase\n\u00a0(b)\nFinish the cell cycle and finally divide\n\u00a0(c)\nLeave the cell cycle and modify to a nondividing state\n\u00a0(d)\nDemonstrate a fall in M phase-promoting factor\n\u00a0(e)\nFinish cytokinesis and generate new cell membranes\n\u00a0\n\u00a0Q9.\nWhich is the most radiosensitive cell cycle phase, and which is the most resistant one?\n\u00a0Q10.\nWhy is immortalization so important for cancer cells?\n\u00a0Q11.\nCells may execute cell death in different ways in response to IR. Please discuss the factors that may influence the pathway elicited.\n\u00a0Q12.\nWhat is the main reason for activation of cell death in response to IR in solid tumor cells?(a)\nDNA damage-induced apoptosis\n\u00a0(b)\nInitiation of senescence as a result of DNA damage\n\u00a0(c)\nMitotic catastrophe following improper segregation of genetic material\n\u00a0(d)\nOxidation-triggered damage to proteins\n\u00a0(e)\nGeneration of ceramide at the plasma membrane via sphingomyelinase\n\u00a0\n\u00a0Q13.\nWhich of the following pathways has been implicated in cellular response to IR:(a)\nAutophagy\n\u00a0(b)\nApoptosis\n\u00a0(c)\nNecrosis\n\u00a0(d)\nMitotic catastrophe\n\u00a0(e)\nAll of a\u2013d\n\u00a0\n\u00a0Q14.\nApoptosis can proceed by two main routes, intrinsic and extrinsic signaling. Describe the initial triggers for these two pathways and how they lead to apoptosis.\n\u00a0Q15.\nCite the different steps of the autophagy process.\n\u00a0Q16.\nConsidering that 800 colonies have grown at 0 Gy for 1200 cells seeded, and that 126 colonies are counted at 2 Gy for 2000 cells seeded, which of the following statements are correct?(a)\nThe plating efficiency at 0 Gy is 66.6%.\n\u00a0(b)\nThe plating efficiency at 2 Gy is 6.4%.\n\u00a0(c)\nThe plating efficiency at 2 Gy is 9.5%.\n\u00a0(d)\nThe surviving fraction at 2 Gy is 9.5%.\n\u00a0(e)\nThe surviving fraction at 1 Gy is 100%.\n\u00a0\n\u00a0Q17.\nWhich alteration is more likely to lead to the death of an embryo? Alteration of the function of an oncogene or a tumor suppressor gene?\n\u00a0Q18.\nWhich cells are mainly involved in inflammation and modulated by low to medium doses of IR?\n\u00a0Q19.\nAre the following statements regarding epigenetic DNA alterations true or false?(a)\n5-Methylcytosine is a common DNA modification.\n\u00a0(b)\nDNA methylation is equally common in all four nucleotides.\n\u00a0(c)\nHistone variants are only synthesized during S phase.\n\u00a0(d)\nThe amino acid lysine in a histone protein is a target for acetylation.\n\u00a0\n\u00a0Q20.\nIs this statement true?\n\u00a0(a)\nOne miRNA regulates only one mRNA target.\n\u00a0Q21.\nIs the following statement true or false: ARS involves a total dose of over 0.7 Gy (70\u00a0rad) from an external source, administered in a few minutes.\n\u00a0Q22.\nIs the following statement true or false: PTEN is a central positive regulator of the PI3-K/AKT pathway.\n\u00a0Q23.\nWhich of the following statements are correct about lncRNAs?(a)\nlncRNAs are translated into regulatory proteins.\n\u00a0(b)\nlncRNAs are short RNA transcripts of around 20 nucleotides.\n\u00a0(c)\nlncRNAs can interact with other RNA subtypes to regulate gene expression.\n\u00a0\n\u00a0Q24.\nWhich of the following statements are correct about extracellular vesicles?(a)\nExtracellular vesicles have a size range of 40 nm to several \u03bcm.\n\u00a0(b)\nExtracellular vesicles cargo only proteins.\n\u00a0(c)\nExtracellular vesicles can indicate cell death.\n\u00a0(d)\nExtracellular vesicles are only formed by cells and tissue undergoing cell death.\n\u00a0(e)\nRadiation effects on cells and tissue only generate extracellular vesicles to protect against radiation-induced cell death.\n\u00a0\n\u00a0Q25.\nIn the field of lipidomics or metabolomics, what is the accurate method to achieve the comprehensive metabolite of a sample using LC-MS/MS?(a)\nMRM method\n\u00a0(b)\nPCR methods\n\u00a0(c)\nElisa methos\n\u00a0(d)\nDicentric assay\n\u00a0\n\u00a0Q26.\nWhat happens to cells irradiated while in G2 with (a) 0.1 Gy and (b) 1Gy?\n\u00a0Q27.\nWhat is the challenge when exploiting HRS in radiotherapy?\n\u00a0Q28.\nWhat is the radiation adaptive response?\n\u00a0Q29.\nPlease refer two mechanisms responsible for the increased radioresistance of cancer stem cells.\n\u00a0Q30.\nExplain why hypoxic cells are more radioresistant than oxygenated cells."}
{"_id": "Radiology$$$e8696122-6c8a-4ef6-974d-932f0f0eeb64", "text": "Which of the following effects of IR produce free radicals within the cell, which can damage the cellular macromolecules?(a)\nDouble ionization\n\u00a0(b)\nDirect action\n\u00a0(c)\nIndirect action\n\u00a0(d)\nSingle ionization"}
{"_id": "Radiology$$$1c190f8f-305f-4003-bc22-63eb9a8a1cbe", "text": "What are the most significant differences between the two repair patterns of the base excision repair (BER) repair mechanism?"}
{"_id": "Radiology$$$22d449d8-aecd-491a-9b19-95674457d37e", "text": "Which repair pathway provides a \u201cbackup\u201d to the replicative proofreading carried out by most (but not all) DNA polymerases during DNA replication?(a)\nBase excision repair\n\u00a0(b)\nNucleotide excision repair\n\u00a0(c)\nNonhomologous end joining\n\u00a0(d)\nMismatch repair"}
{"_id": "Radiology$$$72d6a1fc-23df-40ff-998c-57114b5186b2", "text": "Compare the two principal DNA DSB pathways. What is similar and what is different in these?"}
{"_id": "Radiology$$$3ae426f2-06d7-4b8a-9e4c-26054e7e0fda", "text": "Complex translocation to some extent depends on the radiation quality. Please indicate when they most often occur. Complex translocation types are characteristic especially for cellular exposure to:(a)\nLow-LET radiation\n\u00a0(b)\nHigh-LET radiation\n\u00a0(c)\nPhotonic radiation\n\u00a0(d)\nLET of radiation has no effect on the character of chromosomal translocation"}
{"_id": "Radiology$$$f6444f4e-7ef8-4fa0-bd7a-6d73574bba02", "text": "LET of radiation has no effect on the character of chromosomal translocation"}
{"_id": "Radiology$$$f031b1ec-d363-4287-8805-3c2b99a25544", "text": "Pick one incorrect statement for completing the sentence \u201cThe superoxide anion is \u2026\u201d(a)\nProduced by mitochondria\n\u00a0(b)\nA free radical reactive oxygen species\n\u00a0(c)\nConverted to water by superoxide dismutase\n\u00a0(d)\nAble to react with hydrogen peroxide producing hydroxyl radicals\n\u00a0(e)\nLess lipid soluble than hydrogen peroxide"}
{"_id": "Radiology$$$6cc985ce-2834-42ed-9e3b-7223f3ecb5b1", "text": "For cell transition in the cell cycle, in which phase do the CDK1/cyclin B complex plays a significant role?(a)\nG2 into M\n\u00a0(b)\nG1 into S\n\u00a0(c)\nS into G2\n\u00a0(d)\nG0 into G1\n\u00a0(e)\nM into G1"}
{"_id": "Radiology$$$d19accac-3182-4e95-a9b5-1cc273dd0abc", "text": "What will the cycling cells do when They get a \u201cgo-ahead\u201d indication at the checkpoint?(a)\nDirectly progress into the telophase\n\u00a0(b)\nFinish the cell cycle and finally divide\n\u00a0(c)\nLeave the cell cycle and modify to a nondividing state\n\u00a0(d)\nDemonstrate a fall in M phase-promoting factor\n\u00a0(e)\nFinish cytokinesis and generate new cell membranes"}
{"_id": "Radiology$$$767af267-70c7-4985-8ceb-bd11bf70f93f", "text": "Which is the most radiosensitive cell cycle phase, and which is the most resistant one?"}
{"_id": "Radiology$$$f8a3528a-63b1-4141-8aae-6031f531bfbc", "text": "Cells may execute cell death in different ways in response to IR. Please discuss the factors that may influence the pathway elicited."}
{"_id": "Radiology$$$6a904a87-c011-4db2-8881-0ec57b00c946", "text": "What is the main reason for activation of cell death in response to IR in solid tumor cells?(a)\nDNA damage-induced apoptosis\n\u00a0(b)\nInitiation of senescence as a result of DNA damage\n\u00a0(c)\nMitotic catastrophe following improper segregation of genetic material\n\u00a0(d)\nOxidation-triggered damage to proteins\n\u00a0(e)\nGeneration of ceramide at the plasma membrane via sphingomyelinase"}
{"_id": "Radiology$$$2c99aa2d-3356-46fb-ad46-71f4c0e64f49", "text": "Which of the following pathways has been implicated in cellular response to IR:(a)\nAutophagy\n\u00a0(b)\nApoptosis\n\u00a0(c)\nNecrosis\n\u00a0(d)\nMitotic catastrophe\n\u00a0(e)\nAll of a\u2013d"}
{"_id": "Radiology$$$05d373c1-5e55-4b58-b9ce-08f1ff962824", "text": "Apoptosis can proceed by two main routes, intrinsic and extrinsic signaling. Describe the initial triggers for these two pathways and how they lead to apoptosis."}
{"_id": "Radiology$$$2a348a0b-a4bf-457c-862b-9995b6d4e31b", "text": "Considering that 800 colonies have grown at 0 Gy for 1200 cells seeded, and that 126 colonies are counted at 2 Gy for 2000 cells seeded, which of the following statements are correct?(a)\nThe plating efficiency at 0 Gy is 66.6%.\n\u00a0(b)\nThe plating efficiency at 2 Gy is 6.4%.\n\u00a0(c)\nThe plating efficiency at 2 Gy is 9.5%.\n\u00a0(d)\nThe surviving fraction at 2 Gy is 9.5%.\n\u00a0(e)\nThe surviving fraction at 1 Gy is 100%."}
{"_id": "Radiology$$$aa114536-13ef-4a80-aa35-a9f8edfc4187", "text": "The plating efficiency at 0 Gy is 66.6%."}
{"_id": "Radiology$$$ff02adb4-1d4f-494a-8731-5b8a9d8281a5", "text": "The plating efficiency at 2 Gy is 6.4%."}
{"_id": "Radiology$$$38345424-ffbb-453c-9301-9ee2cd2caef0", "text": "The plating efficiency at 2 Gy is 9.5%."}
{"_id": "Radiology$$$f6d63870-a7b1-4a28-86ba-6991febe1d9f", "text": "The surviving fraction at 2 Gy is 9.5%."}
{"_id": "Radiology$$$6dc9c9b4-7439-41fd-a755-a8ec96d84c5a", "text": "Which alteration is more likely to lead to the death of an embryo? Alteration of the function of an oncogene or a tumor suppressor gene?"}
{"_id": "Radiology$$$131a5a12-74f3-47ce-98fc-9127678bb36e", "text": "Which cells are mainly involved in inflammation and modulated by low to medium doses of IR?"}
{"_id": "Radiology$$$32b5d8eb-f871-4f4a-aeb7-128a1b09f04d", "text": "Are the following statements regarding epigenetic DNA alterations true or false?(a)\n5-Methylcytosine is a common DNA modification.\n\u00a0(b)\nDNA methylation is equally common in all four nucleotides.\n\u00a0(c)\nHistone variants are only synthesized during S phase.\n\u00a0(d)\nThe amino acid lysine in a histone protein is a target for acetylation."}
{"_id": "Radiology$$$d278dd0f-d72c-4134-a69d-83bbdf920f98", "text": "The amino acid lysine in a histone protein is a target for acetylation."}
{"_id": "Radiology$$$8ae718b1-1424-4510-a1ae-2b255b2a5274", "text": "Is the following statement true or false: ARS involves a total dose of over 0.7 Gy (70\u00a0rad) from an external source, administered in a few minutes."}
{"_id": "Radiology$$$eb05cf7e-2c1a-4efb-8fdf-513b1c392627", "text": "Is the following statement true or false: PTEN is a central positive regulator of the PI3-K/AKT pathway."}
{"_id": "Radiology$$$2e7aa333-a875-4ed0-a044-b70d11b1d95d", "text": "Which of the following statements are correct about lncRNAs?(a)\nlncRNAs are translated into regulatory proteins.\n\u00a0(b)\nlncRNAs are short RNA transcripts of around 20 nucleotides.\n\u00a0(c)\nlncRNAs can interact with other RNA subtypes to regulate gene expression."}
{"_id": "Radiology$$$58eb4d12-ce9b-43e5-bd34-2951264302da", "text": "lncRNAs can interact with other RNA subtypes to regulate gene expression."}
{"_id": "Radiology$$$aefdba03-f8ba-49c0-8a9e-7701ab5dee61", "text": "Which of the following statements are correct about extracellular vesicles?(a)\nExtracellular vesicles have a size range of 40 nm to several \u03bcm.\n\u00a0(b)\nExtracellular vesicles cargo only proteins.\n\u00a0(c)\nExtracellular vesicles can indicate cell death.\n\u00a0(d)\nExtracellular vesicles are only formed by cells and tissue undergoing cell death.\n\u00a0(e)\nRadiation effects on cells and tissue only generate extracellular vesicles to protect against radiation-induced cell death."}
{"_id": "Radiology$$$8a0936cd-fdb4-4f21-93e1-bff113e4c55f", "text": "Extracellular vesicles have a size range of 40 nm to several \u03bcm."}
{"_id": "Radiology$$$83c60709-f83a-403b-9688-25852c99eccb", "text": "Extracellular vesicles are only formed by cells and tissue undergoing cell death."}
{"_id": "Radiology$$$adedea68-33b0-43ce-be5a-01367dc00899", "text": "Radiation effects on cells and tissue only generate extracellular vesicles to protect against radiation-induced cell death."}
{"_id": "Radiology$$$7c118b65-d7d6-43cc-952b-42fd5d9d97c1", "text": "In the field of lipidomics or metabolomics, what is the accurate method to achieve the comprehensive metabolite of a sample using LC-MS/MS?(a)\nMRM method\n\u00a0(b)\nPCR methods\n\u00a0(c)\nElisa methos\n\u00a0(d)\nDicentric assay"}
{"_id": "Radiology$$$ca3bdae3-07b8-4fcd-823b-f9acb8f26596", "text": "What happens to cells irradiated while in G2 with (a) 0.1 Gy and (b) 1Gy?"}
{"_id": "Radiology$$$15d22c42-d22e-476c-87e5-f3efc66f3ebb", "text": "Please refer two mechanisms responsible for the increased radioresistance of cancer stem cells."}
{"_id": "Radiology$$$e8dd6c44-1773-4d4f-b547-ef525ad209f9", "text": "SQ1.\nAlternative (c). Free radicals are formed after IR by indirect action.\n\u00a0SQ2.\nThe two BER mechanisms are SP-BER and LP-BER. SP-BER involves replacing the damaged base only. It requires DNA synthesis to replace the missing bases by DNA polymerase \u03b2, and to finalize the process, it uses ligase 3. In LP-BER, up to ten nucleotides are cut out and replaced, and the polymerases used are DNA polymerases \u03b4 and \u03b5 and ligase 1 to finalize the process.\n\u00a0SQ3.\nAlternative (d). Mismatch repair.\n\u00a0SQ4.\nCommon: End termini protection is used to avoid extensive exonuclease activity, but different proteins are important for HR and NHEJ for this purpose. Differences: HR is operative only when there is an undamaged chromosome to work with, i.e., in late S or G2, while NHEJ can operate on DNA DSBs in all cell cycle phases. The fidelity in repair is higher in HR, while NHEJ may cause alterations in DNA sequence as a consequence of the repair which can result in mutations/chromosomal aberrations and which may cause oncogenic transformation of cells.\n\u00a0SQ5.\nAlternative (b). High-LET radiation.\n\u00a0SQ6.\nAlternative (c). Superoxide dismutase converts superoxide anions to hydrogen peroxide.\n\u00a0SQ7.\nAlternative (a). It works in the G2 into M transition.\n\u00a0SQ8.\nAlternative (b). Complete the cycle and divide.\n\u00a0SQ9.\nThe mitosis is most sensitive, and early G1 and late S are most resistant.\n\u00a0SQ10.\nBecause otherwise they would reach their Hayflick limit and proceed to senescence, and thus they would not be able to divide continuously to form large tumors.\n\u00a0SQ11.\nThe type of radiation quality, dose, and dose rate as well as the cellular threshold for DNA damage and repair largely influence the cell death route. The position in the cell cycle when the damage is inflicted as well as functionality of DNA damage sensors, e.g., TP53, influence the decision.\n\u00a0SQ12.\nAlternative (c). Mitotic catastrophe.\n\u00a0SQ13.\nAlternative (e). Cell death after IR can take place via several routes, including mitotic catastrophe, autophagy, apoptosis, and necrosis.\n\u00a0SQ14.\nThe triggers and execution of the two pathways, intrinsic and extrinsic, are depicted in Fig. 3.38. The answer can be found in the legend of the figure.\n\u00a0SQ15.\nInitiation and phagophore nucleation-phagophore elongation-cargo sequestration-autophagosome maturation-fusion of the autophagosome with the lysosome.\n\u00a0SQ16.\nAlternatives (a, b, d, and e). The plating efficiency at 0 Gy is 66.6%, the plating efficiency at 2 Gy is 6.4%, the surviving fraction at 2 Gy is 9.5%, and the surviving fraction at 1 Gy is 100%.\n\u00a0SQ17.\nThe alteration of an oncogene because it then affects the normal embryonic development and causes embryonic lethality. The alteration of a tumor suppressor gene does not affect the embryogenesis; it increases the probability of cancer during life.\n\u00a0SQ18.\nFrom the table, it can be seen that the radiosensitivity is correlated to the existence of TNTs and their density and the complexity of networks formed. If all other properties are the same, the hypothesis which can be formulated is the following: The ability of cells to avoid death after irradiation is connected to the ability of the cells to communicate in a direct and fast manner through TNTs. This might be linked to the rescue effect, where less damaged cells are able to send components needed for the damaged cells to survive.\n\u00a0SQ19.\nMacrophages, endothelial cells, lymphocytes, and PMN.\n\u00a0SQ20.\nAnswers:(a)\nTrue, 5-mC accounts for about 1% of all bases within DNA.\n\u00a0(b)\nFalse, guanine is the predominantly modified base.\n\u00a0(c)\nFalse, histone variants are synthesized throughout the cell cycle.\n\u00a0(d)\nTrue, lysine and arginine are the most frequently acetylated amino acids.\n\u00a0\n\u00a0SQ21.\nNo, each miRNA can act on multiple different target genes, and one target gene can be regulated by many different miRNAs.\n\u00a0SQ22.\nTrue.\n\u00a0SQ23.\nFalse: PTEN is a central negative regulator of the PI3K/AKT pathway.\n\u00a0SQ24.\na.\u2002Wrong, lncRNAs lack protein-coding sequences and they are not translated.\n\u00a0\nb.\u2002Wrong, lncRNAs are defined as transcripts longer than 200\u00a0bp; microRNAs around 20 nucleotides in size.\n\nc.\u2002Correct, for example lncRNAs can interact with mRNAs and microRNAs for regulatory purposes.\nSQ25.\na.\u2002correct. The different sizes of extracellular vesicles are given in Table 3.14.\n\u00a0\nb.\u2002Wrong. Extracellular vesicles cargo in addition to proteins also mRNA/miRNA, long noncoding RNAs, DNA fragments, and lipids.\n\nc.\u2002 Correct. In particular apoptotic bodies; see Table 3.14.\n\nd.\u2002Wrong. Exosomes are generated by viable cells (Fig. 3.52) albeit they may act as communicators in cell death.\n\ne.\u2002Wrong. Extracellular vesicles may via their cargo participate in both cell pro-survival and pro-death signals.\nSQ26.\n(a) MRM method.\n\u00a0SQ27.\n(a) The low dose will not phosphorylate enough ATM to activate the early G2 checkpoint, and the cells will proceed to mitosis with unrepaired damage and die. (b) The cells will be arrested in G2, and the DNA damage that is repairable will be repaired before the cells enter mitosis.\n\u00a0SQ28.\nThe timing between doses may coincide with the duration of early G2 arrest.\n\u00a0SQ29.\nA protection against high radiation doses induced by a low \u201cpriming\u201d dose.\n\u00a0SQ30.\nFor example, to activate pro-survival pathways and to improve DNA repair ability through the activation of DNA damage checkpoint proteins.\n\u00a0SQ31.\nOxygen fixates DNA damage and sensitizes the cells to radiation."}
{"_id": "Radiology$$$aa96fa83-7e8a-4dd0-b2f9-76e4fb3238dd", "text": "Alternative (c). Free radicals are formed after IR by indirect action."}
{"_id": "Radiology$$$c919c249-02b0-433d-8875-5b918598ee81", "text": "The two BER mechanisms are SP-BER and LP-BER. SP-BER involves replacing the damaged base only. It requires DNA synthesis to replace the missing bases by DNA polymerase \u03b2, and to finalize the process, it uses ligase 3. In LP-BER, up to ten nucleotides are cut out and replaced, and the polymerases used are DNA polymerases \u03b4 and \u03b5 and ligase 1 to finalize the process."}
{"_id": "Radiology$$$0e21e046-101d-4b74-80a6-3bf18e2697ca", "text": "Alternative (d). Mismatch repair."}
{"_id": "Radiology$$$1880c81e-f89d-4ddb-8e59-b1313a3006bf", "text": "Common: End termini protection is used to avoid extensive exonuclease activity, but different proteins are important for HR and NHEJ for this purpose. Differences: HR is operative only when there is an undamaged chromosome to work with, i.e., in late S or G2, while NHEJ can operate on DNA DSBs in all cell cycle phases. The fidelity in repair is higher in HR, while NHEJ may cause alterations in DNA sequence as a consequence of the repair which can result in mutations/chromosomal aberrations and which may cause oncogenic transformation of cells."}
{"_id": "Radiology$$$2b32831f-c1b6-4caf-9d70-e288ac6abdf9", "text": "Alternative (b). High-LET radiation."}
{"_id": "Radiology$$$2f6353bf-d21d-48b7-a3a4-8dd64ec5b1c4", "text": "Alternative (c). Superoxide dismutase converts superoxide anions to hydrogen peroxide."}
{"_id": "Radiology$$$b8321011-a776-41ba-bb54-ac5007fe487a", "text": "Alternative (a). It works in the G2 into M transition."}
{"_id": "Radiology$$$c7a7c49e-95b2-4fe1-bf68-76e7f3b457e3", "text": "Alternative (b). Complete the cycle and divide."}
{"_id": "Radiology$$$a0aca8df-d1b2-4ab0-998b-e547b28dfb24", "text": "The mitosis is most sensitive, and early G1 and late S are most resistant."}
{"_id": "Radiology$$$0f1cc518-3def-450e-a5b2-efc0d6e48653", "text": "Because otherwise they would reach their Hayflick limit and proceed to senescence, and thus they would not be able to divide continuously to form large tumors."}
{"_id": "Radiology$$$1503f771-8289-4773-b4bc-fa353163cca1", "text": "The type of radiation quality, dose, and dose rate as well as the cellular threshold for DNA damage and repair largely influence the cell death route. The position in the cell cycle when the damage is inflicted as well as functionality of DNA damage sensors, e.g., TP53, influence the decision."}
{"_id": "Radiology$$$fef003e7-bb57-46df-8f34-d9cd08939795", "text": "Alternative (c). Mitotic catastrophe."}
{"_id": "Radiology$$$e2987b71-0d3d-46d1-8187-e963388032e4", "text": "Alternative (e). Cell death after IR can take place via several routes, including mitotic catastrophe, autophagy, apoptosis, and necrosis."}
{"_id": "Radiology$$$3c4dec18-9743-4ce2-a8cf-dc9f49b2afc3", "text": "The triggers and execution of the two pathways, intrinsic and extrinsic, are depicted in Fig. 3.38. The answer can be found in the legend of the figure."}
{"_id": "Radiology$$$d33e618c-cce3-41c8-b4eb-2a319387a65c", "text": "Initiation and phagophore nucleation-phagophore elongation-cargo sequestration-autophagosome maturation-fusion of the autophagosome with the lysosome."}
{"_id": "Radiology$$$3879601a-df16-4daf-872c-52622d81fdab", "text": "Alternatives (a, b, d, and e). The plating efficiency at 0 Gy is 66.6%, the plating efficiency at 2 Gy is 6.4%, the surviving fraction at 2 Gy is 9.5%, and the surviving fraction at 1 Gy is 100%."}
{"_id": "Radiology$$$2714d584-8bb6-4465-9cd2-805e6fda08b4", "text": "The alteration of an oncogene because it then affects the normal embryonic development and causes embryonic lethality. The alteration of a tumor suppressor gene does not affect the embryogenesis; it increases the probability of cancer during life."}
{"_id": "Radiology$$$d17f2f97-3270-4cd4-9d43-579d46cfed10", "text": "From the table, it can be seen that the radiosensitivity is correlated to the existence of TNTs and their density and the complexity of networks formed. If all other properties are the same, the hypothesis which can be formulated is the following: The ability of cells to avoid death after irradiation is connected to the ability of the cells to communicate in a direct and fast manner through TNTs. This might be linked to the rescue effect, where less damaged cells are able to send components needed for the damaged cells to survive."}
{"_id": "Radiology$$$4095c289-eb4d-4505-8b3a-dba9206fc6e2", "text": "Answers:(a)\nTrue, 5-mC accounts for about 1% of all bases within DNA.\n\u00a0(b)\nFalse, guanine is the predominantly modified base.\n\u00a0(c)\nFalse, histone variants are synthesized throughout the cell cycle.\n\u00a0(d)\nTrue, lysine and arginine are the most frequently acetylated amino acids."}
{"_id": "Radiology$$$c8bee72e-b9d1-46e1-bd8d-555858fd471f", "text": "True, 5-mC accounts for about 1% of all bases within DNA."}
{"_id": "Radiology$$$ea3e13d4-9ef5-4b44-87bb-9b869c90be9b", "text": "True, lysine and arginine are the most frequently acetylated amino acids."}
{"_id": "Radiology$$$89302773-275c-49f5-9f4c-5ea65dc3bd75", "text": "No, each miRNA can act on multiple different target genes, and one target gene can be regulated by many different miRNAs."}
{"_id": "Radiology$$$6372500e-f623-43b0-97ad-51d94e494708", "text": "False: PTEN is a central negative regulator of the PI3K/AKT pathway."}
{"_id": "Radiology$$$4936d540-1683-4f48-a371-785767b2a36f", "text": "a.\u2002Wrong, lncRNAs lack protein-coding sequences and they are not translated."}
{"_id": "Radiology$$$78696644-e124-4c9b-b82f-30202ca0d0e6", "text": "b.\u2002Wrong, lncRNAs are defined as transcripts longer than 200\u00a0bp; microRNAs around 20 nucleotides in size."}
{"_id": "Radiology$$$3212924b-c68f-4f91-9c8b-5fabaaa4d5c1", "text": "c.\u2002Correct, for example lncRNAs can interact with mRNAs and microRNAs for regulatory purposes."}
{"_id": "Radiology$$$667e8921-3797-4632-94c9-9ec8de87af06", "text": "a.\u2002correct. The different sizes of extracellular vesicles are given in Table 3.14."}
{"_id": "Radiology$$$65743473-3116-4931-91e4-1326069bb39f", "text": "b.\u2002Wrong. Extracellular vesicles cargo in addition to proteins also mRNA/miRNA, long noncoding RNAs, DNA fragments, and lipids."}
{"_id": "Radiology$$$5e41574f-8af1-4443-8f8d-0ad7b08c8e87", "text": "c.\u2002 Correct. In particular apoptotic bodies; see Table 3.14."}
{"_id": "Radiology$$$e2b88f81-2db5-492d-8f49-44cb3269e2e8", "text": "d.\u2002Wrong. Exosomes are generated by viable cells (Fig. 3.52) albeit they may act as communicators in cell death."}
{"_id": "Radiology$$$8a5c8972-8b6d-4529-9643-f7b4fe480284", "text": "e.\u2002Wrong. Extracellular vesicles may via their cargo participate in both cell pro-survival and pro-death signals."}
{"_id": "Radiology$$$0607fe2d-d860-4395-8927-788617d7b3b4", "text": "(a) The low dose will not phosphorylate enough ATM to activate the early G2 checkpoint, and the cells will proceed to mitosis with unrepaired damage and die. (b) The cells will be arrested in G2, and the DNA damage that is repairable will be repaired before the cells enter mitosis."}
{"_id": "Radiology$$$dfa0ff2a-7eb8-4cb6-b718-e64b0846c65f", "text": "The timing between doses may coincide with the duration of early G2 arrest."}
{"_id": "Radiology$$$f0c49afc-c491-48e1-ba40-9e10935a7719", "text": "A protection against high radiation doses induced by a low \u201cpriming\u201d dose."}
{"_id": "Radiology$$$02f0ac94-cfce-49c9-843a-385be5e93fab", "text": "For example, to activate pro-survival pathways and to improve DNA repair ability through the activation of DNA damage checkpoint proteins."}
{"_id": "Radiology$$$b4d3f5af-f1a2-49c4-8ad4-5dcbc5415457", "text": "Particle fluence, or planar fluence, \u03a6, is defined as the number of ionizing particles which traverse a finite plane in space some distance from the source. If dN particles are incident on a planar surface of area, dA, then the fluence is \u03a6\u00a0=\u00a0dN/dA [1, 2]."}
{"_id": "Radiology$$$e278bf03-fc38-49f8-a2d1-5c21257d2c9c", "text": "We may also define the energy fluence, \u03a8, which is the radiant energy, dR, which crosses a plane of area, dA, as \u03a8\u00a0=\u00a0dR/dA. The radiant energy, R, of a radiation field is defined as the total energy of the particles that cross the plane, excluding their rest mass energy. The fluence rate may be defined in terms of energy fluence or planar fluence and is simply the rate at which either energy fluence or planar fluence cross unit area. In the context of the amount of radiant energy absorbed in matter, these concepts provide the basis from which all the remaining dosimetric quantities are defined [1, 2]."}
{"_id": "Radiology$$$f4f488ba-3acc-4cff-99db-01db8a0d010c", "text": "Exposure, X, is defined as the total charge which is liberated per unit mass in air by ionizing radiation [1, 2]. Its unit is the Roentgen, R, where one Roentgen is 2.58 \u00d7 10\u22124 C\u00a0kg\u22121. Exposure is related to energy fluence, \u03a8, by the following equation:"}
{"_id": "Radiology$$$3317230b-33b6-419a-9b9b-e33b4e6f3f2f", "text": "(4.1)"}
{"_id": "Radiology$$$01f8415f-a781-47a4-a158-90d22f80eebc", "text": "where (\u03bcen/\u03c1)air is the mass energy absorption coefficient of air which defines the fraction of the energy of a beam of particles which is absorbed per unit mass of air at a particular beam energy. Wair\u00a0=\u00a033.97\u00a0eV is the energy required to produce an ion pair in air and e is the charge of the electron."}
{"_id": "Radiology$$$c3e57a86-43dd-45e8-a85e-a8825a770ca7", "text": "Kerma, K, is defined as the kinetic energy released per unit mass of material by a specific combination of an incident radiation field and an absorbing material. Kerma is related to energy fluence, \u03a8, by the following equation:"}
{"_id": "Radiology$$$ca32f2c2-5fa8-4184-813c-16bd585e94ca", "text": "(4.2)"}
{"_id": "Radiology$$$c2cce098-936d-4591-8626-162a1330cf05", "text": "where \u03bctr/\u03c1 is the mass energy transfer coefficient, which defines the fraction of the incident radiant energy which is released as kinetic energy in charged particles in a given volume of material. More strictly, the Kerma is the amount of energy liberated through ionization in the volume encompassed by a unit mass of an absorbing material [1, 2]. This energy is transferred through ionization of the material at the atomic level and is ultimately manifested in the kinetic energy of ionization electrons in the material. As may be seen from Fig. 4.1, kinetically charged particles or photons, created in collisions between incident ionizing particles and the material, may not deposit their energy in the mass volume. Therefore, Kerma is a measure of the amount of ionizing energy offered for absorption in the material, which in this case is the initial kinetic energy of the primary electron.\n\nA circular diagram indicates interactions between photons, ionization, primary electron, scattered photon, and absorbing volume, mass m.\n\nFig. 4.1\nKerma in relation to interactions between ionizing photons and matter in a unit mass volume"}
{"_id": "Radiology$$$373d2a10-9394-455d-b223-da4ef0a8c5a9", "text": "A circular diagram indicates interactions between photons, ionization, primary electron, scattered photon, and absorbing volume, mass m."}
{"_id": "Radiology$$$d9836c70-5095-42c3-9d6b-46af870ba845", "text": "The energy imparted, \u03f5, by ionizing radiation to the matter in a volume is given by the following equation [3]:"}
{"_id": "Radiology$$$0a89bfc1-edf4-4ae9-b4c0-18872e9ccc42", "text": "(4.3)"}
{"_id": "Radiology$$$efd084b7-9fea-4a72-a22c-e0b690a491fa", "text": "where the first and second terms in the equation, respectively, describe the sums of all the radiant energies of all ionizing radiations entering and leaving a particular volume. The third term denotes the sum of all the mass energies of all the particles produced during the interactions of the ionizing radiations with the matter to which it is imparting energy. In diagnostic radiology, the photon energy is not sufficient to instigate pair production (production of positrons and electrons in the vicinity of a strongly positive nucleus), and therefore particle production does not occur. Thus, for diagnostic energies, the third term on the right-hand side of Eq. (4.3) is zero [1, 4]. Energy Imparted is quoted in the units of energy, the Joule, J."}
{"_id": "Radiology$$$5df6c9ba-92ed-405f-9b60-d6cba5d4e776", "text": "A distinction must be made between the term \u201cEnergy Imparted\u201d and the term \u201cImparted Energy.\u201d Energy Imparted is the term for a gross quantity or concept, where the energy is imparted to matter that has a macroscopic size. Imparted Energy is the energy that is imparted in a single interaction between any particle and the matter in a given volume. The Imparted Energy, d\u03f5, in an interaction is a stochastic quantity, and is difficult to measure, and impossible to infer with any great accuracy [3, 5]. Thus, the Energy Imparted is also a stochastic quantity. However, repeated measurements can establish mean energy imparted, \n\n, which is a non-stochastic quantity (Box 4.1)."}
{"_id": "Radiology$$$a8fda086-c405-4f38-b5b9-737a0c6f508a", "text": "Kerma, K, is defined as the kinetic energy released per unit mass of material by a specific radiation field and it is related to energy fluence, \u03c8\n\nExposure, X, is defined as the total charge which is liberated per unit mass in air by ionizing radiation. Its unit is the Roentgen, R."}
{"_id": "Radiology$$$253416aa-278c-452c-8207-244a7eb0be0d", "text": "Kerma, K, is defined as the kinetic energy released per unit mass of material by a specific radiation field and it is related to energy fluence, \u03c8"}
{"_id": "Radiology$$$e7f02538-85c2-4b7b-b1a4-928527281e33", "text": "Exposure, X, is defined as the total charge which is liberated per unit mass in air by ionizing radiation. Its unit is the Roentgen, R."}
{"_id": "Radiology$$$76889513-222d-4d26-84eb-b4923f7960e3", "text": "The absorbed dose (sometimes referred to simply as \u201cdose\u201d) is the radiant ionizing energy absorbed per unit mass of absorbing material. It is therefore defined as:"}
{"_id": "Radiology$$$bae42857-8f6e-4fa1-9b50-a189cb2c0b60", "text": "(4.4)"}
{"_id": "Radiology$$$81717940-4c62-488a-aef9-e9c099ab81c8", "text": "The quantity \u03b5/m is sometimes referred to as the specific energy. It is stochastic in the same way that the imparted energy in a given interaction is stochastic, but with repeated measurements, and on macroscopic scales involving many single particle interactions, it becomes a measurable quantity ([1], p. 86; [2, 4]). The unit of Absorbed dose is the Gray, Gy, which is equal to J kg\u22121."}
{"_id": "Radiology$$$e3204ef6-c4ab-4889-bcf5-d4ffd7c5e4bd", "text": "The Kerma in Eq. (4.2) may be split into two parts depending on the ways in which the energy of the photon is lost through interactions with the material [1]. Photons may either release their energy through collision interactions in which excitation and ionization of the stopping material occur or through radiative processes in which their energy is radiated through the release of photons. Thus, the Kerma can be expressed as:"}
{"_id": "Radiology$$$09abc84e-6290-4d7b-9ab8-e3826f372868", "text": "(4.5)"}
{"_id": "Radiology$$$833e10c9-672a-4910-825e-18310eb8659d", "text": "where Kc is the portion transferred through collisions, and Kr is the portion transferred through radiative interactions [1]. Radiative interactions generally occur in situations in which charged particles are incident on a material [1]. In the case of diagnostic radiology, Kerma is released through collision interactions, with Collision Kerma therefore given by:"}
{"_id": "Radiology$$$b78c0c0e-e21d-410a-a104-9838b6ecf4d8", "text": "(4.6)"}
{"_id": "Radiology$$$a91e9cde-eb3b-4d80-a6e3-a84ab11ff401", "text": "In diagnostic radiology, a simple relationship between Kerma and Absorbed dose may be derived. When charged particle equilibrium (CPE) exists in a medium, the number of charged particles leaving a unit mass volume is replaced by an equal number entering from other mass volumes. In such a situation, which occurs at the photon energies in diagnostic radiology, all Kerma is absorbed in the unit mass volume. It has been shown by Attix, that for a medium of uniform density and atomic composition, such a situation does indeed exist for a field of X-ray photons and a uniformly irradiated medium [1, 2]. In this case the Absorbed dose, D, and Collision Kerma, Kc, are equal, such that\n\n (4.7)"}
{"_id": "Radiology$$$6702b408-89ab-4805-a5a1-22840302e799", "text": "The Absorbed Dose is the energy absorbed per unit mass of material. The unit of Absorbed Dose is the Gray, Gy, which is equal to J kg\u22121"}
{"_id": "Radiology$$$aec88a42-036f-4379-bcfb-707292f533c1", "text": "In general, radiation detectors  operate by providing the means to measure the energy deposited over time in the detector absorbing material from exposure to a source of ionizing radiation. This is typically measured as the quantity of charge, Q, over time elicited from an absorbing medium forming the main component of the detecting element. An ideal radiation detector is one that gives spatial resolution, temporal resolution, information regarding the energy of the particle, and information regarding the identity of the radiation. In reality, single detectors of this type are difficult to construct such that practical detectors that are used in the field have a focused range of capabilities which should be taken into consideration when a detector is chosen for a particular application [6, 7]."}
{"_id": "Radiology$$$2b668b00-a4e7-48bb-8abd-f053c93435d9", "text": "Ionization chambers are designed to measure the number and/or total energy deposited as a result of the ionizations produced when a charged particle or ionizing photon traverses the detector medium. Therefore, they are not suitable for the detection or analysis of neutral particles. Ionization detectors consist of an isolated detection medium, generally a gas such as air that can be easily ionized (i.e., has a low ionization potential), which is placed between two oppositely charged electrodes (Fig. 4.2). The medium should be chosen such that it does not respond adversely to ionization such that its characteristics will not change with use.\n\nA schematic diagram exhibits the ionization detector of the dashed arrow of the radiation track with both positive and negative ions placed between the rectangular board of high voltage source, bottom connected with the output signal.\n\nFig. 4.2\nSchematic of the basic elements of an ionization detector"}
{"_id": "Radiology$$$61b01679-245a-4929-a3fb-7d20b51241ed", "text": "A schematic diagram exhibits the ionization detector of the dashed arrow of the radiation track with both positive and negative ions placed between the rectangular board of high voltage source, bottom connected with the output signal."}
{"_id": "Radiology$$$c1e68b67-4de6-49ba-819c-1602479b865e", "text": "The charged particle will ionize the detector medium along its path and these ions will then be accelerated towards the detector electrodes. In general, a high electric field is applied between the electrodes to prevent the recombination of ions produced by the traversal of the charged particle. As the charged particle traverses the sensitive region of the detector (i.e., the gas) it produces multiple electron-ion pairs, which begin to drift along the electric field lines and reach the plates of the detector. These ions may produce further ionization of the neutral gas atoms via further collision, ultimately producing a small current that induces a voltage drop across the resistor. These chambers typically generate very low measurement currents per ionizing particle, and therefore require low noise amplifiers to improve their operating performance."}
{"_id": "Radiology$$$2ea8db11-2e64-4692-9711-f675fcc41fbd", "text": "The amplified output signal from the detector may be used to trigger a counting mechanism to measure the number of incident charged particles or ionizing photons (i.e., exposure) or its pulse height may be analyzed to determine the total energy within the beam (i.e., dose). The amount of ionization that is detected is dependent on the nature of the gas used in the detector, the level of the applied electrical field, and the characteristics of the plates used in the detector. How the chambers operate, i.e., as a device for the measurement of absolute energy deposition or number of charged particle incident on the detector, depends on the HV level applied to the detector, as depicted in Fig. 4.3 [7].\n\nAn increasing waveform depicts the number of ion pairs versus V in volts at the different regions are the ionization chamber region, region of proportionality, Geiger region, and discharge region, waves are named alpha, and beta.\n\nFig. 4.3\nSignal response to ionization as a function of the applied voltage for heavily ionizing (top curve) and weakly ionizing particles (lower curve). In the Geiger region, the output does neither depend on the voltage nor on the amount of deposited energy or initial ionization. [Adapted from Fig. 4.12 Martin and Shaw (2006). Copyright (2006), Wiley Publishers]"}
{"_id": "Radiology$$$31e60f8c-82c9-4e27-8a26-26154cd6592b", "text": "An increasing waveform depicts the number of ion pairs versus V in volts at the different regions are the ionization chamber region, region of proportionality, Geiger region, and discharge region, waves are named alpha, and beta."}
{"_id": "Radiology$$$d35a813b-35f8-414e-9128-85a93381aa50", "text": "When the applied voltage is small, the electrons and ions can recombine soon after they are produced and only a small fraction of the ions reach their respective plates in the detector (Fig. 4.3). As the applied voltage between the plates is increased, a region is reached where the output pulse reflects the amount of ionization seen in the chamber (Ionization region). When the voltage is increased still further, the electrons and positive ions released by the initial ionization can themselves cause further ionizations in the medium and thus amplify the ionization pulse (Proportional region). Increasing the applied field still further (Geiger region) creates an avalanche effect and a highly amplified output signal. Any further increases in the applied voltage lead to a continuous discharge of the detector [6]."}
{"_id": "Radiology$$$66205c5a-3336-4c22-bc76-65e3a4948288", "text": "It is possible to determine the typical output current that will be generated by an ionization chamber in the presence of a source of known activity. Consider the case of an in-air ionization chamber (where air has an ionization potential of 30\u00a0eV) which is exposed to alpha particles (E\u03b1\u00a0=\u00a05.486\u00a0MeV) from a 10 MBq Am-241 source. The total number of ionizations produced by a single Am-241 \u03b1-particle will be the ratio of the energy of the alpha particle to the ionization potential of air:"}
{"_id": "Radiology$$$2d0607d4-96d2-48e6-902a-fa30910ff7dc", "text": "In this case, the total number of ionizations produced will be the product of the activity of the source and the number of ionizations produced by a single alpha particle, or N\u00a0=\u00a01.829\u00a0\u00d7\u00a01012 ionizations, which are observed in a single second (as the unit of activity, the Bq is s\u22121 in SI units). The final step is then to compute the product of the total number of ionizations with the charge on the electron such that the total current observed will be:"}
{"_id": "Radiology$$$eedadfb5-4121-44f3-b61f-4ad6f2d97b06", "text": "Frequently, ionization chambers are open to the air to allow for changes in ambient pressure which could collapse or expand a sealed chamber, damaging the thin chamber walls. As a consequence, chamber outputs must be adjusted for changes in ambient temperature, T, and pressure, P, from those at which the chamber was calibrated, Tn and Pn, respectively. In practice, we can multiply the chamber output by the following correction factor to adjust for ambient conditions (where all temperatures are expressed in Kelvin and pressures in Pascals [6]):"}
{"_id": "Radiology$$$4b9b5bda-fee6-48c5-ab14-52ce9c280eb7", "text": "(4.8)"}
{"_id": "Radiology$$$3eccefc5-f60d-4549-b02f-9f6e569ce5c4", "text": "While the ionization chamber provides a device for the measurement of absolute energy deposition, it does not provide information on directionality. Proportional counters are ionization chambers that may be used for both measuring absolute energy deposition (through a measurement of the pulse height) in addition to giving directional information on the path of charged particle (through the output of a given anode wire, each of which is independently amplified)."}
{"_id": "Radiology$$$bc1a3fe1-0388-4564-be0b-41ecd2fe0470", "text": "Multi-wire proportional chambers (MWPCs) such as those shown in Fig. 4.4 are used in high-energy particle physics experiments as a means of tracking the path of charged particles. Anode wires (typically with a ~2 mm separation) are positioned between the cathode plates of the chamber (which have a typical separation of 1\u00a0mm) and the construct is sandwiched between thin mylar windows or some other superstructure, with an operating gas infused into the region between the plates. In practice, several individual chambers may then be joined together to provide fine detail on the direction of passage of individual charged particle, where pulses will be produced on the anode electrodes closest to the path of the charged particle through the detector as a result of ionization of the gas in the region closest to each anode. MWPCs can be used to infer further information on the momentum of beams of charged particles via the degree of their deflection in a magnetic field (which is typically how they have been used in collider experiments such as the LHC at CERN [6]).\n\nA schematic diagram exhibits a multi-wire chamber of the anode placed between the cathode with positive and negative ions with H V, R, A, and O by P.\n\nFig. 4.4\nSchematic of a multi-wire proportional chamber [6, 7]"}
{"_id": "Radiology$$$71600afb-326f-41ab-abd4-26305810c823", "text": "A schematic diagram exhibits a multi-wire chamber of the anode placed between the cathode with positive and negative ions with H V, R, A, and O by P."}
{"_id": "Radiology$$$608035f6-1f96-4fdc-9fda-afc8dedc772b", "text": "Scintillators are materials that react to the passage of a charged particle by the emission of a very small flux of photons of light. Charged particles may excite electrons within atoms of the scintillating material to a higher energy state; these atoms then emit photons as they de-excite to their ground state. Scintillators can be developed from organic (e.g., naphthalene or anthracene) or inorganic (including sodium iodide or cesium iodide) materials and have applications as the first detection element with gamma cameras used in nuclear medicine."}
{"_id": "Radiology$$$4e101773-c35b-4b03-a4c6-a4dffae787dd", "text": "Scintillating materials typically need to be chosen to detect photons of a specific wavelength and may often be doped to achieve specific wavelength sensitivity. They are generally coupled to photomultiplier tubes (PMT) to amplify the intensity of the weak photon signal output from the scintillator, either for photon counting or imaging applications."}
{"_id": "Radiology$$$4df27f3a-1127-4379-935c-c7ea86e2ef4b", "text": "In Fig. 4.5, a schematic of a photomultiplier tube is shown. An incoming charged particle or ionizing photon impacts the scintillator, which emits a photon flux towards a photocathode material (constructed typically with a negatively charged plate covered by a photosensitive material such as gallium\u2013arsenide or indium\u2013gallium\u2013arsenide). Here, the photon flux is converted to an electron flux as they enter the inner (evacuated) environment of the PMT tube. These electrons are accelerated towards the first of several dynodes by the high-voltage field between the photocathode and the anode. When each electron collides with a dynode, it causes the emission of several electrons (typically 5\u201310), which are then accelerated towards subsequent dynode and amplify the electron flux through collision and reemission. At the detector anode, a significant and measurable electric current is then generated as a result of the acquisition of a single photon. Apart from a small degree of signal fluctuation, the current seen at the anode is linearly proportional to the photon  flux seen at the photocathode [6, 7].\n\nA schematic diagram exhibits a photomultiplier tube of incoming radiation, photon, photocathode, dynodes, output pulse, and scintillating material.\n\nFig. 4.5\nSchematic diagram of a photomultiplier tube (PMT) (courtesy of Physics Libretexts, Fig. 31.2.3)"}
{"_id": "Radiology$$$829fb162-6aa3-4fb9-a920-a327bbc6e5e0", "text": "A schematic diagram exhibits a photomultiplier tube of incoming radiation, photon, photocathode, dynodes, output pulse, and scintillating material."}
{"_id": "Radiology$$$3adc645a-8f02-4b9d-851d-cb37eec56072", "text": "Semiconductor detectors  based upon p\u2013n junction diodes offer a practical and robust option for detector construction, operating in a similar manner to an ionization chamber [6, 7]. Here a p\u2013n junction is constructed through the joining together of a piece of p-type semiconductor (such as silicon or germanium) to a piece of n-type silicon. P-type material is doped with atoms of a material with one vacant outer-electron state, such as boron, B, while N-type material is doped with atoms of a material with an extra \u201cfree\u201d electron in its outermost energy level, such as antimony, Sb. At the junction between the two materials a \u201cdepletion layer\u201d is formed where electrons from the N-type material migrate to the P-type material to fill vacant energy states or \u201choles\u201d leaving behind holes in the N-type material surrounding the junction. This creates a region where electrons and holes are depleted around the junction and creates a barrier to conduction. For the purposes of photon or particle detection, the depletion region is the sensitive portion of the electronic detector. When operated in reverse bias (Fig. 4.6a, b), this depletion region is larger and these detectors are typically operated in reverse bias with a voltage of 100\u00a0V to increase the depletion layer and therefore the sensitive region of the detector [6, 7].\n\nA. A schematic diagram p n junction diode operated with both positive and negative ions. B. A graph of concave and convex curves of values approximately 30, and 0.6 volts, with an inflection point 0.\n\nFig. 4.6\n(a) Schematic of a p\u2013n junction diode operated in forward and reverse bias. (b) Operating characteristics of the diode in forward and reverse bias"}
{"_id": "Radiology$$$33597ce4-a19d-4678-afee-7e071f2f7c2f", "text": "A. A schematic diagram p n junction diode operated with both positive and negative ions. B. A graph of concave and convex curves of values approximately 30, and 0.6 volts, with an inflection point 0."}
{"_id": "Radiology$$$7a361448-cca4-429f-85fe-29b8650b9a0c", "text": "When the sensitive element of the detector is exposed to a charged particle or ionizing photon, this causes electrons within the depletion layer to be promoted from the valence band to the conduction band (Fig. 4.7), and their conduction through the junction towards the positive terminal of the detector. Here, the valence band is equivalent to the energy level of the outermost electron, while the conduction band is the energy level of the next vacant energy state above the valence band. A current is produced which is proportional to the energy loss by the charged particle or photon within the depletion layer [6, 7]\n\nA. A schematic diagram p-n junction diode with both positive and negative ions. B. A schematic diagram of 4 horizontal bars of C B, and V B of E subscript gap of e V E subscript gap = h c by lambda.\n\nFig. 4.7\nOperation of a semiconductor particle detector (a) where an incident proton causes the promotion of one or more electrons from the valence to the conduction band within the detector (b)"}
{"_id": "Radiology$$$0ed97041-5373-4ba9-ba35-9c60b8db0904", "text": "A. A schematic diagram p-n junction diode with both positive and negative ions. B. A schematic diagram of 4 horizontal bars of C B, and V B of E subscript gap of e V E subscript gap = h c by lambda."}
{"_id": "Radiology$$$86bf2bfb-3dd8-460e-a420-5a9f58d72b47", "text": "The creation of an electron\u2013hole pair in a silicon or germanium semiconductor requires as little as ~3\u00a0eV in comparison to the 30\u00a0eV required for in-air ionization chambers. Detectors can be constructed and tuned to radiation of a specific wavelength, \u03bb, by altering the energy difference between the valence and conduction bands, or the band gap, Egap, as shown in Fig. 4.7 and Table 4.1.Table 4.1\nTypical semiconducting materials used for radiation detection, including bandgaps, wavelength, and electro magnetic (EM) band sensitivity\n\nMaterial\n\nEgap (eV)\n\n\u03bb (nm)\n\nBand\n\nC (diamond)\n\n5.65\n\n220\n\nUV\n\nGaN\n\n3.45\n\n360\n\nUV\n\nAlGaN\n\n3.45\u20135.64\n\n360\u2013260\n\nUV\n\nCdZnTe\n\n1.4\u20132.12\n\n870\u2013580\n\nVisible\n\nSi\n\n1.12\n\n1100\n\nVisible\n\nGaAs\n\n1.42\n\n875\n\nVisible\n\nGe\n\n0.66\n\n1800\n\nNIR\n\nPtSi\n\n0.41\u20130.25\n\n3000\u20135000\n\nIR\n\nHgCdTe\n\n0.41\u20130.25 or 0.16\u20130.10\n\n3000\u20135000 or 8000\u201312,000\n\nIR\n\nHgCd\n\n0.7\u20130.1\n\n1700\u201312,500\n\nNIR-FIR"}
{"_id": "Radiology$$$8b28dd86-3a12-4170-84d1-020b5909231a", "text": "Semiconducting materials, when incorporated in radiation detectors can therefore produce a large signal in response to irradiation with a small photon flux. The detectors can be constructed very thinly (as little as 200\u2013300\u00a0\u03bcm) for the detection of ionized particles, or larger for stopping of photons. Their performance is approximately linear if an electric field is applied that prevents the recombination of the electrons and holes formed by the radiation [6, 7]."}
{"_id": "Radiology$$$f50f9d29-35b3-44b4-900e-ad51a4c2a8e3", "text": "The phenomenon of Cerenkov radiation was first observed and described by Pavel Cerenkov in 1934 and characterized by Franck and Tamm in 1937. This work resulted in all three being given the Nobel Prize in physics in 1958."}
{"_id": "Radiology$$$968e026b-1e71-4812-a466-d78686b0c724", "text": "To understand the operation of Cerenkov detectors we must first describe the effect itself. Suppose that we have a charged particle traveling at a relatively low velocity though a static medium. As the particle travels slowly relative to the speed at which the ions/molecules of the material can orient and reorient themselves as it passes, the ions/molecules will orient themselves such that the part of the ion/molecule that is charged opposite to the charge of the ionizing projectile would be in the direction of the particle (Fig. 4.8a). The molecules are displaced in an isotropic conformation relative to the position and direction of movement of the charged particle, and therefore there is no overall change in the energy of the medium locally [6, 7].\n\nA. 2 rectangular boxes full of circular-shaped charged particles. B. An overlapping circle with charged particles, along with angle theta at the bottom. C. A schematic diagram of cone formation of Cerenkov light by neutrino or antineutrino, and radionuclide. D. A cubic shape of negative refractive index at the center.\n\nFig. 4.8\n(a) Passage of a charged particle through a medium of refractive index n at velocities that polarize the medium. (b) The generation of coherent light waves via the Cerenkov effect. (c) The formation of a cone of Cerenkov light along the path of the charged particle through a medium with positive and (d) negative refractive index. [Taken from Shaffer et al., Nature Nanotechnology, 12, 106\u2013117 (2017). Copyright Springer Nature]"}
{"_id": "Radiology$$$d9f17c33-3876-4daa-b0f8-da1457b9f5df", "text": "A. 2 rectangular boxes full of circular-shaped charged particles. B. An overlapping circle with charged particles, along with angle theta at the bottom. C. A schematic diagram of cone formation of Cerenkov light by neutrino or antineutrino, and radionuclide. D. A cubic shape of negative refractive index at the center."}
{"_id": "Radiology$$$53ac64ac-df37-4baa-a5d2-77d1f1a4e673", "text": "However, in instances where the velocity of the particle, v\u00a0~\u00a0c/n or v\u00a0>\u00a0c/n, the molecules of the medium that are displaced by the passage of the charged particle are generally anisotropic relative to the position and diNurUhr (Fig. 4.8b). By Huygens principle of wavelets, each of the reoriented molecules of the medium can reradiate the energy delivered to them and do so as point wavelet sources. These sources will be coherent along a direction as shown in Fig. 4.8c. If \u03d1 is the angle at which the point sources reradiate, then it may be shown that\n\n (4.9)"}
{"_id": "Radiology$$$9553f073-00d1-4702-90ae-916e609a94b8", "text": "where n is the refractive index of the medium and \u03b2\u00a0=\u00a0v/c, where v is the velocity of the particle and c is the speed of light."}
{"_id": "Radiology$$$db2fe304-afc8-46f0-93f0-4094298483a6", "text": "It is therefore possible to discriminate the identity of high energy charged particles purely based on the angle of Cerenkov emission or the threshold value of n at which Cerenkov emission is observed [6, 7]. In particle physics, experiments materials of various refractive indices are typically used to provide several potential Cerenkov thresholds for the detection of a variety of radiation types. The weak Cerenkov photons can be detected using PMTs or electronic photodetectors. Cerenkov photons are also observable as a result of the passage of charged particles through human tissue and Cerenkov imaging has seen a recent application for in vivo dosimetry in radiotherapy [8]."}
{"_id": "Radiology$$$b782ca4a-e9c1-476a-a395-168d38d210c3", "text": "Calorimeters allow the estimation of the total energy of a high-energy charged particle or ionizing photon through absorption of its total energy, via successive ionization of the material in the detector in a process that is termed a particle shower (Fig. 4.9), in a detector that is capable of absorbing all of the particles incident radiation. These devices may be ionization chambers as described earlier or semiconductor detectors, or a combination of the two. Depending on the nature and identity of the incident particle, it can create ionizing photons through bremsstrahlung or can produce further \u201chard\u201d ionizing particles that may not be stopped easily in detectors with unsuitable absorbing characteristics, and therefore a single detector type will not achieve the experimental objectives (Box 4.3).\n\nA. A schematic diagram of clusters of particles of the calorimeter. B. The branches of the particle shower are present in the crystal calorimeter.\n\nFig. 4.9\n(a) A particle shower within a calorimeter; (b) a particle shower caused by the incidence of a photon on a calorimeter"}
{"_id": "Radiology$$$c20e8825-0e5e-4bf0-acf5-161bf33bd0af", "text": "A. A schematic diagram of clusters of particles of the calorimeter. B. The branches of the particle shower are present in the crystal calorimeter."}
{"_id": "Radiology$$$8a7ac392-ae21-4af4-8997-25eb2a703136", "text": "Radiation detectors measure the energy deposited over time in the detector-absorbing material\n\nAn ideal radiation detector provides spatial resolution, temporal resolution, information regarding the energy of the particle, and information regarding the identity of the radiation. No single detector can offer these simultaneously\n\nIonization chambers are common dosimeters that measure the ionizations produced when a charged particle or ionizing photon traverses the detector medium (generally a gas, requiring temperature and pressure corrections). An electric field is applied between the electrodes to prevent the recombination of ions produced.\n\nProportional counters are ionization chambers that also provide directional information on the path of charged particles\n\nScintillator materials are also used as dosimeters by relating the flux of photons emitted to the energy deposited. They are generally coupled to photomultiplier tubes (PMT) to amplify the intensity of the photon signal\n\nSemiconductor detectors measure the number of charge carriers produced by the radiation in the detector material. Semiconductor materials are used due to the small energy required to produce electron-hole pairs\n\nCerenkov detectors record light produced by charged particles traveling through materials at a velocity greater than that at which light can travel through the material\n\nCalorimeters quantify the absolute dose absorbed by measuring the increase in temperature produced by radiation"}
{"_id": "Radiology$$$d9c83e97-fa69-4837-af9b-ce8c1e1c654e", "text": "Radiation detectors measure the energy deposited over time in the detector-absorbing material"}
{"_id": "Radiology$$$52532d28-43ed-4153-8c1f-32d2a87c69e9", "text": "An ideal radiation detector provides spatial resolution, temporal resolution, information regarding the energy of the particle, and information regarding the identity of the radiation. No single detector can offer these simultaneously"}
{"_id": "Radiology$$$e7c29b5d-feb2-4c01-859c-cac88dec8eab", "text": "Ionization chambers are common dosimeters that measure the ionizations produced when a charged particle or ionizing photon traverses the detector medium (generally a gas, requiring temperature and pressure corrections). An electric field is applied between the electrodes to prevent the recombination of ions produced."}
{"_id": "Radiology$$$97a80f39-2467-496f-a47c-15b4582367d3", "text": "Proportional counters are ionization chambers that also provide directional information on the path of charged particles"}
{"_id": "Radiology$$$5f18310e-99d0-4b12-9041-338cc8f0e7b3", "text": "Scintillator materials are also used as dosimeters by relating the flux of photons emitted to the energy deposited. They are generally coupled to photomultiplier tubes (PMT) to amplify the intensity of the photon signal"}
{"_id": "Radiology$$$07b655b9-abb4-4a85-96e7-11329287b0e7", "text": "Semiconductor detectors measure the number of charge carriers produced by the radiation in the detector material. Semiconductor materials are used due to the small energy required to produce electron-hole pairs"}
{"_id": "Radiology$$$c5ec91a1-c499-4360-8313-4009ac999c31", "text": "Cerenkov detectors record light produced by charged particles traveling through materials at a velocity greater than that at which light can travel through the material"}
{"_id": "Radiology$$$bc2222ba-32ce-4727-8dcc-23c630f17a98", "text": "Calorimeters quantify the absolute dose absorbed by measuring the increase in temperature produced by radiation"}
{"_id": "Radiology$$$f7fe2735-c8f0-4349-b845-4e60a9c8c02e", "text": "The Monte Carlo (MC) method is a numerical calculation method based on random draws. A succession of draws is carried out in order to sample the random variables of the treated problem to deduce a value of interest. Repeated several times, this procedure allows to obtain a distribution of the values of interest and thus an estimation of their mean and their associated confidence interval. However, the number of samples must be sufficiently large for the empirical mean of the results to be an unbiased estimator of the expectation of the quantity of interest and its distribution as predicted by the central-limit theorem. In this process, the quality of the random number generator is essential. However, only pseudo-random numbers (having a period) can be generated and each Monte Carlo calculation code uses a different mathematical algorithm for that purpose."}
{"_id": "Radiology$$$b19e0acc-a580-462a-ba5f-4874cde4be80", "text": "The Monte Carlo method is currently used in many fields of physics to model the interactions of particles in a medium. In particular, it is used in dosimetry to estimate the energy loss of the particles in the medium and thus the absorbed dose."}
{"_id": "Radiology$$$c7484e03-156b-40f9-abab-afec6ee281ff", "text": "To simulate the course of the particles, MC codes use the notion of cross-sections expressed in barn (b) (1 barn\u00a0=\u00a010\u221222\u00a0cm2). This cross-section is a physical quantity representing the probability of collision between an incident particle and a target, as it is proportional to the ratio between the interaction rate (T) and the incoming particle fluence (\u03c6):\n\n (4.10)"}
{"_id": "Radiology$$$40b9081b-15d4-4f48-90f9-5ab9803c6b7d", "text": "with Ntarget the number of target particles in the target volume, corresponding to the surface S of the beam intercepting the target and starget the number of target particles per surface unit."}
{"_id": "Radiology$$$16c86736-5041-4b4f-b6f7-fbae0b00242d", "text": "Therefore, we can calculate the probability p for a particle to interact with the target in the following way:"}
{"_id": "Radiology$$$912a4c5f-23e1-461e-b907-139addbe7569", "text": "(4.11)"}
{"_id": "Radiology$$$01c20284-4ea4-4511-b216-68f3157a663e", "text": "With NA the Avogadro\u2019s constant, \u03c1 the target medium density, d the target thickness, and A the atomic mass of the target medium. Sigma?"}
{"_id": "Radiology$$$ebb8d1b4-0993-466b-b151-4fc5c3870979", "text": "We see that the probability of interaction depends directly on the quantity (\u03c1\u00a0\u22c5\u00a0d), which has the unit of g\u00a0cm\u22122. Moreover, we see the unit of \u03c3: p appear without dimension, \u03c3 has the dimensions of a surface. One can imagine \u03c3 as a geometrical surface: a particle striking the target in this area would interact, while outside this area it would cross the target without diffusion (Fig. 4.10).\n\nA schematic representation of a cross-section view of a rectangle with 9 circles between fluence phi and S of target diffusion.\n\nFig. 4.10\nSchematic representation of the cross-section for a target with Ntarget\u00a0=\u00a09 and an irradiated surface S"}
{"_id": "Radiology$$$a289b362-89bd-4a8f-8606-451de1236278", "text": "A schematic representation of a cross-section view of a rectangle with 9 circles between fluence phi and S of target diffusion."}
{"_id": "Radiology$$$3652f2f3-ed33-4815-a202-066135ec7ceb", "text": "From this concept of interaction cross-section, it is possible to define the mean free path (\u03bb) of a particle by means of the equation:"}
{"_id": "Radiology$$$113139cc-31eb-45a4-a8e8-c164b3f30e6f", "text": "(4.12)"}
{"_id": "Radiology$$$0f207cf5-f350-44fb-beb5-2210905852ea", "text": "This mean free path corresponds to the average value of a random variable representing the path traveled by a particle between two interactions (l). The probability density of this random variable is given by: \n\n. This probability density allows to sample the distance traveled by a particle between two interactions using a random variable \u03be0 uniformly distributed between 0 and 1 as follows l\u00a0=\u00a0\u00a0\u2212\u00a0\u03bb\u00a0ln\u00a0\u03be0."}
{"_id": "Radiology$$$909dd873-3152-4b8d-b3f3-7a3486061f6a", "text": "Cross-sections used in the MC codes are obtained either experimentally or are calculated from theoretical diffusion models and then used to determine the probability distributions of the random variables related to a trajectory as mean free path but also the type of interaction or the energy loss."}
{"_id": "Radiology$$$54394d7c-b5df-4228-88d4-39497e75ba09", "text": "A key point of these MC calculations is related to the simulation of the electron (and positron) interactions. Indeed, these particles lose a very small part of their energy at each interaction they undergo. Thus, they generate a very large number of events before being finally absorbed into the medium. The detailed simulation of this cascade of interactions and of these weak energy deposits is particularly slow. Thus, most Monte Carlo codes apply simplifying theories called \u201ccondensed histories\u201d or \u201cmultiple scattering\u201d that summarize a certain number of interactions in a single step, allowing to reduce the simulation time. The compromise between the detail of the simulation and the speed of the calculation conditions the performance of the calculation code. Among the most used MC codes in dosimetry, we can highlight PENELOPE \u00ab Penetration and ENErgy LOss of Positrons and Electrons, EGSnrc \u00ab Electron Gamma Shower \u00bb, MCNP6 and MCNPX \u00ab Monte-Carlo N-Particle eXtended \u00bb, or Geant4 \u00ab GEometry And Tracking \u00bb [9\u201313]."}
{"_id": "Radiology$$$7c1d5be0-421b-4bc2-87fb-4f56c438369a", "text": "Thanks to their capacity to include a large part of the physical processes involved in radiation\u2013matter interactions and the possibility of taking into account all the different components of the experimental geometry of the problems, MC codes have clear advantages since they can provide information on the values of certain quantities that cannot be determined experimentally."}
{"_id": "Radiology$$$9d2af54a-bffc-4398-bff3-03d5c2f4c0ff", "text": "In radiotherapy, it is required to deliver a dose to the tumor with an uncertainty equal to or less than 5% [14]. Prescribed dose metrology involves the determination of quantities characterizing the transfer and absorption of energy in the irradiated media. In principle, Monte Carlo simulations allow the dose calculation with the required accuracy using phantoms or even patient\u2019s voxelized images and thus provide information on dose distribution in the organ volume. However, to do this it is necessary to have quite exact knowledge of the beam characteristics, which means the need for detailed consideration of each accelerator including head shielding and structural components, which is very time-consuming and often submitted to industrial secret. Therefore, up to now, Monte Carlo codes have been mainly used to calculate the correction factors, often close to unity, to be applied to the experimental values obtained at the hospital during this metrological control."}
{"_id": "Radiology$$$51474819-f9f9-4238-9cda-b5982f0a957b", "text": "Nevertheless, The Monte Carlo technique is increasingly used for clinical treatment planning by implementing MC-based algorithms that are used in situations where conventional analytical methods used by the Treatment Planning Systems (TPS) of the machines are not enough. To decrease the computation time, most implementations for radiotherapy divide the calculation into two steps. The first one consists in simulating the head of the treatment machine. This part being fixed and independent of the ballistics associated with the treatment of patients, a phase space can be recorded at the output of the treatment head and be reused. The second step consists in tracking the particles previously recorded in the phase space in the specific geometry of a patient for a specific treatment. Both parts must be, of course, experimentally verified by comparisons with percentage depth dose curves (PDD) and absorbed dose profiles at various depths in water or with measurements in situations where electronic equilibrium is not respected, for example, at the interfaces of materials of different densities (Box 4.4)."}
{"_id": "Radiology$$$febd5823-e817-4b64-8012-5a3825bf1fa8", "text": "The Monte Carlo (MC) method is a numerical calculation method used to estimate the dose deposited through simulation of the stochastic events through which radiation deposits energy"}
{"_id": "Radiology$$$0bd2de36-a19a-4998-99a3-ca5b2eaa9f62", "text": "Microdosimetry was first introduced by H.H. Rossi in 1955 and is a fundamental and evolving research field in experimental radiation science [15, 16]. It studies the interaction between radiation and matter in micrometric volumes of cell-like dimensions taking into account the stochastic nature of the energy deposition process."}
{"_id": "Radiology$$$1952610a-5b4e-4cc5-9c8a-1df4ca3eef57", "text": "The interaction between radiation and matter is a stochastic process that manifests itself as energy deposition, \u03b4-electron production, or nuclear reactions. The latter produce charged particles, called secondaries, which in turn interact with surrounding matter, releasing energy, as \u03b4-electrons do. The fundamental quantity in microdosimetry is the lineal energy, y, which aims to quantify the individual energy deposition events. Energy deposition is a stochastic quantity defined as the energy deposited at the point of interaction:\n\n (4.13)"}
{"_id": "Radiology$$$5ba8a16d-2853-4b58-b971-8c46e7138aa1", "text": "where Tin is the energy of the incident ionizing particle (exclusive of rest mass), Tout is the sum of the energies of all ionizing particles leaving the interaction site (exclusive of rest mass), and Q\u0394m is the change of rest mass energy of the atom and all particles involved in the interaction. \u03b5i is usually expressed in eV. The lineal energy, y, is therefore defined by the ICRU report 36 ([17], p. 36) as the quotient of \u03b5tot by l, where \u03b5tot is the total energy imparted to a volume of matter by a single energy deposition event and l is the mean chord length in that volume:\n\n (4.14)"}
{"_id": "Radiology$$$aa588883-05d9-4024-a891-c03ff5c03cee", "text": "The lineal energy is usually expressed in keV/\u03bcm. A single energy deposition event denotes the energy imparted by correlated charged particles. Due to the stochastic nature of radiation interaction, each particle traversal gives rise to a different lineal energy value thus producing a probability distribution function. Such probability distribution functions fully characterize the irradiation at a given point. The individual energy deposition events (opportunely corrected for the detector charge collection efficiency and converted into energy to tissue equivalent material) are collected in a form of spectrum [f (\u03b5) vs \u03b5] where f (\u03b5) is the probability of an energy deposition event \u03b5. From these energy spectra, the lineal energy spectra [f (y) vs y; with y\u00a0=\u00a0lineal energy] can be calculated by dividing the energy events by the average chord length of the detector, which is the average distance that the particle will traverse in the detector. In the case of a spherical detector, this can be demonstrated to be 2/3 of the diameter, while for thin plate detectors in a unidirectional particle beam, this can be approximated to the detector thickness [18]. The probability density function f (y), also called lineal energy frequency distribution, is independent of the absorbed dose or dose rate. Its expectation value \n\nF is called frequency mean lineal energy and, being a mean value, is no longer a stochastic quantity."}
{"_id": "Radiology$$$222691e1-a3f4-49e8-a79e-48a0c595ce1f", "text": "(4.15)"}
{"_id": "Radiology$$$6836bd23-7033-42ba-81b8-67bdd3bc5800", "text": "As the radiation biological damage is proportional to the dose delivered, it is useful to consider also the lineal energy dose distribution d (y), as it provides the fraction of the total absorbed dose in the interval [y, y\u00a0+\u00a0\u03b4y]. The dose-weighted lineal energy distribution d (y) is therefore given by:"}
{"_id": "Radiology$$$61651406-0dff-4f48-a500-067d44efd0bc", "text": "(4.16)"}
{"_id": "Radiology$$$a4ee439c-47ac-49b4-88ee-f9a1d21a5f70", "text": "By definition, this distribution is normalized and is generally plotted as d (y) vs log (y) to make it easier to appreciate the relative contribution of various energy deposition events (see Fig. 4.11).\n\n4 waveforms. A and B are counts versus channel n, and lineal energy y, the peak value is (200, 1300), c and d, f of y, and y d of y versus lineal energy y of the fluctuating values.\n\nFig. 4.11\nThe same microdosimetric spectrum represented through the raw counts per channel acquired (a), counts as a function of the lineal energy (y) after a channel calibration (b), converted into lineal energy frequency (c) and dose (d) distributions"}
{"_id": "Radiology$$$307bfe23-f86f-4bfe-957b-fcfdb2a72e7f", "text": "4 waveforms. A and B are counts versus channel n, and lineal energy y, the peak value is (200, 1300), c and d, f of y, and y d of y versus lineal energy y of the fluctuating values."}
{"_id": "Radiology$$$84caebec-9481-4ee8-9a0c-db4b99f4ab76", "text": "Similar to the frequency mean lineal energy \n\nF, the dose-weighted mean lineal energy \n\nD can be defined as\n\n (4.17)"}
{"_id": "Radiology$$$babc4c6d-20bc-482a-9c05-0891e9b80cf8", "text": "This quantity provides the average lineal energy value when each energy deposition event is weighted based on its contribution to the total dose."}
{"_id": "Radiology$$$633213ec-2214-40f2-8f9a-34df3560616b", "text": "A crucial parameter for the calculation of the lineal energy is the mean cord length (\n\n), as the energy lost by a charged particle traversing a finite volume is proportional to the path traveled (track length) in that volume. The cord length however is itself a random quantity and for microdosimetric calculations, its mean can be estimated through Monte Carlo simulations or, for convex volumes, using the Cauchy formula \n\n = 4\u00a0V/S where V is the body volume and S is its surface area."}
{"_id": "Radiology$$$42ca22db-8004-4780-b5bc-83206fdf8d7b", "text": "The first microdosimeter detector was designed and developed by Rossi in 1955 [16]. It was a spherical proportional counter made of tissue-equivalent plastic walls and filled with low-pressure tissue-equivalent gas (TEPC\u2014Tissue Equivalent Proportional Counter). The low pressure allows to simulate micrometer volumes using a millimeter-size chamber (10\u2013150 mm diameter), which is easier to handle and manufacture. Methane or propane-based gases are typically used at a pressure of ~0.9\u00a0kPa to simulate volumes of a few micrometer in diameter. The electrons produced by the traversal of the radiation through the chamber are amplified and collected by an electric field. Every radiation traversal generates therefore a small current that gives rise to a pulse later processed by the acquisition electronics. This allows the quantification of the energy deposited in micrometer volumes by individual radiation events. TEPCs are still the most common detector for microdosimetry measurements. Their main limitation is related to the wall-effects, which are events generated by the interaction of the incoming radiation with the walls of the device, and to controlling the electron avalanche process caused by high electric fields, which are required to simulate very small volumes. New devices are addressing these limitations with wall-less TEPC where specially designed electrodes are aligned to generate an electric field within a confined volume and reduce electron avalanches (avalanche confinement TEPCs). The new devices are also less cumbersome than the first TEPC designed by Rossi and can be operated in clinically relevant radiation beams."}
{"_id": "Radiology$$$3a533534-7599-41cc-ba6f-4c626d4a9b9c", "text": "More recently, solid-state detectors have been employed as microdosimeters taking advantage of their unique characteristics including compact size, economic development, and low sensitivity to vibrations, which makes them particularly suitable for clinical environment. The working principle is based on the electron-hole pairs produced by the radiation as it crosses the sensitive volume of the semiconductor crystal. The number of electron-hole pairs is proportional to the total energy deposition (\u0394E) and the crystal ionization energy (W; average energy required to produce an electron-hole pair) by"}
{"_id": "Radiology$$$5acf75aa-c76b-4f4e-b9d2-a9088bc33855", "text": "(4.18)"}
{"_id": "Radiology$$$f5a70f70-f41a-4a20-a810-570e6078bc5e", "text": "The ionization energy is specific for each crystal and in the order of a few eV for typical semiconductor materials, which is an order of magnitude lower than that required for gas detectors. Furthermore, it is largely independent of the energy of the incoming radiation. Similar to TEPCs, the current generated by the collection of the produced electrons is used to quantify the energy deposition events. As the sensitive volume of the detector can be of a few micrometers, the pulses generated provide a microdosimetric spectrum of the incident radiation. In order to serve as a microdosimeter, solid-state detectors need to have well-defined and micrometer-sized sensitive volumes coupled to an efficient charge collection mechanism, as the electrical signal generated can be very small. A potential drawback of solid-state microdosimeters is their non-tissue equivalence, which generally requires additional conversion calculations provided by Monte Carlo simulations."}
{"_id": "Radiology$$$b19930a9-d24b-489d-b029-519ac49c6251", "text": "Silicon and diamond microdosimeters have been realized with sensitive volumes as low as 1\u00a0\u03bcm in thickness and a few hundred \u03bcm2 area and collection charges approaching 100%. Their small geometry provides also high-spatial resolution and the possibility to measure full therapeutic beam intensities, as the electronic chain is not saturated by the large number of particles required for clinical use. A main limitation of semiconductor microdosimeters is the electronic noise, as the devices work with little or no electronic gain due to the small voltage that can be applied to the small-volume semiconductor. This limits the lowest energy events that can be detected. The fixed size of the crystal also implies that different detectors may need to be used to obtain microdosimetric information for different sensitive volumes while gas-based detectors can achieve this by varying the gas-pressure. The advantages and disadvantages of both detector types are confronted in Table 4.2.Table 4.2\nComparison of tissue equivalent proportional counters (TEPC) and solid-state microdosimeters\n\u00a0\nTEPC\n\nSolid-state microdosimeter\n\nAdvantages\n\nTissue equivalence\nEasy handling and manufacturing\nOperation for clinically relevant beams\n\nHigh-spatial resolution\nCompact size\nEconomic development\nLow sensitivity to vibrations\nSuitable for clinical environment\n\nDisadvantages\n\nWall-effects\nHigh electric fields\n\nNo tissue equivalence"}
{"_id": "Radiology$$$882d8ccc-fd50-43bd-bcfc-e6f164646846", "text": "In the framework of radiation biology, either the linear energy transfer LET or the lineal energy can be used to specify the radiation quality. While the LET is frequently used, at least for broad classifications of different radiation qualities (high vs low LET, i.e., densely vs sparsely ionizing radiation), the use of the lineal energy is less common due to the limited experimental data and the complexity in analyzing the microdosimetric spectra. However, the use of LET to determine radiation quality is affected by some intrinsic limitations such as different particles of different mass and energy having the same LET being still characterized by a different energy distribution of the secondary electrons. In general, the microdosimetric spectra provide information that is not captured in the LET and it may be very beneficial for fundamental radiobiological studies aimed at linking biological response to energy deposition events, as well as for radiation protection and clinical work, e.g., predicting treatment efficacy."}
{"_id": "Radiology$$$5e2bfd81-2168-4b0a-816c-8a3943002235", "text": "Several LET-based RBE models have been developed over the years. The Microdosimetric Kinetic Model (MKM) is a model based on the dual radiation action theory and specifically developed to link microdosimetric measurements to radiobiological effects [19]. The central hypothesis of the dual radiation action theory is that the number of lethal lesions is, through a linear quadratic relationship, proportional to the specific energy deposited in a microscopic site. The specific energy (z) is defined as the ratio between the energy imparted (\u03b5) and the mass of the microscopic volume (m) [17]:"}
{"_id": "Radiology$$$7a20685d-39d0-4034-a1bb-0e847ec67149", "text": "(4.19)"}
{"_id": "Radiology$$$ce424b31-e563-4512-a77d-5ccc20794abf", "text": "As both the specific energy (z) and the lineal energy (y) measured by microdosimetry are related to a microscopic volume, the two quantities are linked through the microscopic volume mass (m) and mean chord length (l):\n\n (4.20)"}
{"_id": "Radiology$$$19428c75-588f-4e5b-ba00-4dfba6e3b6b2", "text": "with l, m, \u03c1, and rd the mean chord length, the mass, the density, and the radius of the microscopic volume, respectively."}
{"_id": "Radiology$$$26ab6b1f-83fd-47e7-9afc-41d99d0bf1f3", "text": "Kase et al. [20] formalized the link between cell survival fraction SF and the microdosimetric measurements:\n\n (4.21)"}
{"_id": "Radiology$$$872efe1b-3db6-44b8-a89e-b7ef56195912", "text": "with\n\n (4.22)"}
{"_id": "Radiology$$$22c3bc6c-6f45-45e7-a513-2de0e7fbab8a", "text": "where \u03b10 and \u03b20 are the linear quadratic parameters specific for each cell line (usually taken from X-ray measurements), D is the macroscopic dose absorbed by the cell and \u03c1 is the cell density. y0 and rd are fixed parameters accounting for the overkill effect observed at high lineal energy values (usually set at y0\u00a0=\u00a0150\u00a0keV/\u03bcm) and for the sensitive critical volume of the specific cell line, respectively. The parameter y* includes the measured microdosimetric spectrum (f (y)) providing therefore a direct link between radiobiological response and physical measurements. The use of the MKM and microdosimetry is the only approach providing a link between physical and biological measurements, considering that LET values cannot be experimentally determined. Supported by the fast development of technologies that will facilitate microdosimetric measurements, there is renewed interest in this approach. However, the precise estimation of the y0 and rd parameters requires further investigation (Box 4.5)."}
{"_id": "Radiology$$$61a5d789-c8b0-47a4-9e0d-edd808554a06", "text": "Microdosimetry quantifies individual energy deposition events through the lineal energy\n\nMicrodosimetry is performed through tissue equivalent proportional counters (TEPC) or solid state microdosimeters\n\nMicrodosimetry is able to directly link radiobiological response to physical measurements"}
{"_id": "Radiology$$$f026c4b2-6640-48e0-90ff-14a8f1b866be", "text": "Microdosimetry is performed through tissue equivalent proportional counters (TEPC) or solid state microdosimeters"}
{"_id": "Radiology$$$f761a051-59ca-447c-a2d3-c7ce7a314d77", "text": "Microdosimetry is able to directly link radiobiological response to physical measurements"}
{"_id": "Radiology$$$0236d48f-34d2-43a1-bcfc-acdc1273a366", "text": "When ionizing radiation (IR) interacts with a biological sample (which is composed of ~70% water in weight and the rest biological molecules), it can either directly hit the biological molecules or the water molecules. In both cases, these interactions can lead to an energy deposition at the interaction point (inelastic scattering) and the production of secondary particles, mostly electrons that can, in turn, also interact with the target. The ionized or excited molecules, particularly those of water, generate radicals (water radiolysis) that also can attack the biological unit molecules or aggregates, leading to subsequent structural damage of these molecules, which could ultimately have consequences on the functioning of the cell and its outcome."}
{"_id": "Radiology$$$3124919e-3b6c-445d-88f7-b1026a0412af", "text": "In this section, we will review the current state of knowledge concerning the different stages that lead from the physical interactions between ionizing radiation and biological matter (known as the physical stage) to the formation of damage to biomolecules as schematically depicted in Fig. 4.12. As indicated above, this includes the description of the production of radicals and their chemical interactions with molecules (chemical stage) but also the consideration of the geometrical and chemical structure of the target molecules. In particular, we will look at the effect of these interactions on the DNA contained in the cell nuclei, because it is well established that the DNA is a privileged target with regard to the effects of radiation on cells [21]. This continuous description will reveal differences at each stage level between the various types of radiation that will enable us to categorize them according to their capacity to produce these damages in terms of number and complexity.\n\nA schematic diagram exhibits different stages of physical, physicochemical, chemical, biochemical, and biological stages of physical interaction with target molecules, radical creation, radical diffusion, chemical reactions, biological effects, D S B, aberration, and mutations.\n\nFig. 4.12\nSchematic representation of the different processes leading to the damage produced by irradiation in the cells and their characteristic times"}
{"_id": "Radiology$$$b3a52bba-8e8a-47f2-85c5-7db015110813", "text": "A schematic diagram exhibits different stages of physical, physicochemical, chemical, biochemical, and biological stages of physical interaction with target molecules, radical creation, radical diffusion, chemical reactions, biological effects, D S B, aberration, and mutations."}
{"_id": "Radiology$$$e5ccd00c-0a30-467b-a144-cc80ad590fef", "text": "Different experimental techniques have been developed and used in recent years to measure this damage, as we will see in Sect. 4.3.3. However, in most cases, these techniques do not allow to have access to the total number of strand breaks or double strand breaks as well as to the base damage or to the complexity of the damage cluster. Thus, the Monte Carlo simulation method has become the \u201cgold standard\u201d for the prediction of these damages. This means however that it is necessary to know, with the least possible uncertainty, all the data allowing the description of these stages to feed the codes. In Sect. 4.3.4, we will detail what these data or parameters are, their current uncertainties, and therefore the current simulation capabilities with the different codes."}
{"_id": "Radiology$$$cf1eda94-6581-437b-9104-867570ab4de8", "text": "Ionizing radiation interacts with the exposed target through a cascade of random interactions with the atoms of the medium. The result concerns as much the interactions of the primary radiations as the slowing down of the secondary radiations emerging from them. During these interactions, radiation can be scattered or absorbed by gradually losing energy. If these absorption processes lead to sufficiently high energy transfers (typically >10\u00a0eV in radiobiology), they can lead to the ejection of electrons and modify the electronic layer of atoms and molecules and their chemical properties, which gives them the power to induce effects. Indeed, IR can be categorized as directly and indirectly ionizing depending on whether it is composed of charged or uncharged particles, respectively, but in all cases with enough energy to produce ions in matter."}
{"_id": "Radiology$$$93104050-5fd5-4918-bb5d-a3ffde360ce6", "text": "While ionization is considered the most important physical phenomenon to explain radiation-induced effects, excitation, a phenomenon in which electrons are transferred to higher atomic or molecular levels, is also considered among the possible events to be precursors of the radiation-induced effect. It is assumed that the ratio of energy loss by ionization and excitation is stable between radiations of different natures and energies, and, therefore, that the measurement of ionizations alone is sufficient. This approximation is important for the validity of reference dosimetric and microdosimetric measurement techniques using gas detectors. These techniques only \u201csee\u201d the ionizations but apply global physical data such as the average ionization energy (W) that accounts for both phenomena. It is generally recognized that the distinction between ionization and excitation is more blurred in condensed states, which are ultimately the ones targeted in dosimetry using other measurement methods than gas meters, and in radiobiology."}
{"_id": "Radiology$$$58056090-f26d-4972-9cf1-f36ea5ac9aaa", "text": "From a mechanistic perspective, if one wants to identify which energy deposition will result in damage to the structure of the target biomolecules, this proportionality between the number of ionizations in a volume (however small it may be) and the deposited energy is therefore not detailed enough. Indeed, in this context, it is necessary to \u201czoom in\u201d on the scale of the target\u2019s constituents at the nanometric scale to look at all the energy deposits (or energy transfers) produced by the initial radiation, as well as the secondary particles, notably the electrons. This is the study of the so-called track structure of radiation. At this scale, the differences between the spatial distribution of energy deposits defined by the tracks produced by different types of radiation (photons, electrons, energetic ions of different energies, etc.) lead to variations in early damage sufficient to produce a great diversity of later effects at both the cellular and tissue levels."}
{"_id": "Radiology$$$b8e952ea-a906-4e97-87c6-195f772e4ed5", "text": "Thus, for example, in the case of irradiation by high energy ions, we can look at the track they produce as being formed by a \u201ccore\u201d and a \u201cpenumbra\u201d region. The core is formed by the energy deposits of the projectile itself and is almost straight as elastic scattering does not have an important influence on the ion direction at energies under 10 MeV. The penumbra region is formed by the energy deposits of secondary electrons produced during ionizations with energies of ~1\u2013100\u00a0MeV, interacting with many molecules in the target [22, 23]."}
{"_id": "Radiology$$$a42a9f78-9cb5-4a4d-af73-401d34ef6304", "text": "However, when the primary particle ionizes water molecules, the main component of biological matter, many of the electrons are produced with low energy [24, 25]. Indeed, the energy of the emitted electrons for a given material is mainly determined by the oscillator-strength distribution of its valence electronic structure. The long-range of Coulomb interactions and the cross section that peaks at ~20\u201330\u00a0eV and decreases to very low values at 100\u00a0eV leads to the formation of electrons with energies, in general, less than 100\u00a0eV [26]. These low energy electrons (more extensively defined as those \u226410\u00a0keV) have a small penetration range (<1\u00a0\u03bcm) and inelastic mean free path (IMFP) (<10\u00a0nm) in typical condensed media [27] like water or DNA components. Therefore, most of the direct damage is produced around the track and, more specifically, at the track ends, where they are produced in high quantity."}
{"_id": "Radiology$$$139a2ed0-9e1e-4c43-a228-ef5d142fa87d", "text": "In fact, the electrons below ~20\u00a0eV seem to be particularly effective because, in addition to participating in the production of direct damage by ionizations or excitations of the constituents of the DNA, they can undergo resonant scattering with molecules, generating reactive radicals and molecular species, which can themselves contribute to DNA breaks [28] and oxidative damage. Experiments have indicated that electrons (or photons) with energies as low as ~10\u00a0eV can still induce double strand breaks, possibly through a resonance mechanism [29, 30]."}
{"_id": "Radiology$$$5af86c69-2a4c-4706-844d-c3fb2636a2e1", "text": "In the previous section, we were interested in the interactions between IR and the target molecule (DNA) and how some of these interactions can cause damage in a direct way. However, IR interacts in the same way with the surrounding water medium and induces local electronic instability. The physicochemical stage corresponds to the set of rapid electronic and atomic modifications resulting from the readjustments of the medium in order to return to thermal equilibrium. Thus, water molecules that are in an excited or ionized state can dissociate into new chemical species (radiolysis):"}
{"_id": "Radiology$$$148ef8cf-76f5-4925-9f61-20c1e631cbcd", "text": "Among these species, the OH\u00b0 (hydroxyl) radical is particularly interesting in radiobiology, because it can be the origin of DNA damages that are difficult to repair by the cell. This radical is mainly produced from the radiolysis of pure water following different mechanisms (dissociation directly after an ionization or an excitation of the water molecule)."}
{"_id": "Radiology$$$d2f50d76-672d-4d04-a2f6-e59c2212d555", "text": "Moreover, under-excitation electrons (with an energy lower than the last excitation shell of the water molecule, 8.22\u00a0eV) will undergo elastic scattering and will continue to lose energy by vibrational and rotational interactions until reaching the energy of the medium, the so-called thermalization energy. This thermalization process is in competition with two processes of electron capture, either by a neutral water molecule (\u201cdissociative attachment\u201d) or by an ionized water molecule (\u201cgeminal recombination\u201d) and is supposed to be completed within a picosecond after the irradiation."}
{"_id": "Radiology$$$a3ca77ad-0c7d-4e40-8592-039d410df59a", "text": "Beyond the picosecond, the newly created radiolytic species are free to diffuse randomly in the medium and to interact with each other, which is the chemical stage. Initially localized around the energy deposits of the track, they propagate and distribute more homogeneously in the medium as time evolves. The initial distribution of species depends strongly on the LET of the incident particle. In the case of high-energy electron projectiles (low LET), the initial distribution in the form of clusters will be more strongly marked than in the case of ions, where the LET is more important, and thus the energy depositions are more homogenously located all over the track. It is generally accepted that beyond the microsecond, most of the reactions between different clusters are completed and the chemical stage can be considered as finished for a given track."}
{"_id": "Radiology$$$699c6a48-2559-47ab-ae36-342b408e7b67", "text": "As indicated, all the simultaneous reactions are thus in competition and the temporal evolution of the chemical species, as shown in the example in Fig. 4.13, can strongly depend on the initial parameters. These reactions are very numerous in a liquid water medium [31] and increase even more in complex biological media. Thus, even in rigorous radiation chemistry experiments studying the kinetics of elementary chemical reactions, it can be difficult to measure the impact of secondary and competing reactions. In this context, simulation becomes a powerful tool to predict the complex dynamics of macroscopic observables, starting from elementary mechanisms [32].\n\n6 schematic circles of liquid water of 0.01 p s, 6, 23, 55, 76, 100 n s of radiolysis 1-kilo electron volt of electrons present at the center, and the scale of 200-nanometer present at the bottom. The electron is a single dot first and spreads as several dots.\n\nFig. 4.13\nSpatial and temporal evolution of the radiolysis products of a 1\u00a0keV electron in liquid water computed by Monte Carlo simulation (Geant4-DNA)"}
{"_id": "Radiology$$$c2e0858a-9162-4c0f-8e2b-7d617e0ba491", "text": "6 schematic circles of liquid water of 0.01 p s, 6, 23, 55, 76, 100 n s of radiolysis 1-kilo electron volt of electrons present at the center, and the scale of 200-nanometer present at the bottom. The electron is a single dot first and spreads as several dots."}
{"_id": "Radiology$$$1ea98910-ffc4-4faf-8c09-6826a5afc6e1", "text": "To do so, one category of numerical simulations consists in dividing the modeling into two phases with different levels of granularity and acceptable simplifying assumptions. In the first one, each radical species is considered individually, and we are interested in the calculation of the reaction rate, the diffusion coefficient, or the branching ratios. This first phase can be simulated using molecular dynamics (like Born\u2013Oppenheimer or Car\u2013Parrinello) and/or quantum mechanical calculations like TD-DFT. However, this approach is unfortunately prohibitive in terms of computation time for a high number of molecules, which limits their application to systems such as a cell. In the second phase, approximations can be made to significantly reduce the computation time. For example, molecules of the same species can be grouped in order to describe their evolution by a unique variable (concentrations) and two types of methods are often applied: either probabilistic (Gillespie algorithms) or based on the solution of differential equations."}
{"_id": "Radiology$$$1fd546b8-37b4-4194-bb56-ef941074572c", "text": "A second category of numerical simulations consists of describing the medium as a solvent or continuum and only calculating the diffusion and the chemical reactions of particular interesting species. This method is well adapted when the number of molecules is relatively small and, more particularly, when their distribution is inhomogeneous like in this case. Therefore, most of the track structure codes including the simulation of the chemical stage use this approach (Sect. 3.\u200b3.\u200b4) and include other simplifications as considering each molecule spherical and diffusing independently of the other molecules. In this frame of a diffusion-reaction model, their diffusion in the medium can be solved with the Green Function of the Diffusion equation (GFDE). The eventual reaction of two particles is considered when the interparticle distance is smaller than their reaction radius. The reactions can be either fully or partially diffusion-controlled and involve neutral or charged particles. This gives four classes of reactions that were introduced by Green et al. [33]. For totally diffusion-controlled reactions (type I), the rate constant is assumed to be infinite, meaning that the particles react whenever they collide. In this case, the GFDE solution can be calculated using the Smoluchowsky boundary conditions in three dimensions [34]. This reaction mechanism is the one most often triggered when radiolytic species diffuse and encounter a reactive site that is either representing other radicals or a DNA constituent (sugar-phosphate backbone or bases with high rate constants). For other reaction types, including those representing the scavenger effects, please refer to the literature [35, 36]."}
{"_id": "Radiology$$$49f0bd23-018a-4b3c-93c0-1bc04e4b178e", "text": "Within this frame (GFDE), different stochastic simulation techniques have been proposed in order to calculate the probability of reactions to happen depending on the position of each molecule at a given time [33, 37, 38] as the step by step method or the IRT for Independent Reaction Time method."}
{"_id": "Radiology$$$3ba55d88-e383-41f7-b441-aaf9363722ae", "text": "Indirect damages are the consequence of these reactions for the DNA molecule and can represent between 30 and 90% of the total DNA damage depending on the LET of the irradiation. Among them, of importance are the strand breaks produced by the hydroxyl radical capturing the hydrogen of the deoxyribose at the C4 position or the addition of hydroxyl radical to a nitrogenous base, resulting in base alterations. These altered bases are often unstable and can either decompose or react with environmental molecules and radiolytic species. The underlying reactions are therefore multiple and complex [39]. DNA-protein or DNA\u2013DNA bridging can also occur under the effect of radical species produced by radiation [40]."}
{"_id": "Radiology$$$49d03984-00dd-4b02-9d33-95e8dd6a95e8", "text": "It should be noted that the description of the chemical stage process as explained above becomes much more complex if we take into account a more realistic chemistry of the cellular environment adding factors such as the pH, the oxygen concentration, or the presence of more complex molecules around the DNA, commonly called \u201cscavengers\u201d because of their action on the radical species. In particular, the concentration of oxygen has been shown to have a significant impact on radiation resistance: indeed, carcinogenic cells, which are hypoxic, are 2\u20133 times more resistant to radiation than healthy, normoxic cells. This \u201coxygen effect\u201d is also believed to be one of the possible explanations for the protective effect on healthy tissue in the case of FLASH radiotherapy as the depletion of oxygen during irradiation could create a temporary hypoxic environment for both healthy and cancer cells. Nevertheless, this hypothesis is still not completely proven and the mechanism behind this FLASH effect however remains unknown [41]."}
{"_id": "Radiology$$$291e2140-21c5-4e4c-bdc2-124a872501c3", "text": "Radiation-induced damage is multiple and depends on numerous factors such as the type of radiation, the DNA configuration, or the irradiated medium condition. They are the result of the physical, physicochemical, and chemical processes explained in the previous sections and thus generated either by direct or indirect effects. The main DNA damages are strand breaks (simple, double, or clustered), base alterations, protein-DNA, and DNA\u2013DNA bridges. Of these, the radiobiology and simulation communities have historically been most interested in double strand breaks (DSB) or clustered damage including at least one DSB. Indeed, in most repair models this type of DNA damage is called \u201clethal\u201d or \u201csemi-lethal,\u201d as they are considered to lead to misrepair and cell death [42\u201344]. In all cases, and even if they can sometimes be correctly repaired by cellular repair mechanisms, it is established that these complex damages can have important consequences on the cellular survival or its functioning. Moreover, DSB can be detected experimentally and compared to the results of predictions from simulations. Several detection techniques exist, which are adapted according to the irradiation configuration, the dose used, or the cell type. Historically, comet assay or pulsed field electrophoresis (PFE) has been used with high-dose irradiation in order to generate DNA fragments that can be separated and measured leading to a given number of DSB detected. Data obtained in this way, for example, in the case of proton irradiations at different energies or gamma rays [40, 45], have been used extensively to validate codes such as PARTRAC [46], KURBUC [47], or, more recently, Geant4-DNA [48]."}
{"_id": "Radiology$$$8b883638-648d-4268-a3a0-a8aa3c0ffd9e", "text": "Other techniques, used at low dose, consist in using immunofluorescent probes to localize the radio-induced DSB within the genome. For example, in the case of H2AX immunofluorescence; the histone closest to a double strand break that contains the H2AX variant of histone H2A (approximately present at 25% of H2A histones and evenly distributed in the DNA) allows the detection of DNA double strand breaks through its phosphorylation. This phosphorylation is visible using specific antibodies, containing a fluorochrome substance, making the double strand breaks appear as luminous points called \u201cfoci\u201d or IRIF (ionizing radiation-induced foci) [49]."}
{"_id": "Radiology$$$a9b7241f-b4f5-42f5-911c-357ea7a50d63", "text": "An important quantity of experimental data has been obtained recently using this technique or with other fluorescent biomarkers such as the 53BP1 protein, which allows to quantify the DSB produced by different types of radiation and to compare them with the simulation results. However, an important bias of this technique is that, in general, one detectable focus does not correspond to a single DSB formed in the DNA [50], and therefore the irradiation conditions and the geometry of the target must be explicitly considered in the simulation for such validations [51, 52] ."}
{"_id": "Radiology$$$47437821-8ec3-4541-ba0e-15512aa93316", "text": "As we described earlier in this chapter, particle transport through matter using MC codes is generally handled via a \u201ccondensed history\u201d (CH) approach [53], currently used for dosimetry and the majority of microdosimetry applications for very energetic particles. In such a CH approach, many scattering events are grouped into fewer artificial steps, much longer than the mean free path of the particle, using multiple-scattering theories and a continuous energy loss along those steps. However, in order to simulate the physics at the nanoscale and to possibly link it to the biological effects of radiation with track structure properties in the nm regime [54], an event-by-event tracking of the different physical events is necessary to allow for better spatial resolution. Therefore, so-called track structure codes have been developed for applications in micro- and mostly nanodosimetry. In Table 1 taken from [55], we present the list of the main track structure codes that have been developed since the 80\u00a0s of the last century. In this table, it is indicated if the code includes the possibility of simulating the chemical stage and the materials available for the simulation of the physical stage."}
{"_id": "Radiology$$$30ac2b26-db49-4dc5-a866-651cf8714806", "text": "Indeed, in order to model all the physical interactions taking place in the physical stage, these codes need to include cross sections for simulating ionization, electronic excitations below the ionization threshold, and, ideally, vibrational or rotational excitations of the medium, in principle for all the interacting particles but particularly for secondary electrons, for the reasons explained in Sect. 4.3.2. Therefore, track structure codes either rely on pre-parameterized or tabulated sets of total and differential elastic and inelastic cross sections in order to calculate the energy deposition in condensed matter. An important point to consider is that at these low energies, the interaction cross sections depend on the composition of the material but also on its state. That is to say that the cross sections are not the same for a medium in a gaseous or a solid state. This leads to a particular difficulty because it is very difficult (not to say, almost impossible) to obtain experimental cross sections for biological media in their condensed state [24]. Only a few data obtained under very specific conditions exist for liquid water [56, 57] and these data are the basis for the set of models utilized to calculate the cross sections used by most track structure codes."}
{"_id": "Radiology$$$a32f9e26-da45-443d-948c-5aaff70ec93e", "text": "However, still, some track structure codes use atomic ionization/electronic excitation cross sections [58] obtained in the gas phase even if, in principle, they are not suitable for low energy excitations of valence electrons in water, since such excitations are sensitive to the electronic structure of the target [54, 59\u201361]."}
{"_id": "Radiology$$$c9dece19-7ae1-4a7d-8cd3-1f11e5cb5f39", "text": "Nevertheless, most of the theoretical models for the calculation of the cross sections used in these codes are based on the first Born approximation that uses the dielectric formalism. Here, the properties of a given material in terms of characterizing the inelastic interactions with charged particles are given in what is called the Energy Loss Function (ELF). This function allows calculating the mean free path and thus the inelastic cross sections. However, this function depends on the energy and momentum of the charged particles. As the existing experimental data have been obtained in the optical limit (i.e., for a zero momentum transfer), it is necessary to extend the calculation of this function for non-zero momentum transfers. Different dispersion algorithms based on the electron gas theory [53] are then used to redistribute the imaginary part of the function between the different ionization and excitation levels while preserving the agreement of their sum with the initial experimental data."}
{"_id": "Radiology$$$2806beff-bffc-4fec-a714-5aa63f00d217", "text": "However, differences in results of inelastic scattering obtained with different dispersion algorithms to extrapolate optical data to finite momentum transfer reach about a factor 2 in the range 50\u2013200\u00a0eV (and even further at still lower energies) [62] and consequently, these differences impact the obtained results. Recent studies have reported a potentially relevant effect of ionization clustering [63] or DNA damage induction [64]."}
{"_id": "Radiology$$$4b44f0ba-8fcf-421a-a139-c8509380d8fe", "text": "The description of the dielectric function of water also continues to be studied. Thus, only recently have works been published that address exchange and correlation effects based on the electron gas model or that improve the description of effects beyond the first Born approximation [27, 65]. The objective is to improve previous dispersion algorithms [66], to develop new TS codes [67, 68], and to clarify differences in inelastic scattering between different condensation phases [69]. Besides, other authors still work on measuring or adapting the theoretical model, using, for example, pre-parametrized models [70], to obtain cross-sections for targets other than water to be included in TS codes."}
{"_id": "Radiology$$$7ed3468c-030f-48bb-91df-0fcfc010e2b1", "text": "Concerning the elastic scattering models for low-energy electrons, different theoretical approaches are also developed and included in TS codes. Some use screening parameters derived from experiments to enlarge the applicability of the first Born approximation [71] and others use the Dirac partial wave analysis [72, 73]."}
{"_id": "Radiology$$$0f1e4c32-1813-49d1-be07-d60cf6071488", "text": "Overall, the accuracy of the results for water at energies below 100\u00a0eV remains questionable, and it would be desirable to have results for the dielectric function, the electron energy loss and the inelastic mean free path from ab initio TD-DFT approaches, i.e., with no free parameters and which, as a consequence, are prone to have predictive power and to be extended to a variety of targets (Table 4.3).Table 4.3\nMC track structure codes used in various radiation effects studies in biological cells\n\nCode\n\nParticles\n\nEnergy range\n\nTarget materials\n\nChemical stage\n\nCPA100\n\ne\u2212\n\nThermalization \u2212256\u00a0keV e\u2212\n\nWater (l), DNA\n\nYes\n\nDELTA\n\ne\u2212\n\n\u226510\u00a0eV\u201310\u00a0keV e\u2212\n\nWater (v)\n\nYes\n\nEPOTRAN\n\ne\u2212, e+\n\n\u22657.4\u00a0eV\u201310\u00a0keV\n\nWater (l, v)\n\nNo\n\nETRACK\n\ne\u2212, p, \u03b1\n\n\u226510\u00a0eV\u201310\u00a0keV e\u2212\n\nWater (v)\n\nYes\n\nETS\n\ne-\n\n\u226510\u00a0eV\u201310\u00a0keV\n\nWater (l, v)\n\nYes\n\nGeant4-DNA\n\ne\u2212, p, H, \u03b1, ions\n\nThermalization \u22121 MeV e\u2212,\n100\u00a0eV\u2013100 MeV p, H\n1\u00a0keV\u2013400 MeV \u03b1\n0.5\u2013106\u00a0MeV/u ions\n\nWater (l), DNA, gold, N2, and C3H8 (in progress)\n\nYes\n\nIONLYS/IONLYS-IRT\n\ne\u2212, p, ions\n\n0.2\u00a0eV\u2013150\u00a0keV e\u2212, p\n0.1\u2013300 MeV ions\n\nWater (l)\n\nYes\n\nKAPLAN\n\ne\u2212\n\n\u22651\u201310\u00a0keV e\u2212\n\nWater (l, v)\n\nYes\n\nKITrack\n\ne\u2212, ions\n\n\u226510\u00a0eV\u2013100\u00a0keV\n\nWater (l)\n\nNo\n\nKURBUC (KURBUC/LEAHIST/LEPHIST/CHEM-KURBUC)\n\ne\u2212, p, \u03b1, C\n\n10\u00a0eV\u201310 MeV (10\u00a0keV, liq.) e\u2212,\n1\u00a0keV\u2013300\u00a0MeV, p, 1\u00a0keV/u\u20132\u00a0MeV/u \u03b1,\n1\u00a0keV/u\u201310\u00a0MeV/u carbon\n\u22650.3\u00a0MeV/u\n\nWater (l, v)\n\nYes\n\nLEEPS\n\ne\u2212, e+\n\n0.1\u2013100\u00a0keV\n\nAll materials\n\nYes\n\nLEPTS\n\ne\u2212, e+, p\n\nThermalization \u221210\u00a0keV e\u2212, Thermalization \u221210 MeV p\n\nWater (v), CH4, C2H4, C4H8O, SF6, C4H4N2\n\nNo\n\nLion track\n\ne\u2212, p, ions\n\n>50\u00a0eV e\u2212, 0.5\u2013300\u00a0MeV/u p, ions\n\nWater (l)\n\nNo\n\nMC4\n\ne\u2212, ions\n\n\u226510\u00a0eV e\u2212,\n\u22650.3\u00a0MeV/u ions\n\nWater (l, v)\n\nNo\n\nMOCA8B\n\ne\u2212\n\n10\u00a0eV\u2013100\u00a0keV e\u2212\n\nWater (v)\n\nYes\n\nNASIC\n\ne\u2212\n\nThermalization \u22121 MeV e\u2212\n\nWater (l)\n\nYes\n\nNOTRE DAME\n\ne\u2212, ions\n\n\u226510\u00a0eV e\u2212,\n\u22650.3\u00a0MeV/u ions\n\nWater (l, v)\n\nYes\n\nOREC/NOREC\n\ne\u2212\n\n7.4\u00a0eV\u20131 MeV e\u2212\n\nWater (l)\n\nNo\n\nPARTRAC\n\ne\u2212, e+, p, H, \u03b1, ions\n\n1\u00a0eV\u201310 MeV e\u2212\n1\u00a0keV\u20131\u00a0GeV p, H, \u03b1\n1\u00a0MeV/u\u20131\u00a0GeV/u ions\n\nWater (l), DNA\n\nYes\n\nPITS04\n\ne\u2212, ions\n\n\u226510\u00a0eV e\u2212,\n\u22650.3\u00a0MeV/u ions\n\nWater (l)\n\nNo\n\nPITS99\n\ne\u2212, ions\n\n\u226510\u00a0eV e\u2212,\n\u22650.3\u00a0MeV/u ions\n\nWater (v)\n\nYes\n\nPTra\n\ne\u2212, p, \u03b1\n\n1\u00a0eV\u201310\u00a0keV e\u2212,\n1\u201310 MeV \u03b1,\n300\u00a0keV\u201310 MeV p\n\nWater (l, v), DNA, N2, C3H8\n\nNo\n\nRITRACKS/RETRACKS\n\ne\u2212, ions\n\n0.1\u00a0eV\u2013100 MeV e\u2212, ions 10\u22121\u2013104\u00a0MeV/u\n\nWater (l, v)\n\nYes\n\nSHERBROOKE\n\ne\u2212, ions\n\n\u226510\u00a0eV e\u2212,\n\u22650.3\u00a0MeV/u ions\n\nWater (l, v)\n\nYes\n\nSTBRGEN\n\ne\u2212, ions\n\n\u226510\u00a0eV e\u2212,\n\u22650.3\u00a0MeV/u ions\n\nWater (l, v)\n\nYes\n\nTILDA-V\n\ne\u2212, p, H, ions\n\n\u22657.4\u00a0eV e\u2212, 10\u00a0keV/u\u2013100\u00a0MeV/u ions\n\nWater (l, v), DNA\n\nNo\n\nTRAX\n\ne\u2212, p, ions\n\n1\u00a0eV\u2014few MeV e\u2212\n10\u00a0eV\u2014few hundred MeV/u ions\n\nWater (v)\n\nYes\n\nRADAMOL (TRIOL/STOCHECO)\n\ne\u2212, ions\n\n\u22657.4\u00a0eV\u20132 MeV e\u2212,\n\u22650.3\u2013200\u00a0MeV/u ions\n\nWater (l)\n\nYes\n\nTRION\n\ne\u2212, ions\n\n\u226510\u00a0eV e\u2212,\n\u22650.3\u00a0MeV/u ions\n\nWater (l, v)\n\nNo\n\nTRACEL/RADYIE/RADIFF\n\ne\u2212, ions\n\n\u226510\u00a0eV e\u2212,\n\u22650.3\u00a0MeV/u ions\n\nWater (l, v)\n\nYes\n\nAssociated particles, energy ranges, and target media (e.g., whether vapor or/and liquid phase cross sections are used) are indicated. (Taken from [55])"}
{"_id": "Radiology$$$0ab0001e-59b8-4f9f-b035-a7537d494f58", "text": "DNA damage is calculated from the energy depositions at nanometric scale in liquid water simulated with track structure codes and overlaid onto DNA models. DNA geometrical description can be as simple as cylindrical models of the DNA [74, 75] or as complex as a full atomistic description of human chromosomal DNA [76]. Nowadays, some of these models are directly included in the physical stage simulation (see Fig. 4.14) [48, 78], in order to facilitate the use of DNA material cross-sections instead of liquid water if they are available in the MC TS code. Besides, some subcellular structures are implemented in some TS codes [79] for the calculation of energy deposited in mitochondria or cellular membranes, for instance.\n\nA schematic representation of the geometrical model of D N A double helix to two linked nucleosomes, chromatin fiber loop built with voxels, and endothelial cell nucleus model.\n\nFig. 4.14\nExample of DNA target geometrical model used in the mechanistic simulation of DNA radiation-induced damage with the Geant4-DNA code [48]. The generation of this geometrical model was done with the DNAFabric software [77] from the nucleotide description to the complete genome of an eukaryotic cell nucleus in the G0/G1 phase"}
{"_id": "Radiology$$$faff8c84-1301-44ea-8208-39ea1caad5ba", "text": "A schematic representation of the geometrical model of D N A double helix to two linked nucleosomes, chromatin fiber loop built with voxels, and endothelial cell nucleus model."}
{"_id": "Radiology$$$f34d1e94-af09-4c9d-bb6c-318bd9c06696", "text": "From the resulting energy deposition values or interactions registered in the DNA volumes, direct damages are calculated using different approaches depending on the TS code. For instance, in some cases, an energy threshold value (often of 17.5\u00a0eV) in the nucleotide backbone is used to define a direct strand break [30, 80]. Others, as in the case of the PARTRAC code, use a uniform probability linear function from 5 to 37.5\u00a0eV [81] in order to calculate the resulting direct strand breaks, taking into account that very small energy depositions from vibrational excitations can also lead to this kind of DNA damage."}
{"_id": "Radiology$$$fab7530a-e5b0-4dff-bce2-89bc56da2a10", "text": "After the simulation of the physical stage, the geometrical model of the DNA target (essentially the position of all its constituents) as well as the position of the surrounding ionized or excited liquid water molecules are \u201ctranslated\u201d in terms of chemical species and injected in the code for the simulation of the chemical stage as described in Sect. 4.3.3. Here also, different codes use different parameters for the definition or the calculation of the indirect strand breaks depending on the DNA geometrical model; the number of included reactions or the duration of the chemical stage simulation [32]."}
{"_id": "Radiology$$$d2080959-a36a-4931-ad18-66c57306383d", "text": "Finally, in order to quantify the results, an important issue is the definition of double strand breaks and, above all, of clustered damage. Indeed, these notions are fundamental if we want to be able to compare the results of the simulation predictions with the experimental data, representing either the fragments produced (PFE, comet assay) or the signaling of a repair process set in motion by the cell (foci). The way of quantifying the damage predicted by the modeling of the physical, physicochemical, and chemical stages must thus be adapted each time to the characteristics of the experimental observable used for the validation. Nevertheless, for a relative comparison of different radiations, other types of classification can be used. Finally, in order to extend the modeling to later stages and include the repair mechanisms, the scoring method must also be adapted to the initial damage definitions of each repair model. Thus, the definition of a double stranded break is relatively well established as two breaks in the sugar-phosphate group on opposite strands separated by less than 10 base pairs (bp). More complex breaks or clustered damages are very author-dependent: DSBs accompanied by altered bases or single breaks at less than 10\u00a0bp, two double breaks separated by less than 25\u00a0bp, for instance [82], or more complete definitions as the classification proposed by Nikjoo et al. [83]."}
{"_id": "Radiology$$$4a225f8a-a1d2-4f97-be07-df874e2e5619", "text": "Recently, a standardized format for the simulation output results [84] has been proposed by different researches of this community, in order to preserve a maximum of information on the DNA damage simulated by the different codes and their location in the genome. This standard output amounts to a mapping of the individual damages produced (and the information of their direct or indirect origin) so that it can then be adapted to the scoring required for each use of the code, validation with experimental data, or use as input to repair models (Box 4.6)."}
{"_id": "Radiology$$$205584d1-944a-444c-80b8-161abeffb71f", "text": "MC Track structure developed over the years allow the simulation of energy deposition at nanometric scale\n\nFrom these results and a DNA geometrical target model, direct DNA damages can be calculated\n\nChemical reactions between radiation-induced chemical species in the cell nucleus and the DNA target generate the so-called indirect effects that account for up to 70\u201390% of the total strand breaks\n\nThe way of considering damage and its complexity must be adapted to the different experimental methods"}
{"_id": "Radiology$$$0460b73c-856a-45dc-822a-69e5190589ac", "text": "MC Track structure developed over the years allow the simulation of energy deposition at nanometric scale"}
{"_id": "Radiology$$$48802819-6e5a-4b06-84e1-bca6e23d7d6b", "text": "From these results and a DNA geometrical target model, direct DNA damages can be calculated"}
{"_id": "Radiology$$$af3e64e4-83aa-44e3-8126-7aaee9c2016c", "text": "Chemical reactions between radiation-induced chemical species in the cell nucleus and the DNA target generate the so-called indirect effects that account for up to 70\u201390% of the total strand breaks"}
{"_id": "Radiology$$$9a195ce6-56b6-42cf-b23e-058f1cca4c9f", "text": "The way of considering damage and its complexity must be adapted to the different experimental methods"}
{"_id": "Radiology$$$d0aa6787-a0bc-49c5-a1a0-8f4092c7653e", "text": "Conventional radiobiological studies are using broad (in the range of cm) irradiation fields for irradiating a whole cell population with a homogeneous dose in order to be able to screen an average reaction of this population to radiation. Already in the 1950s, the reaction of single cells to homogeneous irradiation or even to irradiation of subcellular parts became of interest [85]."}
{"_id": "Radiology$$$8ffa118b-730c-4ddb-b1cc-e992ffecf40f", "text": "Furthermore, in the 1990s the question arose whether there is a reaction of non-irradiated cells when they are located close to an irradiate one\u2014the so-called bystander effect. To address these and other related topics, it is necessary to be able to apply a single, subcellular-sized radiation beam (in the range of sub-micron to a few micron) with an accuracy in the range of 1/a few \u03bcm. This is the field of microbeam research, where the term microbeam is used for beam sizes at full width at half maximum in the range of ~1 to ~10\u00a0\u03bcm for photon as well as particle beams. Additionally, the development of micro-beams makes it possible to not only apply single beams but also arrays of beams, which can then be used to directly study the kinetics of DNA repair, the movement of damage sites, the connection to chromatin organization, and their relation to radiation quality and outcome."}
{"_id": "Radiology$$$29961a63-ffd6-43b4-a00d-22eca3dc16b1", "text": "When beam sizes get larger (~100\u00a0\u03bcm\u2013~1\u00a0mm), the beam or beam array is then termed minibeam or minibeam array. Here, the beam sizes become large compared to cell size and the difference in the effects switch from single cell differences to differences in cell population. An effect in this size range was described in the 1980s as the so-called dose-volume effect [86]."}
{"_id": "Radiology$$$45fa3c37-21fb-4f06-966c-a0c33e5b85db", "text": "This effect is exploited in modern radiotherapy approaches such as Microbeam radiation therapy (MRT) using photon beams with a beam size around 100\u00a0\u03bcm and particle minibeam radiotherapy (MBRT) using submillimeter-sized beams of protons or heavier ions (Table 4.4).Table 4.4\nDefinition of micro- and minibeam pattern and corresponding beam size and their application\n\nType\n\nSingle beam size (fwhm)\n\nApplication\n\nSingle microbeam\n\n~1\u2013~10\u00a0\u03bcm\n\n\u2013\u2003Radiosensitivity of subcellular\nStructures\n\u2013\u2003Bystander effect\n\u2013\u2003Adaptive effect\n\nArray microbeam\n\n~1\u2013~10\u00a0\u03bcm\n\n\u2013\u2003DNA repair kinetics\n\u2013\u2003Effects of high-LET particles\n\nSingle minibeam\n\n~100\u00a0\u03bcm\u2013~1 mm\n\n\u2013\u2003Dose-volume effect\n\nArray minibeam\n\n~100\u00a0\u03bcm\u2013~1 mm\n\n\u2013\u2003Modern therapy approaches"}
{"_id": "Radiology$$$4ec8b72b-9916-4b73-a030-8ab3385a1752", "text": "A new wave of interest worldwide in the use of micro-beams in radiation biology in the 1990s has led to the development of a number of tools that eventually evolved into facilities with potential clinical utility [87, 88]. Single cell micro-beams provide a unique opportunity to control precisely the dose to individual cells in vitro and the localization of dose within the cell. This makes it possible to study a number of important radiobiological processes in ways that cannot be achieved by other methods. Figure 4.15 shows such micro-beams as single or array application visualized on fluorescent nuclear track detectors and also via the foci of 53BP1 repair protein in human HeLa cells.\n\nA set of 3 radiobiological processes of single, and an array of 5 cross 5 matrix proton at 1 and 5 micrometers, respectively.\n\nFig. 4.15\nProton microbeam with a size of 0.8\u00a0\u03bcm (fwhm) visualized by a fluorescent nuclear track detector. Array of proton micro-beams with a point distance of 5\u00a0\u03bcm in both directions. 53BP1 accumulation in HeLa cells after microbeam array irradiation with a single carbon ion per point [beam size 0.8\u00a0\u03bcm (fwhm) and point distance 5\u00a0\u03bcm]"}
{"_id": "Radiology$$$57ef7e85-548e-48cf-91ca-187c3d2e62df", "text": "A set of 3 radiobiological processes of single, and an array of 5 cross 5 matrix proton at 1 and 5 micrometers, respectively."}
{"_id": "Radiology$$$9a1de154-663f-46f6-9d1c-cfad113593f7", "text": "Specifically, using charged particle micro-beams, it is possible to deliver exactly one particle per cell providing an ideal method for reproducing in vitro situations relevant to environmental exposure to naturally occurring radioactive radon gas, where virtually no cell receives more than one alpha particle traversal in its lifetime [89]. The high-spatial accuracy offered by micro-beams provides also a useful method to investigate subcellular spatial sensitivity such as the radiosensitivity of DNA close to the nuclear membrane [90] or of specific cellular organelles ([91, 92], p. 2019). Finally, single cell micro-beams have played a crucial role in the understanding of the bystander effect elucidating some of the mechanisms responsible for the transmission of the radiation effects from irradiated to non-irradiated cells [93]. Microbeam facilities can be used to selectively irradiate individual cells that can subsequently be revisited to ascertain what changes have occurred to that cell, and to its unirradiated neighbors."}
{"_id": "Radiology$$$40cb347b-0acb-4ea0-b314-8824ae30f069", "text": "There are four key aspects for the development of a single cell radiobiological microbeam: the radiation source, the radiation collimation or focusing, the radiation detection, and the cell alignment. A schematic view of a single cell microbeam can be found in Fig. 4.16.\n\nA schematic diagram exhibits a single cell microbeam of the ion source, accelerator, energy selection magnet, aperture, beam switch, beam scanning, focusing unit, sample, detector, signal, and control unit.\n\nFig. 4.16\nSchematic view of a single cell microbeam for radiobiological research using ions. The ions are produced in the ion source and accelerated. Energy selection is carried out with a 90\u00b0 magnet. Into the focus of this magnet, the aperture needs to be placed, which defines the object that is focused by the focusing unit. The biological sample is placed in its focus. Either in front or behind (shown here) the sample, the ion detector counts the ions and gives the signal to the control unit. Here the signal is processed and the beam switch and scanning unit can be regulated"}
{"_id": "Radiology$$$882751e0-5ce5-49ca-8bf9-50a6340f4f09", "text": "A schematic diagram exhibits a single cell microbeam of the ion source, accelerator, energy selection magnet, aperture, beam switch, beam scanning, focusing unit, sample, detector, signal, and control unit."}
{"_id": "Radiology$$$2a11b5b5-d156-4b90-bdd0-46be0733b800", "text": "As the main aim of single cell micro-beams is to be able to irradiate individual cells with high-spatial accuracy, the majority of micro-beams utilize low-energy radiation sources as penetration is not a requirement and higher radiation energies have stronger focusing or collimating requirements. Linear particle accelerators [94\u201396] or lab bench X-ray sources have been mainly used [93], although synchrotron sources have also been employed [97]. Energy resolution and stability are key parameters in order to achieve small radiation probes. The collimation or focusing system is a crucial element, as it provides a method for reducing the radiation beam to a micron or sub-micron size beam with which to probe the cells. Collimation systems (such as devices with high length-aperture ratio) are generally easier to implement and the final opening can be placed close to the cells in their wet environment, although it is very difficult to achieve beams smaller than a few microns [98]. The focusing approach offers the possibility to achieve sub-micron spot sizes while keeping cells in their physiological environment ([99], p. 2019; [100], p. 2017; [101]). The next important element is the particle detection, as a key aspect of the cellular micro-beams is being able to count single ions so one can deliver an exact number of particles (or dose) to a single cell. Charged particle micro-beams achieve this through individual particle counting systems placed either after the biological samples (in which case the radiation energy has to be high enough to traverse the samples) or between the collimation/focusing system and the cells (which may degrade the radiation spot size). Detector systems using a combination of plastic scintillators and photomultiplier tubes have been successfully employed achieving basically 100% detection efficiencies [87, 88]. The final element consists of imaging and micropositioning devices required to identify the biological targets of interest and align them with the radiation probe. Speed is essential because many assays of biological radiation effect require several hundreds, or even thousands of cells to be micro-irradiated individually. The performance of the various single cell micro-beams varies according to the methods adopted and particularly the radiation used. However, state-of-the-art systems can achieve targeting accuracies in the range of a \u03bcm and detection efficiency approaching 100% [91]. These systems can also irradiate 10,000\u00a0s of cells per hour."}
{"_id": "Radiology$$$eeaef57d-90c3-4311-be2c-d2b2d6863f63", "text": "One of the first key studies to make use of micro-beams was completed using the RARAF facility in New York. Miller et al. [102] demonstrated that the transformation frequency of a single alpha particle traversal is not statistically different that of no traversals. The finding has strong implications for radiation protection, and it supports the threshold hypothesis for radiation risks. Many radiobiological studies using micro-beams have been aimed at investigating the bystander effect. In particular, experiments with co-cultured glioma and fibroblast cells showed that micronuclei formation can be induced through bystander signaling across genotypes [103]. These studies also provided information about the signaling processes involved in the bystander response suggesting nitric oxide (NO) and reactive oxygen species (ROS) play a critical role [103]. Another important radiobiological contribution from micro-beams comes from adaptive response studies [104]. The adaptive response manifests itself as a reduction in the effect of a high dose of radiation when a small (<0.2\u00a0Gy) priming dose is given first, typically a few hours ahead of the high dose. This observation undermines traditional thinking with regard to radiation effects and has been linked to radiation hormesis; the concept that radiation at low doses may actually be beneficial. Also, the investigation of the radiosensitivity of subcellular structures is a key application for ion micro-beams [91, 92, 105]. For example, it could be shown that radiation-induced localized damage with high-LET particles only triggered localized inhibition of rRNA transcription in nucleoli rather than pan-nucleolar reaction, as it was seen in drug treatment or under UV irradiation [91]."}
{"_id": "Radiology$$$92ff57e6-1c96-4049-bb97-ad92ea06bf4a", "text": "Micro-beams cannot only be used in single beam mode but also with an array of micro-beams. Arrays of particle micro-beams are used especially for two applications. First for understanding the kinetics of DNA repair. The major advantage of micro-beams arrays here is that the damage is induced within a known pattern with defined distances at a defined time. With this method, repair kinetics of various proteins such as 53BP1, Rad52, Mdc1 [106], and PARP1 [107] could be measured. Furthermore, it was found that the sites of DSBs induced by micro-beams show a non-directed, sub-diffusion movement within the cell nucleus [108]."}
{"_id": "Radiology$$$b3537c8e-c219-458d-b313-33f094c1fc6f", "text": "Furthermore, by focusing low-LET protons to ~1\u00a0\u03bcm beam size the RBE can be increased. With this information, it was possible to further understand the enhanced RBE of high-LET particles [99, 109\u2013111], which is an effect on several scales. An enhancement of LET is possible when focusing the ions to ~1\u00a0\u03bcm beam size but this enhancement does not reach the RBE of a single high-LET particle, where most of the damage is caused in the core region of a few 100 nm diameter. The explanation of this is that when ions are focused to ~1\u00a0\u03bcm sizes, the DSB get closer together and therefore complex damages occur. If the damage is caused on even smaller scales, single strand breaks will get so close together that they cause further DSB, which enhances the biological effect [110] (Box 4.7)."}
{"_id": "Radiology$$$179df700-dbdc-49da-a2a5-f5d7dee3b9cf", "text": "Micro-beams are beams of photon or particle radiation and have a size of ~1\u2013~10\u00a0\u03bcm\n\nMicro-beams can be applied as a single beam or array of beams\n\nCollimation is easy to implement but beamsize only a few \u03bcm\n\nFocusing is more complex but beamsizes <1\u00a0\u03bcm are possible\n\nMicro-beams can be used to study bystander effect, radiosensitivity of subcellular structures, and the enhanced RBE of high-LET particles"}
{"_id": "Radiology$$$5a9f314f-c22e-4005-b89b-053f302e0f2e", "text": "Micro-beams are beams of photon or particle radiation and have a size of ~1\u2013~10\u00a0\u03bcm"}
{"_id": "Radiology$$$7eda4bd5-26d4-4587-9fce-7587da4b1e82", "text": "Micro-beams can be applied as a single beam or array of beams"}
{"_id": "Radiology$$$0164d405-a440-47e6-abb4-70a29752f3f9", "text": "Collimation is easy to implement but beamsize only a few \u03bcm"}
{"_id": "Radiology$$$2784632d-0ff9-4990-a60e-f6466962aa77", "text": "Micro-beams can be used to study bystander effect, radiosensitivity of subcellular structures, and the enhanced RBE of high-LET particles"}
{"_id": "Radiology$$$525dfe0d-2221-4315-abd2-da8784a61910", "text": "A minibeam is a narrow radiation beam, whose width is in the range from ~100\u00a0\u03bcm to approximately 1 mm. The minibeams play a key role in the development of new therapy approaches, which aim to lower the side effects of external radiotherapy by spatially sparing the healthy tissue, especially in front of the tumor. Using photons, this method is called microbeam radiation therapy (MRT) in order to be able to separate from the particle minibeam therapy (MBRT) using protons and ions. MRT uses beam sizes in the order of 100\u00a0\u03bcm, whereas in pMBRT the beam sizes are a bit larger up to ~1 mm. There are different approaches of how to irradiate the tumor with minibeams; with photons or heavy ions the minibeam pattern with peaks and valleys is typically maintained, while with protons or light ions homogeneous irradiation of the tumor is feasible."}
{"_id": "Radiology$$$a9bdc7d1-aebc-4880-8e2f-2958c5717c3d", "text": "Nevertheless, both methods rely on the same effect, that the smaller the volume which is irradiated, the more dose is tolerated by tissue, the so-called dose-volume effect [86]. This is attributed to undamaged migratory cells surrounding the damaged tissue, which are able to infiltrate and thus reduce tissue necrosis. A further effect that plays a role in the tissue response to submillimeter beams is the microscopic prompt tissue repair effect. For such small irradiation fields, the capillary blood vessels can be repaired within days or even hours. The intact blood vessels are then able to support the repair of surrounding tissue. The detailed underlying radiobiological effects are yet not completely understood and topic of investigation worldwide. Nevertheless, the use of minibeams in radiation therapy is already used in spatially fractionated radiation therapy such as GRID therapy or is on the way to clinical studies (Box 4.8)."}
{"_id": "Radiology$$$d427057a-73b9-49f7-8f3d-b7afd9fbce74", "text": "Minibeams are beams of photon or particle radiation and have a size of ~100\u00a0\u03bcm\u2013~1 mm\n\nMinibeams can be applied as a single beam or an array of beams\n\nCollimation is easy to implement but can give secondary radiation and limits flexibility\n\nFocusing is more complex to implement but has no secondary radiation and full flexibility\n\nMinibeams are used to study the dose-volume effect and the microscopic prompt tissue repair\n\nMinibeams are transferred into clinical application in microbeam radiation therapy (MRT) for photons and minibeam radiation therapy (MBRT) for particles"}
{"_id": "Radiology$$$28615c31-de56-41fc-9827-c677cb321539", "text": "Minibeams are beams of photon or particle radiation and have a size of ~100\u00a0\u03bcm\u2013~1 mm"}
{"_id": "Radiology$$$ec090d37-dfad-4bea-b889-5ee776ee797f", "text": "Minibeams can be applied as a single beam or an array of beams"}
{"_id": "Radiology$$$ba1ac870-f0a7-460e-a30f-5c0608dec273", "text": "Collimation is easy to implement but can give secondary radiation and limits flexibility"}
{"_id": "Radiology$$$4800855c-bbf1-446b-bc02-94b30ce4e1a0", "text": "Focusing is more complex to implement but has no secondary radiation and full flexibility"}
{"_id": "Radiology$$$bfbeb4e5-2316-4b91-a8d7-850c130e40cd", "text": "Minibeams are used to study the dose-volume effect and the microscopic prompt tissue repair"}
{"_id": "Radiology$$$05abbe91-0a41-4883-9517-e21ea9565049", "text": "Minibeams are transferred into clinical application in microbeam radiation therapy (MRT) for photons and minibeam radiation therapy (MBRT) for particles"}
{"_id": "Radiology$$$b0d22aef-1eb0-40df-8943-021ca238c196", "text": "Suppose an object (say a macromolecule) is irradiated. Assume that the radiation deposits one or more primary ionizations (i.e., ion clusters) within the molecule. Assume that the molecule has a particular function within our cells and that this function is destroyed only if the ion cluster destroys one particular part of the molecule and that the molecule still works equally well if the ion cluster damages any other part. The sensitive area inside the molecule is then called the target (Fig. 4.17) (Box 4.9).\n\nA schematic diagram of an irregularly shaped macromolecule irradiated object of a small area of the target with volume v.\n\nFig. 4.17\nOne assumes that the target only consists of a small area of the object being irradiated. The object may be a macromolecule or an organism"}
{"_id": "Radiology$$$9daa6cf6-9e44-40b9-8d34-4002cc4b340e", "text": "A schematic diagram of an irregularly shaped macromolecule irradiated object of a small area of the target with volume v."}
{"_id": "Radiology$$$6da41895-d676-419b-9efa-63f321509fa4", "text": "Target theory postulate: only energy deposits in the target can destroy the function of the object"}
{"_id": "Radiology$$$d7f2c962-36be-46c6-af7d-e4f9af3e02c0", "text": "For the sake of simplicity, assume that one hit represents one primary ionization. This can in some cases be an oversimplification since a primary ionization can give rise to many ion pairs however the probability is largest for a primary ionization to give rise to only one ion pair [112]."}
{"_id": "Radiology$$$3d6b762b-4478-4fbd-bf46-041f8bdfffc6", "text": "We can now introduce the dose as the number of hits per cm3. In an elegant experiment, Rauth and Simpson [113] found that the energy deposition per primary ionization is about 60\u00a0eV on average. Although this is not the exact average energy per hit, it can be used as an approximate value. Since the dose gives the energy deposition per cm3 (it indicates the energy per g or kg, but when we know the density of the irradiated substance we easily convert it to cm3), we can use Rauth\u2019s and Simpson\u2019s measurement to convert the dose to the number of primary ionizations per cm3 and as a first approach use this as an indication of the number of hits per cm3."}
{"_id": "Radiology$$$674373dd-3aec-40ab-96cd-fa14a43a3326", "text": "This theory relies on certain key assumptions1.\nIonizing radiation deposits the energy into discrete energy packages that we call hits.\n\u00a02.\nThe response of a molecule (or cell) occurs only if a number of n hits is deposited in the target.\n\u00a03.\nThe number of hits deposited in the target in the irradiated material must be Poisson distributed."}
{"_id": "Radiology$$$5f063293-4576-4949-9f30-235c935f6674", "text": "Ionizing radiation deposits the energy into discrete energy packages that we call hits."}
{"_id": "Radiology$$$cd6ddceb-ea84-4a41-8318-e55c21837b28", "text": "The response of a molecule (or cell) occurs only if a number of n hits is deposited in the target."}
{"_id": "Radiology$$$a3f7494c-c3eb-4326-b722-93a1d94b08ed", "text": "The number of hits deposited in the target in the irradiated material must be Poisson distributed."}
{"_id": "Radiology$$$25dcf8a6-1148-46ce-96d9-55dbf6b182f7", "text": "Assumption number 3 can generally only be considered satisfied when the dose is high. Note that the average number of hits in a volume equal to the target volume is \u03bc\u00a0=\u00a0vD where the dose is given in hits/cm3 and the target volume, v, is given in cm3. If n is the actual number of hits in the target in a particular irradiated object, the probability of this number of hits being seen is Poisson distributed as:\n\n (4.23)"}
{"_id": "Radiology$$$7dd34e14-a732-4752-aeab-334a366d7acb", "text": "If the irradiated object is a macromolecule in a cell, and if this macromolecule is inactivated (i.e., loses its biological function) if it receives n hits in the target, then the molecule retains its function if the number of hits in the target is n\u22121 or less. We can therefore calculate the probability, pf, for the molecule to retain its function. It must be the sum of the probabilities that it will receive one, two, three, etc., up to n\u22121 hits in the target [112]:\n\n (4.24)"}
{"_id": "Radiology$$$270bd6a4-aed7-40c9-a0a7-978ccb3ffd7a", "text": "or\n\n (4.25)"}
{"_id": "Radiology$$$0d156617-b4be-441e-9fc1-3268099be37a", "text": "Here, pf represents the probability that a target molecule will not be inactivated by the dose D. However, this can also be viewed as pf representing the fraction of the irradiated molecules that do not become inactivated by the radiation [112]. If one irradiates N0 molecules and the number that is not inactivated is N, Eq. (4.25) can be rewritten as:\n\n (4.26)"}
{"_id": "Radiology$$$49fd8183-2cc9-4e54-a8a3-ce643c697037", "text": "If the molecule becomes inactivated by only one hit in its target, n\u00a0=\u00a01 and Eq. (4.26) becomes:\n\n (4.27)"}
{"_id": "Radiology$$$eba4e720-02c2-4088-82da-cb11d9533544", "text": "This is the Single-Hit Single-Target model of radiation survival. While simple, it is a very powerful equation that can provide insights into the characteristics of cellular response to radiation exposure (Fig. 4.18).\n\nA graph of cellular survival L n versus Dose of single-target model. The linear line plotted has a downward slope.\n\nFig. 4.18\nThe relationship between the predictions of the single-hit single-target model on cellular survival versus radiation dose [here N/N0 from Eq. (4.27) is replaced by S/S0 or the ratio of cell survival at any dose D to that at 0\u00a0Gy]"}
{"_id": "Radiology$$$45fd4e70-c9aa-40c1-9a0e-09da431c5629", "text": "A graph of cellular survival L n versus Dose of single-target model. The linear line plotted has a downward slope."}
{"_id": "Radiology$$$21a72564-3b66-4f74-8b0e-5bf61247c9b1", "text": "One key insight is that the equation allows us to determine the molecular weight of the target. From the previous derivation, we know that if we express dose in the unit hits/cm3, we can determine the target volume. If we also know the density of the irradiated molecules we can, based on the target theory, determine the molecular mass of the target. The dose is normally given in Gy so the calculation must be based on this unit:\n\n (4.28)"}
{"_id": "Radiology$$$e7d8aca8-1319-4e51-a72d-520af79ec82c", "text": "using that 1 J\u00a0=\u00a06.242\u00a0\u00d7\u00a01018 eV. From the experiments by Rauth and Simpson, we know that it takes an average 60\u00a0eV to give a primary ionization in an organic material. This value is not necessarily the correct amount of energy needed for a hit, but as an example it can be used. Then we can convert [Gy] into [hits per gram]:\n\n (4.29)"}
{"_id": "Radiology$$$bc05c8aa-7145-4011-8775-c6437833ba5b", "text": "D37 is the dose that gives on average one hit per target, i.e., v\u00a0\u22c5\u00a0D37\u00a0=\u00a01 . The surviving fraction at this dose is e\u2212vD= e\u22121\u00a0\u2248\u00a00.37 = 37%, which gives rise to the name of the quantity. If we assume that we irradiate the molecules with different doses and find the D37, we have on average one hit per target at this dose (v\u00a0\u22c5\u00a0D37\u00a0=\u00a01). Suppose the D37 is given in the unit hits/g. We can then calculate the mass of the target in the unit gas:\n\n (4.30)"}
{"_id": "Radiology$$$28c99792-d350-4de5-b331-b5a928b2e374", "text": "In practice however the dose is in Gy and we must use Eq. (4.29) to convert from hits/g to Gy:\n\n (4.31)"}
{"_id": "Radiology$$$bdb915f6-3eb0-4679-b6fe-aacc274ddf3d", "text": "If the density of the target is \u03c1\u00a0=\u00a0MT/v we can then calculate the target volume:\n\n (4.32)"}
{"_id": "Radiology$$$daae45d9-3d76-4ad1-b20a-36a02c3f757a", "text": "In Eq. (4.32) the dose is in Gy. The final calculation of the target volume is left to the reader."}
{"_id": "Radiology$$$909fec03-2fda-43de-b272-93dd653fecc3", "text": "Complicated molecules or cellular organisms may well have more targets and it also may take more than one hit per target to inactivate the molecule or cell."}
{"_id": "Radiology$$$9ec4f681-a946-4c13-84af-bf66db608ca9", "text": "Recall Eq. (4.25), which calculates the probability that a molecule will not be inactivated if it has one target and that this is deactivated by n hits. The probability of one target being deactivated is then:\n\n (4.33)"}
{"_id": "Radiology$$$2f1e2160-9409-49ab-87a1-a7f7101f09a5", "text": "where Nii means the number of molecules that were inactivated. If we now assume that the molecule has a number of m targets that all must be inactivated for the molecule to be inactivated, the probability of inactivation becomes:"}
{"_id": "Radiology$$$7b552a9a-ec86-4f36-a6b4-d8686b1f5091", "text": "(4.34)"}
{"_id": "Radiology$$$074d3005-bbf5-40c4-8700-d45869c116e8", "text": "and the probability that the molecule will not be inactivated is then:"}
{"_id": "Radiology$$$45e17386-213c-420c-990d-fe6a847ccfbf", "text": "(4.35)"}
{"_id": "Radiology$$$cd4ae834-1e1c-44cc-aeeb-2aeb2a8da378", "text": "In the most likely case, it only takes one hit per target for the molecule to be inactivated, that is, n\u00a0=\u00a01. This gives the following special case:"}
{"_id": "Radiology$$$6a94f951-e6c8-4350-930b-e61eaf4989fe", "text": "(4.36)"}
{"_id": "Radiology$$$fc8c440c-d407-4f4a-a66b-5673a3e0f1de", "text": "This is the famous multi-target single-hit equation. For many decades, this was the model radiobiologists fitted to their dose-response curves when they tested the effect of ionizing radiation on human cells. Much of the formalism of this equation and parameter values are still in use when dose-response curves are discussed and described. Therefore, it is important that we perform an analysis of this function:\nThe equation has a shape with an initial shoulder at small doses followed by, a straight line for large doses. This is seen if the equation is expanded by a power series:"}
{"_id": "Radiology$$$bae825d4-b508-42fb-9ff9-4d60ee6a03a1", "text": "The equation has a shape with an initial shoulder at small doses followed by, a straight line for large doses. This is seen if the equation is expanded by a power series:"}
{"_id": "Radiology$$$3ad7d350-5b2f-4350-ade2-b32e000df4aa", "text": "(4.37)"}
{"_id": "Radiology$$$eb2d399e-83fa-4471-850d-8c2131e1f64e", "text": "Focusing on high-dose regions, all terms with (e\u2212vD)2 and higher power can be ignored. We then end up with the following expression, which only is valid for high doses:\n\n (4.38)"}
{"_id": "Radiology$$$1095e44a-e7c8-4202-a470-9b14bf7e5171", "text": "This is a straight line in a semi-logarithmic plot, and the line intersects the ordinal at point m as shown in Fig. 4.19.\n\nA concave down, decreasing curve graph of L n of S by S 0 versus dose of G y, and the dashed line extrapolation number.\n\nFig. 4.19\nThe relationship between the predictions of the multi-hit single-target model on cellular survival S and radiation dose. S0 is the plating efficiency of the unirradiated controls"}
{"_id": "Radiology$$$9a59e455-8371-411d-beff-9f246bd4e21d", "text": "A concave down, decreasing curve graph of L n of S by S 0 versus dose of G y, and the dashed line extrapolation number."}
{"_id": "Radiology$$$71711853-7abe-4650-8891-32d018acdd93", "text": "Note that in Fig. 4.19, the actual dose-response curve has an initial shoulder followed by a straight line at higher doses. Thus, only the straight line at higher doses is described in Eq. (4.38). The dose-response curve itself is described in Eq. (4.36)."}
{"_id": "Radiology$$$2c29df93-0f0b-4282-bb6d-6ab6575e82d6", "text": "Figure 4.19 illustrates a dilemma with regard to the common definition of radiation sensitivity. It is common to say that the target volume is an expression of radiation sensitivity. For a single-hit, single-targeted model, one obtains a value v\u00a0=\u00a01/D37. For a single-hit, multi-target model like the one shown in Fig. 4.19, we can say that v\u00a0=\u00a01/D0 expresses radiation sensitivity. D0 is the dose, which reduces the surviving fraction by 63% in the linear part of the curve (Box 4.10)."}
{"_id": "Radiology$$$454a109a-3451-4c35-ac0d-6b16451c0501", "text": "This may seem a bit odd: If we have two types of molecules, one with one single target and one with m targets, but where the target volumes are the same, such that D37\u00a0=\u00a0D0, as is the case in Fig. 4.19, then the radiation sensitivity is the same in the two cases and is only given by the slope of the dose-response curves at high doses. Nevertheless, one can immediately see that the curve that has a shoulder shows a higher survival value for a particular dose than the one that does not have a shoulder. This is because it is an advantage for a molecule that the radiation must destroy two or more targets rather than just one to inactivate the molecule. Still, many authors have chosen to use the target size as a mathematical expression of the radiation sensitivity."}
{"_id": "Radiology$$$87100069-d21d-49c3-ab2d-4cf9d6645bac", "text": "One term is important to get into at this stage, namely sublethal damages. So far, we have most talked about irradiating molecules and not cells. However, we can talk about cells in the same way that we have discussed molecules in the hit and target theory. The radiation damage then inactivates some function that the cells usually have. Very often, the effect is referred to as cell death or lethality. This term suggests that radiation should produce some form of death. Often, this will give incorrect associations to the chemical or biological responses we measure. However, the terms lethal, sublethal, and potentially lethal damages have been so incorporated that it is completely impossible to avoid their use."}
{"_id": "Radiology$$$616c5b49-84ff-4919-b8cc-a0d65d880014", "text": "Note that, based on the formalism of the target theory, sublethal damage is damage to the target. A hit outside the target is no damage according to this theory. When damage in the target does not produce any effect, it is because we have a multi-hit system or a multi-target system (Box 4.11)."}
{"_id": "Radiology$$$68e6dda1-d5c7-443f-9f5d-104c2adc91d7", "text": "Sublethal damage refers to damage, or really ion pairs, which is the cell or molecular target, but does not cause any effect in itself"}
{"_id": "Radiology$$$ab8a2bec-bab1-4cc5-8cfc-496df8b42e45", "text": "Later in this chapter, we will talk about dose rate effects. These state that there usually is a stronger effect of a dose when given in a short time than when given over a long period of time. The reason for this is, according to the target theory\u2019s formalism, that the first hit is not enough to inactivate, but that it can interact with the next so that the two or more together can inactivate. However, if the cells or molecules are able to repair the first hit before the next, we will not get such interactions. The fact that this effect decreases with decreasing dose rate is therefore a sign that the radiation damage is repaired."}
{"_id": "Radiology$$$f3a309c5-dfbd-45e1-a22e-70b881e0d63c", "text": "Note also, that the shoulder of the multi-target curve in Fig. 4.19 has nothing to do with repair in the target theory\u2019s formalism. It is just because the cells or molecules can either tolerate one or more hits in their one target or that they have more than one target."}
{"_id": "Radiology$$$7a4f72bd-f809-4618-976e-54dfd5bcfd25", "text": "While target models are useful to generate an initial understanding of the relationship between radiation dose, cell survival, and the process of energy deposition, these models have not been generally adopted because of their use of multiple terms, and also because the \u201ctargets\u201d which the models predict have never been identified. Several models have been developed based on target theory, among which the linear quadratic model (LQ) has emerged for application clinically and preclinically [114]. The expression for cell survival according to the LQ model is:\n\n (4.39)where S represents the probability of cell survival when subjected to dose D and the \u03b1 and \u03b2 parameters determine the linear and quadratic components of cell damage, respectively. The dose-squared dependence implies that the survival plot on a logarithmic scale has the characteristic appearance of a quadratic curve (Fig. 4.20). A linear relationship dominated by the \u03b1-parameter is observed at very low doses, while for higher doses the quadratic relationship governed by the \u03b2 parameter becomes dominant. This characteristic feature of the survival curve is commonly referred to as the shoulder.\n\nA decreasing line graph of surviving fractions versus dose of G y. From the top, a vertical line is labeled alpha by beta, beta D power 2, and alpha D. The line is split into a solid line of alpha by beta high, and dashed line of alpha by beta low.\n\nFig. 4.20\nIllustration of LQ curves for high and low \u03b1/\u03b2 ratios. For the low \u03b1/\u03b2, the shoulder of the curve is more pronounced. The \u03b1/\u03b2-ratio can be found by drawing a line with the initial slope (\u03b1) of the curve and finding the dose where the contribution from the linear and the quadratic terms are equal"}
{"_id": "Radiology$$$dd5223a3-58db-43cd-ac57-4809e783f8a2", "text": "A decreasing line graph of surviving fractions versus dose of G y. From the top, a vertical line is labeled alpha by beta, beta D power 2, and alpha D. The line is split into a solid line of alpha by beta high, and dashed line of alpha by beta low."}
{"_id": "Radiology$$$347a4af6-8d3d-4b94-a9e4-d819ab2e4a57", "text": "The linear quadratic model needs only two parameters and shows a good fit for experimental observations. As for its biological interpretation, different approaches have been presented, such as those of Kellerer and Rossi, Chadwick and Leenhouts, and Bodgi and Foray."}
{"_id": "Radiology$$$aaf025a2-adcc-45ff-915c-2e987b11b7ab", "text": "Kellerer and Rossi sought to analyze the relationship between dose and effect in a way that was invariant to the quality of radiation, as they considered that the biological effect, in addition to its dependence on the deposited energy, also depended on its microscopic distribution [115]. Having observed the simplicity of the relationship between the doses of two different types of radiation with different LET (see Sect. 1.\u200b6) that lead to the same effect (relative biological effectiveness\u2014RBE, see Sect 1.\u200b6) they proposed a theoretical model that arrives at a linear and quadratic relationship with the dose. The model assumes three possible states for the biological entity: non-damage, pre-damage, and effect. The probability of transition between states (without allowing for reversion) depends on the dose and a careful choice of these values results in different models [115]. According to the model, the biological effect can be achieved by a direct transition from the non-damage state to the biological effect or by two consecutive transitions between non-damage to pre-damage and pre-damage to biological effect. The first case represents the situation of reaching the biological effect with one hit (single-hit event), which is dominant for high-LET radiation, and for the second case, two hits (double-hit event) are required."}
{"_id": "Radiology$$$ec5d80e6-db71-435a-b444-582226993b3a", "text": "Chadwick and Leenhouts started from the hypothesis that cell death resulted from a double strand break in DNA (DSB) and that the probability of these events was related in a linear quadratic manner with dose. The model assumes:\nthat DNA is a critical molecule that determines the cell\u2019s ability to reproduce and a DSB is considered critical damage;\n\nradiation produces DNA breaks that can be repaired, and the radiobiological effect reflects the degree of repair [116].\n\nthat the rate of critical breaks relative to dose (dN/dD) is proportional to the number of critical bonds (N) and that a critical event (DSB) can occur in two ways: either as a single radiation event that results in a DSB or as two events each inducing a single strand break (SSB), which is close enough in time and space interact to form a DSB."}
{"_id": "Radiology$$$bc0be306-c824-4f08-bdb0-c6a12200c9e0", "text": "that DNA is a critical molecule that determines the cell\u2019s ability to reproduce and a DSB is considered critical damage;"}
{"_id": "Radiology$$$ea3dac54-0f24-4858-8e6c-d4edd09fc539", "text": "radiation produces DNA breaks that can be repaired, and the radiobiological effect reflects the degree of repair [116]."}
{"_id": "Radiology$$$261ab771-d1cb-462b-8990-b93990c3f0c5", "text": "that the rate of critical breaks relative to dose (dN/dD) is proportional to the number of critical bonds (N) and that a critical event (DSB) can occur in two ways: either as a single radiation event that results in a DSB or as two events each inducing a single strand break (SSB), which is close enough in time and space interact to form a DSB."}
{"_id": "Radiology$$$8d0a2488-e085-4501-8a82-3317e5c0d89a", "text": "Therefore, the combination of these assumptions leads to an exponential model with a linear term and a quadratic term, similar to the one developed by Kellerer and Rossi, producing the linear quadratic model of cell survival."}
{"_id": "Radiology$$$93b29af5-8ed2-463e-b368-eeeec3184809", "text": "There are various ways of interpreting this model. In one, two DSBs can interact and lead to chromosomal aberrations that impair cell division. In particular, asymmetric aberrations, such as the dicentric, the ring, and the anaphase bridge, make cell division impossible. In another interpretation by Hall, the linear and quadratic terms can be interpreted as asymmetric chromosome aberrations produced in one or two radiation events."}
{"_id": "Radiology$$$05b406fc-f856-41e9-a531-3b3c6e08cc94", "text": "In both the interpretations by Chadwick and Leenhouts and Hall, the shoulder of the LQ-curve is a result of sublethal damage, i.e., damage that is not lethal in itself but can interact with other sublethal damage to become lethal. The difference lies in what is regarded as sublethal damage. Hall assumes that one DSB in itself is not lethal such that lethal damage is created only when two DSBs create an asymmetric chromosome aberration. Chadwick and Leenhouts also acknowledge that asymmetric chromosome aberrations are lethal DNA damage, but they adjust for this by multiplying by a factor, which represents a linear relationship between the number of DSB and the number of asymmetric chromosome aberrations. In their interpretation, sublethal damage is a single strand break (SSB), which needs to interact with another SSB close in time and space to form a DSB."}
{"_id": "Radiology$$$243b1537-d301-48ef-9121-c8b419a3de9a", "text": "If the dose is fractionated (i.e., split up into several parts separated in time) or the dose rate is decreased, a linear survival curve will emerge. This is a reflection of the sublethal damage being repaired before it can interact with other sublethal damage to become lethal. With the repair time for DSB and SSB in mind (see Sect. 2.\u200b4), this supports Chadwick\u2019s and Leenhouts\u2019 interpretation."}
{"_id": "Radiology$$$d170cb67-603e-4ff2-b5d0-1ccf5b46e15c", "text": "In 2016, Bodgi and Foray proposed a new model for radiation-induced cell death whose mathematical derivation results in the linear quadratic model. In this model, DSB recognition mechanisms are mediated by ataxia telangiectasia mutated monomers (ATM) that are induced in the cytoplasm by radiation and diffuse to the nucleus (nucleo-shuttling of IR-induced ATM monomers). Once in the nucleus, these monomers participate in the DSB recognition mechanism that allows its repair [117]. The rates of DSB production by radiation and monomerization are assumed to have a linear relationship to dose. The same model also includes the notion of cell tolerance, taking into account that not all DSB lead to cell death, which in this case is assumed to be due to unrepaired DSB in cells entering mitosis. Among unrepaired DSB, those that are not recognized and therefore not repaired are distinguished from those that are recognized but not repaired within a suitable time window. The number of unrecognized DSBs in the model has a quadratic relationship to dose, whereas the number of recognized but unrepaired DSBs has a linear relationship to dose. Finally, unrepaired DSBs are assumed to follow a Poisson distribution, which leads to cell survival being modeled by a linear quadratic exponential. In addition to presenting a biological mechanism of cell death by radiation, this model provides an explanation for cellular hypersensitivity at low doses, since it assumes that radiation does not produce enough ATM monomers to cross the membrane and enter the nucleus. Therefore, there is no recognition of DSB and they remain unrepaired, which leads to cell death."}
{"_id": "Radiology$$$ace3656e-d2b8-4e90-84fc-101f46ff3427", "text": "The linear quadratic model is arguably the most used tool in radiation biology and physics, as it provides a simple relationship between the dose absorbed and the number of surviving cells (or the probability that a single cell will survive). In its basic format (SF\u00a0=\u00a0exp (\u2212\u03b1 \u00d7 D \u2013 \u03b2 \u00d7 D2)), it has been used to analyze and explain both in vivo and in vitro experiments and after some modest simplifying assumptions, it can be related to a number of mechanistic models such as multi-hit and potentially lethal lesion models. However, despite its widespread usage, questions remain about its applicability, particularly at the very low and very high-dose regions where significant discrepancies have been observed between the model predictions and the experimental data. Such questions spring from the complexity of the underlying biology and modern radiotherapy, where the response of cells and tissues can be modulated by both intrinsic genetic factors as well as the cellular environment and the radiation delivery modality. The linear quadratic model has therefore been the subject of extensive investigations and suggestions for modification to better fit the experimental data and therefore to explain a wide range of radiation conditions."}
{"_id": "Radiology$$$f84cee3d-9124-4429-89e4-01ac3c34c1f6", "text": "In the low-dose region, high-resolution in vitro measurements demonstrated increased X-ray effectiveness below 0.6 Gy [118]. The measured survival levels were significantly lower than those predicted by extrapolating the high dose points using the linear quadratic models. The phenomenon, named hypersensitivity, was reported with a range of cell lines and radiation qualities and data suggest that the observed response was unlikely to be due to a subpopulation of radiosensitive cells. In order to account for the increased effectiveness per unit dose at doses lower than 1 Gy and in line with the hypothesis that repair mechanisms are only triggered when sufficient damage has been accumulated, modification to the linear quadratic models has been suggested. Joiner and Johns [119] proposed a simple modification in which the alpha parameter decreases with increasing radiation dose, representing an increased induced radio resistance. The modification only concerns the alpha parameter, as the contribution of the beta parameter is negligible at low doses due to its quadratic influence. The modified linear quadratic models for low doses can therefore be expressed as\n\n (4.40)"}
{"_id": "Radiology$$$4293e255-7d4b-4df6-a66c-aed722a8a8c1", "text": "where dc is the dose at which 63% of the induction has occurred and g is the amount by which the alpha parameter changes at low doses (Fig. 4.21).\n\nAn error line graph of surviving fraction versus dose for fit by induced repair model of errors a subscript s, H R S, d subscript c, I R R. A dashed linear downward line is the extrapolation from the high-dose fit by L Q model.\n\nFig. 4.21\nLow dose hypersensitivity showing a clear downward bend on the survival curve for doses below 1\u00a0Gy, followed by an \u201cincreased radio resistance\u201d at doses above 2 Gy. The image also shows the key parameters for the linear quadratic modification"}
{"_id": "Radiology$$$a8618001-28c1-42d3-a480-d1355d530432", "text": "An error line graph of surviving fraction versus dose for fit by induced repair model of errors a subscript s, H R S, d subscript c, I R R. A dashed linear downward line is the extrapolation from the high-dose fit by L Q model."}
{"_id": "Radiology$$$3d4bb226-891d-48a7-981e-56b0c0df7b95", "text": "The interest in radiotherapy treatments delivered with a smaller number of high-dose fractions (hypofractionation) and stereotactic radiosurgery (SRS) has also instigated investigation into the validity of the linear quadratic model at high doses. A number of investigations have shown that the linear quadratic model in its basic form is not suitable in the high-dose region where it underestimates the surviving fraction and does not reproduce the straightening of the curve observed experimentally [120, 121]. To cope with this drawback, modifications of the linear quadratic model have also been suggested at high doses [122]. The starting point is an early modification of the linear quadratic expression to account for repair during a protracted radiation exposure:\n\n (4.41)"}
{"_id": "Radiology$$$43bda10e-d46a-424c-849d-23628bac47a7", "text": "with \u03bb as the repair rate parameter, T is the delivery time for the dose D, alpha and beta as previously described for the basic linear quadratic model. This version of the LQ model is able to predict survival curves taking into consideration scenarios where significant repair occurs during the dose delivery and is in accordance with other mechanistic models (i.e., Lethal, Potentially Lethal model). In order to reproduce the behavior of acute high doses however an additional term needs to be added to the G parameter:"}
{"_id": "Radiology$$$59845bf5-e10f-4406-a0f4-b5f8517e8e7a", "text": "The new parameter (\u03b4) is introduced to match the final slope of the survival curve and can be interpreted as a reduction in survival due to interaction between lesions. Using Eq. (4.41), it can be shown that at high acute doses G (\u03bbT\u00a0+\u00a0\u03b4D)\u00a0=\u00a01/2 \u03b4D and therefore the modified LQ model assumes the form: SF\u00a0=\u00a0exp (\u2212(\u03b1\u00a0+\u00a0\u03b2/2\u03b4) \u00d7 D), which has a linear behavior. Therefore, this model is referred to as a linear quadratic linear or LQL model (Fig. 4.22).\n\nA decreasing line graph of surviving fraction versus dose for L Q alpha by beta = 3, and 10 grays, the values from (0, 1) to (0.0002, 15), (0.03, 15), (0.04, 15), and (0.1, 15). The values are estimated.\n\nFig. 4.22\nDifference in the surviving fraction predicted by the LQ and the LQL model for cell lines with different radiosensitivity (alpha/beta ratio)"}
{"_id": "Radiology$$$b276f5e0-3061-454e-90a7-dcdbce38f473", "text": "A decreasing line graph of surviving fraction versus dose for L Q alpha by beta = 3, and 10 grays, the values from (0, 1) to (0.0002, 15), (0.03, 15), (0.04, 15), and (0.1, 15). The values are estimated."}
{"_id": "Radiology$$$ddaec4be-b872-4379-b123-d24770462985", "text": "Although both modifications of the linear quadratic model are able to accurately describe experimental data at low and high doses, they introduce new parameters, which need to be experimentally determined."}
{"_id": "Radiology$$$fa546580-13e3-4d10-a42f-f05c327c5d77", "text": "The reaction of cells and tissues to radiation damage involves the repair of DNA and a complex interplay between repair and cell survival. The ability of a cell to repair the damage it experiences depends on the part of the dose it receives, the part of the cell cycle in which it is irradiated, and the rate at which the dose is delivered. Therefore, we must give attention not just to the molecular mechanisms of damage and repair but also to cell cycle regulation of repair and ultimately their biological consequences."}
{"_id": "Radiology$$$e3aca353-3d92-45fe-89e3-28e673729ddb", "text": "Here we return to using the terms sublethal, lethal, and potentially lethal damage. By sublethal damage, we simply mean damage which will not be lethal to the cell even if the damage is not repaired. We will later see that it is still of great importance whether or not these damages are given time for repair hence the temporal aspect."}
{"_id": "Radiology$$$0e8a93db-88df-4b46-a7fb-645aeabb78c0", "text": "Lethal damage is fixed in such a way that they cannot be repaired. Potentially lethal damage may well be repaired but will be lethal if not repaired in time, where the notion of \u201cin time\u201d relates to cell cycle regulation."}
{"_id": "Radiology$$$f9269e6b-0da8-4e14-b0da-1c76cc49bcc6", "text": "If the cell passes through S phase with DSBs, the formation of dicentric chromosomes or rings may take place, which is potentially lethal to the cell [123]. If the cell thereafter enters mitosis with such asymmetric chromosomal aberrations, it may not be able to give each of the daughter cells a complete set of genes. If such asymmetric chromosomal aberrations are formed, they are therefore usually lethal for proliferating cells. However, if cells are given time to repair DSB before they can develop into asymmetric chromosomal aberrations, i.e., before the cell enters into S phase, damage such as DSB are only potentially lethal."}
{"_id": "Radiology$$$21287243-90cd-45be-84db-2dac145d6ddf", "text": "These concepts were supported by early experiments by Stapleton [124] and Phillips [125], where, respectively, culture of cells under suboptimal conditions for growth, or in the presence of inhibitors of the cell cycle produced an increased level of cell survival Seminal experimental findings which support this view include work in vivo by Shipley [126], where rat adenocarcinoma cells were irradiated in situ with gamma rays or neutrons, after which explants of the tumor were grown in vitro either immediately after, or from 4 to 24\u00a0h after irradiation, whereupon the survival of these cells was assessed in terms of their clonogenic capacity. While situated in functioning tissue within the animal, these cells had limited access to nutrients and growth factors, which set a natural limit on cell density thereby limiting cell growth and proliferation. Within tissues, such cells may well be cycling though they could take several days to do so, and as such have time to repair their DNA. When cultured as explants in vitro post-irradiation they have greater access to nutrients and as such proliferate strongly, with surviving cells able to produce colonies. Cells which were cultured immediately after irradiation exhibited lower survival rates than those which remained in situ for a period of time after irradiation. Clearly, cells that could not proliferate in tissue have an increased opportunity to repair their damage owing to them being prevented from progressing within the cell cycle. Further experimental evidence demonstrated that this repair process could continue up to 24\u00a0h after irradiation, indicating the complexity of this repair process [127]."}
{"_id": "Radiology$$$ff8d788a-e87c-4da2-83e2-98c02f07004f", "text": "The experiments by Shipley et al. also showed that there is no increase in cell survival for the cells explanted up to 24\u00a0h after high-LET-neutron irradiation. The implication of this is, that the damage induced by high-LET-neutron radiation must be too complex to allow for successful repair, which would increase the survival. This finding suggests that complex DSB are not reparable, even with non-homologous end joining (NHEJ), which has been reinforced by observations that not all DSB from high-LET irradiation initiate NHEJ-repair [128]."}
{"_id": "Radiology$$$71be8612-088d-4e00-b0b8-3b0f25d413d3", "text": "Following the pioneering development of the clonogenic assay by Puck and Marcus [129], experiments by Elkind and Sutton [130] demonstrated that fractionated irradiation could allow cells to repair their sublethal damage (Fig. 4.23).\n\nA multi-axis graph plots the surviving fraction versus doses. The values are plotted for CLONE A P E = 56.3%, 505 radians PLUS 18.1 hours I N C 37 degree Celsius. 2 decreasing lines of different values.\n\nFig. 4.23\nThe surviving fraction of V-79 Chinese hamster cells irradiated either with a single dose or with two dose fractions separated by 18.1\u00a0h. The first dose fraction of 5.05 Gy was given at time 0 and then the cells were incubated for 18.1\u00a0h at 37\u00a0\u00b0C before the second dose fraction (varied between 2 and 8\u00a0Gy) was given. As seen, the incubation time between the two dose fractions has led to a complete reconstitution of the curve shape. The explanation was that through repair of the sublethal damage induced by the first dose fraction, the cells had regained their sublethal damage potential. Unrepaired, these damages would have added to the new sublethal damages and become lethal [130]. (Adapted with permission from Springer Nature: Elkind and Sutton, X-ray damage and recovery in mammalian cells in culture. Nature, 1959)"}
{"_id": "Radiology$$$d7df15aa-2756-4c78-b191-e5a96e7655cb", "text": "A multi-axis graph plots the surviving fraction versus doses. The values are plotted for CLONE A P E = 56.3%, 505 radians PLUS 18.1 hours I N C 37 degree Celsius. 2 decreasing lines of different values."}
{"_id": "Radiology$$$1c5559dc-88e3-4150-9bc1-fe55de291c35", "text": "In this work, V79 cells of the Chinese hamster were irradiated with one single dose or with two dose fractions where the time between the fractions was varied. The results shown in Fig. 4.23 are from an experiment where they kept the time between the dose fractions constant at 18\u00a0h."}
{"_id": "Radiology$$$887f463e-40d9-4275-8e58-2faf944e7142", "text": "These results aligned with the target theory of the time, whereby the combined effects of several sublethal damage events in DNA may result in lethal damage, such that damage created by hits which are not lethal by themselves may be repaired, but cells will not have time to do such repair if a large dose is given acutely, i.e., at a high dose rate. With a large enough acute dose, the degree of sublethal damage for each cell is so high that it combines to form lethal damage."}
{"_id": "Radiology$$$75e120aa-1aa9-4e71-af7b-a49e4371f25a", "text": "It is well worth reflecting on both the differences and the similarities regarding sublethal damages between the traditional multi-target/single-hit model and the newer LQ model. On the one hand, in the multi-target/single-hit model, one does not make any assumption regarding the nature of the molecular damage induced. Still, it introduces the concept of sublethal damage and shows that such damage inevitably leads to an initial shoulder on the survival curve. Thus, Elkind\u2019s and Sutton\u2019s data show that if cells are given time for repair, DNA damage can be repaired."}
{"_id": "Radiology$$$b4dcafea-ba54-4559-93bd-d9288060be06", "text": "On the other hand, in the LQ model, one assumes two specific types of molecular damages as being sublethal, namely single strand breaks in DNA (SSB) (which are all sublethal separately) and the repairable double strand breaks in DNA (DSB). In reality, no distinction is made between SSB and DSB concerning repair of sublethal damage observed by dose fractionation in the LQ model. According to the LQ model, the dose-response curve has a downward bending, because two sublethal SSB may give rise to a DSB. The DSB may develop into lethal damage and therefore is potentially lethal but probably may also in some cases be sublethal."}
{"_id": "Radiology$$$45f320c8-295e-4365-8dd6-6c53d37b784a", "text": "The question then arises as to the timeframe required for the repair of sublethal damage events. While Elkind and Sutton did go some way towards measuring the value of this variable (suggesting that it was as much as 12\u00a0h), it was not until experiments by Terasima and Tolmach and further experiments by Elkind that refined this estimate and gave an explanation for its value."}
{"_id": "Radiology$$$e47ce501-a414-445c-a627-bba7662cc5dd", "text": "As indicated by Fig. 4.26, the repair curves are different if cells are incubated at room temperature (24\u00a0\u00b0C) between dose fractions compared to at 37\u00a0\u00b0C, where this difference has to do with differences in cell cycle progression. The cell cycle is halted almost completely at room temperature but continues almost uninhibited between dose fractions at 37\u00a0\u00b0C. Thus, the explanation is that the first dose fraction primarily kills more V79-cells in mitosis, G1, and early S than in late S phase where they are resistant (be mindful that V79 cells have a cell cycle duration of approximately 10\u00a0h and almost no G1 phase)."}
{"_id": "Radiology$$$244a1525-d613-422c-a93d-298b0bacf497", "text": "At 24\u00a0\u00b0C, surviving cells stay in the stage of the cell cycle where they are resistant between the dose fractions and therefore their radiosensitivity is constant with time. At 37\u00a0\u00b0C, they continue through the cell cycle after the first fraction and at some time later will have reached a cell cycle stage where they have maximum radiosensitivity, whereupon the second dose fraction is given. Consequently, survival as a function of the time between fractions will decrease with increasing time."}
{"_id": "Radiology$$$63185508-995b-4368-a346-d8c90ff6e6de", "text": "The customary notion for cell cycle progression between dose fractions is redistribution (also denoted as \u201creassortment\u201d). So, this notion is used to state that cells, which have not been lethally damaged by a preceding dose fraction, will move to a different cell cycle phase before the next dose fraction (Fig. 4.24).\n\nA multi-line graph plots the surviving fraction versus the hours between 2 doses. The values are plotted for different incubation temperatures of 3, 24, and 37 degrees Celsius for the dose and cells. 5 lines, 3 begin at (0, 0.007), 1 follows a decreasing trend, 1 follows an increasing trend, and 1 fluctuates, and 2 lines begin at (0, 0.15) and follow a decreasing trend.\n\nFig. 4.24\nChinese hamster V79-cells were irradiated with two dose fractions separated by different time spans (lower abscissa) and with different temperatures in the incubator between dose fractions; respectively 3, 24, and 37\u00a0\u00b0C. In particular, the curves representing 37 and 24\u00a0\u00b0C are of interest since the first one represents cells that cycle between the dose fractions while the other one represents cells, which do not cycle between the dose fractions. (Adapted from [131] with permission, \u00a9 2022 Radiation Research Society [131])"}
{"_id": "Radiology$$$d9b58c8c-442c-498a-a1ab-f0ec383ab411", "text": "A multi-line graph plots the surviving fraction versus the hours between 2 doses. The values are plotted for different incubation temperatures of 3, 24, and 37 degrees Celsius for the dose and cells. 5 lines, 3 begin at (0, 0.007), 1 follows a decreasing trend, 1 follows an increasing trend, and 1 fluctuates, and 2 lines begin at (0, 0.15) and follow a decreasing trend."}
{"_id": "Radiology$$$f8af8717-6c19-4bb8-bc3f-365b72bf3a08", "text": "From Fig. 4.26, one can see that the surviving fraction increases considerably with about 8\u201310\u00a0h repair time at the temperature of 37\u00a0\u00b0C. This increase is not due to repair. It has to do with the fact that some V79 cells reach completion of cell division before the next dose fraction is given (notice that these cells have a median cell cycle duration of just about 10\u00a0h). The consequence of this is that some colony-forming units consist of two daughter cells instead of just one at the time when the second dose fraction is given."}
{"_id": "Radiology$$$3f2c4e25-e0f7-4e97-87ea-373335bc1783", "text": "A simple calculation illustrates the importance of this phenomenon. If the probability to kill a cell is p, the probability for this cell to survive is S\u00a0=\u00a01\u2212p. However, the probability to kill both cells in a doublet or all four cells in a quartet is p2 and p4, respectively. The probability for a doublet or a quartet to form a colony is therefore S\u00a0=\u00a01\u2212p2 and S\u00a0=\u00a01\u2212p4, respectively."}
{"_id": "Radiology$$$dad63e3b-c456-4b6f-9933-c792ec049212", "text": "If we suppose that the number of V79 cells has doubled during a 12\u00a0h period at 37\u00a0\u00b0C following the first dose fraction in Fig. 4.26, we can understand the increased surviving fraction between 10 and 12\u00a0h. It is indicated that the surviving fraction after two dose fractions 2\u00a0h apart with full repair is 0.035. The surviving fraction after the first dose fraction alone is about 0.23. This means that normalized survival after the second dose fraction alone, assuming full repair of the sublethal damage induced by the first fraction, is 0.035/0.23\u00a0=\u00a00.152. The probability that this dose fraction alone would kill a cell is therefore 1\u20130.152\u00a0=\u00a00.848. However, if the cell reaches cell division between the two dose fractions, the probability for the doublet to become unable to form a colony is 0.8482\u00a0=\u00a00.719. The probability for survival therefore increases from 0.152 for the single cell up to 1\u20130.719\u00a0=\u00a00.28 for the doublet. The surviving fraction after both doses and full repair then should be 0.28 \u00d7 0.23\u00a0=\u00a00.065. Thus, the surviving fraction has increased from 0.035 to 0.065 because of a doubling of the cell number per colony-forming unit. From Fig. 4.26 one can see that this corresponds well with the survival observed by Elkind et al. with 12\u00a0h repair time between the dose fractions, quite in agreement with the cell cycle kinetics for V79 cells (cell cycle duration ~10\u00a0h)."}
{"_id": "Radiology$$$06721b01-176a-488f-9d0a-e0f818ed693b", "text": "In radiotherapy, the notion used for cell proliferation between dose fractions is repopulation. By repopulation, we mean that cells which survive a preceding dose fraction get enough time before the next dose fraction to complete the cell cycle and divide. This is an important concept in connection with fractionated radiotherapy. Although cell cycle times in tissues are usually much longer than for V79 cells in culture, 24\u00a0h between the dose fractions is sufficient for at least some proliferation of both cancer cells and normal cells between the fractions."}
{"_id": "Radiology$$$c1b706ef-efbc-452c-a3c5-891bd1ec49be", "text": "From Fig. 4.26, one can furthermore see that the survival increases almost by the same factor over the first 2\u00a0h repair time irrespective of the temperature being 24 or 37\u00a0\u00b0C. As seen, the surviving fraction increases from the single-dose level of 0.005 and up to 0.02 at 24\u00a0\u00b0C and 0.03 at 37\u00a0\u00b0C at 2\u00a0h repair time. Thus, the data indicate that the repair itself is less influenced than the cell cycle progression by the temperature (in fact some DNA repair persists at temperatures as low as 3\u00a0\u00b0C) (Fig. 4.25).\n\nA waveform exhibits surviving fraction versus time between split doses in an hour for repair of S L D, the dotted region is if cells are non-cycling, reassortment or redistribution if cells are cycling, proliferation.\n\nFig. 4.25\nThe increased cell survival with increasing time between two dose fractions (up to 2\u00a0h) is due to increased time for repair of the sublethal damages induced by the first dose fraction. After about 2\u00a0h, all sublethal damage has been repaired. Most surviving cells after the first dose fraction would however be in late S or mid G1, the phases where cells are most radio resistant. If cells are offered optimal growth conditions between the dose fractions (37\u00a0\u00b0C), these surviving cells will continue cell cycle progression and may after 6\u00a0h reach a phase where they are more radiosensitive. If the second dose fraction is given at that instant, the survival will be reduced. Therefore, the curve bends downwards between 4 and 6\u00a0h, before an upwards turn between 6 and 8\u00a0h, when the cells have proceeded to a phase of higher resistance. After a long time, which depends on cell doubling time (typically >12\u00a0h), cell division results in an increased multiplicity of the colony-forming units and we see an increased survival that is caused by repopulation. Curve extracted and generalized from Fig. 4.24"}
{"_id": "Radiology$$$d80ef9ef-919d-4d9a-9f3e-b609843d39d6", "text": "A waveform exhibits surviving fraction versus time between split doses in an hour for repair of S L D, the dotted region is if cells are non-cycling, reassortment or redistribution if cells are cycling, proliferation."}
{"_id": "Radiology$$$4745e3a7-3ef3-4889-ad19-9cb6564d5b96", "text": "In Fig. 4.25, three concepts are listed that are all related to fractionated radiotherapy: repair (meaning in this connection repair of sublethal damage) redistribution (or reassortment), and repopulation (or proliferation). These concepts cover three of the phenomena usually referred to as the 6 Rs of radiotherapy (see Sect. 5.\u200b5). All these mechanisms are interesting from a radiotherapeutic point of view because they can all be manipulated by variations in the fractionation  regime chosen."}
{"_id": "Radiology$$$5365e18b-aea9-407d-9f23-530f3e3d182f", "text": "Elkind and Sutton demonstrated that cells irradiated with several dose fractions separated by enough time for full repair would repeat the repair of sublethal damage over and over again [132]. Steele also demonstrated that an increase in cell survival is observed when a given dose is delivered at a low dose rate [133]. Some consistent features in the cell survival curves for cells irradiated with fractionated or low-dose radiation were also observed:\nWhile the initial slopes of each cell survival curve differed, the final slopes were consistent. Using the LQ model to describe the cell survival curve would indicate that for a given cell line under fractionated or low dose irradiation, the \u03b1-values would change, while the \u03b2-values would remain consistent.\n\nThe differences between the response of cells of different types (with varying radiosensitivity) were more pronounced with low dose rate irradiation than with acute irradiation. This is a first indication of a more general principle, which is of utmost importance for radiotherapy. The sparing effect of fractionated or low dose rate radiation is most pronounced for cells having a dose-response curve with a broad shoulder (or a shallow initial slope)."}
{"_id": "Radiology$$$bc56a759-058d-4344-a5eb-d19c9163f807", "text": "While the initial slopes of each cell survival curve differed, the final slopes were consistent. Using the LQ model to describe the cell survival curve would indicate that for a given cell line under fractionated or low dose irradiation, the \u03b1-values would change, while the \u03b2-values would remain consistent."}
{"_id": "Radiology$$$c9596e2e-8e98-498f-bd9f-907b6f15ef7c", "text": "The differences between the response of cells of different types (with varying radiosensitivity) were more pronounced with low dose rate irradiation than with acute irradiation. This is a first indication of a more general principle, which is of utmost importance for radiotherapy. The sparing effect of fractionated or low dose rate radiation is most pronounced for cells having a dose-response curve with a broad shoulder (or a shallow initial slope)."}
{"_id": "Radiology$$$0dca610a-6eea-4b6a-9f68-52d7fbd3488f", "text": "This latter feature is illustrated by the cartoon in Fig. 4.26, showing an example of a fractionation regime (with dose fractions of d) for two different cell types having dose-response curves characterized by different shoulder regions (curves shown together in the small insert), one with a broad shoulder (small \u03b1) and one with a small shoulder (large \u03b1). The two dashed lines shown in panel (b) indicate the difference in response for the two cell types. If radiation is given continuously at a dose rate low enough for the cells to complete repair of all sublethal damage at the same rate as they were induced, the \u03b2-term of the LQ model will not contribute (all sublethal damage would be repaired before they could cowork to produce potentially lethal damages). This would be equivalent to very many very small doses and the response curve would be a tangent to the initial part of the dose-response curve for acute irradiation. Continuous irradiation at such a low dose rate results in the largest difference obtained for the two cell types.\n\nA and B line graph of surviving fraction versus dose, a decreasing value at an angle d, and the inserted graph of the same.\n\nFig. 4.26\nA cartoon to illustrate the difference in sparing effect of fractionated irradiation versus acute irradiation for two cell types having dose-response curves with a broad (late-responding tissues, panel (a) compared to a small (early-responding tissues, panel (b) shoulder region. The small insert shows the curve shapes after acute irradiation to compare. In conclusion, even if cells characterized by a broad-shouldered dose-response curve are the most sensitive ones to high acute doses, these cells are the most resistant ones to fractionated or low dose rate irradiation"}
{"_id": "Radiology$$$a732695f-1938-416c-ac3d-b40763e25de7", "text": "A and B line graph of surviving fraction versus dose, a decreasing value at an angle d, and the inserted graph of the same."}
{"_id": "Radiology$$$13f0764e-9d2a-4412-a7ce-53e06f3867a2", "text": "One should notice that the final slopes of the single-dose curves indicate that the cells having the broadest shoulder are in fact more radiosensitive than those having the smallest shoulder at high single doses. Still, with fractionated or low dose rate irradiation it is the other way around. This phenomenon is an important principle, which is the basis for radiotherapeutic practice."}
{"_id": "Radiology$$$fbba8348-916f-4943-a97b-28fa0e65c794", "text": "In radiotherapy, it is customary to express this principle in some other words as based on the LQ model. The sparing effect of fractionated or low dose rate irradiation as compared to acute irradiation is most pronounced for cells having a dose-response curve with a small \u03b1-parameter."}
{"_id": "Radiology$$$f349d87e-7a49-4743-a4c7-6ce5bfd9f8e4", "text": "Cellular radiosensitivity varies with cell cycle stage. At the same time, ongoing low dose rate irradiation may activate cell cycle arrest in the various restriction points in the cell cycle as has been explained by the activation of regulatory cascades related to p53 (at G1k) and the ATM-kinase activated by DNA-DSB. This gives rise to an inverse dose-rate effect (Fig. 4.27), where at very low dose rates cells may see an increase in cellular killing.\n\nA decreasing line graph of surviving fraction versus dose for acute high dose rate 1 gray per minute, lower dose rate 0.37 gray per hour, low dose rate 0.8 grays per hour, threshold dose rate, and the increasing dashed line hormesis.\n\nFig. 4.27\nThe effect of dose rate on the cell survival curve. Repair processes are the primary mechanism that adjusts survival curves as the dose rate decreases from an acute level (~1\u00a0Gy/min) to a low level (~0.8\u00a0Gy/h). An increase in the slope of the cell survival curve (indicating an increase in radiosensitivity, the \u201cinverse dose rate effect\u201d) occurs due to the redistribution of cells throughout the cell cycle when the dose rate further decreases from ~0.8\u00a0Gy/h to 0.37\u00a0Gy/h. Finally, increased proliferation of cells occurs as the dose rate decreases further towards a threshold or critical dose rate, which varies by cell type. Notice that this cartoon presents a very special case of a cell type having an inverse dose rate effect, which is probably associated with a simultaneous lack of both p53- and pRB-function. The dose rate that can produce a hormetic effect is unclear and not indicated, but is several orders of magnitude lower than the lowest one depicted here (0.37\u00a0Gy/h)"}
{"_id": "Radiology$$$81750816-0d71-4741-a877-19df5a8ec3a8", "text": "A decreasing line graph of surviving fraction versus dose for acute high dose rate 1 gray per minute, lower dose rate 0.37 gray per hour, low dose rate 0.8 grays per hour, threshold dose rate, and the increasing dashed line hormesis."}
{"_id": "Radiology$$$ba725b1a-f2f8-477d-badd-277cf21a48dc", "text": "The standard approach to the explanation of this effect is that cells progress to G2 and undergo a \u201cblock\u201d in the G2 phase during ongoing very low-dose irradiation. As cells are radiosensitive during G2, much of the radiation is delivered during a radiosensitive phase of the cell cycle. While the mechanism has some clarity, work by Furre et al. in 1999 [134] and 2003 [135] on the effects of lowering dose rates on the survival of a cervical cancer cell line, NHIK 3025, and a breast cancer line, T47-D, has added a further degree of molecular evidence as to the origin of the effect. Of the two cell lines, only the NHIK3025 had an inverse dose rate effect. Both the NHIK 3025 cells and the T-47D cells lack p53-function, but unlike NHIK 3025 cells, T-47D cells have normal pRB-function. They found that T47-D cells accumulated in G2 during low dose rate irradiation in the same manner as the NHIK 3025 cells, but the T-47D cells still remained resistant during the arrest. The effect of pRB-function here appears to be key. Although pRB is normally not bound to the cell nucleus in G2 (only in G1), the nuclear-bound pRB increased in the arrested cells during radiation-induced prolonged G2 arrest. Although the mechanism for this seeming protection is not clear, there are indications that pRB may have a special protective function under severe cellular stress and that this is not limited to any special cell cycle phase."}
{"_id": "Radiology$$$5ab5104f-85bd-4e6a-83ab-13aa1e01b561", "text": "Over time, and as radiobiological experience increased regarding the radiation response of cells of different types and from different organs, etc., it was gradually realized how the initial slope of the dose-response curve is of fundamental importance in radiotherapy. This has to do with the observation demonstrated in Fig. 4.28 above, showing the importance of the initial slope of the dose-response curve regarding cellular sensitivity to a fractionated radiation with time for sublethal damage (SLD)-repair between dose fractions. Of equal importance are the two following general observations:\nCells that are mainly proliferating such as cancer cells or some normal stem cells, all seem to have dose-response curves with a large initial slope (i.e., a large \u03b1). Such cells are denoted as \u201cearly responders\u201d since radiation damage induces cell loss early under ongoing irradiation. Most of these cells enter mitosis within a few days after the start of the radiation treatment. Thus, the cells express a response to the radiation early after the onset of treatment.\n\nCells which are more prone to stay in the resting phase, like differentiated cells or cells in tissues where growth factor or mitogen stimulation is low, largely seem to have dose-response curves with a small initial slope (i.e., a small \u03b1). Such cells are denoted as \u201clate responders\u201d since radiation damage induces cell loss at a late stage after the onset of the treatment. Most of these cells enter mitoses weeks or even months after the start of the treatment. Thus, tissues of such cells express a response to the radiation late; not only late after the onset of the treatment but in many cases long after the end of the treatment.\n\n\nAn error line graph of blood activity versus the total dose of the iso-effect corresponds to a single dose of 16 gray presents at the center. The values are increasing trends.\n\nFig. 4.28\nMice of age 9\u201311\u00a0weeks were given fractionated irradiation with 240\u00a0kV X-rays to the dorsal trunk over a period of 3\u00a0weeks (i.e., more than one fraction per day for regimes with 32 and 64 fractions). Chromium-51-ethylene-diamine-tetra-acetate ([51Cr]-EDTA) was injected intraperitoneally (i.p) 26\u00a0weeks after completed irradiation and the blood level of radioactivity was measured in blood samples taken 60 min after injection. Increasing blood levels indicate reduced kidney filtration capability and the red line indicates an isoeffect level of reduced kidney function. [Modified from [136] with permission [136], \u00a9 2022 Radiation Research Society]"}
{"_id": "Radiology$$$f82cfda2-43be-449d-85d7-eaa6665ac45d", "text": "Cells that are mainly proliferating such as cancer cells or some normal stem cells, all seem to have dose-response curves with a large initial slope (i.e., a large \u03b1). Such cells are denoted as \u201cearly responders\u201d since radiation damage induces cell loss early under ongoing irradiation. Most of these cells enter mitosis within a few days after the start of the radiation treatment. Thus, the cells express a response to the radiation early after the onset of treatment."}
{"_id": "Radiology$$$982d4b67-9fb5-4717-adb1-60b2ec4658ed", "text": "Cells which are more prone to stay in the resting phase, like differentiated cells or cells in tissues where growth factor or mitogen stimulation is low, largely seem to have dose-response curves with a small initial slope (i.e., a small \u03b1). Such cells are denoted as \u201clate responders\u201d since radiation damage induces cell loss at a late stage after the onset of the treatment. Most of these cells enter mitoses weeks or even months after the start of the treatment. Thus, tissues of such cells express a response to the radiation late; not only late after the onset of the treatment but in many cases long after the end of the treatment."}
{"_id": "Radiology$$$c7e4de03-3146-4f8d-8e37-307aa1e9b81b", "text": "An error line graph of blood activity versus the total dose of the iso-effect corresponds to a single dose of 16 gray presents at the center. The values are increasing trends."}
{"_id": "Radiology$$$a45a847b-6fe4-4038-b856-e2c35e08d12e", "text": "This difference is central to the whole concept of radiotherapy. Without this difference, radiotherapy of cancer would probably have had little curative success. The reason is that proliferation is an activity that is typical for almost all cancer tumors but only for a few organs of normal tissues. Resting cells, on the other hand, are largely characteristic of most normal tissues and not of cancer tissues."}
{"_id": "Radiology$$$17594ded-375b-4aa6-a135-c45c02faa0ff", "text": "Thus, while cancer cells largely proliferate and have a large \u03b1-parameter, highly differentiated normal cells largely rest and have a small \u03b1-parameter. The result of this is that if radiation is given over a prolonged time, (either by repeated dose fractions separated by time for repair or by continuous low dose rate irradiation) there is a much more sparing effect on late-responding normal tissues than on most cancer tissues."}
{"_id": "Radiology$$$1543a81f-0f3a-425a-a55b-82561bcd3579", "text": "The interesting question is then, How did we obtain the knowledge that late-responding tissues have cells with a small initial slope on their dose-response curves? These cells are largely not proliferating. They are furthermore seated in tissues and do not grow in culture. So, how is it possible to measure the ability of these cells to form a colony after irradiation? The answer is that we cannot do such measurements directly. Still, as mentioned above, we know that these cells have dose-response curves characterized by a small \u03b1-parameter. This knowledge stems from the use of the LQ model to measure not \u03b1, but the \u03b1/\u03b2-ratio. The \u03b1/\u03b2-ratio is actually the dose (D1) where the contribution to cell inactivation by single event killing matches that from multiple event killing, i.e.,"}
{"_id": "Radiology$$$0d91d0a7-0490-4bc2-b790-abe4e963a470", "text": "(4.42)or\n\n (4.43)"}
{"_id": "Radiology$$$02ae1ff5-a494-434a-a20b-2217dbe22991", "text": "These measurements are based on the following idea: The function of a tissue depends on the functionality of the tissue cells. If the radiation inactivates a certain fraction of the cells, the tissue may lose some of its function and the loss of function can be measured. Such measurements as a result of irradiation are usually denoted as measurements of \u201cFunctional endpoints.\u201d Two examples of such functional endpoints representing late and early-responding tissues, respectively, are: (a) Kidneys, the clearance of a very small amount of an injected substance from the blood can be measured and (b) Skin, the severity of damage to an irradiated area of skin can be observed and graded (from mild reddening to irreparable wounds and necrosis)."}
{"_id": "Radiology$$$d9b33b95-88ca-4c48-977d-88aacdab2b39", "text": "In Fig. 4.28, an example of kidney function damage is shown. As a measure of kidney function, the clearance from blood of the compound ethylene diamine tetra acetate (EDTA) as a function of the total dose given by various fractionation regimes to mice was detected [136]. EDTA was labeled with [51Cr] so that minute amounts in blood could be accurately detected by blood samples taken 1\u00a0h after EDTA injection. The red line indicates an isoeffect level and the numbers 1\u201364 indicate the number of dose fractions given to the animals over a period of 3\u00a0weeks. Kidneys are late-responding tissues (the filtration units of kidneys consist of highly differentiated cells) and therefore the clearance was measured late (26\u00a0weeks) after the end of irradiation."}
{"_id": "Radiology$$$a8cb8d07-0ca8-40ca-90b6-0387678c729d", "text": "Since all fractionation regimes gave the same functional effect along the red line in Fig. 4.30, we assume that cell survival is the same along this red line. For one such fractionation regime with n dose fractions of size d the LQ model predicts the following cell survival as long as time is given for the full repair of SLD between dose fractions:\n\n (4.44)"}
{"_id": "Radiology$$$4fa3f880-fcea-4d57-9e01-57ad67953dee", "text": "We now rearrange to get the following expressions (and we write SD for S(D) and Sd for S(d):\n\n (4.45)"}
{"_id": "Radiology$$$62250de3-8417-4015-b862-41fa0c99c23d", "text": "or\n\n (4.46)"}
{"_id": "Radiology$$$bb670ff6-9434-4c0a-a8cd-dd984a5b63bc", "text": "If we now remember that D\u00a0=\u00a0nd this formula can also be rewritten as follows:\n\n (4.47)"}
{"_id": "Radiology$$$12a3c5cb-5649-4f06-b956-f69a75d91c49", "text": "The data from Fig. 4.28 can be plotted according to Eqs. (4.45) (left panel) and Eq. (4.46) (right panel) as shown in Fig. 4.29 [137].\n\nA. line graph of reciprocal total dose versus dose per fraction of the values (1, 0.14), (2, 0.16), (4, 0.2), to (17, 0.66), values are estimated. B. decreasing line graph of the proportion of full effect versus dose per fraction in the gray of alpha beta = 3 grays.\n\nFig. 4.29\nThe isoeffect data defined by the red line in Fig. 4.30 are replotted after the two transformations described by Eqs. (4.45) (plotted in panel a) and (4.46) (plotted in panel b). Reprinted with permission from [137]"}
{"_id": "Radiology$$$a61a3cd0-3ca3-44e3-ae9f-0cf3dbd32985", "text": "A. line graph of reciprocal total dose versus dose per fraction of the values (1, 0.14), (2, 0.16), (4, 0.2), to (17, 0.66), values are estimated. B. decreasing line graph of the proportion of full effect versus dose per fraction in the gray of alpha beta = 3 grays."}
{"_id": "Radiology$$$933960d7-8788-4e07-8f4a-c0a9775d87a1", "text": "From Fig. 4.29a, one can see that the data points are well-fitted by a straight line as predicted by the LQ formula (Eq. 4.45). Furthermore, according to Eq. (4.45) we have for 1/D = 0 that \n\n and thus that d(1/D\u00a0=\u00a00)\u00a0=\u00a0\u00a0\u2212\u00a0\u03b1/\u03b2.Therefore, since the line crosses the abscissa at d\u00a0=\u00a0\u22123\u00a0Gy, the nominal value of the \u03b1/\u03b2-dose must be 3 Gy."}
{"_id": "Radiology$$$ad1a92e0-b2a3-47cb-97d9-3939c8e106a1", "text": "In Fig. 4.29b, one can see that Eq. (4.46) actually reconstructs the shape of the dose-response curve, but in this case with the survival axis plotted as the fractional effect of a single dose fraction relative to the effect induced by the single-dose acute irradiation of 16 Gy. As indicated in the figure, also this plot results in the \u03b1/\u03b2-dose being 3 Gy since the contributions at 3 Gy by single and multiple event killing as defined in the LQ model are equal. The importance of the value of the \u03b1/\u03b2-dose in relation to fractionated radiotherapy is clearly illustrated by the isoeffect tolerance curves plotted in Fig. 4.30 [137].\n\na and b, scatter plot of the total dose versus the number of fractions of late responding kidney alpha by beta = 3 grays, and early responding skin alpha by beta approximate 12 grays, the scale of dose per fraction present at the bottom.\n\nFig. 4.30\nIn (a), the data of Fig. 4.28 on late-responding mouse kidney are replotted as isoeffect tolerance curves with total tolerated dose in a fractionation scheme as a function of the dose per fraction (both axes logarithmic). In (b), similar data are shown for an early-responding normal tissue, namely mouse skin. Notice that the \u03b1/\u03b2-dose is 3 Gy for the late-responding tissue and 12 Gy for the early-responding tissue. (Reprinted with permission from [137])"}
{"_id": "Radiology$$$ee965cf5-f56c-442f-93cf-f17e346774b3", "text": "a and b, scatter plot of the total dose versus the number of fractions of late responding kidney alpha by beta = 3 grays, and early responding skin alpha by beta approximate 12 grays, the scale of dose per fraction present at the bottom."}
{"_id": "Radiology$$$731c087d-71ce-467c-9171-4b7f1c20d50f", "text": "These isoeffect curves show which total dose is necessary in order to obtain a certain effect as a function of the dose per fraction (or number of fractions) for two different tissues. Notice that both axes are logarithmic. In (a), the mouse kidney data of Stewart et al. are plotted as an example of a late-responding tissue with \u03b1/\u03b2\u00a0=\u00a03 Gy and in (b), data on mouse skin are plotted as an example of an early-responding tissue with \u03b1/\u03b2\u00a0\u2248\u00a012 Gy. Thus, while the upper curve represents a dose-limiting normal tissue, the lower curve represents an early-responding tissue such as cancer or some highly proliferative normal tissues. A list of typical values for \u03b1/\u03b2 can be found in Table 4.5.Table 4.5\nRatios of \u03b1/\u03b2 for early and late radiation reactions in normal tissues, determined from laboratory animal and clinical data (Fowler, copyright \u00a9 2005 Acta Oncologica Foundation, reprinted by permission of Taylor & Francis Ltd) [138]\n\nEarly reactions\n\n\n\n (Gy)\n\nLate reactions\n\n\n\n (Gy)\n\nSkin\n\n9\u201312\n\nKidney\n\n2\u20132.4\n\nJejunum\n\n6\u201310\n\nRectum\n\n2.5\u20135\n\nColon\n\n9\u201311\n\nLung\n\n2.7\u20134\n\nTestis\n\n12\u201313\n\nBladder\n\n3\u20137\n\nMucosa\n\n9\u201310\n\nCNS: Brain, spinal cord\n\n1.8\u20132.2"}
{"_id": "Radiology$$$e3a61a48-01e3-46e8-9bf4-06ab01ce6475", "text": "The arrows in Fig. 4.30 show that four large dose fractions of 10 Gy each will represent an advantage to the early-responding tissue (like the tumor), while 64 small dose fractions of 1 Gy each represent an advantage to the late-responding tissue (normal tissue). If tissues are irradiated continuously with a low dose rate, the cells may repair sublethal damage during irradiation and the lower the dose rate, the smaller the probability will be for two or more sublethal damages to combine to create a potentially lethal damage. For the LQ model, this means that reducing the dose rate results in reduced influence by the \u03b2-term and more and more dominance by the \u03b1-term. The connection between the shape of the dose-response curve and the isoeffect tolerance curves (dashed lines) by continuous irradiation is illustrated in Fig. 4.31. The blue curves represent late-responding tissues (i.e., small \u03b1/\u03b2-ratio of \u22483\u00a0Gy) while the purple curves represent early-responding tissues (i.e., large \u03b1/\u03b2-ratio of \u224812\u00a0Gy). The steep isoeffect tolerance curve at high doses for late-responding tissues indicates good sparing for these tissues by reduced fraction doses and prolonged treatment time. Early-responding tissues will experience much less sparing by prolonged treatment times (Box 4.12).\n\nA multi-line graph of surviving fraction versus dose of late responding tissues, and tumor and early responding tissues. A dashed vertical line for alpha by the beta of late and early on either side.\n\nFig. 4.31\nThese cell survival curves illustrate typical differences in the dose-response curves of early- (purple: \u03b1/\u03b2-ratio of \u22483\u00a0Gy) and late- (blue: \u03b1/\u03b2-ratio of \u224812\u00a0Gy) responding tissues. Note that the \u03b1/\u03b2-dose is the dose where the contributions to the cell kill from the \u03b1D-term is the same as for the \u03b2D2-term, as indicated with brackets for the late-responding tissues"}
{"_id": "Radiology$$$d469eb40-a9aa-4db7-be5c-68aac177af53", "text": "A multi-line graph of surviving fraction versus dose of late responding tissues, and tumor and early responding tissues. A dashed vertical line for alpha by the beta of late and early on either side."}
{"_id": "Radiology$$$a4a5b123-7171-4cec-8d37-c19b3f24029d", "text": "The linear quadratic model is a mathematical model, which is a good fit for cellular survival data in a median dose range. For low and high dose, the model needs modifications\n\nThere have been several biological interpretations of the model\n\nTo compare different clinical fractionations regimens, the biologically effective dose can be calculated from the \n\n-value"}
{"_id": "Radiology$$$86e42bb5-4020-4559-ab4d-625876f4b373", "text": "The linear quadratic model is a mathematical model, which is a good fit for cellular survival data in a median dose range. For low and high dose, the model needs modifications"}
{"_id": "Radiology$$$ec7911c3-3b05-4727-ad4e-9c558961b05d", "text": "To compare different clinical fractionations regimens, the biologically effective dose can be calculated from the \n\n-value"}
{"_id": "Radiology$$$a90e8876-3a42-4476-ab1e-faa674ce8a84", "text": "From the discussion so far, one might get the impression that most problems with radiotherapy can be resolved by just a further increase of the treatment time, using, for example, larger numbers of smaller dose fractions over a longer time period, or by reducing the dose rate in case of continuous low dose rate irradiation. However, such changes are met with other limitations such as recruitment and proliferation (repopulation). The problem is that if the tissue is given a small dose each day, the induced cell loss will after a while induce increased proliferation (and probably recruitment) in the surviving cells to compensate for the cell loss. The point is that this activity favors the malignant tissue more than most normal tissues. The reason has to do with the very difference between early- and late-responding tissues, which was the basis for the notion of early and late. While early-responding tissues start compensatory proliferation early after the onset of the radiation treatment, late-responding tissues start compensatory proliferation much later, and in humans, long after completed treatment. This is illustrated in Fig. 4.32, which is based on experimental data from rodents using mouse skin as a model for early-responding tissue (cancer included) and rat spinal cord as a model for late-responding tissue. One should keep in mind here that a complete fractionation scheme for radical radiotherapy of a solid tumor with external radiation is typically 6\u00a0weeks, i.e., 42\u00a0days.\n\nA graph of extra radiation dose in gray for the extra dose required to counteract proliferation. It has a solid curve of early reaction for mouse skin and a dashed curve of late reaction for rat spinal cord.\n\nFig. 4.32\nThe curves indicate what extra radiation dose is required to counteract only proliferation during treatment with one daily dose fraction in two different rodent tissues. Human tissues react more slowly than rodent tissues. Thus, the time for increased proliferation therefore would probably start at a later time than indicated in the figure for corresponding human tissues. (Adapted with permission from [139])"}
{"_id": "Radiology$$$d04495d2-db31-4010-a0ce-dd6c7fc897f4", "text": "A graph of extra radiation dose in gray for the extra dose required to counteract proliferation. It has a solid curve of early reaction for mouse skin and a dashed curve of late reaction for rat spinal cord."}
{"_id": "Radiology$$$0fdb9934-e00b-431b-8d3d-3f71435680d9", "text": "As indicated, the compensatory proliferation starts after the end of the treatment for nerve tissues, while it starts after just 2 weeks of treatment for the cancer-modeling skin tissues. The compensatory proliferation (repopulation) initiated by fractionated irradiation is thus more favorable for early-responding tissues (including cancer) than for late-responding normal tissues. Therefore, one must be careful not to increase the overall treatment time too much. The 6 weeks that are typical for the duration of conventionally fractionated radiation treatment thus is a compromise taking into consideration several different aspects to obtain the maximal probability for a positive effect on the cancer tumor with a minimum of side effects."}
{"_id": "Radiology$$$c62c0f64-099f-446c-92ab-ab46cbd9eeda", "text": "We can rewrite Eq. (4.45) to:"}
{"_id": "Radiology$$$97cb5e8d-2dc9-4bea-9b50-dc04dc5d3002", "text": "(4.48)"}
{"_id": "Radiology$$$5e292814-121a-42b3-b451-93070c6c9049", "text": "is called the Biologically Effective Dose (BED) and describes the dose needed to induce the same effect as if the number of dose fractions was infinitely large and the single dose fractions d approaching zero. This is the equivalent of continuous irradiation with a dose rate sufficiently small for cells to repair sublethal damage at the same rate as they are induced preventing them to cooperate to create lethal damage. BED is a useful parameter to calculate and compare fractionation regimes."}
{"_id": "Radiology$$$72490578-1d64-4ade-a3b8-679da60afc7e", "text": "Standard treatment for many cancers is 2 Gy daily fractions (for example, over 7\u00a0weeks with five treatment days per week). It is therefore often relevant to compare other fractionation regimes to 2 Gy fractions."}
{"_id": "Radiology$$$c3df8cf5-c6aa-440b-bfd9-d70883896896", "text": "The equivalent total dose D for 2 Gy fractions is called\n\n (4.49)"}
{"_id": "Radiology$$$16b24692-b7e8-4a0d-ba9b-f6c5c0714695", "text": "We then get \n\n, which can be used to calculate fraction dose d and number of fractions n\u00a0=\u00a0Dd/d to get the same BED as 2 Gy fractions to a total dose of EQD2."}
{"_id": "Radiology$$$2ec37eb0-7f68-4d82-9d79-7e2e0b711557", "text": "While it is relatively straightforward to develop a model relating dose to survival at the cellular level, modeling of dose response at the organ and organism (human) level is far more complex. There remains considerable debate regarding the most appropriate model for use in describing the variation in response to dose in humans [140]. However, each of the models has its basis in radiobiology, and the interaction of ionizing radiation with human tissue at the cellular level [140, 141]. The previous section on target theory provides a basis to begin to define models of human radiation survival. The effects of ionizing radiation on cells may be divided into two types: deterministic and stochastic effects [141]. Deterministic effects result from the substantial injury of cells in affected tissues, and the severity of the effect is a function of the absorbed dose. Stochastic effects are those for which the probability of occurrence of an effect, and not its severity, is a function of dose [141]. Deterministic effects have a well-defined dose threshold in mammalian cells of a particular organ and type, while it is assumed that no threshold exists for stochastic effects [142]. Deterministic effects occur at relatively high doses (0.5 Gy and above depending on the organ system involved), while stochastic effects generally occur at relatively low doses (below 0.5\u00a0Gy) [141]. Both sets of effect are modified by the rate at which the dose is administered as well as by the biological damage responses such as DNA repair and immune responses [141]. Stochastic effects usually constitute the mechanisms by which the hereditary (mutagenic) and somatic (carcinogenic) effects of ionizing radiation occur [140]. Carcinogenesis is a multistage process in which radiation may induce one or more of the changes necessary to cause DNA damage, while mutagenesis is usually thought to be the result of single biological changes in germ cells. [140]"}
{"_id": "Radiology$$$4b8f1fc4-07f3-4502-ad0b-82e0a62c4d98", "text": "From Eq. (4.26), we may simplify and introduce a variable change to obtain a single-hit model of radiation survival in cells where the frequency, f, of cells with one or more hits in a given population of cells is:\n\n (4.50)where n is the number of critical hits per cell at dose D, and \u03bb is the mean number of critical hits per cell at dose D. For low frequency hits (low doses), the number of critical hits, n, per cell is small and thus Eq. (4.49) reduces to:\n\n (4.51)"}
{"_id": "Radiology$$$e948fe36-a9aa-4fe0-b89a-1fdd5c4f43e4", "text": "Thus, the dose-response is approximately linear with no threshold. At high hit frequencies, where hit saturation occurs, the equation takes the form of Eq. (4.49), since after the first critical hit in a cell, further hits in it cannot lead to additional effects [140]."}
{"_id": "Radiology$$$21cc0d80-f99f-42ab-9738-e61aa3bb28bf", "text": "Multi-track models may be utilized to describe the effect of the interaction between multiple tracks in a cell. The interaction may either be positive or negative and may result in visible curvature to the dose response [140]. A mathematical description of such a model may be achieved by inserting a general polynomial into Eq. (1.50) as follows [140]:\n\n (4.52)"}
{"_id": "Radiology$$$1c43c080-ee82-4652-95b2-ff265c30a894", "text": "which, for low frequency effects (low doses) reduces to:\n\n (4.53)"}
{"_id": "Radiology$$$3af27aca-eadc-4970-bb7d-434cf4c7f813", "text": "In practice, many models have been found to fit the dose response of various bodily organs, depending on the organ in question [143]. The two most common models used are the linear no threshold, LNT (Eq. 4.50), and the linear quadratic (Eq. 4.52) models [143]. At low doses, in a homogeneous cell population, Eq. 4.50 would be the most appropriate dose-response model theoretically, since it is assumed that every cellular hit may be biologically critical and that a single cell is unlikely to be hit more than once [143]. However, for low doses, other mechanisms come into play, such as low dose hypersensitivity, hormesis, and adaptive response mechanisms, as described in Sect. 2.\u200b9 and non-targeted effects as described in Sect. 2.\u200b10, which will modify the radiation response. In an inhomogeneous cell population, where groups of cells have differing radiosensitivity, the response for single-track events in each subpopulation should follow the form of Eq. (4.52), the overall response should show a decreasing sensitivity with increasing dose, consistent with the LQ model [140]."}
{"_id": "Radiology$$$67ea3268-d339-4b00-8811-ab78e0e327c9", "text": "Historically, the LNT model for radiation risk assessment was introduced after Muller\u2019s discovery of radiation-induced mutations in 1927. After the atomic bombing of Japan in 1945 and the start of the nuclear arms race, ionizing radiation became connected in public mind with nuclear apocalypse. In 1945\u20131956, there was great controversy and extensive arguments pro and contra LNT. In general, it can be said that among scientists \u201cthe data to support the linearity at low dose perspective was generally viewed as lacking but the fear that it may be true was a motivating factor\u201d [144]. In 1956, ICRP officially abandoned the tolerance level concept (that was in use since 1931) and substituted LNT for it. Formally, LNT has been introduced and remains a practical operational model for radiation protection only. De facto however LNT acquired the status of a scientific theory, though supporting evidence is at least inconclusive. Moreover, about 40\u00a0years ago, low dose-induced changes in cell signaling with delayed responses were discovered. There is emerging evidence that low doses induce cellular and intercellular changes, which can lead to stress response (adaptive response) metabolic alterations. Adaptive responses against the accumulation of damage\u2014also of non-radiogenic origin\u2014were also discovered [145]. The above evidence suggests that while high-dose ionizing radiation is certainly harmful, low doses may be beneficial for human health; such an effect is called hormesis [146]. At the joint US ANS/HPS conference \u201cApplicability of Radiation-Response Models to Low Dose Protection Standards\u201d in 2018, neither of the three viewpoints\u2014supporting LNT, tolerance level, or hormesis\u2014was marginal [145]."}
{"_id": "Radiology$$$22c91098-9b20-4e6c-b05f-146009ad4aae", "text": "Q1.\nPrinciples of radiation dosimetry?\n\u00a0Q2.\nRadiation microdosimetry(a)\nWhat is lineal energy?\n\u00a0(b)\nHow is it related to the LET?\n\u00a0\n\u00a0Q3.\nFrom track structure to early DNA damage(a)\nWhat are the main differences between a general MC code and a track structure (TS) MC code?\n\u00a0(b)\nWhat are the main sources of uncertainty in the calculation of DNA damage with MCTS code?\n\u00a0\n\u00a0Q4.\nMicro-beams and minibeams(a)\nPlease allocate the research questions mentioned in the following figure to the irradiation pattern, which is best used for investigation, as it is done in the example.\n\nA block diagram of mini beam, single, array to microbeam, dose volume effect, enhanced R B E of high-L E T particle, mechanisms of M R T, bystander effect, cellular response to single ions, and radiosensitivity of subcellular structures.\n\n\n\u00a0\n\u00a0Q5.\nTarget theory and dose-response models\n\u00a0\nUse the data in the table below (A549 lung cancer cells irradiated with 220\u00a0kV X-rays) to:(a)\nFind the \u03b1/\u03b2-value both from a LQ-fitting and by drawing the initial slope and comparing the contributions from each term (see figure provided in Sect. 4.5 above).\n\u00a0(b)\nCalculate the surviving fraction using \u03b1 and \u03b2 from your LQ-fitting for 5 fractions of 2 Gy (24\u00a0h apart) and compare to a single dose of 10 Gy.\n\u00a0(c)\nHow many fractions of 2 Gy should we give to get the same biological effect as for 1 fraction of 10\u00a0Gy?\n\u00a0\n\nDose [Gy]\n\nSurviving fraction\n\nStandard error\n\n0\n\n1\n\u00a0\n0.5\n\n0.88\n\n0.07\n\n1\n\n0.64\n\n0.06\n\n2\n\n0.41\n\n0.04\n\n5\n\n0.07\n\n0.02\n\n10\n\n0.0008\n\n0.0003"}
{"_id": "Radiology$$$0c3d3c53-6601-40a8-9c88-536be43a3af5", "text": "Radiation microdosimetry(a)\nWhat is lineal energy?\n\u00a0(b)\nHow is it related to the LET?"}
{"_id": "Radiology$$$03c0fa20-41d9-45b8-8d09-dbb0dbf664f3", "text": "From track structure to early DNA damage(a)\nWhat are the main differences between a general MC code and a track structure (TS) MC code?\n\u00a0(b)\nWhat are the main sources of uncertainty in the calculation of DNA damage with MCTS code?"}
{"_id": "Radiology$$$b293aebb-61a9-4825-894e-a403e9809190", "text": "What are the main differences between a general MC code and a track structure (TS) MC code?"}
{"_id": "Radiology$$$3d311806-2688-4247-9745-7c59256da788", "text": "What are the main sources of uncertainty in the calculation of DNA damage with MCTS code?"}
{"_id": "Radiology$$$a3beeccc-ba5c-428d-9fd9-95533869c765", "text": "Micro-beams and minibeams(a)\nPlease allocate the research questions mentioned in the following figure to the irradiation pattern, which is best used for investigation, as it is done in the example.\n\nA block diagram of mini beam, single, array to microbeam, dose volume effect, enhanced R B E of high-L E T particle, mechanisms of M R T, bystander effect, cellular response to single ions, and radiosensitivity of subcellular structures."}
{"_id": "Radiology$$$398a3267-c80b-426a-9f13-c16865e94179", "text": "Please allocate the research questions mentioned in the following figure to the irradiation pattern, which is best used for investigation, as it is done in the example.\n\nA block diagram of mini beam, single, array to microbeam, dose volume effect, enhanced R B E of high-L E T particle, mechanisms of M R T, bystander effect, cellular response to single ions, and radiosensitivity of subcellular structures."}
{"_id": "Radiology$$$40a20bf9-0796-4faf-a9c0-98108687f06c", "text": "A block diagram of mini beam, single, array to microbeam, dose volume effect, enhanced R B E of high-L E T particle, mechanisms of M R T, bystander effect, cellular response to single ions, and radiosensitivity of subcellular structures."}
{"_id": "Radiology$$$480213ba-46b0-438b-8d14-5a0382b9d54c", "text": "Use the data in the table below (A549 lung cancer cells irradiated with 220\u00a0kV X-rays) to:(a)\nFind the \u03b1/\u03b2-value both from a LQ-fitting and by drawing the initial slope and comparing the contributions from each term (see figure provided in Sect. 4.5 above).\n\u00a0(b)\nCalculate the surviving fraction using \u03b1 and \u03b2 from your LQ-fitting for 5 fractions of 2 Gy (24\u00a0h apart) and compare to a single dose of 10 Gy.\n\u00a0(c)\nHow many fractions of 2 Gy should we give to get the same biological effect as for 1 fraction of 10\u00a0Gy?"}
{"_id": "Radiology$$$42e40d9f-c113-4a46-ae2b-1eecf29a170b", "text": "Find the \u03b1/\u03b2-value both from a LQ-fitting and by drawing the initial slope and comparing the contributions from each term (see figure provided in Sect. 4.5 above)."}
{"_id": "Radiology$$$29734fd6-fc43-443e-9c31-2a9c972c10e5", "text": "Calculate the surviving fraction using \u03b1 and \u03b2 from your LQ-fitting for 5 fractions of 2 Gy (24\u00a0h apart) and compare to a single dose of 10 Gy."}
{"_id": "Radiology$$$73abba99-5b08-4166-8e0f-9931f6bd5486", "text": "How many fractions of 2 Gy should we give to get the same biological effect as for 1 fraction of 10\u00a0Gy?"}
{"_id": "Radiology$$$ff7f511f-7ec8-45a2-9bf9-44fe97caee7d", "text": "SQ1.\nPrinciples of radiation dosimetry\n\u00a0SQ2.\nRadiation microdosimetry(a)\nThe lineal energy is the quotient of the total energy imparted to a volume of matter by a single energy deposition event and the mean chord length in that volume.\n\u00a0(b)\nIn large-size targets, the number of interactions is large and the distribution of lineal energy converge to an expected value, which is the LET.\n\u00a0\n\u00a0SQ3.\nFrom track structure to early DNA damage1.\nTwo main characteristics differentiate these two types of MC calculation:(a)\nTS MC codes do not use the condensed history approach for electron transport and they discretely simulate all electron interactions (elastic and inelastic)\n\u00a0(b)\nTS MC codes include electron interaction cross sections to explicitly transport the electrons down to very low energies (of the order of 10 eV), which allows to calculate the energy depositions in micrometric and nanometric volumes.\n\u00a0\n\u00a02.\nCross sections, mainly for liquid water, used by MCTS codes have uncertainties due to the lack of experimental data that could validate them. All the complexity of radiolysis and reactions of radiolytic species with biomolecules is not taken into account. DNA geometrical models require approximations. The conversion of particle interactions or reactions of radiolytic species into damage is a source of interpretation.\n\u00a0\n\u00a0SQ4.\nMicro-beams and Minibeams\n\u00a0(a)\n\n\nA block diagram illustrates connecting of microbeam, single, array, and mini beam to dose-volume effect, enhanced R B E of high-L E T particles, mechanisms of M R T, bystander effect, cellular response to single ions, and radiosensitivity of subcellular structures,\n\n\n\u00a0SQ5.\nTarget theory and dose-response models(a)\n\u03b1/\u03b2 = 12\n\u00a0(b)\nand 0.001\n\u00a0(c)\n8"}
{"_id": "Radiology$$$64bd90db-b23b-4c09-9fa4-4ae17a2745cf", "text": "Radiation microdosimetry(a)\nThe lineal energy is the quotient of the total energy imparted to a volume of matter by a single energy deposition event and the mean chord length in that volume.\n\u00a0(b)\nIn large-size targets, the number of interactions is large and the distribution of lineal energy converge to an expected value, which is the LET."}
{"_id": "Radiology$$$a984407c-5a26-440c-b99a-abf936e00bcd", "text": "The lineal energy is the quotient of the total energy imparted to a volume of matter by a single energy deposition event and the mean chord length in that volume."}
{"_id": "Radiology$$$d33450bb-877b-4c1f-9a64-dd22195b78db", "text": "In large-size targets, the number of interactions is large and the distribution of lineal energy converge to an expected value, which is the LET."}
{"_id": "Radiology$$$1f361e88-b62a-4e93-b13f-4efa9f3b133b", "text": "From track structure to early DNA damage1.\nTwo main characteristics differentiate these two types of MC calculation:(a)\nTS MC codes do not use the condensed history approach for electron transport and they discretely simulate all electron interactions (elastic and inelastic)\n\u00a0(b)\nTS MC codes include electron interaction cross sections to explicitly transport the electrons down to very low energies (of the order of 10 eV), which allows to calculate the energy depositions in micrometric and nanometric volumes.\n\u00a0\n\u00a02.\nCross sections, mainly for liquid water, used by MCTS codes have uncertainties due to the lack of experimental data that could validate them. All the complexity of radiolysis and reactions of radiolytic species with biomolecules is not taken into account. DNA geometrical models require approximations. The conversion of particle interactions or reactions of radiolytic species into damage is a source of interpretation."}
{"_id": "Radiology$$$c683166e-ac5c-4509-b30f-a42a29d4eb4b", "text": "Two main characteristics differentiate these two types of MC calculation:(a)\nTS MC codes do not use the condensed history approach for electron transport and they discretely simulate all electron interactions (elastic and inelastic)\n\u00a0(b)\nTS MC codes include electron interaction cross sections to explicitly transport the electrons down to very low energies (of the order of 10 eV), which allows to calculate the energy depositions in micrometric and nanometric volumes."}
{"_id": "Radiology$$$aa75684c-7ba2-44e5-8c76-0871df7e1834", "text": "TS MC codes do not use the condensed history approach for electron transport and they discretely simulate all electron interactions (elastic and inelastic)"}
{"_id": "Radiology$$$0d3d4c83-1adc-452b-aac3-11874390d846", "text": "TS MC codes include electron interaction cross sections to explicitly transport the electrons down to very low energies (of the order of 10 eV), which allows to calculate the energy depositions in micrometric and nanometric volumes."}
{"_id": "Radiology$$$b9fad97b-a952-4dec-9f41-ec89cbd36a26", "text": "Cross sections, mainly for liquid water, used by MCTS codes have uncertainties due to the lack of experimental data that could validate them. All the complexity of radiolysis and reactions of radiolytic species with biomolecules is not taken into account. DNA geometrical models require approximations. The conversion of particle interactions or reactions of radiolytic species into damage is a source of interpretation."}
{"_id": "Radiology$$$a946b72c-80fa-4df0-a0cd-fe61ec747f7a", "text": "A block diagram illustrates connecting of microbeam, single, array, and mini beam to dose-volume effect, enhanced R B E of high-L E T particles, mechanisms of M R T, bystander effect, cellular response to single ions, and radiosensitivity of subcellular structures,"}
{"_id": "Radiology$$$b85f82c8-50a5-4879-af52-cb5b6e28971a", "text": "Target theory and dose-response models(a)\n\u03b1/\u03b2 = 12\n\u00a0(b)\nand 0.001\n\u00a0(c)\n8"}
{"_id": "Radiology$$$16c8f018-fb49-4663-997b-0a5982ee1497", "text": "and 0.001"}
{"_id": "Radiology$$$b0dc6bf7-2e60-46db-84f3-a7602324b62b", "text": "RT is one of the cornerstones in cancer treatment.\n\nThe objective of RT resides in finding an optimal balance between chances of cure and risk of associated toxicity.\n\nDifferential effect of RT between tumors and normal tissues depends on multiple factors related to both malignant and healthy tissue radiobiology, but also on beam characteristics and treatment schedule.\n\nTechnical advances and sophistication of RT devices improve ballistic accuracy and allows unprecedented changes in treatment schedules, probably changing both malignant and healthy tissue radiobiology."}
{"_id": "Radiology$$$55aed8b5-5196-4fd9-9722-a75e5f6b07c0", "text": "The objective of RT resides in finding an optimal balance between chances of cure and risk of associated toxicity."}
{"_id": "Radiology$$$0a749f43-1cd3-46aa-9b56-cea2f1336e4e", "text": "Differential effect of RT between tumors and normal tissues depends on multiple factors related to both malignant and healthy tissue radiobiology, but also on beam characteristics and treatment schedule."}
{"_id": "Radiology$$$809ce3d1-5725-4b53-a9e0-0d73917b8e4f", "text": "Technical advances and sophistication of RT devices improve ballistic accuracy and allows unprecedented changes in treatment schedules, probably changing both malignant and healthy tissue radiobiology."}
{"_id": "Radiology$$$8bc3a44f-bad9-44f3-a8d8-1523e5c3acf9", "text": "Radiation therapy (RT) is a locoregional treatment modality for cancer. Using radiation for therapeutic purposes began only a few months after the discovery of X-rays by Wilhelm R\u00f6ntgen in 1895. The first \u201ctrue\u201d RT succeeded in managing a case of lupus erythematosus in 1897 by Eduard Schiff (1899). More than 120\u00a0years later, RT is still one of the cornerstones of tumor treatment, with more than half of all cancer patients treated by radiation in the course of their therapeutic management [1] (Box 5.1)."}
{"_id": "Radiology$$$2a1c663b-99ae-4a22-8185-8fedcc81d7de", "text": "The interesting (but also dangerous) properties of ionizing radiation (IR) reside in its ability to penetrate more or less deeply in biological tissues, depending on its energy, and to react with the environment. These reactions consist in direct energy deposition and the generation of free radicals near and within living cells. The consequence of energy deposition is damage to the DNA structure leading to cell death if unrepairable [2]. Of course, all cells are concerned, tumor cells as well as cells in the healthy tissues, and within the irradiated volume, no difference is made between tumor and healthy cells. Treating a tumor would be easily achievable by the administration of a very high dose if it was not surrounded by the patient. Therefore, several strategies have been developed to ensure both the best tumor control and the least consequences ensuing from healthy tissues exposure, taking advantage of differences between tumor and healthy cells, known as the benefit/risk balance (Fig. 5.1).\n\nThe diagram displays the benefit of radiation therapy which is tumor control and the risk is the normal tissue toxicity.\n\nFig. 5.1\nThe benefit/risk balance. The objective of RT is to control the tumor while sparing normal tissues, to ensure the patient\u2019s cure without unacceptable side effects"}
{"_id": "Radiology$$$dc368a93-0dfd-4627-b198-81aa06d8da9f", "text": "The diagram displays the benefit of radiation therapy which is tumor control and the risk is the normal tissue toxicity."}
{"_id": "Radiology$$$400221a2-fc5d-4e1b-a243-91781d0af9ad", "text": "Some biological processes favor the benefit/risk ratio in RT and the differential effect between tumor and healthy cells. Except for some very radiosensitive or radioresistant tumors, healthy and tumor cells demonstrate quite similar radiation sensitivities. However, DNA damage is less efficiently repaired by tumors than by healthy cells. This is the basis for the dose fractionation principle, demonstrated by Claudius Regaud and applied in the clinic by Henri Coutard in 1934, and which still is used today in modern RT. The total dose necessary to control the tumor is generally delivered in a series of small daily doses. The time lapse between each fraction allows DNA damage to be repaired by healthy cells whereas tumor cells do not repair or do so to a lesser extent. The biological effectiveness (the chances of tumor control but also the risk of damage to normal tissues) is reduced when using fractionated doses due to DNA repair and cell repopulation in both tumors and healthy tissues [3]. Numerous parameters associated with fractionation regimens, such as the total dose, the dose per fraction, and the time between fractions and the total treatment time, will influence both tumor response and normal tissue damage and will be described in more detail below [4]. Another biological factor participating in the differential effect is radiation-induced cell death. In a majority of cases, the initial radiation exposure is not what kills cells but rather unrepaired DNA damage, which condemns them to death as soon as they re-enter in the cell cycle. Rapidly proliferating tumor tissues will suffer significant cell death under these conditions compared to slowly proliferating healthy tissues. However, some healthy tissues such as oral and intestinal mucosa or hematopoietic cells proliferate rapidly and may be susceptible to early mitotic cell deaths if present in the irradiated volume. Finally, tumor control will also depend on other factors such as tumor heterogeneity (the tumor cannot be simply considered as a cluster of tumor cells), oxygenation status before RT and variations during treatment, tumor vascularization, resident and recruited immune cells, and so forth. Considering all these biological factors, the objective of treatment planning in RT is to find the best compromise between chances of cure and risk of associated toxicity [5]."}
{"_id": "Radiology$$$bf1a69cf-e904-479b-8113-5080dc17da46", "text": "In an ideal world, RT may target only the tumor volume; however, in real life, this is never the case. For healthy tissues, besides dose and fractionation, the volume exposed is of paramount importance in determining the risk of developing toxicity. Technical advances in dose delivery, planning systems and associated imaging devices have helped to achieve ever increasing ballistic accuracy. Advanced technologies, such as volumetric modulated arc therapy (VMAT), image-guided radiotherapy (IGRT), stereotactic body radiotherapy (SBRT), heavy ions [6], or proton therapy have all contributed to progress [7]. Consequently, the use of highly focused beams reduces the volume of normal tissues present within the irradiated volume and can spare very sensitive organs, thus minimizing the risk of toxicity. Reducing the volume also permits changes in fractionation schedules. For example, SBRT uses hypofractionation, delivering ablative doses per fraction between 8 and 20 Gy instead of the conventional 2\u00a0Gy/fraction. The gain in biological effectiveness strongly increases tumor control as illustrated in early-stage primary lung cancer. These changes in fractionation schemes may also induce a \u201cnew\u201d radiobiology of tumors and healthy tissues in response to very high doses of IR, an area that remains to be explored [8]. Finally, ultra-high dose rate FLASH RT demonstrates a very sharp differential effect between tumor and healthy tissues and is the subject of intense research for future clinical applications [9]."}
{"_id": "Radiology$$$607b3b0f-40af-4513-bf13-5c7998f69d44", "text": "Technical advances have strongly contributed to the chances of cure for numerous cancers and increased patients\u2019 survival. This increased life expectancy following cancer treatment, however, favors the emergence of side effects, especially long-term sequelae. Normal tissues can be divided into \u201cearly\u201d and \u201clate\u201d responding tissues. Early-responding tissues (intestinal mucosa, hematopoietic system, skin, gonads) are characterized by the presence of cell proliferation compartments and are mostly implicated in acute radiation-induced toxicity. Late-responding tissues demonstrate no distinct cell proliferation compartment and are mostly implicated in late toxicity. For each normal tissue, dose constraints, which vary depending on the RT technique used, may be applied. These constraints help to minimize the risk of developing severe treatment-associated toxicity [10]."}
{"_id": "Radiology$$$559b7eb9-af47-407c-a6bb-489c9309b0ce", "text": "RT still plays a significant role in cancer cures. Its efficiency depends on numerous parameters related to both tumor and normal tissue radiobiology. The objective of cancer therapy, using modern RT often concurrently with other therapeutic strategies (surgery, chemotherapy, immunotherapy, etc.) is for the patients to survive without debilitating sequelae. This goal may be achieved using technological advances in RT, combined with strategic knowledge of both tumor and healthy tissue radiobiology."}
{"_id": "Radiology$$$6c117212-c6a6-43c0-87ac-bba527b838e0", "text": "Therapeutic window: The difference between tumor control probability (TCP) and normal tissue complication probability (NTCP) at identical irradiation dose.\n\nTherapeutic ratio: The relation between TCP and NTCP or efficacy to toxicity ratio."}
{"_id": "Radiology$$$d17026b4-dc7e-47b7-aa76-9a1e1a23085f", "text": "Therapeutic window: The difference between tumor control probability (TCP) and normal tissue complication probability (NTCP) at identical irradiation dose."}
{"_id": "Radiology$$$5b15a65d-7398-4571-977a-d09375b97645", "text": "Therapeutic ratio: The relation between TCP and NTCP or efficacy to toxicity ratio."}
{"_id": "Radiology$$$2096b0c7-e8bc-4eaf-8c22-3725b1a022c3", "text": "RT is one of the most effective treatment modalities in cancer therapy. However, despite modern precision RT, it is generally unavoidable to deposit IR to the tumor volume without risk of radiation injury to the surrounding healthy normal tissues or organs. Hence, the therapeutic effectiveness of radiation is dependent on the balance between tumor control and normal tissue adverse effects. In fact, the tolerance dose of the normal tissues or organs at risk determines the dose which can be safely applied to the tumor volume. For almost all normal tissues and organs, dose-volume constraints are well documented in the literature, for example, the QUANTEC (QUantitative Analysis of Normal Tissue Effects in the Clinic) data, as guidance in the clinical practice (see Sect. 5.13.6) [11]. The so-called therapeutic window is a conceptual window of opportunity between the tumor control probability (TCP) and normal tissue complication probability (NTCP) (Fig. 5.2).\n\nLocal tumor control and normal tissue complication probability versus dose plots upward trends for tumor sensitization, hypoxic and non hypoxic modification, biological targeting, tumor microenvironment, D N A repair, Immunotherapy, improved radiation delivery, and normal tissue protection.\n\nFig. 5.2\nIllustration of the therapeutic window. For an identical delivered dose, the curves show the difference between tumor control probability and normal tissue complication probability and methods to widen the window. (Reprinted from Drug radiotherapy combinations: review of previous failures and reasons for future optimism; Figure from Higgins et al. [12], with permission)"}
{"_id": "Radiology$$$ae0de919-0a8a-4137-8eac-06ae896d0436", "text": "Local tumor control and normal tissue complication probability versus dose plots upward trends for tumor sensitization, hypoxic and non hypoxic modification, biological targeting, tumor microenvironment, D N A repair, Immunotherapy, improved radiation delivery, and normal tissue protection."}
{"_id": "Radiology$$$5544b8c4-4b1d-4fba-a74f-18fdd81e9427", "text": "The ultimate aim of RT in the clinic is accomplished when the therapeutic window is large, with an optimized balance between benefits and risks, hence a treatment that is highly likely to be effective and safe. The shape and position of the dose\u2013response curves for tumor control and toxicity to the normal tissues (Fig. 5.2) determines the probability that enough radiation is delivered to destroy the tumor cells without serious complications. The position of the curves determines the feasibility of the application of RT to the patient. The therapeutic window is large in radiosensitive tumor types like lymphoma, but small for other tumor types such as brain and pancreatic cancer. If the dose\u2013response curve for normal-tissue toxicity is positioned at the left side of the tumor control curve or in case the curves are close together, the aimed tumor response could only be achieved at the cost of a high complication risk. The standard RT treatment is that one with tumor control probability (TCP)\u00a0\u22650.5 and normal tissue complication probability (NTCP) \u22640.05 [13]."}
{"_id": "Radiology$$$de839aa4-d8e1-4c63-9008-8c7853317590", "text": "It is worth noting that Fig. 5.2 illustrates an ideal situation. The TCP curve might in particular however deviate for two main reasons. First, tumors are more heterogeneous compared with normal tissue; subsequently, the expression of the TCP curve becomes shallower than that of the NTCP curve. Secondly, not only the region of interest does contain the malignant cells, but there might be metastatic extensions outside the irradiation treatment volume. Hence, it is unlikely that the TCP curve for local control of specific tumors scores 100% [14, 15]."}
{"_id": "Radiology$$$2ad05b6b-2ce8-4915-ab43-ee03036a526e", "text": "Several treatment parameters influence the therapeutic window. For example, when the overall treatment time is prolonged, the therapeutic window is narrowed (Fig. 5.3) [15, 16]. It is however difficult to practice this strategy because each complication translates the effect of a treatment parameter on the therapeutic window differently.\n\nA line graph represents response versus radiation dose in gray. The dotted curve for split-course treatment, and the solid curve for conventional fractionation treatment have the same upward trend, before slightly declining at the endpoint.\n\nFig. 5.3\nProlongation of the overall treatment time narrows the therapeutic window. Conventional irradiation course in 6\u00a0weeks versus a split-course course in 10\u00a0weeks. (Adopted from [16])"}
{"_id": "Radiology$$$5c7d7678-68a3-4a23-a774-b49baa02d43c", "text": "A line graph represents response versus radiation dose in gray. The dotted curve for split-course treatment, and the solid curve for conventional fractionation treatment have the same upward trend, before slightly declining at the endpoint."}
{"_id": "Radiology$$$6a5ca61c-4b26-4b30-a302-cd577ee56e9b", "text": "Several methods can be used to widen the therapeutic window, to increase the probability of complication-free tumor control:\nFractionated RT. See Fig. 5.4. Decrease of the organ or tissue at risk volume using precision RT techniques allowing optimal dose distribution (e.g., stereotactic irradiation/particle irradiation).\n\nCombination therapy with molecular targeting or immune-modulating drugs. Optimally, drugs should be carefully chosen to selectively sensitize tumor and not normal tissue cells, taking the 6R\u2019s or Hallmarks of Radiobiology into account (see Sect. 5.4).\n\n\nTwo line graphs represent probability versus dose in gray. The plotted data in each graph, T C P and N T C P, are in an upward trend, while uncomplicated cures are in a downward trend.\n\nFig. 5.4\nFractionation as an effective method to widen the therapeutic window. Curves schematically represent the probability of normal tissue side effects (NTCP, red curve), the probability of tumor control (TCP, blue curve) as well as the complication free tumor control curve (green) following single-dose radiation (a) and dose fractionation (b). (Figure from Shrieve and Loeffler [17], with permission from Wolters Kluwer Health, Inc.)"}
{"_id": "Radiology$$$679eef3c-5028-40d2-95bb-42e5b34aea08", "text": "Fractionated RT. See Fig. 5.4. Decrease of the organ or tissue at risk volume using precision RT techniques allowing optimal dose distribution (e.g., stereotactic irradiation/particle irradiation)."}
{"_id": "Radiology$$$592a7366-ccfd-4d04-8ed6-80ff8fe4ec00", "text": "Combination therapy with molecular targeting or immune-modulating drugs. Optimally, drugs should be carefully chosen to selectively sensitize tumor and not normal tissue cells, taking the 6R\u2019s or Hallmarks of Radiobiology into account (see Sect. 5.4)."}
{"_id": "Radiology$$$c1f2ccbf-d738-4193-a491-fc6dc3e8ee15", "text": "Two line graphs represent probability versus dose in gray. The plotted data in each graph, T C P and N T C P, are in an upward trend, while uncomplicated cures are in a downward trend."}
{"_id": "Radiology$$$e61e6974-ba29-4359-89c3-597f123419e3", "text": "The therapeutic ratio or therapeutic index is an imperative measure used in the treatment planning to ensure that the RT course achieves its goals [18]. The ratio represents the difference between the TCP and NTCP curves for the same delivered dose at a fixed endpoint of NTCP [14]. Therefore, it represents the quantity used in the tumor treatment planning for the purpose of disease cure without complications. The ratio is defined as the relationship between TCP and NTCP, i.e., efficacy/toxicity ratio. Chang et al. stated that a common method used to calculate the therapeutic ratio which is the probability of cure without complications [19] and given by:"}
{"_id": "Radiology$$$48ddb7d1-b539-4248-8366-e06edce6c747", "text": "As the difference between TCP and NTCP becomes large it means that TR approaches 1 and treatment is fairly effective for tumor control than for causing normal tissue morbidity, but the pattern is reversed when the difference between TCP and NTCP becomes small. That is, TR approaches 0 and the treatment may fail and be relatively more toxic [14]. As explained above, there are many treatment parameters and methods that affect the therapeutic ratio, for example, combination therapy with a radiosensitizing agent or drug. This effect is revealed in practice as increasing tumor cure rate with improved quality of life as a result of a therapeutic gain [13, 16]. In this circumstance, the therapeutic ratio is the ratio of dose-modifying factors (DMFs) of tumor over that for normal tissues."}
{"_id": "Radiology$$$11ff3024-0241-4811-8565-82dac5bb7309", "text": "Finally, the therapeutic ratio differentiates between early and late responding normal tissues in terms of their response to concomitant RT and chemotherapeutics or targeted agents. While the therapeutic ratio of early responding tissue is usually <1, the therapeutic ratio of late responding tissues is >1 which reflects the advantageous consequence of concomitant RT and chemotherapy. This may lead to a high level of early injury, but a neutral level of late damage to late responding tissues. Fortunately, early side effects can be relieved by using either extensive supportive care or adaptation of the standard treatment. The combination of RT and chemotherapy may prove effective if selective radiosensitization of malignancy is obtained and the probability of late-responding normal tissue damage is not increased. However, early toxicities might also be a concern."}
{"_id": "Radiology$$$4f3578ce-05eb-44e1-b27f-e9427e7bbbc7", "text": "Tumor control probability (TCP) is guided by dose, tumor characteristics, and normal tissue radiation sensitivity.\n\nKilling of clonogenic cells within a tumor partly explain TCP during RT, but the effect is also influenced by host factors, for example, immune cell attack."}
{"_id": "Radiology$$$73320378-0ee2-4db0-981a-c63739144119", "text": "Tumor control probability (TCP) is guided by dose, tumor characteristics, and normal tissue radiation sensitivity."}
{"_id": "Radiology$$$7fec7634-d44a-40c8-87ab-f220a82cbab9", "text": "Killing of clonogenic cells within a tumor partly explain TCP during RT, but the effect is also influenced by host factors, for example, immune cell attack."}
{"_id": "Radiology$$$a4bf699f-3174-4514-adc1-a05f4bb00c26", "text": "The main objective of curative RT is to successfully achieve local tumor control [16]. The relationship between TCP and radiation dose is shown in Fig. 5.5 which illustrates that there is poor tumor control with low dose, but high tumor control with high dose [20]. The steepness of the curve depends on differences in tumor size, tumor cell radiation sensitivity and repopulation as well as other factors. These factors give rise to variation in TCP of different tumors but also inter-patient variation in clinical practice. Subsequently, this improvement in tumor control is reflected in an increase in the life expectancy of cancer patients. To this end, it is preferable to evaluate RT success based on tumor control.\n\nA schematic diagram of tumor control versus radiation dose. The therapeutic effect and normal tissue are in an upward trend, with the therapeutic index at 50% of tumor control.\n\nFig. 5.5\nTumor Control Probability (TCP) and radiation dose relationship. The scheme demonstrates the sigmoid relationship of probability of tumor control and normal tissue damage to radiation dose"}
{"_id": "Radiology$$$057b7e69-0331-464a-aca7-c4fdd0871115", "text": "A schematic diagram of tumor control versus radiation dose. The therapeutic effect and normal tissue are in an upward trend, with the therapeutic index at 50% of tumor control."}
{"_id": "Radiology$$$f19166a1-818f-4233-a357-40b0b79c7ee7", "text": "Complete tumor control requires that every clonogenic cell is destroyed. Unfortunately, cell killing is randomly distributed within a population of tumor cells, and there are about 109 cells in each gram of tumor. A small fraction of these cells (about 1%), in reality, contains cells with clonogenic-forming ability; so, a human tumor could have billions of clonogenic cells; therefore, eliminating every such cell is a great challenge. The likelihood of obtaining tumor control is related to radiation dose, features of control probability of the tumor and the number of surviving clonogenic tumor cells (Fig. 5.6.).\n\nA graph represents cell kill versus dose in gray. The plotted data, the cell with clonogenic ability has a downward trend.\n\nFig. 5.6\nThe response of clonogenic tumor cells at 2\u00a0Gy/fraction as a function of the total dose. Assuming that each 2 Gy fraction reduces the clonogenic cell population with 50%, 30 fractions of 2 Gy will reduce 1010\u00a0clonogenic tumor cells to ten surviving cells. In order to eliminate each clonogenic tumor cell, additional fractions of 2 Gy are required to reach tumor control"}
{"_id": "Radiology$$$52d09cad-e5ab-442a-9395-9079ad85c8de", "text": "A graph represents cell kill versus dose in gray. The plotted data, the cell with clonogenic ability has a downward trend."}
{"_id": "Radiology$$$c1d7234e-075f-41a7-b96c-d7e6db7fb6ce", "text": "The tumor growth rate can be used to determine how a cancer will respond to RT treatment by predicting or understanding the key features of the tumor tissue response to radiation. The tumor growth rate was developed for examining the capacity of clonogenic-forming cells of a tumor and assumes that the regrowth component is a function of repopulation by the surviving of cells with colony-forming ability [20, 21]."}
{"_id": "Radiology$$$06623f93-d9e3-4c57-9b80-0e66df94018d", "text": "There are considerable differences in growth rate between different tumors due to differences in size and biology. Therefore, the tumor growth curve has exponential and non-exponential parts when plotted on a logarithmic scale. That is, the tumor volume doubling time (VDT), the duration of time required for the tumor to double in size, increases for small tumors because there is a sufficiency in nutrient and oxygen supply resulting in a reduction of cell cycle, a higher proportion of cycling cells or and a lower cell death rate. As a result, the slope of the growth curve, which reflects the doubling time of the cells, has an exponential pattern for small tumors. Conversely, VDT decreases for large tumors because of the limitation of nutrient and oxygen supply. This leads to a prolongation of cell-cycle progression but also a high rate of cell death. As a result, the slope of the growth curve has no exponential patterns for large tumors. The Gompertz equation describes such progressively slowing tumor growth:"}
{"_id": "Radiology$$$fece4e9d-7b94-454d-90d0-2674608a980f", "text": "(5.1)where V0 is the volume at arbitrary zero time while A and B are parameters that determine the speed of growth [16]. VDTs are remarkably variable in human tumors, both between primary and metastatic lesions and among tumors with different histology (Table 5.1). Please also note that even within one tumor entity (localization, histology, and primary or metastasis similar) there is a range in VDT illustrating the problem of tumor heterogeneity.Table 5.1\nVolume Doubling Times (VDTs) for different human tumors (adapted from [16])\n\nTumor site, histology\n\nPrimary vs metastasis\n\nNumber of tumors measured\n\nMean VDT (days) (confidence limits)\n\nColon-rectum\n\nPrimary\n\n19\n\n632\n[426\u2013938]\n\nColon-rectum, adenocarcinoma\n\nMetastasis\n\n55\n\n95\n[84\u2013107]\n\nLung, squamous cell carcinoma\n\nPrimary\n\n85\n\n85\n[75\u201395]\n\nLung, adenocarcinoma\n\nPrimary\n\n64\n\n148\n[121\u2013181]\n\nLung, undifferentiated\n\nPrimary\n\n55\n\n79\n[67\u201393]\n\nBreast\n\nPrimary\n\n17\n\n96\n[68\u2013134]\n\nBreast carcinoma\n\nSuperficial metastasis\n\n66\n\n19\n[16\u201324]\n\nBreast, adenocarcinoma\n\nMetastasis\n\n44\n\n74\n[56\u201398]\n\nHead and neck, squamous cell carcinoma\n\nMetastasis\n\n27\n\n57\n[43\u201375]\n\nHead and neck, teratoma\n\nMetastasis\n\n80\n\n30\n[24\u201338]\n\nHead and neck, osteosarcoma\n\nMetastasis\n\n34\n\n65\n[46\u201393]\n\nHead and neck, fibrosarcoma\n\nMetastasis\n\n28\n\n69.5\n[46\u201393]\n\nKidney, adenocarcinoma\n\nMetastasis\n\n14\n\n60\n[37\u201398]\n\nThyroid, adenocarcinoma\n\nMetastasis\n\n16\n\n67\n[44\u2013103]\n\nUterus, adenocarcinoma\n\nMetastasis\n\n15\n\n78\n[55\u2013111]"}
{"_id": "Radiology$$$f65aea70-eb7e-4929-90bd-2e6a16ba4cff", "text": "The growth fraction (GF) refers to the proportion of cycling cells that has highly colony-forming ability and is in the active process of cell cycling (omitting cells in G0 phase), with capacity of DNA duplication and cell division [22]. Similarly, as in normal tissue, some tumor cells are not involved in active proliferation for different reasons, for instance as a result of hypoxia, differentiation, and catabolic insufficiency. Moreover, it is estimated that about 50% of cells in a tumor are not neoplastic cells but are cells making up the tumor stroma. Therefore, it is clear that the cell population in tumors contains quiescent (Q) cells, and since GF is defined as the proportion of cycling cells, it can be calculated as stated by [13, 22]:"}
{"_id": "Radiology$$$c0f9b053-e961-44e3-9f4d-a77ec8610eeb", "text": "(5.2)where p is proliferating cells."}
{"_id": "Radiology$$$8cf68b05-e509-4380-8a24-717966f3b1f9", "text": "For estimation of the cell-cycle kinetics (TC), three principal methods are used: (1) bromodeoxyuridine (BrdUrd) or thymidine analogues iododeoxyuridine (IdUrd), (2) 3H-thymidine for the synthesis of DNA and (3) positron emission tomography (PET) imaging of the tumors in vivo by radiolabeled 18F-fluoro-3\u2032-deoxy-3\u2032-l-fluorothymidine (FLT) [13, 16]."}
{"_id": "Radiology$$$7ae395bf-a1c5-43a9-a179-269f0ba02948", "text": "The first method includes labeling of the cells with BrdUrd or IdUrd. When cells pass through the S-phase, these labels are incorporated into the newly created DNA strand. An antibody against BrdUrd or IdUrd as well as a DNA-specific dye are used to stain a single-cell suspension prepared from a cell culture in vitro or a tumor biopsy, and the duration of the S phase (TS) and fraction of cells in S phase are assessed using flow cytometry."}
{"_id": "Radiology$$$289b4463-4627-4e49-b7d0-9b7311ff1df8", "text": "In the second method, cell-cycle kinetics (TC) is estimated from labeled cells by measuring the duration of the cell cycle by either pulse or continuous labeling with 3H-thymidine. The labeling agent is incorporated into the DNA as cells progress through S-phase and the cell-cycle kinetics (TC) is estimated from the labeled cells [16]."}
{"_id": "Radiology$$$9b47d94c-8ae1-463f-b67d-f58b6e25d509", "text": "The third principal method applies PET tracers to detect and evaluate tumor proliferation in vivo. In this method, radiolabeled 18F-fluoro-3\u2032-deoxy-3\u2032-l-fluorothymidine (FLT) is used. FLT is phosphorylated by thymidine kinases (TK) and since regulation of TK activity occurs in the S-phase, it means that metabolites of FLT (mono-, di-, and tri-phosphates) are reflecting the number of cells in S-phase and hence replication status. The FLT tracer activity in a tumor is subsequently evaluated by a PET scanner from which the cell-cycle kinetics can be estimated [16]."}
{"_id": "Radiology$$$0fda07ee-5348-469a-9f4d-26ab8b60bf9b", "text": "For estimation of the GF, according to literature the GF is obtained by assessment of two distinct cell subpopulations, one that does not grow and another which grows with a uniform cell-cycle distribution [13, 21]. This method includes the exposure of a growing culture of cells with 3H-thymidine for the synthesis of DNA, and then after the period of at least one complete cell cycle to ensure all cells producing DNA pass through the S-phase and are labeled, an autoradiography of tumor section is taken, and GF is calculated by:"}
{"_id": "Radiology$$$d0b6dd17-f5ef-4808-9cbd-ba129aaeaa49", "text": "There is also a possibility to take proliferation into account by immunohistochemistry assessment of tumor tissue sections by staining of the nuclear antigen Ki-67, which in tumors has different levels depending on the tumor proliferation. The method includes staining of tumor cell cultures or a tumor biopsy with a Ki-67 specific antibody followed by counting the number of positive tumor cells. The GF growth fraction is estimated from labeled cells by measuring the proportion of proliferating cells using continuous labeling. Although the method is frequently used to assess S-phase cells, recent results have indicated that Ki-67 also has different functions in other cell-cycle phases which may in fact influence proliferation estimations [23]."}
{"_id": "Radiology$$$4babfd3b-57a4-41f5-bfcf-1a8ed46b4ca5", "text": "\u201cThe potential doubling time (Tpot) of a tumor is defined as the cell doubling time without any cell loss.\u201d There are two methods used to estimate Tpot. In the first method, DNA is labeled with thymidine analogues and then the cells fraction in S phase (LI) and the duration of the S phase (TS) are estimated by using flow cytometry to calculate Tpot by:"}
{"_id": "Radiology$$$5fda93ff-d5a8-4acc-a723-f964607c8c78", "text": "(5.3)where \u03bb is a correction parameter for the non-rectangular age distribution of growing cell populations, in the order of 0.7\u20131."}
{"_id": "Radiology$$$0b71fc14-f57b-4e63-8075-05da6b501619", "text": "Different tumor tissues have different values of LI, but they have similar TS, in the range of 12\u00a0h. As a result, Tpot has a spectrum of values ranging from 4 to 34\u00a0days, as shown in Table 5.2. Of note, it has been demonstrated that in a clinical RT context, the pre-treatment Tpot does not predict outcome as one also needs to consider the repopulation rate of colony-forming cells [13].Table 5.2\nCell kinetic parameters of human tumors derived from in vivo labeling with iodo-deoxyuridine (IdUrd) or bromo-deoxyuridine (BrdUrd) and monitored by flow cytometry (adapted from [16])\n\nTumor site\n\nTumor type\n\nPatients number\n\nAverage Tpot (days)\n\nAverage LI (%)\n\nAverage TS (h)\n\nSkin\n\nMelanoma\n\n24\n\n7.2\n\n4.2\n\n10.7\n\nHematological\n\n\u2013\n\n106\n\n9.6\n\n13.3\n\n14.6\n\nHead and neck region\n\n\u2013\n\n712\n\n4.5\n\n9.6\n\n11.9\n\nCNS\n\n\u2013\n\n193\n\n34.3\n\n2.6\n\n10.1\n\nBreast\n\n\u2013\n\n159\n\n10.4\n\n3.7\n\n10.4\n\nGIT (upper intestine)\n\n\u2013\n\n183\n\n5.8\n\n10.5\n\n13.5\n\nGIT (colorectal)\n\n\u2013\n\n345\n\n4\n\n13.1\n\n15.3\n\nKidney\n\nRenal cell carcinoma\n\n2\n\n11.3\n\n4.3\n\n9.5\n\nBladder\n\n\u2013\n\n19\n\n17.1\n\n2.5\n\n6.2\n\nProstate\n\n\u2013\n\n5\n\n28\n\n1.4\n\n11.7\n\nOvarian\n\n\u2013\n\n55\n\n12.5\n\n6.7\n\n14.7\n\nCervix\n\n\u2013\n\n159\n\n4.8\n\n9.8\n\n12.8"}
{"_id": "Radiology$$$f65428c4-cc51-4728-a1a7-31c4bab2b8eb", "text": "Slow tumor growth is not only explained by the fact that not all cells within a tumor are proliferating but also due to considerable cell loss where multiple parameters regulate these two factors. If there was no cell loss and if every tumor cell was actively proliferating, the tumor doubling time would imitate the cell-cycle kinetics (TC). Therefore, when there is cell loss the TD is long and when there is reduced GF the Tpot of the tumor is longer than the time of cell cycle [14]."}
{"_id": "Radiology$$$10d6b089-b502-464e-a8d8-56b05e01a36c", "text": "The net growth rate, or the VDT, of tumors results from the balance of cell production and cell loss. In clinical settings, the GF and knowledge of the cycle time of the individual cells does not reflect the speed of tumor growth; namely, the cycle time of the individual cells is much faster than the speed of tumor growth. Such discrepancy is attributed to cell loss which can be considered by calculating cell loss factor (CLF). The cell-loss factor refers the ratio of the cell loss rate to the production of new cells, and it can be calculated by:"}
{"_id": "Radiology$$$d35364ab-5bee-4052-80e5-705b95561fb1", "text": "(5.4)where Tpot is the potential tumor doubling, and VDT is the tumor volume doubling time that is calculated by the essential time for the tumor to double its volume (V) by using:\n\n (5.5)"}
{"_id": "Radiology$$$86ac8e8a-2336-4cbf-9916-edc40955d612", "text": "When the cell loss factor is high, it means that there is loss of newly produced cells from the GF; thus, tumor growth is slow. Cell loss has been attributed to different parameters [16, 24]: (1) Cells are in the inactive phase of cell cycling (in G0 phase) which is a non-proliferative compartment, (2) There is inadequate nutrition and oxygen levels due to the tumor outgrowth that gives rise to pushing cells into areas at a distance from blood supply, (3) Metastasis, (4) Immune cell killing of the tumor, and (5) Exfoliation (the complete removal of a single epithelial cell or group of cells from a layer of epithelium by spontaneous or induced means). In animal models of tumors, this would not apply but could be a mechanism by which cells lose their integrity in carcinomas of the gastrointestinal tract, for example, where the epithelium is renewed rapidly (Box 5.4)."}
{"_id": "Radiology$$$b410f5c4-bd6c-4622-b889-70a7888055a5", "text": "Tumor volume doubling time (VDT) is influenced by tumor localization site, primary or metastatic status as well as histology but also by intra-tumor heterogeneity factors.\n\nThere are differences in growth rates between different tumor types and metastatic lesions tend to grow faster than primary lesions.\n\nA logarithmic scale can be used to judge treatment effectiveness. An estimate of tumor growth rate is determined by cell-cycle kinetics, the growth fraction, the cell loss rate (CL), and the potential doubling time (Tpot). Even among tumors of the same histological type, these parameters differ greatly. Cell kinetics cycle of cells and growth fraction in tumors can be monitored ex vivo using various DNA-labeling strategies and in vivo using PET tracers.\n\nKi67 immunohistochemistry staining of tumor biopsies is a method for assessing S-phase cell proportion.\n\nThe potential doubling time (Tpot) refers to the time it would take for volume to double without loss of cells. Consequently, the potential doubling time and the observed volume doubling time are different because tumors show a high amount of cell loss.\n\nTumor cell loss also contributes to VDT and may be attributed to limited nutrition and oxygen supply, metastatic propensity, immune cell killing, and tumor cell exfolia."}
{"_id": "Radiology$$$971435db-2174-4606-be36-8ebad4cc77d6", "text": "Tumor volume doubling time (VDT) is influenced by tumor localization site, primary or metastatic status as well as histology but also by intra-tumor heterogeneity factors."}
{"_id": "Radiology$$$1f92e9af-4c3c-4c1d-b6a4-d82c1a6f52e6", "text": "There are differences in growth rates between different tumor types and metastatic lesions tend to grow faster than primary lesions."}
{"_id": "Radiology$$$00182f21-4c0e-49e4-8d03-6cf0f81af156", "text": "A logarithmic scale can be used to judge treatment effectiveness. An estimate of tumor growth rate is determined by cell-cycle kinetics, the growth fraction, the cell loss rate (CL), and the potential doubling time (Tpot). Even among tumors of the same histological type, these parameters differ greatly. Cell kinetics cycle of cells and growth fraction in tumors can be monitored ex vivo using various DNA-labeling strategies and in vivo using PET tracers."}
{"_id": "Radiology$$$d950c059-f1ee-4bc3-9fcc-9421fc3e18b7", "text": "Ki67 immunohistochemistry staining of tumor biopsies is a method for assessing S-phase cell proportion."}
{"_id": "Radiology$$$7ff30b7b-1322-4008-92ad-1180493ec124", "text": "The potential doubling time (Tpot) refers to the time it would take for volume to double without loss of cells. Consequently, the potential doubling time and the observed volume doubling time are different because tumors show a high amount of cell loss."}
{"_id": "Radiology$$$761ae3ba-f97e-4729-b9ae-8e4deb0a467b", "text": "Tumor cell loss also contributes to VDT and may be attributed to limited nutrition and oxygen supply, metastatic propensity, immune cell killing, and tumor cell exfolia."}
{"_id": "Radiology$$$06bb61ab-5079-45d0-856c-64ca8fed1f65", "text": "The Hallmarks of Radiobiology or 6R\u2019s are six typical molecular, cellular, or tissue processes which determine the effects of radiation on both malignant and healthy tissues.\n\nThe 6R\u2019s are: Radiosensitivity, Repair, Redistribution, Repopulation, Reoxygenation, Reactivation of the immune response."}
{"_id": "Radiology$$$4f7bff3d-7395-48aa-b4c7-fadd68d63d8c", "text": "The Hallmarks of Radiobiology or 6R\u2019s are six typical molecular, cellular, or tissue processes which determine the effects of radiation on both malignant and healthy tissues."}
{"_id": "Radiology$$$82b4ef08-08c7-4d39-a958-38ed15c7f924", "text": "The 6R\u2019s are: Radiosensitivity, Repair, Redistribution, Repopulation, Reoxygenation, Reactivation of the immune response."}
{"_id": "Radiology$$$c7bd97c2-4d4e-4ab4-a103-8675781aa135", "text": "The so-called 6R\u2019s are six biological features which determine the outcome of RT in the clinic: the balance between the complication rate (side effects due to normal tissue injury) and the tumor control rate (palliation or curation due to tumor cell sterilization) (Fig. 5.7). These basic principles or Hallmarks of Radiobiology have been evolved from Withers\u2019 4R\u2019s\u2014\u201cRecovery/repair, Redistribution, Repopulation and Reoxygenation\u201d\u2014[25] via Steels\u2019 5R\u2019s\u2014the addition of \u201cintrinsic cellular Radiosensitivity\u201d [26] to 6R\u2019s by including \u201cReactivation of the immune response\u201d [27] (Box 5.5).\n\nA spoke diagram of the biological effect of ionizing radiation includes repair or recovery, radiosensitivity, reactivation of the immune response, repopulation, redistribution, and reoxygenation.\n\nFig. 5.7\nThe Hallmarks of Radiobiology, the 6R\u2019s"}
{"_id": "Radiology$$$10b07afd-8628-43ac-9f81-850909fe41d7", "text": "A spoke diagram of the biological effect of ionizing radiation includes repair or recovery, radiosensitivity, reactivation of the immune response, repopulation, redistribution, and reoxygenation."}
{"_id": "Radiology$$$490cbf75-941a-4e77-9b78-0150053d3e62", "text": "The six Hallmarks of Radiobiology (Fig. 5.7) in brief:\nRadiosensitivity: Intrinsic and acquired radioresistance of normal tissue cells and tumor cells to radiation, in particular cancer (stem) cells among the heterogenic tumor cell population.\n\nRepair capacity, efficiency, and mechanisms of sublethal DNA damage repair, and related sensitivity to fractionated irradiation\u2014which is high for most healthy tissues and low for most tumors.\n\nRedistribution of cells in the cell-cycle affects their radioresistance. Cells in mitosis are most sensitive to radiation, while cells in the S-phase are radioresistant. Redistribution following irradiation will push radioresistant S-phase cells towards a radiosensitive cell-cycle phase.\n\nRepopulation: Cell repopulation of\u2014not by radiation eradicated cancer cells\u2014involved in the (accelerated) repopulation of the tumor\u2014which is detrimental\u2014and beneficial repopulation of normal tissue cells recovering from acute injury.\n\nReoxygenation: Cells in hypoxic niches within the tumor are radioresistant. Reoxygenation between multiple radiation fractions given in a radiation course is an important phenomenon by which originally hypoxic tumor cells will be reoxygenated and hence radiosensitized.\n\nReactivation of the immune response: Local irradiation induces a systemic immune activation to attack distant tumor cell niches which can be located outside the irradiated volume (abscopal effect)."}
{"_id": "Radiology$$$35075d4d-79f2-4452-9b94-c07431f43d72", "text": "Radiosensitivity: Intrinsic and acquired radioresistance of normal tissue cells and tumor cells to radiation, in particular cancer (stem) cells among the heterogenic tumor cell population."}
{"_id": "Radiology$$$25b2abba-1644-4c8a-8315-5ae852cdc09f", "text": "Repair capacity, efficiency, and mechanisms of sublethal DNA damage repair, and related sensitivity to fractionated irradiation\u2014which is high for most healthy tissues and low for most tumors."}
{"_id": "Radiology$$$e5ffe778-eb7c-41db-85d7-270a1f6302d8", "text": "Redistribution of cells in the cell-cycle affects their radioresistance. Cells in mitosis are most sensitive to radiation, while cells in the S-phase are radioresistant. Redistribution following irradiation will push radioresistant S-phase cells towards a radiosensitive cell-cycle phase."}
{"_id": "Radiology$$$c92e3e1f-f56b-422c-8066-102e31e09d61", "text": "Repopulation: Cell repopulation of\u2014not by radiation eradicated cancer cells\u2014involved in the (accelerated) repopulation of the tumor\u2014which is detrimental\u2014and beneficial repopulation of normal tissue cells recovering from acute injury."}
{"_id": "Radiology$$$17ae975f-1463-4309-9da5-340332c5d3ad", "text": "Reoxygenation: Cells in hypoxic niches within the tumor are radioresistant. Reoxygenation between multiple radiation fractions given in a radiation course is an important phenomenon by which originally hypoxic tumor cells will be reoxygenated and hence radiosensitized."}
{"_id": "Radiology$$$f961cf89-ce4a-4a9f-8732-321b1957be5e", "text": "Reactivation of the immune response: Local irradiation induces a systemic immune activation to attack distant tumor cell niches which can be located outside the irradiated volume (abscopal effect)."}
{"_id": "Radiology$$$27974cd4-99fa-486c-97d4-7dce849e4bc8", "text": "Many authors refer to the radiosensitivity as the degree of tumor and normal tissue regression following irradiation. There are many factors that determine the radiosensitivity which are the proportion of cells with clonogenic capacity, growth rate and reproduction rate, mitosis activity, metabolic rate, tissue type, radiation dose, inherent radiosensitivity, and hypoxia. For example, cells with fast growth or high metabolic rate are highly radiosensitive. Essentially, since the reproductive capacity of cancer cells is higher than the reproductive capacity of late responding normal tissue cells, cancer cells are more sensitive to radiation, but this depends on the cancer tissue type."}
{"_id": "Radiology$$$17a16b32-9cf8-4dba-866e-7cf41173cbcb", "text": "Tumor and normal cells differ in terms of repair after radiation-induced damage. Unlike normal cells, the repair process and mechanism of tumor cells are defective. While normal tissue cells do repair their radiation-induced DNA damage efficiently, malignant cells often cannot."}
{"_id": "Radiology$$$37630a81-b782-4fc7-9e62-a6fd33f577d0", "text": "There are three types of radiation damage to mammalian cells:1.\nPotentially lethal damage (PLD): Cell death depends on the environmental conditions. In a normal situation, damaged cells will not repair and die, but in case of reformed environmental conditions, cells can repair their DNA damage.\n\u00a02.\nSublethal damage (SLD): The death of a cell depends on the sublethal damage condition. DNA damage can be repaired if no extra injury is taking place. The recovery kinetics, the repair time, lies in the range of a few hours following DNA double strand break (DNA DSB) induction.\n\u00a03.\nLethal damage (LD): Irreparable and irreversible damage leading to cell death."}
{"_id": "Radiology$$$2cfb45da-1b38-4c84-91f6-cbf95d0df4a8", "text": "Potentially lethal damage (PLD): Cell death depends on the environmental conditions. In a normal situation, damaged cells will not repair and die, but in case of reformed environmental conditions, cells can repair their DNA damage."}
{"_id": "Radiology$$$4f74be0b-219a-409a-a165-d8604840629f", "text": "Sublethal damage (SLD): The death of a cell depends on the sublethal damage condition. DNA damage can be repaired if no extra injury is taking place. The recovery kinetics, the repair time, lies in the range of a few hours following DNA double strand break (DNA DSB) induction."}
{"_id": "Radiology$$$9097176b-f12b-4526-bb13-11f9d5f8de5d", "text": "Lethal damage (LD): Irreparable and irreversible damage leading to cell death."}
{"_id": "Radiology$$$59cfb736-3a47-4d49-ae45-dcf5a3dbc074", "text": "The main reason for cell death is the production of the asystematic generation of chromosomal aberrations, including rings and di-centric aberrations that result from an interaction between more than one DNA DSB [28]. Details regarding the DNA Damage Response and repair pathways are given in Chap. 3."}
{"_id": "Radiology$$$4e4da958-f785-46e3-83c7-e051be7e0252", "text": "Figure 5.8, panel a shows the distribution of eukaryotic cells over the four cell-cycle phases, which include the G1 phase, S-phase (synthesis phase), G2 phase (interphase phase), and M phase (mitosis and cytokinesis). Cells in the different phases of the cell cycle vary in radiation sensitivity. Cells in the S-phase are resistant to radiation (Fig. 5.8, panel a) while cells in the M and G2 phase are sensitive to radiation [14].\n\nA diagram of radiation fraction leads to cell culture then phases sensitivity of cell cycle to radiation. 4 phases are in a falling trend for surviving fraction versus dose in gray. A cancer cell is surrounded by G 1, G 1 per S checkpoint, S, G 2, G 2 per M checkpoint, M, and M per G 1 checkpoint.\n\nFig. 5.8\nThe cell-cycle phase and radiation sensitivity. Cell survival curves of V79 Chinese hamster cells irradiated at different phases of the cell cycle on the left side"}
{"_id": "Radiology$$$3824113a-d80f-4817-ab2b-b2d63cd6dc57", "text": "A diagram of radiation fraction leads to cell culture then phases sensitivity of cell cycle to radiation. 4 phases are in a falling trend for surviving fraction versus dose in gray. A cancer cell is surrounded by G 1, G 1 per S checkpoint, S, G 2, G 2 per M checkpoint, M, and M per G 1 checkpoint."}
{"_id": "Radiology$$$4c69615f-72c5-49c7-bbc4-f6b61ecd886f", "text": "When cells experience radiation-induced insult, three effects occur:1.\nRecruitment: Stem cells of some tumors are in the G0 phase, which is a radioresistant phase; therefore, they may repair their damage and survive. In order to kill these cells efficiently, these cells are recruited into the cell cycle so as to arrive in a radiosensitive phase.\n\u00a02.\nCells are blocked in the radiosensitive phase (G2). Cells in G2 are highly likely to be sterilized by the first radiation dose.\n\u00a03.\nCells are allowed to re-assort and progress to the radiosensitive phase. Cells in radio-resistant phases survive, yet since they continue to cycle, there is a likelihood that they will arrive at a sensitive phase and be sterilized by a second or later fraction."}
{"_id": "Radiology$$$e2d7725a-4bf2-4585-b978-ed34190a30e5", "text": "Recruitment: Stem cells of some tumors are in the G0 phase, which is a radioresistant phase; therefore, they may repair their damage and survive. In order to kill these cells efficiently, these cells are recruited into the cell cycle so as to arrive in a radiosensitive phase."}
{"_id": "Radiology$$$6afca51d-1266-439a-98b7-4778dddd03f1", "text": "Cells are blocked in the radiosensitive phase (G2). Cells in G2 are highly likely to be sterilized by the first radiation dose."}
{"_id": "Radiology$$$cd2d2458-874e-4816-9a0a-2175948b9c8c", "text": "Cells are allowed to re-assort and progress to the radiosensitive phase. Cells in radio-resistant phases survive, yet since they continue to cycle, there is a likelihood that they will arrive at a sensitive phase and be sterilized by a second or later fraction."}
{"_id": "Radiology$$$6566d86b-5473-47b5-90b4-397b774b120e", "text": "The renewal capability of tissue clonogenic cells that follows the reduction of tissue cells, with clonogenic-forming capacity, is referred to as repopulation (regeneration). Following radiation-induced tissue injury, the tissues will react by repopulation of surviving clonogenic cells, i.e., compensation for the lost cells occurs relatively quickly, with decreasing clonogenic doubling times from 9.8 to 3.4\u00a0days. This will result in a larger number of tumor cells which is detrimental. For normal tissue injury, repopulation from the stem cell compartment will regenerate the damaged tissue, there with reducing early radiation toxicity [16]."}
{"_id": "Radiology$$$7216989c-7093-4b7b-9ef0-24ea95b61d9c", "text": "Biologically, there are three reasons for accelerated repopulation. Firstly, when tissue is exposed to radiation, cell kinetics, which may be reminiscent of a normal epithelium is stimulated; thus, this response causes regenerative reaction of clonogenic cells to initiate repopulation by activating growth factors, such as keratinocyte growth factor (KGF). Secondly, reoxygenation will occur during the course of fractionated RT, facilitating tissue regeneration. Finally, signaling such as that via the epithelial growth factor receptor (EGFR) is activated after irradiation; hence, this signal works as the regulated regenerative response [22]."}
{"_id": "Radiology$$$36dbe367-a87e-40db-9170-5b0b12024214", "text": "The onset of repopulation in many cases is thought to be about 3 weeks after the start of fractionated RT. Its mechanism and kinetics depend on tissue types and might be dose dependent [29] (see also Chap. 6). From the clinical point of view, the total dose should be delivered over a controlled period of time. Any reduction in overall time is limited by the radiation tolerance of acutely responding normal tissues, but an extended overall treatment time might lead to diminished tumor response due to the increase of cells as a result of repopulation."}
{"_id": "Radiology$$$28a4dc32-14d7-4daa-a772-8e0db24dbb09", "text": "The empirical observation that oxygen levels in tumors may be enhanced in the period after irradiation is known as reoxygenation. Reoxygenation of originally hypoxic tumor cells, besides exploiting differences in DNA repair between normal tissue cells and tumor cells, is an important mechanism and reason for fractionated RT. During the fractionation course, lethally damaged cells are removed, and the blood supply increases. Thereby, initially radioresistant hypoxic cells are gradually reoxygenated and become sensitive to radiation (Fig. 5.9).\n\nA diagram of the oxic cell and the hypoxic cell goes through reoxygenation for the overall radiation treatment time in days to weeks.\n\nFig. 5.9\nSimplified illustration of the reoxygenation process. Tumor cell compartments include anoxic, hypoxic, and aerated cells. Most tumors show a heterogeneous pattern of hypoxia with gradients of oxygen pressure decreasing with increasing distance from blood vessels. The oxygen status of the tumor cells is not constant; it is a dynamic, constantly changing phenomenon. Following exposure to irradiation, well-oxygenated cells will be sterilized, but many hypoxic cells will not. During the course of fractionated RT hypoxic cells can be reoxygenated, and therefore become sensitive to radiation and can be sterilized. (Figure was adapted from [13])"}
{"_id": "Radiology$$$ebdc7e56-1399-48e5-aced-9e330c4c0b50", "text": "A diagram of the oxic cell and the hypoxic cell goes through reoxygenation for the overall radiation treatment time in days to weeks."}
{"_id": "Radiology$$$df3a79b5-d7c5-4955-b55b-67b2eb802a0b", "text": "The oxygen enhancement ratio and the role of oxygen in the radiation response has been explained in Chap. 2. If reoxygenation is efficient between dose fractions, the presence of hypoxic cells does not have a significant effect on the outcome of a multi-fractionation scheme. In a hypofractionation regimen, the time period to obtain full reoxygenation of hypoxic tumor cells might however be too short (discussed in Chap. 6)."}
{"_id": "Radiology$$$4a723154-88cd-4c07-8ddb-46569dface69", "text": "When irradiating a tumor, the tumor microenvironment (TME) will also be exposed. Such exposure of the TME might affect the immune system, both locally and systemically. Activation of an anti-tumor response depends on the treatment regimen, i.e., the fractionation schedule, dose, and timing because these factors disturb the balance between immunosuppressive and immune-stimulatory effects. As a result, a specific radiation treatment protocol can induce an anti-tumor immune reaction. When cells of tissues are exposed to radiation, the immune response to attack tumor cells is generated in a few steps (Fig. 5.10).\n\nA flow diagram of radiation induced systematic immune activation features 5 steps from debris of damaged D N A and T A A released by cell lysis to T A A released from damaged tumor cells cause further amplification of immune signals.\n\nFig. 5.10\nIllustration of the steps of radiation-induced systemic immune activation contributing to attack on distant/metastatic tumor cells"}
{"_id": "Radiology$$$3f51e4bd-acbf-4599-bca2-fd16d5d638f9", "text": "A flow diagram of radiation induced systematic immune activation features 5 steps from debris of damaged D N A and T A A released by cell lysis to T A A released from damaged tumor cells cause further amplification of immune signals."}
{"_id": "Radiology$$$78a71e9f-a604-4184-9692-169113b9299d", "text": "Different radiation treatment schemes with respect to the total dose and fraction size have been shown to have diverse effects on the immune response, and therewith also on target expression with consequences for combination treatments like with immunotherapy. To obtain optimal modulation of the radiation response, specific immunomodulating or targeted drugs can be selected. The radiation-induced TME effects modulating the immune response requires further research to find the ideal immunotherapy and RT regimen [30]."}
{"_id": "Radiology$$$f8b549d4-d1c5-4661-8450-da70a0a357ee", "text": "The 6R\u2019s offer options for modulation of the radiation response. Modulation strategies, such as via combination therapy with immunomodulating agents, should be aimed to widen the therapeutic window (Sect. 5.12) using approaches such as via radioprotection of the normal tissues thus decreasing the NTCP or by tumor radiosensitization by increasing TCP. Options for clinical application of such strategies are highly dependent on the tumor and normal tissue type included in the radiation treatment volume. Finally, to be noted is the close link between the Hallmarks of Radiobiology and the Hallmarks of Cancer [31] and therewith related therapeutic options, which have been discussed in detail elsewhere [32, 33]."}
{"_id": "Radiology$$$4ff358b2-783f-4ee1-87d8-4e3e3c39c746", "text": "Clinically used fractionation schemes are aimed at eradicating malignant tissue while sparing late responding healthy tissue.\n\nThe biological rationale of fractionated irradiation is based on the typical radiation response of the dynamic and heterogeneous exposed tissue and cell population.\n\nDose rates used in clinical RT vary from low dose rate with exposure times in hours-days to ultra-high dose rates with radiation dose delivery in the millisecond range.\n\nThe biological effect of radiation decreases with decreasing dose rate to a larger extent for normal tissue with low \u03b1/\u03b2 ratio than for tumors with high \u03b1/\u03b2 ratio.\n\nExperimental data demonstrate that ultra-high dose rate irradiation might better spare late responding normal tissue.\n\nThe 6R\u2019s of radiobiology are the biological processes involved in the dose rate effect."}
{"_id": "Radiology$$$fbe99fff-5f92-4185-bb13-cf7214fa4944", "text": "Clinically used fractionation schemes are aimed at eradicating malignant tissue while sparing late responding healthy tissue."}
{"_id": "Radiology$$$c3295d0b-8175-45ee-afa1-88f5b4f77eef", "text": "The biological rationale of fractionated irradiation is based on the typical radiation response of the dynamic and heterogeneous exposed tissue and cell population."}
{"_id": "Radiology$$$0ae3f87a-0d34-4ca1-89d4-3d6bf3875fa4", "text": "Dose rates used in clinical RT vary from low dose rate with exposure times in hours-days to ultra-high dose rates with radiation dose delivery in the millisecond range."}
{"_id": "Radiology$$$504e35c5-00a2-4392-bfcb-4565455f11d0", "text": "The biological effect of radiation decreases with decreasing dose rate to a larger extent for normal tissue with low \u03b1/\u03b2 ratio than for tumors with high \u03b1/\u03b2 ratio."}
{"_id": "Radiology$$$8ea8e0aa-289d-4316-ab60-e0d902433cc4", "text": "Experimental data demonstrate that ultra-high dose rate irradiation might better spare late responding normal tissue."}
{"_id": "Radiology$$$358b4a90-6821-441c-b0dd-f96a564ce9b4", "text": "The 6R\u2019s of radiobiology are the biological processes involved in the dose rate effect."}
{"_id": "Radiology$$$9d6b12ad-ca5a-4460-85b7-df55de5b5509", "text": "In the early years of RT, radiation oncologists soon realized that a radiation treatment course delivered in multiple fractions over several weeks resulted in better tumor control than a treatment course delivered in a single fraction and also reduced normal tissue toxicity [21]. The history of RT and fractionation is described in detail in Chap. 2. Generally spoken, a treatment course consisting of 30 daily 2 Gy fractions (total dose 60\u00a0Gy) is, at isoeffective normal tissue late response level, more effective in eradication of the tumor than a treatment course consisting of a few high dose fractions. Hence, if the total prescribed dose is divided into multiple small radiation fractions with a time interval between the fractions, tumor control could be enhanced at an acceptable level of associated morbidity, relative to a single large dose fraction [13]. However, modern RT techniques allow to give higher dose per fraction while sparing more efficiently the surrounding normal tissue. This may affect this fractionation concept further in future."}
{"_id": "Radiology$$$92e8f530-48e6-487b-a6c8-ae24701bf098", "text": "The irradiated cell population comprises the malignant tissue as well as acute and late responding healthy (\u201cnormal\u201d) tissues. When an RT dose is delivered in several fractions, there are advantages and disadvantages in terms of tumor cell kill and normal tissue cell sparing, which are discussed in detail in Sect. 5.14."}
{"_id": "Radiology$$$2545fffa-30f6-4b21-a8e1-6dd13d5fabba", "text": "Acute normal tissue effects of RT depend on both fraction size and the overall treatment time. The intensity of acute reactions depends on weekly applied total dose, i.e., the dose per fraction and number of fractions in a week. After an acute reaction has peaked, further stem cell killing cannot increase the intensity of acute reactions but can prolong the healing time. A persistent early response from severe depletion of regenerating cells is termed a consequential late injury [13]. In contrast, non-consequential late normal tissue effects depend predominantly on fraction size, while the overall treatment time has little influence. Therefore, during hypofractionation, late effects are severe while early effects are matched by appropriate dose adjustment, as discussed in detail in Chap. 6 (Sects. 6.\u200b2 and 6.\u200b3)."}
{"_id": "Radiology$$$0700a82d-33f8-4a14-8b3b-3114dbb24858", "text": "Another important parameter is the inter-fraction interval. Due to the slow repair kinetics of sublethal damage (SLD) in late responding tissues, a minimum of 8 h of inter-fraction interval is recommended for most tissues. The overall treatment time affects both acute effects and tumor control. Prolongation of the overall treatment time (within normal RT range) has a large sparing effect on early responding normal tissues but little sparing effect on late responding normal tissues. However, excessive prolongation of overall treatment time causes the surviving tumor cells to proliferate during treatment. For any prolongation in treatment time, extra dose is required to counteract tumor cell proliferation, due to the phenomenon of accelerated repopulation. For example, in head and neck cancer, after a lag period of 4 weeks during a course of RT, the tumor doubling rate could increase due to triggering of surviving clonogens to divide more rapidly as tumor shrinks after initiation of treatment. A dose of up to 0.6 Gy of each daily dose would be \u201cwasted\u201d due to increased tumor cell load [34]. When the overall treatment time is prolonged, for each extra day, local control would decrease by 1.4% (0.4\u20132.5%) due to accelerated repopulation."}
{"_id": "Radiology$$$42b925cf-88b6-4173-b204-9f8828b4cfde", "text": "Differential responses of normal and cancerous tissues when fractionating RT doses can be explained by biological factors that are known as the 6R\u2019s (see Sect. 5.4). During fractionation, tumor cells are redistributed and reoxygenated, causing further tumor damage. Moreover, the fractionation process will spare normal tissues by allowing repair of SLD between dose fractions and by allowing repopulation with new cells to occur over the overall treatment time. Therefore, a prolonged radiation treatment given over several weeks results in a greater therapeutic ratio than one or few short duration sessions because of tumor reoxygenation and early reacting normal tissue regeneration."}
{"_id": "Radiology$$$ac6a7e3d-5be9-4dae-8128-4a547d0e21fd", "text": "Radiation fractionation can lead to biologically optimal RT when the equi-effective total dose is related to the dose per fraction for tumors, early responding tissue, and late responding tissue. This relationship is determined by dose per fraction number, fraction number, tumor type, treatment site, and treatment plan. Using different normal tissues as models, it was found that with decreasing dose per fraction, the isoeffective total dose increases more rapidly than for acute effects or tumor response. This relationship can be described by the linear-quadratic (LQ) model. According to the LQ model, with appropriately chosen \u03b1/\u03b2 values to represent isoeffect dose relationships at least at the 1\u20136 Gy dose range, a standard fractionation scheme with five small sized fractions per week over a few weeks would be beneficial regarding the tumor cure-normal tissue complication balance. Hence, deviation from standard fractionation affects the Biological Effective Dose (BED), which includes schedules with different fraction size and inter-fraction time as well as overall treatment duration. The BED is the total dose required to produce a particular effect in small dose fractions, used as the quantity to compare different fractionation regimens, see Table 5.3 for models that are used to deal with a deviation from standard fractionation.Table 5.3\nModels of biological effective dose (BED) for isoeffect calculations for modified fractionation regiment (adopted from [16])\n\nModel\n\nFormula\n\nStatement\n\nEquivalence dose 2 Gy (EQD2)\n\n\n\n\nD is total dose and d is dose per fraction.\n\n\u2022 EQD2 is the 2 Gy dose that carries the same biological effect as a total dose D with a fraction size d Gy.\n\u2022 The purpose of this model is to compare the effectiveness of schedules containing doses per fraction and different total doses. This is equivalent to converting each schedule into a 2-Gy fraction that has the identical biological effect.\n\nTotal effect (TE)\n\nE/\u03b2\u00a0=\u00a0D[(\u03b1/\u03b2)\u00a0+\u00a0d]\u00a0=\u00a0TE\nE\u00a0=\u00a0isoeffect\n\n\u2022 It is used for schedules with different doses per fraction.\n\u2022 TE and BED are conceptually similar and have been cited in literature, but E is divided by \u03b2 instead of \u03b1.\n\nExtrapolated tolerance dose (ETD)\n\n(\n\n)\u00a0=\u00a0D((1\u00a0+\u00a0d(\u03b1/\u03b2))\u00a0=\u00a0BED\n\n\u2022 The ETD refers to levels of effectiveness that imply full tolerance. It is used for schedules with different doses per fraction.\n\nBasic EQD2 formula with incomplete repair factors (Hm).\n\n\n\n\n\n\u2022 Used for tolerance calculations, taking into account the increase in the overall damage caused by interaction of subsequent fractions.\n\nBasic EQD2 formula with Incomplete repair factors (g factors).\n\n\n\n\n\n\u2022 Used for low dose rate exposures."}
{"_id": "Radiology$$$821de7a7-d7f5-409c-a749-0e11d3297c42", "text": "The dose rate is defined as the ratio of the radiation dose to the duration of the radiation exposure. The term should be used only in the context of short periods of time, for example, dose per second or dose per hour, the SI dose rate unit is Gy/h. Acute exposure refers to a high radiation dose delivered in seconds or minutes, and chronic exposure means that the radiation dose is delivered over a longer period of continuous exposure over hours to days to even months and years. The spectrum of dose rates used in radiation oncology is presented in Table 5.4.Table 5.4\nDose delivery conditions used in the clinic, for internal radiation therapy (brachytherapy) and external beam irradiation, and related dose rates (ICRU 38 definitions and FLASH)\n\nDose delivery condition\n\nDose rate (Gy/h)a\n\nLow dose rate (LDR)\n\n<2\n\nMedium dose rate (MDR)\n\n2\u201312\n\nHigh dose rate (HDR)\n\n>12\n\nPulsed dose rate (PDR)\n\n\u00b175% HDR, \u00b125% MDR and LDR\n\nUltra-high dose rate (FLASH)\n\n\u2265144.000\n\naThe International System of Units (SI) defined dimension for the dose rate is \u201cGy/h\u201d"}
{"_id": "Radiology$$$575224d1-b208-46a1-a8f5-2919279fb6ec", "text": "Physical aspects of the dose rate are presented in Chap. 2. The application of low dose rate irradiation in brachytherapy in the clinic, is discussed in Chap. 6. FLASH is a novel RT treatment technique using ultra-high dose rates. Using FLASH, multiple studies indicate sparing of healthy tissue acute and late toxicities while maintaining tumor control, hence widening the therapeutic window (Sect. 5.2). FLASH is discussed in detail in Chap. 6. The radiation dose rate has a large biological impact on exposed cells and tissues. Both in vitro and in vivo experimental data revealed that, for a defined biological endpoint, for example, cell survival or a certain late normal tissue reaction like myelitis of the spinal cord, the biological effect decreases with decreasing dose rate. With decreasing dose rate, the total dose to obtain a certain isoeffective biological endpoint\u2014for example, a probability of 50% loss of kidney function or reduction of the cell survival with a fraction of 0.4, is increased. Dose rate sparing is almost absent for acute responding normal tissues and tumors."}
{"_id": "Radiology$$$c004dfb7-53fe-47c8-9344-a69dd2fa86e2", "text": "In terms of fractionation, the decrease in dose rate can be considered as lowering the fraction size of the total radiation dose to be delivered in external beam HDR radiotherapy (Fig. 5.11). Referring to the LQ model (Sect. 5.5) for comparison of biological effectiveness of different radiation treatment schemes, low dose rate irradiation could be considered as super-fractionation (Fig. 5.11 and Box 5.7).\n\nA line graph represents cell survival in Log 10 versus the total dose in gray. The plotted data, the dotted curve for continuous L D R, the solid curve for fractionated H D R, fraction number, and dose rate, gray per hour feature a downward trend.\n\nFig. 5.11\nThe dose rate effect seen as an extreme form of fractionation. Cell survival following fractionated HDR irradiation with increasing number of fractions (solid curves). With an infinite number of tiny fractions, and complete sublethal damage repair, the dose-squared \u03b2 parameter of the LQ tends to zero, and only the dose-linear \u03b2 parameter plays a role. Then, the Biologically Effective Dose (BED) is reached for a certain endpoint effect E. Similar sparing phenomenon with decreasing dose rate in continuous LDR exposure (dotted curves)"}
{"_id": "Radiology$$$67aa31c7-6cab-422e-ad46-51181d21a13b", "text": "A line graph represents cell survival in Log 10 versus the total dose in gray. The plotted data, the dotted curve for continuous L D R, the solid curve for fractionated H D R, fraction number, and dose rate, gray per hour feature a downward trend."}
{"_id": "Radiology$$$6a5a9a1e-6568-48b5-94ff-24a95f146ee1", "text": "At extremely low dose rate, i.e., irradiation with an infinitely large number of infinitesimally small dose fractions, the theoretical total dose required to produce an isoeffect is the Biological Effective Dose (BED) of the LQ model."}
{"_id": "Radiology$$$5cc448da-8f8c-4e45-85eb-82c50f669ff9", "text": "Thus, as exposure is elongated, the shoulder of the cell survival curve tends to become shallower, this is because the \u03b1 parameter of the linear-quadratic model does not change significantly, while the \u03b2 parameter tends towards 0."}
{"_id": "Radiology$$$a1fa9b41-2caf-42fb-950d-d0b39405f5b2", "text": "This situation also implies, dependent on the fractionation sensitivities of irradiated tumor and normal tissues involved (i.e., their repair capacity characteristics expressed in their \u03b1/\u03b2 values) as well as of their DNA repair kinetics (the half time for sublethal damage repair T1/2), an optimal therapeutic ratio situation. For the LQ model adaptation to correct for the dose rate effect and incomplete repair, additional parameters are introduced (e.g., Joiner and van der Kogel [16]). The dose rate effect of continuous low dose irradiation is discussed in view of the 6R\u2019s of radiobiology in Sect. 5.4 below."}
{"_id": "Radiology$$$4d19f9d1-daf6-4931-ac2c-50d533e7ecef", "text": "The repair process of radiation-induced DNA lesions has been explained in depth in Chap. 3. DNA DSB, if not repaired, are lethal to the cell. A DNA DSB can either be induced by single-track action or double-track action. A single-track X-ray lesion is independent of dose rate and linearly proportional to dose (the contribution of \u03b1 in the LQ model). In double-track action, the two interactive single strand DNA lesions are produced by different tracks of X-ray photons, and the formation of double strand lesions is therefore dependent on the dose rate and is proportional to the radiation dose squared (the contribution of \u03b2 in the LQ model). In fact, the protracted delivery of a given radiation dose reduces the effect of double-track action because time offered between lesions is long enough for repair to occur [28] (Fig. 5.12).\n\nAn illustration displays the X-ray penetrates the cancerous cell and goes through a single track action and double track action. A line graph below represents proportion of full effect versus dose per fraction. The linear and nonlinear are in a downward trend.\n\nFig. 5.12\nIllustration single-track action and double-track action. In single-track action, the two interactive lesions are produced by a single track of ionization induced by an X-ray photon that subsequently produces a dose which is independent of dose rate and linearly proportional to dose. In double-track action, the two interactive lesions are produced by a different track of ionization induced by X-rays which subsequently produces a dose which is dependent on the dose rate (decreasing the dose rate reduces double-track action) and non-linearly proportional to the radiation dose squared"}
{"_id": "Radiology$$$3aef6e83-037c-44f6-a64e-41537b522ff7", "text": "An illustration displays the X-ray penetrates the cancerous cell and goes through a single track action and double track action. A line graph below represents proportion of full effect versus dose per fraction. The linear and nonlinear are in a downward trend."}
{"_id": "Radiology$$$a88a648f-4ed5-4b79-be87-4e951a9bb0f0", "text": "Figure 5.13 shows that lowering the dose rate has greater effect on cells or a tissue with a low \u03b1/\u03b2 ratio, for example, 3 Gy than with a high \u03b1/\u03b2 ratio of, for example, 10 Gy. At a low \u03b1/\u03b2 ratio, the curves are spread out more, implying that late responding normal tissues are particularly spared relative to tumors when decreasing the dose rate.\n\nTwo line graphs represent effect versus dose in gray. The plotted data in each graph features a decreasing dose rate.\n\nFig. 5.13\nThe effect of lowering the dose rate on the survival of cells. (a) Cells characterized with an \u03b1/\u03b2 ratio of 10 Gy (typical for a tumor or early responding normal tissue). (b) Cells with an \u03b1/\u03b2 ratio of 3 Gy (typical for a late responding normal tissue). See text for details. (Figure from Shrieve and Loeffler [17], with copyright permission from Wolters Kluwer Health, Inc.)"}
{"_id": "Radiology$$$4608de74-12b0-4593-a223-ccaf1af57370", "text": "Two line graphs represent effect versus dose in gray. The plotted data in each graph features a decreasing dose rate."}
{"_id": "Radiology$$$4f20a925-c4c2-4789-bb4a-9e946b22f1bb", "text": "Also, for a tissue having an equivalent \u03b1/\u03b2 ratio, larger sparing is obtained with decreasing tissue-specific half time (T1/2) for sublethal damage repair. Similarly, as with fractionated radiation, this can be attributed to incomplete repair between the \u201cfractions\u201d or during continuous exposure. Hence, at longer repair half time, low dose rate irradiation is causing more damage, and less discriminative between tissues with different \u03b1/\u03b2 ratio."}
{"_id": "Radiology$$$6c3df467-63fe-48ce-8933-924c0f7c8056", "text": "It is well recognized that cells in the G2 or M phase of the cell cycle are more sensitive to radiation than cells in the G1, G0, or S cell-cycle phases (Sect. 5.4, Fig. 5.8). During continuous low dose rate irradiation, the process of redistribution would push initially relative radioresistant cells into a radiosensitive cell-cycle phase. This process is dependent on numerous cellular and tissue factors, and therefore difficult to predict."}
{"_id": "Radiology$$$07e8dc84-bda4-41e3-8933-d87282c471db", "text": "Another phenomenon that might occur is the inverse dose rate effect, which represents a reversal of the typical pattern of the conventional sparing with decreasing dose rate. For the same radiation dose, radiation delivered at a certain specific lower dose rate increases the radiosensitivity of cells in comparison to radiation delivered at a higher dose rate. This is illustrated in Fig. 5.14.\n\nA diagram displays the G 2 block to G 1 where G 1 leads to G 2 cells and then to the tumor, where it progresses to colon cancer, and then goes through the continuous low dose rate exposure of the tumor value.\n\nFig. 5.14\nThe inverse dose rate effect. When the dose rate delivered to HeLa cells is decreased from 1.54 to 0.37\u00a0Gy/h, the efficiency of cell killing increases, with damage generated similar to that from an acute exposure [35]. When cells are exposed to higher dose rates, they are kept in the phase of the cycle in which they are at the beginning of irradiation. However, use of lower dose rates may allow cells to continue cycling during irradiation. When cells are exposed to 0.37\u00a0Gy/h, cells tend to progress from other phases of the cell cycle and arrest in G2, which is a radiosensitive phase of the cycle. As a result, an enriched population of G2 cells is responsible for increasing the radiosensitivity of cells"}
{"_id": "Radiology$$$046bd105-f915-4c35-b3f9-147c295c46d3", "text": "A diagram displays the G 2 block to G 1 where G 1 leads to G 2 cells and then to the tumor, where it progresses to colon cancer, and then goes through the continuous low dose rate exposure of the tumor value."}
{"_id": "Radiology$$$37c0d358-92ce-4111-92e7-a187cbaeca43", "text": "Tumor cell repopulation during continuous low dose rate (LDR) exposure might negatively influence treatment outcome since a larger number of cells have to be sterilized if the repopulation rate outflows the duration of exposure, which might occur with fast repopulating tumor cells (e.g., cell doubling time of 24\u00a0h)."}
{"_id": "Radiology$$$1646d1b1-b281-443a-a970-a9e6076e67de", "text": "The impact of irradiation on the immune response has been shown to be dependent on the radiation dose (see Chap. 6), and the dose rate of exposure is likely to play a role [36]. The effect of low dose rate irradiation regarding reactivation of the immune response is however not well described."}
{"_id": "Radiology$$$090bc173-2d60-4317-9d4a-42136bc0993d", "text": "Chronic low dose rate exposure will not cause oxygen depletion in initially well-oxygenated tumor cells. Initially, hypoxic cells might benefit from reoxygenation during long-term radiation exposure. However, as pointed out in Sect. 5.4, the kinetics of reoxygenation is very much dependent on the tumor type."}
{"_id": "Radiology$$$e4dbbd2c-bd95-4e4b-b612-ea02c2479c7a", "text": "Whole-body irradiation (WBI) or total body irradiation (TBI) refers to the therapeutic protocol in which a patient\u2019s total body is irradiated with \u03b3/X-rays. WBI is used as part of the conditioning regimen for transplantation of bone marrow or hematopoietic stem cells for lymphoma, leukemia, or multiple myeloma and as a palliative regimen in selected cases of lymphoma and leukemia [37]. WBI implicates irradiation of the total body, with reduction of the dose to the lungs, to lessen the hazard of radiation-induced lung toxicity [38, 39]. Historically, in the fifth and sixth decade of the last century scientists trying to reverse early responding tissue effects of radiation, demonstrated experimentally that bone marrow engrafted with hematopoietic stem cells from a donor animal \u201ccould recapitulate the blood system\u201d and thus showed that previously irradiated bone marrow could be rescued. This contributed to the development of therapeutic techniques involving bone marrow ablation followed by bone marrow engraftment with hematopoietic stem cells for the treatment of some marrow cancers, for example, leukemia or multiple myeloma [37]. This procedure is mainly used to eliminate residual cancer cells in the transplant recipient, and to further suppress or destroy the immune system; subsequently, it serves to prevent immunologic rejection of blood stem cells or transplanted donor bone marrow. Thus, the chances of engraftment are increased, and the bone marrow stromal cells of the patient are spared [38, 39]."}
{"_id": "Radiology$$$1804f656-2334-4116-b516-00959d082c7a", "text": "Since a characteristic of WBI is that it can sterilize small numbers of widely spread cells that are sensitive to radiation, this makes it a treatment option for (residual) marrow disease. Biologically, leukemia is associated with a spectrum of intrinsic cellular radiosensitivity that ranges from notable radiosensitivity to significant radioresistance, which determine the extent of leukemic cell killing. The molecular biology responsible for the variety in radiosensitivity of leukemia is not entirely known, but increased apoptosis seems to require functional p53, c-myc, and Bcl2 genes. Therefore, it seems that radiosensitivity results from the apoptosis retention after activating p53, c-myc, and Bcl2 genes by radiation [40]. RT in conjunction with a wide range of treatment modalities such as (myeloablative) chemotherapy and the subsequent graft-versus-tumor effect are therefore required to obtain significant eradication of malignant clones [22, Chap. 16]."}
{"_id": "Radiology$$$8bc44aa7-6965-4e48-9634-7c0e9f807c2d", "text": "Bone marrow stem cells typically have D0 values ranging from 0.5 to 1.4 Gy. These cells are therefore intrinsically radiosensitive. Even though hematopoietic rescue (i.e., stem cells) could allow the delivery of high doses that eliminate the recipient\u2019s marrow cells which in turn prepares the stem cell microenvironment for repopulation to occur, this procedure is associated with long-term or life-threatening consequences. Critical organs of concern in WBI are those described as late responding tissues. Fortunately, as effect on these tissues is dependent on total dose, dose rate and fractionation, appropriate scheduling of the treatment allows some protection. While a modest number of cancer cells being radiosensitive will be killed, complete cancer cell killing may not always be possible with radiation alone. Therefore, TBI often needs to be given together with chemotherapy. Moreover, incomplete bone marrow ablation may result in mixed chimerism of bone marrow after transplant [22, 40]."}
{"_id": "Radiology$$$f1af6238-525a-48d6-93ed-47ee3f61140a", "text": "As a result of immunological mismatch between recipient and donor, rejection of donor stem cells may occur. In order to avoid this, TBI is used to prevent the recipient from rejecting donor stem cells."}
{"_id": "Radiology$$$312cb915-890a-4973-ab4a-a1fafaef8198", "text": "Bone marrow transplantation results are influenced by the treatment schedule. Lymphoid cells repair a large amount of radiation-induced DNA damage during the time interval between fractions. Hence, the effectiveness of fractionated TBI is reduced significantly in comparison with single-dose TBI and results in more graft rejections. However, the fractionation effect is reversed for bone marrow stromal cells (\u201ccolony-forming unit fibroblasts\u201d). The success of engraftment is based on the likelihood of sparing bone marrow stromal cells, and when treatment is delivered as single-dose TBI, the likelihood of damaging both bone marrow stromal cells and their progenitors increases. Importantly, the effectiveness of single-dose TBI is increased significantly in comparison with fractionated TBI, but at the cost of increased long-term toxicity [22]."}
{"_id": "Radiology$$$d915e52c-2227-449f-a9c5-1ee6b6ff03bd", "text": "Unlike curative RT, palliative RT is used to control the symptoms of advanced, incurable cancer (the primary tumor or metastatic deposits) by slowing down tumor growth, controlling symptoms and causing cancer to regress [41]. WBI may be effective for palliation, especially for advanced leukemia or lymphoma, using rather low doses in the order of 0.1\u00a0Gy/fraction. In experiments with solid tumors, tumor cells with colony-forming abilities in both experiments of formation of artificial metastases and naturally developing metastases, these tumors could be suppressed with specific low doses [42]. It is assumed that either chronic TBI or low dose total body irradiation may stimulate the immune system to eliminate metastatic cancer cells. However, nowadays, TBI is only very rarely used for this indication. For further information, see tumor microenvironment changes and abscopal effect discussed in Sect. 5.15."}
{"_id": "Radiology$$$2f367ee7-49c5-4b00-86a7-62b1e1e30906", "text": "In WBI, the doses delivered for transplantation of bone marrow or stem cells are in the range of 10\u201312 Gy [43]. To reduce long-term complications in the recipient, this dose is typically divided into 2 Gy fractions [14, 44]. In the so-called reduced conditioning regimens, single fractions of 2 Gy or two fractions of 2 Gy are given. When WBI is split into multiple small fractions and spread over a period of time, outcomes are generally improved, and toxicity is diminished. While the former is due to the fact that the dose is still adequate to eradicate both any cells of residual malignant tissue and the recipient\u2019s bone marrow, the latter is explained in Sect. 5.2 [45]."}
{"_id": "Radiology$$$c16461a6-5dbe-4906-b9cd-ff8a351b1820", "text": "The dose rate in RT influences the effectiveness of the radiation exposure. An explanation of how a survival curve may become shallower at low dose rates was discussed in Sect. 5.5. In WBI, the pattern is different from localized RT because the effect of radiation dose depends on the tissue type. When low dose rate is used, the incidence of normal tissue toxicity is decreased in comparison with high dose rates [46\u201348]. However, changing the radiation dose rate from the low dose rate to high does not affect the probability of engraftment success [49, 50]."}
{"_id": "Radiology$$$3b890620-5277-4558-a35d-b2a9eacdd009", "text": "Functional parameters including reoxygenation, redistribution, repopulation, repair, and radiosensitivity are traditionally used to define radio-responsiveness.\n\nThe role of repopulation also proved to be a robust predictive marker as illustrated in head and neck cancer where increased tumor expression of EGFR indicates efficacy of accelerated radiation.\n\nDNA, RNA, and proteins have recently been identified to define tumor RT responsiveness yet few of them have attained clinical validation and/or application."}
{"_id": "Radiology$$$5f5db974-96cb-4d2d-bd17-e8eef9f05ced", "text": "Functional parameters including reoxygenation, redistribution, repopulation, repair, and radiosensitivity are traditionally used to define radio-responsiveness."}
{"_id": "Radiology$$$72578f8e-535e-4746-b95e-27e945566a15", "text": "The role of repopulation also proved to be a robust predictive marker as illustrated in head and neck cancer where increased tumor expression of EGFR indicates efficacy of accelerated radiation."}
{"_id": "Radiology$$$92f350c7-4a0e-4192-96b9-045202763be9", "text": "DNA, RNA, and proteins have recently been identified to define tumor RT responsiveness yet few of them have attained clinical validation and/or application."}
{"_id": "Radiology$$$7c6e363b-c0f0-44da-aed0-bb5d51731af9", "text": "Radiation treatment has been improved greatly over the last two decades by integrating 3-D anatomy into planning systems, and developing of image-guided (IGRT), intensity-modulated (IMRT) and intensity modulated arc radiation therapy (IMAT) techniques, resulting in individualization of treatment. Radiation treatment portals and arcs are much more tailored to the anatomy of each patient\u2019s tumor and normal tissue. Today medical professionals prescribe RT taking into account the type of primary tumor, its grade, stage, location, size, biological characteristics, and concomitant treatments. However, these clinical parameters do not give an accurate prediction of the effect of RT since wide variations in response occur between patients given the same treatment and having similar tumors [51\u201353]. Furthermore, diverse treatment options are now available. Moreover, several tumor RT sensitizing strategies using different drugs which can enhance the effects of RT, especially those that target the molecular pathways, are becoming available now. Treatments frequently employ combined approaches. One such avenue currently underway involves trials that combine chemotherapy/RT with immunotherapy."}
{"_id": "Radiology$$$2b412c0b-f7e1-4288-8a7f-23b943a29c08", "text": "RT can differentially affect tumor responses due to a variety of radiobiological factors, which are referred to as the 6R\u2019s. Among them, hypoxia, proliferation, and radiosensitivity have proved to be fairly good predictive markers [51\u201334]. Beyond these well-known classical biomarkers (BMs), there are also a number of promising candidate molecular biomarkers currently being tested in preclinical and clinical studies such as genetic and epigenetic factors as discussed in Sect. 5.10. In this section, classical and modern BMs as well as their role in predictive assays will be discussed in addition to the available methods used to detect them."}
{"_id": "Radiology$$$d2d1d94a-7302-4fe4-8440-c96023837466", "text": "RT constitutes approximately 60% of cancer treatment. If a clinical assay could successfully predict the RT response, it would have wide-ranging clinical implications. A broad group of old-fashioned radiobiological variables that affect RT outcome including tumor oxygen status, the degree of repopulation or proliferation rate, intrinsic radiosensitivity, and both individual and tumor radiosensitivity is shown in Fig. 5.15.\n\nA spoke diagram of radiotherapy outcome includes hypoxia, redistribution, and repopulation.\n\nFig. 5.15\nReview of classical biomarkers used to obtain information on relevant features of radiobiology"}
{"_id": "Radiology$$$3eb995b2-7d21-4eac-ba7d-58a974735902", "text": "A spoke diagram of radiotherapy outcome includes hypoxia, redistribution, and repopulation."}
{"_id": "Radiology$$$bc7f9177-ffa5-474b-9647-1ea1176e65fd", "text": "Predictive factors in therapy may relate more directly to primary tumors and their local control. Metastatic disease may need to be considered separately even though it clearly plays a significant role in survival of the patient. Research to develop predictive assays for tumor RT response should generally measure local control and normal tissue effects [16, 51, 52]."}
{"_id": "Radiology$$$0eb7c3d7-d18b-49d6-a120-1700ebb0b0dc", "text": "Tumor vascular beds differ significantly from those in normal tissues in their structure and physiological characteristics. Tumor-related blood vessels are composed of single-layered endothelium, commonly containing gaps between the endothelium taken up by tumor cells, resulting in immature capillaries. A dysfunctional blood supply through the tumor reduces oxygen delivery, resulting in areas of tumor hypoxia, acidic intra-TME nutritional deprivation, and therewith the tumor response to IR For more information about predictive tests to assess Oxygen Effect to Tumor Hypoxia see Sect. 5.8."}
{"_id": "Radiology$$$7db4010d-42da-41a3-9576-a7d0a87899a2", "text": "Tumor repopulation is a key factor contributing to treatment failure after RT. Alternative fractionation schemes have been proposed as methods for modulating interfraction tumor repopulation. A phase III randomized trial in over 1000 patients with head and neck cancer showed significant improvement in regional control following accelerated and hyperfractionated RT as compared to conventional fractionated RT. Additional evidence, which has shown the importance of proliferation, demonstrated that higher doses are needed to control a tumor when overall time of treatment is prolonged. Clinical evidence that tumor repopulation is an important mechanism for treatment failure is notably apparent in a subset of patients. Therefore, evaluation of tumor repopulation has been a priority for developing predictive tests [52]. Table 5.5 shows several tests that can be performed in vitro and in vivo to measure tumor repopulation.Table 5.5\nDescription of biomarkers and laboratory assays for assessing repopulation\n\nTest\n\nProcedure\n\nMethod\n\nStatements\n\nThe mitotic index\n\nUsing tissue sections to calculate mitosis ratios\n\nBiopsy staining\n\nA correlation exists between outcome results and the labeling index, but it is weak\n\nDNA flow cytometry\n\nCalculating the percentage of cells that are in the S phase of the cell cycle\n\nFlow cytometry\n\u00a0\nThe tumor potential doubling time, Tpot\n\nUsing bromodeoxyuridine as a stain in a tumor biopsy\n\nFlow cytometry\n\nTpot is not a significant predictor for RT response\n\nEndogenous markers (Ki67)\n\nProliferation-associated proteins can be detected using antibodies\n\nGene signature, biopsy studies, or plasma/serum\n\u00a0\nMolecular marker profiles (p-53, Bcl-2, Ki-67, or EGFR expression)\n\nMeasuring the level of these markers\n\u00a0\nContinuous hyperfractionated accelerated radiotherapy (CHART) is recommended in head and neck cancer patients who have high expression of EGFR in tumor or low organized patterns of Ki-67 and is negative for Bcl-2 or p53 expression"}
{"_id": "Radiology$$$28493702-6d24-4fa6-aa6f-4e9ec53f316a", "text": "Various types of cell death, such as apoptosis and autophagy, which also result in a loss of colony-forming ability, contribute to tissue reactions caused by IR. Many publications proposed that cellular radiosensitivity could be measured by the clonogenic assay. A technical challenge of dispersing tumor cells ex vivo has interfered with its clinical application, however [52]."}
{"_id": "Radiology$$$4ddfefba-effd-4e7a-96c8-23c32fa84320", "text": "For more information about predictive tests to assess radiosensitivity, see Chap. 7."}
{"_id": "Radiology$$$83825a97-ea34-4e0a-9832-bbf50b821483", "text": "Radiation responsiveness was traditionally defined using the 6R\u2019s (see Sect. 5.4) but only three factors proved reliable as prognostic markers: hypoxia, repopulation, and radiosensitivity, and hence RT regimens have been modified according to fraction size, dose per fraction, and overall treatment time as depicted in Fig. 5.16. Individual assessments of these parameters could have predictive value since each of these parameters has a substantial effect on the outcome of the RT. Assays based on measurements of these parameters, however, had mixed success in developing predictive assays for many reasons. Firstly, the lack of success may be explained by the fact that few quantitative differences exist between human tumors and normal tissues, and their heterogeneity overlaps in many ways. Secondly, it was intended that the 6R\u2019s can be used to understand emerging phenomena in radiation biology rather than predicting its outcomes.\n\nA diagram of modern predictive assays includes proteins endpoint, D N A endpoint, and R N A endpoint.\n\nFig. 5.16\nReview of modern biomarkers used to obtain information on relevant features of radiobiology"}
{"_id": "Radiology$$$000d03ab-e703-4611-961b-9e1cbfa99989", "text": "A diagram of modern predictive assays includes proteins endpoint, D N A endpoint, and R N A endpoint."}
{"_id": "Radiology$$$0d979400-f488-4580-99ae-3448c305deb9", "text": "The first molecular techniques were applied to radiobiology about two decades ago and soon revealed the existence of proteins and genes that respond to and influence the cellular outcome of IR [53]. Radiation response of tumors is associated with a complex series of gene and protein alterations some which also are influenced by the underlying genomic alterations, for example, mutations. When cells experience IR-induced damage, it was early on observed that key proteins are induced [57, 58]. An example is the p53 protein which upon exposing cells to a photon beam is induced and control multiple pathways. For instance, a single fraction of 20 Gy X-rays was observed to induce key proteins such as MDM2 and CDKN1A in some cell lines, both which is regulated by p53 [58]. Furthermore, the response to radiation is influenced by polymorphisms in genes encoding proteins that participate in DNA damage repair, as well as by mutations affecting these genes. When cells experience radiation insult, multiple genes undergo a series of up and down regulations interacting through many pathways including p53-regulated genes such as p21 (CIP1/WAF1) and GADD45A. Also, the response to radiation is influenced by methylation, acetylation, ubiquitylation, phosphorylation, and sumoylation of genes and proteins which control the DNA damage repair. For instance, the presence of hyper-methylated promoters means that a gene is becoming actively transcribed; hyper-methylation of promoters attracts proteins that inhibit transcription and turn it off. Non-coding RNAs also contribute to radiation response. There are complementary forms of RNA, namely microRNA (miRNA) that are not translated into protein and play an important role in the initiation and progression, repopulation and programmed cell death (see Chap. 3). Therefore, this mechanism is reflected in terms of sensitivity or resistance to IR [16, 59]. Overall, gene and protein expression are altered in the tumor itself and by radiation which affects cellular outcomes and causes a heterogeneity of RT response in tumors. Accordingly, protein, DNA and RNA analysis can be used to obtain information on relevant features of radiobiology using several types of measurements such as genomics, transcriptomics, epigenomics, or proteomics, which analyze DNA, RNA, DNA\u2013chromatin interactions and proteins, respectively, as described in Fig. 5.17 and Table 5.6.\n\nA schematic diagram of the different types of biomarkers. These are the nucleus, chromosome, nucleosome, cell, proteomics, transcriptomics, R N A, chromatin, D N A, genomics, epigenomics, and phenomics.\n\nFig. 5.17\nSchematic view of biomarkers. Proteins, DNA chromatin, DNA, or RNA that are analyzed by proteomics, genomics epigenomics, genomics, or transcriptomics, respectively\nTable 5.6\nDescription of modern biomarkers and assays for analyses of RT response\n\nMarker\n\nAdvantage\n\nAssay\n\nProtein\n\nExpression profiling at the protein level can be a good candidate marker as proteins are responsible for the actual cellular functions.\n\nTissue microarrays for high-throughput immuno-histochemistry, luminex technology for multi-analyte immunobead-based profiling, mass spectrometry methods and antibody chip.\n\nDNA\n\nThe DNA level can be a good candidate marker because everyone is genetically unique, cancer is caused by genetic changes, and is characterized by genomic instability. Variation in individual genes influences risk for cancer development. Variations in a patient\u2019s response to treatment are ascribed to the heterogeneity of genetic changes in cancer.\n\nIn situ hybridization (ISH) for identifying a DNA sequence in tumor tissue, genetic variation sequence for analyses of duplications and deletions of large region DNA (copy number variation (CNV) and Single Nucleotide Polymorphisms (SNPs), epigenetic variation sequence for chromatin modification and DNA acetylation, ubiquitylation, phosphorylation, sumoylation, and methylation.\n\nRNA\n\u00a0\nLow-density Taqman arrays for detecting small signatures after whole genome profiling, ISH and FISH for detecting RNA in sample in situ. Quantitative polymerase or real-time chain reaction for quantify and amplify a targeted DNA molecule. Gene expression array for deriving profiles, classifiers or signatures associated with prediction of treatment results or prognosis. Next-generation sequencing technologies for the study of gene expression profiles of different species of mRNA."}
{"_id": "Radiology$$$e03e41c8-d9c1-4285-b638-825c2aef9cfb", "text": "A schematic diagram of the different types of biomarkers. These are the nucleus, chromosome, nucleosome, cell, proteomics, transcriptomics, R N A, chromatin, D N A, genomics, epigenomics, and phenomics."}
{"_id": "Radiology$$$ccdfd1b5-0dc1-4d85-9e31-30699a6b2ded", "text": "Hypoxia refers to conditions with low oxygen. The oxygen concentration of most normal tissue in the human body is around 5\u20137% and tissues with less than 3% oxygen are regarded as hypoxic. Hypoxic cells are known to be more resistant to radiation and chemotherapy. Hypoxia is also a potent microenvironmental factor promoting metastatic progression of cancer  [60]."}
{"_id": "Radiology$$$6e23a17e-ffc1-49bf-aaee-eb472fd9b2ef", "text": "Hypoxia in tumor cells can be of two types\u2014acute hypoxia or chronic hypoxia. Acute hypoxia is a transient perfusion-limited hypoxia due to transiently occluded blood vessels [61]. Chronic hypoxia is a diffusion-limited hypoxia and can lead to necrosis [62]."}
{"_id": "Radiology$$$2f6dd625-41fe-48e7-8d5b-fd3b1601e5fd", "text": "Oxygen can generally diffuse approximately 150 \u03bcm at the arterial end of the capillary and less at the venous end (Fig. 5.18). Therefore, when the radius of the tumor is less than 160 \u03bcm, there is no central necrotic region. Between 160 and 200 \u03bcm, there may or may not be a hypoxic center. When the radius is more than 200 \u03bcm, the central portion consists of anoxic necrotic cells while the next layers consist of cells with different degrees of hypoxia and aerobic actively dividing cells at the outer layer [62]. The central portion becomes necrotic because the cells are deprived of both oxygen and nutrients.\n\nA diagram of the components of the oxygen passing through the tumor in small amounts. These are the blood vessel, aerobic cells, hypoxic viable cells, and anoxic necrotic cells, all with increasing chemotherapy and radiation resistance.\n\nFig. 5.18\nDiffusion of oxygen through tumor. As the distance from the blood supply increases, the oxygen levels available for the cells decreases. As the cells grow more hypoxic, they become more radioresistant"}
{"_id": "Radiology$$$114d3bf7-000e-4eab-b466-8946bb6819ba", "text": "A diagram of the components of the oxygen passing through the tumor in small amounts. These are the blood vessel, aerobic cells, hypoxic viable cells, and anoxic necrotic cells, all with increasing chemotherapy and radiation resistance."}
{"_id": "Radiology$$$939256c2-e632-4f9f-adcd-8646a5eda6b7", "text": "As hypoxic cells are more radioresistant than oxygenated cells (Chap. 3), irradiation of a tumor will predominantly kill the outer layer of cells leaving the hypoxic cells. One way to reduce this problem is to divide the radiation dose into many daily fractions, which will allow the hypoxic cells nearest to the oxygenated cells to be reoxygenated after the oxygenated cells have been killed [63]. In this section, we will give an overview of the most important mechanisms and pathways induced by hypoxia since these are potential targets in connection with treatments."}
{"_id": "Radiology$$$eb86449d-7372-4efa-871f-9a0871278900", "text": "As described in Chap. 3, oxygen modifies the biological effects of low LET IR. For such radiation, DNA damage predominantly occurs through the indirect effect of radiation-induced water radicals. In the absence of oxygen, DNA radicals can become chemically restituted through donation of hydrogen atoms by SH-compounds (such as glutathione). However, if molecular oxygen is present, RO2\u00b7 is produced which cannot be restored. Oxygen thus \u201cfixes\u201d the damage produced by free radicals (i.e., makes the radiation damage permanent). Therefore, cells are more sensitive to radiation in the presence of oxygen than in its absence."}
{"_id": "Radiology$$$a70eebb0-053e-4b50-b816-ae0c2142d444", "text": "The relative radiosensitivity of cells increases dramatically when the oxygen tension increases from 3\u00a0mmHg (0.4% O2) to about 30\u00a0mmHg (4% O2), which corresponds to the oxygen concentration in venous blood [64]. Beyond this, it reaches a plateau with no further effect of increasing the oxygen tension. In order to compete with restitution, molecular oxygen must be present during or within microseconds after the radiation exposure because the lifetime of the free radicals generated by the radiation is less than about 10\u22125\u00a0s."}
{"_id": "Radiology$$$12b7c60f-8493-473b-8014-e6bc8edcd550", "text": "The oxygen enhancement ratio (OER) is the ratio of doses under hypoxic to aerated conditions that produce the same biologic effect. In vitro studies have shown OER of X-rays to be around 3.5 for high doses and around 2.5 in low dose regions of the cell survival curves [65]."}
{"_id": "Radiology$$$a6196d39-467b-438c-9254-746065bda804", "text": "High LET radiations like alpha particles cause direct and complex damage to DNA with little possibility for restitution. Therefore, there is no enhanced effect with presence of oxygen (i.e., OER is 1). It is intermediate for neutrons and comparatively high for low LET radiations such as X-rays and gamma rays [66, 67]. OER decreases as LET increases. The OER falls slowly until about 60\u00a0keV/\u03bcm of LET, then falls rapidly and reaches 1, i.e., no oxygen effect, when LET reaches about 200\u00a0keV/\u03bcm [66]. Thus, one way to target hypoxia is to use high LET radiation (Box 5.9)."}
{"_id": "Radiology$$$88c56a7d-e37f-4b0f-99d7-5fa6482d8ac6", "text": "The oxygen enhancement ratio varies with:\nCell cycle phase\n\nType/quality of radiation\n\nRadiation dose and dose rate"}
{"_id": "Radiology$$$8d1e7022-14fe-48bd-999e-3122e25ecac9", "text": "When a tumor grows, the existing vasculature will not be able to provide oxygen and nutrients to the more distant cells resulting in regions of hypoxia. During hypoxic conditions, the cells that survive are those that undergo adaptive responses, which are not only critical to survival but also promote malignancy and metastasis. The main purposes of the adaptive responses are to uphold ATP production and save energy as well as nutrients. ATP production is maintained by the formation of new blood vessels (angiogenesis), increased production of red blood cells (erythropoiesis), switch to anaerobic metabolism, and migration to a more favorable environment (metastasis). The processes to save energy include reduction of protein synthesis and recirculation of nutrients (autophagy). The signaling pathways regulating these processes are induced by upregulation of hypoxia-inducible factors (HIFs) and activation of the unfolded protein response (UPR)."}
{"_id": "Radiology$$$de37b96f-a848-4863-9e2d-cdf2c029077a", "text": "HIF-1 was discovered in 1995. Its importance is emphasized by the award of the Nobel prize in Physiology or Medicine 2019 to William Kaelin Jr., Peter J. Ratcliffe and Gregg L. Semenza for their work in elucidating how HIF senses and adapts cellular response to oxygen availability. The HIF protein family consists of three different alpha subunits (HIF-1\u03b1, HIF-2\u03b1, HIF-3\u03b1), which bind to the same type of \u03b2-subunit. In this section, we will only discuss HIF-1, which is the only one which is ubiquitously expressed and the most well studied. In the presence of molecular oxygen, proline-hydroxylase enzymes (PHD) hydroxylate HIF-1\u03b1, i.e., PHDs add two OH-groups to proline residues on HIF-1\u03b1 using oxygen as a cofactor. Hydroxylated HIF-1\u03b1 is recognized by von-Hippel-Lindau (VHL)-ubiquitin ligase complexes, which then adds ubiquitin-groups that target HIF-1\u03b1 for degradation. Without oxygen, HIF-1\u03b1 is stabilized allowing it to bind to the \u03b2-subunit and activate gene transcription."}
{"_id": "Radiology$$$804e5da6-65d8-4378-ba61-258a9551f7a6", "text": "HIF-1 is known to induce transcription of more than 60 genes by binding to a common promoter called hypoxia response element (HRE). Some of these genes are involved in increasing oxygen supply, such as VEGF (which induces angiogenesis), erythropoietin (which stimulate red blood cell production), and iron transport to erythroid tissue. HRE-regulated genes are also involved in cell proliferation, such as insulin-like growth factor-2 (IGF-2) and transforming growth factor-\u03b1 (TGF-\u03b1). HIF-1 also induces transcription of genes involved in switching of metabolic pathways to use glycolysis as a primary mechanism of ATP production. HIF thus regulate transcription of genes involved in glucose transport into the cell (i.e., GLUT1 and GLUT3), and in maintaining intracellular pH during increased lactate production such as carbonic anhydrase 9 (CAIX) and monocarboxylate transporter 4 (MCT4)."}
{"_id": "Radiology$$$bda906b4-80df-4120-98b9-f3b45950b9b2", "text": "In addition to promoting hypoxia tolerance, HIF-1 also upregulates transcription of genes involved in several steps of metastasis: angiogenesis, epithelial-mesenchymal transition (EMT), cell motility, intra/extravasation, and the formation of a premetastatic niche facilitating colonization of metastatic tumor cells."}
{"_id": "Radiology$$$ce2f1f9c-e08a-4cbd-a42d-ad0b8d9b4abe", "text": "Stabilization of HIF and activation of its downstream pathways occur at relatively moderate levels of hypoxia (<about 2% O2) as compared to radiation resistance, which occurs below about 0.1% O2 [68]."}
{"_id": "Radiology$$$3a7ed583-d5d8-4478-85c9-2d2a69b05254", "text": "Similar to IR resistance, activation of the unfolded protein response (UPR) occurs below about 0.2% O2 and contributes to hypoxia tolerance by reducing protein synthesis and inducing autophagy. UPR is activated by accumulation of unfolded and misfolded proteins in the endoplasmic reticulum (ER). Such accumulation takes place under hypoxia because post-translational disulfide bond formation, which is necessary for correct protein folding, have been shown to be oxygen dependent [69]. There are three ER stress sensors in the ER membrane, PERK (protein kinase RNA-like endoplasmic reticulum kinase), IRE1a (inositol requiring kinase 1a), and ATF6 (activating transcription factor 6). All three are activated by the release of BiP (Binding immunoglobin Protein) from the ER membrane. Activated PERK phosphorylates eIF2\u03b1 (Eukaryotic translation initiation factor 2 subunit \u03b1), which inhibits translation of protein except for some key proteins, which remain translated [70]. One of these is ATF4 (activating transcription factor 4), which induces transcription of genes required for autophagy, amino acid synthesis and import, redox balance, and angiogenesis [71]. However, if the stress becomes excessive, ATF4 can switch from pro-survival to pro-death and induce apoptosis [72]. Active IRE1\u03b1 (Inositol-requiring transmembrane kinase/endoribonuclease 1\u03b1) reduces protein synthesis through the degradation of selected mRNAs. It also activates an inflammatory response and promotes autophagy as well as apoptosis. BIP release allows ATF6 translocation to Golgi, where cleavage of this protein results in release of transcriptionally active ATF6 (DNA-binding cytoplasmic domain of ATF6), which contributes to restoring ER homeostasis [70]."}
{"_id": "Radiology$$$61a691a3-59da-4184-997e-eb0660abd2ed", "text": "Hypoxia in tumor cells can be measured using oxygen probes or protein markers for hypoxia. Polarographic electrodes, in particular Eppendorf electrodes, have long been regarded as the gold standard for measuring tumor hypoxia. The limitations of these are that they must be inserted into the tumor damaging the tissue and that they consume oxygen resulting in a high signal-to-noise ratio for low oxygen levels [73]. Fiber-optic probes have also been developed [74], but the disadvantage of both is that this is an invasive method, which can only be used in accessible tumors. Another method is injection of pimonidazole to patients before biopsies or total resection of the tumor. Pimonidazole is a 2-nitroimidazole compound, which binds to thiol-containing proteins specifically in hypoxic cells, and it can be used in immunohistochemical analyses to quantitative assessment of tumor hypoxia [75]."}
{"_id": "Radiology$$$848113f8-5e97-4966-960e-61e5a27650eb", "text": "A noninvasive alternative method is hypoxia PET imaging. 2-Nitroimidazoles have been developed as radiosensitizers due to their ability to undergo up to six electron reductions. However, they can also be used as radiotracers carrying a positron emitter. The reduction requires the activity of reductases that are only present in viable hypoxic cells resulting in the radiolabeled molecules being accumulated in hypoxic regions visible to PET imaging. Examples of nitroimidazole or nitroimidazole-derivative tracers are 18F-Fluoromisonidazole (18F-FMISO), 18F-Fluoroazomycin-Arabinofuranoside (18F-FAZA), 18F-labeled fluoroerythronitroimidazole (18F-FETNIM), 18F-fluoroetanidazole (18F-HX4), and 18F-2-(2-Nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl) acetamide (18F-EF5) [73, 76]. Other redox-sensitive compounds include Copper(II) diacetyl-bis (N4-methylthiosemicarbazone) (60Cu-ATSM) and 123I-iodoazomycinarabinoside (123I-IAZA) [77]. Of these, 18F-MISO is the most extensively used in both preclinical and clinical studies. F-MISO is highly lipophilic, which means it can easily diffuse across cell membranes but also that the clearance of the tracer from normoxic tissue is very slow. This results in a low tumor to blood ratio and the need to wait for typically 2\u00a0h between tracer injection and imaging. A general problem in PET imaging is the low spatial resolution."}
{"_id": "Radiology$$$e67c67f3-db29-4a16-a641-65c382b9668c", "text": "Magnetic resonance imaging (MRI) is non-ionizing and has a better spatial resolution than PET. Different MRI techniques have been evaluated for quantification of the blood oxygenation level in tissue. Blood oxygen level-dependent MRI (BOLD-MRI) uses the paramagnetic quality of deoxyhemoglobin in contrast to oxygenated hemoglobin. This can be measured as an increase in T2*-relaxation rate. A similar technique, tissue oxygen level-dependent MRI (TOLD-MRI) uses an increase in T1 relaxation caused by the presence of dissolved oxygen. A third technique is dynamic contrast-enhanced MRI (DCE-MRI) in which a paramagnetic contrast agent such as gadolinium is used and imaged over time [78]."}
{"_id": "Radiology$$$423d66b3-2d18-4294-85d1-fb883626b5a4", "text": "HIF and its target proteins such as CA9 and GLUT1 are upregulated under hypoxia (see above). Accordingly, they have been studied as endogenous markers for hypoxia and seem to co-localize with 2-nitroimidazoles. However, their expression can also be regulated by other factors than oxygen, which reduces their reliability in quantifying tumor hypoxia."}
{"_id": "Radiology$$$ded47b11-1b59-46cd-927f-2db7056d65a2", "text": "Tumor hypoxia is a major barrier for effectively treating cancer patients. Various approaches have been investigated both in vitro and in vivo to overcome hypoxia in tumor cells. The main clinical strategies to mitigate treatment resistance due to tumor hypoxia are either to improve oxygenation, mimic the effect of oxygen, use drugs that are cytotoxic only in hypoxic cells, apply dose escalation to hypoxic areas, or inhibit pathways that are important for cell survival under hypoxia (Table 5.7).Table 5.7\nA summary of different approaches to improve treatment of hypoxic tumors\n\nApproaches\n\nRationale\n\nHigh LET radiotherapy\n\nDirect damage to DNA, less dependent on oxygen levels\n\nHyperbaric oxygen\n\nImprove tumor oxygenation\n\nBlood transfusion\n\nImprove oxygen supply\n\nPerfluorocarbons\n\nArtificial blood substances to improve oxygen supply\n\nNicotinamide\n\nVitamin B3 analogue to overcome acute hypoxia\n\nCarbogen\n\n95% oxygen + 5% carbon dioxide to overcome chronic hypoxia\n\nHypoxic cell radiosensitizers\n\nCompounds that mimic oxygen and can radio-sensitize tumors\n\nBioreductive drugs\n\nReduces to cytotoxic form during hypoxic conditions\n\nHypoxia-targeted radiotherapy\n\nDose escalation/adaptation in hypoxic sub-volumes of tumor\n\nDichloroacetate\n\nInhibits pyruvate dehydrogenase kinase 1, alter tumor metabolism, enhances efficacy of hypoxic cytotoxins\n\nElectron transport chain inhibitors\n\nDecreased oxygen consumption in mitochondria and increased radiosensitivity"}
{"_id": "Radiology$$$486bb746-c2da-4f77-be91-e363f9362d3a", "text": "The simplest approach to reduce tumor hypoxia is to let the patient breathe hyperbaric oxygen (HBO) (2\u20134 atmosphere 100% oxygen). However, this may cause vasoconstriction. To avoid this, a mixture of 5% carbon dioxide and 95% oxygen called carbogen was introduced. Carbogen breathing reduces chronic diffusion limited hypoxia. For acute hypoxia, nicotinamide can be used to mitigate transient fluctuations in tumor blood flow [79]. In the ARCON strategy, a combination of carbogen and nicotinamide was used in association with accelerated hyperfractionated RT to reduce tumor proliferation during treatment and spare normal tissues [80]."}
{"_id": "Radiology$$$81e603db-7a23-43c4-a8b3-fb23bb97cf58", "text": "Hypoxic cell radiosensitizers are chemical or pharmacologic agents that can increase the radiosensitivity of cells, which are deficient in oxygen. These agents are oxygen substitutes that diffuse into poorly vascularized areas of tumors and penetrate to reach hypoxic cells within the tissue. Therefore, when administered with radiation these agents cause fixation of the free radical damage caused by IR and thereby increases its lethal effect. A radiosensitizer should have an increased effect on tumors relative to normal cells to achieve a therapeutic window/gain. An ideal hypoxic cell radiosensitizer should be chemically stable; have low metabolic breakdown; be highly soluble in water and lipids; act at all phases of cell cycle; be active at low doses of radiation; and cause low toxicity to normal cells [81]."}
{"_id": "Radiology$$$8de353be-2855-4161-8472-b978f5a300e1", "text": "The commonly used hypoxic cell radiosensitizers belong to the nitroimidazole group of drugs. In the nitroimidazole ring structure, a nitro group can be present in any of positions 2\u20135. Based on the position of the nitro group, drugs are named 2-nitroimidazole to 5-nitroimidazole. The presence of the nitro group in position 2 increases electron affinity and IR sensitization capacity [82]. Therefore, 2-nitroimidazole is a more efficient hypoxic cell radiosensitizer. Three widely used nitroimidazole compounds in clinical trials and their characteristics are summarized in Table 5.8.Table 5.8\nNitroimidazole group hypoxic cell radiosensitizers (adapted from [13])\n\nCompound name\n\nPosition of nitro group\n\nProperties\n\nToxicity\n\nMisonidazole\n\n2-Nitroimidazole\n\nLipophilic, crosses blood\u2013brain barrier\n\nNeurotoxic\u2014dose limiting\n\nEtanidazole\n\n2-Nitroimidazole\n\nHydrophilic, shorter half-life, does not cross blood\u2013brain barrier\n\nLess neurotoxic\n\nNimorazole\n\n5-Nitroimidazole\n\nLess active\n\nLess toxic"}
{"_id": "Radiology$$$daace936-bc98-4d95-a958-1c491bd7bb58", "text": "The enhancement ratio is the ratio of X-ray doses needed to control 50% of the tumors in the absence and presence of the drug. It was found to be around 1.82 for misonidazole in a mouse mammary tumor model for a single-dose treatment but for multifraction regimens, it is usually less [83]."}
{"_id": "Radiology$$$ef35a7a9-5db5-41fe-bba2-881129a98beb", "text": "The Danish Head and Neck Cancer 5 (DAHANCA 5) study which comprised 422 patients with pharyngeal and supraglottic carcinomas found a clear benefit of using nimorazole as a radiosensitizer. Thus, no increase in late radiation toxicity and a highly significant benefit in 5-year local control rates and disease-free survival rates. The use of nimorazole as a radiosensitizer in head and neck cancer is standard practice in Denmark [55]."}
{"_id": "Radiology$$$0ade6c55-8e63-404a-bfee-5a01ae7bd945", "text": "Bioreductive drugs are drugs that are reduced by cells to form active cytotoxic agents only under hypoxic conditions while being non-reduced in an oxic cell. Thus, the differential action on hypoxic cells (i.e., tumor cells) compared to oxic cells, i.e., normal cells) gives a therapeutic window/gain. Unlike the direct action of hypoxic cell radiosensitizers, which increases the radiosensitivity of cells, bioreductive drugs act synergistic with radiation to improve tumor cell kill [84]."}
{"_id": "Radiology$$$4f4951c9-17f6-4cff-a798-93dd132d3afa", "text": "The hypoxic cell cytotoxicity ratio (HCR) is the dose of a drug required to kill a certain fraction of oxic cells compared to the dose of drug required to kill an equal fraction of hypoxic cells. HCR varies for different classes of bioreductive drugs [85]. The main classes of bioreductive compounds are fused ring benzoquinones (e.g., mitomycin C), organic N-oxides (e.g., tirapazamine), and nitroheterocyclic compounds (e.g., RSU-1089), among which tirapazamine is the widely investigated drug."}
{"_id": "Radiology$$$52cdca7a-203d-42d1-8d7f-62923461fe9c", "text": "As described above, imaging techniques such as PET and MRI can be used to identify hypoxic regions within the tumor. They are used in RT treatment planning to define radioresistant sub-volumes that can be targeted with boost dose or dose escalation. Targeting hypoxic sub-volumes in tumors by adaptive RT/dose painting can lead to improved tumor control. There is early clinical evidence from a phase 2 randomized trial that dose escalation to hypoxic volumes using 18F-FMISO PET is feasible without increased normal tissue toxicity in head and neck cancers [86]. The utility of hypoxia-directed RT dose painting is being studied in other cancer subsites such as lung, pancreas, and cervix cancer [87\u201389]."}
{"_id": "Radiology$$$819f33c0-9ec3-4b55-95e8-ae19df503cf1", "text": "Drugs that target specific molecules to improve radiosensitivity in hypoxic tumors are being investigated in preclinical and clinical studies. Examples are dichloroacetate, electron transport chain inhibitors, and other pathway inhibitors."}
{"_id": "Radiology$$$6046cda8-dec2-4109-bb73-62ffe373ad0e", "text": "Dichloroacetate (DCA) is a specific inhibitor of the pyruvate dehydrogenase kinase (PDK), which has been shown to increase ROS production in hypoxic cancer cells but not in aerobic cells leading to radiosensitization of hypoxic tumor cells [90]. Electron transport chain inhibitors have been developed to reduce oxygen consumption and thereby improve tumor oxygenation. One such is an anti-diabetic drug, Metformin, which has been shown to reduce oxygen consumption through inhibition of mitochondrial complex I and thus improve tumor oxygenation and response to RT [91]. Other approaches include inhibition of pathways that are important for cell survival under hypoxia (e.g., HIF-1\u03b1, CAIX, MCT4, VEGF, and lactate dehydrogenase-A (LDHA) [92]."}
{"_id": "Radiology$$$e28284dc-9690-4e61-93c2-90bdcdd628e7", "text": "Tumor hypoxia can be acute (perfusion-limited) or chronic (diffusion-limited).\n\nTumor hypoxia leads to resistance to RT and chemotherapy.\n\nHypoxic tumor cells undergo adaptive responses that are critical to survival but also promote malignancy and metastasis.\n\nStrategies to either increase oxygenation or interfere with the hypoxic response pathways can improve the outcome of RT.\n\nDrugs that either mimic the effect of oxygen or are toxic under hypoxic conditions can be used to increase the effect of RT."}
{"_id": "Radiology$$$bb94d803-5e77-474b-a032-74aa004d2490", "text": "Hypoxic tumor cells undergo adaptive responses that are critical to survival but also promote malignancy and metastasis."}
{"_id": "Radiology$$$b4dd6381-d8c2-476e-bd79-d9f6bccd6a97", "text": "Strategies to either increase oxygenation or interfere with the hypoxic response pathways can improve the outcome of RT."}
{"_id": "Radiology$$$d3411f84-2978-4355-ada9-c792b19af19d", "text": "Drugs that either mimic the effect of oxygen or are toxic under hypoxic conditions can be used to increase the effect of RT."}
{"_id": "Radiology$$$338fcc4c-a845-41c2-badb-ddf22ab1b351", "text": "RT is an effective cancer treatment, but a large portion of patients subsequently experience radioresistance and recurrence of their cancers.\n\nMechanisms of radioresistance in cancer treatment are related to several factors: Increased DNA damage repair capacity, cell-cycle redistribution, cancer stem cell resilience, signaling pathways, epithelial-mesenchymal transition (EMT), and tumor metabolism."}
{"_id": "Radiology$$$08934493-2586-4a3e-993a-ed0a2bc26169", "text": "RT is an effective cancer treatment, but a large portion of patients subsequently experience radioresistance and recurrence of their cancers."}
{"_id": "Radiology$$$1f94693c-f4b9-4af9-8621-d8a2c96def18", "text": "Mechanisms of radioresistance in cancer treatment are related to several factors: Increased DNA damage repair capacity, cell-cycle redistribution, cancer stem cell resilience, signaling pathways, epithelial-mesenchymal transition (EMT), and tumor metabolism."}
{"_id": "Radiology$$$3c2e7ad9-ba41-4ce0-af74-a65dfbf0ae88", "text": "RT is one of the most efficient therapeutic regimens for various tumors. The main factor in determining the therapeutic effect is the tumor radiation response that is correlated to intrinsic or acquired radioresistance after the treatment [93].  Intrinsic radioresistance relies on inherent characteristics of the tumor (for instance, the presence of cancer stem cells (CSCs). The acquired radioresistance is a process of tumor adaptation to the RT-induced changes and develop resistance to the IR. This complex process involves multiple genes, factors, and mechanisms [94, 95]. Radioresistance leads to poor prognosis in cancer patients, and it represents the main reason for RT failure, which can ultimately lead to tumor recurrence and/or progression/metastases [95]. Radioresistance of tumors is influenced by several factors, including increased DNA damage repair capacity, cell-cycle redistribution, CSCs resilience, signaling pathways, epithelial-mesenchymal transition (EMT), and tumor metabolism (Fig. 5.19).\n\nA spoke diagram of treatment failure includes cancer stem cells, D N A repair, cell cycle redistribution, extracellular signaling pathways, epithelial-mesenchymal transition, and tumor metabolism.\n\nFig. 5.19\nDescription of the tumor biological responses to radiation and the mechanisms for its resistance"}
{"_id": "Radiology$$$9b4dffcc-e919-41a8-9c72-db04e017d8bd", "text": "A spoke diagram of treatment failure includes cancer stem cells, D N A repair, cell cycle redistribution, extracellular signaling pathways, epithelial-mesenchymal transition, and tumor metabolism."}
{"_id": "Radiology$$$45fd5321-d6b9-4c05-b24f-20c3c306e169", "text": "RT kills cancer cells mostly by inducing DNA damage. Radiation-induced DNA lesions are multiple including base and sugar modifications, cross-links, single-stranded breaks (SSBs), and double-stranded breaks (DSBs) [96] (see also Chap. 3). DNA DSBs are responsible for most of IR-induced cell killing [97]. To respond to DNA damage, cells initiate signaling pathways named DNA damage response (DDR) signaling. The capacity of tumor cells to trigger a DDR following radiation, through initiation of DNA repair and cell-cycle checkpoints, promotes radiation resistance and tumor cell survival. In radiobiology, it is considered that cells with a high capacity to trigger DSBs repair will be radioresistant, while cells with frail repair ability will be more sensitive in response to radiation [93]."}
{"_id": "Radiology$$$47cd2181-5bd6-4e2e-acba-edbc76787fe8", "text": "Activation of DDR and proper repair of DNA lesions are of paramount importance for cellular integrity, survival, and genomic stability [98]. There are four main DNA repair pathways in tumor cells: DNA DSB repair, base excision repair (BER), nucleotide excision repair (NER), and mismatch repair (MMR) [99]. BER and SSB repair (SSBR) are important for repairing altered bases and SSBs. Besides DSBs caused directly by IR unrepaired damaged bases and SSBs, can generate DNA DSBs when they face a replication fork. Non-homologous end joining (NHEJ) and homologous recombination (HR) two principal cellular DSB repair pathways (see Chap. 3)."}
{"_id": "Radiology$$$6f20b5c4-9b44-4114-9cfa-bedf58f2964a", "text": "Defects in DNA repair factors are a characteristic of many cancers which promote genomic instability and mutation in cells [98, 100\u2013102]. Deficiency of DDR and DNA repair genes caused diseases such as Xeroderma pigmentosum, Ataxia Telangiectasia (ataxia telangiectasia mutated (ATM)), Nijmegen breakage Syndrome (Nibrin (NBS1)), Werner syndrome (WRN), Fanconi anemia (FA), associated breast cancer syndrome (BRCA1 and BRCA2), lead to cancer susceptible disease syndromes (reviewed in [98, 102] and in Chap. 7). Cancers present germ line mutations, somatic mutations or distinctive expression of DDR components that lead to the impairment of DDR and altered checkpoints. In addition, DNA replication stress due to oncogene stimulation also causes initiation of DDR and tumor progression."}
{"_id": "Radiology$$$b461e056-4eee-4abd-94ee-635b9443f116", "text": "The same DNA repair deregulation that commenced carcinogenesis is associated with cancer progression, aggressiveness [102]. There are situations in which the tumor is preserved after the therapy, becoming even more aggressive. It is known that IR can activate stress and adaptive response to DNA lesions causing cancer progression, metastatic behavior [103]. Several dysfunctional DDR signaling genes are found in cancer and correlated with radioresistance (Table 5.9).Table 5.9\nExamples of dysfunctional DNA damage response signaling genes found in cancer and linked with cancer radioresistance and progression\n\nMolecule\n\nFunction(s)\n\nType of defects\n\nReference\n\nATM\n\nDDR\u2014DSBs\nCell-cycle redistribution\n\nMutations; increased copy number and autophosphorylation, overexpression\n\nSquatrito et al. [104], Zhang et al. [105]\n\nDNA PKcs\n\nNHEJ\n\nOverexpression\n\nKotula et al.  [106]\n\nLigase IV/XRCC complex\n\nNHEJ\n\nPolymorphism in LIG4 gene\n\nSrivastava et al. [107]\n\nRAD51\n\nHRR\n\nOverexpression\n\nChen and Kuo [96] Bhattacharya and Asaithamby [98]\n\nRPA\n\nHRR\n\nOverexpression\n\nLiu et al. [93]\n\nBRCA1 and BRCA2\n\nHRR transcriptional regulation of many DNA repair genes\n\nLoss-of-function mutation; BRCA1 overexpression\n\nKan and Zhang [108]\n\nHSP90\n\nRegulates HRR\nRegulates protein related to DDR signaling (ATM, NBS1, ATR)\n\nOverexpression\n\nKinzel et al. [109]\n\nAPE1 (apyrimidinic endonuclease 1)\n\nBER\n\nOverexpression\n\nKiwerska and Szyfter [102], Madhusudan [110]\n\nDNA polymerase \u03b2 (pol \u03b2)\n\nBER\n\nOverexpression; missense mutations in pol \u03b2 gene coding for variant proteins\n\nBhattacharya and Asaithamby [98]\n\nPARP\n\nPARP 1 and PARP 2-SSB, BER\n\nOverexpression\n\nLi et al. [111]\n\nKu 70/80\n\nNHEJ\n\nOverexpression\n\nBaptistella et al. [112]\n\nMSH6/MSH2\n\nMMR\n\nReduced expression\n\nUraki et al. [113]\n\nERCC1\n\nNER\n\nOverexpression\nPolymorphism\n\nKiwerska and Szyfter [102], Peng et al. [114]\n\nXRCC1\n\nExcision repair\n\nPolymorphism\n\nLi et al. [115], Liu et al. [93]"}
{"_id": "Radiology$$$6de1cb04-d489-46ef-856f-b3dca6629343", "text": "Activation of cell-cycle checkpoints is important downstream IR-induced DDR signaling. Several molecules in the cell-cycle checkpoints regulate and block cell-cycle progression to allow for DNA repair and prohibit premature entering into mitosis with unrepaired DNA lesions. The same machinery responsible for DNA damage recognition, ATM and ATR, activates the cell-cycle checkpoints kinases CHK1 and CHK2 to regulate the checkpoints and repair DNA damage. Two distinct signaling cascades, the ATM-Chk2 and ATR-Chk1 axes respond to DSBs damages, respectively, to ssDNA. Activated Chk1 and Chk2 inactivate CDC25C by phosphorylation. In the absence of CDC25C phosphatase activity, WEE1 kinase impedes cyclin-dependent kinase 1 and 2 (CDK1/2) activity triggering cell-cycle arrest in the G2/M phase and promoting DNA damage repair (reviewed in [93, 95, 111]). Molecules in the cell-cycle checkpoints were also found to be linked with the development of radioresistance (e.g., ATM, p53, p21, Chk2, Cdc2)."}
{"_id": "Radiology$$$c0b214af-198a-4d8d-8915-8ceebe9f0528", "text": "A considerable amount of research has been done on the modulation of cellular signaling pathways in response to IR and many of them are involved in radioresistance, including extracellular and intracellular signaling cascades. This subsection focuses specifically on the major oncogenic signaling pathways such as Ras and phosphatidylinositol-3\u2032-kinase pathways (PI3K)/AKT that contribute to radioresistance (Fig. 5.20).\n\nA spoke diagram of resistance to radiation includes the suppressors L K B 1, Ras pathway, suppressor P T E N, and P I 3 K, A K T pathway.\n\nFig. 5.20\nReview of tumor suppressors and the molecular signal pathways that contribute to radioresistance"}
{"_id": "Radiology$$$4634a895-2b84-47c0-81c4-8244c371546a", "text": "A spoke diagram of resistance to radiation includes the suppressors L K B 1, Ras pathway, suppressor P T E N, and P I 3 K, A K T pathway."}
{"_id": "Radiology$$$55611463-c578-45d0-b232-0f507d12e94e", "text": "Radiation causes many behavioral changes in the extracellular domain of EGFR as well as to its kinase domain, including truncations and common mutations of an extracellular domain of EGFR [16, 116, 117]. Photon radiation can cause EGFR aberrations that over-activate downstream pro-oncogenic signaling pathways, including the RAS-RAF-MEK-ERK MAPK and AKT-PI3K-mTOR pathways that modulate cell processes, including cell resistance to RT, angiogenesis, migration, invasion, and apoptosis [118\u2013120]."}
{"_id": "Radiology$$$2a237704-f65b-4fc7-abc3-ff0976dd9358", "text": "When EGFR is activated by photon radiation, this activation, triggers the RAS-RAF-MEK-ERK MAPK pathways. Radiation resistance is associated with this pathway targets due to its pro-survival nature, and mutated RAS has been associated with resistance to photon-irradiation in cancer cells [121\u2013124]."}
{"_id": "Radiology$$$fe172984-4512-40d0-9e51-7b56c48fd03e", "text": "Also, when EGFR is activated by photon radiation, this triggers the AKT-PI3K-mTOR pathways and activated EGFR induces the phosphorylation of PI3K and downstream AKT phosphorylation [124]. Radiation resistance is also linked to activation of this target with tumor cells being protected by decreased autophagy and apoptosis, as well as increased DNA repair capacity [125]."}
{"_id": "Radiology$$$2ae65ba8-3148-46c2-844d-b3b3e2d8c21e", "text": "Overall resistance to photon irradiation appears to be modulated by the transmembrane protein EGFR but also repression of tumor suppressors. In this circumstance, the tumor suppressors LKB1 and PTEN has been reported to correlate to resistance."}
{"_id": "Radiology$$$75051f59-a703-41e3-bad7-b33ba4c8c69e", "text": "EMT is a series of changes involving epithelial cells that phenotypically transform into mesenchymal cells [126]. To acquire local invasiveness, the first step involves a profound phenotypic shift within the primary tumor of cancer cells. The progression of cancer is dependent on tumor cells undergoing the EMT and invading blood vessels [127, 128]. This results in invasion and distant metastasis, the main cause of cancer-related death. Normal epithelial cell layers cannot accommodate the motility and invasiveness of malignant carcinoma cells, yet this epithelial organization plan continues to be recognized in many primary carcinomas. Despite their overall topology differing quite a bit from that of comparable normal epithelia, these tumors contain well-organized sheets of epithelial cells. Although it\u2019s not confirmed, cancer cells require a partial or complete EMT to become invasive as in the following steps [129]:1.\nFactors, including growth factor (GF), initiate EMT by promoting E-cadherin replacement by N-cadherin.\n\u00a02.\nDue to its ability to allow these tumor cells to form homotypic interactions with a variety of types of mesenchymal cells, N-cadherin increases the affinity of cancer cells for stromal cells composed of fibroblasts, which support tumor cell invasion.\n\u00a03.\nN-cadherin forms a weaker intermolecular band than E-cadherin, so molecules whose intermolecular bands are weaker favor motility."}
{"_id": "Radiology$$$e7b558fb-6938-4503-8368-82fd3b939d50", "text": "Factors, including growth factor (GF), initiate EMT by promoting E-cadherin replacement by N-cadherin."}
{"_id": "Radiology$$$b69560d0-d336-47b2-a027-c8251d4bc184", "text": "Due to its ability to allow these tumor cells to form homotypic interactions with a variety of types of mesenchymal cells, N-cadherin increases the affinity of cancer cells for stromal cells composed of fibroblasts, which support tumor cell invasion."}
{"_id": "Radiology$$$2eb2f698-c571-4ab0-8b10-6332a03e1143", "text": "N-cadherin forms a weaker intermolecular band than E-cadherin, so molecules whose intermolecular bands are weaker favor motility."}
{"_id": "Radiology$$$19d75b23-ec6a-48bc-b5a1-e6c8e9923c77", "text": "When normal cells transform into cancerous cells, E-cadherin turns into N-cadherin and such cancer cells can escape their keratinocyte neighbors. Thus, the switch from E- to N-cadherin expression promotes invasion of the stroma. N-cadherin allows cancer cells to form homotypic interactions with mesenchymal cells, including endothelium, fibroblasts, and others in the stroma of the organ (Fig. 5.21).\n\nA diagram of the epithelial to mesenchymal transition. Some of the steps are Epithelial, stable defined polarity, E M 1, E M 2, E M 3, meta-stable, Apico-Basal polarity loss, gain of front-back polarity, mesenchymal, stable, front-back polarity, and metastasis, cancer cell in blood stream.\n\nFig. 5.21\nAn overview of a typical EMT program that causes cadherin shifts in the cell and invasion of cancers"}
{"_id": "Radiology$$$0f0013e5-2890-4559-ac12-e264d43b75fb", "text": "A diagram of the epithelial to mesenchymal transition. Some of the steps are Epithelial, stable defined polarity, E M 1, E M 2, E M 3, meta-stable, Apico-Basal polarity loss, gain of front-back polarity, mesenchymal, stable, front-back polarity, and metastasis, cancer cell in blood stream."}
{"_id": "Radiology$$$15bb095c-264c-4e93-96f1-355dc4bf27ed", "text": "In vitro and in vivo, EMT is induced by a variety of factors, including radiation, ROS, hypoxia, and transforming growth factor [130\u2013132]. Radiation causes many changes in a cell, which are directly affiliated with epithelial cancer. These include aberrant multicellular organization, genomic instability, dysregulation of differentiation, and phenotypic transition, i.e., EMT. Multiple evidence suggests that Notch1 signaling is essential for EMT [133]. Unlike normal tissue, when cancerous tissues experience radiation insult, the irradiated cells show overexpression of an active Notch-1 protein in both cytoplasm and nucleus. This results in decreased expression of E-cadherin and increased expression of vimentin and fibronectin, which consequently alleviate radiation-induced EMT as reported both in in vitro and in vivo models [134, 135]. Furthermore, low dose IR promotes NF-\u03baB p65 signaling in cervical cancer cells. The transcription factor NF-\u03baB regulates tumorigenesis as well as apoptosis and is essential for the initiation and maintenance of EMT. This signaling subsequently induces EMT that downregulates of expression of the epithelial markers E-cadherin and Cytokeratin 18 (CK-18), which is a hepatocyte-secreted protein that is released into the blood during apoptosis and necrosis while it upregulates vimentin and the mesenchymal markers N-cadherin. Therefore, this leads to improving the progression of cancer cells [136]. Additionally, a variety of evidence indicates that Granulocyte Colony-Stimulating Factor (G-CSF) (formerly believed to promote granulocytes) is strongly associated with lung cancer progression [137]. Moreover, it has been reported that IR activates Granulocyte Colony-Stimulating Factor Receptor (G-CSFR)/JAK/STAT3 signaling pathways via secreted G-CSF, resulting in EMT in non-small cell lung cancer cells (NSCLCs) [137]. The matrix metalloproteinase (MMP) family proteins are essential for EMT, as well. The \u03b3-IR treatment of nodular NSCLC cells was associated with increased invasion via EMT induction, which is characterized by a highly active MMPs system [138]. Following irradiation, an EMT program is induced, causing breast cancer cells to develop a resistance and progression behavior. The proto-oncogene tyrosine-protein kinase (SRC), being a non-receptor kinase, integrates diverse signal transduction pathways that contribute to a variety of cellular processes including survival, proliferation, angiogenesis, differentiation, migration, and angiogenesis. Upon irradiation, SRC is activated, which promotes EMT through AKT, p38, and PI3K activation. Similarly, fractionated IR inhibits PTEN-related expression, which is associated with activation of the Drosophila embryonic protein SNAI1 (Snail) protein accumulation and Akt/GSK-3\u03b2 signaling and provoking EMT [139]. As a result of radiation, GSK-3\u03b2 is phosphorylated at serine 9 residue, and silencing the tank-binding kinase-1 (TBK1) tones down the phosphorylation, indicating that TBK1 inhibition is associated with activating GSK-3\u03b2. Indeed, GSK-3\u03b2 functions in several key signaling pathways that can contribute to EMT, such as the Wnt, TGF-\u03b2, Hedgehog, Notch, and PI3K pathways. Upon phosphorylation at its N-terminus, GSK-3\u03b2 can be inactivated and Snail is stabilized and succumbs to EMT. In this way, it is suggested that TBK1 inhibition has the potential to reduce radiation-induced Zinc Finger E-Box Binding Homeobox 1 (ZEB1) expression via activation of GSK-3\u03b2. This hypothesis is supported by the observation that pre-treatment of cells with the GSK-3\u03b2 inhibitor SB216763 increases TBK1 inhibition, increases E-cadherin expression, and reduces ZEB1. In conclusion, it was seen that TBK1 signaling is influenced by GSK-3\u03b2 in radiation-induced EMT [140]. RT can cause both lessening of tumor cells and killing of them as it can also lead to damage to normal tissues, radioresistance, invasion, and distant metastases. Several studies have suggested that EMT generates malignant characteristics such as a propensity to recurrence, resistance to treatment, and dissemination of metastatic cells. Radiation is generally considered a key initiating factor for EMT, as it activates signal pathways that initiate the process."}
{"_id": "Radiology$$$92d86e8c-2dda-479f-acc0-bcc2b9859e32", "text": "Radiation resistance has in multiple studies been linked to tumor metabolism alterations as a result of radiation-induced changes in mitochondrial metabolism or glycolysis [141, 142]. The development of radioresistance is closely related to glucose- as well as mitochondrial metabolism. The radiosensitivity of the tumors can be explained by radiation-induced metabolic changes in glucose and mitochondrial functions or by tumor-induced metabolic changes (Table 5.10).Table 5.10\nGlucose and mitochondrial metabolism induced by the tumor itself that contribute to tumor resistance and progression\n\nEntity\n\nType\n\nCause\n\nEffect\n\nOutcome\n\nNicotinamide adenine dinucleotide phosphate (NADPH)\n\nGlucose metabolism\n\nThe decrease in OxPhoslevels in mitochondria and the pentose phosphate pathway (PPP)\n\nIncreasing tumor dependence on glycolysis and reducing intracellular ROS levels\n\nTumor proliferation\n\nAn organic compound (dinitrophenol)\n\nGlucose metabolism\n\nMitochondrial respiratory modulators\n\nIncrease in the glycolytic index\n\nRejoining of DNA strand breaks that leads to reducing the probability of cancer cells damage by radiation\n\nProteins (GLUT1)\n\nGlucose metabolism\n\nGLUT family in cell membrane\n\nUpregulated under hypoxic circumstances\n\nPoor prognosis, radioresistance, oncogene activation and inhibition of tumor suppressors, stimulation of hypoxia, and the regulation of different signaling pathways, including PI3K/AKT and MAPK\n\nLactic acid\n\nGlucose metabolism\n\nProducts of glycolysis\n\nAccumulation in tumor tissues\n\nPromoting recurrence, tumor metastasis and radioresistance\n\u00a0\u00a0\u00a0\nFibroblasts in tumors release hyaluronic acid in response to lactic acid\n\nNeovascularization, cell clustering, migration, and VEGF secretion\n\nLactate dehydrogenase (LDHA)\n\nGlucose metabolism\n\nDistribute in human tissues\n\nEnzyme helps make lactic acid from pyruvate\n\nOverexpression indicates hypoxic conditions, which can be associated with radioresistance, lower survival rate, local recurrence, and distant metastases\n\nSoluble adenylate cyclase (sAC)\n\nGlucose metabolism\n\nActivation of BRAF/ERK1/2 signaling\n\nRelease of LDHA\n\nThe anti-irradiation effects and cell proliferation.\n\nHIF-1\u03b2\n\nGlucose metabolism\n\nActivated in hypoxic environments\n\nThe adaptive cellular responses to hypoxia, important mediator of the conversion of OxPhos to glycolysis in the metabolism of carbohydrates convert ADP and phosphoenolpyruvate into ATP and pyruvate\n\nRadioresistance by removing ROS from the cells and activating cell autophagy\n\nPyruvate kinase (PK)\n\nGlucose metabolism\n\nEnzyme involved in glycolysis\n\nConvert ADP and phosphoenolpyruvate into ATP and pyruvate\n\nPK expression correlates with radioresistance\n\nHexokinase 2 (HK2)\n\nGlucose metabolism\n\nA critical role in glucose metabolism\n\nUpregulation of this enzyme can induce glycolysis\n\nHK induces glycolysis, making it essential for the progression and maintenance of tumors\n\nAntigen 2 (NG2)\n\nMitochondrial metabolism\n\nA glial cell antigen\n\nBy interacting with serine protease OMI/HtrA2 of mitochondria, protect oligodendrocyte precursor cells from oxidative stress\n\nDevelopment of radioresistance\n\nProtein 3A (ATAD3A)\n\nMitochondrial metabolism\n\nCancer patients\n\nActivating ATAD3A leads to the expressions of histone H3, H2AX and ATM increase\n\nInhibit the IR-induced apoptosis in glioblastoma cells\n\nMatrix metalloproteinase\n\nMitochondrial metabolism\n\nThe extracellular protein\n\nRadiation resistance is induced by molecules or signaling pathways that increase MMP or inhibit its decrease\n\nRadiation resistance"}
{"_id": "Radiology$$$ae762213-d03a-4c7c-adc2-cc0a96cdc4c2", "text": "After the tumor cells have been exposed to radiation for an extended period of time, these cells experience alteration in the glucose metabolic pathway. As an important kinase, AKT regulates multiple biological processes, including cellular metabolism. As described in the previous section AKT is phosphorylated in cells after IR exposure to radiation which results in radioresistance of tumor cells through the AKT-mediated alteration of cellular glucose metabolism. A disruption in glucose metabolism also occurs after radiation exposure of tumor cells, resulting in an accumulation of lactic acid. This is the primary product of glycolysis and contributes to the development of malignant tumors. Moreover, glycolysis may cause tumor metastasis, recurrences, and resistance to RT."}
{"_id": "Radiology$$$86a0ac7c-e80f-46e1-ba67-d0351ab1dce2", "text": "Radiation exposure of tumor cells likewise disrupts mitochondrial metabolism. In the post-RT setting, manganese superoxide dismutase (MnSOD) activity increases significantly in pancreatic cancer cells irradiation. MnSOD is the enzyme which catalyzes the formation of superoxide anion radicals, fighting the effects of oxidative stress ROS-induced damage. As a consequence, G2 checkpoint block is activated and cells are protected against mitochondrial oxidative stress by mitochondrial antioxidant systems, promoting radioresistance development. Radiation exposure to Burkitt lymphoma similarly disrupts mitochondrial metabolism by inducing the proteins (mitochondrial proteomes) that prompt radioresistance. Radiation of tumor cells targets Mitochondrial MAPK phosphatase (MKP1). Radiation increases MKP1 expression in breast cancer cells, where it translocates into the mitochondria and inhibits apoptosis by phosphorylating the c-Jun N-terminal kinase (JNK)."}
{"_id": "Radiology$$$95035d4c-dbe3-44f4-bcca-e41dacd0cf61", "text": "Palliative RT may be used to slow down tumor growth, prevent or treat symptoms, and improve quality of life.\n\nCommon applications include prevention of bleeding and pain and treatment of metastases.\n\nBrain and spinal cord metastases are often treated to relieve neurological symptoms.\n\nPalliative RT is often hypofractionated with potentially unique radiobiology.\n\nThe radiobiological mechanisms of palliative RT are currently not well understood."}
{"_id": "Radiology$$$d5b8d73f-67b8-4cca-a9ff-e372386baf0c", "text": "Palliative RT may be used to slow down tumor growth, prevent or treat symptoms, and improve quality of life."}
{"_id": "Radiology$$$1e41fe86-e7a5-4b61-92d2-bdc886b4e215", "text": "Common applications include prevention of bleeding and pain and treatment of metastases."}
{"_id": "Radiology$$$caefc2de-fb13-4a6a-a3fb-f9c56d192aa4", "text": "Brain and spinal cord metastases are often treated to relieve neurological symptoms."}
{"_id": "Radiology$$$f8eee9a3-97ba-4658-baff-335ecd83859e", "text": "The radiobiological mechanisms of palliative RT are currently not well understood."}
{"_id": "Radiology$$$6403507a-fba0-441d-bbae-55f312545e5c", "text": "While radical RT aims to eliminate cancer cells with the intention of cure, palliative RT is used to slow down tumor growth, to prevent or treat symptoms and improve quality of life. It is estimated that more than 50% of RT patients receive palliative RT. This is particularly relevant in populations in less well-resourced countries where the burden of advanced disease is high, and palliation is commonplace (Box 5.11)."}
{"_id": "Radiology$$$1534968d-858b-4daf-af7b-5b55b0e9b994", "text": "Typically, palliative RT is used to treat or prevent bleeding [143\u2013146] or obstruction [147]. In addition, palliative RT is commonly used to treat pain, particularly bone pain, as well as brain and spinal cord metastases to address neurological symptoms [148]. Sites frequently treated palliatively include bone, brain, pelvis, and lung."}
{"_id": "Radiology$$$a6d5db6c-eff5-40a0-975e-eb48a9a9cbe3", "text": "Despite the widespread use of RT with palliative intent, the radiobiology of palliative RT is not well understood. Radiation can reduce tumor burden by targeting proliferating tumor cells, and thus reduce tumor growth and result in relief of obstructions and pressure. However, mechanistic effects of how RT can stop bleeding and pain are still somewhat obscure. It has been speculated that cytokine modulation may alter pain levels and targeting of vascular components may prevent bleeding [149]. Palliative regimens are also typically shorter and frequently involve hypofractionated approaches or single (7\u20138\u00a0Gy) fraction schedules, which may induce differential biological effects to those induced by typical conventionally fractionated radical treatments. Enhanced vascular targeting and immune modulation have been implicated [150]."}
{"_id": "Radiology$$$97b2e400-b451-4d4e-93a1-4e1447a57d54", "text": "Tumor microenvironments (TME) can recourse the tumor origination, expansion, invasion, metastasis, and its response to therapies like RT and chemotherapy.\n\nRT immunomodulates the TME to induce a local anti-tumor immune response leading to tumor regression."}
{"_id": "Radiology$$$4d7c1426-d518-4b0f-a2a3-4b2483a40236", "text": "Tumor microenvironments (TME) can recourse the tumor origination, expansion, invasion, metastasis, and its response to therapies like RT and chemotherapy."}
{"_id": "Radiology$$$89323657-b178-4eeb-8cf8-e375804c6a90", "text": "RT immunomodulates the TME to induce a local anti-tumor immune response leading to tumor regression."}
{"_id": "Radiology$$$25cee9e8-8351-47ef-af01-b116a1df692d", "text": "The tumor microenvironment (TME) is an \u201cecological niche\u201d to facilitate the promotion and the succession of cancer cells. TME intricacy is coupled with tumor expansion, metastasis, and reaction to therapy. Potent alteration stirring in the TME is the basis of tumor cell variant selection, which may endorse genomic instability [31]. Cancer is an exceptionally assorted disease as the cells within the tumor have diverse mutations at different locations within the primary tumor and the metastatic site. Tumor growth and development are not only by actions relating tumor cells, but also by the milieu they inhabit, the TME. In 1889, Stephen Paget introduced \u201cseed and soil\u201d proposition which recommended that metastasis does not occur due to accidental events, but some tumor cells (the \u201cseeds\u201d) nurture ideally in particular organs (the \u201csoil\u201d) and metastases only emerges when the appropriate seed and soil combination takes place [151] (Box 5.12)."}
{"_id": "Radiology$$$9128a123-d3c7-4b20-bfa1-11b95058fbef", "text": "Tumors are normally greatly heterogeneous and intricate in genetics. Different cell types, such as adipocytes, fibroblasts, immune cells, endothelial cells, and neuroendocrine (NE) cells, possess unique purpose in TME (Table 5.11). Acellular constituents of the TME like the extracellular matrix (ECM), extracellular vesicles (EVs), and cytokines remain adjacent to these cells. Physical and chemical uniqueness of the TME that are considered as vital the microenvironmental components comprise of the high interstitial pressure, hypoxia, fibrosis, and low pH. Further, communications involving cells and stromal elements also play an important role in cancer evolution and development [152].Table 5.11\nFunctions of various components of the tumor microenvironment (adapted from [152])\n\nTME components\n\nFunction\n\nNeutrophils\n\nAugmentation of angiogenesis and metastasis; associated with poor diagnosis.\n\nTumor-associated macrophages (TAMs)\n\nPromote deterioration of the extracellular matrix; support the increase of inflammatory cytokines (TNF-\u03b2); augment of angiogenesis and remodeling.\n\nCD8+ cytotoxic T cells (CTL)\n\nProvoke apoptosis, necrosis, and growth arrest by secreting INF-\u03b3 and other cytotoxic cytokines; set up an anti-tumor environment.\n\nRegulatory T cells (Tregs)\n\nExude cytokines such as IL-10, TGF-\u03b2; set up an immunosuppressive environment; associated with poor diagnosis.\n\nMyeloid-derived suppressor cells\u2003(MDSCs)\n\nLinked with tumor development and neoangiogenesis; repress T cells and NK cells; differentiating into TAMs in a hypoxic environment.\n\nMesenchymal stem cells (MSCs)\n\nDifferentiating into mesenchymal tissues such as bone, cartilage, and fat tissues, vasculogenic mimicry; form the premetastatic niche; promoting cancer initiation and malignancy.\n\nEndothelial cells\n\nConstitutes of tumor blood vessels; secreting angiocrine factors such as adhesion molecules; intercommunicating with tumor cells via secreting EVs including CD106, CD49a.\n\nAdipocytes\n\nRegulating the balance of systematic energy and metabolism; secreting exosomes, cytokines, chemokines, and hormones; promoting cancer progression.\n\nNeuroendocrine cells (NE cells)\n\nPromoting proliferative signaling; secreting neurotransmitters, including CgA, chromophilic, and vasoactive polypeptide; regulating NK cell migration and toxicity ability.\n\nVascular network\n\nProviding oxygen, clearing carbon dioxide, and metabolizing wastes; providing nutrition support for cancer cells; promoting angiogenesis and metastasis.\n\nLymph vessels\n\nHelping immune cells to avoid immunity and dissemination; providing a physical link between lymph nodes and tumor.\n\nExtracellular matrix (ECM)\n\nForming the complex macromolecular network; controlling cancer invasion and metastasis, angiogenesis; contribution to growth and proliferation signaling, inhibiting cancer cell apoptosis.\n\nExtracellular vesicles (EVs)\n\nCarrying biologically active molecules such as proteins, miRNAs, and lncRNAs from donor cell to recipient cell; regulating key signaling pathways, proliferation, drug resistance, and stemness; reprogramming stromal cells to create a niche for survival.\n\nCancer-associated fibroblasts (CAFs)\n\nSustaining proliferative signaling; activating angiogenesis and metastasis; tumor-promoting inflammation; evading immune destruction; reprogramming cellular metabolism; promoting genome instability and mutation."}
{"_id": "Radiology$$$d115aa74-1e3a-4119-a4c8-7431b723b3ec", "text": "IR can modify exchanges among tumor cells and their microenvironment. The TME does not only persuade tumor cell proliferation, invasion and metastasis of cancer cells, angiogenesis, modulation of immune cell infiltration and the immune response, but also has a brunt on the therapeutic response [151]. The effects of radiation on the TME diverge with dose and fractionation plan. Radiation stimulates the cellular and DNA damage that can lead to both production as well as release of tumor-associated neo-antigens and secretion of cytokines from tumor and the stromal cells. These proceedings can budge the equilibrium towards an immuno-reactive microenvironment, as contrasting to immunosuppressive microenvironment, causing the recruitment and activation of cytotoxic T cells. Figure 5.22 gives an overview as to how radiation affects the TME.\n\nA diagram of the effects of radiation on the tumor microenvironment involves the cancer cell, dying cancer cell, N K cell, C D 8 plus T cell, T subscript reg cell, D C, activated D C, T A M, C A F, M D S C, endothelial cell, and ionizing radiation.\n\nFig. 5.22\nOverview of effects of radiation on the tumor microenvironment. (Figure adapted from Barker et al. [153], with permission)"}
{"_id": "Radiology$$$ff98cd1d-7fdd-46b3-be6e-1f9434e046b1", "text": "A diagram of the effects of radiation on the tumor microenvironment involves the cancer cell, dying cancer cell, N K cell, C D 8 plus T cell, T subscript reg cell, D C, activated D C, T A M, C A F, M D S C, endothelial cell, and ionizing radiation."}
{"_id": "Radiology$$$9510f64a-b084-4a48-a136-6b28056d7ca8", "text": "The damage induced by IR affects many cells in the TME. The sensitivity of tumor cells is higher to radiation and their death commences the inflammatory signaling cascade. Also, the levels of intercellular adhesion molecule 1 (ICAM) and vascular cell adhesion molecule 1 (VCAM) expression go high as that of the cells of the innate immune system. Interestingly, the upregulation of the integrins present on the endothelial cells is associated with better survival as it acts as a system for radioresistance. Vascular diminution heightened the effect of hypoxia inducing the HIF-1\u03b1 signaling. It also leads to the pro-angiogenic and pro-vasculogenic stimuli through VEGF and chemokine (C-X-C motif) ligand 12 (CXCL12). Following radiation cancer-associated fibroblast (CAF) activation stimulated the altered growth factor secretion and secret several ECM and cytokine modulators. Also, the transforming growth factor-\u03b2 (TGF-B) signaling pathway is not only complex but also pleiotropic. It directly affects the tumor cells and CAFs, driving the HIF-1 signaling and reducing the activation of T cells and the dendritic cells (DC). In the immune compartment, due to high levels of mTOR there is not only an increase in the accessibility of tumor cell antigen but also a boost in the processing of the antigen in combination with damage-associated molecular pattern (DAMP) related Toll-like receptor (TLR) responses. Also, there is an increased pro-inflammatory cytokine signaling to activate the DCs and as a consequence T cells. The activated DCs move to the proximal lymph nodes. In the TME, such signaling is frequently obstructed by high Treg cytotoxic T lymphocyte antigen 4 (CTLA-4) suppression of co-stimulation. Radiation upregulates the NKG2D signals on the tumor cells that enforce direct cytotoxic effects by the CD8+ T cells and NK cells. However, there are other tumor cells which getaway with the PD-L1 signaling but the MDSC derived IL-10 immunosuppression remains intact."}
{"_id": "Radiology$$$077fc175-c43e-42ba-a981-170809bc0a9a", "text": "Hence, depending on the organ, there are organ-specific interstitial cells such as the presence of astrocytes in the central nervous system or the osteoblasts in bone tissues. Such cells are collectively called as the stroma of the tumor and along with other essential factors like the surrounding pH, oxygen levels, extracellular matrix make up the microenvironment of the tumor [139]."}
{"_id": "Radiology$$$53be5cbd-1e0b-4fde-9249-1513bbe3096c", "text": "The tumor cells are known to interact with the stroma or the adjacent milieu. The tumor stroma comprises of a range of diverse cells, and extracellular matrix (ECM), that are known to advocate in limiting the host immune reaction against tumor cells. The tumor stroma puts forward a versatile complex network that maintains the tumor propagation by secreting immunosuppressive cytokine, diverse cellular processes and metabolic alterations [154]. Stromal cells involving the endothelial cells and adipocytes can modify the radiosensitivity by their roles in angiogenesis and vasculogenesis, and their secreted adipokines, respectively. The extracellular matrix can control radiation sensitivity by manipulating the oxygen proximity and managing the equilibrium and bioavailability of growth factors and cytokines [155]. Even though several RT-mediated stromal transformations like the renewal of or polarization towards tumor-suppressing immunity are valuable, RT can operate as a double-edged sword in tumors."}
{"_id": "Radiology$$$0eed99b4-e7fc-44fb-bed9-8c9f4d3f03b1", "text": "Chronic inflammation is one of the radiation effects on the stroma which acts as a chief driver of fibrosis during which there is occurrence of persistent immune responses in addition to tissue remodeling and repair processes. Some of the radiation-induced alteration on the TME is by altering the way CAFs manage their collagen assembly. In addition, CAFs that receive RT-undergo variation and modification in terms of their variety, secretome, and phenotype. Moreover, RT augments the stimulation of the proliferating machinery linking the RAS and mitogen-activated protein kinase (MAPK) signaling pathway; the invasion pathway that is associated with tumor evolution, resistance, and metastasis. When the stroma receives RT, there is augmentation in the invasiveness of the tumor because of the augmented hepatocyte growth factor (HGF)/c-Met (HGF receptor) signaling and MAPK activity. This aids the improvement in the tumor movability which can prove to be fatal. RT can also stimulate the stromal traits that can potentially impart resistance to therapy. Studies are still ongoing in understanding as to how fractionated RT alters the TMEs stromal machinery and how all the modifications can affect after the cancer cells response to RT [155]."}
{"_id": "Radiology$$$d631b07e-82fe-40f4-aee6-b0adeef73d21", "text": "An important feature of solid tumors is the vascular network that develops from the vasculogenesis, angiogenesis, and fibroblasts. A characteristic of these vessels is that they lack their supporting pericytes or basement membrane, which makes them vulnerable to radiation [156\u2013158]. When tumor tissue is exposed to radiation, blood vessels at the level of the microvessel network are firstly destructed and the degree of this destruction depends on the radiation dose. The vessel\u2019s thickness increases, which raises the risk of atherosclerotic changes and intimal proliferation, since the destructed microvessel network reduces distance between functional vessels and vascular density, resulting in hypoperfusion. Irradiation not only modulates the vessel structure, but it also has long-term effects, including medial necrosis and fibrosis, but these effects are affected by radiation dose. When a radiation dose is high, for instance, blood flow is permanently reduced; necrosis and fibrosis are produced, and the tumor is revascularized by vasculogenesis, which is a disorganized process of vessel growth in comparison to angiogenesis. Secondly, radiation to tumor tissue induces the chemokine receptor CXCR4 which induces bone marrow of matrix metalloprotease 9 that is responsible for radiation vasculogenesis and subsequent post irradiation [159, 160]."}
{"_id": "Radiology$$$625d712f-ee0a-4574-b19f-0cecdc10cdff", "text": "IR kills cancer cells directly (atomic ionization) and indirectly (radiolysis of water) [16, 20, 158]. IR also induces a host immune response to tumor cells and facilitates tumor recognition and healing. These effects occur in a variety of ways, including immune response signaling. When cells are dying, they translocate calreticulin (ERp57) and their endoplasmic reticulum (ER) protein complex to the cell membrane which functions as a \u201ceat me\u201d signal. Secondly, upon IR of a tumor, inflammatory molecules, such as ATP and high mobility group protein B1 (HMGB1), are released, promoting a T cell and DC response. Signaling of this type uses three types of signals in anti-tumor immune responses, which are:1.\nDCs take captive of released danger signals and process them.\n\u00a02.\nDanger signals are presented into T cells by MHC molecules. As a result, na\u00efve tumor-specific T cells are activated and become effector T cells.\n\u00a03.\nFinally, macrophages and DCs may be recognized by cytotoxic T cells, and they destroy remaining cells of tumor tissues through their circulation through the bloodstream [161\u2013165]."}
{"_id": "Radiology$$$d5b9f3c5-af2f-4359-8c35-c0fcb0b3fb65", "text": "Danger signals are presented into T cells by MHC molecules. As a result, na\u00efve tumor-specific T cells are activated and become effector T cells."}
{"_id": "Radiology$$$997a8f7f-c346-4308-8250-2ce16e8215a7", "text": "Finally, macrophages and DCs may be recognized by cytotoxic T cells, and they destroy remaining cells of tumor tissues through their circulation through the bloodstream [161\u2013165]."}
{"_id": "Radiology$$$8e76b921-af6e-48dc-947c-a2c1b084752b", "text": "However, not all irradiated cells sustain damage, and some survive. These IR surviving cells may expose surface molecules like antigen-presenting molecules of major histocompatibility complex class I (MHCI), death receptor Fas, and ICAMs which lead to an improvement in the recognition and killing of tumors by immune cells that are reactivated by tumor antigens."}
{"_id": "Radiology$$$3202c85f-bf5a-4970-9111-d1ccad8ce3ab", "text": "To cure tumors, radiation needs to cause cell death. There are five different types of cell death depending on the pathways in the response system of DNA damage, namely, apoptosis, senescence, autophagy, mitotic catastrophe, and necrosis [13, 157, 158]. Via apoptosis pathways macrophages may be triggered to clean out these dying cells which causes polarized M1 macrophages thereby driving an anti-tumor immune response and indirectly killing of tumors. However, this process may also contribute to carcinogenesis and inflammation [163]."}
{"_id": "Radiology$$$f88d6f72-629a-4175-8035-3e1e8537bd67", "text": "The most well-known tumors in declining order of radiosensitivity as follows: (1) lymphoma, (2) embryonal tumors, (3) cellular anaplastic tumors, (4) basal cell carcinoma, (5) adenoma and adenocarcinoma, (6) desmoplastic tumors, such as squamous carcinoma, (7) fibroblastic sarcoma; osteosarcoma; neurosarcoma. Tumors composed of fast-growing cells like the embryonal tumors are sensitive to radiotherapy."}
{"_id": "Radiology$$$8a5e1e28-d5d1-4105-b25c-4baa46d2938c", "text": "Lymphoid cells are predominantly vulnerable to radiation. On the other hand, the radioresistant category comprises of the neurosarcomas, gliomas, and melanomas. Tumor sensitivity to radiation is affected by the variation on the radiosensitivity exhibited by the subgroups of major cancer forms. There are numerous factors affecting the cancer radiosensitivity and at times they are even obscure. The most important factor that plays the most vital role in influencing the tumor behavior under RT is the general condition of the patient. Also, there is an explicit association between radiosensitivity and the grade of malignancy which might not be uniform always. Hence, all these factors should be carefully evaluated before imparting radiotherapy and predicting its outcomes."}
{"_id": "Radiology$$$9033fddf-4975-4c49-9bcc-a1913b343fda", "text": "One of the most prominent factors imparting the tumor radiosensitivity and which was recognized very early on was the high metabolism of the tumor cells. This is similar to the fast growth and also understood as the tumor growth rate imparting radiosensitivity. Augmented or uneven vascularity also goes with fast growth. These factors combined provide the rapidly growing tumor cells with sensitivity to radiation. Especially when tumors are bulky hypersensitivity can be encountered in the treatment of such tumors. Therefore, to avoid accidents like bulky necrosis or interstitial hemorrhage appropriate precaution should be taken. Other factors like the large quantity of autolytic cell ferments and susceptibility of mitotic nuclei are also crucial in imparting tumor sensitivity to rapidly growing tumor cells. It is seen that the tumors exhibiting the embryonic trait in the origin cells provide the complete group of embryonal tumors a very high radiosensitivity. Hence, their response to radiation treatment is probably quicker and complete compared to other tumors. Therefore, such tumors should be identified as especially favorable."}
{"_id": "Radiology$$$ad0c732d-052e-4d1d-8f7c-d91889c5f5ac", "text": "While radiation effects classically result from direct damage to cells and tissues within the target, effects outside the field also known as abscopal effects have been observed in both tumors and normal tissue. For example, irradiation often leads to systemic fatigue [166], and bilateral pneumonitis sometimes occurs after unilateral lung irradiation [167]. Occasionally, metastatic tumors have been observed to regress dramatically outside the primary irradiation field, which is a manifestation of the systemic anti-tumor effect [168]."}
{"_id": "Radiology$$$d38c6302-c56c-4dfd-82fa-655253b7c60c", "text": "An illustrative example is the case of a man diagnosed with ulcerated malignant melanoma in his left arm [169]. The arm was resected, and no further treatment was indicated. Twenty months later, the patient had a painful skin lesion on the head and an asymptomatic metastatic lesion in the lung. The skin lesion was irradiated with 3 Gy in 10 sessions, after which the lesion and pain disappeared. Unexpectedly, the lung lesion also disappeared although it had never been treated. Reports of cases of abscopal effects in melanoma are relatively common. Another example is the case of a woman with squamous carcinoma of the anal canal with metastases to pelvic lymph nodes, liver, and bone. After palliative RT limited to the pelvis with sensitizing chemotherapy, complete regressions were observed 4\u00a0months after treatment not only in the primary tumor but also in the bone and liver metastases, an effect that persisted 4\u00a0years later [170]. Figure 5.23 gives an overview as to how radiation induces Abscopal Effects.\n\nA diagram of a patient with the tumor metastasized to the head and lungs after 12 months display inset images of tumor antigens, cell death, tumor neoantigens, and danger signals that forwards to an anti-tumor immune response.\n\nFig. 5.23\nThe abscopal effect of RT. On the left side of this schematic case, the patient suffers from a tumor in the shoulder (e.g., a melanoma) that has metastasized to the lung. The treatment protocol consisted of surgery of the primary tumor and the metastatic nodules were treated with a combination of RT and immune checkpoint blockade, which promotes abscopal anti-tumor immunity. On the right side of this schematic case, RT triggers the release of tumor antigens, neoantigens, and DAMPs, which are recognized and processed by macrophages and DCs. Subsequently, these antigen-presenting cells present these tumor antigens to T cells in a draining lymph node of the tumor. The antigen-presenting cells are then taken up by cytotoxic T cells, which subsequently destroy the remaining cells of the cancerous tissue"}
{"_id": "Radiology$$$946be3c5-c30a-4034-848a-0e1f61a60203", "text": "A diagram of a patient with the tumor metastasized to the head and lungs after 12 months display inset images of tumor antigens, cell death, tumor neoantigens, and danger signals that forwards to an anti-tumor immune response."}
{"_id": "Radiology$$$9cc4c14f-b64e-4d96-8454-e101b0999d7c", "text": "The previous clinical cases showing unexpected regression of tumors outside the irradiated field are examples of a phenomenon first described by Mole as the \u201cabscopal effect\u201d [171]. The word abscopal comes from the Latin ab (position away from) and Scopus (target). However, there is now clear evidence that the abscopal effects associated with RT are due to systemic anti-tumor immune responses triggered by the RT. However, despite millions of patients receiving RT, abscopal effects are too unpredictable to be a therapeutic target, as only a limited number of cases have been identified. In a recent study, only 46 cases were identified between 1969 and 2014 [172]. With the advent of immune checkpoint blockade therapy, clinical interest has soared. Since the introduction of the anti-CTLA-4 antibody ipilimumab into clinical practice in 2011, abscopal effects have been observed in several patients who received RT while taking ipilimumab [173, 174]. Other immune checkpoint therapies have also shown promise. There are reports of abscopal effects following treatment with RT and anti-PD1 therapies such as pembrolizumab or nivolumab [175]. In this section, we will cover the biological events in cancer cells that precede the occurrence of radiation-induced abscopal effects."}
{"_id": "Radiology$$$9cd02c3a-7ecd-4a9a-bba2-70cb740151f5", "text": "Radiation can alter the immunogenicity of tumors by promoting tumor antigens, neoantigens, and danger signals."}
{"_id": "Radiology$$$bf416f2a-3d20-4d18-82b1-3e9d0b10ca65", "text": "Tumor antigens result from protein degradation due to damage to cellular proteins caused by radiation-induced free radicals. Radicals such ROS are generated during radiation-induced radiolysis of water. RT then causes cellular damage that is independent of DNA and leads to an increase in the pool of peptides, i.e., tumor antigens that bind to the major histocompatibility complex (MHC) [176]."}
{"_id": "Radiology$$$0aefc006-0752-45af-ba88-52715fd4d38d", "text": "Tumor neoantigens are tumor-specific antigens resulting from the expression of a large number of mutations which may be a result of tumor genetic instability but also due to severe DNA damage. The degrees of DNA damage can strongly influence the immunogenicity of the tumor. In this context, RT leads to DNA SSBs or DSBs or other DNA alterations (see Chap. 3) [177]. DSBs are the most lethal DNA lesions if not repaired. Repair depends on the type of radiation causing the damage. Low LET radiation causes simple DSBs, which are repaired by NHEJ pathway. High LET radiation causes clustered DNA lesions (or multiple damaged sites) that are usually repaired by HR. Non-DSB lesions at clustered DNA damage sites are corrected with Base Excision Repair. If the DNA repair mechanisms are not sufficient to repair the damage, or if the RT itself causes defects in the DNA repair mechanisms, mutations occur that can lead to the expression of tumor neoantigens. These neoantigens are then processed by tumor cells and presented by MHCs [178]."}
{"_id": "Radiology$$$fb44e768-8ae8-4b8c-bf09-33eb16f47a1b", "text": "Damage signals properly known as Damage-Associated Molecular Patterns (DAMPs) are endogenous molecular signals released by irradiated cells after damage or when dying [176]. These signals enable enhanced recognition and killing of the tumor by macrophages and DCs resulting in antigen presentation to T cells [161, 164]. Some of the most frequently found radiation-induced DAMPs in tumor cells are:\nFragmented double-stranded DNA and micronuclei. These self-DNA fragments and micronuclei appear as cytosolic DNA in tumor cells, which are later recognized by immune cells.\n\nHigh mobility group box 1 (HMGB1) is a nuclear protein associated with chromatin that is released extracellularly by dying tumor cells, normally necrotic cells [179]. HMGB1 binds to Toll-like receptor 4 (TLR4) expressed by DCs and activates them.\n\nNucleotide release by apoptotic cells function as a chemotactic signal for phagocytic myeloid cells including DCs by stimulating the Purinergic receptor 2 (P2RY2) [180].\n\nExtracellular ATP can also function through the activation of Purinergic receptor 7 (P2RX7) to initiate inflammasome activation and subsequent Interleukin 1\u03b2 production. This mechanism was shown to be required for the induction of tumor antigen-specific CD8+ T cells following challenge with dying tumor cells [181].\n\nCalreticulin is an ER protein that gets translocated to the cellular membrane after RT. Calreticulin is essential for efficient uptake of dying tumor cells by antigen-presenting cells [182].\n\nChemokines are a frequent part of DAMPs. Chemokines, such as C-X-C motif (CXC) ligand 16, 10, and 19 (CXCL16, CXCL10, and CXCL9), are known for being released after radiation exposure; they trigger differentiation of immune cells, and stimulate immune modulators such as Interferons, Tumor necrosis factor \u03b1, and Interleukin 1\u03b2 [162, 183\u2013185]."}
{"_id": "Radiology$$$8d17d49b-94ed-421e-98a3-e172c71eff7e", "text": "Fragmented double-stranded DNA and micronuclei. These self-DNA fragments and micronuclei appear as cytosolic DNA in tumor cells, which are later recognized by immune cells."}
{"_id": "Radiology$$$7a7b7440-5558-4d9a-aabc-441bc1d9a836", "text": "High mobility group box 1 (HMGB1) is a nuclear protein associated with chromatin that is released extracellularly by dying tumor cells, normally necrotic cells [179]. HMGB1 binds to Toll-like receptor 4 (TLR4) expressed by DCs and activates them."}
{"_id": "Radiology$$$e347eaa3-def9-430e-b413-65e2008f160d", "text": "Nucleotide release by apoptotic cells function as a chemotactic signal for phagocytic myeloid cells including DCs by stimulating the Purinergic receptor 2 (P2RY2) [180]."}
{"_id": "Radiology$$$115ad0fc-69e9-4817-8e2b-d2c37f1a4194", "text": "Extracellular ATP can also function through the activation of Purinergic receptor 7 (P2RX7) to initiate inflammasome activation and subsequent Interleukin 1\u03b2 production. This mechanism was shown to be required for the induction of tumor antigen-specific CD8+ T cells following challenge with dying tumor cells [181]."}
{"_id": "Radiology$$$ba312bec-eb15-4c53-a970-235ffb2eac0e", "text": "Calreticulin is an ER protein that gets translocated to the cellular membrane after RT. Calreticulin is essential for efficient uptake of dying tumor cells by antigen-presenting cells [182]."}
{"_id": "Radiology$$$0a5f87f7-ba87-4bf1-9037-8bbe6a934094", "text": "Chemokines are a frequent part of DAMPs. Chemokines, such as C-X-C motif (CXC) ligand 16, 10, and 19 (CXCL16, CXCL10, and CXCL9), are known for being released after radiation exposure; they trigger differentiation of immune cells, and stimulate immune modulators such as Interferons, Tumor necrosis factor \u03b1, and Interleukin 1\u03b2 [162, 183\u2013185]."}
{"_id": "Radiology$$$1db8ce84-1c89-4c5b-8316-8897f35605ef", "text": "In summary, radiation increases the immunogenicity of tumors by simultaneously promoting the release of tumor antigens, neoantigens, and DAMPs. This radiation-induced immunogenicity may counteract the progression of tumors that have escaped immune surveillance, especially if an abscopal effect can be triggered."}
{"_id": "Radiology$$$ef121c3c-f609-45c4-aaca-bc77b2b153f8", "text": "To reproduce the radiation-induced abscopal effect has been challenging as its underlying biological mechanisms are not fully understood. However, some crucial cellular signaling pathways have been identified alongside the IR doses that appear to be fundamental for their occurrence.\nThe accumulation of cytosolic double-stranded DNA fragments (dsDNA) is usually a sign of microbial infection and alerts the host\u2019s innate immune system to initiate a defense response. Interestingly, the accumulation of dsDNA after RT has been shown to be an essential step in the abscopal response. Mitochondrial DNA and dsDNA are recognized by cyclic GMP-AMP synthase (cGAS), which produces messengers that bind and activate the transmembrane protein Stimulator of interferon genes (STING), triggering a robust innate immune response [186]. In particular, activation of the type I interferon signaling pathway (IFN-1) and production of Interferon \u03b2 cytokines by cancer cells trigger the accumulation of basic leucine zipper ATF-like transcription factor 3 (Batf3)-dependent DCs, which are required for the maturation of anti-tumor CD8+ T cells.\n\nThe irradiation dose and fractionation schemes are crucial for the induction of abscopal effects. With increasing radiation dose, more dsDNA fragments accumulate in the cytoplasm of cancer cells. However, the increased radiation dose of over 12 Gy also triggers the activation of three prime repair exonuclease 1 (Trex1), which degrades dsDNA and prevents an immune response. Interestingly, Interferon \u03b2 production can be enhanced with repeated radiation doses that do not trigger Trex1 [186]. Radiation regimens that have been shown to be effective in preclinical and clinical studies are 3\u00a0\u00d7\u00a08 and 5\u00a0\u00d7\u00a06 Gy.\n\nTransforming growth factor beta (TGF-\u00df) is a potent immunosuppressive cytokine in established tumors that impairs the antigen presentation function of DCs, prevents T cell priming and thus inhibit the abscopal effect [164].\n\nTGF-\u03b2 expression increases in irradiated tissues. However, the abscopal effect can be restored if TGF-\u03b2 neutralizing antibodies are administered during RT. Current research is investigating if the use of dual-function drugs that simultaneously target TGF-\u03b2 and PD -L1 in combination with RT can be a good strategy to overcome tumor immune escape [187]."}
{"_id": "Radiology$$$fdcc1cf0-747f-40ce-856e-9e79af5c2b5e", "text": "The accumulation of cytosolic double-stranded DNA fragments (dsDNA) is usually a sign of microbial infection and alerts the host\u2019s innate immune system to initiate a defense response. Interestingly, the accumulation of dsDNA after RT has been shown to be an essential step in the abscopal response. Mitochondrial DNA and dsDNA are recognized by cyclic GMP-AMP synthase (cGAS), which produces messengers that bind and activate the transmembrane protein Stimulator of interferon genes (STING), triggering a robust innate immune response [186]. In particular, activation of the type I interferon signaling pathway (IFN-1) and production of Interferon \u03b2 cytokines by cancer cells trigger the accumulation of basic leucine zipper ATF-like transcription factor 3 (Batf3)-dependent DCs, which are required for the maturation of anti-tumor CD8+ T cells."}
{"_id": "Radiology$$$7e206dd6-6d00-4345-a023-a6898e4bcc24", "text": "The irradiation dose and fractionation schemes are crucial for the induction of abscopal effects. With increasing radiation dose, more dsDNA fragments accumulate in the cytoplasm of cancer cells. However, the increased radiation dose of over 12 Gy also triggers the activation of three prime repair exonuclease 1 (Trex1), which degrades dsDNA and prevents an immune response. Interestingly, Interferon \u03b2 production can be enhanced with repeated radiation doses that do not trigger Trex1 [186]. Radiation regimens that have been shown to be effective in preclinical and clinical studies are 3\u00a0\u00d7\u00a08 and 5\u00a0\u00d7\u00a06 Gy."}
{"_id": "Radiology$$$b6085e58-6cdb-4f99-9009-9066e5926710", "text": "Transforming growth factor beta (TGF-\u00df) is a potent immunosuppressive cytokine in established tumors that impairs the antigen presentation function of DCs, prevents T cell priming and thus inhibit the abscopal effect [164]."}
{"_id": "Radiology$$$b461793f-0b9a-4580-9fb5-318c8b040a58", "text": "TGF-\u03b2 expression increases in irradiated tissues. However, the abscopal effect can be restored if TGF-\u03b2 neutralizing antibodies are administered during RT. Current research is investigating if the use of dual-function drugs that simultaneously target TGF-\u03b2 and PD -L1 in combination with RT can be a good strategy to overcome tumor immune escape [187]."}
{"_id": "Radiology$$$252b32d4-b04a-4b43-a741-1c25fae917dc", "text": "The tolerance of normal tissues to RT is the limiting factor in delivering a radiation dose high enough to eradicate tumor cells [188, 189]. The dose delivered to the target structure is limited by the dose constraints to the organs at risk (OAR), which are in close proximity to the tumor. In the case of external RT, standard recommendations for OAR doses have been issued based on the volumes irradiated and are regularly updated to reflect new practices."}
{"_id": "Radiology$$$234d1176-cb9c-4d1c-b202-4f2c21ff147f", "text": "Despite ongoing technical and technological advances, the planning target volume (PTV) necessarily contains a volume of normal tissue for several reasons. First, the target volume, which receives the prescribed dose, is always larger than the actual tumor volume. Indeed, this volume must take into account the visible tumor volume (gross tumor volume, GTV), the possible microscopic extension of the tumor (clinical target volume, CTV), the movements of the different volumes (internal target volume, ITV), small errors in patient set-up and technical precision, all together making up the PTV. Secondly, the tumor contains normal tissues such as soft tissues and blood vessels, which receive the entire prescribed dose. Finally, especially for external beam RT, the radiation beam inevitably passes through normal tissue, depositing doses that may be clinically relevant. Effective RT is therefore necessarily associated with a risk of adverse effects. Side effects may occur during RT or a few weeks after treatment (acute effects). In the long term, late effects, which may occur months or years after RT, are the most critical because they are chronic, disabling, painful, and most often irreversible."}
{"_id": "Radiology$$$5f918618-fccb-4b49-b869-bc4d6b8b12e6", "text": "Limiting adverse events to reduce morbidity and optimize the therapeutic index of RT remains a priority in the fight against cancer. To this end, NTCP modeling is widely used in treatment planning as a tool to differentiate treatment plans [11]. In future, cellular and animal models of radiotoxicity aimed at understanding the sequence of molecular and cellular events that drive the pathogenesis of early and late normal tissue radiation injury should enable the development of tools to reduce the impact of RT on normal tissues [190]."}
{"_id": "Radiology$$$e99cfb7c-f4b4-42db-a91f-bd21d8df6501", "text": "Acute effects of radiation are observed in days to weeks after exposure.\n\nThe time scale of clinical manifestation of most acute responses is independent of the radiation dose and related to the proliferative rate of injured cells.\n\nAcute effects are transient and reversible.\n\nTypical acute responding normal tissues are: intestine, mucosa, skin, hair follicles, bone marrow."}
{"_id": "Radiology$$$026f9297-eda2-466f-a4d7-4ab19739de25", "text": "Acute effects of radiation are observed in days to weeks after exposure."}
{"_id": "Radiology$$$e49a5436-a594-4c16-8d8c-a9b14929709c", "text": "The time scale of clinical manifestation of most acute responses is independent of the radiation dose and related to the proliferative rate of injured cells."}
{"_id": "Radiology$$$7a817c6a-84a3-44cc-b528-225e8965066d", "text": "Typical acute responding normal tissues are: intestine, mucosa, skin, hair follicles, bone marrow."}
{"_id": "Radiology$$$26369824-09eb-4d30-8147-c23e419f14fa", "text": "Acute responses are primarily observed in tissues with rapid cell renewal where cell division is required to maintain the function of the organ. In these renewing tissues, physiological cell loss occurs constantly from the post-mitotic tissue compartments while actively cycling cell populations in the germinal parts of the tissue proliferate to replenish them. The radiation response is related to death of critical cell populations such as the stem cells in the crypts of the small intestines, in the bone marrow, or in the basal layer of the skin. When sufficiently large numbers of critical cell populations are affected, cell production capacity is no longer able to compensate for the physiologically occurring cell loss, leading to hypoplasia and cell depletion. For this reason, the time scale of clinical manifestation of most acute responses is independent of dose and instead reflects the rate of loss of functional cells and the demand of proliferation of the supporting stem cells of the different tissues (Box 5.13)."}
{"_id": "Radiology$$$3c542a70-afde-40d2-8823-668c340b78de", "text": "In general, acute responses are transient, but sensitive to the overall radiation treatment time. Recovery may occur by rapid repopulation from the surviving stem cell compartment or by recruitment of stem cells from neighboring sites (non-irradiated/damaged areas). Hence, the latent period of manifestation of tissue reactions is specific, depending on the cell type and its proliferation rate (Table 5.12) as well as on its intrinsic sensitivity to radiation and capacity to repair damaged DNA.Table 5.12\nTissue and target cell-specific latency times\n\nTissue\n\nTarget cells\n\nLatency times (after single exposure)\n\nEpidermis\n\nBasal cells\n\n3\u20134\u00a0weeks\n\nGI-tract\n\nCrypt cells\n\n<1\u00a0week\n\nBone marrow\n\nHematological stem cells and precursor cells\n\n0.5\u20132\u00a0weeks\n\nTestes\n\nSpermatogonial stem cells\n\n2\u20134\u00a0weeks"}
{"_id": "Radiology$$$44670a08-9a02-462c-87e3-11e5cf006070", "text": "Apart from the number of sterilized cells, several other non-lethal mechanisms like proliferative impairment and disturbances in molecular cell signaling play a role in the acute tissue reaction to radiation. For example, the release of 5-hydroxytryptamine by mast cells have been shown to be responsible for several early clinical reactions such as erythema following irradiation of the skin and nausea/vomiting following irradiation of the intestines. Immunological reactions associated with local and systemic release of cytokines have also been demonstrated. In the hematopoietic system, apoptosis plays an important role in acute normal tissue response. Apoptotic death directly following irradiation, particularly of the lymphoid lineage, causes additional cell loss on top of the physiological cellular loss rate of circulating cells and explains earlier onset particularly for the lymphoid lineage. Furthermore, the typical tissue or organ architecture has a principal role in the response to irradiation. Threshold irradiation doses (Table 5.13) are often dependent on the irradiated normal tissue volume.Table 5.13\nThreshold radiation doses for a selected group of tissues. Estimate of threshold doses for an approximate 1% incidence of morbidity for early and late tissue reacting human tissues and organs following acute exposure to radiation (modified after Table 4.4 from [191])\n\nOrgan/tissue\n\nThreshold dose (Gy)\n\nBiological effect\n\nLatency period\n\nTestis\n\n~0.10\n\nTemporary sterility\n\n3\u20139\u00a0weeks\n\nTestis\n\n~6\n\nPermanent sterility\n\n3\u00a0weeks\n\nOvaries\n\n~3\n\nPermanent sterility\n\n<1\u00a0week\n\nBone marrow\n\n~0.5\n\nDepression of hematopoiesis\n\n3\u20137\u00a0days\n\nSkin (large areas)\n\n<3\u20136\n\nMain phase of skin reddening\n\n1\u20134\u00a0weeks\n\nSkin (large areas)\n\n5\u201310\n\nSkin burns\n\n2\u20133\u00a0weeks\n\nSkin\n\n~4\n\nTemporary hair loss\n\n2\u20133\u00a0weeks\n\nSkin (large areas)\n\n10\n\nLate atrophy\n\n>1\u00a0year\n\nSkin (large areas)\n\n10\n\nTelangiectasia at 5\u00a0years\n\n>1\u00a0year\n\nEye\n\n~0.1 per 5\u00a0yearsa\n\nCataract (visual impairment)\n\n>20\u00a0years\n\nBrain\n\n0.1\u20130.2\n\nCognitive defects infants <18\u00a0months\n\nSeveral years\n\nCarotid artery\n\n~0.5\n\nCardiovascular disease\n\n>10\u00a0years\n\nKidney\n\n~7\u20138\n\nRenal failure\n\n>1\u00a0year\n\na\u00a0An equivalent dose limit for the lens of the eye of 20\u00a0mGy/year is recommended for workers. The dose should be spread over defined 5\u00a0years periods, with no single year exceeding 50\u00a0mGy [192]"}
{"_id": "Radiology$$$aa90e763-13b9-4a00-a43b-97c6c6f03143", "text": "The tissue architecture is generally organized in the so-called functional subunits (FSUs). Some tissues are built of anatomically demarcated FSUs, like nephrons in the kidney, liver- and lung lobules. These types of organs\u2014with a parallel arrangement of FSUs show large reserve capacity. Non-radiation exposed volumes of the organ can take over the function of the damaged tissue. Other tissue types like the spinal cord and mucosa do not show clear anatomical demarcation in FSUs. In such serial arranged FSUs tissues, radiation injury to a small tissue volume can result in function loss of a larger volume or even the whole organ. The threshold radiation dose can be defined as the safe, tolerated, dose below which no tissue-specific reaction occurs. This particular dose is difficult to determine [191]. In general, it is the estimated dose that is required to cause a typical tissue reaction in 1% of the exposed individuals (ED1) relative to non-irradiated controls. To be noticed is that radiation doses <ED1 could also induce biological effects above baseline levels in non-irradiated, age-matched individuals, i.e., above natural incidence. Table 5.13 lists threshold doses and latency times for tissue reactions to a single radiation exposure for a selected number of healthy tissues and organs."}
{"_id": "Radiology$$$e56b37ca-3763-4073-b490-14beea362de2", "text": "Late effects of radiation occur months, years, or decades after radiation therapy.\n\nLate effects are progressive and irreversible.\n\nThe latent phase of chronic reactions is inversely proportional to the radiation dose.\n\nThe late effects are based on an interactive response of parenchymal cells, vascular endothelium and fibroblasts, with a contribution from immune cells, especially macrophages, as well as other cells.\n\nTissues and organs are affected by atrophy, fibrosis, and/or necrosis, which can severely impair their functions and lead to a loss of function."}
{"_id": "Radiology$$$08aae0d7-c807-4987-bb6d-d4d5a0181263", "text": "Late effects of radiation occur months, years, or decades after radiation therapy."}
{"_id": "Radiology$$$0d75e252-34ee-41bc-b474-7328b5303974", "text": "The latent phase of chronic reactions is inversely proportional to the radiation dose."}
{"_id": "Radiology$$$0549dca8-b712-4042-aeb5-f19ae8d07536", "text": "The late effects are based on an interactive response of parenchymal cells, vascular endothelium and fibroblasts, with a contribution from immune cells, especially macrophages, as well as other cells."}
{"_id": "Radiology$$$e585b969-5596-4583-8de1-362a429e9dc4", "text": "Tissues and organs are affected by atrophy, fibrosis, and/or necrosis, which can severely impair their functions and lead to a loss of function."}
{"_id": "Radiology$$$11914bd5-8612-40ed-9984-22498a370728", "text": "The classification that distinguishes between early and late effects is based exclusively on the time of first diagnosis of pathological changes, with a threshold arbitrarily set at 3\u00a0months after the start of RT [5, 193]. Unfortunately, there is no general biological rationale for this threshold, whereas a classification of early and late effects is clinically relevant and essential for comparing studies. Nevertheless, there are specific biological characteristics of early and late effects that distinguish them (Tables 5.13 and 5.14). As discussed in Sect. 5.13.2, the early symptoms most often appear in highly proliferative tissues, such as the intestinal mucosa, epidermis, and bone marrow. In these tissues, irradiation causes a progressive but potentially reversible depletion of cells by preventing their physiological renewal, associated with a direct or indirect radiation-induced inflammatory reaction. In contrast, late side effects can affect all tissues. The pathogenesis leads to fibrosis, atrophy, vascular damage as well as other detrimental side effects on normal tissues such as hormonal deficiencies, infertility, and second malignancies (discussed in Chap. 7). Late side effects are chronic, progressive, in most cases irreversible and their severity tends to increase over time (Fig. 5.24 and Box 5.14).Table 5.14\nTypical characteristics of acute and late responding normal tissues and organs. Please note that early as well as late effects could occur in the same tissue or organ\n\u00a0\nEarly reactions\n\nLate reactions\n\nCell turnover of target cells\n\nHigh\n\nLow\n\nLatency\n\n<90\u00a0days\n\n>90\u00a0days\n\nTime factor\n\nShorter time\n\nNo influence of time\n\n>Damage\n\nClinical course\n\nTransient\n\nIrreversible\n\nFractionation sensitivity\n\nLow\n\nHigh\n\n\u03b1/\u03b2 ratio\n\n~10 Gy\n\n~3 Gy\n\nExamples:\n\nMucositis dermatitis bone marrow depletion (tumor response)\n\nMyelopathy\n\nIntestinal fibrosis\n\nTelangiectasia\n\n\nA diagram of the late or chronic normal tissue responses from months, years, to decades for repair and remodeling cycles and chronic inflammation with 3 stages from vascular and parenchymal damage to dysfunction or loss of function.\n\nFig. 5.24\nRadiation-induced chronic damage to healthy tissues. Late damage develops within months to decades post RT and may concern all normal tissues. Successive cycles of tissue remodeling and repair, together with chronic inflammation induce vascular and parenchymal damage leading to tissue atrophy/fibrosis/necrosis compromising organ function"}
{"_id": "Radiology$$$009c0822-b36d-4679-b56a-c73437f82ea1", "text": "A diagram of the late or chronic normal tissue responses from months, years, to decades for repair and remodeling cycles and chronic inflammation with 3 stages from vascular and parenchymal damage to dysfunction or loss of function."}
{"_id": "Radiology$$$11b2e4db-eedd-4ed5-b4de-78567af7f5df", "text": "The mechanisms that lead to these effects are more complex than for acute effects. They involve organ-specific changes in parenchymal cells, including cell death and alterations in cellular metabolism. Consequential late effects from severe acute reactions may contribute to chronic damage due to unresolved regeneration of rapidly proliferating tissues which contributes additional damage to connective tissue and endothelium [194]."}
{"_id": "Radiology$$$cf25ab7f-faba-4ea0-b4cf-acafff697c5e", "text": "The pathogenesis leading to radiation-induced fibrosis is a result of fibroblast differentiation into myofibroblasts, proliferation of surviving fibroblasts and extracellular matrix and collagen deposition. Seen as wound healing that goes wrong, this pathological process plays a key role in the development and expression of most late effects. Atrophy is caused by the loss of fibroblasts and collagen reabsorption. Examples of fibrotic-atrophic response include hardening and shrinkage of an irradiated breast, or strictures and malabsorption of irradiated small intestine. Vascular damage is caused by either small vessel dilation or constriction as well as losses of the vascular endothelial cells from small blood vessels and capillaries. Vascular damage results, for instance, in skin telangiectasias, bleeding, ischemia with intestinal perforation and fistula formation. The immune system also contributes significantly to the tissue response through the involvement of macrophages and mast cells, which interact with other cells in the irradiated tissue and other organs through the release of cytokines and growth factors [195\u2013198]. More generally, the response of a tissue is mediated by different types of cells such as inflammatory, stromal, endothelial, and parenchymal cells that actively communicate through the release of cytokines, chemokines and growth factors, and/or the activation of molecular pathways downstream of these messengers. Altogether, these effects lead progressively to parenchymal damage and potentially to loss of organ function in the irradiated volume."}
{"_id": "Radiology$$$6ff32457-5815-4390-8025-dbc83dbffb24", "text": "The tissues of cancer survivors treated with RT still bear the traces of RT to varying degrees. Although patients are usually asymptomatic, all irradiated patients, especially those with late effects, have a common histological feature of radiation-induced fibrosis and atrophy. Fibrosis predominates in the breast, skin, small intestine, lungs, kidneys, and liver, while atrophy and necrosis predominate in the later stages after RT alone or in combination with surgery and local trauma to bone (osteoradionecrosis of the mandible, ORN), nerve, or brain. The clinical severity correlates with the extent of the underlying pathophysiological process, which is usually invisible and often depends on the level of parenchymal cell loss."}
{"_id": "Radiology$$$c44029f3-7158-4eb1-9b85-5136b8a1a495", "text": "It is often mentioned that 5\u201310% of patients, and sometimes up to 20% for the treatment of pelvic malignancies, including prostate, rectal and cervical cancer, develop late side effects. However, some authors believe that the rates of patients with late side effects may be greatly underestimated [193]. For example, in the case of abdominal or pelvic cancers, more than half of patients would suffer from some form of chronic bowel dysfunction [199]. Most of the effects observed today were caused several years ago by RT techniques that are less used today (2D- and 3D-CRT), and which are progressively being replaced by more precise and more efficient techniques and technologies (IMRT, SBRT and their derivatives, hadrontherapy, and maybe FLASH RT in the future). It is therefore likely that the landscape of side effects will be completely different in a few years."}
{"_id": "Radiology$$$a0a13c17-8542-4edf-9b27-f674f6c8eb3f", "text": "As cancer detection and management continue to improve, there is an increase in the number of long-term cancer survivors in the more economically developed countries. For example, in the USA, the 5-year survival rate has increased from 49% in the period 1975\u20131977 to 67% in the period 2010\u20132016 (American Cancer Society, Cancer Facts and Figures, Atlanta, Georgia, 2021). On the other hand, given that about half of patients are treated with RT, it can be estimated that several tens of thousands of patients will develop side effects each year in this country. Worldwide, with more than 19 million new cancer cases in 2020 (and about 30 million expected in 2040), and an estimated 5-year prevalence of more than 50 million [200], the number of patients developing side effects affecting their quality of life is expected to be in the millions each year. Beyond the fact that the late side effects of RT still limit the effectiveness of this treatment, these figures reveal a real public health concern facing the public authorities and the medical profession."}
{"_id": "Radiology$$$858a39d4-cf35-43b4-a1cc-1f2af9e88905", "text": "Radionecrosis is a late toxicity phenomenon with the occurrence depending on radiation dose, the tissue affected and a number of site-specific risk factors; as treatment options are scant, preventive measures should be facilitated by providing the treatment team with the forecasted 3D RT isodose curves (Box 5.15)."}
{"_id": "Radiology$$$7cc947ce-bd3c-48a7-b1b8-9faa74299019", "text": "Radiation accidents and therapy have shown that, in principle, all human tissues can suffer from necrosis as a late toxicity as result of progressive ischemia of irradiated tissues in the context of chronic inflammation. Pathologic samples show necrosis with fibrinous exudates and dystrophic changes of the vessels in the exposed tissues. In daily practice, radionecrosis most commonly involves bone (head and neck (jaws-masto\u00efd-temporal bone-larynx-cartilage)/femoral head), breast, CNS, bowel, skin and rarely ribs or sclera (Sect. 5.14.3). Even when standard dosage schedules are followed, serious radiation complications would occur in 5\u201310% of long-term survivors. Yet, general incidence rates on most tissues are difficult to present as most studies have specific settings and constraints resulting in large heterogeneity of data. In the following section, osteonecrosis of the jaws and brain radionecrosis will be discussed in greater detail."}
{"_id": "Radiology$$$636b294c-37e0-464d-b55a-7daf25774dd5", "text": "Osteoradionecrosis (ORN) of the jaw is a late complication of RT in the treatment of head and neck cancer. It is defined as exposed irradiated bone that fails to heal over a period of 3\u00a0months without any evidence of persisting, recurrent tumor or metastatic disease. ORN occurs in bone that was exposed to a radiation total dose exceeding 60 Gy. However, in the presence of concomitant risk factors, lesions can develop in bone exposed to a lower dose, usually above 50 Gy. The overall susceptibility ratio between mandible and maxilla is for the development of ORN 24/1, with the posterior areas of the mandible most at risk and the upper jaw rarely affected."}
{"_id": "Radiology$$$b86a6e0e-c194-461f-b89d-5253d3ed782c", "text": "The overall incidence of ORN in IMRT patients is reported to vary between 5.1% and 12.4% [201] with excess figures (up to 25.5%) [202] in the presence of risk factors and higher figures with longer follow-up. ORN usually develops during the first 3 to 24\u00a0months after RT; however, the real risk for ORN lasts a lifetime and can occur at any time following RT."}
{"_id": "Radiology$$$91b05ce3-c2dc-4b9f-8a89-3fa77f4f56b9", "text": "The pathophysiology of ORN is still uncovered. In essence, the viability of the irradiated bone is lost due to ischemic necrosis in the irradiated atrophic tissue without sufficient capability of repair, leading to secondary soft tissue breakdown and exposure of bone. Pathological fractures following ORN typically form no callus formation [203], illustrating the absence of periosteal healing. The presence of Actinomyces in necrotic bone is best detected with a PCR-based method and its role needs further investigation."}
{"_id": "Radiology$$$b6fb3992-fb9b-4069-89eb-a67943a7d69b", "text": "ORN may remain asymptomatic for a prolonged period but signs and symptoms may also occur before the development of bony exposure. Presenting clinical features include pain, tooth mobility, mucosal swelling, erythema, ulceration, malocclusion, dysphagia, trismus, paresthesia, or even anesthesia of the associated branch of the trigeminal nerve."}
{"_id": "Radiology$$$db688622-5033-4190-841b-d7ff60f1b433", "text": "Different classifications of ORN exist, usually based on following criteria: extent of the lesion [204], symptoms [204, 205] and response to hyperbaric oxygen therapy. The extent of lesions can vary and range from a non-healing extraction site to exposure and necrosis of large sections of the jaw. Late stage ORN often present with fistula from the oral mucosa or skin, complete devitalization of bone, pathological fractures, and even life-threatening complications."}
{"_id": "Radiology$$$94ee7645-cb8c-49d2-8be6-2d68ab00c43e", "text": "Panoramic radiographs are mostly used for diagnosis, follow-up, and monitoring patients who are at risk of osteonecrosis. However, only at a loss of 30\u201350% in bone density injury will be visible on X-ray. CBCT, CT, and MRI allow to analyze the jaws more extensively and to better assess the extent of injuries and are also very helpful in differentiating osteonecrosis from other causes of osteolysis."}
{"_id": "Radiology$$$d221917e-3de9-4581-9c35-863381c4e9ed", "text": "Although ORN may occur spontaneously [206], most ORN develop after dental surgery (extractions of teeth, dento-alveolar surgery, dental implant placement)."}
{"_id": "Radiology$$$87228fba-cc63-4f49-a7a4-05c9e3d0eef4", "text": "The most important risk factors for ORN are dose >50\u201360 Gy and post-RT dento-alveolar surgery in the high-risk zone. Other factors are tumor size, proximity of the tumor to bone, age\u00a0>60 years, diabetes mellitus, poor oral hygiene, concomitant chemotherapy, active smoking, excessive alcohol consumption, and chronic use of corticosteroids [207]. Many of these published risk factors still need confirmation with robust data and study designs."}
{"_id": "Radiology$$$4504b730-20fd-4235-acc0-8e4ddf5a5539", "text": "Pre-treatment dental screening aims to reduce the risk of developing ORN after RT by eliminating all teeth with an elevated risk in an area of bone that will get exposed to a high dose of IR. It is therefore mandatory to provide the dentist and/or oral surgical team with the forecasted 3D RT isodose curves (Fig. 5.25) to allow a differential approach for teeth within and outside the high ORN risk perimeter [208].\n\nFour three-dimensional images of the removal of high-risk teeth in I R exposed bone in 40 grey, 50 grey, and 60 grey.\n\nFig. 5.25\n3D RT isodose curves"}
{"_id": "Radiology$$$7097632a-bef7-4d7e-9a29-760576d135c4", "text": "Four three-dimensional images of the removal of high-risk teeth in I R exposed bone in 40 grey, 50 grey, and 60 grey."}
{"_id": "Radiology$$$72cfbeb0-e3a2-4b7e-abbf-5e2e79d71bd3", "text": "In the areas with a high risk of developing ORN (>50\u00a0Gy), an extraction is done whenever teeth represent a risk for future need for extraction of a risk for future infection. Teeth which will be extracted as part of the surgical resection approach can be left in situ. In other areas of the jaws, the extraction therapy will depend on regular extraction guidelines, the clinical experience of the supervising surgeon considering the level of oral hygiene of the patient and the expected future limitation of mouth opening. In the upper jaw, due to the far lower incidence of ORN, most clinicians opt for regular extraction guidelines."}
{"_id": "Radiology$$$61ea7317-8911-48db-bf5b-a413e0cf3755", "text": "Depending on the extent of the affected area (both soft tissues and bone), the symptoms, the existence of a pathological fracture the treatment will vary from a conservative to a surgical approach. In early stages, conservative measures such as antibiotics, debridement, and irrigation will be preferred while surgical resection and reconstruction (reconstruction plates, free vascularized osteomyocutaneous flaps) are reserved for more advanced cases. Whenever resection of ORN is needed, 3D RT isodose curves should be allowed to be included in the virtual planning of the procedure."}
{"_id": "Radiology$$$2b887f04-c37e-46ab-8503-97923b1490f7", "text": "HBO as adjunctive therapy to conventional treatment has not been proven to yield consistently significantly favorable results compared to conventional treatment alone. Therapeutic regimens composed of Pentoxifylline and Tocopherol combined have been shown to have a synergistic effect in treating small areas of ORN with visual and symptomatic resolution of the condition. Clonodrate, a first-generation non-aminobisphosphonate, has been described as effective when combined with pentoxifylline and tocopherol for refractory ORN (PENTOCLO-protocol)."}
{"_id": "Radiology$$$0b37097d-65fe-431e-a637-cd2ce8c850df", "text": "Lifestyle changes should accompany both conservative and surgical procedures: proper oral hygiene, smoking and alcohol cessation, healthy and adequate nutrition intake, well-fitting dentures [209]. Dento-alveolar surgical procedures in a highly radiated mandible should be avoided if possible and whenever needed following principles should be kept in mind: minimal periosteal degloving, antibiotic coverage, local anesthesia without epinephrine."}
{"_id": "Radiology$$$aee3267c-d85d-4e0b-b48d-aec4882cb48d", "text": "Brain radionecrosis (RN) is an irreversible late radiation-induced tissue complication that can occur after irradiation of brain parenchyma inducing a vascular lesion of the white matter, developing in the irradiation field, secondary to chronic inflammation of the brain parenchyma, with a tendency for spontaneous extension [210]. Its pathophysiology is not yet clear. Brain RN induces hypocellular zones of necrosis and fibrinous exudates with degenerative or dystrophic changes in the vasculature, with telangiectasia, hyaline thickening of vessels, and fibrinoid necrosis including intravascular thrombosis responsible for an increase of vascular permeability. The occurrence and severity are correlated with dose-volume parameters [211]. An actuarial incidence of brain RN up to 34% two years after stereotactic radiotherapy (SRT) was recently reported\u2014symptomatic and sometimes lethal or severely debilitating in 10\u201317% of the patients [212]. Approximately 80% of cases occur within 3\u00a0years from the completion of RT."}
{"_id": "Radiology$$$cc5fba74-d2a0-4595-95b6-20e87fe4791e", "text": "The symptoms of RN are those of a non-specific intracerebral expansive process. A seizure is inaugural in half of the cases, signs of intracranial hypertension and a progressive deficit syndrome (sensory, motor, or aphasia) are frequently present. The semiology often reproduces the initial signs of the primary tumor. In pituitary tumors, lesions preferentially affect the chiasma and the optic nerves causing severe visual disturbances; damage to the temporal, frontal, and hypothalamus lobes is often associated, causing cognitive impairment."}
{"_id": "Radiology$$$3e9b2d8b-57ec-4bbc-9212-88222499dd4d", "text": "The main differential diagnosis is tumor progression due to very similar clinical and radiological characteristics."}
{"_id": "Radiology$$$b1a5b182-61ed-4fbe-a048-bb768bd91adc", "text": "The gold standard for the diagnosis with certainty is the pathological analysis. On histological analysis, 50% of lesions are pure RN, the remaining 50% associated with radionecrosis and tumor cells without predicting their viability."}
{"_id": "Radiology$$$797be344-017c-4f9d-ba2f-2889b45014a8", "text": "There is not yet a validated imaging technique that distinguishes the two entities though advanced imaging techniques such as DTI (ADC and fractional anisotropy ratios), perfusion MR imaging (CBV, rPH, and relative PSR), MR spectroscopy, and amino acid PET hold promise [213]. The MRI shows a persistent central hypointense and an enlargement of a pre-existing enhancement in T1 gadolinium associated with a hypersignal in T2 with an appearance of \u201cSwiss cheese\u201d or \u201csoap bubble.\u201d Perfusion MRI, spectro-MRI and PET amino acid imaging may provide additional arguments. Other avenues are showing interest in the differential diagnostic strategy\u2014notably radiomics."}
{"_id": "Radiology$$$4d5e41b5-18c9-45cc-ab2c-eeaaeb5b32e9", "text": "When this documentation is not possible, the decision-making process is guided by clinical and imaging criteria collected over a significant period of follow-up. Such criteria were proposed by the Association of Neuro-Oncologists of French Expression (ANOCEF) [214]. The treatment options of brain RN include steroids, bevacizumab, surgical resection, and hyperbaric oxygen."}
{"_id": "Radiology$$$e56be720-9d0e-4f63-89bc-767fd5bee113", "text": "Cellular depletion by radiation-induced death is not the only one responsible for initiation and progression of lesions.\n\nRadiation-induced effects on the vascular endothelium drive the propagation of the inflammatory response and chronic effects.\n\nMolecular and cellular damage after exposure to IR impacts cellular homeostasis and potentially leads to chronic organ dysfunction.\n\nThe notion of a continuum of effects, orchestrated by all the compartments and chronic cytokine cascades, opens up fields of therapeutic approaches."}
{"_id": "Radiology$$$8a270c35-5f7f-4a53-bace-39d7acbdd1d0", "text": "Cellular depletion by radiation-induced death is not the only one responsible for initiation and progression of lesions."}
{"_id": "Radiology$$$709b79c7-cbb2-47e7-bbd8-fb74a7c85066", "text": "Radiation-induced effects on the vascular endothelium drive the propagation of the inflammatory response and chronic effects."}
{"_id": "Radiology$$$e9dca249-652d-4a04-8590-7f9f9b1783a6", "text": "Molecular and cellular damage after exposure to IR impacts cellular homeostasis and potentially leads to chronic organ dysfunction."}
{"_id": "Radiology$$$d3cad73b-b5cf-4f18-b8de-2cd385c2bb87", "text": "The notion of a continuum of effects, orchestrated by all the compartments and chronic cytokine cascades, opens up fields of therapeutic approaches."}
{"_id": "Radiology$$$a5d14513-acc8-41d7-913e-d8aeade3db43", "text": "Improving the quality of life of patients by reducing sequelae of cancer treatment is one of the main future challenges. Beyond the dose itself to the organs at risk, the probability of occurrence of side effects is related to a multitude of factors: the nature of the radiation (photons, electrons, charged particles), the volume irradiated, the fractionation, the spread, the dose rate, but also the nature of the exposed tissue (hierarchical versus flexible tissue, in parallel or in series organization) or the individual susceptibility of the patient. Furthermore, in a simplified manner, acute toxicity is mainly observed in rapidly proliferating tissues (skin, gastrointestinal tract, and hematopoietic system) and late effects are observed in slower proliferating tissues (central nervous system, kidney, heart) [215]. Historically, tissue response to radiation has long been explained by the target cell concept which suggests that the severity of tissue effects is mainly due to the depletion of cells in a target compartment by radiation-induced death resulting in a functional impairment of the organ. This hypothesis can be considered for early effects but is more questionable for late effects. Cellular depletion by radiation-induced death is an important element of the tissue response, but it is not the only one responsible for the initiation and progression of lesions. Molecular and cellular damage after exposure to IR will disrupt cellular homeostasis and potentially lead to chronic organ dysfunction. It is now agreed that the tissue response to IR is the result of the activation and integrated involvement of all the compartments that make up the tissue (Fig. 5.26 and Box 5.16).\n\nA diagram involves the coagulation system activation, endothelial cells activation, inflammatory response, recruitment of circulating cells, and D N A repair cell death or survival progresses that lead to fibrosis necrosis.\n\nFig. 5.26\nIrradiation and progression of radiation-induced normal tissues damage. Tissue damage results from several acute events such as cell loss and endothelial cells activation. Damage progression includes a continuum of effects orchestrated in time and space leading to tissue fibrosis/necrosis and organ dysfunction"}
{"_id": "Radiology$$$3fa89daf-9487-474e-8be4-bd1c18f1f7a5", "text": "A diagram involves the coagulation system activation, endothelial cells activation, inflammatory response, recruitment of circulating cells, and D N A repair cell death or survival progresses that lead to fibrosis necrosis."}
{"_id": "Radiology$$$bebcc7c1-64cd-4016-aea5-8c8b61f00ac9", "text": "The notion of a continuum of effects, orchestrated by all the compartments and chronic cytokine cascades, opens up fields of investigation into various therapeutic approaches [190]. The contemporary view involves several cell types and molecular mechanisms, which together form an orchestrated response, and contribute to the initiation, progression, and chronicity of radiation-induced injury. A better understanding of these event kinetics should allow the identification of molecular and cellular targets, associated functions, and relevant times for therapeutic action. Radiation-induced effects on the vascular endothelium and epithelial barriers are important for the propagation of the inflammatory response and the recruitment of immune cells. The concept that the microvasculature plays a central role in the radiation toxicity of many tissues is emerging and demonstrated now. Irradiation leads to endothelial cell apoptosis, increased vascular permeability, and acquisition of a pro-inflammatory and pro-coagulant phenotype. Moreover, tissue-specific deletion in the endothelium of key molecular actors impacts the severity of acute and normal tissue injury [216]."}
{"_id": "Radiology$$$411c318a-35dd-4f10-aeda-f54ac646df8d", "text": "Rapidly after exposure to IR, damage to the endothelium and epithelial cells leads to the release of damager signals (such as DAMPS) and the activation of adhesion molecules. This reaction allows the recruitment of a large panel of immune cells to the damaged site, which are able to repair the tissue but which, in the case of chronic inflammation, can strongly also participate in the installation of fibrosis [196]. For example, macrophages are rapidly recruited after irradiation and are a heterogeneous immune cell population with multiple pro- or anti-inflammatory as well as pro- or anti-fibrosis functions. The recruitment dynamics of macrophages, as well as their phenotypic orientation impacted by their microenvironment over time, are increasingly shown to play an essential role in the evolution of radiation-induced injury [195]. Radiation-induced immune effects are propagated by a large panel of cytokines including interferon-\u03b3 (IFN\u03b3), Interleukin-1\u03b2 (IL-1\u03b2), Interleukin-6 (IL-6), CC-chemokine ligand 2 (CCL2), tumor necrosis factor (TNF), and transforming growth factor-\u03b2 (TGF\u03b2). Interestingly, beyond their roles in the inflammatory response, some of these cytokines also play essential roles in several other processes contributing to the evolution of radiation-induced lesions. TGF\u03b2 induces the differentiation of fibroblasts into myo-fibroblasts with a consequent increase in the extracellular matrix. In addition, in association with other cytokines such as IL-1\u03b2, TGF\u03b2 promotes endothelial-mesenchymal (endoMT) [217] and EMT, two key processes also demonstrated in radiation-induced lesions to healthy tissues [218]. Finally, it has recently been shown in several studies that senescence also contributes to the pathogenesis of radiation-induced injury to healthy tissue. Senescence is a durable cell-cycle arrest with a persistent pro-inflammatory Senescence-Associated Secretory Phenotype (SASP) characterized by the secretion of multiple growth factors and cytokines, the senescence-messaging secretome (SMS) [219]. Premature senescence can be produced by a large panel of DNA-damaging agents and genotoxic stress including IR. In several preclinical models of radiation-induced lung injury, it has been shown that many types of cells bear senescence marks such as pneumocytes, macrophages, and endothelial cells [220, 221]. Interestingly, senolytic agents that selectively can kill senescent cells limit radiation-induced lung injury provided the evidence that senescence participates to the pathogenesis and that senolytic drugs could be a good strategy to reduced late normal tissue damages [222]."}
{"_id": "Radiology$$$1a8c1ce0-9a50-40b8-bc59-8c0b773525e2", "text": "Recent research clearly shows that normal tissue injury is a dynamic and progressive process. The main challenge in the future will be to perfectly decipher this dynamic of events for each organ and its own characteristics. This will allow to propose new molecular and functional tools to predict, prevent, and treat damage to healthy tissues after irradiation."}
{"_id": "Radiology$$$39f04ae8-b03a-4e9e-b5a5-12135bdaa963", "text": "The evaluation of treatment plans in the treatment planning system is based on dose-volume histogram analysis for PTV and critical organs. Final plan quality evaluation should be based on plan complexity, plan robustness, and dose distribution analysis including dose-volume control. Constraints for any dose-volume relationship should be connected to the radiobiological outcome."}
{"_id": "Radiology$$$71e8fefc-b190-45f7-8be3-9b1620adf72d", "text": "In 2010, a series of articles were published in the International Journal of Radiation Oncology Biology Physics as a meta-analysis of published dose\u2013response observations for different critical organs. The project called Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC) aimed to review meaningful data published in the previous 18\u00a0years for common critical organs in terms of dose/volume values connected to radiobiological effects [223]. This endeavor was a challenge because it involved the amalgamation of different analytic methodologies, calculation methods, endpoints, and grading schemes, which were used in different studies to address the relationship between dosimetric parameters and the clinical outcomes of normal tissues."}
{"_id": "Radiology$$$adf9ba0c-45a4-445f-bbf5-0148ccd73dcb", "text": "QUANTEC consists of two introductory papers about the overview and history with some scientific issues related to the QUANTEC effort and about the suggestions on how to rationally incorporate the QUANTEC metrics/models into clinical practice. The core of the QUANTEC project is described in 16 articles for different organs at risk or complications:\nBladder\n\nBrain\n\nBrainstem\n\nEsophagus\n\nHearing loss\n\nHeart\n\nKidney\n\nLarynx and pharynx\n\nLiver\n\nLung\n\nOptic nerves and chiasm\n\nPenile bulb\n\nRectum\n\nSalivary gland\n\nSpinal cord\n\nStomach and small bowel"}
{"_id": "Radiology$$$101b85e4-d58e-4e75-8854-d8b5065b563f", "text": "For each organ, there are associated sections describing: clinical significance, endpoints, challenges in defining volumes, review of dose/volume data, factors affecting risk, mathematical/biological models, special situations, recommended dose/volume limits, future toxicity studies, and toxicity scoring."}
{"_id": "Radiology$$$ae70c9d2-3e54-481b-9ca4-089baea5cd9a", "text": "The QUANTEC reviews provide focused summaries of the dose/volume/outcome information for many organs, but these were usually obtained for 3D conformal RT or other techniques that have in many cases already been replaced by more modern techniques, such as VMAT or SRT. It should be emphasized that dose/volume constraints and other information in QUANTEC are expected to be updated in the future for relevant techniques. The data is not intended to be extrapolated to pediatric patients. Pediatric Normal Tissue Effects in the Clinic (PENTEC) is a recent initiative to review tolerance constraints for children, who may have different tolerance to that of adults [224]."}
{"_id": "Radiology$$$16513362-614d-44b6-8be8-dfc860001565", "text": "For hypofractionated RT such as SRS or SBRT, relatively small target volumes receive hypofractionated RT schedules, typically in 1\u20135 fractions. As an extension to QUANTEC and other previous guides to tissue tolerance, high dose per fraction, Hypofractionated Treatment Effects in the Clinic (HyTEC) was published as a series of articles [225]. This project served to provide guidance on dose/volume constraints for hypofractionated regimens for 7 normal tissues as well as 9 disease sites (TCP). Interestingly, the possibility of so-called \u201cnew radiobiology\u201d of hypofractionation is also alluded to\u2014the possibility that large fractions may induce enhanced radiobiological effects in tumors by additional vascular targeting and anti-tumor immune responses [150]. Radiobiological aspects of hypofractionation are discussed in detail in Chap. 5."}
{"_id": "Radiology$$$57843505-20b2-402a-b6bd-3765999e5a14", "text": "Overall, the recommendations of QUANTEC, PENTEC, HyTEC, and other constraint guidelines should be used judiciously as a guide and should not replace clinical judgment."}
{"_id": "Radiology$$$a3a5d71b-8dd9-45bb-b368-36ed8185db2f", "text": "Normal tissue complication probability (NTCP) describes the probability of organ/structure complication related to radiation treatment specified by physical and clinical factors in radiation oncology.\n\nThere are various approaches to NTCP modeling which usually are based on different statistical distributions.\n\nThe predictive power of the NTCP model is dependent on the parameters of models, which can include dosimetry as well as other clinical and treatment conditions."}
{"_id": "Radiology$$$eff6aa20-54f8-4119-895c-89f96d33b40a", "text": "Normal tissue complication probability (NTCP) describes the probability of organ/structure complication related to radiation treatment specified by physical and clinical factors in radiation oncology."}
{"_id": "Radiology$$$ab884a59-7c55-4280-8e2e-bb49b93f66ec", "text": "There are various approaches to NTCP modeling which usually are based on different statistical distributions."}
{"_id": "Radiology$$$17d038e4-fb08-4fbd-95e0-00648f6c6b77", "text": "The predictive power of the NTCP model is dependent on the parameters of models, which can include dosimetry as well as other clinical and treatment conditions."}
{"_id": "Radiology$$$10fc5423-0bbe-40d7-a149-3450fd62d39c", "text": "The normal tissue complication probability (NTCP) is the probability that for a given dose distribution organ or structure complication can be expected. These complications can be multiple for one organ or structure and usually are called as endpoints in the models. NTCP is aimed at quantification of dependence of tolerance dose for a certain radiation effect on the size of treated volume. The NTCP models are supposed to be predictive and to be used to estimate the complication risk for organs at risk (OARs) after RT. OARs can be used to individualize the tumor dose for a given acceptable NTCP (Box 5.17)."}
{"_id": "Radiology$$$0c98ba51-18af-41df-8c50-acf72aadcf83", "text": "NCTP models are used to describe dose\u2013response curve shape for particular endpoint for an organ at risk, which is usually sigmoidal. These models are usually connected to Dose-Volume Histogram (DVH) of the applied treatment plan; therefore the models are sometimes called DVH-reduction models. More complex approach [226] moves towards spatial dose distribution in the patient and not dose-volume reduction only. When voxel-based evidence on organ radiosensitivity was acknowledged and attempts were made to develop a probabilistic atlas for NTCP in radiation oncology. However, there are other clinical factors that influence complications, such as chemotherapy, fraction size, pre-existing medical conditions, and comorbidities. The predictive strength for models can be enhanced with considering other important clinical and medical features for the patient. This information is expected to provide a boost for further deployment of biological models in the clinical treatment planning process."}
{"_id": "Radiology$$$c7e4c09f-6c4d-4de9-a3f3-c12dd0031c12", "text": "Common NTCP models as described by [227] are:1.\nLyman-Kutcher-Burman (LKB) model (Gaussian)\n\u00a02.\nParallel architecture model (Logit)\n\u00a03.\nWeibull model (Weibull)\n\u00a04.\nCritical element model (Poisson)\n\u00a05.\nRelative seriality model (Poisson)\n\u00a06.\nCritical volume model (Binomial)\n\u00a07.\nInverse tumor model (Poisson)"}
{"_id": "Radiology$$$a1db651d-ae9d-45ad-a605-af7a04e7cf88", "text": "Models are based on different statistical distributions (in parentheses). The first four models are using cell-survival-based response, while others are phenomenological. However, each model may be expressed in terms of the parameters D50 (dose that is associated with the 50% response probability) and \u03b350 (gradient of the dose-response curve at the level of the 50% response probability). The steepness of the NTCP curve can be expressed in the models by parameter m. It is inversely proportional to the steepness of the dose response."}
{"_id": "Radiology$$$1b977a05-a828-40a2-b8d6-8ad62ba91984", "text": "Commonly used model is the Lyman-Kutcher-Burman (LKB) model. This model assumes that the tolerance dose increases inversely as power of n of the partial volume irradiated. Examples of NTCP curves obtained for the LKB model are presented in Fig. 5.27.\n\nTwo line graphs represent N T C P in relative units versus dose in grey. The plotted line in graph A rises before plateauing with N T C P = 0.5000, D 50 = 50.0, and m = 0.50. In graph B, the plotted line is in an upward trend with N T C P = 0.4338, D 50 = 60.0, and m = 1.00.\n\nFig. 5.27\nNTCP curves calculated from Lyman-Kutcher-Burman model for two parameters combinations. Parameter m is inversely proportional to the steepness of the curve. (a) NTCP curve calculated by LKB model for D50\u00a0=\u00a050 Gy and m\u00a0=\u00a00.50. For a dose of 50\u00a0Gy, the value of NTCP is 0.50. (b) NTCP curve calculated by LKB model for D50\u00a0=\u00a060 Gy and m\u00a0=\u00a01. For a dose of 50\u00a0Gy, the value of NTCP is 0.43"}
{"_id": "Radiology$$$5a0db091-12ac-445d-8e2a-2136992d3505", "text": "Two line graphs represent N T C P in relative units versus dose in grey. The plotted line in graph A rises before plateauing with N T C P = 0.5000, D 50 = 50.0, and m = 0.50. In graph B, the plotted line is in an upward trend with N T C P = 0.4338, D 50 = 60.0, and m = 1.00."}
{"_id": "Radiology$$$dfaf4702-a009-4676-b4fd-c7494a23b957", "text": "Serial (critical element models) and parallel (critical volume models) are also common models. These mechanistic models are based on tissue architecture. It is assumed that organs consist of functional subunits, which can be organized in chains for serial organs or independently for parallel organs. Damage of one functional subunit impairs the function of the whole organ, while the function of a parallel organ is more dependent on the irradiated volume."}
{"_id": "Radiology$$$f9427250-f1b6-4eed-aa14-75e8e036a2ad", "text": "NTCP models are usually incorporated into in-house developed software in RT centers. Currently, they are also available in commercial treatment planning systems. Parameters for different NTCP models adopted from literature must be used with caution when the probability estimation is applied as a decision criterion for the treatment plan. NTCP can be used also for comparisons between different treatment plans or RT modalities. In these cases, NTCP is used as a relative value in the plan evaluation process and this approach is safer. However, the software should always allow the user to update model parameters. There should be detailed documentation for the models available. It is obvious that the value of NTCP is strongly dependent on the parameters of the model, and therefore should be used with caution."}
{"_id": "Radiology$$$b506be07-31c5-47e4-ba40-485215caacf6", "text": "Stem cells have been described as undifferentiated cells which are found in most adult mammalian tissues. Stem cells are divided into two principal groups: embryonic and adult stem cells. Embryonic cells, which have a pluripotency phenotype have the blastocyst inner cell mass as their origin. It means that they can be differentiated into all cells from the three main germ layers (endo-, meso-, and ectoderm). On the other hand, adult stem cells can be differentiated into cell types according to their origin tissue, thus they are multipotent. Under physiological conditions, adult stem cells are slow growing with a long G0 cell-cycle phase. The main function of such stem cells is to maintain tissue homeostasis including continuous regeneration and associated constant number of cells. The way they are divided is as follows: from the origin stem cell arises one daughter cell with stem cell properties and one progenitor cell with a higher proliferative capacity [228]. Below the normal stem cells in different tissues are described alongside cancer stem cells and their IR response or resistance together underlying molecular mechanisms."}
{"_id": "Radiology$$$56ad4145-5d1c-4a6b-ae2d-427db69ef1df", "text": "In the healthy human tissue, there are multiple cell populations with different stem cell phenotypic characteristics and radiation sensitivity. These different stem cell niches are discussed below based on the tissue localization."}
{"_id": "Radiology$$$cf436502-327d-4e07-8923-a5a5af75ae6c", "text": "Stem cells of the bone marrow are divided into two groups: hematopoietic and mesenchymal stem cells. From the hematopoietic stem cells arise leukocytes, erythrocytes, and thrombocytes and from the mesenchymal stem cells adipocytes, chondrocytes, myocytes, and osteocytes are generated [229]. One function of mesenchymal stem cells is to establish the hematopoietic stem cell niche [230]. When it comes to IR toxicity, the progenitors from the hematopoietic stem cells are more sensitive than the origin, more primitive, stem cells. Such a difference is linearly dose dependent in the progenitor cells and is one of the factors causing the development of one of the early radiation effects, the hematopoietic syndrome [231]. Importantly, both of these stem cell populations are responsible for the repopulating of the damaged bone-marrow homeostasis after IR exposure."}
{"_id": "Radiology$$$1550695a-1690-4718-97f1-001c545a89a7", "text": "The neural stem cell pool can be divided according to the localization. Hence, we recognize the subventricular and the subgranular group [232]. Even within these two subtypes are heterogenous. Thus, one can distinguish four main types of cells from the subventricular niche: activated neural stem cells, dormant neural stem cells, progenitor cells, and quiescent neural stem cells [233]. Generally, neural stem cells can differentiate into multiple neuronal- and glial cell types. The most IR sensitive populations are activated neural stem cells and progenitor cells because IR induces their cell death, for example, apoptosis. Such effects lead to a reduced population of new neurons. To prevent the negative effects of IR on the neural stem cells different protective strategies have been tested, for example, administration of lithium [234, 235] or the natural polyphenol resveratrol [236]. It has been shown that lithium pre-treatment can reduce DNA damage and increase microglial activation [234, 235]. Resveratrol, on the other hand, has a neuroprotective effect, because it can reduce oxidative stress [236]."}
{"_id": "Radiology$$$04f1de65-0a60-4d38-8c85-42d89105ccf6", "text": "Several types of the stem cells exist in the skin which can differentiate into more than two dozen cell types, including epidermal-, keratinocyte-, and melanocyte stem cells [237]. The keratinocytes progenitors are the most IR sensitive ones, if damaged they are eliminated thereby contributing to the high epidermal sensitivity to IR. In contrast, more primitive keratinocyte stem cells possess active repair mechanisms and increased cell survival, but their rapid and faultier repair contribute to the genomic instability. Interestingly, while the keratinocyte stem cells favor repair of DNA damage, the melanocyte stem cells are not involved in tissue regeneration after IR damage [231]."}
{"_id": "Radiology$$$1a393194-f603-4813-9b3b-f592d471c638", "text": "Gastrointestinal syndrome, a known acute toxicity response to IR, promoted the first exploration of intestinal stem cells in radiation biology studies, which included the exposure of mice to doses greater than 14\u00a0Gy, inducing death after 7 to 12\u00a0days due to small intestine damage. This high sensitivity has been attributed to the fast cell turnover in the intestinal mucosa which, in mice, completely renews the epithelium every 5\u00a0days [231]. These studies allowed the characterization of intestinal regeneration, revealing the presence of a stem cell population near the bottom of the intestinal crypt. These actively cycling cells are highly sensitive to IR, undergoing apoptosis in response to doses as low as 1 Gy although this sensitivity seems to be dependent upon their position within the crypt [238]. Another stem cell subpopulation, known as crypt base columnar cells and characterized by the expression of Lgr5 (Leucine-Rich Repeat Containing G Protein-Coupled Receptor 5), are less radiosensitive than the previously described cells yet more sensitive than small intestine progenitor cells. Radiation toxicity can occur at low doses; however, crypt loss is only observed after exposure to higher radiation doses. This may be because crypts only disappear after total loss of the stem cell population, which only happens at doses greater than 8 Gy. This radiosensitivity could be caused by the accumulation of DNA damage or pro-apoptotic proteins after genotoxic stress, i.e., p53, ATM, and PUMA. The difference in radiosensitivity between the small intestine and the colon could be due to a more efficient p53 signaling, DNA repair and G2-phase checkpoint delay in the latter. The high expression level of the anti-apoptotic protein Bcl-2 in colon progenitors could be another reason. Paradoxically, the risk of developing cancer after exposure to IR is lower in the small intestine, suggesting the interplay between cell resistance and lower genomic stability. It should be noted that most of this knowledge is based on studies in mice; therefore, human models are still required in order to understand the intestinal stem cell radiation biology [231] (Box 5.18)."}
{"_id": "Radiology$$$74ee1428-fa75-4c2b-a038-379c0eadf225", "text": "Stem cells are divided into two principal groups, embryonic and adult stem cells, respectively. Some examples are bone marrow-, neural, skin, and intestinal stem cells.\n\nThe main function of stem cells is to maintain the tissue homeostasis.\n\nIn the normal human tissue, there are multiple cell populations with different stem cell phenotypic characteristics and different IR sensitivity."}
{"_id": "Radiology$$$0e5080f1-12bf-410e-9ac8-f9886bce1f9c", "text": "Stem cells are divided into two principal groups, embryonic and adult stem cells, respectively. Some examples are bone marrow-, neural, skin, and intestinal stem cells."}
{"_id": "Radiology$$$f085af2e-b03a-41a0-97b6-dd582791272d", "text": "The main function of stem cells is to maintain the tissue homeostasis."}
{"_id": "Radiology$$$e483ae40-24da-4a44-9e99-7497b8896e6d", "text": "In the normal human tissue, there are multiple cell populations with different stem cell phenotypic characteristics and different IR sensitivity."}
{"_id": "Radiology$$$e2d63c4e-ff8c-41b0-bd34-5fb55a21c30a", "text": "Tumor heterogeneity is found among patients with the same histological diagnosis as well as within each patient\u2019s tumor as a result of genetic or phenotypic variations [31]. Further, the tissue of origin also influences the inter-tumoral heterogeneity because some of the driving signaling networks (e.g., those that maintain genomic integrity) may vary. Moreover, tumor progression, treatment sensitivity including towards RT and tumour aggressiveness are largely influenced by the origin of the carcinogenic transformation as well as the TME. Tumor heterogeneity plays a significant role in cancer cell survival, thus setting a significant challenge in the development of effective cancer treatment, or in the prevention of tumor progression and metastasis [239]."}
{"_id": "Radiology$$$730175f1-7b25-4325-8b7d-ddb0bb965850", "text": "Recent studies describe two models, i.e., clonal evolution and cancer stem cells (CSCs) which in part can explain tumor heterogeneity as well as alterations during progression of malignancy. The clonal evolution model shares the idea that all cells can accumulate genetic mutations; therefore, any cell has tumorigenic potential [240, 241]. On the other hand, the CSCs\u2019 model describes a hierarchy system in which tumor growth and progression can be maintained with a small proportion of cancer cells displaying stem-like characteristics, such as self-renewal. These stem-like cancer cells can drive tumorigenesis and differentiation, which can to some extent explain tumor cell heterogeneity [240, 242, 243]. It is believed that CSCs originate from the malignant transformation of normal stem cells or progenitor cells. Thus, CSCs possess key properties such as self-renewing and differentiation capacity, thereby being able to produce a phenotypically variable progeny [244]. Due to these characteristics, CSCs are thought to be important for tumor formation, recurrence, and resistance. Indeed, experimental data from xenograft studies in mice where different tumor cells with diverse CSCs characteristics have been engrafted and formed tumors, have demonstrated that CSCs are involved in tumor growth and metastasis and that they are resistant to a multitude of cancer treatments including RT [245\u2013251]. It has been noted that only a few surviving CSCs in a heterogeneous tumor are enough to cause local tumor relapse after RT but also to promote metastasis [243, 247]. It is difficult to calculate the frequency of CSCs within a tumor as it is dependent on the type of malignancy. Further, the identification of CSCs is challenging as specific markers are not entirely clear. This is in part due to the high intra- and inter-tumor heterogeneity as well as by tumor plasticity, and variable genotypes and phenotypes. Regardless, a few markers, i.e., CD44, CD98, CD90, CD44+/CD24\u2212, and CD133, are robust enough to be used in the identification of CSCs (Table 5.15) in breast cancer, small-cell lung cancer (SCLC), esophageal cancer, larynx, head and neck cancer, non-small cell lung cancer (NSCLC), etc. Interestingly, these markers are also associated with response to RT as illustrated in NSCLC and glioblastoma [245, 246, 248\u2013251].Table 5.15\nExample of cancer stem cells (CSCs) Markers\n\nType of tumor\n\nCSC markers\n\nReferences\n\nBreast cancer\n\nCD44+/CD24, CD44\u2212/CD24\u2212/low ALDH1\n\nCoppes and Dubrovska [247], Filipova et al. [243]\n\nEsophageal cancer\n\nCD44\nCD133\nCD90\n\nSmit et al. [252], Yang et al. [253]\n\nGlioma\n\nCD133\n\nBao et al. [245]\n\nHead and neck cancer\n\nCD98\n\nCoppes and Dubrovska [247], Digomann et al. [254] Martens-de Kemp et al. [255]\n\nLarynx\n\nCD44\nCD133\n\nYang et al. [253]\n\nSmall cell lung cancer\n\nCD133\n\nSarvi et al. [256]\n\nNon-small cell lung cancer\n\nCD133\n\nBertolini et al. [246], Lundholm et al. [250], Moro et al. [251], Shien et al. [257]"}
{"_id": "Radiology$$$7c1fd798-1b85-432e-a565-bc0fa4400c2e", "text": "The variable phenotype of CSCs has a strong association with cells of origin thus making the comparison between different tumors complicated. In addition, the number of CSCs within a tumor is relatively small; therefore, the use of CSC markers is a poor predictor for treatment response [258]. Regardless, the characterization of CSCs remains important, as it may provide essential information in the development of more efficient treatment strategies and the prevention of tumor relapse as well as metastasis [240, 247\u2013249, 251, 259]."}
{"_id": "Radiology$$$48f55818-d445-4dc3-8b69-385f6780d908", "text": "A successful RT treatment largely depends on the elimination of cells with tumorigenic capacity, i.e., the number of clonogenic cells, which in part are CSCs, seeking to inactivate these permanently and to take control of tumor growth. Should a single CSC survive, the possibility of tumor relapse is tangible, with the consequent concern that this new tumor may now be RT resistant. In part RT resistance of tumors depends on the number of CSCs within the tumor mass, with greater numbers often being responsible for the failure of therapy [240, 260]. Some of the signaling networks involved are shown in Fig. 5.28.\n\nA diagram displays the tumor environment leads to pro-inflammatory cytokines hypoxia, and the apoptosis goes through low R O S level. The pro-inflammatory cytokines hypoxia and the low R O S level both forward to radio resistance.\n\nFig. 5.28\nIonizing radiation and factors associated with cancer stem cells and tumor microenvironment contribute to tumor resistance to IR. (Adapted from [240, 260])"}
{"_id": "Radiology$$$385e6f2f-6f82-49fa-99f6-7d5a8bc581db", "text": "A diagram displays the tumor environment leads to pro-inflammatory cytokines hypoxia, and the apoptosis goes through low R O S level. The pro-inflammatory cytokines hypoxia and the low R O S level both forward to radio resistance."}
{"_id": "Radiology$$$ee33291a-e6b8-4b54-8919-266957b48db3", "text": "CSCSs are also reported to have activated DDR signaling and increased DNA repair capacity, for example, ATM, Chk1/2, and NHEJ [245, 250], increased cell death resistance as well as upregulation of the signaling pathways involved in cell survival and proliferation, such as HIF-1\u03b1, WNT (Wingless-related integration site), NOTCH, or Hedgehog [247]. Moreover, it was recently shown that tumors with a higher count of CSCs had an impaired local control of the tumor and lower effect of RT than tumors with less CSCs [240, 261]. Several studies have suggested that RT sensitization is linked to the same signaling pathways involved in the preservation of CSCs cells, for example, WNT, NOTCH, or Hedgehog signaling pathways; therefore, these pathways have been indicated as possible targets for CSC-targeted therapies [247, 253]. Other strategies propose the inhibition of the DNA damage response (ATM, Chk1/2), the promotion of apoptosis, and the inhibition of epigenetic-related proteins, for example, histone deacetylase (HDAC), Enhancer of zeste homolog (EZH2). [247]. However, at present very few of these strategies have been clinically tested, due to complex cellular characteristics of CSCs. Nevertheless, further CSCs exploration and their signaling networks could reveal new potential therapeutic targets (Box 5.19)."}
{"_id": "Radiology$$$f12667c9-e092-4b8d-b9bc-7fca51b2becf", "text": "Tumor heterogeneity is explained by theory of clonal evolution and/or existence of CSCs.\n\nClonal evolution presumes accumulation of genetic mutation(s) while CSCs model describes a hierarchy system of tumor growth and progression maintained with only by a small subpopulation of CSCs.\n\nFew specific markers are at hand for characterization of CSCs due to high inter- and intra-tumor heterogeneity, tumor plasticity, and variable genotypes and phenotypes.\n\nTumors with a higher count of CSCs show lower efficacy of RT and impaired local tumor control.\n\nMultiple signaling cascades controlling DDR signaling, cell death, EMT, and hypoxia are reported to be altered in CSCs of tumors offering a putative way for RT sensitization for the future."}
{"_id": "Radiology$$$ebfdf7f1-aae3-4b57-ac45-b876adab827c", "text": "Tumor heterogeneity is explained by theory of clonal evolution and/or existence of CSCs."}
{"_id": "Radiology$$$d09afddd-1640-4164-b4f4-ec206dc14834", "text": "Clonal evolution presumes accumulation of genetic mutation(s) while CSCs model describes a hierarchy system of tumor growth and progression maintained with only by a small subpopulation of CSCs."}
{"_id": "Radiology$$$95636729-4b0e-45ab-8fe7-41c877150054", "text": "Few specific markers are at hand for characterization of CSCs due to high inter- and intra-tumor heterogeneity, tumor plasticity, and variable genotypes and phenotypes."}
{"_id": "Radiology$$$9ce7fae5-2486-45df-b38e-7681a9d77c42", "text": "Tumors with a higher count of CSCs show lower efficacy of RT and impaired local tumor control."}
{"_id": "Radiology$$$f15bc59a-09ea-4119-9ba6-e1cfc8f1d527", "text": "Multiple signaling cascades controlling DDR signaling, cell death, EMT, and hypoxia are reported to be altered in CSCs of tumors offering a putative way for RT sensitization for the future."}
{"_id": "Radiology$$$86c926a1-563f-4cfc-99a4-f2906b2e80e9", "text": "The microbiota is composed of many microorganisms such as bacteria (most represented and studied), viruses, fungi, and archaea.\n\nThe microbiota plays a key physiological role in maintaining the gut health and well-being of the host.\n\nComposition and abundance of the microbiota can be modified by various stresses and a stable alternative state of the microbiota can lead to pathologies.\n\nReduction of the fecal microbiota diversity and composition after RT are consistently associated with intestinal toxicity.\n\nThe microbiota can modify the tumor response effectiveness of RT.\n\nThe microbiota can be a therapeutic target for personalized medicine that might be used to increase patient\u2019s quality of life during or after RT."}
{"_id": "Radiology$$$12bbec97-5080-4d3d-ab07-bca7de25ee4c", "text": "The microbiota is composed of many microorganisms such as bacteria (most represented and studied), viruses, fungi, and archaea."}
{"_id": "Radiology$$$328120e2-cc50-4b04-9c4b-e13fac7e32b3", "text": "The microbiota plays a key physiological role in maintaining the gut health and well-being of the host."}
{"_id": "Radiology$$$d2aafc7f-ea37-4998-a730-3f250be99192", "text": "Composition and abundance of the microbiota can be modified by various stresses and a stable alternative state of the microbiota can lead to pathologies."}
{"_id": "Radiology$$$e2477535-06fd-4cec-b3ac-8d205ed2c71e", "text": "Reduction of the fecal microbiota diversity and composition after RT are consistently associated with intestinal toxicity."}
{"_id": "Radiology$$$cc3e6e7f-2797-4ef0-a753-8090ac025abd", "text": "The microbiota can be a therapeutic target for personalized medicine that might be used to increase patient\u2019s quality of life during or after RT."}
{"_id": "Radiology$$$4e48e261-5522-4094-9c8c-cfe2fad16ed6", "text": "The human body has around 500 billion cells including microorganisms such as bacteria, viruses, fungi, and archaea, on the surface of organs in contact with the outside. All of these microorganisms, hosted by the body, represent the human microbiota. Several microbiotas exist in an organism: in the digestive tract system (from mouth to anus), in the respiratory system, in the urogenital tract, and on the skin. Nevertheless, the larger community of microorganisms resides in the digestive system. The intestinal microbiota can be considered as an organ, given that it has specific functions of its own. Indeed, the intestinal microbiota makes it possible to maintain intestinal homeostasis by transforming nutrients that cannot be digested by the intestine into essential metabolites, by maintaining an effective epithelial barrier avoiding intestinal colonization by pathogens and also by participating to the development as well as the function of the immune system."}
{"_id": "Radiology$$$3d16fe12-c90b-4bc8-af68-21f2b443b480", "text": "Among microorganisms, the most prevalent and studied ones are bacteria. The human GI tract is colonized by more than 2000 different individual bacteria species. Proportional representation and genus level distribution are dependent on the organ localization and vary with diet, age, and geographical localization of the host. As other microorganisms within the microbiota, bacteria have an important role in maintaining the health and well-being of the host. In the healthy gastrointestinal tract, Firmicutes and Bacteroidetes represent the predominant phylum in the microbiota (up to 80%). Other phylums which are less represented in the microbiota are Actinobacteria (3%), Proteobacteria (1%), Verrucomicrobia, and Fusobacteria (less than 1%)."}
{"_id": "Radiology$$$83bedfbd-d121-4930-85da-d361a37b2333", "text": "In a physiological environment, the microbiota is in a state considered stable and healthy, also called eubiosis, where very little modifications take place in its composition. The relationship between host and microbiota is therefore beneficial for both entities. However, multifactorial events can cause transitory disturbances in the microbiota state and therefore population reorganization. Because of the resilience ability of the microbiota, such modifications are often transient. The microbiota then has the capability to return to its basic stable healthy state. However, the microbiota can also tend towards another stable state, called alternated state or dysbiosis, which becomes deleterious for the host [262]. Dysbiosis is defined as a condition where there is an excessive presence of pathogenic microorganisms, a defect in the communities of beneficial microorganisms and a loss of ecosystem structure, i.e., decrease in richness and diversity of microorganism species and increase of the low-grade inflammation, the intestinal permeability, and the oxidative stress. The dysbiotic state of the microbiota questions the scientific and medical community about its involvement in the development of certain pathologies like inflammatory bowel disease (IBD), metabolic disease (obesity or diabetes), neurological pathology (Alzheimer, autism, or Parkinson) but also cancers. Recently, dysbiosis was also reported in patients treated by RT (Fig. 5.29).\n\nA block diagram shows microbiota changing state due to disturbances. The original stable state changes to a transient state after resilience. It is followed by an alternative stable state called dysbiosis.\n\nFig. 5.29\nFrom microbiota healthy state to dysbiosis and pathologies: case of RT effects"}
{"_id": "Radiology$$$878c915e-75c2-479b-b27e-abc293ab4979", "text": "A block diagram shows microbiota changing state due to disturbances. The original stable state changes to a transient state after resilience. It is followed by an alternative stable state called dysbiosis."}
{"_id": "Radiology$$$f4f92c11-ac1c-4c96-879d-9d780d271fd4", "text": "Currently, at least eight prospective clinical studies assessed the effect of RT combined [263\u2013266] or not [267\u2013270] with other anti-tumors treatments, like chemotherapy, on the gut microbiota dysbiosis. The results of these studies have recently been presented in Byeongsang Oh\u2019s review in 2021 [271]. Fecal microbiota changes by pelvic cancers (gynecological, colorectal/rectal, prostate, lymph node, and anal cancers) and/or after RT are briefly summarized below. Prior to RT, patients suffering from pelvic cancers have a loss of their fecal microbial diversity [266, 269]. The clinical studies also performed taxonomic analyses at the phyla level in feces from cancer patients. Results highlight variations of the relative bacteria abundance with an increase of the Firmicutes [269] and the Actinobacteria [266] and decrease of the Bacteroidetes [269] and the Fusobacteria [266]. Low fecal bacterial diversity has also been described in patients during and after pelvic RT [266, 267, 269]. Pelvic RT gradually reshapes microbiota bacterial composition in such cancer patients. Indeed, the prospective clinical studies demonstrate that during pelvic RT, the fecal relative abundance of the phylum Bacteroidetes tends to decrease and conversely that of the Fusobacteria significantly increases [266]. After the completion of pelvic RT, fecal relative abundance of the phyla Firmicutes is reduced [266, 269] and that of the phylum Bacteroidetes, Fusobacteria [266], Proteobacteria [270], and Actinobacteria [267] are enhanced."}
{"_id": "Radiology$$$a43e6d47-275d-4437-b25f-fdeae251bca0", "text": "The prospective clinical studies described above, also show that the reduction of the fecal microbial diversity during and after pelvic RT, are consistently associated with radiation toxicity and therefore with intestinal complications, i.e., enteropathy, enteritis, and diarrhea [266\u2013269]. Indeed, as suggested by a personal view of Andreyev\u2019s team published in The Lancet Oncology in 2014 [272], clinical data seem to indicate that microbiota through its composition change might be an actor involved in radiation-induced intestinal toxicity. In 2018, Gerassy-Vainberg et al. [273] published preclinical data supporting this assumption. Indeed, results show that, rectal irradiation by brachytherapy leads to microbial dysbiosis in chronic post-exposure phase (6\u00a0weeks). Irradiated microbiota transplantation in germ-free mice transmits susceptibility to radiation damages at least in part through the production by epithelial cells of Interleukin-1 (IL-1). Nevertheless, in 2020, data published in Science by Guo Hua et al. show that gut microbiome-metabolome network plays a crucial role in substantial protection against radiation-induced toxicity though host defense regulation [274]. Indeed, a small proportion of mice named \u201celite-survivors\u201d can survive a high dose of total body irradiation and that these individuals also reduce their susceptibility to radiation-induced digestive toxicity and damages. The families Lachnospiraceae and Enterococcaceae, together with downstream metabolites represented by propionate and tryptophan pathway members, contribute substantially to radioprotection. Even if a role of the gut microbiota is suggested on RT-induced tissue toxicity or protection, very little data exists concerning its involvement and the underlying mechanisms. Wang et al. showed that the reduction of the fecal microbial diversity is even more pronounced in patients with pelvic cancers who later progressed to RT-induced side effects (fatigue, diarrhea) [269]. Mitra et al. propose that compositional characteristics of microbiota in cancer patients could also be relevant to be predictive of end-of-anti-cancer treatment bowel toxicity [265]."}
{"_id": "Radiology$$$babbce7f-ee57-4fff-bc4a-5a0ea519a1d8", "text": "RT efficiency, regarding anti-tumor effects, passes in part through the induction of immunogenic cell death in which CD8+ cytotoxic T cell, CD11b+ myeloid cells and dendritic cells all have been described as major actors [275]. There is growing evidence of the existence of bidirectional effects of RT and microbiome composition. Indeed, RT-induced reduction of gut microbiota diversity, richness, and composition could be followed by the host immune response alteration which in turn could lead to an effectiveness change of the anticancer treatment themselves. In 2021, data published by Shiao et al. in the Cancer Cell, robustly demonstrated that, within the gut microbiota, commensal bacteria and fungi differentially regulate tumor response to RT [276]. Indeed, commensal bacteria are required for efficient immune anti-tumor effect (activation of T cells) of RT. Currently, no study has identified bacterial subjects involved in RT efficiency. By contrast, Shiao et al. demonstrated that commensal fungi regulate the immunosuppressive microenvironment of tumor (with combined effects on T cells and macrophages) after RT leading to a reduction of treatment efficiency. They highlighted a role of Saccharomycetales orders and specific Candida Albicans genera in fungal effect after RT."}
{"_id": "Radiology$$$959e7eeb-28e8-4d80-a8c6-37c7c316ccd9", "text": "Fecal microbial signature in patients with pelvic cancers may be a tool for RT risk assessment and/or efficiency. In order to robustly demonstrate this assumption, further experiments and clinical trials should be performed. The use of high-throughput data generation by multi-omics approaches (e.g., microbiota shotgun sequencing or metabolomics analyses) and mathematical models will give an added value compared to previous studies. After RT, a better understanding of individual states of different microorganism populations within the microbiota or more largely within the intestinal ecosystem could help to guide personalized medicine. Indeed, prophylactic or curative treatments like rich fiber diet, probiotic or fecal microbiota transplantation could prevent or reduce RT-induced toxicity and/or improve radiotherapy efficiency on tumor control."}
{"_id": "Radiology$$$319091b2-d381-434a-a5b8-3238ba16de31", "text": "In radiation research, different techniques are used to measure complete molecular- or genomic profiles of organisms, resulting in various collected data types. Omics, a general term for specified measurements and studied biological fields, include genomics, proteomics, transcriptomics, metabolomics, phenomics, lipidomics, and many more. The suffix \u201comics\u201d indicates interest in all molecules or genes of a specified type and their interactions rather than individual observations. For example, in genomics studies the genome, a set of all genes expressed in the cell, tissue, or organism, and their relationships with each other and with the environment is analyzed. So other omics-based platforms such as proteomics and transcriptomics study proteome (all proteins) and transcriptome (all types of transcripts like mRNAs and miRNAs), respectively. Omics data analysis helps to understand the influence of molecules and genes on a phenotype. The measurements can be obtained with techniques like microarrays, high-throughput sequencing technologies (Illumina, Oxford Nanopore, etc.), mass spectrometry (MS) (including MS imaging), flow-, and mass cytometry. The amount of collected data may vary from few records to millions, and the measurements may be taken for one point in time or more. With increased throughput, a large amount of data is generated, which requires advanced methods to perform a comprehensive analysis. By combining the domain expertise and knowledge of mathematics and statistics, data science extracts insights from big data."}
{"_id": "Radiology$$$ad5a62b7-e502-49ad-9a10-d7d1f7773cce", "text": "Different statistical approaches are applied depending on the experimental design, type of data, sample size, number of replicates, number of time points, and so on. The first step of any analysis is data preprocessing that includes data cleaning and normalization. Omics data may have missing values, duplicated observations or outliers which need to be handled. Outliers are observations that deviate from other observations due to equipment failure or recording errors. An outlier can be corrected or removed from the analysis. There are many outlier detection methods that can detect one or more anomalies, like Chauvenet\u2019s criterion, Grubbs\u2019 criterion, Dixon\u2019s procedure, Tukey\u2019s or Huberta\u2019s method. Which one to choose depends mainly on the data distribution and sample size. Observations with missing values can be ignored, removed or the values may be imputed with mean, median, mode, or constant value. Missing data imputation can also be carried out with, for example, the Nearest Neighbor algorithm, which finds k nearest observations to the observation with missing values and the aggregate of these measurements, as mean/median value, is used to impute the missing one. Before the analysis, data should be normalized to guarantee their numerical scale similarity across different experiments. The standardization techniques, asz-, t-score transformation, or local re-scaling, are often applied to partially correct the batch effect or reference instability."}
{"_id": "Radiology$$$bbcb5432-f501-4ace-9ab9-20aec4496eec", "text": "For a comparative study, depending on the data distribution, a variety of statistical tests can be applied. Usually, if data contain one or two experimental groups, one-step testing is performed. Three or more groups or measurements collected from several time points (time series) require a two-step procedure to determine the difference profile\u2014the omnibus type test (from ANOVA family, for example) followed by pairwise comparisons. The test hypothesis is verified with a p-value, the probability that the test statistics would take a value at least as extreme as observed, assuming the null hypothesis is true. The lower the p-value, the stronger the evidence against the null hypothesis, and if the value is equal or smaller than the assumed significance level \u03b1, it confirmed the presence of the effect studied."}
{"_id": "Radiology$$$35f75b9b-43df-413e-940e-4ab115faa3c7", "text": "Due to the number of data collected, the omics analyses usually require more than one hypothesis to be verified, which leads to the problem of multiple testing. In the case of a single test performed, the first type of error is controlled by significance level, but in the case of multiple testing, the number of false-positive results has to be maintained for the whole test family. This can be done with the use of Bonferroni correction, Simes-Hochberg procedure, Dunn-\u0160id\u00e1k, Holm, or Hommel methods to control family-wise-error (FWER) or Benjamini and Hochberg procedure or Storey\u2019s algorithm when focusing on false-discovery-rate (FDR). However, the p-value depends on sample size, and if the sample is sufficiently large, the statistical test will almost always indicate a significant difference. Therefore, in big data, it is recommended to calculate effect size together with the p-value. Effect size is a quantitative measure of the strength of a phenomenon calculated based on data and is independent of the sample size. A lot of different measures of effect size exist, and they can be divided into two categories: for indicating differences between groups (e.g., risk difference, risk ratio, odds ratio, Cohen\u2019s d, Glass\u2019s delta, Hedges\u2019 g, the probability of superiority, \u03c92) and estimating measure of similarity between variables (e.g., the correlation coefficient r, R2, Spearman\u2019s \u03c1, Kendall\u2019s \u03c4, \u03c6 coefficient, Cramer\u2019s V, Cohen\u2019s f, \u03b72)."}
{"_id": "Radiology$$$334ffea3-5ae4-4e03-85dc-731f8c6b4a90", "text": "It is possible to integrate data and results from different experiments to get a unified view to them, in situations when the same experiment is performed on a different set of data or the same data is used in a different experiment (different method) but concerning the same characteristic (null hypothesis). The p-value integration can be carried out, among others, with Fisher product, Lancaster, Stouffer method, or weighted z-transformation. The adaptive rank truncated product method can also be applied at the pathway analysis level."}
{"_id": "Radiology$$$68a85499-0d0e-491f-beed-eadcdb47536a", "text": "If measurements were taken for multiple characteristics to estimate the relationship and its strength between them (between a dependent variable and independent variables), a regression analysis can be conducted. Regression is a statistical method that tries to fit a model (function) to the data. The model has different forms, the most common one is a linear function, which is a line that closely fits the data according to a specific criterion. In other words, the dependent variable is a linear combination of the model parameters."}
{"_id": "Radiology$$$b2193be5-ab23-439c-a94d-1923c9a20e9a", "text": "In radiation oncology, data science (incorporating the disciplines of computer science and statistics) attempts to provide clinical insight and clinical decision support using structured or unstructured clinical data that incorporates multiple variables descriptive of patient cohorts [277]. Daily clinical workflows produce a vast array of data comprising of electronic health records, treatment information, genomic data, multimodal imaging, and patient outcomes [278]. Inconsistencies in annotations of medical records presents a problem when utilizing unstructured data [279]. Here machine learning and artificial intelligence are key to detecting patterns within these vast data matrices [280, 281], providing opportunities for the development of diagnostic and prognostic tools. Increasingly clinical data and -omics data on the intrinsic biological characteristics of the patient are being integrated to derive models predictive of outcome metrics such as cancer survival and treatment response [282]. As the volume of clinical data available increases, innovative methods to process and interpret the data is required, translating the information into useable knowledge."}
{"_id": "Radiology$$$d28855e5-c2b5-42c6-8976-53ccfbeb98c7", "text": "Machine learning (ML) and artificial intelligence (AI) approaches are capable of both identifying intrinsic patterns within data (termed unsupervised techniques) and developing models linking matrices of clinical data to identifying factors such as diagnostic or prognostic criteria (termed supervised techniques) [283]. For the latter type of model, the standard approach is to randomly separate the available data from patients into a training set which is presented to a machine learning algorithm capable of identifying important variables that link the patient data to the target variable (which is itself representative of the diagnostic or prognostic criterion). Subsequently, the generalizability of the learnt algorithm to new data is interrogated by presenting the algorithm with the unseen test data which remains from the available dataset after separation of the training data."}
{"_id": "Radiology$$$8bc97f2e-a2d3-4144-91b5-d68b1d8b4817", "text": "Typical applications of these approaches include prediction of toxicity to radiation therapy with dosimetric factors in head and neck cancer [284] to prediction of survival in pancreatic cancer [282]. A key advantage of machine learning in predicting therapy outcomes over conventional models such as NTCP and TCP which use dosimetric data [285] is the application of additional clinical and biochemical data [284, 286]. Many models demonstrate high performance owing to validation taking place using data which bears a close relationship to the training dataset. This is a particular concern when translating algorithms to a clinical setting, as models may not be evaluated on an external dataset [287, 288], and as such their generalizability is in question. In general, clinical translation of AI-based technologies requires generalizable, robust models which are validated in prospective, randomized clinical trials, and this represents a key challenge to their adoption [289]."}
{"_id": "Radiology$$$784ef625-9c39-4d50-bc1d-a3be8c2af30d", "text": "Recently, deep learning-based algorithms have been employed, which perform automated image segmentation [290, 291] without the requirement for feature engineering, though the potential for overfitting and a lack of generalizability can persist with such approaches. Deep learning (DL) is a widely researched area in radiobiology and radiation oncology with models being developed for tasks such as modeling outcomes using dose-volume metrics, radiomic feature discovery, image and tumor segmentation, and treatment outcome prediction."}
{"_id": "Radiology$$$49f68841-5352-4e0b-aa24-51dcc6538a6f", "text": "One area where machine learning approaches have seen substantial application is in the development of methodologies utilizing medical imaging data such as CT, MRI, and PET for predictive modeling, particularly of radiotherapeutic outcome. In this instance, the field has been termed radiomics [292, 293]. Here the lack of standardized image acquisition protocols (e.g., slice thickness and tube current in CT) can affect the quality and reliability of the radiomic features extracted by automated algorithms [248, 249, 294, 295]. Often manual clinical delineation of regions of interest of prognostic value prior to modeling (which is termed \u201cfeature engineering\u201d) is utilized though this can introduce interobserver variability [296]."}
{"_id": "Radiology$$$e30fcbde-101f-41e4-bde7-37b13c4a1166", "text": "The success of radiomics in this context is in the development of \u201cinterpretable\u201d machine learning or AI algorithms for a range of applications. Features may be extracted from 2D and 3D imaging data, reducing them to multiple features describing tumor intensity, shape, and texture [297]. These may subsequently be utilized to quantify tumor heterogeneity, where tumors with high heterogeneity have been shown to demonstrate resistance to treatment [298]. Once the features have been extracted machine learning or statistical learning can be applied to match feature patterns to \u201cground truth\u201d data. Radiomic approaches have been applied to multiple imaging formats including CT, MRI, PET, and ultrasound [299\u2013302]. These approaches have been successfully applied to segmentation and detection problems such as the differentiation of prostate cancers with Gleeson grade 6 and 7 [303], the discrimination of breast cancer subtypes [304] and in TNM staging [305]. Potential clinical applications of radiomics-based classification extend to the detection of lung nodules providing a prognostic and diagnostic aid to the clinician [306]. In terms of personalization of treatment, these approaches have been used to identify prostate cancer patients at risk of biochemical recurrence post-treatment from MRI-based imaging [307], to distinguish between HPV-positive and HPV-negative head and neck cancers [308] and to monitor the response to RT [309]. Similarly, ML models are also being examined in radiation genomics, or radiogenomics, which explores tumor and normal tissue response to radiation at a genomic level [310]. Linking imaging characteristics with genomic data has the potential to aid clinical cancer research and improve decision-making capabilities and personalize therapy [310\u2013312]. Various deep learning methodologies are currently used to generate new knowledge from radiogenomic data including convolutional neural networks (CNNs) [313] and deep neural networks (DNNs) [314]."}
{"_id": "Radiology$$$e9432950-5e72-4746-b09c-3d95c4b2eaf7", "text": "However, as highlighted earlier, significant challenges remain regarding the clinical interpretability of radiomic and radiogenomic analyses and models, image acquisition standardization and data storage in the era of \u201cbig data\u201d [292, 312, 315, 316]. Randomized controlled trials will remain the gold standard in evaluating diagnostic and prognostic interventions that are AI or ML based will be evaluated in oncology [317, 318], where data science approaches can also provide complementary information [319, 320]."}
{"_id": "Radiology$$$d8560ba4-44f1-4acb-8325-fe2d8241a513", "text": "Several imaging modalities exist in radiology and nuclear medicine with different physical, acquisition, and reconstruction principles which have strengths and weaknesses but all of them are indispensable for differential diagnosis.\nUltrasound sonography (USG) uses high-frequency mechanical waves to differentiate tissues based on various reflectivity on the tissue edges. USG is an affordable and inexpensive modality with minimal burden for the patient.\n\nRoentgenography (X-ray imaging, RX) uses electromagnetic waves with energy in the X-ray range most often between 40 and 120\u00a0keV. RX is a fast and inexpensive modality with small radiation exposure. If one collects thousands of 2D RX images from different angles, one can use computer algorithms for creating 3D images and one is talking about CT. Advantages of CT are in special resolution, high contrast, and 3D information; however, at the cost of high radiation exposure and higher price than RX.\n\nMRI also uses also electromagnetic waves as well as RX of CT but with an energy in the radio range most often between 240 and 500 neV which cannot ionize biological tissue (no radiation exposure) which is together with high tissue contrast advantage of MRI. The disadvantages are longer examination time (15\u201345\u00a0min), price, availability, and several contraindications."}
{"_id": "Radiology$$$154a9e33-082f-4a72-ac29-fff7d47586df", "text": "Ultrasound sonography (USG) uses high-frequency mechanical waves to differentiate tissues based on various reflectivity on the tissue edges. USG is an affordable and inexpensive modality with minimal burden for the patient."}
{"_id": "Radiology$$$10c212fc-737f-499c-928e-e6ffe9289ead", "text": "Roentgenography (X-ray imaging, RX) uses electromagnetic waves with energy in the X-ray range most often between 40 and 120\u00a0keV. RX is a fast and inexpensive modality with small radiation exposure. If one collects thousands of 2D RX images from different angles, one can use computer algorithms for creating 3D images and one is talking about CT. Advantages of CT are in special resolution, high contrast, and 3D information; however, at the cost of high radiation exposure and higher price than RX."}
{"_id": "Radiology$$$c3b829e5-23f0-4502-ab89-530f536d264e", "text": "MRI also uses also electromagnetic waves as well as RX of CT but with an energy in the radio range most often between 240 and 500 neV which cannot ionize biological tissue (no radiation exposure) which is together with high tissue contrast advantage of MRI. The disadvantages are longer examination time (15\u201345\u00a0min), price, availability, and several contraindications."}
{"_id": "Radiology$$$5af26dd1-65cb-4c6a-8644-021bbc3c42cc", "text": "Imaging methods in nuclear medicine are characterized by lower spatial resolution than the radiological methods mentioned above, but they contain very specific functional information. Small amount of a specific radiopharmaceutical is injected into the patient and then emitted gamma photons are detected. Depending on the isotope used, one speaks of positron emission tomography (PET, beta+ tracer) or single photon emission computed tomography (SPECT, gamma tracer). Both methods can be combined into hybrid modalities mostly with CT for obtaining anatomical information."}
{"_id": "Radiology$$$0d3512ad-bee4-44da-9fd9-d6680d4c9256", "text": "In the first step, it is necessary to find the pathological area(s) and make a basic description. The process that identifies such areas or, in general, region of interest (ROI) is named segmentation or delineation and can be done manually or with the support of ML algorithms. Manual segmentation is a time consuming and demanding task, with relatively low level of reproducibility so it is beneficial to use semi- or fully automatic methods."}
{"_id": "Radiology$$$a3629067-d82a-42a2-9bb3-a9cfbf4cbfe0", "text": "Sometimes it is helpful to segment the pathology based on different histological tissue types, for example, necrotic part, active tumor, or edema but also precise anatomical localization, diameter or volume, shape, intensity, and changes compared to the previous examination."}
{"_id": "Radiology$$$1fbe65b6-5e19-45f9-9a6b-6ca3068693f9", "text": "After all variables are collected, the radiologist must decide which kinds of pathologies it could be. Occasionally, the radiological diagnoses are not unequivocal, for example, the pathology looks like high grade gliomas but with non-negligible probability it could be metastasis of some other primary tumor and the treatment of such different entities are completely different. Each hospital produces thousands of images per day, and it is obvious that usage of the same kind of computer algorithms or AI can save time, increase reproducibility and precision of diagnosis."}
{"_id": "Radiology$$$cc9e8332-8cc3-4f41-814d-c6c80194eb05", "text": "The concept of radiomics appeared in 2012 [321]. While the traditional analysis of imaging is based on the visual interpretation of simple features\u2014such as tumor size, general shape, contrast uptake, or signal intensity\u2014radiomics processes any type of imaging computationally and translates into complex quantitative data. Radiomics is based on qualitative and quantitative analyses, combining numerical data from medical imaging with clinical and biological characteristics to obtain predictive and/or prognostic information about patients. Indeed, the study of cellular interaction within tissues and intrinsic characteristics of medical imaging reflect the physiology and pathophysiology of the affected organ. The radiomics approach is: (1) Noninvasive; (2) Allows an evaluation of the studied tissues in their globality, thus characterizing their spatial heterogeneity; (3) Represents an easy way to follow the patient over time, allowing understanding the changes throughout the history of the disease and the therapeutic sequence. A typical radiomics workflow follows five steps as illustrated in Fig. 5.30.\n\nA workflow diagram begins with data selection, followed by imaging and segmentation, feature extraction and selection, modeling, and then to reporting results.\n\nFig. 5.30\nTypical radiomics workflow. The different steps are: (1) Data selection: choosing the image to analyze, the imaging protocol to use and the correlated outcome. (2) Imaging and segmentation with (semi-) automatic methods to improve reproducibility. (3) Feature extraction and selection with appropriate algorithms. (4) Modeling using available machine learning models. (5) Reporting results. (Adopted from Keek et al. [322] with permission)"}
{"_id": "Radiology$$$1c23d122-1b57-4645-805e-3d27055397a2", "text": "A workflow diagram begins with data selection, followed by imaging and segmentation, feature extraction and selection, modeling, and then to reporting results."}
{"_id": "Radiology$$$c694bfba-9729-4159-ac3a-2bf1ee4e251f", "text": "Combining radiomics features with deep learning features or semantic features may further improve prognostic performance. The changes over time may also be integrated (delta-radiomics). Several studies have proven the effectiveness of using these features independently in predictive modeling. As was mentioned above, radiologists make basic descriptions of pathology like volume, shape, etc. but the number of these descriptors are limited by the radiologist\u2019s time and his/her eyes. But there exist tens or hundreds of different descriptors which can describe pathology and a method which analyses all these descriptive parameters is called Radiomics and these parameters are called features."}
{"_id": "Radiology$$$179abf2e-12d9-4d8f-bc43-00e511c9270c", "text": "One can divide radiomics features into several classes like: (1) First order; (2) Two and three (2D/3D) Shape and; (3) Grey level class (e.g., Size zone, Neighboring tone, Run length, Co-occurrence, Dependency)."}
{"_id": "Radiology$$$184a99e9-1974-4643-8923-7172f95e1142", "text": "The first order features (more than 15) characterized distribution of voxels intensities so they can be commonly known histogram parameters like median, mean, or several quartiles. But they also include mathematically sophisticated parameters like energy, entropy, mean absolute deviation, root mean squared, skewness, or kurtosis (\u201cSharpness of the peak\u201d)."}
{"_id": "Radiology$$$44859ac3-886b-4d1f-b78e-ce0a345e6c4d", "text": "Shape features (2D or 3D, more than 20) are intensity-independent parameters which are extracted from segmented binary mask image or triangle mash. For example, 2D features can be mesh surface, perimeter, sphericity, maximum 2D diameter or elongation. As 3D shape features, one can mention, for example, mesh volume, surface area to volume ratio, compactness, or flatness."}
{"_id": "Radiology$$$f41b11fc-a199-457d-91f5-e09caace5102", "text": "The biggest features class (which can be subdivided) with more than 50 features is grey level class. For example, grey level size zone features are trying to quantify connected voxels in an image which share the same intensity and one can extract features like grey level non-uniformity, size-zone non-uniformity, grey level variance or zone entropy, etc. Neighboring grey tone features quantify differences between intensity of voxel and average intensity of neighbors\u2019 voxels within defined distance and one can extract features like coarseness, contrast, complexity, or strength."}
{"_id": "Radiology$$$f0b659c5-f723-42c0-9c86-733e849d5315", "text": "Radiomics create a model to predict clinical outcomes based on extracted features. Not all features have to be used, selection of features are done before modeling because lots of them are correlated to each other or can be unstable across a dataset. Clinical outcome which radiomics model can be diagnosis (benign or malignant, subtype or stage), treatment evaluation, or prognosis (survival coefficients)."}
{"_id": "Radiology$$$4b714292-668d-4e36-ba8b-43daabf26074", "text": "These days there exist hundreds of papers which evaluate the usefulness of radiomics in clinical practice mostly on CT data, but MRI and PET are becoming more common. Radiomics can be used in diagnosis as well as treatment evaluation of different oncological diseases like brain tumors, breast, lung-, prostate-, or colorectal cancer. Radiomics are being applied in the field of oncology in different settings to help decision-making such as:\nDifferentiation between human papillomavirus-positive and human papillomavirus-negative oropharyngeal tumors on contrast-enhanced CT [323].\n\nPrediction of tumor aggressiveness in prostate cancer [324].\n\nAssistance to automatic segmentation and sub-target volume definition in prostate cancer [325].\n\nPrediction of treatment response and outcome in head and neck and lung cancer (with combination of genomic features) [326\u2013328], rectum [329], esophageal [330], or prostate cancer [331].\n\nPrediction of toxicity in head and neck (xerostomia) [332] and lung (pneumonitis) [333] cancers.\n\nDifferential diagnosis between recurrence and RT-induced radionecrosis in brain [334]."}
{"_id": "Radiology$$$bbe19a3a-83d8-4e0a-bd93-4192dfc07d76", "text": "Differentiation between human papillomavirus-positive and human papillomavirus-negative oropharyngeal tumors on contrast-enhanced CT [323]."}
{"_id": "Radiology$$$a98c7942-d26f-48d2-9ca7-0da9b3e9c2df", "text": "Assistance to automatic segmentation and sub-target volume definition in prostate cancer [325]."}
{"_id": "Radiology$$$3e23135d-0717-4c21-9f19-f55e37e444a5", "text": "Prediction of treatment response and outcome in head and neck and lung cancer (with combination of genomic features) [326\u2013328], rectum [329], esophageal [330], or prostate cancer [331]."}
{"_id": "Radiology$$$c64ca552-38e4-4a0e-9f4d-1c20cf0981cd", "text": "Prediction of toxicity in head and neck (xerostomia) [332] and lung (pneumonitis) [333] cancers."}
{"_id": "Radiology$$$a81c089a-5a32-4e32-be5f-cd4dd4acb097", "text": "Although promising, the predictive power sometimes evidenced in the pilot studies need to be externally validated in independent datasets with numerous methodological pitfalls including imaging technique standardization."}
{"_id": "Radiology$$$faa8b02e-ade5-48ec-91a4-9cf77c600cdf", "text": "Q1.\nWhat is meant by the \u201ctherapeutic window\u201d? Mention several methods to widen the therapeutic window.\n\u00a0Q2.\nThe tumor volume doubling time (VDT) is heterogeneous among tumors and influences RT response. Discuss and reflect on different parameters that control VDT of tumors.\n\u00a0Q3.\nIt is important to estimate the growth fraction (GF) of tumors and several methods may be used in vitro and in vivo to assess this. Give some examples of methods and in what context they are applied.\n\u00a0Q4.\nDiscuss the link between the Hallmarks of Radiobiology and the Hallmarks of Cancer.\n\u00a0Q5.\nWhich of the below statements is wrong?(a)\nLowering the dose rate leads to greater sparing of late responding normal tissues than of tumors.\n\u00a0(b)\nThe process of redistribution might push cells from a radioresistant to a radiosensitive cell-cycle phase.\n\u00a0(c)\nDuring chronic low dose rate exposure, cells with long repair half times will be spared relative to their counterparts with rapid DNA damage repair.\n\u00a0(d)\nLow dose rate irradiation can be considered as a form of extreme fractionation.\n\u00a0\n\u00a0Q6.\nHow can dose rate affect be explained in terms of linear-quadratic model?\n\u00a0Q7.\nWhat are the classical factors that are used to predict RT response in a tumor?\n\u00a0Q8.\nList four techniques which are used to measure biomarkers to predict RT response.\n\u00a0Q9.\nOxygen enhancement ratio (OER) is seen with some but not all IR qualities. Please indicate which type (a\u2013d) that doesn\u2019t have OER.(a)\nX-rays\n\u00a0(b)\nGamma-rays\n\u00a0(c)\nNeutrons\n\u00a0(d)\n\u03b1-particles\n\u00a0\n\u00a0Q10.\nAll of the following statements about hypoxic cell radiosensitizers are true except one, please indicate and explain.(a)\nIncreases radiosensitivity of hypoxic cells\n\u00a0(b)\nNitroimidazole groups of drugs are commonly used\n\u00a0(c)\nPresence of nitro group in second position, decreases electron affinity and sensitization\n\u00a0(d)\nDose-limiting toxicity of Misonidazole is neurotoxicity\n\u00a0\n\u00a0Q11.\nGive some examples how photon radiation can induce modification extracellular signaling pathways.\n\u00a0Q12.\nTwo principal mechanisms of tumor metabolism participate in radiation resistance. Give their names.\n\u00a0Q13.\nWhat is radiation-induced abscopal effect in oncology?\n\u00a0Q14.\nDescribe the typical acute and late effects following exposure of the skin to radiation. Hints: target cells at risk, latent period, volume effect, pathology, recovery.\n\u00a0Q15.\nDefine and describe the late adverse effects of RT.\n\u00a0Q16.\nCan radionecrosis be avoided by choosing a more appropriate radiation modality?\n\u00a0Q17.\nHow can access to the forecasted 3D RT isodose curves allow for a better prevention of osteoradionecrosis of the mandible?\n\u00a0Q18.\nWhat is the main function of the stem cells?\n\u00a0Q19.\nWhat is the most radiosensitive group of stem cells?\n\u00a0Q20.\nDescribe some different characteristics of cancer stem cells which may contribute to RT resistance?\n\u00a0Q21.\nDescribe potential role of the intestinal microbiota in RT-induced adverse side effects (gut toxicity) or in RT efficiency concerning anti-tumor effects."}
{"_id": "Radiology$$$009ea9fe-6831-4b83-a075-c9111c6fa390", "text": "What is meant by the \u201ctherapeutic window\u201d? Mention several methods to widen the therapeutic window."}
{"_id": "Radiology$$$e01f655e-8cc0-490f-96a0-81d7f81b3a06", "text": "The tumor volume doubling time (VDT) is heterogeneous among tumors and influences RT response. Discuss and reflect on different parameters that control VDT of tumors."}
{"_id": "Radiology$$$61a6d2c5-a2a6-4b8f-8897-8aab88a2409c", "text": "It is important to estimate the growth fraction (GF) of tumors and several methods may be used in vitro and in vivo to assess this. Give some examples of methods and in what context they are applied."}
{"_id": "Radiology$$$349e985c-f783-42fa-9d5b-69ecd9a9ff3b", "text": "Discuss the link between the Hallmarks of Radiobiology and the Hallmarks of Cancer."}
{"_id": "Radiology$$$9c2b082b-6745-4a63-ac62-41ed5e60baff", "text": "Which of the below statements is wrong?(a)\nLowering the dose rate leads to greater sparing of late responding normal tissues than of tumors.\n\u00a0(b)\nThe process of redistribution might push cells from a radioresistant to a radiosensitive cell-cycle phase.\n\u00a0(c)\nDuring chronic low dose rate exposure, cells with long repair half times will be spared relative to their counterparts with rapid DNA damage repair.\n\u00a0(d)\nLow dose rate irradiation can be considered as a form of extreme fractionation."}
{"_id": "Radiology$$$08895f48-2c2b-4064-b271-faf9343a9d1b", "text": "Lowering the dose rate leads to greater sparing of late responding normal tissues than of tumors."}
{"_id": "Radiology$$$59f677b7-d4d6-4564-acd6-774ca904354b", "text": "The process of redistribution might push cells from a radioresistant to a radiosensitive cell-cycle phase."}
{"_id": "Radiology$$$49ae99c8-2e75-42c3-ba56-a60748926d9a", "text": "During chronic low dose rate exposure, cells with long repair half times will be spared relative to their counterparts with rapid DNA damage repair."}
{"_id": "Radiology$$$1e623d46-9ffa-4740-bc4d-e4991a5077e4", "text": "Low dose rate irradiation can be considered as a form of extreme fractionation."}
{"_id": "Radiology$$$03d363e3-fefc-4dd4-bd52-643f54318cfc", "text": "How can dose rate affect be explained in terms of linear-quadratic model?"}
{"_id": "Radiology$$$5c0b28bc-0d83-411d-8a53-c8c0762456cc", "text": "What are the classical factors that are used to predict RT response in a tumor?"}
{"_id": "Radiology$$$d30ac2e6-4639-4ec9-afa6-df76cfd243d3", "text": "List four techniques which are used to measure biomarkers to predict RT response."}
{"_id": "Radiology$$$87ef1175-8792-4f22-9a55-af07315c51a3", "text": "Oxygen enhancement ratio (OER) is seen with some but not all IR qualities. Please indicate which type (a\u2013d) that doesn\u2019t have OER.(a)\nX-rays\n\u00a0(b)\nGamma-rays\n\u00a0(c)\nNeutrons\n\u00a0(d)\n\u03b1-particles"}
{"_id": "Radiology$$$e14e28c5-f157-49d3-8ab3-2b7e6963e9d5", "text": "All of the following statements about hypoxic cell radiosensitizers are true except one, please indicate and explain.(a)\nIncreases radiosensitivity of hypoxic cells\n\u00a0(b)\nNitroimidazole groups of drugs are commonly used\n\u00a0(c)\nPresence of nitro group in second position, decreases electron affinity and sensitization\n\u00a0(d)\nDose-limiting toxicity of Misonidazole is neurotoxicity"}
{"_id": "Radiology$$$1cb9a3d1-40b9-4132-b633-7c9e64b50d71", "text": "Presence of nitro group in second position, decreases electron affinity and sensitization"}
{"_id": "Radiology$$$3e575547-1883-410c-9504-52ec23287856", "text": "Give some examples how photon radiation can induce modification extracellular signaling pathways."}
{"_id": "Radiology$$$96d3ea0c-a8f5-4e5f-84b1-58827af8a269", "text": "Two principal mechanisms of tumor metabolism participate in radiation resistance. Give their names."}
{"_id": "Radiology$$$46aa215d-921c-4fac-8e6a-24be45e9a207", "text": "Describe the typical acute and late effects following exposure of the skin to radiation. Hints: target cells at risk, latent period, volume effect, pathology, recovery."}
{"_id": "Radiology$$$d759fab1-8890-43f1-8efd-6227c94398f9", "text": "Can radionecrosis be avoided by choosing a more appropriate radiation modality?"}
{"_id": "Radiology$$$8fcb39e6-514c-4acc-a7f9-e99bb3c9b147", "text": "How can access to the forecasted 3D RT isodose curves allow for a better prevention of osteoradionecrosis of the mandible?"}
{"_id": "Radiology$$$1186f5c0-bf74-4495-bca5-f1d4198e37de", "text": "Describe some different characteristics of cancer stem cells which may contribute to RT resistance?"}
{"_id": "Radiology$$$da11c68e-2bac-4bfa-af7c-71d1188233f8", "text": "Describe potential role of the intestinal microbiota in RT-induced adverse side effects (gut toxicity) or in RT efficiency concerning anti-tumor effects."}
{"_id": "Radiology$$$fd034889-7c0a-4714-b0d8-3ffae313e342", "text": "SQ1.\nTherapeutic window: The difference between tumor control probability and normal tissue complication probability at identical irradiation dose. Methods to widen the therapeutic window: Dose fractionation, reduction of the normal tissue/organ at risk exposed volume, combination therapy.\n\u00a0SQ2.\nVDT is influenced by localization of the tumor, i.e., tumor site. It is also influenced if the tumor is a primary or a metastatic lesion where the latter often have reduced VDT as a result of limited nutrition and oxygen levels. VDT is also influenced by histology of the tumor, i.e., the inherited growth capacity of the cells. Finally, VDT is influenced by tumor heterogeneity in proliferative signaling cascades which is a consequence of different genomic- and signaling make ups of the individual tumors.\n\u00a0SQ3.\nIn vitro tumor cell progression through S-phase can be monitored by BrdUrd or IdUrd-labeling of cells. These tracers are incorporated into DNA as tumor pass through S-phase and by using an antibody against BrdUrd or IdUrd, cells in S-phase can be determined using flowcytometry. Another method utilizes 3H-thymidine to assess DNA-synthesis by flow cytometry. The third method is based on PET-analyses of tumors in vivo which have been pulsed with radio-labeled 18F-fluoro-3\u2032-deoxy-3\u2032-l-fluorothymidine (FLT). FLT is phosphorylated by Thymidine Kinase 1 which has an S-phase activity. Hence, FLT tracer levels are a surrogate for S-phase cells which can be evaluated by PET scanning. Finally, the proliferation rate in a tumor biopsy can be analyzed by immunohistochemical staining for the nuclear Ki-67 antigen, reflecting S-phase proportion of cells.\n\u00a0SQ4.\nLikely links are shown below.\nHallmark of radiobiology\n\nHallmark of cancer\n\nRepair\n\nGenomic instability and mutations, enabling replicative immortality\n\nRedistribution\n\nSustaining proliferative signaling\n\nRepopulation\n\nEvading growth suppressors, sustaining proliferative signaling, tumor-promoting activation\n\nRadiosensitivity\n\nResisting cell death, deregulating cellular energetics\n\nReoxygenation\n\nInducing angiogenesis\n\nReactivation of the immune response\n\nAvoiding immune destruction, tumor-promoting activation, activation invasion and metastasis\n\n\u00a0SQ5.\nAlternative (c) is the wrong answer. Accumulation of DNA damage is larger in cells with long repair half times than for cells which show rapid repair of their DNA damages.\n\u00a0SQ6.\nSingle-track and double-track actions can both induce DNA double strand breaks. There is no correlation between dose rate and single-track X-ray lesion (\u03b1contribution in the LQ model). In a double-track action, different X-ray photon tracks produce the two interactions of single strand DNA lesions, and therefore the formation of double strand lesions is proportional to the radiation dose squared (\u03b2 in the LQ model).\n\u00a0SQ7.\nTumor oxygen status, the degree of repopulation or proliferation rate and intrinsic radiosensitivity.\n\u00a0SQ8.\nProteomics, genomics, epigenomics, genomics, or transcriptomics, used for measuring proteins, DNA/chromatin, DNA, or RNA and transcription, respectively.\n\u00a0SQ9.\nAlternative (d). OER is 1 for high LET radiation like \u03b1- particles.\n\u00a0SQ10.\nAlternative (c). The presence of the nitro group in second position, increases electron affinity and radiosensitization.\n\u00a0SQ11.\nPhoton beam activates major oncogenic signaling pathways such as Ras, MAPK/ERK, and PI3K/AKT in part via the epidermal growth factor receptor (EGFR) cascade. Radiation resistance is associated with these signaling cascades due to their pro-survival nature. For example, when AKT is phosphorylated, tumor cells are protected by decreased autophagy and apoptosis, as well as increased DNA repair capacity. Mutated RAS has also been associated with resistance to photons in cancer cells.\n\u00a0SQ12.\nThe mitochondrial and or glucose metabolism, respectively.\n\u00a0SQ13.\nAbscopal effects are radiation-induced systemic anti-tumor immune responses in which irradiation of a primary tumor or large metastasis causes remission of distant, non-irradiated lesions.\n\u00a0SQ14.\nAcute effects: Dry skin (impairment of cell production), epilation (injury to hair follicles), erythema (vascular leakage). Latency time: Few weeks. Large volume effect: The smaller the volume, the higher the tolerance to radiation. Transient effect: Reversible injury. Late effects: Gangrene, ulcer, telangiectasia (vascular damage), fibrosis (increase in collagen fibers). Latency: Months-years. Large volume effect: The smaller the volume, the higher the tolerance to radiation. Chronic, irreversible injury.\n\u00a0SQ15.\nLate effects of radiation are progressive, irreversible and occur months, years, or decades after radiation therapy. They are based on an interactive response of parenchymal cells, vascular endothelium and fibroblasts, with a contribution from immune cells, especially macrophages. Tissues and organs are affected by atrophy, fibrosis, or necrosis, which can severely impair their functions and lead to a loss of function.\n\u00a0SQ16.\nNo. Since the risk of radionecrosis remains life-long the affected tissues are at danger with the total radiation dose being the primary risk factor for the tissue involved, combined with other risk factors.\n\u00a0SQ17.\nAdapting the preventive extraction of teeth to the risk zone of >50\u201360 Gy would allow for a more appropriate dental management: more aggressive in the >60 Gy zone and far less aggressive in the other areas of the jaw, improving the quality of life of these patients. The fewer extractions in highly irradiated areas, the lesser the risk for ORN.\n\u00a0SQ18.\nThe principal function of stem cells is to maintain tissue homeostasis including continuous regeneration and associated constant number of cells.\n\u00a0SQ19.\nBone marrow stem cells.\n\u00a0SQ20.\nThe answer is displayed in Fig. 5.29. In brief, CSC may have (1) Increased DNA repair capacity which allows them to handle IR-induced DNA DSBs; (2) Increased signaling networks that block IR-induced cell death including deficient pro-apoptotic signaling and increased anti-apoptotic signaling; (3) CSCs have slow proliferation and may therefore not be so sensitivity to IR-induced DNA damage.\n\u00a0SQ21.\nStudies showed evidence of the existence of bidirectional effects of RT on the tumor and on the intestinal microbiota. In prospective clinical studies, a reduction of the fecal microbial diversity during and after pelvic RT was measured in patients suffering from intestinal complications. Also, RT-induced modification of microbiota diversity and composition can modify the host immune response and in turn the effectiveness of the anticancer treatment themselves including RT."}
{"_id": "Radiology$$$70deb499-f4ee-469e-befe-474e4a45f2ca", "text": "Therapeutic window: The difference between tumor control probability and normal tissue complication probability at identical irradiation dose. Methods to widen the therapeutic window: Dose fractionation, reduction of the normal tissue/organ at risk exposed volume, combination therapy."}
{"_id": "Radiology$$$698998b3-47fc-4743-9080-1cc8e3f8ef7a", "text": "VDT is influenced by localization of the tumor, i.e., tumor site. It is also influenced if the tumor is a primary or a metastatic lesion where the latter often have reduced VDT as a result of limited nutrition and oxygen levels. VDT is also influenced by histology of the tumor, i.e., the inherited growth capacity of the cells. Finally, VDT is influenced by tumor heterogeneity in proliferative signaling cascades which is a consequence of different genomic- and signaling make ups of the individual tumors."}
{"_id": "Radiology$$$61347262-2ebf-45d7-a864-1d86c4a538de", "text": "In vitro tumor cell progression through S-phase can be monitored by BrdUrd or IdUrd-labeling of cells. These tracers are incorporated into DNA as tumor pass through S-phase and by using an antibody against BrdUrd or IdUrd, cells in S-phase can be determined using flowcytometry. Another method utilizes 3H-thymidine to assess DNA-synthesis by flow cytometry. The third method is based on PET-analyses of tumors in vivo which have been pulsed with radio-labeled 18F-fluoro-3\u2032-deoxy-3\u2032-l-fluorothymidine (FLT). FLT is phosphorylated by Thymidine Kinase 1 which has an S-phase activity. Hence, FLT tracer levels are a surrogate for S-phase cells which can be evaluated by PET scanning. Finally, the proliferation rate in a tumor biopsy can be analyzed by immunohistochemical staining for the nuclear Ki-67 antigen, reflecting S-phase proportion of cells."}
{"_id": "Radiology$$$36b0b533-307c-4128-89b6-4c8d098ac7f8", "text": "Likely links are shown below.\nHallmark of radiobiology\n\nHallmark of cancer\n\nRepair\n\nGenomic instability and mutations, enabling replicative immortality\n\nRedistribution\n\nSustaining proliferative signaling\n\nRepopulation\n\nEvading growth suppressors, sustaining proliferative signaling, tumor-promoting activation\n\nRadiosensitivity\n\nResisting cell death, deregulating cellular energetics\n\nReoxygenation\n\nInducing angiogenesis\n\nReactivation of the immune response\n\nAvoiding immune destruction, tumor-promoting activation, activation invasion and metastasis"}
{"_id": "Radiology$$$61076522-0ea6-4034-9cb0-86ec7e5f2187", "text": "Alternative (c) is the wrong answer. Accumulation of DNA damage is larger in cells with long repair half times than for cells which show rapid repair of their DNA damages."}
{"_id": "Radiology$$$58bb716d-146f-4f3a-9f5a-728a06119560", "text": "Single-track and double-track actions can both induce DNA double strand breaks. There is no correlation between dose rate and single-track X-ray lesion (\u03b1contribution in the LQ model). In a double-track action, different X-ray photon tracks produce the two interactions of single strand DNA lesions, and therefore the formation of double strand lesions is proportional to the radiation dose squared (\u03b2 in the LQ model)."}
{"_id": "Radiology$$$dee3fe80-414a-4761-8ee1-da1522f0ce90", "text": "Tumor oxygen status, the degree of repopulation or proliferation rate and intrinsic radiosensitivity."}
{"_id": "Radiology$$$b47a011c-f559-4707-a7e8-a6e986a46cb9", "text": "Proteomics, genomics, epigenomics, genomics, or transcriptomics, used for measuring proteins, DNA/chromatin, DNA, or RNA and transcription, respectively."}
{"_id": "Radiology$$$89a5db8b-3100-4e3c-bbc1-c09f4b2ec07e", "text": "Alternative (d). OER is 1 for high LET radiation like \u03b1- particles."}
{"_id": "Radiology$$$51636063-4f95-47c2-82b2-d16a8369c85d", "text": "Alternative (c). The presence of the nitro group in second position, increases electron affinity and radiosensitization."}
{"_id": "Radiology$$$fce2d654-e64d-4c27-a5ce-535a6c53c39f", "text": "Photon beam activates major oncogenic signaling pathways such as Ras, MAPK/ERK, and PI3K/AKT in part via the epidermal growth factor receptor (EGFR) cascade. Radiation resistance is associated with these signaling cascades due to their pro-survival nature. For example, when AKT is phosphorylated, tumor cells are protected by decreased autophagy and apoptosis, as well as increased DNA repair capacity. Mutated RAS has also been associated with resistance to photons in cancer cells."}
{"_id": "Radiology$$$84ce03f7-2a25-404a-8fff-900a77c99309", "text": "Abscopal effects are radiation-induced systemic anti-tumor immune responses in which irradiation of a primary tumor or large metastasis causes remission of distant, non-irradiated lesions."}
{"_id": "Radiology$$$f43a4cac-ac6f-4d1c-89fb-0404f0556536", "text": "Acute effects: Dry skin (impairment of cell production), epilation (injury to hair follicles), erythema (vascular leakage). Latency time: Few weeks. Large volume effect: The smaller the volume, the higher the tolerance to radiation. Transient effect: Reversible injury. Late effects: Gangrene, ulcer, telangiectasia (vascular damage), fibrosis (increase in collagen fibers). Latency: Months-years. Large volume effect: The smaller the volume, the higher the tolerance to radiation. Chronic, irreversible injury."}
{"_id": "Radiology$$$01bb3b46-46f7-4fe6-9ac5-fda007356556", "text": "Late effects of radiation are progressive, irreversible and occur months, years, or decades after radiation therapy. They are based on an interactive response of parenchymal cells, vascular endothelium and fibroblasts, with a contribution from immune cells, especially macrophages. Tissues and organs are affected by atrophy, fibrosis, or necrosis, which can severely impair their functions and lead to a loss of function."}
{"_id": "Radiology$$$c186badd-0ddc-4df8-b824-f9859fc277c6", "text": "No. Since the risk of radionecrosis remains life-long the affected tissues are at danger with the total radiation dose being the primary risk factor for the tissue involved, combined with other risk factors."}
{"_id": "Radiology$$$38b461be-1fde-44b9-8960-d861ab15beae", "text": "Adapting the preventive extraction of teeth to the risk zone of >50\u201360 Gy would allow for a more appropriate dental management: more aggressive in the >60 Gy zone and far less aggressive in the other areas of the jaw, improving the quality of life of these patients. The fewer extractions in highly irradiated areas, the lesser the risk for ORN."}
{"_id": "Radiology$$$eace6b76-2ea7-4d21-94ba-e46f8917a78d", "text": "The principal function of stem cells is to maintain tissue homeostasis including continuous regeneration and associated constant number of cells."}
{"_id": "Radiology$$$2692ba28-19f4-4b82-b7e3-37f4640bd0e3", "text": "The answer is displayed in Fig. 5.29. In brief, CSC may have (1) Increased DNA repair capacity which allows them to handle IR-induced DNA DSBs; (2) Increased signaling networks that block IR-induced cell death including deficient pro-apoptotic signaling and increased anti-apoptotic signaling; (3) CSCs have slow proliferation and may therefore not be so sensitivity to IR-induced DNA damage."}
{"_id": "Radiology$$$d89cd71d-9072-41ba-b15a-f9aedd7438ac", "text": "Studies showed evidence of the existence of bidirectional effects of RT on the tumor and on the intestinal microbiota. In prospective clinical studies, a reduction of the fecal microbial diversity during and after pelvic RT was measured in patients suffering from intestinal complications. Also, RT-induced modification of microbiota diversity and composition can modify the host immune response and in turn the effectiveness of the anticancer treatment themselves including RT."}
{"_id": "Radiology$$$e1285792-56b1-4905-975c-1f1a4766dd74", "text": "Radiotherapy (RT) relies on the effect of ionizing radiation (IR) to biological matter, i.e., cells. The radiation is transferring its energy to atoms and molecules present in the cells, which lie in the path of the radiation, and therefore ionizing them. These ionizations, i.e., the removal of electrons from the atom, lead to the breaking of chemical bonds in the molecules. If these ionizations occur in the cell nucleus, the DNA, carrier of the human genome, is damaged. In RT, the capability of radiation to damage the genome is exploited to kill tumor cells. The most important quantity to define the damage, which is caused, is the dose\n\n (6.1)i.e., the energy transferred from the ion to the matter (dE) by unit mass (dM). In general, one can say that the higher the dose, the larger the damage and the higher the probability of killing a cell. However, the same physical dose of different types of radiation can cause different damage in the cells. Various types of radiation are utilized for RT. These types of radiation can be distinguished by the so-called depth dose distribution, which is the dose which is transferred to matter along the path of radiation as shown in Fig. 6.1.\n\nA line graph presents relative dose versus depth. Cobalt 60, 2 M V photons, and 250 M e V electrons rise before declining, while 15 M e V electrons, 250 M e V per u carbon, and 150 M e V protons rise and drop before plateauing, with 250 M e V electrons having the highest value at the endpoint.\n\nFig. 6.1\nComparison of the relative depth dose distribution of 15 MeV electrons (green), 250 MeV electrons (purple), 2 MeV photons (red), 150 MeV protons (dark blue), and 250\u00a0MeV/u carbon (turquoise) and cobalt 60 (orange)"}
{"_id": "Radiology$$$de379211-84b4-4a76-8fe5-b859ecd78fc4", "text": "A line graph presents relative dose versus depth. Cobalt 60, 2 M V photons, and 250 M e V electrons rise before declining, while 15 M e V electrons, 250 M e V per u carbon, and 150 M e V protons rise and drop before plateauing, with 250 M e V electrons having the highest value at the endpoint."}
{"_id": "Radiology$$$89dbaf87-5bd8-42b2-9af6-61ca661b69c3", "text": "Electron radiation transfers most of its energy just after it interacts with matter, i.e., tissue, making it suitable for the treatment of tumors close to the skin. If one uses electrons with higher energy, such as the shown 250 MeV electrons, the dose peak can be shifted deeper into the tissue. However, this comes with the disadvantage that the maximum range is also longer, resulting in more dose to the normal tissue beyond the tumor. Furthermore, such electron beams are quite complicated to produce. For photon beams used in RT, the dose increases in the so-called build-up region until it reaches the maximal dose and then gradually decreases. The depth of the maximal dose can be a few \u03bcm (for kV beams, i.e., beams with particle energy in the kilovolt regime) or several mm or cm (for MV (megavolt) beams). In contrast to electrons and photons, particles such as protons or high linear energy transfer (LET) carbon ions show a totally different dose distribution depth. The ions deliver a low dose when entering tissue. With depth this transfer is slowly increasing, while the ion gets slower. With further energy loss and decreasing speed, the dose drastically increases and reaches a maximum just before the ion stops in the tissue. This unique dose distribution is called the Bragg curve in honor to the physicist William Henry Bragg, who discovered this behavior in 1904 [1]. To widen the treatment depth range, a spread-out Bragg peak (SOBP) is created by varying the energy of the incident proton beam. As a result, a uniform dose can be delivered to the tumor. The radiobiological impact of particles with high LET is higher compared to photons, and it increases dramatically in the distal edge and fall-off. The uncertainty in relative biological effectiveness (RBE) of ion beams is still a limitation in its clinical application and should be considered during the treatment planning as a part of the process leading to a robust treatment plan. A detailed description about the physical and biological interactions of radiation to biological matter and the consequences for the biological effect can be found in Chaps. 2 and 3."}
{"_id": "Radiology$$$f9074e5a-6954-4a68-ad1f-52b53e789287", "text": "Typical conventionally fractionated irradiation schemes use 2 Gy fractions, 5 fractions per week for 3\u20137\u00a0weeks, depending on the tumor type.\n\nAlternative radiation schemes, i.e., either smaller or larger sized fractions, multiple fractions per day, or different overall treatment time should be based on the various biological processes and response characteristics of both the normal and malignant tissues in the exposed volume."}
{"_id": "Radiology$$$4109da14-6df2-4135-86a1-a0d6f2174b98", "text": "Typical conventionally fractionated irradiation schemes use 2 Gy fractions, 5 fractions per week for 3\u20137\u00a0weeks, depending on the tumor type."}
{"_id": "Radiology$$$870a2c7b-aba8-4d50-82f8-b1397681530c", "text": "Alternative radiation schemes, i.e., either smaller or larger sized fractions, multiple fractions per day, or different overall treatment time should be based on the various biological processes and response characteristics of both the normal and malignant tissues in the exposed volume."}
{"_id": "Radiology$$$a154fdeb-72a1-4ac3-990e-64365286c0d8", "text": "When using radiation for cancer treatment purposes, the total radiation dose is generally applied in a regimen with multiple small fractions, aiming to reach tumor kill while sparing adjacent normal, healthy tissues, and organs. Most tumors are treated with a conventional fractionation regimen, which is characterized by daily fractions of 1.8\u20132\u00a0Gy, 5\u00a0days per week, for a duration of 3\u20137\u00a0weeks, reaching a total dose of 30\u201370 Gy. However, considering the radiation sensitivity and volume of the particular tumor type to be irradiated, as well as that of the normal tissue or organs at risk (OAR), an alternative irradiation regimen might be preferred. The use of an alternative radiation scheme should be motivated, either technically, e.g., by minimizing the volume of the normal tissue in the radiation field by using precision RT or on the basis of the biological characteristics of the malignant tissue, i.e., the 6R\u2019s (see Chap. 5). Apart from technical and radiobiological arguments, department logistics as well as patients\u2019 condition or patients\u2019 comfort might justify the choice of an alternative radiation treatment (Box 6.1). Typical characteristics of fractionation regimens and their radiobiological rationale are presented in Table 6.1 and discussed below.Table 6.1\nCharacteristics of radiotherapy treatment regimen and involved radiobiological processes. (Reproduced with permission from [2])\n\nRadiation treatment regimen\n\nConventional fractionation\n\nHyperfractionation\n\nAccelerated fractionation\n\nHypofractionation\n\nSBRT and SRS\n\nTotal dose (Gy)\n\n70\n\n\u226570\n\n<70\n\n<70\n\n<30\n\nFraction size (Gy)\n\n1.8\u20132\n\n<1.8\n\n\u22652\n\nMostly 2.5\u201310\n\nMostly ~12\u201325\n\nNumber of fractions per day\n\n1\n\n2\u20133\n\n1\n\n1\n\n1\n\nTreatment (days per week)\n\n5\n\n5\n\n6\n\n\u22645\n\n1 or a few\n\nOverall treatment time (weeks)\n\n7\n\n7\n\nUp to ~5\n\nUp to ~5\n\n\u2013\n\nRadiobiological reasoning\u2014note the 6 Rs of Radiobiology\n\nNormal tissue sparing via Repair and Repopulation. Tumor control via Redistribution and Reoxygenation. Reactivation of the immune response.\n\nExploitation of differences in Radiosensitivity and Repair and\u2014kinetics between normal and tumor cells. Reactivation of the immune response.\n\nOvercoming tumor cell Repopulation. Reactivation of the immune response.\n\nOvercoming tumor cell Repopulation.\n\nOvercoming tumor cell Repopulation."}
{"_id": "Radiology$$$7cf9b729-cf6e-45ad-814c-3e230c7c3cc1", "text": "The relationship between the number of fractions and the total dose for a clinical radiation regimen is presented in Fig. 6.2.\n\nA graph of total doses versus number of fractions. Radiosurgery has a vertical rise from (1, 10) to (1, 25), hypo-fractionation rises from (2, 15) to (10, 30), conventional fractionation rises from (8, 11) to (40, 80), and hyperfractionation increases from (30, 45) to (80, 80). Data are estimated.\n\nFig. 6.2\nFractionation regimen used in clinical practice. (Reproduced with permission from [3])"}
{"_id": "Radiology$$$ef90c7ce-4c5a-436c-901e-8e1c425fec63", "text": "A graph of total doses versus number of fractions. Radiosurgery has a vertical rise from (1, 10) to (1, 25), hypo-fractionation rises from (2, 15) to (10, 30), conventional fractionation rises from (8, 11) to (40, 80), and hyperfractionation increases from (30, 45) to (80, 80). Data are estimated."}
{"_id": "Radiology$$$ea7b709b-e161-45b3-bc3b-740061040864", "text": "The biological rationale of hyperfractionation is the advantage of application of multiple small-sized fractions compared with conventional 2 Gy fractions to further spare the normal tissues relative to the malignant tissues. Because of the higher total dose, hyperfractionation could increase the tumor control probability. To limit the duration of the overall treatment time, generally 2\u20133 fractions per day, typically ~1.4\u00a0Gy, separated 4\u20136\u00a0h between the fractions are given. Some hyperfractionation clinical trials, however, showed an increase in late normal tissue side effects, which has been ascribed to the short time interval between fractions for complete repair of sublethal DNA damages, since late-responding tissues do have long repair half times in the order of 2\u20134\u00a0h. Additionally, hyperfractionation puts a heavy logistical burden on the RT department and the patient, especially in children who may need anesthesia."}
{"_id": "Radiology$$$6aefdf15-8cb5-4513-ae24-e307f01533f1", "text": "The rationale of both hypo- and accelerated fractionation strategies can be found in shortening the overall treatment time to anticipate tumor cell proliferation/repopulation. Generally, fractions larger than 2 Gy fractions are applied with few fractions per week, allowing to shorten the overall treatment duration with a few weeks versus conventional regimens. The hypofractionation approach has become feasible because of currently available precision radiation techniques and technology, with optimized radiation dose distribution."}
{"_id": "Radiology$$$e1b80fbc-a0b7-49bb-a18d-8b2c124344ec", "text": "The drawback of using high fraction sizes, the rationale, pro- and contra biological arguments, is discussed in the next Sect. 6.3."}
{"_id": "Radiology$$$910c23f0-4d85-41c8-ba68-281dc32aef51", "text": "The term accelerated fractionation applies to the use of multiple fractions per day, or increasing the number of treatment days per week (e.g., continue radiation during the weekend) to deliver a higher average total radiation dose than conventionally used. Hence, the overall treatment time of accelerated regimen is reduced. Often, both hypo- and hyperfractionated irradiation fit in this definition of accelerated fractionation. A typical example is the Continuous Hyperfractionated Accelerated RadioTherapy (CHART) treatment scheme, with 36 fractions of 1.5\u00a0Gy, total dose of 54 Gy in 12\u00a0days. In that scheme three fractions of 1.5 Gy were applied per day, with an interfraction time interval of 6\u00a0h, for 12\u00a0days, including the weekend. Details regarding the CHART clinical trials and outcomes are available in the literature. In particular, head and neck cancer patients with high epidermal growth factor receptor (EGFR) expressing tumors benefited from CHART [4]."}
{"_id": "Radiology$$$7888d0ed-a993-494e-aedd-d545b3f29ea4", "text": "Historically, the term stereotactic radiotherapy was used for a type of external RT of the brain that uses dedicated equipment being a stereotactic frame fixed to the head with screws just penetrating the outer part of the skull. This frame was used to immobilize the head, position the patient, and create a stereotactic \u201cspace\u201d with a coordinate system that allows target definition in an X-, Y-, and Z-axis. The term stereotactic radiosurgery (SRS) is used when a single fraction of stereotactically guided conformal irradiation is delivered to a coordinate-defined target. More modern fixation systems no longer require the placement of an invasive frame, but make use of advanced thermoplastic masks combined with position verification and adaptation systems of the treatment machine\u2019s table. Different delivery systems can be used for radiosurgery: the originally SRS-dedicated GammaKnife system (using 201 small 60-Co sources) or linac-based systems (linear accelerator, CyberKnife, Tomotherapy)."}
{"_id": "Radiology$$$7962d989-5a23-40ba-b275-e0a6605949b7", "text": "Typical indications are single (or up to 3\u20135) brain metastases, meningiomas, acoustic neuromas, or arteriovenous malformations, all smaller than 3 cm in diameter. Depending on the indication, doses range between 12 Gy (benign lesions) and 20\u201325 Gy (metastases). Some centers also use radiosurgery to treat benign conditions like epilepsy and trigeminal neuralgia, requiring doses of 20\u201325 Gy up to 60\u201380\u00a0Gy, respectively."}
{"_id": "Radiology$$$37a0fe38-963c-4c38-b5d7-c2d422112d1a", "text": "The appearance of the effect of radiosurgery usually takes several months and may be accompanied by an inflammatory reaction that mimics tumor growth in the first 1\u20133\u00a0years. In some cases, overt brain radionecrosis may develop, requiring treatment with steroids or rarely the need for surgical removal of the affected area (see also Chap. 5) (Box 6.2)."}
{"_id": "Radiology$$$421c5bc5-3d90-45ae-8314-1cafc1d10653", "text": "Hypofractionation is the use of radiation dose fractions considerably larger than the conventional fraction size of 2 Gy.\n\nHypofractionation could be beneficial over conventional fractionation because of precision RT together with specific biological phenomena such as hypoxia and sensitivity to dose fractionation of both the tumor target volume and organs at risk."}
{"_id": "Radiology$$$56f4a402-b0d6-498f-b160-7d8f619ea42a", "text": "Hypofractionation is the use of radiation dose fractions considerably larger than the conventional fraction size of 2 Gy."}
{"_id": "Radiology$$$d144a24d-50f6-4808-9906-f507fbf5dfd7", "text": "Hypofractionation could be beneficial over conventional fractionation because of precision RT together with specific biological phenomena such as hypoxia and sensitivity to dose fractionation of both the tumor target volume and organs at risk."}
{"_id": "Radiology$$$815057c7-a04b-41bc-ac9f-e0f38ac23d41", "text": "Fractionated RT, using multiple small-sized fractions of 1.8\u20132\u00a0Gy, is the standard treatment of cancer patients. Over many decades, large evidence has been obtained from experimental studies in\u00a0vitro or in\u00a0vivo and later in clinical studies regarding the biological rationale of fractionated irradiation. Abundant evidence exists on the differential effect of fractionation between late-responding normal tissues and early responding normal tissues or tumors. Most normal tissues and organs benefit from fractionated RT, meaning that they can tolerate a higher total dose, while tumors are only slightly spared by dose fractionation. The smaller the fraction size\u2014taking the overall treatment time allowing tumor cell repopulation into account\u2014the wider the therapeutic window. Having learned that fractionation is a great method to spare normal tissues while keeping tumor control equal, hypofractionation, i.e., the use of dose fractions substantially larger than conventional 2 Gy fractions (see also Chap. 5) sounds not as a good idea. However, for two main reasons, hypofractionation has gained importance in radiation oncology: \u03b1"}
{"_id": "Radiology$$$72992717-26fe-418b-93c5-9ff9bc6ab25f", "text": "(1) Clinical data have shown that some tumor types like prostate carcinoma, malignant melanoma, and liposarcoma, are almost as sensitive to fractionated irradiation as their surrounding normal tissues. Such tumors can tolerate a higher biological dose than formerly thought when treated with 2 Gy fractions, hence behaving like late-responding normal tissues and thus are relatively spared by fractionation. Indeed, these tumor types are characterized with a low \u2329\u03b1/\u03b2 value of ~1\u20132 Gy in the Linear Quadratic (LQ) model. Breast and esophageal cancers also have \u03b1/\u03b2 values close to those for normal tissues, in the order of ~5 Gy. (2) With the implementation of high precision RT techniques, highly conformal 3D dose distributions to the target volume can be obtained, with minimal radiation exposure to adjacent critical normal tissues and OAR. The HyTEC initiative (Hy dose per fraction, hypofractionated Treatment Effects in the Clinic) is to systemically pool published peer-reviewed clinical data to further define dose, volume, and outcome estimates for both normal tissue complication probability and tumor control [5] for SRS and SBRT, where single high radiation doses are common practice. Under certain conditions, like high conformity of RT with steep dose gradients toward the surrounding normal tissues, hypofractionation could be beneficial over conventional fractionation. In this section, the radiobiological pro- and contra arguments of hypofractionation, listed in Table 6.2 are discussed.Table 6.2\nHypofractionation: pro and contra biological arguments\n\nPros\n\n\u2022\u2003If \u03b1/\u03b2 ratio tumor\u00a0<\u00a0\u03b1/\u03b2 ratio normal tissue\n\n\u2022\u2003Only if small normal tissue/OAR volumes are exposed: high conformity RT\n\n\u2022\u2003Direct vascular injury\n\n\u2022\u2003Shorter overall time: beneficial in case of rapid proliferating tumors\n\n\u2022\u2003If the onset of accelerated tumor cell repopulation is faster using high-dose fractions, dose reduction without loss of tumor control could be achieved while diminishing late toxicity\n\n\u2022\u2003\u201dBiological dose\u201d escalation, which might result in better tumor control\n\n\u2022\u2003Activation of the immune response to attack tumor cells inside the irradiated volume and at distance, the abscopal effect\n\n\u2022\u2003Lower probability of induction of secondary tumors\n\nCons\n\n\u2022\u2003Mostly, \u03b1/\u03b2 ratio tumor\u00a0>\u00a0\u03b1/\u03b2 ratio normal tissue\n\n\u2022\u2003High-dose fractions are detrimental for normal tissues: higher probability of normal tissue complications, unless dose gradients are steep and the irradiated volume small\n\n\u2022\u2003No benefit from sensitization of hypoxic tumor cells via reoxygenation between fractions\n\n\u2022\u2003Radiosensitizing agents are potentially less effective when combined with high-dose fractions"}
{"_id": "Radiology$$$af3c3468-29b6-406d-9d58-04e3b1184d54", "text": "The validity of the LQ model at high fraction sizes above approximately 6 Gy is questionable, and alternative radiobiological models are proposed. However, a strong pro-argument was derived from clinical data from non-small cell lung cancer patients treated with SBRT, either with a single dose or hypofractionated with 3\u20138 fractions. From the study [6], it was evident that the clinically observed increase in tumor could be ascribed to radiation dose escalation, i.e., an increased Biologically Effective Dose (BED) according to the LQ equation. BED values were calculated for the various hypofractionation schemes including SBRT fraction sizes of 22 Gy. No adaptation or correction was made when using the conventional LQ model. The analysis showed a clear correlation between treatment outcome and the BED, even at extreme high BED values. Hence, there is still a discrepancy between theoretical and experimental validity of the LQ model. However, since the model describes the clinical data on tumor control over a wide range of dose, fraction sizes, and treatment durations [6], it might still be valid in predicting RT outcomes in certain conditions."}
{"_id": "Radiology$$$fe315789-ae05-42d6-a0c6-c0f07289d28a", "text": "Hypoxia is a state of reduced oxygen availability or decreased oxygen partial pressure below a critical threshold (generally at pO2 of 2.5 or 5\u00a0mmHg). The Oxygen Enhancement Ratio (OER) is around 3 for most cells: for sterilization of hypoxic cells, a three times higher irradiation dose is required than for normoxic cells. Hence, hypoxia can cause resistance to RT, which has been observed in many tumor types. Information about the role of oxygen in RT, the OER, and related radiation sensitivity is given in Chap. 5."}
{"_id": "Radiology$$$454824d3-6fa1-411a-9759-c0024455e578", "text": "In fractionated RT, during the time interval between daily applied irradiation fractions and during the full course of RT, hypoxic cells can be re-oxygenated and become more sensitive to the next irradiation dose (see Chap. 5). If reoxygenation is efficient between dose fractions, the presence of hypoxic cells does not have a significant effect on the outcome of a multi-fractionation scheme. In a hypofractionation regimen, the time period to obtain full reoxygenation of hypoxic tumor cells might be too short. Animal data on the kinetics of reoxygenation of different tumor types demonstrated that full reoxygenation takes about 72\u00a0h [7]. Also, preclinical data and radiobiological modeling studies have demonstrated that tumor hypoxia is a greater detrimental factor for single dose treatments than for repeated conventional fraction sizes. To fully exploit reoxygenation between fractions, 6\u20138 fractions might be optimal, separated in a time frame of 72\u00a0h [7]. However, there are also advantages to large high-dose fractions of ~10 Gy. Relatively radioresistant hypoxic cells might be directly sterilized and vascular endothelial cells might be injured. Since one endothelial cell is subtending about 2000 tumor cells, direct vascular damage might largely contribute to tumor cell kill in hypofractionated RT [8]."}
{"_id": "Radiology$$$1d122127-060c-439d-9c64-d47187758709", "text": "Tumor cell repopulation refers to an increase in the number of cells as a result of proliferation of surviving clonogenic tumor cells (see Chap. 5). Accelerated repopulation of tumor cells during the course of RT is starting after a lag period of ~4\u00a0weeks. One strategy discussed here is to cope with tumor cell repopulation by limiting the overall treatment time for fast repopulating tumors using a small number of higher sized fractions. As a consequence of high fraction sizes, the total irradiation dose should be reduced to overcome an increase in late normal tissue toxicity. Hypofractionation allows shortening of the overall treatment time, which might be more effective than long duration conventional fractionation in the treatment of rapidly proliferating tumors. However, care should be taken when using too short schedules, because they could lead to an increase in acute toxicity."}
{"_id": "Radiology$$$7a6c96e4-6805-4848-9b58-f7b63a96da62", "text": "To be noticed is the large LQ model based analysis of the tumor control probability (TCP) from randomized trials on in total 7283 head and neck cancer (HNC) patients, featuring wide ranges of doses, times, and fractionation schemes [9]. In the analysis, two different LQ based models were used, assuming a dose-independent (DI) and a dose-dependent (DD) acceleration of tumor cell repopulation. Accelerated Repopulation (AR) was assumed to be triggered by the level of tumor cell killing, with other words, to begin at a time when the surviving fraction of the tumor clonogenic cells falls below a critical value. This starting point of AR of tumor cells was assumed to be dose-dependent and therefore reached at an earlier time point after high fraction sizes than after low fraction sizes. The DD model of AR provided significantly improved descriptions of a wide range of randomized clinical data, relative to the standard DI model. This preferred DD model predicted that, for currently used HNC fractionation regimen, the last 5 fractions did not increase TCP, but simply compensated for increased accelerated repopulation (Fig. 6.3). A hypofractionation scheme of 25 fractions of 2.4 Gy (total dose of 60 Gy in 33\u00a0days) was found to be superior over 35 fractions of 2 Gy (total dose of 70 Gy in 47\u00a0days), both regarding the probability of tumor control and late normal tissue complications. In a next study, on basis of radiobiological model calculations with the DD model, an optimized hypofractionated treatment scheme for HNC patients was proposed with 18 daily fractions of 3\u00a0Gy, i.e., a total dose of 54 Gy in 24\u00a0days [10].\n\nA line graph depicts that T C P of 2.4, 2, and 1.8 gray per f x is at around 19 to 28 on X-axis and 0.5 T C P. The N T C P sub late for 2.4, 2, and 1.8 gray per f x is at around 29 to 40 on X-axis and 0.25 N T C P sub late, where 2 and 1.8 gray per f x are below the N T C P sub late values.\n\nFig. 6.3\nPredicted TCP values by the DD model (solid curves) as a function of the number of fractions delivered, for stage T1/2 head and neck cancer (HNC) patients. Dose per fraction (fx): 1.8 Gy (blue), 2.0 Gy (red) or 2.4 Gy (black), administered daily, 5 fx/week. NTCP late predictions for late toxicity (dashed curves) were made with the standard LQ model normalized to a 13.1% value (grade 3\u20135 late toxicity at 5\u00a0years) for 35\u00a0\u00d7\u00a02 Gy fractions. The solid circles represent current standard treatment regimens. Thus, the final week of 5 fractions could be eliminated without compromising TCP, but resulting in significantly decreased late sequelae due to the lower total dose. (Reproduced with permission from [9])"}
{"_id": "Radiology$$$7996aac9-cf57-4ab2-af2d-dfa02e22271f", "text": "A line graph depicts that T C P of 2.4, 2, and 1.8 gray per f x is at around 19 to 28 on X-axis and 0.5 T C P. The N T C P sub late for 2.4, 2, and 1.8 gray per f x is at around 29 to 40 on X-axis and 0.25 N T C P sub late, where 2 and 1.8 gray per f x are below the N T C P sub late values."}
{"_id": "Radiology$$$7ce9e336-1226-4e35-9a2d-993ad6c3e291", "text": "Radiation has long been thought to suppress the immune system, and total body irradiation is up to date applied for that reason. Studies in the past have demonstrated that local irradiation not only had a direct effect on tumor cells in the treatment volume, but also a systemic effect on the immune system (see Chap. 5). Therewith, local irradiation can induce abscopal effects, i.e., the immunological rejection of tumors or metastatic lesions distant from the irradiated site (see Chap. 5). Different radiation treatment schemes regarding the total dose and fraction size were shown to have diverse effects on the immune response, with a subsequent effect on combination therapy with immune-modulating agents [11]. The abscopal effect might best be exploited using 3\u20135 fractions of <10 Gy [12]. The immune-editing effects of radiation will probably also benefit from repeated intermediate high fraction sizes [13]."}
{"_id": "Radiology$$$1862d5b9-0717-452b-890d-172cc9b6575f", "text": "Hyperthermia and chemotherapeutic agents, e.g., cisplatin, gemcitabine, temozolomide and targeted drugs such as inhibitors of PARP-1 and EGFR may potentiate the effects of radiation. The LQ model is a very suitable tool to quantify the effects of the combination of irradiation and radiosensitizers, which can be either additive or synergistic. The most commonly used test to study interaction between irradiation and modulating agents is the clonogenic assay (see Chap. 3), being the golden standard test for determination of cell survival. LQ model analysis of the typical shaped cell survival curve allows to separately establish the effect of combination therapy on the \u2329 and \u00ae \u03b1/\u03b2 parameters of the model. The parameter \u2329 \u03b1 determines the effectiveness at low doses, on the initial slope of the cell survival curve, while the parameter \u00ae \u03b2 represents the increasing contribution from cumulative damage thought to be due to interaction of two or more separate lesions. Preclinical studies have shown that most radiosensitizing agents cause an increase of the \u03b1-parameter, while the \u03b2-parameter is rarely affected [14]. With conventional small-sized dose fractions, the value of the \u03b1-parameter therefore determines to a large extent the effectiveness of combination treatments. The interaction between chemotherapeutic agents and high-dose irradiation fractions will be minimal. For clinical hypofractionation regimen, it is to be expected that effects of radiosensitizing agents are smaller than when combined with conventional fractionation regimen."}
{"_id": "Radiology$$$5046868f-891c-4bd6-bf2d-ef3364670e7c", "text": "Long-term follow-up studies that address carcinogenic effects of fractionated high-dose RT describe the incidence of secondary malignancies, type of induced cancers, latency time, risk period as well as the shape of the dose\u2013risk relationship curve. The dose\u2013risk curve following curative RT is organ specific and is either linear, plateau, or bell-shaped. Radiobiological\u2014LQ model based\u2014calculations for estimation of the cancer risk following exposure to irradiation showed that both carcinoma and sarcoma risk decreased with increasing fraction size [9]. Via model calculations, it has been estimated that hypofractionated RT has the potential to reduce the second cancer risk [15]."}
{"_id": "Radiology$$$af29882a-98e6-4cc0-ab8f-e2740e046895", "text": "The basic principle of SBRT is to deliver a tumoricidal dose to the target in a few fractions and minimize dose to normal tissue using highly conformal radiation.\n\nThe high-dose per fraction used in SBRT can cause vascular damage through endothelial cell apoptosis and stem cell death.\n\nSBRT is commonly used in treatment of tumors in lung, liver, spine, prostate, and pancreas."}
{"_id": "Radiology$$$d065386e-b32f-4cc6-b2c7-2a28b232ccef", "text": "The basic principle of SBRT is to deliver a tumoricidal dose to the target in a few fractions and minimize dose to normal tissue using highly conformal radiation."}
{"_id": "Radiology$$$d8ab08ae-2a74-434e-a6cc-77c9462e2893", "text": "The high-dose per fraction used in SBRT can cause vascular damage through endothelial cell apoptosis and stem cell death."}
{"_id": "Radiology$$$840222ee-6302-4276-94cd-90931560583a", "text": "SBRT is commonly used in treatment of tumors in lung, liver, spine, prostate, and pancreas."}
{"_id": "Radiology$$$eb0782d2-14cb-4583-93c3-70a56517ae3a", "text": "Stereotactic Body Radiation Therapy (SBRT) also known as Stereotactic Ablative Radiotherapy   (SABR) refers to stereotactic image-guided delivery of highly conformal radiation to a small extracranial target using high-dose per fraction delivered in 1\u20135 fractions with a tumor-ablative intent [16]. The key requirements for SBRT are small well-circumscribed tumors (maximum cross-sectional diameter up to 5\u00a0cm), stringent patient immobilization, small or no margin for beam penumbra, high conformality and accurate radiation delivery as well as image guidance for geometric verification [17]."}
{"_id": "Radiology$$$e6369fce-2484-4246-b7f2-78b8a1372f8e", "text": "The aim of SBRT is to deliver tumoricidal dose to target in a few fractions and minimize dose to normal tissue by delivering highly conformal radiation under image guidance. A high-dose per fraction is more tumoricidal than conventional fractionation dose by its direct damaging action on tumor cells [6]. As discussed in Chap. 5 and earlier in this chapter, the effect on late-responding normal tissues is greater with high-dose per fraction. Few malignancies such as prostate cancer have low \u03b1/\u03b2 values in the range of 1.5\u20133 Gy and show high sensitivity to fractionation (similar to late-responding normal tissues). In such malignancies, hypofractionation leads to better therapeutic benefit. On the other hand, delivering high-dose per fraction can increase toxicity in acute-responding tissues(see Chap. 5). To minimize this, a highly focused and conformal dose is delivered to the tumor with a steep dose gradient. It is achieved by reducing planned target volume (PTV) margins under image guidance, using multiple non-coplanar beams with careful treatment planning, and by delivering the total dose in two to five fractions (2\u20133 fractions per week) [7]."}
{"_id": "Radiology$$$33bf65f3-76dc-4068-93ca-59c4002332e2", "text": "As discussed in Chap. 5, the bigger the tumor size the more is the hypoxic component and vice-versa. The advantage of reoxygenation seen during conventional fractionation is compensated in hypofractionated SBRT by selectively treating small tumors, which are relatively well oxygenated with a little hypoxic component. Furthermore, the hypoxic cells in tumors are depopulated by the direct damaging effect of large doses per fraction [6]. The same effect is responsible for overcoming the disadvantage of lack of reassortment of tumor cells to sensitive phases of cell cycle during fractionation. The high-dose per fraction counteracts the differences in radiosensitivity of cells in different phases of cell cycle by causing cell cycle arrest and interphase death in all phases (see Chap. 3)."}
{"_id": "Radiology$$$418cc9c7-cda7-4508-8ad0-f771396e77df", "text": "Unlike conventional fractionation RT, owing to the short overall treatment time, tumor cell repopulation and interfraction repair of sublethal damage do not play a major role during SBRT (see Sect. 6.3). This is beneficial in terms of tumor control but detrimental to normal tissues. However, when the treatment time of an individual fraction is prolonged for more than half an hour, intrafraction repair of some sublethal damage in rapidly proliferating tumor cells may occur [7]. However, such longer fraction treatment time and faster intrafraction repair result in greater loss of BED [18]. This can be overcome by increasing the dose rate with use of flattening filter free (FFF) beams."}
{"_id": "Radiology$$$7b0f5700-6c7a-47f0-88ba-5f020de8024e", "text": "It is postulated that the radiobiologic effect of SBRT also depends on two other mechanisms. One is the vascular damage due to endothelial cell apoptosis caused by high-dose per fraction. It has been reported that this occurs due to the structural abnormalities of tumor vessels that are dilated, tortuous, elongated and have a thin basement membrane [19]. The second mechanism is through radiation-induced immunologic responses. The strong T-cell response triggered after exposure to high-dose per fraction RT enhances cytotoxic effects [12]. In addition, SBRT when combined with immune checkpoint inhibitors, i.e., Programmed Cell Death Protein-1/Programmed Cell Death Ligand-1 (PD-1/PD-L1) targeting antibodies, e.g., pembrolizumab or cytotoxic T-lymphocyte-associated protein-4 (CTLA4) antibodies, e.g., ipilimumab has shown to trigger an immunologic response that produces an abscopal effect [12] as described in Chap. 5."}
{"_id": "Radiology$$$85d2b803-f36d-4476-a7de-eb8cf694d2dd", "text": "Conventional fractionation RT is modelled by the LQ model cell survival curve but at higher dose per fraction, it is thought that LQ model overestimates the effects of radiation [20]. Therefore, alternative radiobiological models like universal survival curve (USC) were proposed. Instead of the BED in the LQ model, USC calculates the standard effective dose (SED) which is the total dose administered in 2 Gy per fraction to produce the same effect [21]. There are arguments that the LQ model still holds good till a certain level of dose per fraction."}
{"_id": "Radiology$$$a9c0b4cf-8760-407e-8768-e755088d6d2c", "text": "The RT treatment planning for SBRT involves various steps allowing proper delivery of SBRT. After appropriate patient selection, VacLoc bags are used for stringent patient immobilization and setup. The next step is to acquire treatment planning images using computed tomography (CT)/magnetic resonance (MR)/18F-fluorodeoxyglucose (18FDG) positron emission tomography (PET) simulator with patient setup in treatment position with immobilization devices [22]. Usually, images are taken in 1\u20133 mm slice thickness and scan length extends at least 5\u201310 cm superior and inferior beyond RT treatment field borders for coplanar beams and 15 cm for non-coplanar beams [22]. For tumors in the thorax and upper abdomen, respiration-induced organ and tumor motion may be an issue. Therefore, motion management strategies are utilized while treating these tumors (Table 6.3).Table 6.3\nMotion management methods in radiotherapy. Adapted from [23]\n\nMotion management method\n\nRationale\n\nFree breathing technique\n\u2022\u2003Based on 4D CT\n\nGenerating of internal target volume (ITV) which covers the full range of tumor motion\n\nMotion dampening techniques\n\u2022\u2003Abdominal compression using paddle, pneumatic belts, etc.\n\u2022\u2003Breath holding technique such as deep inspiratory breath hold (DIBH), active breath coordinator (ABC)\n\nLimiting the diaphragm expansion and tumor motion by devices or by controlling breathing\n\nRespiratory gating technique\n\u2022\u2003Internal gating using internal surrogates for tumor motion\n\u2022\u2003External gating using external devices to monitor respiration, a surrogate for tumor motion [such as real-time position management (RPM) system]\n\nTreating the tumor only in discrete phases of respiratory cycle\n\nReal-time tumor tracking\n\u2022\u2003ExacTrac (Kilo-Voltage image-based system)\n\u2022\u2003Cyberknife (Kilo-Voltage image-based robotic system)\n\u2022\u2003Calypso (radiofrequency localization system)\n\nIntrafraction tumor localization and repositioning of treatment beam toward the target"}
{"_id": "Radiology$$$04294335-7a2e-4613-8152-2a02f48ac2cb", "text": "For SBRT, the target volumes and OARs are contoured as per the The International Commission on Radiation Units and Measurements (ICRU) 50 and 62 reports. The RT treatment planning is based on the American Association of Physicists in Medicine Task Group (AAPM TG) 101 recommendations [22]. Unlike uniform dose prescription in conventional RT, in SBRT, dose is prescribed to the low isodoses (e.g., 80% isodose line) with small or no margin for beam penumbra to improve sharp dose falloff outside the target volume, thereby reducing dose to adjacent normal tissues. Hence, dose heterogeneities and hotspots occurring within the target volumes are accepted in SBRT, unlike traditional RT where homogeneous dose distribution is desired. For obtaining an optimal SBRT treatment plan with better target dose conformality as well as isotropic dose gradient, multiple planar or non-coplanar treatment beams are used, and treatment is delivered using multileaf collimator (MLC) of width 5 mm or less [24]. The calculation grid size used in the treatment planning system (TPS) affects the accuracy of calculated dose distribution. Hence, an isotropic grid size of 2 mm or finer is recommended."}
{"_id": "Radiology$$$900b0009-4775-4d75-8405-c102d833288e", "text": "The normal tissue tolerances derived from conventional fractionation studies do not apply to the high fractional doses delivered in SBRT. Therefore, bioeffect measures such as BED, normalized total dose (NTD), and equivalent uniform dose (EUD) are calculated to evaluate the effectiveness and safety of SBRT dose distributions [18, 25, 26]. BED and NTD are used to determine the biologic effectiveness of different dose fractionation schedules, whereas EUD is applied to rank different treatment plans based on their expected tumor effect [22]. The normal tissue tolerances for different SBRT fractionation schemes are still evolving. Apart from the traditional metrics reported in a RT treatment plan, SBRT plans must specify conformity index (CI\u00a0=\u00a0prescription isodose volume/PTV), heterogeneity index (HI\u00a0=\u00a0highest dose received by 5% of PTV/lowest dose received by 95% of PTV), and intermediate dose spillage (D50%\u00a0=\u00a0volume of 50% of prescription isodose curve/PTV or D2 cm\u00a0=\u00a0maximum dose at 2 cm from PTV) [22]."}
{"_id": "Radiology$$$96cf7f60-5728-4c4c-bb90-47ca9c23a482", "text": "Recent advances in RT techniques and machines facilitate delivery of SBRT. Volumetric modulated arc therapy (VMAT) is an advanced RT technique that delivers radiation dose continuously in arcs where gantry rotation speed, treatment aperture, and dose rate vary simultaneously [27]. The newer linear accelerators (LINAC) capable of delivering flattening filter free (FFF) beams increases dose rate from 300 to 600 monitor units (MU)/min to 1200 to 2400 MU/min. Thereby, the time required to deliver the large number of MUs needed for high-dose per fraction in SBRT is decreased [28]. The FFF beams also have other advantages such as less off-axis beam hardening, less photon head scatter, less field size dependence, and less leakage outside beam collimators [29]."}
{"_id": "Radiology$$$c2ffc505-ab40-4738-a7a5-cbd5e53599db", "text": "The clinical application of SBRT gained much interest over the past two decades. SBRT is commonly used in treatment of malignant tumors in lung, liver, pancreas, prostate, kidney, and spine (Table 6.4). It is also widely recommended for treating oligometastatic disease that has spread to liver, lung, bone, adrenals, or lymph nodes. Its clinical utility in breast cancer as well as head and neck cancers is being investigated. The common cancer subsites and clinical scenarios where SBRT has a role are summarized in Table 6.4.Table 6.4\nClinical application of SBRT at various cancer subsites. (Adapted from [30])\n\nCancer subsite\n\nIndications\n\nLung\n\n\u2022\u2003Early-stage inoperable non-small cell lung cancer (NSCLC)\u2014T1, T2, usually <5\u00a0cm, N0\n\n\u2022\u2003Boost following definitive chemoradiation for locally advanced NSCLC\n\n\u2022\u2003Recurrence/re-irradiation\n\n\u2022\u2003Oligometastatic disease\n\nLiver\n\n\u2022\u2003Hepatocellular carcinoma (HCC)\u2014unresectable/medically inoperable patients, unsuitable/refractory to radiofrequency ablation, or transarterial chemoembolization\n\n\u2022\u2003Oligometastatic disease\n\n\u2022\u2003Portal vein tumor thrombosis (PVTT)\n\nPancreas\n\n\u2022\u2003Locally advanced unresectable disease\u2014radical SBRT/SBRT boost following conventional fractionated RT\n\n\u2022\u2003Borderline resectable disease\u2014poor performance status\n\n\u2022\u2003Re-irradiation\n\nProstate\n\n\u2022\u2003Low risk\u2014SBRT monotherapy\n\n\u2022\u2003Low volume intermediate risk\u2014SBRT monotherapy/boost\n\n\u2022\u2003High/very high/node positive disease\u2014SBRT boost\n\n\u2022\u2003Residual disease after RT\u2014salvage/re-irradiation\n\nSpine metastases\n\n\u2022\u2003Primary spinal cord neoplasms: medically inoperable/adjuvant/salvage SBRT\n\n\u2022\u2003Spine metastases: limited disease, life expectancy more than 3\u00a0months, medically inoperable\n\n\u2022\u2003Re-irradiation\n\nKidney\n\n\u2022\u2003Unilateral, medically inoperable disease\n\n\u2022\u2003Bilateral/recurrent contralateral disease\n\nHead and neck\n\n\u2022\u2003Re-irradiation: single, small volume recurrence, node negative\n\n\u2022\u2003SBRT boost following definitive chemoradiation in locally advanced nasopharyngeal cancer\n\n\u2022\u2003Palliation"}
{"_id": "Radiology$$$350a71cf-026b-4112-8d2a-238e3d449b04", "text": "Numerous phase 1/2 clinical trials have shown encouraging results regarding safety and efficacy of SBRT in different types and stages of cancer [31]. However, the major drawbacks of these trials are the adoption of variable radiation dose, fractionation schemes, and limited number of treated patients. Therefore, randomized phase 3 trial results on clinical outcomes and long-term toxicities are needed to recommend SBRT as the standard of care."}
{"_id": "Radiology$$$4bf492d2-084f-4a3f-801f-81d81ab6ccca", "text": "FLASH RT is emerging as a new tool for sparing normal tissue from ablative doses, as it is able to protect normal tissue while maintaining antitumor ablation [32]. FLASH RT targets tumors with ultra-high dose rates (>100\u00a0Gy/s) to reduce the administration time from minutes to less than 200\u00a0ms, as this is key to sparing normal tissue [32]. The biological mechanism behind the sparing of normal tissue, known as the \u201cFLASH effect,\u201d is based on the following hypothesis:"}
{"_id": "Radiology$$$dc698d2f-9c19-4f94-a599-9a71a878d90d", "text": "The oxygen depletion hypothesis describes the rapid consumption of local oxygen by ultra-high dose rates resulting in transient radioprotection and transient local tissue hypoxia. It is known that hypoxic tissue is more radioresistant because the low concentration of molecular oxygen during radiation-induced DNA damage allows DNA repair, while in the presence of molecular oxygen, the DNA lesion binds to molecular oxygen and produces peroxyl radicals leading to the degradation of nucleic acids and lipids [32]. Therefore the oxygen depletion hypothesis suggests that FLASH RT may be able to prevent or reduce Reactive Oxygen Species (ROS)-mediated cellular damage [33]. However, this hypothesis has recently been challenged as studies showed that FLASH RT does not significantly decrease tissue oxygen concentration compared with conventional RT when measured with a solid optical sensor [34]. The differential ROS-damage recovery hypothesis describes that normal and tumor cells have different capabilities to \u201cdetoxify\u201d themselves from ROS [32]. According to this hypothesis, normal cells have a greater capacity to eliminate peroxidized compounds compared to tumors. This would explain why tumors exposed to FLASH RT respond equally under either physiologic or hypoxic conditions."}
{"_id": "Radiology$$$23bf3925-ae9d-4d1c-9d48-30b13ea6bebe", "text": "Preclinical studies of FLASH RT confirmed its efficacy in various animal models (mice, pigs, cats, zebrafish) as well as in different tissues (lung, brain, intestine, skin) and led to the first use of FLASH RT in the clinic. One example is a man that had a cutaneous lymphoma that had spread over the entire surface of his skin. He had already received several sessions of conventional RT and the skin\u2019s tolerance was exhausted. FLASH RT was indicated as a way to spare the skin while achieving equivalent tumor control to conventional RT. The lesion received 15 Gy as a single dose in 90\u00a0ms. The treatment was successful, with no skin toxicity and complete ablation of the tumor as reported 6 months after treatment [33] (Fig. 6.4).\n\n3 photos of a treated lesion. A displays day 0 where P T V delineated limits around the lesion at 4 inches in diameter. B is the lesion after 3 weeks, which presents the lesion healing and decreasing in diameter. C is the lesion after 5 months where 4 arrows denote the fully healed lesion on the skin.\n\nFig. 6.4\nTemporal evolution of the treated lesion: (a) before treatment with the limits of the PTV delineated in black; (b) at 3\u00a0weeks, at the peak of the skin reaction (grade 1 epithelitis NCI-CTCAE v 5.0); (c) at 5\u00a0months. (Reproduced with permission from [33])"}
{"_id": "Radiology$$$ff8bdba9-9fdc-48a3-ba98-dd7bd6df7562", "text": "3 photos of a treated lesion. A displays day 0 where P T V delineated limits around the lesion at 4 inches in diameter. B is the lesion after 3 weeks, which presents the lesion healing and decreasing in diameter. C is the lesion after 5 months where 4 arrows denote the fully healed lesion on the skin."}
{"_id": "Radiology$$$b0a5c480-e312-4ba4-9d9f-adf49bdf284f", "text": "Apart from this successful case, the current use of FLASH RT in the clinic is limited to enrolling participants in clinical trials. However, in the near future patients with tumors in organs described as late-responding tissues would be good candidates for FLASH RT, as preclinical studies have shown that ultra-high dose rates dramatically reduce the incidence of pulmonary fibrosis and neurocognitive impairment. Patients with painful bone metastases in the extremities would also be good candidates to investigate the feasibility and safety of FLASH RT."}
{"_id": "Radiology$$$961b52e9-05d1-4878-97d3-754ddf08c460", "text": "Before starting treatment with FLASH RT, one needs to be aware of the importance of the radiation source, the quality of the radiation, and the physical parameters of the beam.\nRadiation sources are currently standardized to deliver dose rates of about 0.1\u20130.4\u00a0Gy/s in 2 Gy daily fractions. FLASH RT, on the other hand, relies on facilities capable of delivering ultra-high dose rates in large doses in one or more pulses over microseconds. This capability has only been achieved in a few places by modifying clinical devices to deliver photons, protons, or electrons. There are large irradiation facilities such as the European Synchrotron that can deliver X-rays at dose rates of up to 16,000\u00a0Gy/s [35]. However, clinical trials using synchrotrons are not yet an option.\n\nThe quality of the radiation must also be considered, as most research on FLASH RT has been done with electrons. FLASH RT with electrons has been shown to be effective in at least one human patient, while FLASH RT with photons and protons is still in the preclinical phase. Regardless of preclinical or clinical status, the quality of radiation needs to be considered to account for (1) the impact of the linear energy transfer on the mechanisms behind the FLASH effect and (2) the use of a continuous beam in the case of protons versus a pulsed beam in the case of electrons and synchrotron X-rays [32].\n\nThe physical parameters of FLASH RT need to be defined much more precisely than in conventional RT. A team of experts from Switzerland has suggested that the number of pulses, the instantaneous intra-pulse dose rate (\u2265104\u00a0Gy/s), and the total exposure time (<100\u00a0ms) should be included in all studies of FLASH RT [33, 35]. These parameters mostly derive from FLASH RT with electrons and therefore should be carefully applied to FLASH RT with photons or protons."}
{"_id": "Radiology$$$6b6318da-1fa1-49ef-ba13-312c8ca45663", "text": "Radiation sources are currently standardized to deliver dose rates of about 0.1\u20130.4\u00a0Gy/s in 2 Gy daily fractions. FLASH RT, on the other hand, relies on facilities capable of delivering ultra-high dose rates in large doses in one or more pulses over microseconds. This capability has only been achieved in a few places by modifying clinical devices to deliver photons, protons, or electrons. There are large irradiation facilities such as the European Synchrotron that can deliver X-rays at dose rates of up to 16,000\u00a0Gy/s [35]. However, clinical trials using synchrotrons are not yet an option."}
{"_id": "Radiology$$$f9d5a7c4-fa3e-4bb5-ad9b-776858a5ccba", "text": "The quality of the radiation must also be considered, as most research on FLASH RT has been done with electrons. FLASH RT with electrons has been shown to be effective in at least one human patient, while FLASH RT with photons and protons is still in the preclinical phase. Regardless of preclinical or clinical status, the quality of radiation needs to be considered to account for (1) the impact of the linear energy transfer on the mechanisms behind the FLASH effect and (2) the use of a continuous beam in the case of protons versus a pulsed beam in the case of electrons and synchrotron X-rays [32]."}
{"_id": "Radiology$$$a131acbd-7149-4551-80b5-d5b6e0338d26", "text": "The physical parameters of FLASH RT need to be defined much more precisely than in conventional RT. A team of experts from Switzerland has suggested that the number of pulses, the instantaneous intra-pulse dose rate (\u2265104\u00a0Gy/s), and the total exposure time (<100\u00a0ms) should be included in all studies of FLASH RT [33, 35]. These parameters mostly derive from FLASH RT with electrons and therefore should be carefully applied to FLASH RT with photons or protons."}
{"_id": "Radiology$$$6d74fe86-000d-4f4a-ab88-8cfd330735f2", "text": "In summary, FLASH RT is not yet actively used in the clinic. However, it is now clear that FLASH RT requires very precise management of the radiation quality and beam."}
{"_id": "Radiology$$$2f038fb1-7ad5-4061-b85a-85266058d568", "text": "The patient population that would benefit from clinical trials with FLASH RT are those who still have radioresistant tumors for which even the most sophisticated intensity-modulated RT has not been successful. In this context, FLASH RT could be combined with immunotherapy to achieve a synergistic effect. This strategy is supported by the immune hypothesis, which builds on the oxygen depletion hypothesis by proposing that FLASH RT protects circulating and resident immune cells that are normally radiosensitive. This radiosensitivity is particularly important when radiation fields affect bone marrow and/or circulating blood cells [36], as doses as low as 0.5 Gy can reduce lymphocyte survival by 90% [37]. Therefore, FLASH RT has the potential to spare immune cells from the radiation dose and allow recognition of tumor antigens to potentially trigger an antitumor immune response [33]."}
{"_id": "Radiology$$$5608f1cc-cda1-4941-a941-33db93bf4bf7", "text": "The basic principle of BNCT is selective targeting of tumor cells while sparing normal tissues using boron-carrier agents and low-energy neutrons.\n\nThree boron-delivery agents approved for human clinical trials are sodium borocaptate (BSH), boronophenylalanine (BPA), and sodium decaborane (GB-10).\n\nThe clinical trials on BNCT were conducted predominantly in brain malignancies, malignant melanoma, and recurrent head and neck cancers."}
{"_id": "Radiology$$$b53c724c-558c-4aca-a937-3112bcdff366", "text": "The basic principle of BNCT is selective targeting of tumor cells while sparing normal tissues using boron-carrier agents and low-energy neutrons."}
{"_id": "Radiology$$$891fdd5b-cbf5-4bfb-ac9c-9628ebbdbfcd", "text": "Three boron-delivery agents approved for human clinical trials are sodium borocaptate (BSH), boronophenylalanine (BPA), and sodium decaborane (GB-10)."}
{"_id": "Radiology$$$2455f602-90e1-4192-8f4c-43bb0d1701f5", "text": "The clinical trials on BNCT were conducted predominantly in brain malignancies, malignant melanoma, and recurrent head and neck cancers."}
{"_id": "Radiology$$$d1d01a9c-a0d0-4e90-8adc-ec58d8bbeaa1", "text": "The basic principle of BNCT is to deliver a boron-containing drug that selectively attaches to cancer cells and has a large cross-section capable of capturing a low-energy neutron. After administration of the boron-containing compound, the patient is exposed to a beam of thermal or epithermal neutrons. The compound goes into an excited state after neutron capture and undergoes a nuclear fission reaction to produce densely ionizing alpha particles. The range of these high LET particles in tissues is limited around 7.6\u00a0\u03bcm on an average (range 5\u20139\u00a0\u03bcm) [38, 39]. Therefore, these particles lead to localized release of a substantial amount of energy within the tumor, sparing the normal tissues. The boron neutron chemical reaction is as follows:\n\n (6.2)"}
{"_id": "Radiology$$$cca514e2-4a74-4813-b5b5-b92800624e0e", "text": "A photon of 0.48 MeV is released in most of the fission events which is useful for monitoring the reaction and has little significance in terms of cell killing [40]. Similarly, the radiobiologic effect of the low-energy thermal neutrons themselves is little."}
{"_id": "Radiology$$$74974ac5-87e5-4c5c-8505-830c998beec1", "text": "The success of BNCT largely depends on the properties of the boron compound used. An ideal boron compound should be non-toxic, have a high absolute boron concentration in tumors, have high specificity for malignant cells, and accumulate in low concentrations in adjacent normal tissues and blood [40]. To summarize, an ideal boron-carrier compound should have a high tumor-to-normal tissue ratio (around 3\u20134:1) [41]."}
{"_id": "Radiology$$$5a61b848-591b-4c71-ab04-db89a7b1abfc", "text": "Based on the molecular weight, there are two classes of boron compounds such as low-molecular weight (LMW) agents and high-molecular weight (HMW) agents. The LMW agents can cross the cell membrane and retain inside the cell. Examples are sodium borocaptate and boronophenylalanine. HMW agents are boron-containing monoclonal antibodies, bispecific antibodies, liposomes, nanoparticles, or conjugates of epidermal growth factor. They are highly specific to tumors but cannot cross the blood\u2013brain barrier in adequate concentration to be of some utility clinically. However, they can be used only when blood\u2013brain barrier is disrupted, or when delivered directly intracerebrally [41]."}
{"_id": "Radiology$$$462f2b2f-0ec5-4a0a-b105-970cfc438d06", "text": "The boron-carrier agents that are approved for human clinical trials are sodium mercaptoundecahydro-closo-dodecaborate (Na2B12H11SH) also known as sodium borocaptate (BSH), (l)-4-dihdroxy-borylphenyalanine also known as boronophenylalanine (BPA) and sodium decaborane (GB-10) [42]. Among the three, only BPA has a relatively higher tumor-specific uptake. It gets concentrated in cells synthesizing melanin. BPA is capable of taking up 18F, therefore 18F incorporated BPA positron emission tomography (PET) imaging is done to assess the boron concentration in tumor cells [43]."}
{"_id": "Radiology$$$7b32c4c5-62fd-4513-929f-fbeb2bac7b1f", "text": "The low-energy neutrons used in BNCT are produced from nuclear reactors through nuclear fission reactions and are either thermal neutrons or epithermal neutrons (Table 6.5).Table 6.5\nNeutrons used in BNCT and their characteristics. (Adapted from [41])\n\nType of neutrons\n\nEnergy (eV)\n\nCharacteristics\n\nThermal/slow neutrons\n\n0.025\n\n1. Attenuates rapidly in tissues\n2. Half value layer is about 1.5 cm\n3. Reacts with boron to produce high-LET particles\n\nEpithermal\n\n1\u201310,000\n\n1. Peak dose at about 2\u20133 cm\n2. Rapid falloff beyond peak dose\n3. Do not react with boron but degrades to thermal neutrons by collisions with hydrogen atoms in tissues"}
{"_id": "Radiology$$$26269617-f8c8-4a2a-9401-01ae511c8540", "text": "Thermal neutrons have the same average kinetic energy as gas molecules in the environment, which is little. Whereas epithermal neutrons are intermediate energy range neutrons formed during the transition of energetic neutrons to slow/thermal neutrons [44]. If a tumor at a depth of more than few centimeters is to be treated effectively with BNCT using thermal neutrons, then the normal tissues at the surface will be irradiated with a very high dose. Whereas with epithermal neutrons, the very high surface dose can be avoided [41]. But the depth dose distribution with both the types of neutrons is poor. In addition, the low-energy neutrons produced in nuclear reactors are contaminated with gamma rays and fast neutrons, both of which have different radiobiologic properties. Apart from this, there are capture reactions taking place with the naturally occurring isotopes in tissues such as 1H, 12C, 14Ni, 16O, 35Cl, etc. These contaminants cause biologic damage even in normal tissues without 10B concentration."}
{"_id": "Radiology$$$d276016f-d45c-475f-b3f6-9721fb155cf2", "text": "The dose in the radiation field is expressed as RBE-weighted dose, Gyw. A weighted dose is used to take into consideration the radiobiological effects of alpha particles, gamma rays, fast neutrons and capture reactions occurring with the use of nuclear reactor-generated neutron beams. The weighting factor depends on the boron-delivery agent used, which determines the concentration of 10B in cells and which in turn dictate the effectiveness of BNCT [42, 45]. Boron levels in a patient\u2019s blood can be measured but the concentration in tumor cells and adjacent normal tissues are based on earlier experimental studies [42]. Therefore, different weighting factors are used for tumor cells and normal tissues in the region of interest."}
{"_id": "Radiology$$$54e289b1-5d76-45c5-a138-94b89e62e6f2", "text": "The Monte Carlo method is utilized for RT dose calculation. Unlike conventional dose planning algorithms, the Monte Carlo method takes into consideration the influence of inhomogeneities on dose delivered by primary radiation as well as scattered radiation [46]. This makes it appropriate from the BNCT standpoint where the dose contribution is from different by-products of nuclear fission reactions and contaminants in low-energy neutron beams from nuclear reactors. RT is delivered in single fraction or multiple fractions using oppositional or multiple fields."}
{"_id": "Radiology$$$de80a272-aa8d-401c-b0e4-a7aa13aea772", "text": "The early human clinical trials carried out in Brookhaven National Laboratory and Japan did not show encouraging results with BNCT. It was widely tried out for treating central nervous system (CNS) malignancies. In these trials, 10B-enriched boric acid derivatives were used as boron-delivery agents, which showed high blood-to-tumor 10B concentration leading to endothelial damage in blood vessels but with no therapeutic benefit [47]. In the Japanese trials, BSH was used as a boron-carrier agent [48]. Though BSH achieved better tumor-to-blood concentration compared to previous boron-carrier agents used, it was however excluded by normal blood\u2013brain barrier, and the 10B concentration in brain tumors was suboptimal [49, 50]. In addition, the thermal neutrons used in these trials were poorly penetrating. Therefore, open craniotomy and general anesthesia during the entire treatment time (about 4\u20138\u00a0h) were needed to deliver BNCT [50]. The shortcomings of earlier studies were rectified in the modern clinical trials. In majority of the subsequent trials, high energy epithermal neutron beam was used instead of thermal neutron beam. Thereby, avoiding the need for open craniotomy. Instead of previous boron-carrier agents, newer agents such as BPA were used, either alone or in combination with BSH."}
{"_id": "Radiology$$$a089d91d-92e9-4dc8-96c1-df63cb9f5b97", "text": "The recent trials have aimed to find the optimal radiation fractionation, radiation fields, radiation dose, normal tissue tolerance, and pharmacokinetics of boron-carrier agents used in BNCT for treatment of different cancer subsites. In the twenty-first century, there were clinical studies experimenting and expanding the role of BNCT in other cancer subsites such as recurrent head and neck cancers as summarized in Appendix. However, there are no randomized controlled clinical trials on BNCT reported so far."}
{"_id": "Radiology$$$b05ef8eb-f294-463a-a0b5-a047ec677612", "text": "There are few limitations that hamper the widespread use of BNCT in cancer treatment. The main shortcoming is the lack of 10B carrier agents capable of achieving high tumor specificity and boron concentration. Secondly, the poor penetration of thermal neutrons into tissues. Thirdly, usage of nuclear reactors as the source of thermal neutrons for BNCT. The problems with nuclear reactors are that the low energy-neutron beams produced from them are contaminated with gamma rays and fast neutrons, which can cause damage to normal tissues even without boron concentration. Additionally, there is a shortage of nuclear reactors capable of delivering BNCT with a treatment delivery and monitoring room and they are also often located far away from population center. Fourthly, the interaction of low-energy neutrons with normal tissues results in capture reactions that cause biological damage."}
{"_id": "Radiology$$$e47cb352-c2ab-48bc-b184-097a3b5ff2be", "text": "Currently, active translational and clinical research focused on overcoming the above hurdles are being conducted. Newer boron-carrier agents based on purines, pyrimidines, thymidines, nucleotides, nucleosides, peptides, and porphyrin derivatives are being designed [39, 51, 52]. To avoid the hindrances associated with nuclear reactor-based treatment, alternative sources of neutrons such as radioactive decay of californium-252 (252Cf) and particle accelerators are being investigated. 252Cf is not available in the required amount to be utilized for BNCT [40]. On the other hand, particle accelerator-based treatment appears to be a promising alternative and would make hospital-based delivery BNCT feasible. However, the applicability of results from previous clinical trials conducted in reactor-based treatment centers to a larger population to be treated in particle accelerator-based treatment centers in future is questionable and warrants further studies [50]."}
{"_id": "Radiology$$$9c9cfec9-c854-4a20-b771-f77418df36fa", "text": "Combining RT with other oncological treatments is central for clinical management of tumors. A key approach is to combine RT with other pharmaceutical treatments. Given that RT has an effect on diverse cellular signaling networks, there are a number ways to combine it with agents and/or regiments that affect such processes, e.g., chemotherapy, targeted therapy, immunotherapy, hyperthermia, hormonal therapy, short-term starvation, etc. (Fig. 6.5).\n\nA circular diagram of the radiation resistent phenotype surrounded by the different radiotherapy combinations. It includes evading cell death, hyperthermia, D N A repair, short time starvation, cell cycle proliferation, inflammation immune evasion, hypoxia angiogenesis, and hormone therapy.\n\nFig. 6.5\nOverview of radiotherapy combinations influencing different hallmarks of cancer"}
{"_id": "Radiology$$$1b96c224-ac12-482a-a955-cf71511c126a", "text": "A circular diagram of the radiation resistent phenotype surrounded by the different radiotherapy combinations. It includes evading cell death, hyperthermia, D N A repair, short time starvation, cell cycle proliferation, inflammation immune evasion, hypoxia angiogenesis, and hormone therapy."}
{"_id": "Radiology$$$a99115ae-0f59-4ad8-a632-d440e946cd0e", "text": "RT is often combined with chemotherapy in a diverse set of tumor types to increase locoregional control as well as to combat metastatic growth [53]. These combined regiments have emerged as a result of exploring chemotherapeutic agents that presented some single drug activity in a certain cancer malignancies for additive or synergistic effect when combined with RT at doses and time frames that had acceptable toxicity [54]."}
{"_id": "Radiology$$$81af4669-f5e6-4d45-ae40-a2a40910e833", "text": "Combined chemotherapy and RT might refer to sequential association or to concomitant association. Chemotherapy may sensitize for RT by influencing one or several cellular effects including chromosome or DNA damage and subsequent repair, effect on cell cycle progression allowing cells to be accumulating in a RT sensitive phase, impact on different cell death routes including apoptosis, mitotic catastrophe as well as on autophagy. Moreover, in the tissue such combination may also impact on the hypoxic tumor environment/reoxygenation status. In a clinical setting it is most likely that a key benefit is the inhibition of tumor cell proliferation by drugs during the radiation interfraction interval [54]."}
{"_id": "Radiology$$$b497b6a0-3284-4055-b828-fe94bd199ca8", "text": "The combined use of chemotherapy with RT has typically translated into a significant benefit in overall survival in sites where RT plays a substantial role."}
{"_id": "Radiology$$$1d6de70a-a7a8-41fe-a05e-9f109e3158d2", "text": "Concurrent RT and chemotherapy yielded an almost 10% higher survival rate relative to RT alone. Unfortunately, the complication rates of combined regimens are also higher than those of RT only [54]."}
{"_id": "Radiology$$$b84c027f-740e-4691-ae5a-0662c305d533", "text": "Concomitant administration of chemotherapy and radiation gives increased early normal tissue toxicity due to inhibition of stem cell or precursor-cell proliferation. Late normal tissue damage is likely to be enhanced through inhibition of DNA repair, and by specific mechanisms of drug toxicity in sensitive tissues [55]."}
{"_id": "Radiology$$$98adcea9-a9d9-42f3-a71a-9918236a6366", "text": "Several randomized trials with concomitant chemoradiotherapy have been conducted in most cancer types showing a significant increase in locoregional control in many disease sites with a consequent improvement in patient survival. Meta-analyses of available data of randomized trials in head and neck cancer (HNC) undertaken a few years ago showed that despite a high initial response rate, multi-agent chemotherapy given before radiation treatment (i.e. in a neoadjuvant setting) has a small impact on the locoregional control and survival rates [54]. Numerous single institutions and cooperative groups have investigated the use of concurrent RT and chemotherapy in the management of patients with localized esophageal and gastric cancer, either as definitive or adjuvant therapy. A significant body of information suggests that chemotherapeutic agents such as 5-fluorouracil, capecitabine, cisplatin, oxaliplatin, carboplatin, mitomycin C, gemcitabine, irinotecan, docetaxel, and paclitaxel have a greater additive effect when used in combination with RT [54]."}
{"_id": "Radiology$$$d40d7da9-248b-48fc-835f-280279747a12", "text": "In all the reported studies, the therapeutic ratio (defined as the advantage in efficacy over the disadvantage in toxicity) was, however, less clearly assessed and/or reported. In general, an increase in early toxicity was observed in all the trials. For late toxicity, systematic reporting of data is lacking, but the few available reports also indicate an increase in late radiation effects."}
{"_id": "Radiology$$$59add68f-6a1e-4266-baf5-2b68f7eb085b", "text": "A drug may sensitize the radiation or may kill cells by independent means. Alternatively, a drug may inhibit cellular repopulation or act as a cytoprotector. Limited studies have presented drug mechanisms mathematically in order to estimate the equivalent radiation effect of a drug. In fact if cytotoxic drug effects could be expressed in terms of equivalent biologically effective dose of radiation, then relative contributions of radiation and chemotherapy in combined treatments could be assessed and consequently optimum schedules could be designed [54]."}
{"_id": "Radiology$$$03afeb6e-8547-46fa-aca0-21b28ff418fe", "text": "An ideal global model of tumor control in an attempt to simulate clinical reality would incorporate the effects of radiation dose, fractionation, hypoxia, blood flow, and concomitant drug therapy [55]."}
{"_id": "Radiology$$$c7666f1c-3d76-48b9-bbcd-09ef673319ea", "text": "Chemotherapy combined with RT improves the therapeutic ratio by the following mechanisms:1.\nSpatial cooperation\u2014consists of administering the chemotherapeutic agent and RT separately in different anatomical sites.\n\u00a02.\nToxicity independence\u2014both treatments have different side effects, the treatment with the combination modality is less toxic.\n\u00a03.\nNormal tissue protection\u2014chemotherapy drugs with a protective effect against normal tissue allow a higher dose of radiation to be administered.\n\u00a04.\nRadiosensitivity\u2014is a mechanism that leads chemotherapeutic agents to enhance the cytotoxic effects of RT treatment. Increased damage from radiation, inhibition of repair processes, interferance with the cell cycle progression through different phases, exerting greater activity against hypoxic cells, and helping to improve RT are some mechanisms of radiosensitivity that can influence these treatments."}
{"_id": "Radiology$$$dc0909e2-9e6b-45a0-85f8-c76bcb4f66a0", "text": "Spatial cooperation\u2014consists of administering the chemotherapeutic agent and RT separately in different anatomical sites."}
{"_id": "Radiology$$$0ed6d4ec-bc24-444c-b004-e3430fe782f3", "text": "Toxicity independence\u2014both treatments have different side effects, the treatment with the combination modality is less toxic."}
{"_id": "Radiology$$$ce9e88ff-b3c9-4bfd-a6cb-d9cfa9a81581", "text": "Normal tissue protection\u2014chemotherapy drugs with a protective effect against normal tissue allow a higher dose of radiation to be administered."}
{"_id": "Radiology$$$630aadc4-9ed5-4bfd-9acc-185b4d14f792", "text": "Radiosensitivity\u2014is a mechanism that leads chemotherapeutic agents to enhance the cytotoxic effects of RT treatment. Increased damage from radiation, inhibition of repair processes, interferance with the cell cycle progression through different phases, exerting greater activity against hypoxic cells, and helping to improve RT are some mechanisms of radiosensitivity that can influence these treatments."}
{"_id": "Radiology$$$38a6ea45-5d71-42ba-91a8-e09233385b99", "text": "Combination of chemotherapy with RT can be in three ways, with a sequential treatment where RT is followed by chemotherapy or chemotherapy is followed by RT. These treatments can reduce large tumor mass with a first modality and with the second one can increase the effectiveness, and thus control the disease. In concurrent treatment, chemotherapy and RT are given together. RT can be given daily, while chemotherapy could be given once a week or every 3\u20134\u00a0weeks. Finally, alternative treatment would be based on giving chemotherapy and RT on alternately weeks, such as every 1\u20133\u00a0weeks, with no concurrent treatments. This last option would reduce side effects and also allow full administration of the dose for each modality."}
{"_id": "Radiology$$$7c97ffd8-6cb0-49c1-afd2-82bf4455fb99", "text": "Molecular mechanisms of interaction between combination therapies [53]:1.\nEnhance DNA/chromosome damage and repair\nLittle is known about the capacity of chemotherapeutic agents to increase the efficiency with which IR induces DNA damage. Several commonly used chemotherapy agents have been shown to inhibit the repair of radiation damage (i.e., DNA and/or chromosome damage). Some of these drugs inhibit the repair processes by interfering with the enzymatic machinery involved in the restoration of the DNA/chromosome integrity.\n\u00a02.\nCell cycle synchronization\nMany of the chemotherapeutic agents inhibit cell division, that is, they exert their action on proliferating cells.\nDue to this cell cycle selective cytotoxicity by the cell cycle phase after the action of chemotherapeutic drugs, the remaining surviving cells will synchronize.\nIf RT is given when cells are synchronized in the most radiosensitive phase of the cell cycle, then the effect of radiation is enhanced.\n\u00a03.\nEnhanced apoptosis\nApoptosis is a mechanism of cell death induced by chemotherapeutic agents. These can trigger one or more pathways of apoptosis. To ensure a robust apoptotic response, chemotherapeutics must be incorporated into DNA. The combination of these therapies, where RT is very effective in inducing DNA single strand breaks (SSBs) or double strand breaks (DSBs), could facilitate the incorporation of these agents into DNA and thus induce an enhanced apoptotic reaction.\n\u00a04.\nReoxygenation\nHypoxia is associated with a worse response to RT treatment, and the reason is the inadequate diffusion of oxygen in the tumor mass due to insufficient tumor vascularization.\nIf we combine the treatments, chemoRT, chemotherapy induces a certain degree of shrinkage in the tumor that facilitates the diffusion of oxygen in a more uniform way, increasing tumor oxygenation and therefore tumor radiosensitivity.\n\u00a05.\nInhibition of cell proliferation\nA mechanism of interaction between both treatments combined is the possible inhibition of cell proliferation, a mechanism that occurs during dose fractionation in RT. The exact timing and schedule between the chemotherapy and RT must be taken into account, since it would be best to administer the drug toward the end of radiation treatment because that is when tumor cell repopulation has been activated."}
{"_id": "Radiology$$$cc019579-b264-428d-af11-7ed069d6024d", "text": "Little is known about the capacity of chemotherapeutic agents to increase the efficiency with which IR induces DNA damage. Several commonly used chemotherapy agents have been shown to inhibit the repair of radiation damage (i.e., DNA and/or chromosome damage). Some of these drugs inhibit the repair processes by interfering with the enzymatic machinery involved in the restoration of the DNA/chromosome integrity."}
{"_id": "Radiology$$$e25ce12a-e30f-4298-995b-4befeb6cb599", "text": "Many of the chemotherapeutic agents inhibit cell division, that is, they exert their action on proliferating cells."}
{"_id": "Radiology$$$cf4ee153-3b41-41bd-ba98-32e94e3169bc", "text": "Due to this cell cycle selective cytotoxicity by the cell cycle phase after the action of chemotherapeutic drugs, the remaining surviving cells will synchronize."}
{"_id": "Radiology$$$3f7bb6f0-6fc3-4cb0-96e2-925cce1ef219", "text": "If RT is given when cells are synchronized in the most radiosensitive phase of the cell cycle, then the effect of radiation is enhanced."}
{"_id": "Radiology$$$70ecb749-b86d-433e-bc55-2c8bdccbea6c", "text": "Apoptosis is a mechanism of cell death induced by chemotherapeutic agents. These can trigger one or more pathways of apoptosis. To ensure a robust apoptotic response, chemotherapeutics must be incorporated into DNA. The combination of these therapies, where RT is very effective in inducing DNA single strand breaks (SSBs) or double strand breaks (DSBs), could facilitate the incorporation of these agents into DNA and thus induce an enhanced apoptotic reaction."}
{"_id": "Radiology$$$b922a211-808c-41e0-ba56-adedbd3095fb", "text": "Hypoxia is associated with a worse response to RT treatment, and the reason is the inadequate diffusion of oxygen in the tumor mass due to insufficient tumor vascularization."}
{"_id": "Radiology$$$0cdde4ab-4e83-4e90-8a82-a44b7b371be8", "text": "If we combine the treatments, chemoRT, chemotherapy induces a certain degree of shrinkage in the tumor that facilitates the diffusion of oxygen in a more uniform way, increasing tumor oxygenation and therefore tumor radiosensitivity."}
{"_id": "Radiology$$$5c95fb37-ec6e-4bc6-bfca-2db54948cde9", "text": "A mechanism of interaction between both treatments combined is the possible inhibition of cell proliferation, a mechanism that occurs during dose fractionation in RT. The exact timing and schedule between the chemotherapy and RT must be taken into account, since it would be best to administer the drug toward the end of radiation treatment because that is when tumor cell repopulation has been activated."}
{"_id": "Radiology$$$c0e09ab5-b7fc-482e-a5c5-c8b4121ddbae", "text": "The combination of these treatments can increase both acute and late toxicity. ChemoRT as two cytotoxic treatments produces an increase in damage in the volume of damaged normal cells, being more evident during the concurrent chemoRT. By combining these therapies, if these side effects appear, you may require to reduce the dose of chemotherapy."}
{"_id": "Radiology$$$203ff5db-dd47-4fd8-89e5-30402f615427", "text": "Side effects from combining chemotherapy with RT can be increased fatigue, lowering of blood counts, cardiac dysfunction, cognitive dysfunction, and second malignancies."}
{"_id": "Radiology$$$5b106169-e693-465c-9855-a97f1a79fbcd", "text": "Some aspects to consider to reduce toxicity when combining both treatments are:\nIf we optimize the schedule and sequence of the combined treatments, we can reduce toxicity.\n\nWith an adequate selection of patients, we can avoid these side effects in patients with a poor performance status or patients with comorbidities.\n\nUsing a genetic and molecular analysis of the tumor, we can avoid chemotherapy for patients with lower scores, avoiding chemotherapy toxicity.\n\nIn patients with p16 oropharyngeal cancer, it has been possible to reduce the dose of RT and thus reduce toxicities.\n\nAdvances in imaging techniques, such as IMRT and IGRT, have led to a decrease in the dose around normal tissues, resulting in minimizing the risk of complications from chemoRT.\n\nFinally, supportive care that involves adequate nutrition, adequate hydration, managing nausea, pain, and depression are essential to mitigate side effects when both therapies are combined (Table 6.6).\nTable 6.6\nChemotherapeutic agents used in combination with radiotherapy in different tumor types and associated side effects\n\nTumor type\n\nTreatment\n\nSide effects\n\nBrain tumors\n\nCarmustine\n\nMyelosuppression\n\nTemozolomide\n\nNeutropenia, anemia, thrombocytopenia, constipation\n\nHead and neck cancer\n\nCisplatin\n\nNephrotoxicity, ototoxicity, nausea, vomiting, neurotoxicity/neuropathy\n\nDocetaxel\n\nMyelosuppression\n\nFluorouracil\n\nMyelosuppression, gastrointestinal (GI) effects, mucositis, oral ulcers, diarrhea\n\nBreast cancer\n\nCyclophosphamide\n\nHemorrhagic cystitis, myelosuppression, nausea, vomiting\n\nDocetaxel\n\nMyelosuppression\n\nDoxorubicin\n\nCardiotoxicity (including recall effect)\n\nMethotrexate\n\nStomatitis, leucopenia and nausea\n\nLung cancer\n\nCarboplatin\n\nNephrotoxicity, ototoxicity, nausea, vomiting, neurotoxicity\n\nDocetaxel\n\nMyelosuppression\n\nEtoposide\n\nMyelosuppression\n\nGastrointestinal cancer\n\nFluorouracil\n\nMyelosuppression and mucositis\n\nGemcitabine\n\nAnemia, thrombocytopenia, nausea/vomiting\n\nOxaliplatin\n\nNephrotoxicity, ototoxicity, nausea, vomiting and neurotoxicity\n\nIrinotecan\n\nDiarrhea, immunosuppression\n\nMitomycin C\n\nBone marrow damage, lung fibrosis, renal damage\n\nLymphoma\n\nBleomycin\n\nLung fibrosis\n\nDTIC (dacarbazine)\n\nLoss of appetite, vomiting, low white blood cell or platelets count\n\nDoxorubicin\n\nCardiotoxicity\n\nVinblastine\n\nPeripheral neuropathy, bone marrow suppression\n\nVincristine\n\nHair loss, constipation, difficulty walking, headaches, neuropathic pain, lung damage, or low white blood cell counts"}
{"_id": "Radiology$$$eaffeec1-64cd-4cd2-a3aa-6708f14d456a", "text": "If we optimize the schedule and sequence of the combined treatments, we can reduce toxicity."}
{"_id": "Radiology$$$b9510a87-769d-4e4b-b3ac-7dec14fc2e46", "text": "With an adequate selection of patients, we can avoid these side effects in patients with a poor performance status or patients with comorbidities."}
{"_id": "Radiology$$$9f3e8dfe-9895-41b9-a29e-b143859caca5", "text": "Using a genetic and molecular analysis of the tumor, we can avoid chemotherapy for patients with lower scores, avoiding chemotherapy toxicity."}
{"_id": "Radiology$$$ee5351d4-462e-43b6-a00f-ecb949e69f83", "text": "In patients with p16 oropharyngeal cancer, it has been possible to reduce the dose of RT and thus reduce toxicities."}
{"_id": "Radiology$$$bc269fa7-f34e-4383-9fef-3c3f3ce68a60", "text": "Advances in imaging techniques, such as IMRT and IGRT, have led to a decrease in the dose around normal tissues, resulting in minimizing the risk of complications from chemoRT."}
{"_id": "Radiology$$$38a19157-0256-4b4a-ac1c-f57e2a71e9d4", "text": "Finally, supportive care that involves adequate nutrition, adequate hydration, managing nausea, pain, and depression are essential to mitigate side effects when both therapies are combined (Table 6.6)."}
{"_id": "Radiology$$$8a2e8872-fe7f-4275-b055-7d3a827eb817", "text": "The incorporation of targeted therapies into treatment regimens helps to improve radiosensitization. Multimodal therapy uses these agents on a concurrent schedule [53]."}
{"_id": "Radiology$$$dcacabab-39b9-4949-a6a8-b25144e3d3a0", "text": "Multimodal management for optimum cancer treatment with surgery, chemotherapy, and RT is one of the most significant advances in cancer treatment in the last 25\u00a0years. This combined therapy increases locoregional control and patient survival, as well as reduces the side effects of treatment, toxicities [53]."}
{"_id": "Radiology$$$9db045e1-4b15-4453-a75b-7c9b3cca40c1", "text": "It is difficult to know the real underlying mechanisms of the interaction of this combination therapy of chemotherapy and RT, normally the clinical trials that are carried out do not allow to obtain this information [56] (Box 6.5)."}
{"_id": "Radiology$$$66c0a18e-21b2-423a-ba84-342681da3db9", "text": "RT and chemotherapy can, when combined, improve locoregional disease control.\n\nConcomitant administration of RT with chemotherapy gives increased early normal tissue toxicity but late toxicity of normal tissues may also be increased."}
{"_id": "Radiology$$$6ebc179b-7422-4ad3-a72e-7c0be7227cd3", "text": "Concomitant administration of RT with chemotherapy gives increased early normal tissue toxicity but late toxicity of normal tissues may also be increased."}
{"_id": "Radiology$$$73e0ada5-93c5-477b-bd48-08539b2e92c3", "text": "Radiation-induced signaling is multifaceted, and these cellular events are affected by different growth factor signaling cascades controlled by oncogenic drivers and activated kinases in the tumors [57]. These radiation-induced signaling events as well as the tumor microenvironment interplay have been explored for RT sensitization purposes (Fig. 6.5)."}
{"_id": "Radiology$$$ed37be7c-c212-42c8-8094-15a3116b44c9", "text": "Some of the RT sensitizing approaches based on targeting oncogenic drivers, DNA damage and repair, chromatin remodeling, cell cycle progression, cell death regulation and angiogenesis/hypoxia are shown in Table 6.7.Table 6.7\nRT sensitizing strategies and examples of drugs that are in clinical evaluation in combination with RT or in combined RT and chemotherapy regimen\n\nType of mechanism\n\nTarget or target mechanism\n\nExample inhibitors\n\nRT sensitized tumor\n\nReference or clinical trial No.a\n\nDNA damage and repair\n\nATM\n\nAZD1390\n\nGlioblastoma, other brain tumors\n\nNCT03423628\n\nATR\n\nBAY-1895344; M6620\n\nAdvanced solid tumor, esophageal cancers\n\n[58]\nNCT03641547\n\nDNA-PKcs\n\nNedisertib, peposertib, AZD7648\n\nHead and neck cancer, advanced solid tumors\n\n[59]\nNCT03907969\n\nPARP\n\nOlaparib, veliparib, rucaparib, niraparib\n\nBreast cancer, prostate cancer, non-small cell lung cancer, small-cell lung cancer, glioblastoma/glioma, rectal cancer, cervical cancer, head and neck cancer\n\n[60]\nNCT03542175; NCT04837209; NCT01477489; NCT02227082; NCT03945721; NCT03598257; NCT03109080; NCT03212742; NCT03581292; NCT01514201; NCT04790955; NCT04728230; NCT02412371; NCT01589419; NCT03644342; NCT02229656\n\nChromatin remodeling\n\nHistone deacetylase (HDAC)\n\nVorinostat\n\nHead and neck cancer\n\n[61]\n\nCell cycle progression\n\nWEE1\n\nAdavosertib\n\nPancreatic cancer\n\n[62]\n\nCDK 4/6\n\nPalbociclib, ribociclib, abemaciclib\n\nGlioma, breast cancer, head and neck cancer, meningiomas\n\n[63]\nNCT03691493; NCT03870919; NCT04563507; NCT03024489; NCT03389477; NCT03355794; NCT02607124; NCT04585724; NCT04298983; NCT04923542; NCT04220892; NCT02523014\n\nCell death regulation\n\nBcl-2\n\nAT-101 (Gossypol)\n\nHead and neck cancer\nBrain tumors\n\n[64]\nNCT00390403\n\nCD95/FAS ligand\n\nAsunercept (APG101)\n\nGlioblastoma\n\n[65]\n\nSMAC mimetics\n\nXevinapant (Debio 1143)\n\nAdvanced head and neck cancer\n\n[66]\n\nOncogenic drivers\n\nEGFR\n\nErlotinib/gefitinib/osimertinib cetuximab\n\nNon-small cell lung cancer, head and neck cancer\n\n[67, 68]\n\nSTAT3\n\nDovitinib\n\nHepatocellular carcinoma\n\n [69]\n\nAngiogenesis\n\nVEGF, VEGFR2\n\nBevacizumab, vandetanib (Caprelsa)\n\nGlioblastoma, esophagogastric cancer\n\n[70, 71]\n\nHypoxia\n\nOxygen mimetic\n\nNimorazole\n\nHead and neck cancer\n\n[72]\n\naThe trial number refers to its citation on https://\u200bclinicaltrials.\u200bgov/\u200b"}
{"_id": "Radiology$$$683a8546-414c-4702-a314-c8c8168db9e3", "text": "Three principal DNA damage response (DDR) kinases, the phosphatidylinositol-3-kinase-related kinases (PIKKs), ataxia-telangiectasia mutated (ATM), ATM- and Rad3-related (ATR), and the non-homologous end joining (NHEJ) component, DNA-dependent protein kinase, catalytic subunit (DNA-PKcs) are central in RT responses (see Chap. 3). These kinases execute their cellular action by phosphorylating targets that regulate DNA repair, e.g., histone H2AX, or cell cycle progression, e.g., WEE-1 and cell cycle checkpoint kinases (CHKs)."}
{"_id": "Radiology$$$1dfa8be1-455a-4300-87e4-d1f613790e0b", "text": "Multiple trials of ATR inhibitors are ongoing as single agents or combined with chemotherapy, yet fewer attempts have been made with ATR inhibitors and RT [60]. The ATR inhibitors BAY-1895344 and M6620 (see clinicaltrial.\u200bgov; NCT03641547) were tested in phase I trials in various solid tumors in an advanced stage setting including esophageal cancer [58]. As the kinase pocket of ATM is similar to other PIKKs, early attempts to develop specific inhibitors were unsuccessful [60]. However, the ATM inhibitor AZD1390 is currently undergoing trials in conjunction with RT in glioblastoma patients (NCT03423628). Attempts have also been made to target DNA-PKcs, a key component of the NHEJ repair cascade (see Chap. 3) [60]. Thus, AZD7648 has been demonstrated to enhance RT effect when combined with the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib in both tumor cell lines in\u00a0vitro as well as in tumor-bearing mice. This DNA-PKcs inhibitor is at present tested further in a phase I clinical trial (NCT03907969). Moreover, other DNA-PKcs inhibitors are similarly evaluated when combined with RT in phase I trials involving patients with, e.g., head and neck (HNC) cancer where a clear improved local control was found."}
{"_id": "Radiology$$$ab7c1014-e2a0-453b-af14-34bd8a92547d", "text": "Another class of DNA repair inhibitors is those targeting the PARP-1 repair enzyme [58, 60]. It has been demonstrated that in tumor cells which had mutations in certain DDR genes, e.g., BRCA1/2, causing impairment of their DNA damage sensing function, blockade of a back-up repair pathway, e.g., by PARP-1 inhibitors (PARPi) resulted in tumor-specific cell killing, a concept called synthetic lethality. Multiple PARPi, e.g., olaparib, rucaparib, and veliparib were developed and tested in different tumor types, e.g., breast cancer (BC), ovarian carcinoma (OC), and prostate cancer (PCa) (reviewed in [60]). In the context of RT, PARPis are currently tested or planned to be evaluated in several different tumor types (Table 6.7). Apart from the \u201cBRCAness\u201d tumor concept, the PARPi is also explored in tumors driven by other DDR-alterations, e.g., ATM and ATR."}
{"_id": "Radiology$$$54fedf56-2152-4655-8bf6-7c810fef52e6", "text": "Multiple cyclin-dependent kinase 4 and 6 inhibitors (CDKIs), e.g., palbociclib, ribociclib, and abemaciclib which alter the cell cycle progression, have become an important new treatment of metastatic- or locally advanced BC including combinations with RT [63]. Albeit multiple studies are ongoing, no consensus has been reached underpinning the clinical benefit of combining RT with CDKIs [63]. For palbociclib, there are studies ongoing in BC and HNC, ribociclib is evaluated with RT in multiple trials as is abemaciclib (Table 6.7). In addition, there is an attempt to study abemaciclib in patients with solid tumors that have brain metastasis where CDK genomic testing is done (NCT03994796)."}
{"_id": "Radiology$$$db526304-9f1d-4d17-a014-a8f693b1bc75", "text": "The CDK1/2 is in part controlled by the WEE1 G2 checkpoint kinase which via Ser/Th protein phosphorylation blocks their activity resulting in a G2/M cell cycle checkpoint activation. Indeed, the WEE1 inhibitor adavosertib was assessed alongside a dual RT and gemcitabine treatment regimen in advanced PCa patients where a clear response was evident by an increased overall survival [62]."}
{"_id": "Radiology$$$ecea6754-f6dd-418c-b20b-603bfab03d41", "text": "Constitutively increased activity of epidermal growth factor receptors (EGFRs) by mutation or gene amplification (which is found in multiple tumor types) is responsible for resistance to CT/RT [68]. Moreover, downstream PI3K/AKT or Ras-Raf mitogen-activated protein kinases (MAPK) signaling cascades may also influence RT response via regulation of cell cycle, cell death signaling, or by interfering with the DDR network [73]. Treatment with the antibody cetuximab, a EGF ligand blocker has been shown to improve RT sensitivity in HNC. However, results presented from a meta-analysis covering 13 studies with 5678 patients on CT/RT-based treatment and receptor tyrosine kinase inhibition for solid cancers (ROCKIT) emphasized that targeting EGFR could not ameliorate overall survival yet causing increased toxicity [67]. In the context of metastatic Non-small cell lung cancer (NSCLC) driven by EGFR mutation, there is also an interest in combining small EGFR tyrosine kinase inhibitors (TKIs) together with RT for patients with oligometastatic disease as well as to consolidate tumor lesions resistant to a given EGFR targeting TKI [68]."}
{"_id": "Radiology$$$d1b8fe72-145a-4414-b69f-38f2192a1f31", "text": "The transcription factor signal transducer and activator of transcription 3 (STAT3) regulate inflammation, malignant cells initiation, progression, and therapy resistance. STAT3 is overexpressed in cancers of the gastrointestinal tract, NSCLC, OC, and brain tumors and thus it may cover a valuable target for precision therapy. One example is the drug dovitinib which was shown to sensitize hepatocellular carcinoma to RT by targeting Src homology region 2 (SH2) domain-containing phosphatase 1 (SHP-1)/STAT3 signaling [69]."}
{"_id": "Radiology$$$e3d16b08-2c63-4416-b1cf-569bc539f0ce", "text": "RT resistance is in part a result of impaired cell death initiation and/or execution (see Chap. 3) and targeted strategies aim to restore such signaling. Multiple signaling components of different apoptotic routes including the B-cell lymphoma 2 (Bcl-2) family members, inhibitor-of-apoptosis-proteins (IAPs), e.g., x-linked IAP (XIAP) or survivin and the Cluster of Differentiation 95 (CD95)/FAS signaling network have all been explored [74, 75]. Inhibition of the IAP survivin, for instance, is reported to increase apoptosis as well as autophagy, to impact on the cell cycle and to hamper DNA damage repair, resulting in a radiosensitization [75]."}
{"_id": "Radiology$$$5a320b6d-1244-4627-8a24-5ffbce39bed2", "text": "Another example is the pan-Bcl-2 inhibitor AT-101 (Gossypol), which sensitized HNC cells to RT-induced apoptosis indicating its therapeutic potential for tumors with high Bcl-2 expression levels [64]. An additional  example is navitoclax (ABT-263) which impairs the anti-apoptotic function of Bcl-2/Bcl-xL and which was reported to potentiate RT cell death [76]. Finally, the anti-IAP smac mimetic, xevinapant (Debio 1143) has been tested in HNC in combination with cisplatin and RT where locoregional control was achieved in some patients [66]. Concerning RT sensitization via the extrinsic apoptotic route, focus has been on interfering with the FAS/CD95 signaling cascade [65]. Thus, it was demonstrated in relapsed glioblastoma patients that addition of the Fc-fusion protein asunercept (APG101) which blocks ligand engagement prolonged patient survival."}
{"_id": "Radiology$$$10a77adb-6855-4186-98a5-1bfa3e37b696", "text": "Targeting the tumor microenvironment is another RT sensitizing approach that involves attack on hypoxia directly or the underlying aberrant angiogenesis/vascularity of tumors, respectively. By this, hyperbaric oxygen therapy (HBOT) and agents which are specifically activated in hypoxic tumor cells/parts of the tumor or are prodrugs which are triggered to activity under hypoxic conditions or impact on angiogenesis/vasculature (by impairing the function of the vascular endothelial growth factor (VEGF) or its receptor signaling) are tested. One prime example is the electron-affinic nitroimidazoles, such as the clinically proven oxygen mimetic nimorazole, which covers the standard of care in HNC patients that are given RT in some countries [72]. Moreover, it has been demonstrated in glioblastoma patients that temozolomide-based CT/RT can be enhanced resulting in improved progression free survival if an anti-VEGF monoclonal antibody bevacizumab (avastin) is included in the treatment regimen [71]. In contrast, addition of bevacizumab to capecitabine and RT did not improve outcome in rectal cancer [77]. Further, vandetanib (ZD6474), a tyrosine kinase inhibitor targeting VEGFR, was shown to improve outcome of esophagogastric carcinoma patients when applied after RT or different CTs [70] (Box 6.6)."}
{"_id": "Radiology$$$207b3177-ec6c-49db-a399-023f6f1bc4e5", "text": "Inhibitors of the DDR signaling network, e.g., ATM, ATR, DNA-PKcs, and PARP-1 or interfering with cell some cycle regulating kinases offer sensitization for RT.\n\nBlockade of signaling from oncogenic drivers, e.g., growth factor regulated kinases via antibodies or small molecule inhibitors can sensitize tumors to RT.\n\nRestoring cell death pathways, e.g., apoptosis is another RT sensitizing strategy.\n\nModulating the tumor microenvironment, e.g. hypoxia and aberrant angiogenesis allow for tumor RT sensitization."}
{"_id": "Radiology$$$7313facc-6454-4609-9b45-1f60679fbeb9", "text": "Inhibitors of the DDR signaling network, e.g., ATM, ATR, DNA-PKcs, and PARP-1 or interfering with cell some cycle regulating kinases offer sensitization for RT."}
{"_id": "Radiology$$$3a66b4c1-c0fc-420d-aec1-85af10522a92", "text": "Blockade of signaling from oncogenic drivers, e.g., growth factor regulated kinases via antibodies or small molecule inhibitors can sensitize tumors to RT."}
{"_id": "Radiology$$$8c191421-9351-4634-941e-8d064e20ee48", "text": "Restoring cell death pathways, e.g., apoptosis is another RT sensitizing strategy."}
{"_id": "Radiology$$$0500cfb9-ddcb-4d7a-9d19-754fb1f5be9f", "text": "Modulating the tumor microenvironment, e.g. hypoxia and aberrant angiogenesis allow for tumor RT sensitization."}
{"_id": "Radiology$$$459aa3f8-0e6a-4eaa-ad26-71f3acec53a1", "text": "For a very long time, it was assumed that the X-rays directly, or indirectly through the formation of ROS, only affect the radiation-sensitive DNA in the cell and that other structures are spared. However, today it is clear that in addition to the so-called targeted local effects of radiation on DNA, numerous so-called non-targeted effects occur, such as general stress responses of the irradiated cells, which then also can be transmitted to other cells and even the entire organism."}
{"_id": "Radiology$$$8cfd8850-b364-4c97-ace7-7b4e41409085", "text": "Radiation-induced oxidative stress and DNA damage activate numerous signaling pathways in cells that influence the expression of genes and consequently trigger a broad spectrum of cellular responses ranging from promotion of cell survival to cell death (see Chap. 3). Thereby, the immunological phenotype of cells as well as the tumor microenvironment may change (see Chap. 5). It has been demonstrated that RT increases the expression of MHCI molecules, death receptors, and stress ligands on the tumor cell surface, and fosters the release of so-called damage-associated molecular patterns/danger-associated molecular patterns (DAMPs) such as adenosine triphosphate (ATP), HMGB1, and Heat Shock Protein 70 (HSP70) (see Chap. 5). Also, RT causes increased levels of immunostimulatory cytokines mainly through the induction of immunogenic tumor cell death (ICD) and in combination with additional immune stimulation [78]."}
{"_id": "Radiology$$$91bd8d7e-114e-40a1-a2af-b3488a2553dd", "text": "Irradiation of tumors also affect immune cells that circulate through the tumor vasculature even though the functionality of the remaining immune cells is still appropriate. One has to keep in mind that different subtypes of immune cells differ in their radiosensitivity and antigen-presenting cells as key initiators of adaptive antitumor immune responses, are quite radioresistant [79]. RT has also immune suppressive properties directly on the tumor cells and their microenvironment. Local irradiation increases the expression of immune checkpoint molecules such as programmed death-ligand 1 (PD-L1) and induces the release of transforming growth factor (TGF)-beta. Which of these changes that predominates varies greatly from individual to individual and ultimately determines whether, in addition to the local effects of tumor cell killing, local and systemically acting antitumor immune responses are triggered by RT alone [80]. The immune responses triggered by local radiation and acting systemically are referred to as \u201cabscopal effects\u201d of RT (for definition see Chap. 5). However, since radiation has both immune-activating and immune-suppressing effects (Fig. 6.6), the abscopal effect is usually only observed in the clinic when RT is used in combination with immunotherapies.\n\nA diagram presents the tumor enveloped in the micro-environment and normal tissue is targeted in irradiation. The enumerated effects of radiotherapy include fractionation, immune stimulating effects, immune suppressive effects, and primary local effects.\n\nFig. 6.6\nRadiotherapy has multiple immune stimulating and immune suppressive effects which depend on dose"}
{"_id": "Radiology$$$9c4d7601-3486-47f0-b534-8ee756782126", "text": "A diagram presents the tumor enveloped in the micro-environment and normal tissue is targeted in irradiation. The enumerated effects of radiotherapy include fractionation, immune stimulating effects, immune suppressive effects, and primary local effects."}
{"_id": "Radiology$$$8594d83a-af5c-484f-869d-7f7fceb2a008", "text": "If ICD is induced by local tumor irradiation and the tumor vasculature is changed in such a way that more immune cells can migrate into the tumor, this can already trigger effective antitumor immune responses [81]. In terms of radiation immunology, it is now believed that a single dose of 2 Gy is more likely to promote immune cell infiltration and a dose of >2 Gy is more likely to induce ICD [82]. Importantly, non-linear dose\u2013effect relationships often prevail. For example, the immunogenicity of tumor cells is reduced again after irradiation with a single dose that is too high, because enzymes are activated that degrade the immunogenic DNA found in the cytoplasm after irradiation or because immune-suppressing immune checkpoint molecules (ICM) are increasingly expressed on the tumor cells [83]."}
{"_id": "Radiology$$$6b85db15-5d5c-4dc1-9cc8-db4954680a72", "text": "Expression of immune suppressive ICM was the key starting point for a combination of radiation and immunotherapies. Inhibition of ICM in parallel with or shortly after RT has led to local and systemic antitumor immune responses in animal models and in the clinic, and the so-called radio-immunotherapies are increasingly being used in multimodal oncological treatment [84]. Further, immunologically-based patient selection based on induction chemo-immunotherapies is increasingly taking place [85]. Particularly exciting is the re-emergence of tumor vaccination in this context and the stratification of patients based on immunological factors of the peripheral blood (see Chap. 6) (Box 6.7)."}
{"_id": "Radiology$$$cd1b573d-7a94-4e4d-8c4a-576d535258c2", "text": "Radiation affects DNA and via stress responses other cellular compartments.\n\nRadiation induces local and systemic effects.\n\nRT has both immune stimulatory and immune suppressive effects.\n\nNon-linear dose relationships also apply for radiation-induced immune effects.\n\nRT is well combinable with immune therapy."}
{"_id": "Radiology$$$f244df0b-fa26-4b47-8f67-ffa69ea9c927", "text": "Hormone sensitive tumors which are dependent on certain hormones for their growth can be slowed down or stopped by hormone therapies.\n\nIn prostate cancer patients with a high risk of progression, hormone therapy in combination with RT is the treatment of choice as hormone therapy or RT alone remain inadequate"}
{"_id": "Radiology$$$515658f0-91b8-4bbd-bc3e-8336a1a4a377", "text": "Hormone sensitive tumors which are dependent on certain hormones for their growth can be slowed down or stopped by hormone therapies."}
{"_id": "Radiology$$$7d8d3ef7-94c4-4245-8a8c-de53d6f5eb03", "text": "In prostate cancer patients with a high risk of progression, hormone therapy in combination with RT is the treatment of choice as hormone therapy or RT alone remain inadequate"}
{"_id": "Radiology$$$528f0d39-7395-472b-8071-50b17b68ef60", "text": "A combination of RT and hormone therapy is used in the management of breast and prostate cancers. Hormone therapy is considered to be quite effective and comparatively non-toxic in tumors that are driven by hormones such estrogen in breast cancer (BC) and testosterone in prostate cancer (PCa). The hypothalamic pituitary gonadal pathway controls the concentration of testosterone and estradiol in the serum. Estradiol is mainly produced in the ovaries of premenopausal women, however, in case of postmenopausal women; aromatase found in the peripheral fat tissue aids the peripheral conversion of adrenal androgens. Hormonal therapy is principally accomplished by chemical castration (usage of chemicals or drugs like the gonadotropin-releasing hormone agonists or luteinizing hormone-releasing agonists that stop the production of the sex hormone) in case of men with PCa and premenopausal women with BC (Box 6.8)."}
{"_id": "Radiology$$$7e947915-cc60-4b1d-9960-bb15d73b707a", "text": "With respect to BC, approximately 50% of all premenopausal and 80% of all postmenopausal women suffer from a hormone receptor-positive malignancy. In the histochemical analysis of such tumor cases, the expression of estrogen (ER) and progesterone receptors (PR) are evaluated to understand the degree of positivity. The levels of ER/PR expression in BC are used as a guiding parameter for prognosis as well as for what systemic treatment to give. Recent studies have also shown that patients who overexpress the human epidermal growth factor receptor 2 (HER-2) have a low probability to benefit from hormone monotherapy. Hence it is necessary to target ER and PR as well as the HER-2 receptor. PCa can be hormone-dependent or non-dependent and have functional androgen receptors (AR). Hormone therapy is frequently part of curative therapy for both BC and PCa and where it is either used neoadjuvantly, i.e., for primary cancer size reduction before RT/radical surgery or adjuvantly, i.e., to decrease the risk of tumor recurrence."}
{"_id": "Radiology$$$e1fa8cfc-0547-4d33-a036-c8d07ae6b92a", "text": "For ER/PR-positive BC patients, hormone therapy is usually given along with postoperatively RT. The combined treatment of tamoxifen with RT has shown a synergistic effect in\u00a0vivo which can be attributed to the alterations in the tumor microenvironment. Further studies are required to shed light on the complex communications among the 17beta-estradiol and p53/p21(WAF1/CIP1)/Rb signaling pathways. IR is known to induce direct as well as indirect DNA damages via the ROS production. The DNA breaks generated; stimulate various signaling pathways associated with ATM (Ataxia telangiectasia-mutated gene), ATR (Ataxia telangiectasia-mutated gene Rad3-related), and DNA-PK (DNA-protein kinase). These kinases lead to the cell growth arrest after phosphorylation checkpoint kinase 2 (CHK2) or p53. The downstream effectors like p53/p21(WAF1/CIP1)/Rb, CDC25A, 14-3-3 sigma determine if the cell cycle arrest will be in the G1/S or G2/M transition. Interestingly, these pathways can be regulated at various stages by 17beta-estradiol (E2) in the irradiated cells. The ROS production can also be reduced by 17beta-estradiol, thereby reducing the subsequent effects of RT. This can be achieved either by reducing the p53 activation or by suppression of ROS induced DNA damage. Additionally, while 17beta-estradiol acts on S-phase kinase-associated protein 2 (SKP2) and P27 to allow G2/M transition, it also augments the expression of CCND1 and MYC that control the cell cycle promoting the G1/S transition. In contrast, tamoxifen, with its anti-estrogen activity obstructs the effects of 17beta-estradiol. This anti-estrogenic effect can strengthen the IR induced growth inhibition as depicted in Fig. 6.7 [86].\n\nA diagram displays the various signaling pathways of the genomic effect of estradiol, tamoxifen, and Ionising radiation on the cell cycle progression.\n\nFig. 6.7\nProspective direct genomic effect of estradiol, tamoxifen, and IR on inhibition of cell cycle progression. (Reproduced with permission from [86])"}
{"_id": "Radiology$$$fca22486-a562-4631-b448-b8024593d8b5", "text": "A diagram displays the various signaling pathways of the genomic effect of estradiol, tamoxifen, and Ionising radiation on the cell cycle progression."}
{"_id": "Radiology$$$e159549c-d3d2-48dc-b51c-32f30d535969", "text": "The usage of TAM is however limited because of the pharmacological side effects like endometrial changes that can lead to endometrial cancers or the thromboembolic events. Keeping this in mind, other endocrine drugs that might endow a comparable efficiency with boosted acceptability in early disease conditions can be utilized. Hence, Letrozole (LTZ), an aromatase inhibitor, is considered as a potent drug in the adjuvant settings. It can be delivered after surgery or in combination with RT with a long-term follow-up to identify the treatment- associated cardiac side effects and evaluate cancer-specific results. LTZ, when combined with radiation, arrests cancer cells in the G1 phase with a significant decrease of cells in the S phase and G2 phase of the cell cycle [87]. Table 6.8 gives the list of hormone therapies for breast and prostate cancers.Table 6.8\nHormone therapies used for breast and prostate cancer. (Reproduced with permission from [88])\n\nDrug\n\nType\n\nDose/route\n\nMode of action\n\nTamoxifen\n\nAnti-estrogen\n\nOrally, (20\u00a0mg) daily\n\nFor ER binding, competes with estradiol\n\nAnastrazole\n\nNon-steroidal aromatase inhibitor\n\nOrally, (1\u00a0mg) daily\n\nInhibition of competitive aromatase\n\nExemestane\n\nSteroidal aromatase inhibitor\n\nOrally, (25\u00a0mg) daily\n\nIrreversible aromatase inhibition\n\nGoserelin\n\nLHRH agonist\n\n(3.6\u00a0mg) every 28\u00a0days or\n(10.8\u00a0mg) every 3\u00a0months SC\n\nReduced pituitary production of LH and FSH\n\nBicalutamide\n\nNon-steroidal antiandrogen\n\nOrally, (50\u00a0mg) combination dose or (150\u00a0mg) single agent daily\n\nCompetitive AR inhibition\n\nPrednisolone\n\nCorticosteroid\n\nOrally, (5\u201310\u00a0mg) daily\n\nSuppression of Adrenal\n\nER estrogen receptor, LHRH luteinizing hormone-releasing hormone, LH luteinizing hormone, FSH follicle-stimulating hormone, AR androgen receptor, SC subcutaneous, IM intramuscular"}
{"_id": "Radiology$$$a7946107-dd9e-4099-8404-5f398a66f06e", "text": "During the course of the disease, a majority of PCas express the androgen receptor (AR) which is known to specifically direct the cancer cell behavior and this has solidified the significance of androgen signaling in the pathogenesis of PCa [89]. Hence, androgen deprivation therapy (ADT) is a foundation of PCa therapy. ADT is typically utilized to cut down the levels of serum testosterone to a castrate level. This can be accomplished by surgical or chemical castration. Chemical castration can be accomplished by using estrogens or LHRHa; and it is likely to be reversible. The consequence of initial use of LHRHa results in follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone surge in the serum, which makes the symptoms worse. Hence, patients are advised to take oral antiandrogens for 1\u20132\u00a0weeks prior to the LHRHa injection. ADT is mostly given with RT as a neoadjuvant therapy which can be continued throughout and even further than RT. Although evidence suggests that the combinatorial treatment of PCa with ADT and RT has improved therapeutic effects, there is still a lot of improvement that can be made on the biochemical front as demonstrated by the clinical trials. ADT might also boost the efficacy of RT by inhibiting successive PCa cell repopulation and by enhancing reoxygenation and radiosensitization. Many preclinical studies involving tumour cell lines in vitro and in\u00a0vivo tumor xenografts have suggested that ADT works by suppressing the mechanisms associated with the DNA damage response, particularly the NHEJ repair. This increases the anticancer effect induced by RT. Preclinical studies have also shown that the synergistic effect of RT and ADT enhances apoptosis by suppressing the DNA repair machinery. The combinatorial treatment not only increases the tumor oxygenation but also radiosensitizes the PCa cells. The first phase III, EORTC 22863, study demonstrated a noteworthy overall survival when RT was combined with ADT in men with locally advanced PCa. The results showed that the combination arm had a significantly higher OS compared to that of the RT alone (58.1% vs. 39.8%, p\u00a0=\u00a00.0004). Short-term and long-term follow-up of the EORTC studies showed that only 74% patients exhibited a 5-year disease-free survival with combined RT and ADT [89, 90]."}
{"_id": "Radiology$$$ce332467-2bb6-485f-a3ce-54f430633458", "text": "Hyperthermia as an adjuvant treatment to RT or chemotherapy considers heating of the tumor (area) above a physiological temperature up to 40\u201343\u00a0\u00b0C for approximately an hour. Hyperthermia can be applied as whole body, local invasively (intraperitoneal, interstitial, or intracavitary) and locoregional."}
{"_id": "Radiology$$$9eb7f38d-6619-48d9-a203-524f74c6541f", "text": "Hyperthermia as a radiosensitizer or chemosensitizer has been proven its effectiveness in many different tumor types, such as locally advanced cervical cancer, recurrent breast cancer, malignant melanoma, and head and neck cancer. The size, location, and type of tumor(s) determine whether hyperthermia should be applied only locally in combination with RT or chemotherapy, or whether hyperthermia should be applied to a larger area in combination with only chemotherapy. Hyperthermia has also been demonstrated to regulate the innate and adaptive immune system [91, 92]."}
{"_id": "Radiology$$$f569cc48-b745-40f0-9d1a-d83d2c32a6c8", "text": "For metastases from, e.g., colon or ovarian origin which are located in the peritoneal area, a heated chemotherapy solution can be circulated through the peritoneal area (called hyperthermic intraperitoneal chemotherapy; HIPEC) [93]. For urinary bladder cancer, a heat solution can be circulated through this organ (endocavity). Since all of these heated solutions are combined with chemotherapy, these hyperthermia setups will not be further discussed in this chapter. Generally, hyperthermia modifies the cytotoxicity of many chemotherapeutic agents. Furthermore, for some drugs, like the platinum compounds, hyperthermia was found to make resistant cells platinum-responsive again [94]. Whether hyperthermia has this effect on other drugs, needs to be investigated."}
{"_id": "Radiology$$$2743107d-7ff0-4127-8fd9-75c367cb80ea", "text": "Locoregional hyperthermia combined with RT is an approach for patients with locally advanced cervical carcinoma (deep hyperthermia) or recurrent breast cancer (superficial hyperthermia) in Europe and USA. Locoregional hyperthermia combined with RT has been used in the clinic already since the early 1980s [95]. It is also possible to implant a heat source in the tumor itself (interstitial), which mainly has been used for brain tumors or locally advanced head and neck tumors [96]. Hyperthermia weakens DNA damage repair enzymes and thereby retards the repair of radiation-induced DNA damage. An increased amount of unrepaired DNA damage causes more cells to die from the radiation injury. Importantly, the synergy between radiation and heat is highest when given simultaneously or closely together in time (within 4\u00a0h) [97]."}
{"_id": "Radiology$$$6e262e75-5554-410a-ac97-d100687e6bfb", "text": "Based on the preclinical knowledge gained in the last few years [91, 92], ongoing clinical trials are conducted with complementary translational studies focusing on immune alterations of patients receiving hyperthermia in combination with RT and/or chemotherapy. These data will form the basis for the design of multimodal cancer therapies in which hyperthermia will be combined additionally to radio- and/or chemotherapy with immune therapies such as immune checkpoint inhibitors."}
{"_id": "Radiology$$$288c751d-5034-420c-9635-52f044ff4a40", "text": "Hyperthermia can be applied using different techniques such as capacitive radiofrequency heating, radiative radiofrequency and microwave heating, infrared and laser, ultrasound, conductive heating, and by hyperthermic perfusion [63]. One of the most commonly used techniques which is validated within clinical trials is microwave heating and hyperthermia is induced with one or more antennas. An applicator containing one antenna is used for superficial hyperthermia, such as breast cancer or malignant melanomas. This applicator can be placed on the surface area. For deep hyperthermia, the patient lies on a mobile bed that can move through a circle with 4 or 6 antennas. This non-invasive method is used for deeper located tumors such as cervical cancers."}
{"_id": "Radiology$$$1dfc49e6-2b19-434a-aefd-9b34d7b55293", "text": "Macroscopical effects of hyperthermia: Hypoxic and nutrient-deprived areas of a tumor are the least sensitive to RT or chemotherapy, while these areas are especially sensitive to hyperthermia. By local heating of the tumor, an increased blood flow occurs, which increases reoxygenation [95]. As a consequence, more radiation-induced DNA damages are formed and fixed (Fig. 6.8). Moreover, increased tumor perfusion by hyperthermia allows the chemotherapeutic agent to penetrate deeper into the tumor.\n\nMicroscopical effects of hyperthermia: Besides increasing the radiation-induced DNA breaks within cancer cells, hyperthermia temporality inhibits DNA DSB repair (Fig. 6.8). This occurs by degrading the essential BRCA2 protein, and thereby temporarily inhibiting the homologous recombination DNA repair pathway. In HPV-positive cervical cancers, hyperthermia was found to disrupt the interaction between the HPV protein (E6) which in normal circumstances suppresses p53. Activation of p53 in these cancer cells results in cell death [95].\n\nImmune effects of hyperthermia: Dependent on the temperature, certain immunological processes are triggered by hyperthermia (Fig. 6.8). Starting with temperatures of 39\u00a0\u00b0C, an increased infiltration and activation of immune cells in the tumor can be observed in preclinical model systems. At higher temperatures, heat-induced cell death has certain characteristics of \u201cimmunogenic cell death\u201d (ICD). This means that the dying and dead cells activate rather than suppress the immune system. In this scenario, the heat shock protein 70 (HSP70) is a major player. While inside the cell, it acts as chaperon and protects cells (known as thermotolerance), outside of the cell when being, e.g., released by heat-induced necrotic cells, it activates dendritic cells and delivers antigen to these key immune cells that bridge innate and adaptive immunity. Thus, dendritic cells take up tumor antigens, present them with co-stimulation to CD8+ T cells, and subsequently trigger cellular antitumor immunity by priming cytotoxic T cells [99]. Additionally, HSP70 can directly activate further cells of the innate immune system, such as natural killer cells [100]. Based on this preclinical knowledge gained in the last years, ongoing clinical trials are conducted with complementary translational studies focusing on immune alterations of patients receiving hyperthermia in multimodal settings.\n\n\nA diagram illustrates that radiotherapy induces D N A damage, but with the addition of mild hyperthermia, there is perfusion and reoxygenation, and immune response among others, and inhibition of D N A repair temporarily which causes D N A damage, cell cycle arrest, and apoptosis in the tumor cell.\n\nFig. 6.8\nMild hyperthermia enhances radiotherapy by initiating multiple intracellular and intercellular processes. While radiotherapy induces DNA damages, hyperthermia can enhance the induction of radiation-induced DNA damage by increasing the perfusion and reoxygenation; hyperthermia can temporarily inhibit the DNA repair processes which causes cell cycle arrest and subsequently cell death of the tumor cells such as apoptosis; hyperthermia can also trigger an immune response and disturb the tumor microenvironment eventually all causes of increased tumor cell kill"}
{"_id": "Radiology$$$fe982d24-4689-4e8c-84fd-431e1a162899", "text": "Macroscopical effects of hyperthermia: Hypoxic and nutrient-deprived areas of a tumor are the least sensitive to RT or chemotherapy, while these areas are especially sensitive to hyperthermia. By local heating of the tumor, an increased blood flow occurs, which increases reoxygenation [95]. As a consequence, more radiation-induced DNA damages are formed and fixed (Fig. 6.8). Moreover, increased tumor perfusion by hyperthermia allows the chemotherapeutic agent to penetrate deeper into the tumor."}
{"_id": "Radiology$$$c848c3bf-358d-45fb-ba35-13112a967005", "text": "Microscopical effects of hyperthermia: Besides increasing the radiation-induced DNA breaks within cancer cells, hyperthermia temporality inhibits DNA DSB repair (Fig. 6.8). This occurs by degrading the essential BRCA2 protein, and thereby temporarily inhibiting the homologous recombination DNA repair pathway. In HPV-positive cervical cancers, hyperthermia was found to disrupt the interaction between the HPV protein (E6) which in normal circumstances suppresses p53. Activation of p53 in these cancer cells results in cell death [95]."}
{"_id": "Radiology$$$7fe5c455-49b4-4f67-a9d1-c3ed46658a35", "text": "Immune effects of hyperthermia: Dependent on the temperature, certain immunological processes are triggered by hyperthermia (Fig. 6.8). Starting with temperatures of 39\u00a0\u00b0C, an increased infiltration and activation of immune cells in the tumor can be observed in preclinical model systems. At higher temperatures, heat-induced cell death has certain characteristics of \u201cimmunogenic cell death\u201d (ICD). This means that the dying and dead cells activate rather than suppress the immune system. In this scenario, the heat shock protein 70 (HSP70) is a major player. While inside the cell, it acts as chaperon and protects cells (known as thermotolerance), outside of the cell when being, e.g., released by heat-induced necrotic cells, it activates dendritic cells and delivers antigen to these key immune cells that bridge innate and adaptive immunity. Thus, dendritic cells take up tumor antigens, present them with co-stimulation to CD8+ T cells, and subsequently trigger cellular antitumor immunity by priming cytotoxic T cells [99]. Additionally, HSP70 can directly activate further cells of the innate immune system, such as natural killer cells [100]. Based on this preclinical knowledge gained in the last years, ongoing clinical trials are conducted with complementary translational studies focusing on immune alterations of patients receiving hyperthermia in multimodal settings."}
{"_id": "Radiology$$$0bf21282-d177-463e-ba44-299f93582796", "text": "A diagram illustrates that radiotherapy induces D N A damage, but with the addition of mild hyperthermia, there is perfusion and reoxygenation, and immune response among others, and inhibition of D N A repair temporarily which causes D N A damage, cell cycle arrest, and apoptosis in the tumor cell."}
{"_id": "Radiology$$$60767933-9666-4278-8bfb-15ecd8c18311", "text": "Superficial tumors: Hyperthermia is, e.g., standard of care in the Netherlands, Germany, and Japan for patients with recurrent breast cancer (BC), who have received a full radiation treatment course for treatment of their primary tumor. Retreatment with a similar radiation dose as used for their primary tumors is not possible, therefore hyperthermia is applied to prevent severe radiation-induced toxicities. To accomplish the same effectiveness without severe normal tissue toxicity, RT is combined with hyperthermia. The latter gives a boost to the treatment effectiveness. Nevertheless, hyperthermia treatment is not refunded by insurances for treatment of most heatable tumor entities, since big randomized trials are still missing. Besides BC, malignant melanoma and head and neck cancers are prominent superficial tumor entities which are accessible for hyperthermia. The clinical outcomes using locoregional hyperthermia with RT and-/or chemotherapy have been summarized [101]. For soft tissue sarcomas, optimized strategies with multimodality approaches including chemotherapy, regional hyperthermia, and immunotherapeutic agents have been shown to improve survival in high-risk patients [102]. However, more randomized phase III studies, as carried out in an exemplary manner for soft tissue sarcoma [103], are urgently needed to bring hyperthermia as standard tumor therapy in multimodal settings into the clinics (Figs. 6.9 and 6.10).\n\nDeeper located tumors: In most countries, RT combined with chemotherapy is standard treatment of care for cervical cancer patients. However, chemoradiation is less beneficial in tumors of higher stage, whereas hyperthermia as an adjuvant to RT has shown its additional value. Especially in this group, chemoradiation was found to be not very effective. Moreover, chemoradiation seems to result in more toxicities, whereas hyperthermia in addition to RT did not increase radiation-induced toxicities [104].\n\nTreatment course: Both superficial and deep hyperthermia are applied in combination with either RT or chemotherapy. Depending on the tumor type, e.g., BC, cervical cancer, etc. and The International Federation of Gynecology and Obstetrics (FIGO) stage, a radiotherapy or chemotherapy scheme is chosen. While external beam RT is mainly given in daily fractions with low doses, hyperthermia is only applied once or twice per week, for 5 weeks in a row. For each treatment session, the target temperature should be above 40\u00a0\u00b0C for approximately 1\u00a0h. Moreover, a short time interval on the day that both RT and hyperthermia are given can be more beneficial, but research is ongoing in providing more evidence [105, 106] (Box 6.9).\n\n\n4 diagrams present how addition of hyperthermia to R T for patients suffering from melanoma, breast cancer and H N S C C increases C R from 35, 41 and 42.4% to 62, 59 and 76.6%, respectively and also drives an increase in 10 year overall survival in patients suffering from sarcoma.\n\nFig. 6.9\nImproved clinical responses after addition of hyperthermia in superficial tumor types. In malignant melanoma, superficial breast cancer and head and neck squamous cell carcinoma, complete responses were much better in patients treated with RT combined with hyperthermia, compared to RT alone. In soft tissue sarcoma, the addition of RT plus hyperthermia to neoadjuvant chemotherapy, leads to a8.6% higher 10-year overall survival\n\n\n Three diagrams of the improved clinical responses and additional effects after addition of hyperthermia in cervix cancer. The complete response to radiotherapy plus hyperthermia patients is 83% in C R, 37% in O S, and 56% in P C. \n\nFig. 6.10\nThe additional effect of hyperthermia in a deep located tumor (cervical cancer)"}
{"_id": "Radiology$$$958b3ebf-7201-494a-a710-9e935a964b6a", "text": "Superficial tumors: Hyperthermia is, e.g., standard of care in the Netherlands, Germany, and Japan for patients with recurrent breast cancer (BC), who have received a full radiation treatment course for treatment of their primary tumor. Retreatment with a similar radiation dose as used for their primary tumors is not possible, therefore hyperthermia is applied to prevent severe radiation-induced toxicities. To accomplish the same effectiveness without severe normal tissue toxicity, RT is combined with hyperthermia. The latter gives a boost to the treatment effectiveness. Nevertheless, hyperthermia treatment is not refunded by insurances for treatment of most heatable tumor entities, since big randomized trials are still missing. Besides BC, malignant melanoma and head and neck cancers are prominent superficial tumor entities which are accessible for hyperthermia. The clinical outcomes using locoregional hyperthermia with RT and-/or chemotherapy have been summarized [101]. For soft tissue sarcomas, optimized strategies with multimodality approaches including chemotherapy, regional hyperthermia, and immunotherapeutic agents have been shown to improve survival in high-risk patients [102]. However, more randomized phase III studies, as carried out in an exemplary manner for soft tissue sarcoma [103], are urgently needed to bring hyperthermia as standard tumor therapy in multimodal settings into the clinics (Figs. 6.9 and 6.10)."}
{"_id": "Radiology$$$74a64549-541f-4a53-a569-30770979f996", "text": "Deeper located tumors: In most countries, RT combined with chemotherapy is standard treatment of care for cervical cancer patients. However, chemoradiation is less beneficial in tumors of higher stage, whereas hyperthermia as an adjuvant to RT has shown its additional value. Especially in this group, chemoradiation was found to be not very effective. Moreover, chemoradiation seems to result in more toxicities, whereas hyperthermia in addition to RT did not increase radiation-induced toxicities [104]."}
{"_id": "Radiology$$$0e05f341-6d4e-47a2-941b-f50dbed15408", "text": "Treatment course: Both superficial and deep hyperthermia are applied in combination with either RT or chemotherapy. Depending on the tumor type, e.g., BC, cervical cancer, etc. and The International Federation of Gynecology and Obstetrics (FIGO) stage, a radiotherapy or chemotherapy scheme is chosen. While external beam RT is mainly given in daily fractions with low doses, hyperthermia is only applied once or twice per week, for 5 weeks in a row. For each treatment session, the target temperature should be above 40\u00a0\u00b0C for approximately 1\u00a0h. Moreover, a short time interval on the day that both RT and hyperthermia are given can be more beneficial, but research is ongoing in providing more evidence [105, 106] (Box 6.9)."}
{"_id": "Radiology$$$00a5967b-df47-4b34-9dbc-9e052097e5ac", "text": "4 diagrams present how addition of hyperthermia to R T for patients suffering from melanoma, breast cancer and H N S C C increases C R from 35, 41 and 42.4% to 62, 59 and 76.6%, respectively and also drives an increase in 10 year overall survival in patients suffering from sarcoma."}
{"_id": "Radiology$$$6624fb1d-1dd3-4c54-a92b-54cc9eeaedbe", "text": "Three diagrams of the improved clinical responses and additional effects after addition of hyperthermia in cervix cancer. The complete response to radiotherapy plus hyperthermia patients is 83% in C R, 37% in O S, and 56% in P C."}
{"_id": "Radiology$$$4c4a0de9-6590-4c20-9133-45512ef871a6", "text": "Hyperthermia enhances blood perfusion and reoxygenation, triggers an immune response, and disturbs the tumor microenvironment.\n\nHyperthermia increases RT and chemotherapy-induced DNA damage, inhibits the DNA damage repair pathways, increases cell cycles arrest, and induces cell death such as apoptosis and necrosis.\n\nHyperthermia was proven to be effective in many different tumor types, such as superficial breast cancer, soft tissue sarcoma, and cervical cancer."}
{"_id": "Radiology$$$ca670da8-4488-428a-8481-b164badd3b9d", "text": "Hyperthermia enhances blood perfusion and reoxygenation, triggers an immune response, and disturbs the tumor microenvironment."}
{"_id": "Radiology$$$b4a3c8c3-2d23-4a5d-81c0-462f3f742bc6", "text": "Hyperthermia increases RT and chemotherapy-induced DNA damage, inhibits the DNA damage repair pathways, increases cell cycles arrest, and induces cell death such as apoptosis and necrosis."}
{"_id": "Radiology$$$0e3d285d-5196-498e-814a-fc001776120b", "text": "Hyperthermia was proven to be effective in many different tumor types, such as superficial breast cancer, soft tissue sarcoma, and cervical cancer."}
{"_id": "Radiology$$$98474541-c901-408d-a4d9-c01ab80a9dc0", "text": "Voluntary fasting is a part of religious services in many cultures like Buddhism, Christianity, Hinduism, etc. Fasting/short-term fasting (STS) is also known as calorie restriction (CR) which is associated with diets with a wide alteration in the growth factors and the metabolites levels. This produces a milieu that diminishes the cancer cell competency to get acclimatized and endure which results in improved outcomes for cancer therapy. In normal cells, STS and fasting selectively boost the chemotherapy resistance which is not the case with cancer cells. STS endorses rejuvenation of normal cells, thereby averting the toxic and harmful effects of the treatment. Clinical as well as in\u00a0vivo studies suggest that the low calorie-fasting mimicking diet (FMD) cycles are promising and also safe, in patients that can barely endure STS/fasting. Hence, it can be predicted that the combination of STS or FMDs with chemotherapy, immunotherapy as well as other therapies holds a promise in increasing the cancer treatment efficacy, preventing the acquired resistance and minimizing the aftereffects [107]. This can be correlated with one of the emerging hallmarks of cancer, i.e., the susceptibility of cancer cells to nutrient deficiency and their addiction for explicit metabolites. Three of the nutritional interventions of food withdrawal strategies like fasting, FMD, and calorie CR from the myriad of strategies have increasingly exhibited a valuable effect on metabolism and shown a promising anticancer activity. STS is typically done on an average of 3\u20135 successive days. In fasting, only water is consumed, for a time-span ranging from 12\u00a0h to 3\u00a0weeks. For CR, there is a 20\u201340% decrease in calorie ingestion with decrease in all constituents without intercepting the ingestion of minerals and vitamins, typically used by specialists as a synonym to dietary restriction."}
{"_id": "Radiology$$$59c0242a-6e98-4c77-a00e-935fa3fb7731", "text": "Cancer cells are distinguished from normal cells by means of their irregular metabolic and signaling pathways that lead to circumventing the antiproliferative signals, distorted mitochondrial function, and increased glucose uptake. Fasting or STS exhibits a differential consequence on cancer cells and normal cells which can be attributed to drop in the glucose, insulin-like growth factor-1, and insulin levels, amplification in ketone bodies and insulin-like growth factor-binding protein 1 (IGFBP1). This phenomena force cancer cells to depend on the limited amounts of factors and metabolites that are present in the blood, thereby eventually resulting in cell death. The response mechanisms of differential stress sensitization (DSS) and differential stress resistance (DSR) caused by fasting/STS stimulate the normal cell protection but pushes the cancer cell toward cell death. One of the major classical responses of radiation is the dys-functioning of the cell cycle arrest [108]."}
{"_id": "Radiology$$$4d9fb0de-983d-4cbc-984f-a6d2de2fd1cc", "text": "There is a growing body of evidence from the preclinical studies on STS which enhances the efficacy of a wide variety of chemotherapy drugs that are used in treatments of several types of tumors. Some of clinical trials (NCT00757094, NCT00936364, NCT01304251, and NCT01954836) have proven to be safe and feasible with reduction in the chemotherapy associated side effects. Since STS has demonstrated favorable traits to fight cancer, it would be logical to combine STS with RT as it presents clinical gain. In preclinical studies, combining STS with RT has already exhibited enhanced RT effects. Clinical and preclinical trials of STS and RT are also picking pace to exhibit the efficacy of this combination. STS can be considered as a personalized dietary approach that can be conveniently combined with RT in clinics in the path forward (Box 6.10)."}
{"_id": "Radiology$$$21bf7d3c-ddd0-406a-a4ae-c73b934dd952", "text": "Short-term starvation (STS) in combination with RT leads to an increased effect of RT on metastatic cancer cells, and at the same time also protects normal cells.\n\nShort-term starvation (STS) or fasting can particularly safeguard normal cells in mice and probably in patients receiving chemo without reducing the therapeutic effect on cancer cells.\n\nFasting dependent decrease in IGF-1 and glucose are arbitrate components involved in the DSR and DSS effects."}
{"_id": "Radiology$$$4a085fc1-0172-4d67-bfe8-184fd4020e53", "text": "Short-term starvation (STS) in combination with RT leads to an increased effect of RT on metastatic cancer cells, and at the same time also protects normal cells."}
{"_id": "Radiology$$$692fe24c-81a0-4bd4-b583-4a2993777c5a", "text": "Short-term starvation (STS) or fasting can particularly safeguard normal cells in mice and probably in patients receiving chemo without reducing the therapeutic effect on cancer cells."}
{"_id": "Radiology$$$20619943-7565-4fc8-ba5d-5f6f0d449b42", "text": "Fasting dependent decrease in IGF-1 and glucose are arbitrate components involved in the DSR and DSS effects."}
{"_id": "Radiology$$$6627aed5-14ba-4105-ad6a-9571640e95ac", "text": "Spatial fractionation is a method that reduces damage to normal tissue.\n\nSmall beams of radiation are applied in a grid-like pattern.\n\nHigh doses are applied in the beam path, while (almost) no or very low dose is delivered between the beams, resulting in high peak-to-valley dose ratio  (PVDR)."}
{"_id": "Radiology$$$7fe96773-5ba3-4ee4-8d79-b5fe6dd8dcae", "text": "Spatial fractionation is a method that reduces damage to normal tissue."}
{"_id": "Radiology$$$fa43c1cc-4e74-43b3-b3d3-b8198d24bd94", "text": "High doses are applied in the beam path, while (almost) no or very low dose is delivered between the beams, resulting in high peak-to-valley dose ratio  (PVDR)."}
{"_id": "Radiology$$$ce03a203-f0e9-48be-b801-ab6117943509", "text": "Spatial fractionation of photons is in clinical use.\n\nGRID therapy uses 2D pattern with beam width of ~1\u20131.25 cm and center to center (ctc) of 2.2\u20132.4 cm.\n\nLATTICE is the 3D extension of GRID therapy."}
{"_id": "Radiology$$$dc53dd7a-e6c2-4c97-9137-681d5b72650d", "text": "GRID therapy uses 2D pattern with beam width of ~1\u20131.25 cm and center to center (ctc) of 2.2\u20132.4 cm."}
{"_id": "Radiology$$$83bf74c7-f8ba-485c-bbf7-9dc83305a31c", "text": "Minibeam RT (MBRT) is a modern therapy approach using protons and heavier ions, which is at the moment in preclinical stage or investigated in clinical trials.\n\nIn proton MBRT, the beam widen and overlap in the tumor.\n\nFurther sparing of healthy tissue can be achieved using interlacing methods."}
{"_id": "Radiology$$$a7d939a1-998a-42e0-a14b-08f6939121ef", "text": "Minibeam RT (MBRT) is a modern therapy approach using protons and heavier ions, which is at the moment in preclinical stage or investigated in clinical trials."}
{"_id": "Radiology$$$51f1f167-465b-432a-8ccd-6e06358dd0d6", "text": "In proton MBRT, the beam widen and overlap in the tumor."}
{"_id": "Radiology$$$65097f17-9c63-4d22-9e1c-93357ba9aa6a", "text": "Further sparing of healthy tissue can be achieved using interlacing methods."}
{"_id": "Radiology$$$0a375cac-1444-48b5-81a1-b6154a25d9f3", "text": "The concept of spatial fractionation of radiation in tumor therapy aims to widen the therapeutic window by sparing healthy tissue by simply sparing parts of it from radiation. It was introduced as GRID therapy by Alban K\u00f6hler in 1909 by the use of a grid of centimeter-wide pencil beams in X-ray therapy [109]. In the 1990s, when more powerful X-rays became available from synchrotron facilities, GRID therapy was moved to the micro level with the development of microbeam radiotherapy (MRT) and to the submillimeter level in the later 2000s with minibeam radiotherapy (MBRT) [110]. It was then that GRID, MRT, and MBRT were classified under a broader term of spatially fractionated radiation therapy (SFRT)."}
{"_id": "Radiology$$$3c1cdd26-276c-4bc4-85b4-870f4fd38795", "text": "In SFRT, the spatial arrangement of the radiation allows irradiating tumors with a heterogeneous dose, with high doses in the radiation channels and low doses in the so-called valleys in between."}
{"_id": "Radiology$$$f7051ace-d8df-4d47-b911-05674bf08b48", "text": "In recent years, advances in the use of spatial fractionation in particle therapy have also been investigated. Proton minibeam radiotherapy (pMBRT) is making rapid progress [111]. Thanks to small-angle scattering, the radiation channels overlap and the tumor is irradiated with a homogeneous dose, while the normal tissue is spared due to the spatial fractionation of the dose (Box 6.11, 6.12, and 6.13)."}
{"_id": "Radiology$$$4bcf973a-3a1e-48a9-8d9e-9b41050a336c", "text": "Schematic representations of SFRT, proton and ion MBRT is shown in Fig. 6.11.\n\nA schematic displays conv and grid where the tumor is at the center under photons, and conv, proton and ion M B R Ts where the tumor is at the tail end on the right under particles. Below is a table that provides information on dose pattern, photon S F R T, proton and ion M B R T.\n\nFig. 6.11\nSchematic view of spatial fractionation in RT. The blue object represents the tumor"}
{"_id": "Radiology$$$6cdcac62-f016-4b65-8592-49a7c457571b", "text": "A schematic displays conv and grid where the tumor is at the center under photons, and conv, proton and ion M B R Ts where the tumor is at the tail end on the right under particles. Below is a table that provides information on dose pattern, photon S F R T, proton and ion M B R T."}
{"_id": "Radiology$$$5925e96d-e976-4759-97e6-79cee24f1ac2", "text": "Spatial fractionation of radiation means that new parameters must be introduced and controlled in treatment planning and therapy. First and foremost, beam size and the distance between two beams become the most important variables. Beam size, or beam width, is the full width at half maximum (FWHM) of the lateral intensity profile of a beam. The distance between two beams, also called center-to-center distance (ctc), is defined as the length of the direct connection between the maximum intensity (also called center) of the two beams [112]."}
{"_id": "Radiology$$$36cee2ed-a8aa-4be2-b965-6ca3584acf03", "text": "Another important quantity is the dose ratio between the dose in the center of the beam (peaks) DP and the dose in the middle between two beams (valleys) DV, the peak-to-valley dose ratio (PVDR):\n\n (6.3)The PVDR defines the strength of spatial fractionation. It is ~1 for homogeneous irradiation and approaches infinity for small valley doses [113]."}
{"_id": "Radiology$$$19cdc0b8-7315-4dc3-ab39-8d133808ffe0", "text": "The parameters of beam width, ctc, and PVDR determine the possibility of sparing normal tissue and also the dose applied to the tumor, thus influencing tumor control."}
{"_id": "Radiology$$$c1f55cb0-cb65-4b96-af89-bf1ca383f39d", "text": "Finally, the geometric arrangement of the beams is also crucial. Spatial fractionation uses beams that have either a pencil (Fig. 6.12a, b) or a planar structure (Fig. 6.12c). Pencil beams have a completely round or Gaussian shape and can be arranged in either a square or hexagonal lattice. For treatment planning, it is important to know the dimensions of a beam. For this purpose, the unit cell of a beam is used. The unit cell is the smallest unit in which a beam can be considered a beam and the entire dose distribution is covered. The unit cell is assembled to form the entire lattice and cover the tumor.\n\n3 diagrams, a to c, with respective minibeams and c t c sub q. A depicts c t c sub q connects 2 unit cells above the square. B depicts c t c sub h diagonally connects the unit cell inside and outside the hexagon. C depicts the unit cell and c t c sub p is parallel with each other.\n\nFig. 6.12\nQuadratic (a) and hexagonal (b) pencil minibeam and planar minibeam (c) arrangements on a 2D lattice with view direction in the direction of the beam. The dose is color coded and normalized to a mean dose D0. The black lines indicate the unit cell, and the white lines indicate the corresponding ctc. (Reproduced with permission from (CCBY) [112])"}
{"_id": "Radiology$$$05fd36cd-d27e-489e-a73e-4356197ac8b5", "text": "3 diagrams, a to c, with respective minibeams and c t c sub q. A depicts c t c sub q connects 2 unit cells above the square. B depicts c t c sub h diagonally connects the unit cell inside and outside the hexagon. C depicts the unit cell and c t c sub p is parallel with each other."}
{"_id": "Radiology$$$b1b55595-b3e9-4a7b-8c76-ffb459b52743", "text": "The basic mechanism of tissue sparing by spatial fractionation lies in the ability of undamaged cells in the vicinity of the radiation beam paths to migrate to this region and support wound healing. This is described as the dose-volume effect, i.e., the ability of skin and subcutaneous tissue in particular to tolerate more dose as the irradiated volume decreases. Furthermore, the microscopic prompt tissue repair is another beneficial effect resulting in better tolerance of tissue to submillimeter sized beams. When tissue is damaged in such small areas, capillary blood vessels can be rapidly restored within days or even hours by the regeneration of cells from the undamaged area. The intact blood vessels also support healing of the damaged tissue located between the beams. The extent to which the bystander effect plays a role is still unknown and is currently being investigated."}
{"_id": "Radiology$$$f211db5f-bff3-482d-9d4e-2c92aa0aac11", "text": "Spatial fractionation of photons is already being used clinically, but other treatment strategies are being tested simultaneously in preclinical and clinical studies. The application of photon SFRT in the clinic can be distinguished into GRID and LATTICE therapy. In GRID therapy, based on the original method of Koehler et al. in 1909, portions of the radiation field are blocked by the use of collimators placed in front of the patient to produce a non-conformal dose in both healthy tissue and tumor, as shown in a therapy plan in Fig. 6.13b [109].\n\nTwo sets of three magnetic resonance images in lattice and 2 D grid configurations. \n\nFig. 6.13\nTreatment planning of a lung tumor patient in LATTICE (a) and GRID (b) therapy. (Reproduced with permission from [114])"}
{"_id": "Radiology$$$4c294db3-58c7-46df-a60b-d3f82f5dfac9", "text": "Two sets of three magnetic resonance images in lattice and 2 D grid configurations."}
{"_id": "Radiology$$$4e73f134-b8d4-404e-ba71-b554bfd75f56", "text": "Optimal geometries of collimators for tissue sparing and therapeutic outcome are hole sizes from 1 to 1.25 cm and ctc from 2.2 to 2.4 cm [114]. The pattern can be generated either with a block collimator with a defined hole pattern or with multileaf collimators (MLCs), which can be flexibly adapted to the needs of the treated tumor. The disadvantage of MLCs in the clinic is that treatment time is prolonged because each spot must be applied in a step-and-shoot procedure. Although faster irradiations are possible with MLCs by moving the target across the beam, this is currently only possible preclinically. A more advanced method is the hybrid use of an MLC and a block collimator, which combines the advantages of both methods but has the disadvantage of lower PVDR along the diagonal [115]."}
{"_id": "Radiology$$$68232469-7312-435f-8474-bf4b644d8189", "text": "The efficiency of GRID therapy has been demonstrated in various clinical trials with different tumor types and by using different collimators [114, 115]. A modern approach to photon SFRT is LATTICE therapy, which can be used with arc-based therapy and is the 3D extension of GRID therapy. In LATTICE therapy, the beams are applied to form multiple small spheres of high dose, called vertices, in the tumor (Fig. 6.13a). The LATTICE application further reduces damage to normal tissue and has also been used in clinical trials [116]."}
{"_id": "Radiology$$$e3a85ca7-8075-451b-8842-d21d354ad6e3", "text": "While the use of SFRT in the clinic started with GRID and LATTICE, there are two other spatially fractionated modalities that are being studied preclinically. These are MRT, which uses spatially fractionated photons in the form of rectangular beams 25\u2013100\u00a0\u03bcm wide (Fig. 6.14), and MBRT, which also uses rectangular photon beams but 400\u2013700\u00a0\u03bcm wide.\n\nA hematoxylin and eosin stain image of the cerebellum of a rat displays the leftward arrows denote the track of the microbeams. An immunostaining image of the different section of the cerebellum of a rat exhibits the four vertical green staining.\n\nFig. 6.14\nCerebellum of a rat 8\u00a0h after exposure to synchrotron MRT. The peak dose was 350\u00a0Gy, and each microbeam was 25\u00a0\u03bcm wide and spaced 200\u00a0\u03bcm from the center of the next microbeam. (a) H&E staining of the cerebellum. The track of the microbeams can be seen as two vertical bands of dark blue dots (yellow arrows) consisting of cells with nuclear pyknosis (irreversible condensation of chromatin in the nucleus of cells undergoing necrosis). (b) Immunostaining of a different section of the cerebellum with gamma-H2AX. The track of the microbeam can be seen as green staining, indicating large amounts of DNA damage. The blue color indicates nuclear staining with DAPI"}
{"_id": "Radiology$$$b025f384-c3ad-4785-be62-7fc8f95bfdd4", "text": "A hematoxylin and eosin stain image of the cerebellum of a rat displays the leftward arrows denote the track of the microbeams. An immunostaining image of the different section of the cerebellum of a rat exhibits the four vertical green staining."}
{"_id": "Radiology$$$5b71b1d6-d20a-49ea-a0d7-5273d5785054", "text": "MRT has the distinction of using extremely thin microbeams, which exploits the dose-volume effect and allows very high doses of radiation (300\u2013600\u00a0Gy) to be delivered with minimal toxicity to normal tissue. In addition, synchrotron facilities such as the European Synchrotron can deliver radiation at ultra-high dose rates (12,000\u201316,000\u00a0Gy/s), making synchrotron MRT a spatially fractionated FLASH RT [117]."}
{"_id": "Radiology$$$7ba88e51-8182-4ce4-bc59-2b8d90b7d8b4", "text": "The benefits of MRT over conventional RT are many:\nNormal tissue is spared from the effects of radiation by two unique mechanisms: (1) volumetric sparing due to spatial fractionation of microbeams and (2) sparing of normal tissue due to ultra-high dose rates, known as the FLASH effect [117]. More details of FLASH radiotherapy are discussed in Sect. 6.\u200b4.\u200b2.\n\nMRT produces unique vascular effects that preferentially damage tumor vessels rather than those of healthy tissue. Peak doses selectively affect rapidly growing \u201cimmature\u201d tumor vasculature, triggering transient tumor ischemia and neutrophil infiltration [117].\n\nStrong immune responses have been observed after MRT. For example, MRT can activate natural killer and cytotoxic CD8+ T cells, induce higher levels of pro-inflammatory genes in tumors, trigger the release of chemokines that attract monocytes, and recruit leukocytes to malignant tissues [118]."}
{"_id": "Radiology$$$4b55b623-010e-4eb6-b2fd-370453b40295", "text": "Normal tissue is spared from the effects of radiation by two unique mechanisms: (1) volumetric sparing due to spatial fractionation of microbeams and (2) sparing of normal tissue due to ultra-high dose rates, known as the FLASH effect [117]. More details of FLASH radiotherapy are discussed in Sect. 6.\u200b4.\u200b2."}
{"_id": "Radiology$$$118eb51f-cb5a-473f-8bff-1cc326e19050", "text": "MRT produces unique vascular effects that preferentially damage tumor vessels rather than those of healthy tissue. Peak doses selectively affect rapidly growing \u201cimmature\u201d tumor vasculature, triggering transient tumor ischemia and neutrophil infiltration [117]."}
{"_id": "Radiology$$$698d4174-6af6-4785-8a3c-a50b9e5b47c9", "text": "Strong immune responses have been observed after MRT. For example, MRT can activate natural killer and cytotoxic CD8+ T cells, induce higher levels of pro-inflammatory genes in tumors, trigger the release of chemokines that attract monocytes, and recruit leukocytes to malignant tissues [118]."}
{"_id": "Radiology$$$73495af4-1d1f-4caa-886e-c6ab172f2339", "text": "MRT currently requires ultra-high dose rates to deliver the radiation fast enough to prevent the beam from smearing across tissue due to the cardiovascular motion. Therefore, preclinical and future clinical research on MRT is currently limited to synchrotron facilities. However, a compromise can be achieved by delivering photon MBRT, since beam smearing is not a problem with submillimeter beams. The same logic is now being applied to MBRT ion therapy research and will be discussed next."}
{"_id": "Radiology$$$15c0d380-46f7-4577-9e68-11c59816cb5d", "text": "The method of applying spatially fractionated RT using particles, also called minibeam RT, is still in its infancy. Preclinical research points to drastically lowered side effects, with at least same tumor control, thus clearly widening the therapeutic window. In MBRT, one distinguishes between proton MBRT and ion MBRT, most commonly carbon and helium. The major difference lies in the application of the dose to the tumor originating from different physical properties of the particles. When particles traverse matter, interactions with the atoms and molecules occur. At high energies, as used for therapy, the interactions are dominated by Coulomb interactions with the electrons of the target material. These mechanisms mainly cause the ions to lose energy and define the well-known Bragg curve of energy loss. But these interactions also cause scattering of the ions and thus deflection, called small-angle (Coulomb) scattering. In each interaction, the particle is only scattered by a small angle, causing a roughly gaussian broadening of an incident ion beam. The beam is thus widening with increasing penetration depth. The FWHM of the beam due to scattering, which is in the order of several millimeters for therapy relevant energies, is proportional to the ion charge z its kinetic energy Ekin and the distance covered in medium x:\n\n (6.4)Therefore for helium and carbon ions, this results in a reduction of beam width compared to protons of a factor of ~2 and ~3, respectively, as shown in Fig. 6.15.\n\nLine graph A presents f w h m versus depth in water. The proton, helium, carbon, and neon exhibit an upward trend, with proton having the highest value. B exhibits width in centimeters versus distance in centimeters where helium ion and proton beam widen as the distance increases.\n\nFig. 6.15\n(a) Beam width for proton, helium, and carbon ion beams with penetration depth. No incident beam size and divergence is used, both have to be added to the FWHM. (b) Widening of a helium ion and a proton beam with penetration depth"}
{"_id": "Radiology$$$294fe4ac-9267-44e3-9b82-92d11b0108a3", "text": "Line graph A presents f w h m versus depth in water. The proton, helium, carbon, and neon exhibit an upward trend, with proton having the highest value. B exhibits width in centimeters versus distance in centimeters where helium ion and proton beam widen as the distance increases."}
{"_id": "Radiology$$$6c77bbb0-99a4-4338-af64-ad4ee009b8c2", "text": "Therefore MBRT for protons works with the principle that the beams start to clearly widen, while traversing tissue as shown in Fig. 6.16. The planning is done in a way that at the beginning of the tumor, the beams overlap and the tumor is irradiated with a small PVDR or even a homogeneous dose distribution.\n\n2 conceptual therapy plans of homogenous and minibeam for a box-shaped tumor. Minibeam exhibits the pencil and the planar beams overlap and penetrate the skin and the healthy tissue and then widen at the beginning of the tumor. On the right is the scale for dose distribution from 0% to above 120%.\n\nFig. 6.16\nConceptual therapy plans comparing conventional proton therapy (homogeneous) with pMBRT (Minibeam) for a box-shaped tumor"}
{"_id": "Radiology$$$1a5d5850-8c26-4560-9978-031bf4d2d33f", "text": "2 conceptual therapy plans of homogenous and minibeam for a box-shaped tumor. Minibeam exhibits the pencil and the planar beams overlap and penetrate the skin and the healthy tissue and then widen at the beginning of the tumor. On the right is the scale for dose distribution from 0% to above 120%."}
{"_id": "Radiology$$$35fe1bec-4d9a-48b7-9e26-5ea9d081b912", "text": "For helium and carbon, the beams don\u2019t overlap, thus giving potential for further sparing of healthy tissue also close to the tumor volume. Although there is evidence for tumor control using heterogeneous tumor dose, it seems appropriate to find a way of applying an (almost) homogeneous dose to the tumor [119]. This is achieved through so-called interlacing, where the beams of different irradiation fields are arranged in a way that in the tumor the dose peaks interlock and homogeneous dose distribution is formed. Figure 6.17 shows different possibilities of interlacing using either pencil or planar beams compared to single direction irradiation.\n\n6 diagrams of the interlacing geometries in M B R T. 1- and 2-direction pencil p M B R T, 1- and 2-direction planar p M B R T, and 2- and 4-direction planar p M B R T, where the beams of different irradiation fields are arranged for the homogeneous irradiation of a box-shaped tumor.\n\nFig. 6.17\nPossible interlacing geometries in MBRT for pencil (a, b) or planar (c\u2013f) beams for homogeneous irradiation of a box-shaped tumor (black dashed line). (Reproduced with permission (CCBY) from [119])"}
{"_id": "Radiology$$$baeab1e9-ba27-47c3-8f37-26a482efe1b2", "text": "6 diagrams of the interlacing geometries in M B R T. 1- and 2-direction pencil p M B R T, 1- and 2-direction planar p M B R T, and 2- and 4-direction planar p M B R T, where the beams of different irradiation fields are arranged for the homogeneous irradiation of a box-shaped tumor."}
{"_id": "Radiology$$$d9a398c6-0fa4-4eb1-9c02-9ebd111faa2b", "text": "Up to now, the method of MBRT is still in the preclinical state and especially proton MBRT is investigated here, as the possible spreading is more promising as more proton therapy centers than other particle therapy centers exist worldwide. Up to now it could be shown that pMBRT has lower early and late side effects in the skin of mice and rats [113, 120]. Furthermore, in a rat brain model, it could be shown that less histological and behavioral changes occur after pMBRT [120]. Already tumor treatment was performed in glioma bearing rats, where animal survival could be clearly enhanced while tumor control was kept. First therapy planning in brain tumor patients shows reduced dose to organs at risk, while the same dose distribution in PTV could be achieved (Fig. 6.18) [121]. These promising preclinical results cleared the way for clinical trials. First results on treatment of ten patients treated with pMBRT, called proton GRID therapy, in a clinical study (NCT01255748) show the possible advantages of pMBRT, regarding sparing of healthy tissue and tumor control [122]. Furthermore, the integration of pMBRT to clinical facilities is under investigation and especially the combination with FLASH RT seems promising [113]. An important task which needs to be solved is the production of mini beams with a small enough size without producing secondary radiation, which can harm the patient. The two possible ways of minibeam production are via the focusing of a proton beam or via the use of a collimator. Both methods are complementary, and their use in clinical practice needs to be further investigated.\n\n4 treatment plans for meningioma. Plans 1 and 2 are homogeneous plans while 3 and 4 display single field p M B R T plans that directly target P T V in the brain. Below, a line graph of volume versus dose. Right lobe, brain, and brain stem depict a downward trend while P T V plateau before declining.\n\nFig. 6.18\n(a) Treatment plan comparison of a meningioma patient. Plan 1 and 2 are homogeneous plans, with different planning methods. Plan 3 and 4 show single field pMBRT plans with ctc of 4 mm and 6\u00a0mm, respectively. (b) Comparison of dose-volume histograms for plan 2 (homogeneous, dashed line) and plan 3 (pMBRT, solid line)"}
{"_id": "Radiology$$$909dba2a-e328-4309-a82b-78a0f83a1f81", "text": "4 treatment plans for meningioma. Plans 1 and 2 are homogeneous plans while 3 and 4 display single field p M B R T plans that directly target P T V in the brain. Below, a line graph of volume versus dose. Right lobe, brain, and brain stem depict a downward trend while P T V plateau before declining."}
{"_id": "Radiology$$$b80b2a32-9eba-44cf-bd2e-df6f54d9c4b9", "text": "According to the dose rate brachytherapy can be divided into three types: low dose rate (LDR) with dose rates 0.4\u20132\u00a0Gy/h, medium dose rate (MDR) with dose rates 2\u201312\u00a0Gy/h, and high-dose rate (HDR) with dose rates excessing 12\u00a0Gy/h.\n\nBrachytherapy can be delivered with sealed radionuclide sources and electronic brachytherapy using kV X-rays.\n\nBrachytherapy is mostly used for treatment of cervix, prostate, and skin cancers and some rare sarcomas."}
{"_id": "Radiology$$$42480809-8453-4575-8b85-d3da62e34791", "text": "According to the dose rate brachytherapy can be divided into three types: low dose rate (LDR) with dose rates 0.4\u20132\u00a0Gy/h, medium dose rate (MDR) with dose rates 2\u201312\u00a0Gy/h, and high-dose rate (HDR) with dose rates excessing 12\u00a0Gy/h."}
{"_id": "Radiology$$$f3caba58-9ea1-4f86-9809-2dcf05a4a78e", "text": "Brachytherapy can be delivered with sealed radionuclide sources and electronic brachytherapy using kV X-rays."}
{"_id": "Radiology$$$7094978a-eaa1-4589-accd-4d3897a1ff98", "text": "Brachytherapy is mostly used for treatment of cervix, prostate, and skin cancers and some rare sarcomas."}
{"_id": "Radiology$$$38493255-f927-40a7-8c15-0ffb49488147", "text": "Brachytherapy is a treatment technique in which radiation sources are placed into the tumor (or the tumor bed to be treated after surgery) or its proximity. For conventional brachytherapy, sealed radionuclide sources are used, but electronic brachytherapy with X-ray has recently become available. The advantage of brachytherapy is a very high dose gradient around the sources, which are, contrary to external RT, extremely close to the treated area. Sharp dose decrease allows for a high level of conformity when dose is delivered locally. However, the technique is available only for easily accessible treatment areas."}
{"_id": "Radiology$$$1c19b90c-d719-4243-a311-80533982d98e", "text": "The fractionation scheme is different in comparison to the external RT with lower number of fractions and higher doses per fraction."}
{"_id": "Radiology$$$c1a2502c-59fe-4666-8e7b-702e8cbdd655", "text": "Usually, radionuclide implants are applied to deliver the treatment which can be either temporary or permanent. The radionuclides need to have convenient physical characteristics (half-life, type of disintegration, mean energy, nominal specific activity, etc.)."}
{"_id": "Radiology$$$fd527f35-3e68-4e02-9200-80c4a39afa8d", "text": "According to the dose rate brachytherapy can be divided into three types: low dose rate (LDR) with dose rates 0.4\u20132\u00a0Gy/h, medium dose rate (MDR) with dose rates 2\u201312\u00a0Gy/h, and high dose rate (HDR) with dose rates exceeding 12\u00a0Gy/h (which is 0.2\u00a0Gy/min). Higher source energies are used for temporary brachytherapy with HDR sources compared to permanent LDR brachytherapy. Pulsed dose rate (PDR) uses series of short exposures of 10\u201330 min every hour to approximately the same total dose in the same overall treatment time as with the LDR. Characteristics of frequently used radionuclides are presented in Table 6.9.Table 6.9\nPhysical characteristics of radionuclides used for brachytherapy\n\nCharacteristic\n\n192Ir\n\n60Co\n\n137Cs\n\n125I\n\n103Pd\n\nType of disintegration\n\n\u03b2\u2212 (95.1%), Electron capture (4.9%)\n\n\u03b2\u2212\n\n\u03b2\u2212\n\nElectron capture\n\nElectron capture\n\nHalf-life\n\n73.83\u00a0days\n\n5.27\u00a0years\n\n30.07\u00a0years\n\n59.4\u00a0days\n\n17.0\u00a0days\n\nMean gamma energy (keV)\n\n372.2\n\n1252.0\n\n661.7\n\n35.5\n\n137.1\n\nNominal specific activity (\u00d7105 TBq/kg)\n\n3.4\n\n0.41\n\n3.2\u00a0\u00d7\u00a010\u22122\n\n6.5\n\n27\n\nAir kerma-rate constant (\u00d710\u221218 Gy\u00a0m2/(Bq\u00a0s))\n\n15\n\n85\n\n6.1\u00a0\u00d7\u00a010\u22125\n\n9.9\n\n9.0"}
{"_id": "Radiology$$$21bbc6a2-da72-49d2-8481-a2b9b23284b5", "text": "Electronic brachytherapy is a non-invasive procedure and is a good option for skin cancers in the facial area, especially around the eye and nose. It is also an option after breast conserving surgery to treat the tumor bed when intraoperative RT is used according to an accelerated partial breast irradiation (APBI) procedure. Kilovoltage X-rays generators are used with voltage potential 30\u201350\u00a0kVp."}
{"_id": "Radiology$$$94162eee-8286-4e37-be30-dda42ca4e2bb", "text": "There are several types of brachytherapy depending on the site and organ type to be treated [123]."}
{"_id": "Radiology$$$50f717bd-15ef-4d5c-83b5-365f2971532f", "text": "Intracavitary brachytherapy uses sources that are placed in body or organ cavities. It is mostly used to treat early cervical and uterine (endometrial) cancer, but also in a heterogeneous group of gynecological cancers (ovary, fallopian tubes, body of the uterus, vagina, and vulva). Early rectal cancer can be treated with electron brachytherapy, but the standard of care in rectal cancer is still surgery, especially in case of bulky tumors and more advanced disease, preceded by radio(chemo)therapy."}
{"_id": "Radiology$$$5cb87f9b-80c4-4e5d-9edc-267a4386b3e8", "text": "Interstitial brachytherapy employs sources placed into the tumor, or to its proximity, using needles. It has primarily been used to treat prostate or breast cancer (PCa, BC), but recently it has also been combined with intracavitary brachytherapy to treat bulky cervix tumors. This combination improves coverage of the target volume which was not achievable intracavitary techniques only. PCa brachytherapy can be performed with permanent seeds (for LDR) or temporary sources (for HDR). For breast brachytherapy, interstitial multicatheter brachytherapy is used for boost or partial breast irradiation (PBI)/accelerated PBI (APBI). APBI treats only the lumpectomy bed with 1\u20132 cm margin, rather than the whole breast [124]. HDR sources are usually applied to deliver prescribed doses of 30.3\u201334 Gy in 7\u201310 fractions for APBI and 15\u201320 fractions with LDR/PDR (pulsed dose rate) or 8.5\u201310 Gy with HDR for breast boost treatment. Soft tissue sarcomas are sometimes also treated with brachytherapy alone or in combination with external RT after surgery."}
{"_id": "Radiology$$$1dc17d02-4e6b-4de3-ae79-a29432e64288", "text": "When sources are placed into tubular organs such as trachea, lungs, esophagus, or bile duct, the term intraluminal brachytherapy is used. For lung cancer, the ability of patients to tolerate bronchoscopy is essential. The main indication is treatment of significant, endotracheal, or endobronchial symptoms. Endobronchial brachytherapy is mainly palliative, however it has been used with curative intent in a small number of cases of early-stage tumors with good results."}
{"_id": "Radiology$$$b092db06-1d58-47d1-b37d-edcc71349ea2", "text": "Skin cancer can usually be treated by placing the sources on the skin in the desired geometry, therefore it is sometimes referred to as contact brachytherapy. Skin cancer is a very common cancer, and brachytherapy is used mainly for areas such as face, scalp, ears, hands, legs, especially when surgery would result in poor cosmetic results or require (extensive) plastic reconstructions. Most cancers are either squamous or basal cell carcinomas. Contact applicators or surface molds can be used. The applied dose is tumor size dependent. For LDR and PDR brachytherapy, doses of 60\u201366 Gy are delivered to tumors less than 4 cm and 75\u201380 Gy for those more than 4 cm. For HDR brachytherapy, typical total dose is 30\u201340 Gy delivered in 8\u201310 fractions. Other options for skin treatment include superficial X-rays, orthovoltage X-rays, megavoltage photons, or electron beam irradiation."}
{"_id": "Radiology$$$f447e7a8-6b92-45a1-abc4-e5bac560dd85", "text": "Ocular brachytherapy can be used to treat uveal malignant melanoma. Currently, the most frequently used radionuclides are I-125, Ru-106/Rh-106, Pd-103, Cs-131."}
{"_id": "Radiology$$$adb4d42e-c9b3-47f8-8ebe-3bb1302f6c04", "text": "Intravascular brachytherapy is a rarely used treatment option. It can be used to treat restenosis following percutaneous angioplasty of cardiac arteries. The sources are temporarily placed within cardiac stents in which restenosis has occurred to prevent restenosis. Typically, beta emission sources like P-32, Ir-192, or Rh-188 are used for the treatment. P-32 coated stents have also been used, but with the development of drug-eluting stents, intravascular brachytherapy has lost a lot of its attractivity."}
{"_id": "Radiology$$$9fc06e92-d572-40b8-9021-2d07e3584b84", "text": "The application of brain brachytherapy has decreased a lot since highly conformal RT radiotherapy and stereotactic radiosurgery are available. However, brachytherapy can still be used to treat gliomas with a maximum diameter of 5 cm if not too close to organs at risk."}
{"_id": "Radiology$$$00b7c6da-d77a-44f1-bb8f-40ef9a105323", "text": "Three main radiobiology parameters in brachytherapy are dose rate, cell cycle redistribution, and reoxygenation."}
{"_id": "Radiology$$$04151ace-4688-42b2-935b-895fa8cf19e4", "text": "Brachytherapy can be used as a single strategy or can be combined with other treatment modalities. When combining brachytherapy with external beam RT, total dose to the tumor and organs and risk must be considered. As an example, for the cancer of the cervix, both radiation treatment modalities are usually combined [125]. In such a case, the doses to the tumor and to the critical organs should be always considered as a summation of radiobiological doses to each structure. The LQ model l is recommended with the concept of equi-effective dose (EQD2) [126]. For simple estimations and HDR brachytherapy, the LQ model without any corrections can be applied to calculated EQD2. However, there are some radiobiological factors relevant to brachytherapy for continuous treatment or for multiple fractions per day. Repair rates (called \u03bc values) are used to correct doses for repair of sublethally damaged cells. Average repair half-lives for mammalian tissues are usually 0.5\u20133\u00a0h. There exists evidence that tumor recovery half-lives are probably shorter than those for late-reacting normal tissues."}
{"_id": "Radiology$$$ddc9802e-87a9-4e44-a06b-d9b74ea487b7", "text": "In fractionated treatment with HDR, there should be at least 6 or 8\u00a0h between individual fractions to enable the cells of normal tissues to repair. HDR brachytherapy delivers treatment with dose rates exceeding 12\u00a0Gy/h with 192-Ir or 60-Co sealed sources. Pulsed dose rate (PDR) brachytherapy is fractionated treatment but with a special time schedule. The treatment is delivered with continuous hourly pulses. This approach is supposed to give a similar effect as a hyperfractionation. It was shown that if the time interval between pulses does not exceed 1\u00a0h, overall treatment time is not modified, total dose is the same, and the dose rate is not above 0.5\u20130.6\u00a0Gy/h."}
{"_id": "Radiology$$$e61672f7-fb5c-4ef9-a9b4-3f746a96d3d5", "text": "Radiobiological modeling demonstrated that the PDR technique rather than continuous LDR radiation allows to exploit differences between the half times for sublethal damage repair (T1/2) of late-responding normal tissues and tumors. Repair half times for tumors are estimated to be in the range of 1\u20132\u00a0h, while for late-responding normal tissues, these could be as long as 3\u20134\u00a0h. By matching the pulse frequency with tissue repair kinetics, in a fixed overall treatment time, a therapeutic benefit, i.e., normal tissue sparing while keeping the same tumor control probability, can be obtained relative to continuous LDR radiation. On the basis of those modeling data, an office hours PDR boost regimen was designed for substitution of the continuous LDR boost in breast conserving therapy [127]. A next theoretical study on the optimal fraction size in hypofractionated HDR brachytherapy demonstrated large dependency on the treatment choices (the number of fractions, the overall time, and time between the fractions) and the treatment conditions (reference LDR dose rate tissue repair parameters). The data revealed that hypofractionated HDR might have its opportunities for widening of the therapeutic window for a specific combination of those choices and conditions."}
{"_id": "Radiology$$$a49bf33b-5730-4290-9839-be1e7a3b5a55", "text": "In general, tumor reoxygenation occurs during fractionated treatment. In LDR brachytherapy, the contribution of reoxygenation is low. The lower the dose rate, the lower the oxygen enhancement ratio due to the reduction in sublethal damage repair capability in hypoxic cells."}
{"_id": "Radiology$$$c1c57fd0-a1f0-4432-9728-a0df51264a9b", "text": "It is well known that cells have different sensitivity to radiation due to their position in the cell cycle phases. With HDR brachytherapy, delivered in fractions, it can be more difficult to synchronize cells in these cell cycle phases. On the other hand, with LDR brachytherapy the cell distribution in certain cycle phases can be better and earlier synchronized. Cell cycle changes were also observed later for PDR, however, which were more long-lasting and more pronounced [128]."}
{"_id": "Radiology$$$1bfa2c50-2ca6-4052-b513-99e0f72ddd51", "text": "Radioembolization is based on a vascular selectivity process resulting in a differential effect that leads to a higher concentration of radioactivity within tumor tissue than in non-tumoral liver.\n\nTreatment course includes several steps, notably a treatment planification process aiming to personalize the activity of radioembolization to administer.\n\nRadioembolization is commonly used in treatment of primary and metastatic liver diseases."}
{"_id": "Radiology$$$483e5a00-e36f-4b20-ad19-bcc5dc9a15b9", "text": "Radioembolization is based on a vascular selectivity process resulting in a differential effect that leads to a higher concentration of radioactivity within tumor tissue than in non-tumoral liver."}
{"_id": "Radiology$$$7c8b1b4b-63d5-4b02-a58c-5318a003935e", "text": "Treatment course includes several steps, notably a treatment planification process aiming to personalize the activity of radioembolization to administer."}
{"_id": "Radiology$$$047b9faa-ab65-4d3b-b6c9-9a5472cfcf05", "text": "Radioembolization is commonly used in treatment of primary and metastatic liver diseases."}
{"_id": "Radiology$$$e8a14489-fa76-4028-87f2-1a1b9b065c8b", "text": "Yttrium-90 radioembolization, also called Yttrium-90 selective internal radiotherapy (SIRT), is a type of brachytherapy based on intrahepatic arterial administration of yttrium-90 (90Y)-loaded biocompatible microspheres (90Y-microspheres) [129]. Two types of microsphere loaded with 90Y are commercially available: one made of resin (SIR-Spheres\u00ae, Sirtex, St. Leonards, Australia) and an alternative made of glass (TheraSphere\u00ae, Boston Scientific, Marlborough, MA, USA). The rationale for this approach is that both primary and metastatic tumors in the liver receive their blood supplies primarily from the hepatic artery, whereas the non-tumoral liver (NTL) is fed essentially entirely via the portal vein rather than the hepatic artery [130]."}
{"_id": "Radiology$$$1ee14b13-15f0-4015-b8bc-a0287aa09bdd", "text": "90Y is a therapeutic radionuclide with a physical half-life of 2.67\u00a0days (64.05\u00a0h) and combined electron (\u03b2\u2212) and positron (\u03b2+) emission. The maximum and average energies of \u03b2\u2212 emissions from 90Y are 2.28 MeV and 934\u00a0keV, with a mean tissue penetration of 4.1 mm and a maximum of 11 mm. As in other RTs, 90Y \u03b2\u2212 absorbed dose deposition induces direct or indirect damage to DNA in exposed tissue, leading to early or delayed cellular death [130]. To avoid serious adverse events such as radiation pneumonitis secondary to lung contamination via hepato-pulmonary shunts or radioembolization-induced liver disease (REILD), the irradiation of liver malignancies is limited by unintended exposure to NTL and lung parenchyma."}
{"_id": "Radiology$$$1e131b9c-6aa9-4920-bbf2-30f9020017d7", "text": "Although the branching ratio is very low, the \u03b2+ emission enables 90Y-microsphere positron emission tomography (PET) imaging after radioembolization. It is also possible to image the 90Y-microsphere distribution based on the \u03b2\u2212 bremsstrahlung emission spectrum by bremsstrahlung emission computed tomography (BECT)."}
{"_id": "Radiology$$$696bef35-08f8-4c8f-b19a-64e6df0c5a87", "text": "Therefore, the efficacy of radioembolization is based on a vascular selectivity process resulting in a differential effect that leads to a higher concentration of radioactivity within tumor tissue than in NTL. The stronger the differential effect, the more effective the treatment will be. Due to their size, the tumor\u2019s vascular properties, and the hemodynamics of the vascular system used for targeting, 90Y-microspheres are permanently implanted into the micro-vessels of the tumor/NTL without any biological degradation (although physical decay of 90Y still occurs)."}
{"_id": "Radiology$$$acc9bdc7-f219-4714-8828-a08e95b594e9", "text": "Radioembolization has been broadly adopted as a locoregional therapy for advanced primary or metastatic liver disease [129, 130]. The most common indications for radioembolization are hepatocellular carcinoma (HCC), liver metastases from colorectal cancer (mCRC), intrahepatic cholangiocarcinoma (IH-CCA), and neuroendocrine tumors (NET) [129, 131]. Very little scientific evidence (level 1 or 2) derived from prospective randomized controlled trials supports the use of radioembolization as a first- or second-line treatment option in various treatment algorithms. Prospective data have been obtained for HCC and mCRC patients, and prospective studies in IH-CCA and NET are underway [132]. In the HCC management guidelines for the European Association of Medical Oncology (ESMO), radioembolization is considered as the last-line treatment. The ESMO guidelines for the management of mCRC patients include radioembolization as a second-line treatment for patients with liver-limited disease in whom the available chemotherapeutic options have failed."}
{"_id": "Radiology$$$df7db99a-f4f7-4d49-818f-4708562007b6", "text": "The treatment course, illustrated in Fig. 6.19, includes several steps [132]:\nFirst, patients are selected for radioembolization by the multidisciplinary tumor board, based upon individual characteristics. Radioembolization requires a holistic view of the patient and the disease. Disease stage, long-term and immediate treatment aims, morphological features [assessed using computed tomography (CT) or magnetic resonance imaging (MRI)], metabolic/functional properties [e.g., assessed using [18F]-fluorodeoxyglucose (18F-FDG) hybrid PET coupled with CT (PET/CT) imaging], and biological characteristics of the tumor, and the surrounding liver are all considered when establishing a radioembolization treatment plan.\n\nThen, a pre-treatment 3D hepatic CT angiogram is performed. The goal is to decide into which artery the 90Y-resin microspheres will be injected and to determine the best catheter position to optimize the selectivity of treatment.\n\nTo simulate the treatment, a 2D hepatic angiogram is performed, generally accompanied by a 3D cone-beam CT (CBCT). The catheter is placed at the position defined by the 3D CT angiogram, and 99mTc-labeled macroaggregated-albumin (99mTc-MAA) is injected into the hepatic artery. Given the similar median size of MAA particles (10\u201350\u00a0\u03bcm) and resin microspheres (20\u201360\u00a0\u03bcm), the MAA distribution pattern serves as a surrogate for how 90Y-microspheres will localize.\n\nTo visualize the distribution of 99mTc-MAA, planar scintigraphy, generally accompanied by hybrid single-photon emission CT and CT imaging (SPECT/CT), is acquired within 2\u00a0h after administration. This allows validation of the catheter position, identification of potential extrahepatic visceral contamination, and evaluation of the lung shunt and the targeting of the lesions; in addition, it can be used to determine the activity to administer in future therapy. This practice prevents post-therapy complications and selects patients with a good potential outcome.\n\nAfter this pre-treatment phase, treatment with 90Y-microspheres is performed according to the pre-treatment catheter position and prescribed activity. With catheter-directed therapies such as radioembolization, it is important to verify that the position/location of the catheter during the 99mTc-MAA simulation is consistent with the position during the administration of 90Y-microspheres to best reproduce the MAA distribution.\n\nFollowing administration of 90Y-microspheres, a qualitative and quantitative assessment is performed (1) to verify that the treatment was performed as planned and identify any technical failures and (2) to detect any possible extrahepatic activity, which could cause serious complications such as gastrointestinal bleeding. Post-radioembolization imaging of 90Y distribution may be performed using hybrid 90Y-PET/CT or 90Y-BECT/CT. However, many studies show qualitatively superior resolution and contrast with 90Y-PET/CT relative to 90Y-BECT/CT, and only 90Y-PET/CT is available for quantification in clinical routine (90Y-BECT/CT quantitative imaging is still under development).\n\nFinally, treatment response is evaluated. Clinical and biochemical assessment after radioembolization for any significant side effects is typically performed 1\u20132\u00a0months post-radioembolization. Imaging assessment of the tumor response should be performed 1\u20133\u00a0months post-radioembolization and every 2\u20133\u00a0months thereafter. The clinically relevant \u201ctreatment response,\u201d and thus the most suitable imaging technique, is defined differently depending on the type of tumor (e.g., variable 18F-FDG avidity) and treatment intent (e.g., bridging-to-surgery, downstaging, etc.) [131].\n\n\nA flow diagram of the treatment course. It involves patient selection, treatment planning, treatment 7 to 15 days after simulation, and patient follow up 6 to 8 weeks after treatment.\n\nFig. 6.19\n90Y-resin microspheres radioembolization treatment course. Example of a patient treated for neuroendocrine neoplasia"}
{"_id": "Radiology$$$11f8de79-15d3-49b7-aac3-7decff989c51", "text": "First, patients are selected for radioembolization by the multidisciplinary tumor board, based upon individual characteristics. Radioembolization requires a holistic view of the patient and the disease. Disease stage, long-term and immediate treatment aims, morphological features [assessed using computed tomography (CT) or magnetic resonance imaging (MRI)], metabolic/functional properties [e.g., assessed using [18F]-fluorodeoxyglucose (18F-FDG) hybrid PET coupled with CT (PET/CT) imaging], and biological characteristics of the tumor, and the surrounding liver are all considered when establishing a radioembolization treatment plan."}
{"_id": "Radiology$$$aefba5a7-de14-4709-aea0-0e3d321ac644", "text": "Then, a pre-treatment 3D hepatic CT angiogram is performed. The goal is to decide into which artery the 90Y-resin microspheres will be injected and to determine the best catheter position to optimize the selectivity of treatment."}
{"_id": "Radiology$$$95df9d9f-4371-45a6-ba5f-8c9cc66d7044", "text": "To simulate the treatment, a 2D hepatic angiogram is performed, generally accompanied by a 3D cone-beam CT (CBCT). The catheter is placed at the position defined by the 3D CT angiogram, and 99mTc-labeled macroaggregated-albumin (99mTc-MAA) is injected into the hepatic artery. Given the similar median size of MAA particles (10\u201350\u00a0\u03bcm) and resin microspheres (20\u201360\u00a0\u03bcm), the MAA distribution pattern serves as a surrogate for how 90Y-microspheres will localize."}
{"_id": "Radiology$$$07d6bbd9-2071-4792-bda6-635a75dffa6d", "text": "To visualize the distribution of 99mTc-MAA, planar scintigraphy, generally accompanied by hybrid single-photon emission CT and CT imaging (SPECT/CT), is acquired within 2\u00a0h after administration. This allows validation of the catheter position, identification of potential extrahepatic visceral contamination, and evaluation of the lung shunt and the targeting of the lesions; in addition, it can be used to determine the activity to administer in future therapy. This practice prevents post-therapy complications and selects patients with a good potential outcome."}
{"_id": "Radiology$$$db8126a7-add4-4f68-a8c8-d7624ef37424", "text": "After this pre-treatment phase, treatment with 90Y-microspheres is performed according to the pre-treatment catheter position and prescribed activity. With catheter-directed therapies such as radioembolization, it is important to verify that the position/location of the catheter during the 99mTc-MAA simulation is consistent with the position during the administration of 90Y-microspheres to best reproduce the MAA distribution."}
{"_id": "Radiology$$$16f6e366-25c9-477f-879f-495693d75c5c", "text": "Following administration of 90Y-microspheres, a qualitative and quantitative assessment is performed (1) to verify that the treatment was performed as planned and identify any technical failures and (2) to detect any possible extrahepatic activity, which could cause serious complications such as gastrointestinal bleeding. Post-radioembolization imaging of 90Y distribution may be performed using hybrid 90Y-PET/CT or 90Y-BECT/CT. However, many studies show qualitatively superior resolution and contrast with 90Y-PET/CT relative to 90Y-BECT/CT, and only 90Y-PET/CT is available for quantification in clinical routine (90Y-BECT/CT quantitative imaging is still under development)."}
{"_id": "Radiology$$$6fdbe6ca-65f3-4663-bd86-5fb137ff952d", "text": "Finally, treatment response is evaluated. Clinical and biochemical assessment after radioembolization for any significant side effects is typically performed 1\u20132\u00a0months post-radioembolization. Imaging assessment of the tumor response should be performed 1\u20133\u00a0months post-radioembolization and every 2\u20133\u00a0months thereafter. The clinically relevant \u201ctreatment response,\u201d and thus the most suitable imaging technique, is defined differently depending on the type of tumor (e.g., variable 18F-FDG avidity) and treatment intent (e.g., bridging-to-surgery, downstaging, etc.) [131]."}
{"_id": "Radiology$$$0b1ee0d6-3729-4a07-8d14-3c8eddd5f0f9", "text": "A flow diagram of the treatment course. It involves patient selection, treatment planning, treatment 7 to 15 days after simulation, and patient follow up 6 to 8 weeks after treatment."}
{"_id": "Radiology$$$585c0ee3-91ad-4641-a583-5e5522b0de95", "text": "Curative setting: Radioembolization can be used in a preoperative setting (for solitary or limited-multifocal/oligometastatic tumor) when the ambition is to cure the patient. It can be used as bridging-to-surgery, to stabilize or slow down tumor growth and multiplicity thereby keeping a patient as a potential surgical candidate for liver resection or transplantation. Alternatively, radioembolization can be applied as a downstaging approach to induce a clinical shift from a non-resectable stage to a potentially resectable or transplantable stage by decreasing tumor size or number [129, 130].\n\nNon-curative setting: In patients with advanced multifocal bilobar/lobar tumor distribution in whom curative approaches are not feasible, radioembolization can be used alone or in combination with other therapies as a life-prolonging treatment and palliative care [129, 130]."}
{"_id": "Radiology$$$de5cc497-dacc-4f95-ba66-60621670a6c0", "text": "Curative setting: Radioembolization can be used in a preoperative setting (for solitary or limited-multifocal/oligometastatic tumor) when the ambition is to cure the patient. It can be used as bridging-to-surgery, to stabilize or slow down tumor growth and multiplicity thereby keeping a patient as a potential surgical candidate for liver resection or transplantation. Alternatively, radioembolization can be applied as a downstaging approach to induce a clinical shift from a non-resectable stage to a potentially resectable or transplantable stage by decreasing tumor size or number [129, 130]."}
{"_id": "Radiology$$$5dc7b241-7b57-4378-9c3d-2b693485679f", "text": "Non-curative setting: In patients with advanced multifocal bilobar/lobar tumor distribution in whom curative approaches are not feasible, radioembolization can be used alone or in combination with other therapies as a life-prolonging treatment and palliative care [129, 130]."}
{"_id": "Radiology$$$cd080117-60e7-43bd-9337-43a97ed32f08", "text": "Whole-liver treatments: In the case of bilobar multifocal tumor distribution, the whole liver must be treated. Single injection within the common hepatic artery or a bilobar (left and right hepatic artery) approach is performed. The bilobar approach can be performed on the same day or staged (i.e., on separate days).\n\nLobar and segmental treatments: Unilobar or segmental treatments are considered when the disease is limited to a unique lobe or a segment. These approaches enable the preservation of the untreated liver, and if some loss of function in the treated lobe/segment is permissible, they allow more aggressive treatment.\n\nLobectomy and Segmentectomy: Radiation lobectomy, with the intent to induce contralateral lobe hypertrophy while achieving tumor control, may be considered in patients with unilobar disease and a small anticipated future liver remnant in an attempt to facilitate curative surgical resection.\n\nRadiation: segmentectomy may be considered for localized disease (one or two segments) supplied by a segmental artery that is not amenable to other curative therapies because of tumor localization or patient comorbidities."}
{"_id": "Radiology$$$cb744e7f-b3ba-43d2-b446-499099068c4d", "text": "Whole-liver treatments: In the case of bilobar multifocal tumor distribution, the whole liver must be treated. Single injection within the common hepatic artery or a bilobar (left and right hepatic artery) approach is performed. The bilobar approach can be performed on the same day or staged (i.e., on separate days)."}
{"_id": "Radiology$$$497110d1-c64f-49ec-8b47-430b7523a6a4", "text": "Lobar and segmental treatments: Unilobar or segmental treatments are considered when the disease is limited to a unique lobe or a segment. These approaches enable the preservation of the untreated liver, and if some loss of function in the treated lobe/segment is permissible, they allow more aggressive treatment."}
{"_id": "Radiology$$$039b675e-9b20-4ca3-a53a-15290a598267", "text": "Lobectomy and Segmentectomy: Radiation lobectomy, with the intent to induce contralateral lobe hypertrophy while achieving tumor control, may be considered in patients with unilobar disease and a small anticipated future liver remnant in an attempt to facilitate curative surgical resection."}
{"_id": "Radiology$$$3818f73a-6af2-4385-9824-ee501437efb4", "text": "Radiation: segmentectomy may be considered for localized disease (one or two segments) supplied by a segmental artery that is not amenable to other curative therapies because of tumor localization or patient comorbidities."}
{"_id": "Radiology$$$ca1d5d5a-140d-414f-ada8-41b4cb01b030", "text": "Until recently, the prescription of 90Y-microspheres was based upon the body surface area method (resin microspheres) or on a dose limit to the whole treated liver volume without distinction between tumor and non-tumoral liver (glass microspheres). Both approaches lead to inherent risks of under- or overdosing, with considerable interpatient variations [130, 132]. To tackle those pitfalls, the concept of personalized radioembolization has recently emerged and provides an optimal framework to improve patient selection and maximize tumor response while sparing non-targeted tissues undesired toxicities. The patient-specific definition of a radioembolization therapeutic window is now assessed by integrating multidisciplinary teamwork, multimodal imaging techniques, advanced treatment planning algorithm, and by considering relationships between radiation dose and treatment outcomes. Precision radioembolization with dosimetry is now recommended as the standard approach in recent international recommendations [132, 133]. Recently, a prospective randomized phase II clinical study in HCC, the DOSISPHERE-01 trial, provided the first level one scientific evidence that personalized radioembolization significantly improves overall survival compared to the standard semi-empirical approach [134]."}
{"_id": "Radiology$$$ebb8a290-c1f3-4b0b-8608-9edab49f22eb", "text": "The concept of using radiation to treat cancer and other diseases found its origin in the discovery of X-rays in 1895. After Pierre and Marie Sklodowska-Curie discovered radium as a source of IR further interest was sparked. However, it wasn\u2019t until the 1950s that external beam radiation became a key treatment modality for cancer. Since then, external beam RT has become one of the most efficient tools for treatment of locally confined cancers. However, its effect is limited for treatment of more advanced and disseminated disease. In the early twentieth century, first potential for using Iodine-131 as a targeted therapeutic was discovered by nuclear pioneers such as Saul Hertz [135]. This discovery was the start of the field of radionuclide therapy and today, several types of radionuclide therapy exist. Each of the different types will be discussed in this section."}
{"_id": "Radiology$$$e2a18d53-d77c-40e6-b0ee-710ed73ce36f", "text": "Cancer cells often express certain molecules on their membrane surface, called receptors, which are not or to a lesser extent present on healthy cells. These receptors on cancer cells can be targeted by several molecules, being a peptide, small molecule or (parts of) antibodies, which will be termed as the ligand. When talking about radiopharmaceuticals, the cancer-targeting moiety is linked to a chelator molecule, responsible for entrapping a radionuclide into the structure as shown in Fig. 6.20.\n\nA schematic diagram of the radiopharmaceutical structure. From bottom to top, targeting moiety is connected to the linker molecule which entraps the chelator plus radionuclide. \n\nFig. 6.20\nSchematic representation of the structure of a radiopharmaceutical. The purple circle represents the cancer-targeting moiety, which can be a peptide, small molecule, or antibody. This targeting moiety is connected to a chelator (blue circle) entrapping a radionuclide (for diagnostics or therapy) directly to the targeting moiety or via a linker molecule (grey)"}
{"_id": "Radiology$$$5004ab04-f9d5-491c-a5e0-f66467590dc9", "text": "A schematic diagram of the radiopharmaceutical structure. From bottom to top, targeting moiety is connected to the linker molecule which entraps the chelator plus radionuclide."}
{"_id": "Radiology$$$6bea08f5-f890-4d50-b4e8-5c7158a93e13", "text": "As already explained in Chap. 2, based on the purpose of the radiopharmaceutical, being diagnostic or therapeutic, different radionuclides can be used. For diagnostic purposes, gamma (\u03b3)-emitting radionuclides are used. Radionuclides that are usually used for therapy are alpha (e.g., actinium-225), beta (e.g., lutetium-177), or Auger electron (e.g., iodine-125) emitters."}
{"_id": "Radiology$$$6a1a4780-1f00-4222-8430-3865e3d3fb8f", "text": "Upon binding of the ligand to its receptor, the radioligand complex gets internalized. Upon internalization, the radionuclide will emit its toxic IR from inside the cell and cause damage to cellular structures including DNA and cell membrane, resulting in cancer cell death, as shown in Fig. 6.21.\n\nA schematic depicts oral and systemic routes of administration will enter the bloodstream in a systemic circulation and proceeds to the target issue either through natural affinity radionuclides with affinity based uptake or vectorized radionuclide therapy with uptake based on protein expression.\n\nFig. 6.21\nOverview of the general principle or radioligand therapy. A radionuclide (either ingested orally or injected systemically) will enter the bloodstream. Via the bloodstream, the radionuclide will find its way to the target tissue either through its natural affinity for the target tissue (i.e., the natural affinity radionuclides) or via expression of certain molecules on the target tissue (i.e., vectorized radionuclide therapy)"}
{"_id": "Radiology$$$0dad4c81-0f69-4789-9362-9985b5c08cf6", "text": "A schematic depicts oral and systemic routes of administration will enter the bloodstream in a systemic circulation and proceeds to the target issue either through natural affinity radionuclides with affinity based uptake or vectorized radionuclide therapy with uptake based on protein expression."}
{"_id": "Radiology$$$ef509076-298d-4270-9a99-3e867c5adea8", "text": "Radioligand therapy (RLT) can in theory be used to target any type of cells (over)expressing the target molecule and can thus be used to attack multiple (micro) metastases instead of only targeting the primary tumor, in contrast to external beam RT (EBRT) that focus on one or several, geographically limited target volumes. Furthermore, RLT enables specific targeting of cancer lesions (including metastatic cancer cells), while causing minimal damage to surrounding healthy tissues and thus minimizing the amount of side effects [136] (Box 6.16)."}
{"_id": "Radiology$$$aeee461d-bf37-4bd8-9915-de62475d36a5", "text": "Human cancers express molecules on their membrane surface that can be targeted for therapy.\n\nA radioligand is comprised of a cancer-targeting moiety (small molecule, peptide, or (part of) antibody) linked to a chelator entrapping the radionuclide.\n\nRadioligand therapy enables specific targeting of cancer cells, with minimal harm to surrounding healthy tissues."}
{"_id": "Radiology$$$52c86a0a-6214-4c90-b319-2b735be84d8b", "text": "Human cancers express molecules on their membrane surface that can be targeted for therapy."}
{"_id": "Radiology$$$3e8daa7f-7c12-4a40-b381-3162529c7a0c", "text": "A radioligand is comprised of a cancer-targeting moiety (small molecule, peptide, or (part of) antibody) linked to a chelator entrapping the radionuclide."}
{"_id": "Radiology$$$920934aa-ff1e-4b3c-b683-75f0e6521183", "text": "Radioligand therapy enables specific targeting of cancer cells, with minimal harm to surrounding healthy tissues."}
{"_id": "Radiology$$$a6e576c6-1af4-4833-95f6-7c17ab4c6d50", "text": "Theranostics, the combination of therapy and diagnostics, is emerging in personalized medicine approaches. The main goal is to use diagnostic imaging to follow-up (radio)therapeutic interventions and improve or alter them along the way, thereby increasing efficacy and limiting toxicological effects. The ideal theranostic pair, i.e., for imaging or therapy, respectively, has the same pharmacokinetics, meaning that the pair should be distributed, metabolized, and cleared similarly [137]. If this is the case, the diagnostic counterpart can be used to accurately determine the accumulation and absorbed dose in different organs, including tumor, that would result upon injection of the therapeutic radiopharmaceutical. The imaging thus further allows selection of patients with high probability of response to the therapy (i.e., predictive biomarkers) and can provide guidance on the total activity of the therapeutic counterpart to be administered. It can also be used for treatment response evaluation in follow-up. Several therapeutic radionuclides (e.g., 177Lu, 131I) intrinsically decay via both particle- and \u03b3-emission which can be used for both imaging and therapy that said after administration of vastly different injected activities [137]. Different radioisotopes of the same element have the greatest theoretical appeal to use in the theranostic approach. Examples are the radioisotopes of iodine (123/124/131I), terbium (149/152/155/161Tb), and yttrium (86/90Y) [138]. Although the biological behavior of these radiopharmaceuticals will be similar, the use in clinical practice might be limited due to unfavorable decay properties, long T1/2, availability, and cost of production. In this respect, radiopharmaceuticals which use the same vector molecule but different radiometals are often applied for this purpose as they have similar pharmacokinetics. A prime example is the somatostatin receptor targeting vector DOTATATE, which can be radiolabeled with the PET radionuclide 68Ga and the therapeutic radionuclide 177Lu, harnessing the diagnostic potential of PET (which have higher resolution and sensitivity for radioactivity) to enable efficient therapeutic approaches [139]. Of note, current efforts are being made to include [18F]AIF into the armamentarium to eventually replace 68Ga [140]."}
{"_id": "Radiology$$$b5d1c36a-14e0-4943-a6c4-ec95dcfacb0d", "text": "Radiotheranostics is being applied to the different branches of radiopharmaceutical development, including radioimmunotherapy (with, for example, nanobodies, antibodies, or similar affinity reagents), peptide receptor radionuclide therapy, radiolabeled microspheres/nanoparticles, and small molecules. This combination of therapy and diagnostics can help to reduce the toxic side effects by appropriate patient selection and determination of administered activity. The benefit and safety of using repeated treatment have also been proven in several studies."}
{"_id": "Radiology$$$0c2f18c6-f83d-4241-83a9-84565d590766", "text": "A key aspect to note is the uptake and retention of the radionuclides at the target site. Logically, tumor-to-background ratios should be as high as possible for both diagnostic and therapeutic radionuclides. However, diagnostic imaging is typically performed in a time scale of several minutes to 1\u00a0h and thus optimally, radionuclides with a short T1/2 should be applied. On the other hand, radionuclides with a longer T1/2 are typically used for therapy, which can result in a more selective tumor irradiation, with higher dose to the tumor than to the healthy tissues (Fig. 6.22). The most important requirement for a therapeutic radiopharmaceutical is to have a high ratio between the integral of the time-activity curve (previously known as the residence time) of the tumor vs. normal organs (Box 6.17).\n\n2, line graphs of concentration versus time. The area of the timeframe for static imaging between two time-activity curves is denoted in the diagnostic radionuclide and the area of the high selectivity for damage to the tumor over plasma is displayed in the therapeutic radionuclide, left and right, respectively.\n\nFig. 6.22\nHypothetical representation of time-activity curves (TACs) of a vector radiolabeled with a diagnostic (T1/2\u00a0=\u00a030\u00a0min) and therapeutic radionuclide (T1/2\u00a0=\u00a06\u00a0h)"}
{"_id": "Radiology$$$697da37a-09ce-4ba4-a894-48f810d7aa7d", "text": "2, line graphs of concentration versus time. The area of the timeframe for static imaging between two time-activity curves is denoted in the diagnostic radionuclide and the area of the high selectivity for damage to the tumor over plasma is displayed in the therapeutic radionuclide, left and right, respectively."}
{"_id": "Radiology$$$e5806641-e4dd-436b-8048-491a220cc144", "text": "The theranostic approach makes use of diagnostic and therapeutic nuclear medicine.\n\nTheranostics utilizes different isotopes of the same element.\n\nTherapeutic radiopharmaceuticals can use radionuclides with a longer half-life compared to diagnostic radiopharmaceuticals.\n\nRadiopharmaceutical vector molecules can include peptides, antibodies, nanobodies, nanoparticles, and small molecules."}
{"_id": "Radiology$$$6f8347fe-18a5-4aba-8770-ed3211b93f02", "text": "The theranostic approach makes use of diagnostic and therapeutic nuclear medicine."}
{"_id": "Radiology$$$831a2be5-359f-46f1-8bc9-5a456550fa65", "text": "Therapeutic radiopharmaceuticals can use radionuclides with a longer half-life compared to diagnostic radiopharmaceuticals."}
{"_id": "Radiology$$$9bbcf547-1e6e-4ee4-8081-fd8d979b2abb", "text": "Radiopharmaceutical vector molecules can include peptides, antibodies, nanobodies, nanoparticles, and small molecules."}
{"_id": "Radiology$$$70e574a5-877e-41c9-8e55-27f56c5cc3bd", "text": "To obtain specific targeting, a radiopharmaceutical usually comprises a moiety capable of binding a cancer-specific overexpressed entity (e.g., a receptor, an enzyme, a transporter, etc.). However, this is not always required as certain elements show a natural affinity for certain tissues. Examples are iodine, which is concentrated in the thyroid gland, and radium, a calcium mimetic naturally taken up in remodeling bone. This enables specific targeting of these tissues without the need for elaborate organic chemistry nor radiochemistry."}
{"_id": "Radiology$$$79451fbb-448e-48b2-97a0-1c9595e3af20", "text": "Radiopharmaceutical development started with the research of Hamilton and Soley into diagnosis and treatment of thyroid disease. In the thyroid gland, iodine plays an important role in the production of thyroid hormones, which in turn have important functions in the human body. Naturally, because of the importance of iodine for the thyroid gland, all ingested iodine is taken up by the thyroid gland, where it is converted into iodide and remains trapped. Radioactive iodine (iodine-131) can be used to treat thyroid diseases because the thyroid gland is not able to distinguish between the stable iodine (iodine-127) and its radioactive isotope. Like stable iodine, iodine-131 is concentrated in the thyroid gland after ingestion. Treatment of thyroid disease using iodine-131 in the form of sodium-iodine (Na131I) can be considered as a historic pillar of radiopharmaceutical design as the usage of Na131I has paved the way for further radiopharmaceutical development."}
{"_id": "Radiology$$$e8f2bc38-b9ea-42d7-a913-10d52924b2b4", "text": "The primary site for metastasis in prostate cancer (PCa) is the bone, resulting in severe morbidity due to so-called skeletal related events (e.g., fractures) and bone marrow failure. To control the disease in castrate-resistant PCa patients, the Food and Drug Administration (FDA) approved radium-223 chloride (223RaCl2, Xofigo\u00ae) for treatment of bone metastasis in 2013. Radium-223 is an alpha-emitting radionuclide that accumulates in bone areas with increased bone turnover due to its similarity with calcium ions and its capability to form complexes with hydroxyapatite (which is the mineral component of bone). In the decay process of radium-223 to the stable lead-207, four alpha particles and two beta-particles are generated which induce local damage to bone sites with increased bone turnover, such as areas of bone metastasis."}
{"_id": "Radiology$$$dae344ea-3e59-4aa2-a8c1-5b11be49e07d", "text": "Na131I is administered in patients suffering from benign thyroid disease such as an overactive thyroid (autonomic hyperthyroidism, Graves\u2019 Disease), goiter (enlarged thyroid), or well differentiated thyroid cancers (papillary or follicular thyroid cancer). The thyroid incorporates iodide in two forms of thyroid hormones, triiodothyronine (T3) and thyroxine (T4). These hormones control metabolism and protein synthesis. An overactive thyroid leads to increased metabolic rate, sweating, fatigue, tachycardia, intestinal problems, and other life debilitating issues. As iodide is taken up in the thyroid in large excess, it is a valuable approach in treating an overstimulated or enlarged thyroid. Due to the high uptake via the intestinal tract, Na131I is administered per os. Iodine-131 is taken up by the sodium-iodide symporter into the thyroid cells and will subsequently irradiate the thyroid cells. One potential side effect of this treatment is a complete loss of thyroid function (hypothyroidism), which can result in the necessity for daily lifelong thyroid hormone (levothyroxine) substitution. The occurrence of hypothyroidism depends on the type of indication, with a low fraction seen in autonomic disease but with a 100% occurrence in patients treated for thyroid cancer (with treatment occurring post-thyroidectomy to ablate the so-called remnant). Of note, these pills are generally inexpensive and are taken per os once daily [141]."}
{"_id": "Radiology$$$9cbf102a-9ce7-4c7f-baf5-d8308287ecd6", "text": "To date, 223RaCl2 is the only alpha-emitting radiopharmaceutical that has been FDA approved and is now in routine clinical use for treatment of bone metastasis in patients with metastatic castration-resistant prostate cancer. The ALSYMPCA phase III clinical trial investigated safety and efficacy of 223RaCl2 compared to placebo (i.e., saline injection). The results of this trial led to the FDA approval of 223RaCl2 for patients with metastatic castration-resistant prostate cancer with symptomatic bone metastasis as this clinical trial showed that treatment was well-tolerated, prolonged overall survival, and improved the quality of life of patients [142, 143]."}
{"_id": "Radiology$$$1cae34ec-c435-443c-ab91-3850067ebd1c", "text": "Na131I is typically administered as a pill or in rare cases as a liquid per os. The required activity to treat hyperthyroidism is typically small (148\u2013370\u00a0MBq). Usually one treatment cycle will suffice to have a satisfying effect on the thyroid function after 2\u20133\u00a0months [144]. For patients suffering from differentiated thyroid cancer, the administered activity depends on the disease stage (after previous resection in so-called remnant ablation, used as adjuvant therapy, metastatic disease) and can range from 1.1 to 7.4 GBq [145]. Before treatment, patients need to have sufficient blood levels of thyroid-stimulating hormone (TSH) (TSH\u00a0>\u00a030\u00a0mU/L), by stopping uptake of thyroid hormone supplements or by injections of recombinant THS, to increase the uptake of the administered iodine radioisotope. Several days after treatment, a post-therapy scintigraphy is made to document the targeting of thyroid tissue and to detect potential metastatic disease. After ablation, levothyroxine treatment is started to compensate for the loss of thyroid function. Afterwards follow-up is necessary to assess therapy response and to rule out recurrence, with regular determination of thyroid function, thyroglobulin, and thyroglobulin antibodies."}
{"_id": "Radiology$$$8b02e4d9-12cc-46ba-8806-7d8b1495719c", "text": "Radium-223 dichloride is injected intravenously in adult patients with castration-resistant prostate cancer with bone metastases. The treatment schedule comprises six injections of 55 kBq per kg body weight at 4-week intervals. A single complete blood count is performed 10 days prior to administration of a treatment cycle. An additional complete blood count might be performed 2\u20133 weeks after administration if necessary. Clinical follow-up complemented with bone scintigraphy and CT is the cornerstone of follow-up, but with more recent evidence pointing to the utility of also modern imaging tools such as PET/CT or MRI. Several biomarkers, including prostate-specific antigen, lactate dehydrogenase, and alkaline phosphatase, might be checked during the treatment course to monitor treatment response, but they are not considered to be reliable indicators of treatment response."}
{"_id": "Radiology$$$b4845cbc-bdd7-495e-b2a3-ee759bcfa03c", "text": "Peptide receptor radionuclide therapy (PRRT) consists of the injection of a tumor-targeting peptide into the systemic circulation of a patient. This radiopharmaceutical will subsequently bind to a specific peptide receptor leading to tumor-specific retention. Several receptors have been studied over the last few years, including the somatostatin receptor (SSTR), glucagon-like peptide-1 receptor, cholecystokinin type 2, and melanocortin receptors. At present, SSTR is the only target that is used in routine clinical practice. The SSTR is overexpressed on a range of tumors, including neuroendocrine tumors (NETs), which arise from neuroendocrine cells present in a range of organs (e.g., gastrointestinal tract, pancreas, and bronchi) and neural-crest derived tumors (e.g., pheochromocytoma, paraganglioma, neuroblastoma). Humans have five subtypes of SSTRs, with subtype 2 being the most important for theranostics. The randomized controlled trials PROMID and CLARINET have proven that treatment with non-radioactive somatostatin analogues (SSAs) leads to an antiproliferative effect in metastatic enteropancreatic NETs. In the late 1980s and early 1990s, the Rotterdam group uncovered the potential of using the SSTR for radionuclide-based imaging and demonstrated that radiolabeled SSAs have a high uptake and retention in tumoral tissue and a limited uptake in normal, mainly endocrine, organs. An interesting therapeutic avenue was explored: treatment of SSTR-positive tumors with radionuclide therapy (RNT). Several radiopharmaceuticals were developed in the last two decades including the first generation 111In-pentetreotide (an Auger emitter), the second generation 90Y-DOTATOC (a high-energy \u03b2\u2212-emitter), and the third generation 177Lu-DOTATATE (a low-energy \u03b2\u2212-emitter and a \u03b3-emitter). A major benefit of lutetium-177 is that its decay is associated with \u03b3-emission, which allows imaging and dosimetry of absorbed doses to tumors and risk-organs (e.g., kidneys and bone marrow). The combination of the high-energy yttrium-90 \u03b2\u2212-emitter for targeting lesions with a larger size and/or heterogeneous uptake (with more crossfire effect), and the medium-energy lutetium-177 emitter/\u03b3-emitter for targeting smaller lesions (with a higher fraction of the total energy deposited within the tumor itself, and not in the surrounding tissue), is called \u201ctandem or duo PRRT.\u201d Theoretically, a synergistic effect can be achieved by combining these two radionuclides with different absorption properties, but RCTs are awaited to demonstrate the superiority of this concept before widespread clinical use can take place. At present, 177Lu-DOTATATE is considered the clinical standard and is the only radiopharmaceutical approved for PRRT by the American Food and Drug Administration (FDA 2018) and European Medicines Agency (EMA 2017). A promising fourth generation of PRRT-radiopharmaceuticals is emerging, with the entrance of \u03b1-emitters in the radionuclide therapy scene. PRRT \u03b1-emitters include 213Bi-DOTATOC, 225Ac-DOTATATE, and 212Pb-DOTAMTATE. Preliminary clinical results provide proof-of-principle evidence that \u03b1-PRRT can overcome resistance to \u03b2-PRRT, reflected by higher objective response rates (ORRs) in favor of \u03b1-emitters [146]."}
{"_id": "Radiology$$$22b20121-6e29-4023-82a0-d5e1263eb67c", "text": "Patients with advanced NET and clinical, biochemical, and/or radiological disease progression after first-line treatment with SSA are eligible for second-line treatment with PRRT if sufficient tracer uptake on a so-called theranostics SSTR scintigraphy is present. The development of PRRT and its clinical trials were academia-driven which contrasts with the current novel anticancer drugs which are mainly pharma industry-driven. For a long period, no standard radiopharmaceutical or standard regimen was determined, which explains the heterogeneous literature involving PRRT [146]. At present, the only published randomized controlled trial with 177Lu-DOTATATE is the phase III NETTER-1 trial, which included patients with advanced midgut NETs. One hundred sixteen patients were randomized to the PRRT arm (4\u00a0cycles of 7.4 GBq 177Lu-DOTATATE plus best supportive care including octreotide long-acting repeatable (LAR) 30\u00a0mg) and 113 patients were randomized to the control arm (octreotide LAR 60\u00a0mg). An ORR of 18% was seen in the 177Lu-DOTATATE group versus 3% in the control group (p\u00a0<\u00a00.001). An estimated progression-free survival (PFS) at 20\u00a0months of 65.2% (95% confidence interval (CI): 50.0\u201376.8%) was achieved in the PRRT arm and 10.8% (95% CI: 3.5\u201323.0%) in the control arm, with a hazard ratio for progression or death of 0.21 (95% CI: 0.13\u20130.33; p\u00a0<\u00a00.001) [147]. The final overall survival (OS) analysis revealed a median OS of 48\u00a0months in the 177Lu-DOTATATE group versus 36.3\u00a0months in the control group. This difference was not statistically significant but can be considered as clinically significant. The lack of statistical significance was most likely caused by a high rate (36%) of crossover of patients in the control group to PRRT after progression. In addition, the NETTER-1 trial has confirmed that PRRT causes a significant improvement in the quality of life of patients and aids to substantially reduce tumoral symptoms (e.g., abdominal pain, diarrhea, and flushing) [146]."}
{"_id": "Radiology$$$c3122856-ec13-4889-8484-c4687a242080", "text": "The eligibility for PRRT is determined via mandatory pre-treatment SSTR imaging, preferentially by SSTR PET, blood analysis, and clinical evaluation. 18F-FDG PET/CT provides additional information, and all lesions should show sufficient SSTR expression, in particular the 18F-FDG-avid ones. The conventional treatment schedule for 177Lu-DOTATATE is based on the Rotterdam/NETTER-1 protocol. This consists of four cycles of 7.4 GBq administered in 8-week intervals. Nephroprotection is performed by administering a co-infusion of an amino acid solution during PRRT-administration; this solution will reduce renal uptake of the radiopeptide by ~25\u201350%. Acute side effects include nausea and vomiting which are provoked by the co-infusion of the nephroprotective amino acids and which can be controlled by an antiemetic treatment. Four to six weeks after each cycle of PRRT, a blood analysis and clinical evaluation are performed. After completion of the four cycles PRRT, further follow-up with SSTR and 18F-FDG PET/CT, blood analysis, and clinical evaluation are warranted. The most severe long-term side effect of PRRT is the development of persistent hematological dysfunction (PHD) caused by bone marrow irradiation. However, PHD after PRRT has a low incidence of 1.8\u20134.8%, with a median latency of 41\u00a0months after completion of the treatment [146]. Other subacute (occurring within days/week) side effects include subacute myelosuppression (typically mild and transient), fatigue, and hair loss. Long-term side effects, besides PHD, are kidney failure, observed in up to 9.2% of patients treated with 90Y-DOTATOC and <1% in patients with 177Lu-DOTATATE [148, 149]. In patients with good response after a first PRRT regimen, with disease control for at least a year, a novel course of PRRT can be administered with 177Lu-DOTATATE, called \u201csalvage PRRT,\u201d if the patient\u2019s organ function is still adequate and SSTR expression is still present on all lesions. As such, PRRT has proven to be an adequate treatment in patients with advanced NETs. Several promising prospective trials are ongoing to further optimize PRRT (e.g., \u03b1-emitters, individualized dosimetry, and SSTR-antagonists) (Box 6.18)."}
{"_id": "Radiology$$$01d15793-da01-4f14-8665-da7fc09a8eac", "text": "PRRT consists of the injection of a tumor-targeting radiolabeled peptide, which will subsequently bind to a specific receptor leading to tumor-specific binding and retention.\n\nSeveral radiopharmaceuticals were developed in the last two decades, with the third generation 177Lu-DOTATATE being the current clinical standard and the only radiopharmaceutical approved for PRRT by the FDA and EMA.\n\nMultiple promising prospective trials are ongoing to further optimize PRRT (e.g., \u03b1-emitters, individualized dosimetry, and SSTR-antagonists)."}
{"_id": "Radiology$$$477fb153-efb3-4cdc-ba43-6a9baf04fb37", "text": "PRRT consists of the injection of a tumor-targeting radiolabeled peptide, which will subsequently bind to a specific receptor leading to tumor-specific binding and retention."}
{"_id": "Radiology$$$e4612411-207b-464c-b73e-cedc2199fe91", "text": "Several radiopharmaceuticals were developed in the last two decades, with the third generation 177Lu-DOTATATE being the current clinical standard and the only radiopharmaceutical approved for PRRT by the FDA and EMA."}
{"_id": "Radiology$$$25904232-c040-40a6-9ca9-e4dc85e30e57", "text": "Multiple promising prospective trials are ongoing to further optimize PRRT (e.g., \u03b1-emitters, individualized dosimetry, and SSTR-antagonists)."}
{"_id": "Radiology$$$85c8bc8e-979c-4e4c-9f66-4a1d6eed46d6", "text": "At present, another well-known example of radioligand therapy (RLT) has demonstrated a significant survival benefit in patients with metastatic castration-resistant PCa. [177Lu]Lu-PSMA-617 is a prostate-specific membrane antigen (PSMA) targeting small molecule consisting of PSMA-617 with the \u03b2\u2212-emitting radionuclide lutetium-177 (Fig. 6.23). The PSMA-617 binds to the enzymatic pocket of PSMA after which it is internalized, resulting in the delivery of toxic doses of IR to PCa cells. The VISION trial has demonstrated a significant increase in imaging-based PFS and OS in a randomized controlled trial where it was compared to standard of care (i.e., chemotherapy, RT and ADT), resulting in the FDA approval of [177Lu]Lu-PSMA-617 for patients with metastatic castration-resistant PCa in March 2022 [150]. Since PSMA poses such an interesting target for RLT, due to the high overexpression on PCa cells, more PSMA-targeting radioligands are currently under clinical investigation, as summarized in Table 6.10.\n\nA schematic diagram of the P S M A 617 structure displays the linker in between the D O T A chelator and P S M A targeting moiety. \n\nFig. 6.23\nSchematic representation of the structure of the PSMA-targeting compound PSMA-617. The blue circle shows the PSMA-targeting moiety. The purple circle highlights the DOTA-chelator used to entrap radionuclides. The grey circle represents the linker molecule that connects the PSMA-targeting moiety with the DOTA-chelator\nTable 6.10\nExamples of RLT compounds under clinical investigation\n\nCompound\n\nClinical trial phase\n\nTrial numbera\n\nDisease\n\nPSMA-targeting RLT\n\n[177Lu]Lu-PSMA-617\n\nPhase III\n\nNCT03511664\n\nMetastatic castration-resistant PCa\n\n[64Cu]Cu-SAR-PSMA\n\nPhase II\n\nNCT04868604\n\nMetastatic castration-resistant PCa\n\n[177Lu]Lu-PSMA-I&T\n\nPhase II\n\nNCT04188587\n\nMetastatic castration-resistant PCa\n\n[225Ac]Ac-PSMA\n\nEarly phase I\n\nNCT04225910\n\nMetastatic castration-resistant PCa\n\n[177Lu]Lu-PSMA-R2\n\nPhase I/II\n\nNCT03490838\n\nMetastatic castration-resistant PCa\n\n[131I]I-PSMA-1095\n\nPhase II\n\nNCT04085991, NCT03939689\n\nMetastatic castration-resistant PCa\n\nBombesin-targeting RLT\n\n[177Lu]Lu-NeoB\n\nPhase I/IIa\n\nNCT03872778\n\nAdvanced or metastatic solid tumors: breast, lung, prostate, GIST, GBM tumor\n\nOthers\n\n[177Lu]Lu-FAP-2286\n\nPhase I\n\nNCT04939610\n\nAdvanced metastatic solid tumor\n\n[177Lu]Lu-DOTA-Biotin (ST2210)\n\nPhase I\n\nNCT02053324\n\nColorectal cancer with liver metastases\n\naThe trial number refers to its citation on https://\u200bclinicaltrials.\u200bgov/\u200b"}
{"_id": "Radiology$$$2130f460-e554-4550-b29a-8a5e57125b78", "text": "A schematic diagram of the P S M A 617 structure displays the linker in between the D O T A chelator and P S M A targeting moiety."}
{"_id": "Radiology$$$7c39edaa-762d-4c14-b889-7ba540ca36a8", "text": "The development of RLT is not strictly limited to PCa and targeting PSMA. Several other compounds with other targets are also undergoing clinical trials. One such target is the bombesin receptor family. Many common tumors, including breast, prostate, and lung cancer, show overexpression of one of the bombesin receptors, resulting in the development of several compounds targeting this receptor family [151]. Compared to the development of PSMA-targeting compounds, the development of bombesin-targeting agents is still in its infancy as illustrated in Table 6.10 by the limited number of compounds undergoing clinical investigation. Thus, at present, research into bombesin-targeting compounds remains largely preclinical."}
{"_id": "Radiology$$$64314cc9-14f2-4025-9c08-222b17091a4f", "text": "Besides PSMA and bombesin, other targets can also be used for RLT of a variety of human cancers. Other examples of clinical trials of radioligand therapy using other targets are summarized in Table 6.10."}
{"_id": "Radiology$$$dab00d2f-bda4-4015-add5-f6627d4673d5", "text": "At present, [177Lu]Lu-PSMA-617 is FDA approved in PCa patients with metastatic castration-resistant disease in whom standard treatments, including hormone deprivation therapy and chemotherapy, have failed. Patients eligible for treatment also need to have at least one PSMA-positive lesion (observed by 68Ga-PSMA-11 PET\u2013CT imaging at baseline), a life-expectancy of at least 6\u00a0months, sufficient organ function (e.g., bone marrow, kidney), and capability of self-care (defined by Eastern Cooperative Oncology Group performance status \u22642) [150]. Other types of RLT are under investigation for treatment of other types of advanced tumors, such as advanced solid tumors of breast and lung or colorectal cancer with liver metastases."}
{"_id": "Radiology$$$db8d514e-99d2-4742-bee9-a1600ee143a0", "text": "For the different types of RLT, treatment schedules can differ. For PSMA-RLT, and [177Lu]Lu-PSMA-617 in particular, a conventional treatment schedule consists of four treatment cycles administered in 6-week intervals. In each cycle, the administered activity ranges from 6 to 7.5 GBq. After each therapy cycle, treatment response and the overall condition of the patient are monitored in order to decide if treatment can be continued or not [152]. The VISION trials showed that [177Lu]Lu-PSMA-617 (hazard ratio 0.46) therapy was generally well tolerated and was able to improve both OS and PFS compared to standard of care treatment [150]. These clinical trials and the recent FDA approval of [177Lu]Lu-PSMA-617 show the potential of RLT for treatment of PCa and in the future, results of the ongoing clinical trials of RLT using other targets will also be published and contribute to the development of RLT as a new cancer treatment modality (Box 6.19)."}
{"_id": "Radiology$$$3c60629a-b2e8-429f-9088-34ccb5bd80d4", "text": "Besides peptide receptor radionuclide therapy, other radioligand therapies are also under investigation for treatment of different cancer types (e.g., PCa).\n\nAn FDA-approved compound for RLT is [177Lu]Lu-PSMA-617 for the treatment of metastatic-castration resistant PCa.\n\nMore compounds for RLT are under clinical investigation for multiple cancer types (summarized in Table 6.11).\nTable 6.11\nComparison of the accelerator types used for therapy\n\nAccelerator types\n\nProperties\n\nCyclotron\n\nCircular\n\nSmall\n\nMainly for protons\n\nSynchrotron\n\nCircular\n\nLarge\n\nSuitable also for heavier ions\n\nLINAC\n\nLinear\n\nLong but slim\n\nTechnically challenging"}
{"_id": "Radiology$$$f1e243e6-cb47-419b-b87b-4e2cdac19c84", "text": "Besides peptide receptor radionuclide therapy, other radioligand therapies are also under investigation for treatment of different cancer types (e.g., PCa)."}
{"_id": "Radiology$$$3539f13c-8cda-4e02-9f66-bae2cb2d293f", "text": "An FDA-approved compound for RLT is [177Lu]Lu-PSMA-617 for the treatment of metastatic-castration resistant PCa."}
{"_id": "Radiology$$$a21ec4fe-2684-439e-a965-b7256d8cdb83", "text": "More compounds for RLT are under clinical investigation for multiple cancer types (summarized in Table 6.11)."}
{"_id": "Radiology$$$6c79dd04-b274-454b-a32a-99eead26a224", "text": "In 1900, the German Nobel laureate Paul Ehrlich was the first person to introduce the \u201cmagic bullet\u201d concept, with reference to antibodies that can be used to treat diseases by specifically targeting receptors or biochemical pathways in bacteria or cancer cells. More than half a century later, the invention of hybridoma technology by Georges Kohler and C\u00e9sar Milstein paved the way for the production of monoclonal antibodies against almost any antigen. Kohler and Milstein received a Nobel Prize in 1984 for their work."}
{"_id": "Radiology$$$5b24ddf4-449f-478e-b229-2e6068bb1e50", "text": "A large proportion of therapeutic antibodies have since then been developed and approved by the FDA or EMA for the treatment of cancer. There are several mechanisms through which immunoglobulins function in the body, including, but not limited to antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), alteration of signal transduction, inhibition of angiogenesis, and immune checkpoint blockade [153]."}
{"_id": "Radiology$$$ec80e6c5-5459-4c90-bcdb-8bf6b85177b4", "text": "Another important modality through which antibodies can mediate a therapeutic effect is through their conjugation to a radionuclide that emits IR in the form of \u03b1 particles, \u03b2 particles, \u03b3-rays, or Auger electrons. By virtue of the antibody\u2019s specificity and selectivity, it will bind to a specific target overexpressed on a cancer cell and deliver a lethal dose of radiation to the cell. This approach is called radioimmunotherapy (RIT), though several other names have also been used in the literature. Most radioimmunoconjugates use the IgG class of antibodies, with an average molecular weight of 150\u00a0kDa and a biological half-life from 2 to 5 days."}
{"_id": "Radiology$$$90e20e10-84a4-4226-9d8d-dcce62fb0e03", "text": "Early clinical trials with radioimmunoconjugates used the readily available 131I radionuclide which allowed for their application in SPECT imaging as well as therapy. Today, a wide arsenal of radionuclides has been used in different RIT studies, each with different properties."}
{"_id": "Radiology$$$5bd224d5-ae32-4a2d-8513-2eab63f41848", "text": "There is currently only one FDA-approved RIT targeting the CD20 antigen on B-Cell Non-Hodgkin\u2019s Lymphoma (B-NHL): 90Y-ibritumomab tiuxetan or Zevalin\u00ae. The immunoconjugate is a result of the conjugation of the monoclonal antibody ibritumomab to the chelator tiuxetan. The antibody is a murine IgG-1 kappa antibody toward CD20, and the tiuxetan chelator is ideal for the chelation of Indium-111 or Yttrium-90. In the following paragraphs, we will look with more details into the use of 90Y-ibritumomab tiuxetan."}
{"_id": "Radiology$$$691318c5-539e-4215-aeeb-839950c454c7", "text": "The Zevalin\u00ae therapeutic regimen is used to treat adult patients either with newly diagnosed follicular NHL following a response to initial anticancer therapy, or patients with low-grade or follicular B-cell NHL that have relapsed during or after treatment with other chemotherapies. The prescription medication consists of three parts: two infusions of rituximab to reduce the number of B-cells in blood, and one injection of 90Y-ibritumomab to treat the NHL."}
{"_id": "Radiology$$$2de4e284-ff81-4aa9-9b37-7f6fe6d8bfb3", "text": "The Zevalin\u00ae therapeutic regimen should be initiated between 6 and 12\u00a0weeks following the last dose of first-line chemotherapy, after platelet counts have recovered to 150,000/mm3 or more. Patients with platelet counts less than 100,000/mm3 are not treated with Zevalin\u00ae."}
{"_id": "Radiology$$$452293fb-e46b-48e0-b14d-ae25bfb86ccb", "text": "Treatment is initiated with an IV infusion of 20\u00a0mg/m2 rituximab. The same infusion is re-administered 7\u20139\u00a0days after the first infusion. Within 4\u00a0h of administering the second rituximab infusion, an IV injection of 90Y-ibritumomab tiuxetan is administered at a dose of 0.4\u00a0mCi/kg for patients with normal platelet count, or 0.3\u00a0mCi/kg for relapsed or refractory patients with lower platelet counts (100,000\u2013149,000/mm3). The total dose administered should not exceed 32\u00a0mCi (or 1184\u00a0MBq)."}
{"_id": "Radiology$$$9a844180-150f-40ec-ae3f-a511e5464840", "text": "Although Zevalin\u00ae is the only FDA-approved RIT that is currently in use, there are a lot of other radioimmunoconjugates at different stages of clinical development, targeting different cancer-associated antigens. Figure 6.24 shows some of the antigens targeted in RIT.\n\nA schematic diagram of the antigens targeted in R I T. Inset images of the tumour cell, B cell, A M L, and targeting vectors that target for radioimmunotherapy include antibodies, nanobodies, diabodies, affibodies, and minibodies. \n\nFig. 6.24\nDifferent targeting vectors and molecular targets used in RIT. In RIT, the targeting vectors are designed to recognize certain molecules present on the surface of tumor cells (e.g., PSMA, CEA, B7-H3, CAIX, or CD45), cancer-associated fibroblasts (FAP\u0251), tumor-infiltrating T cells (CD4 or CD8), and/or circulating immune (e.g., CD45, CD19, CD37, or CD22) or tumor cells (e.g., CD45 or CD33)"}
{"_id": "Radiology$$$6b70dfbf-468f-4967-b55d-4260bc4a6bde", "text": "A schematic diagram of the antigens targeted in R I T. Inset images of the tumour cell, B cell, A M L, and targeting vectors that target for radioimmunotherapy include antibodies, nanobodies, diabodies, affibodies, and minibodies."}
{"_id": "Radiology$$$6bb18c42-931d-414a-bf50-d6bfffceec52", "text": "Clinical trials designed with a direct comparison of the radiolabeled antibody with its non-radiolabeled counterpart allow to tease out the therapeutic benefit of RIT over conventional mAb immunotherapy for cancer patients. One example of such a study is a phase III randomized controlled trial of patients with relapsed or refractory CD20-positive NHL patients [154]. In this study, 143 patients were divided into two groups, a \u201ccontrol\u201d group receiving intravenously (IV) the CD20-targeting antibody rituximab for 4 weeks, while the other group received a single (IV) dose of Zevalin\u00ae RIT. The latter group was pretreated with two rituximab doses to improve biodistribution and one dose of 111In-ibritumomab tiuxetan for imaging and dosimetry. The control group had an overall response rate (ORR) of 56% while the RIT group showed an ORR of 80%. The complete response (CR) rates were 16% and 30%, respectively. The primary toxicity observed with Zevalin\u00ae was reversible myelosuppression, which is also the most common side effect of conventional cancer therapies [155]."}
{"_id": "Radiology$$$02e4550c-ca0b-4ac2-982c-6e26ec51d912", "text": "It is worth mentioning that the clinical impact observed in RIT of hematological cancers has not been replicated in solid tumors yet, due to a number of outstanding challenges encountered which lead to high bone marrow absorbed doses and insufficient dose delivery to tumors. Several promising strategies have been developed to overcome these challenges, such as the use of antibody fragments (e.g., single-domain antibodies and affibodies) instead of whole immunoglobulins, allowing for higher imaging contrast, deeper tumor penetration, and improved pharmacokinetics [156]. Another important strategy, known as pretargeting, is based on separating the antibody from the radionuclide and letting the two agents combine in vivo. A review by Verhoeven et al. nicely summarizes the different RIT in which pretargeting has been applied [157]."}
{"_id": "Radiology$$$fd1325c9-7afb-42e3-9174-a3e7acd8e4fa", "text": "The undisputable efficacy of radionuclide therapy (RNT) has been documented in the last decade in a series of landmark trials. With a plethora of targeting vectors directed to tumor-specific molecular targets (some in routine clinical use, others in development) and a large panel of radionuclides characterized by different physical properties, the targeted treatment of both solid and hematological tumors is now a clinical reality. The concept of RNT emerged in the 1940s with the use of iodine-131 for thyroid cancer management and was the first FDA-approved radiopharmaceutical (in 1951). Since then, numerous other RNT radiopharmaceuticals have been developed and successfully used, including the most recent FDA- and EMA-approved radiopharmaceutical 177Lu-DOTATATE. However, their success may be limited by healthy tissue toxicity and/or tumor intrinsic or acquired resistance. One strategy to overcome these limitations is the use of combination therapies aiming at achieving an increase in treatment efficacy while remaining at a low toxicity level [158]. This will subsequently lead to an increased therapeutic index and hence improved treatment outcome. If rationally designed, these combination therapies can lead to synergistic effects by targeting adequate molecular pathways, ultimately causing lethal damage to the tumor cell. Indeed, radiobiological mechanisms underlying the effects of RNTs could serve as a very promising basis for the design of combination clinical trials."}
{"_id": "Radiology$$$302b0c69-627e-4df2-a844-acdb357f242a", "text": "The rationale behind the use of the combination approach with RNT, using two or more therapeutic agents, may be multiple and vary according to the physical properties of the radioisotope used and the biology of the tumor considered. Combination strategies may aim at reducing hypoxia, improving the radiopharmaceutical delivery (in case of a poor tumor vasculature preventing drug delivery) via increased perfusion of the tumor, enhancing the therapeutic effect based on radiosensitization mechanisms, or improving the immune control. RNT has been basically evaluated in combination with all cancer pillar therapies, e.g., chemotherapy, external beam RT(EBRT), immune and targeted therapies. Different combination strategies with RNT are summarized in Fig. 6.25.\n\nA circular diagram of the combination therapies with radionuclide therapy. It include chemotherapy, D D R inhibitors, E B R T, tandem or duo, immunotherapy, and targeted agents.\n\nFig. 6.25\nOverview of combination therapies with radionuclide therapy"}
{"_id": "Radiology$$$530564f0-4ce4-4959-a621-68939134f6f7", "text": "A circular diagram of the combination therapies with radionuclide therapy. It include chemotherapy, D D R inhibitors, E B R T, tandem or duo, immunotherapy, and targeted agents."}
{"_id": "Radiology$$$2d33026d-9068-4758-98b6-9a7941ab4e73", "text": "The use of chemotherapy with EBRT in many common cancers (including lung, head and neck, cervical cancers) and different settings (e.g., neoadjuvant, curative, etc.) has fostered its combination with RNT."}
{"_id": "Radiology$$$6372df56-7731-4dda-9d5d-3613c3883aa4", "text": "Several clinical studies have been published combining PRRT with 5-fluorouracil (5-FU), capecitabine or temozolomide, a therapy called peptide receptor chemoradionuclide therapy (PRCRT). A population of interest for PRCRT are the highly proliferating NETs characterized by tumor dedifferentiation, higher tumor grade, worse OS outcome, and most commonly 18F-FDG-avidity of the tumor lesions. PRCRT (combination of 177Lu-DOTATATE and 5-FU) was retrospectively investigated in 52 patients with 18F-FDG-avid disease and the majority having grade 2 advanced NETs [159]. A high DCR of 98% was achieved and 27% of the patients achieved complete metabolic response on 18F-FDG PET/CT despite having residual SSTR-positive disease, most likely due to the eradication of the dedifferentiated lesions by PRCRT. It was expected that the prognosis in this patient cohort would be poor, however a median PFS of 48\u00a0months was achieved and a median OS was not reached during a median follow-up time of 36\u00a0months. Toxicity was low, despite the fact that 67% of the patients had received prior chemotherapy."}
{"_id": "Radiology$$$fa717e09-3408-47fb-b6bb-ba621b5f2b9e", "text": "Capecitabine, a prodrug of 5-FU, has the additional advantage that it can be administered orally. A 2-arm cohort analysis compared concomitant 177Lu-DOTATATE plus capecitabine (n\u00a0=\u00a088) with 177Lu-DOTATATE monotherapy (n\u00a0=\u00a079) and revealed an increased OR in favor of 177Lu-DOTATATE plus capecitabine (43.1% and 14%, respectively). In addition, a significant lengthening of OS in the 177Lu-DOTATATE plus capecitabine group was observed compared to the 177Lu-DOTATATE monotherapy group (median OS not reached vs. 48\u00a0months, respectively, after a mean follow-up of 32.4\u00a0months; p\u00a0=\u00a00.0042) [160]. The combination of 177Lu-DOTATATE and capecitabine was also evaluated in paragangliomas, however the study failed to prove the superiority of the combination over 177Lu-DOTATATE monotherapy [161] which might be attributed to a too small number of patients included and the typically lower proliferation rate in this cancer type."}
{"_id": "Radiology$$$38e6e75b-c5d6-48ce-b59b-f97c1ca4c6eb", "text": "A decreased sensitivity of tumors to the alkylating agent temozolomide has been associated with the expression of O(6)-methylguanine-DNA methyltransferase (MGMT), a DNA repair protein involved in the removal of O(6)-methylguanine DNA lesions induced by temozolomide. MGMT deficiency was more frequently observed in pancreatic NET (pNET) compared to lung or small intestine NET and may explain the different sensitivity profiles of pNET compared to NET of other origins. A synergistic effect is apparent when combining capecitabine and temozolomide (CAPTEM), most likely due to the depletion of MGMT caused by capecitabine, which strengthens the effect of temozolomide. This is the reason why the treatment regimens add temozolomide after substantial exposure to capecitabine [162]. Preliminary results of the phase II \u201cCONTROL NET\u201d RCT have been presented. This trial compares a combination of 177Lu-DOTATATE plus CAPTEM (experimental arm) versus 177Lu-DOTATATE monotherapy (control arm) in patients with low to intermediate grade midgut NETs. Forty-seven patients were included. The 15-months PFS was 90% versus 92% and ORR was 25% versus 15% for PRRT plus CAPTEM versus PRRT monotherapy, respectively. However, grade 3/4 toxicity occurred more frequently in the PRRT plus CAPTEM arm."}
{"_id": "Radiology$$$ff2c7645-9d2b-45e4-b5e2-bb0d6cf0dfd8", "text": "Overall, combining RNT with chemotherapy appears safe and efficient based on data with the beta-emitter lutetium-177. However, multicenter prospective RCTs are lacking to prove superiority of the combination over RNT alone. Although the mechanism of the radiosensitizing effect of chemotherapy is not elucidated, it is thought to act as a radiosensitizer of RNT by increasing DNA damage. However, one preclinical study also pointed out the effect of increased perfusion induced by a chemotherapeutic agent, temozolomide, which may improve 177Lu-DOTATATE delivery to the tumor, as well as increase tumor oxygenation which may also have a radiosensitizing effect [163]."}
{"_id": "Radiology$$$7105cffc-c935-4cc5-a219-164633fc322b", "text": "177Lu-PSMA and radium-223 have also been combined with chemotherapy, although less data are available compared to 177Lu-DOTATATE. A phase I/II study showed that the alpha-emitter radium-223 (55\u00a0kBq/kg every 6\u00a0weeks for 5\u00a0cycles) in combination with docetaxel (60\u00a0mg/m2 every 3\u00a0week) was well tolerated in bone-predominant metastatic castration-resistant prostate cancer patients. Exploratory efficacy data even suggested enhanced antitumor activity in the combination arm [164]. This will be further explored in a phase III clinical trial that is currently recruiting patients (NCT03574571)."}
{"_id": "Radiology$$$75cc38c3-df91-40da-8dc7-a636d7852ae8", "text": "The combination of 177Lu-PSMA with docetaxel, a taxane impairing microtubules polymerization dynamics and therefore preventing cell mitosis, is currently evaluated in metastatic hormone-na\u00efve prostate cancer in a randomized phase II study (UpFrontPSMA trial\u2014NCT04343885) [165]. Patients are randomized 1:1 to the 177Lu-PSMA plus docetaxel arm (177Lu-PSMA 7.5\u00a0GBq, 2\u00a0cycles intended, every 6\u00a0weeks followed 6\u00a0weeks later by docetaxel 75\u00a0mg/m2, 6\u00a0cycles intended, every 3\u00a0weeks) or the docetaxel monotherapy arm."}
{"_id": "Radiology$$$6586299c-7373-419d-9a73-4b4851cdc243", "text": "In addition to chemotherapy, RNT has also been evaluated in combination with targeted agents in order to potentiate the therapeutic effect of RNT. Targeting relevant pathways may aid in eliminating (radio-)resistant clones as well as overcoming tumor heterogeneity."}
{"_id": "Radiology$$$57ee1bab-96b6-487a-b453-10eaeea085ec", "text": "The mammalian target of rapamycin (mTOR) inhibitor everolimus was combined with 177Lu-DOTATATE in the phase I NETTLE proof-of-concept study in order to establish an optimal safe dose of everolimus in this combination setting. Nephrotoxicity was the dose-limiting factor, leading to the maximum tolerated dose of 7.5 mg everolimus in combination with PRRT [166]."}
{"_id": "Radiology$$$f560bc74-348a-4092-9f19-6fa8896e0ef5", "text": "Among targeted agents, DNA damage response (DDR) inhibitors have recently been widely adopted. Preventing the repair of radiopharmaceutical-induced DNA damage by targeting DNA repair pathways is considered an interesting strategy. PARP is involved in the repair of DNA SSBs and has been targeted by PARP inhibitors (PARPi) in combination with chemotherapy and EBRT. Following favorable results from preclinical studies combining 177Lu-DOTATATE and PARPi [167], the combination is now assessed in phase I/II clinical trials with 177Lu-DOTATATE (NCT05053854, NCT04375267, NCT04086485) and 177Lu-PSMA (NCT03874884). Different treatment schedules are used within the trials, with PARPi commencing either before or after RNT administration, and also with variable duration of PARPi (first few days of each RNT administration or daily continuous administration). Study results are awaited and might already provide some evidence about the optimal treatment schedule to be used."}
{"_id": "Radiology$$$a365fc7f-bbd2-435e-9984-38362d89c732", "text": "Phase I studies evaluating the combination of 177Lu-DOTATATE and other DDR inhibitors, such as peposertib (NCT04750954) and triapine (NCT04234568), are also underway. Peposertib is an inhibitor of DNA-PK, a serine/threonine protein kinase playing a critical role in DNA DSB repair via the NHEJ pathway while triapine is an inhibitor of ribonucleotide reductase, an essential enzyme for DNA replication and repair."}
{"_id": "Radiology$$$42a82a0c-b42d-472e-ac20-8b2bec7df7b0", "text": "Other promising combinations are evaluated in the preclinical setting [168]. These include inhibitors of several pathways or molecules: DNA damage response, HSP 90, DNA topoisomerase, hedgehog signaling pathway, and EGFR."}
{"_id": "Radiology$$$dd2c973b-f993-4d8c-8932-1f37b930f6b6", "text": "Combining RNT with EBRT has several advantages [169]. Firstly, there should not be overlapping toxicities because of different dose-limiting organs, being the surrounding tissues (the ones close to the tumor or that are in the path of incident beams) for EBRT and mainly bone marrow and kidneys for RNT (but will depend according to the RNT type). Therefore, an escalation of the combined radiation absorbed dose without exceeding the maximum tolerated dose of the limiting organs should be allowed. Secondly, the advantages of both radiation-based therapies may be combined: EBRT delivers a precise and homogeneous high dose of radiation locally, to the bulk tumor, while the administration of RNT allows the targeted treatment of systemic disease, including (micro)-metastases and residual tumor cells, albeit with less control of the tumor dose and a heterogeneous dose depending on perfusion and target expression."}
{"_id": "Radiology$$$19cb2b0e-746d-4477-8370-6bc7d774a349", "text": "Very few clinical studies are being conducted, and most of them are based on sequential and not concurrent administration of both therapies. This combined regimen is mostly studied in bone metastases as well as in brain and liver tumors but also meningioma. Promising data have been obtained in meningioma where 177Lu-DOTATATE and EBRT have been combined and showed the feasibility of such an approach. Interestingly, in seven patients out of ten, for which a follow-up 68Ga-DOTATATE PET/CT was available, increased uptake of the radiotracer was observed compared to the pre-therapeutic scan [170]. This observation was corroborated in several preclinical studies in which up-regulation of somatostatin receptors was observed following low doses of EBRT [171]. Increased tumor perfusion might also be the cause of an increased radiotracer uptake seen on PET/CT. This finding is significant, as such a combination could be beneficial to patients currently not eligible for peptide receptor radionuclide therapy due to a too low uptake on 68Ga-DOTA-SSA PET/CT."}
{"_id": "Radiology$$$aa11a8b6-cf6e-40ae-96bf-1a3b7f7b52ad", "text": "A synergistic effect of 4-l-[131I]iodo-phenylalanine (131I-IPA) and EBRT has been observed in preclinical models of glioblastoma multiforme, and the first results of a phase I/II trial (IPAX-1 trial\u2014NCT03849105) should be available soon."}
{"_id": "Radiology$$$9a158a7a-4b90-4a9f-903e-855a3f2e7044", "text": "RT with EBRT has been shown to increase tumor immunogenicity and antigen presentation and therefore enhance tumor cell destruction by T cells. Hence there is a rationale to investigate the combination of immunotherapy and RNT. Preclinical studies have shown the added value of an immune checkpoint blockade to RNT on survival."}
{"_id": "Radiology$$$229bf97a-078f-40e8-9556-678a664c3d6b", "text": "The combination of PRRT with the immune checkpoint inhibitor nivolumab has recently been explored clinically in a phase I study including nine patients with advanced lung neuroendocrine neoplasms [172]. Dose level 1 consisted of 177Lu-DOTATATE 3.7 GBq (8-week interval, 4\u00a0cycles intended) plus nivolumab 240 mg (2-week interval), and dose level 2 consisted of 177Lu-DOTATATE 7.4 GBq (8-week interval, 4\u00a0cycles intended) plus nivolumab 240 mg (2-week interval). Only one dose-limiting toxicity, consisting of a grade 3 rash, was noted in one patient being treated at dose level 2."}
{"_id": "Radiology$$$c0c02e3f-9ebe-4797-8592-6ea91a2835cd", "text": "Phase I and II clinical trials combining 177Lu-DOTATATE (NCT03325816, NCT04261855, NCT03457948) or 177Lu-PSMA (PRINCE trial\u2014NCT03658447, NCT03805594) with anti-PD1 or PD-L1 antibodies are under way."}
{"_id": "Radiology$$$22f86252-595e-4d6c-92e0-48faee2b54a7", "text": "There exists a huge potential in terms of a combined regimen with RNT. Promising combination strategies used with EBRT frequently serve as arguments to extrapolate to RNT. However, EBRT and RNT are characterized by major differences such as the delivery route (external versus \u201cinternal\u201d), the dose (homogeneous dose versus heterogeneous dose), and the dose rate (very high and constant versus low and exponentially decreasing dose rate). The maximum therapeutic benefit one can derive from RNT will be achieved thanks to clever combinations exploiting synergistic interactions, used in the optimal doses and sequences [173] and using biomarkers with an individualized approach. Preclinical studies can bring valuable information and can serve as a basis to design proper clinical trials."}
{"_id": "Radiology$$$ab8304ab-196b-42f4-9cb1-3e9a74c165aa", "text": "Novel treatment combinations are emerging and are now in the early phases of clinical trials, aiming at evaluating the feasibility and the toxicity of the combinations. Later, large prospective randomized trials will be needed to prove the superiority of the combinations over the monotherapies. Combination strategies might also enter in an entirely new realm when targeted alpha-emitters will become available for clinical trials in the upcoming years, with many new combination possibilities."}
{"_id": "Radiology$$$c134509b-46fe-4c43-b9a0-f2da491fe84a", "text": "Compared to conventional RT (using X-rays), particle therapy has major advantages. The depth of penetration into the body is determined by the particle\u2019s acceleration energy and thus energy deposition increases over distance up to a high peak at the end of their range, the so-called Bragg peak. Simply said, the energy transfer is proportional to the inverse square of its velocity where the ionization density increases as the speed of the particle slows down:\n\n (6.5)where Z is the charge of the particle and v its velocity. This happens until very close to the end of their range where the high-dose Bragg peak phenomenon is formed (Fig. 6.26a). In the clinics, expanded Bragg peak also known as Spread out Bragg peak (SOBP) is then used to cover the entire tumor volume, this is formed by adding up all single Bragg curves for ions of different energy and therefore range (Fig. 6.26b).\n\nA. Dose versus water depth plots a line that peaks at around (10.5, 1) before declining. B. Dose versus z, where the spread out Bragg peak rises and fluctuates before declining, and the pristine Bragg peaks rises to their highest peaks before declining and plateauing. Below, 4 magnetic resonance images of intensity-modulated radiation therapy and protons dose distribution.\n\nFig. 6.26\n(a) Absorbed dose of a 121 MeV proton in water forming the Bragg peak [174]. (b) Spread Out Bragg Peak formed by overlaying ions with different energy forms the spread out Bragg peak as used for therapy [175]. (c) Dose distribution of one patient with locally advanced non-small cell lung cancer (NSCLC) planned with intensity-modulated radiation therapy (IMRT) (left) or protons (right), depositing no dose behind the tumor [176"}
{"_id": "Radiology$$$63d9713d-5910-44e9-bb11-8003525f76aa", "text": "A. Dose versus water depth plots a line that peaks at around (10.5, 1) before declining. B. Dose versus z, where the spread out Bragg peak rises and fluctuates before declining, and the pristine Bragg peaks rises to their highest peaks before declining and plateauing. Below, 4 magnetic resonance images of intensity-modulated radiation therapy and protons dose distribution."}
{"_id": "Radiology$$$f5a1a6dc-7020-481b-a6f2-daff21b9d11a", "text": "Beyond the Bragg peak (known as tail), there is a rapid falloff of the dose, allowing for sparing of the normal tissue [177] as the tissue behind the tumor doesn\u2019t receive any radiation dose. Tumors which have an organ at risk (OAR) lying close to the tumor are especially suited for radiotherapy using particles, as this unique dose distribution can be exploited here. The OAR behind the tumor can thus effectively be spared from radiation damage (Fig. 6.26c)."}
{"_id": "Radiology$$$0fa309c3-9c7f-4131-97b0-30978361391f", "text": "At the moment, mainly protons are used in particle therapy but also carbon ions. Furthermore other ions such as helium are getting more and more in the focus of particle RT."}
{"_id": "Radiology$$$72e45616-4aec-4144-ac99-01b10b3a5ebd", "text": "These physical advantages ensure precise localization of dose distribution to the tumor while minimizing dose (thus DNA damage) to the surrounding normal tissues. Currently, particles heavier than carbon are not well investigated for clinical purposes due to the dose distribution at the tail where the dose increases with the charge of the particle resulting in increased dose to normal tissue. Furthermore, for equal velocities, the ionization density for carbon ions (Z\u00a0=\u00a0six, A\u00a0=\u00a012) is 36 times greater than that of the proton. However, a carbon ion has 12 times more total kinetic energy, so the range of the carbon ion is about three times lower. Thus, the heavier the particle, the shorter the penetration depth. Finally, following the recommendations of the Ion Beam Therapy Workshop Report, heavy ion beam therapy should be limited to tumors (a) exhibiting a high risk of local failure post photon (or proton) RT, (b) radioresistance due to histology, hypoxia, and other factors, (c) recurring, (d) efficient at repairing cellular damage, or (e) adjacent to critical normal structures, in particular if resection could lead to a substantial loss of organ function."}
{"_id": "Radiology$$$0a238cd3-abda-44d7-b1c1-eb59afd68ba0", "text": "Proton therapy is nowadays widely used all over the world and in some cases is more appropriate for patient treatment than the mostly used X-ray RT, due to the physical properties of protons (the Bragg curve). A detailed historical overview can be found in Elaimy et al. [178]."}
{"_id": "Radiology$$$fd2e686c-dad4-4885-a7e2-a78cdcb58d42", "text": "Clinical advantages of a proton beam were first suggested by Wilson in 1946 in his paper about the radiological use of high-energy protons. Animal studies began as soon as the first high-energy synchrocyclotron (340\u00a0MeV) was completed at the University of California Lawrence Berkeley Laboratory, USA (LBL). These first experiments on mice, Tradescantia microspores, and yeast cells showed that the RBE of high-energy protons (340\u00a0MeV) is comparable to that of 200\u00a0kVp X-rays."}
{"_id": "Radiology$$$66f6c2de-3917-416c-8b50-d6cf6b57061d", "text": "The first patient proton treatment in LBL took place in 1954. A few years later, in the late 1950s, the Gustaf Werner Institute in Uppsala, Sweden also used protons for patient treatment. In 1961, the Massachusetts General Hospital began treating small intracranial targets with radiosurgical techniques at the Harvard Cyclotron Laboratory (HCL) in Cambridge. Prior to the patient treatment, a radiobiological investigation on monkeys demonstrated experimentally the feasibility of the method. Later Koehler and others developed a technique to scatter the beam laterally and also range modulation wheels to produce SOBP to cover extended target volumes, thus it was possible to start treating larger treatment volumes in HLC in 1974."}
{"_id": "Radiology$$$055b411a-0194-4402-97a6-e4900cb7b584", "text": "During the late 1960s and in the decade of the 1970s, several Russian physics research facilities initiated their proton therapy programs. For example, the Joint Institute for Nuclear Research in Dubna in 1968, the Moscow Institute for Theoretical and Experimental Physics in 1969, and the Central Research Institute of Roentgenology and Radiology in Saint Petersburg in 1975."}
{"_id": "Radiology$$$e5c32782-abcf-4052-863c-0c3302704a64", "text": "The National Institute for Radiological Sciences in Chiba, Japan started proton therapy treatments in 1979. They were also the first that developed a spot scanning system for proton treatment delivery in 1980. Since then is proton therapy spread more and more\u2014Clatterbridge, England in 1989, France at Nice and Orsay (1991), iThemba Labs in Cape Town, Africa (1993), Paul Scherrer Institut at Villigen, Switzerland (1996), Hahn Meitner Institute in Berlin, Germany (1998), National Cancer Center in Kashiwa, Japan (1998), and Joint Institute for Nuclear Research in Dubna, Russia (1999)."}
{"_id": "Radiology$$$b2c45a6c-1113-4d2f-a985-18eb29565ca8", "text": "The first hospital specialized in proton therapy started treating patients in 1990 at the Loma Linda University Medical Center in Loma Linda, California, USA. In the same period, the Proton Therapy Cooperative Group was formed, later renamed to the Particle Therapy Cooperative Group (PTCOG) [179]. It is a non-profit organization making statistics and organizing meetings about protons, light ions, and heavy charged particles RT."}
{"_id": "Radiology$$$8bee62b7-82e0-4175-a296-5e880b69461f", "text": "Nowadays, there are more than 100 proton therapy centers all over the world with technological equipment from several companies such as IBA, Varian, Mitsubishi, Sumitomo, Hitachi, Mevion, ProNova, Protom based on cyclotrons or synchrotrons. More about the facilities and also patient statistics can be found, for example, on the PTCOG website."}
{"_id": "Radiology$$$d6125f2d-d5cc-4b48-b0a7-10702c303fcb", "text": "The generation of protons is obtained via hydrogen ionization. Protons are then accelerated inside a particle accelerator, typically a cyclotron or a synchrotron. A cyclotron produces a proton beam with a fixed energy, on the other hand, the proton energy in a synchrotron is adjustable [180]."}
{"_id": "Radiology$$$774c95f0-624e-417f-b191-7b8b2e2c4f5d", "text": "In both cases (cyclotron and synchrotron), the beam needs to be spread longitudinally, to produce an SOBP for the patient treatment. This is done by superposing several beams with different energies and weights. In the case of a cyclotron, an adjustable amount of material has to be placed in the way of the beam to reduce the beam energy to the one needed. This is achieved by the use of a degrader just after the beam extraction or by placing a stack with a variable number of plates (a range shifter), a plate with ripples (a ridge filter), or a rotating wheel with an azimuthally changing thickness (a range modulation wheel) inside the nozzle in the irradiation room. In the case of synchrotron, the energy is adjusted inside the accelerator, as was already mentioned, so there is no need for any additional devices [180]."}
{"_id": "Radiology$$$51cfe1da-4155-46ff-8bd3-ce1b2affd250", "text": "The physical depth dose curve of a SOBP has a broad, quite homogeneous dose region, as is shown in Fig. 6.30. This makes it possible to deliver a higher dose to the tumor region than to the OAR, and therefore to spare these tissues."}
{"_id": "Radiology$$$5e89898e-f05c-49ed-afff-ef8792c8b93a", "text": "There are two modes enabling the lateral beam spread, passive or active modes. Examples of passive modes are the Single or Double Scattering (SiS or DS) and an example of active mode is the Pencil Beam Scanning (PBS). For the passive modes, the beam passes through scatters (one or two, SiS or DS, respectively). In the active modes, scanning magnets are used, which redirect the narrow proton beam to several positions according to the treatment plan. The dose is then delivered to each layer of the volume spot by spot."}
{"_id": "Radiology$$$c6e02951-cf51-4d97-8596-e2c59e796a76", "text": "The energy spectrum, and thus the LET of protons in the SOBP is changing with depth in tissue, since the protons are slowing down traveling through the tissue. At the distal parts of the SOBP, the LET is much higher than in the proximal part. High LET values are connected to increased DNA damage, and thus to lower cell survival."}
{"_id": "Radiology$$$dacca3cb-0e1e-4f92-b900-074e5d895334", "text": "The International Commission on Radiation Units and Measurements (ICRU) has recommended the use of a generic RBE value equal to 1.1 in the whole range of proton therapy, and most of the proton therapy centers around the world have adopted this value [181]. This means that the same fractionation scheme as for X-ray RT can be used, with the difference that instead of 2 Gy 1.82 Gy per fraction will be used with protons."}
{"_id": "Radiology$$$99768ed3-afb4-4a12-a277-4856814e1aef", "text": "This recommended value is based on experimental studies done in vitro and in vivo mostly using passive scattering modes in the early days of proton therapy. From the in vitro studies, mostly performed on Chinese Hamster cell lines, with cells placed in the middle of SOBP, the range of estimated RBE values was from 0.86 to 2.10 with a mean of 1.22\u00a0\u00b1\u00a00.02. The RBE from the mid-SOBP in vivo studies ranged from 0.73 to 1.55 with a mean of 1.10\u00a0\u00b1\u00a00.01 [181]."}
{"_id": "Radiology$$$7e99fd55-6cb4-45f9-a14b-b71a6e09c573", "text": "Later studies showed that the RBE is not a constant value but it varies depending on a wide range of parameters, such as the beam range, dose per fraction, position in the SOBP, cell line or tissue origin, and also the studied biological endpoint [182]. Another problem when comparing RBE values from different publications is the reference radiation used for the establishment of the RBE values. Several reviews on this topic exist, as, for example, where a collection of data from several groups are sorted by cell lines referring also to the used reference radiation [183]."}
{"_id": "Radiology$$$d9556ea0-0b67-40d3-84c1-73b419a5e6bd", "text": "Some studies report RBE values at the distal falloff of the SOBP near to 3 [184]. One of the claimed advantages of proton therapy is the steep distal falloff of the Bragg peak. Due to this fact, many times the proton beam is often directed to stop in the proximity of the patient\u2019s OAR. The mentioned studies highlight the inaccuracies in the generic RBE value used in the whole range of proton therapy. These inaccuracies are much more crucial at the distal falloff of the beam and can lead to the damage of healthy tissues behind the treatment volumes."}
{"_id": "Radiology$$$9c05ad9b-5ccc-41b3-bafc-65974e8e11f8", "text": "In recent years, there is an increased interest in using the PBS mode, thanks to the spot-weighted dose delivery, which facilitates a more conformal dose delivery to the treatment volumes and sparing of healthy tissue. Another advantage of PBS is the much lower secondary-induced radiation (mostly neutrons) from the components of the technological constructions or patient-specific devices (i.e., collimators and compensators) needed in passive modes."}
{"_id": "Radiology$$$5da51fca-d180-458f-95f9-df27f17c07f5", "text": "The dose rate in each spot is however much higher than the dose rate in passive modes, which could maybe influence the cell response inside the treated volume in a different way than it is expected. Anyhow, there are several studies showing that there is not any significant difference between the biological response of cells using passive or active modes [185]. In clinical applications, there is some evidence that passive scattering may be associated with more toxicity than pencil beam scanning techniques [186]."}
{"_id": "Radiology$$$c11fe67a-d87c-4476-8e94-d585f2e0668d", "text": "Carbon ion radiobiology finds its origin from the use of ions in cancer RT. Research on carbon ions and their clinical potential started in 1975, with the installation of the BEVALAC at the Lawrence Berkeley Laboratory [187]. In response to the initial success, the Japanese government began construction on the world\u2019s first heavy ion facility designated for medical applications at the National Institute of Radiological Sciences (NIRS) in 1984. The Heavy Ion Medical Accelerator in Chiba (HIMAC) was completed in 1993 and carbon ion RT clinical trials began in June 1994 [188]."}
{"_id": "Radiology$$$999f3d74-1faf-43c0-9caa-00f778080e2f", "text": "Talking about energy deposition, it is important to mention the Linear Energy Transfer (LET\u2014keV/\u03bcm) which is the energy deposited per unit of length along the particle track\n\n (6.6)with dE\u00a0=\u00a0deposited energy and dx\u00a0=\u00a0distance covered. Therapeutic beams of carbon ions (100\u2013400\u00a0MeV/n) have LET ranging from 10 to 100\u00a0keV/\u03bcm [189]. LET is also at the origin of produced biological effects that cause radiation damage. As the particle species and their energy influence LET, the LET of carbon ions is higher than the LET of photons and hence causes a higher fraction of clustered DNA damage foci from direct DNA-ion interaction (Fig. 6.27).\n\nA schematic diagram of the g H 2 A X arranged in a diagonal line in carbon ions and the scattered g H 2 A X in photons. \n\nFig. 6.27\nSchematic representation of gH2AX after exposure to carbon ions versus photons. DAPI in blue, gH2AX in green"}
{"_id": "Radiology$$$9303cefd-f738-4bb6-a0b0-6379323add40", "text": "A schematic diagram of the g H 2 A X arranged in a diagonal line in carbon ions and the scattered g H 2 A X in photons."}
{"_id": "Radiology$$$ee8905eb-6521-41b2-b8b1-41b823d9d659", "text": "Comparison of biological effects of different LET (beam qualities) is expressed as the relative biological effectiveness (RBE). For the same biological effect, RBE is described as the dose ratio of the reference beam quality experiment to the test beam quality experiment\n\n (6.7)with Dr\u00a0=\u00a0Absorbed dose at reference beam quality experiment (usually photon) and D\u00a0=\u00a0Absorbed dose at test beam quality experiment."}
{"_id": "Radiology$$$2a23be7b-765c-429b-a1c7-5fb9310c7550", "text": "RBE is a function of multiple parameters such as the dose, dose rate, LET, oxygen concentration, and cell cycle phase to mention a few. The dependency of these parameters is particularly true at low LET (<10\u00a0keV/\u03bcm) but less with increasing LET (>10\u00a0keV/\u03bcm) such as for carbon ions. The RBE value of photons (<10\u00a0keV/\u03bcm) is considered equal to ~1.0 and tends to increase gradually until it comes to a maximum at around LET\u00a0=\u00a0100\u00a0keV/\u03bcm and finally decreases. This phenomenon is also known as the overkill effect. Generally, the RBE of carbon ions is around 3.0. However, with increasing LET, dose delivered to the surrounding tissue (entrance dose and tail) also increases. Therefore, a compromise between RBE and dose delivered to the surrounding tissue is needed. As an optimal RBE is said to be achieved around a LET of 100\u00a0keV/\u03bcm, carbon ions became the best compromise between RBE and dose delivered to the surrounding tissue and is therefore the most studied and clinically applied ion in particle therapy [188, 190]. Yet, little is known on healthy tissue toxicity and the correlated molecular and cellular mechanisms linked to carbon ion irradiation."}
{"_id": "Radiology$$$8c8d55c8-720e-4896-836d-dadc3ec346db", "text": "Under normoxic conditions, DNA damage caused by low LET radiation (such as photons or protons) is enhanced by generated DNA radicals, which in the presence of molecular oxygen are fixed or become permanent (also known as the indirect interaction). The existing oxygen also hinders repair mechanisms. Under hypoxic conditions, this phenomenon is not present, DNA radicals become reduced by sulfhydryl groups causing less damage and repair mechanisms are promoted. Consequently, a major cause of radiation resistance in RTy has been attributed to hypoxic cancer cells. On the other hand, with high LET radiation (such as carbon ions), the particle directly acts on the phosphodiester bond of DNA inducing thus clustered damage which is then less amenable to be repaired. From these observations came the concept of Oxygen Enhancement Ratio (OER), which is an inverse relationship between dependence on oxygen, inducing cellular damage and the mass of the ion species (Fig. 6.28).\n\nA line graph presents R B E versus L E T. The O E R and R B E curves intersect, where O E R slowly declines while R B E rises to its highest peak before declining.\n\nFig. 6.28\nSchematic representation of the relationship between OER and RBE in function of LET"}
{"_id": "Radiology$$$1c181839-d5c9-4295-a6fc-ef38e98bffc2", "text": "A line graph presents R B E versus L E T. The O E R and R B E curves intersect, where O E R slowly declines while R B E rises to its highest peak before declining."}
{"_id": "Radiology$$$f7e970f7-aa65-48b0-b1ca-fcdf6173f1b0", "text": "The cell cycle status has been shown to be influential in determining radiation sensitivity [191]. Cells in the G2/M phases of the cell cycle are most sensitive to radiation while cells in late S phase are most resistant. This increased radiation sensitivity in G2/M appears to be related to chromatin condensation as effective DNA damage repair is hindered. Unlike low LET radiation, no significant effects of radiation sensitivity on the cell cycle distribution were observed when employing high LET radiation such as carbon ions [192]."}
{"_id": "Radiology$$$bce93966-ab16-48ab-860c-4783bab908d8", "text": "The rationale behind fractionated RT, beside the cell-sparing effect, is based on cell cycle radiation sensitivity. Fractionation allows tumor cells in a radiation resistant cell cycle phase to switch/move into a more radiation sensitive phase before the next fraction is applied [193]. However, as the cell cycle distribution is not affecting radiation sensitivity for high LET radiation, fractionated RT would therefore be less beneficial. Overall, carbon ion RT has several benefits (Fig. 6.29).\n\nA diagram illustrates that the energy, L E T, and R B E are represented by isosceles triangles with the apex pointing to the left, while O E R, cell cycle dependence, and fractionation dependence have the apex of isosceles triangles pointing to the right.\n\nFig. 6.29\nSummary comparison between photon irradiation and carbon ion irradiation"}
{"_id": "Radiology$$$d00b1121-7ea0-4da9-bab0-29df5ff73b38", "text": "A diagram illustrates that the energy, L E T, and R B E are represented by isosceles triangles with the apex pointing to the left, while O E R, cell cycle dependence, and fractionation dependence have the apex of isosceles triangles pointing to the right."}
{"_id": "Radiology$$$fdee5f12-9510-4423-bab3-b0663585871d", "text": "Hadrontherapy with carbon ion (carbon therapy, CT) is a RT technique intended to destroy cells by irradiating them with a beam of carbon ions particles. This therapy requires heavy, specific equipment derived from research in particle physics including source and particle accelerator (synchrotron or cyclotron), device for controlling the treatment beam and preparation devices, for the conduct and control of processing. This equipment leads to very heavy material and financial investments and the need for multidisciplinary cooperation for their use."}
{"_id": "Radiology$$$2168ba39-b864-4c31-a7e1-23738e2e3988", "text": "Compared to X-rays (conventional RT) which pass through the whole body and therefore irradiate as healthy cells pass, the carbon ions stop at the desired depth (therefore at the level of the tumor). These ions, once arrived in the tumor cells, create more serious lesions than with other treatments at the level of its genetic material. As their action is intense and the beam precisely defined, tumor cells can be very precisely targeted. These tumor cells do not die immediately, but they are no longer able to multiply and lose their immortality. In addition, the number of sessions in carbon therapy can be much smaller than that required in conventional RT. Moreover, additional chemotherapy is rarely required, which means less fatigue for the patient."}
{"_id": "Radiology$$$8f39358d-1368-49c7-a0ff-9157a1c8dc43", "text": "Carbon therapy can target inoperable tumors and particularly radioresistant, in particular when they are in a situation of hypoxia, a common cause of failure of conventional RT. Accordingly, carbon therapy is intended for the treatment of inoperable tumors or incompletely resectable as well as radioresistant surrounded by radiosensitive healthy tissue. The main indications of this therapy are cystic adenoid carcinomas, tumors of the sinuses of the face and salivary glands, mucous malignant melanomas, chordomas and chondrosarcomas of the base of the skull, sarcomas of the axial skeleton and soft tissues, unresectable or in resection incomplete, unresectable local recurrences of rectal cancer, large hepatocarcinomas (diameter greater than 4\u20135\u00a0cm), choroid malignant melanomas and eye tumors, prostate tumors, tumors of the cervix, and stage I NSCLC [188, 194]."}
{"_id": "Radiology$$$10e80a66-1c50-4b1e-8039-94a7aebd9aaa", "text": "All these pathologies to which carbon therapy is applied form a heterogeneous group for which there is a wide variety of therapeutic approaches ranging from surgery to very high-techRT, with or without the combination of several other treatments. According to the ClinicalTrials.\u200bgov website, 31 clinical trials comparing C-ions to either protons or photon therapy were found as recruiting, active or completed."}
{"_id": "Radiology$$$1f2f14de-1326-45db-af9f-32c06edfae34", "text": "According to a global assessment of clinical experiences in Japan, the optimization of the therapeutic protocol has progressed over many years and is dependent on the tumor site [195]. For a given disease entity, the therapeutic schedule (e.g., carbon therapy alone, with chemotherapy or in a preoperative setting) is initially based on scientific evidence."}
{"_id": "Radiology$$$1eddd96c-58f0-43ca-81af-292a2cb80f2d", "text": "Some of the previously published clinical studies suggest that carbon-therapy would potentially be more effective than conventional RT in case of cystic adenoid carcinomas of the head and neck, tumors of the salivary glands in absence of complete resection, chordomas and chondrosarcomas of the base of the skull, and NSCLC tumors while late toxicities which have been reported in particular in some cases of chordomas and skull base chondrosarcomas, soft tissue and skeletal sarcomas axial, choroid melanomas and eye tumors [196\u2013198]."}
{"_id": "Radiology$$$41663090-05ab-4d48-a06e-62ae6392c0e1", "text": "In total, the analysis of the most recent literature and agency reports of evaluations are consistent to indicate that there is still little data available to conclude definitively on the efficiency-safety balance. Carbon therapy appears to be a promising technique for the treatment of certain not resectable or radioresistant tumors, surrounded by healthy radiosensitive tissue and is currently studied in clinical trials. The long-term side effects are also not yet well known. Indeed, looking at the dose/depth profile of particle beams, the effect of entrance dose and fragment tail on the surrounding healthy tissue is highly reduced compared to conventional therapy. Yet, this dose is not negligible and is an underdeveloped field in radiation research."}
{"_id": "Radiology$$$796446bb-d219-487d-addb-8bc1e5316050", "text": "As described previously, only protons and carbon ions are the types of hadrons used to treat solid tumors so far, however several kind of hadrons, such as neutrons, charged pions, antiprotons, helium ions, and other light ions nuclei (like lithium, oxygen, up to silicon ions) have been either used or planned to be tested for oncological treatment [199]."}
{"_id": "Radiology$$$92155d0f-1542-4df5-a974-4f45ecb39241", "text": "In recent years, thanks to their physical and biological properties complementary to protons and carbon ions, a renewed interest in using helium ions (4He) for RT has been observed. This is also tangible from the fact that the first European He-ion treatment is about to go into operation at the Heidelberg Ion-beam Therapy (HIT) center and that at NIRS, in Japan, a multi-ion therapy concept including He ions is currently set up [200, 201]. In addition, the National Center for Oncological Hadrontherapy (CNAO) in Italy is also planning to treat patients with He ions in the future since a source will be available for non-clinical/preclinical research by Spring 2023. In the past, about 2000 patients were successfully treated at the Lawrence Berkeley National Laboratory with passively scattered He ions in the US heavy ion therapy project [202]."}
{"_id": "Radiology$$$71fe370d-f9aa-4fb0-afb3-49447ab327b9", "text": "He ions are very attractive for cancer treatment because they can overcome some of the limitations of protons and carbon ions, while keeping their advantages. Specifically, they can provide favorable biophysical characteristics like the reduced lateral scattering and enhanced biological damage to deep-seated tumors like heavier ions, while simultaneously lessening particle fragmentation in distal healthy tissues as observed with lighter protons [203]."}
{"_id": "Radiology$$$beccedf0-a8cc-445b-adf4-dd0ddba15712", "text": "Radiobiologically speaking, helium ions, being in a similar LET range as protons, offer an improved RBE and OER, while potentially allowing for less demanding biological modeling compared to carbon ions. The helium ions radiobiological characterizations performed so far showed a higher RBE in the Bragg Peak region of up to 1.6, and the OER at 10% survival was found to decrease from 2.9 to 2.6 in the peak region when compared to protons [204]. These are certainly advantageous features for eradication of radioresistant hypoxic tumors. In addition, helium offers a decreased lateral scatter effect versus proton, with less fragmentation tail dose versus carbon [205]."}
{"_id": "Radiology$$$8a6f7c8a-6dc6-411d-a92e-2102c122ee18", "text": "Especially for pediatric patients, helium ions could have the potential to reduce the volume of irradiated normal tissue, without bringing the disadvantage of additional dose caused by the fragmentation tail, like it is observed for carbon ions [206]. This could not only improve the dose distribution for small tumor lesions, but also reduce the total overall dose for children suffering from large tumors, also considering that it is expected that the number of secondary neutrons is very low and the dose due to neutrons may even be lower than in proton therapy [207]. Last but not least, it is important to take into account that helium hadrontherapy would also be less expensive than carbon ions, as they may be produced in cyclotrons rather than synchrotrons."}
{"_id": "Radiology$$$8c5e4bd6-b12c-4947-938c-c986ea337c87", "text": "From the modeling point of view, the very few RBE models existing for these ions still need to be integrated and benchmarked by experimental data on radiation-induced tumor cell killing, as well as normal cell response. However, He-ion RBE data for cell survival are still very scarce, and intensive experimental campaigns need to be performed [203]."}
{"_id": "Radiology$$$20699de7-2203-41d7-93e2-16d6d85015df", "text": "Oxygen ions are currently considered as a potential alternative to carbon ions. Because of their mass, they have less lateral scattering which is in favor of the tumor conformality. The high LET of oxygen ions when compared to carbon ions is associated with higher RBE and therefore to better treatment effectiveness in particular with respect to hypoxic tumors. Compared to carbon ions, oxygen ions produce more nuclear fragments, which need to be carefully investigated, not only in-field but also out-of-field, laterally and beyond the Bragg peak, to study the effect of the mixed radiation field in the healthy tissues surrounding the tumor target [208] (Box 6.20)."}
{"_id": "Radiology$$$641eb4b8-d362-452c-aa6c-db1a9cfd0ca5", "text": "Helium ions versus Protons:\n\u2193 Lateral scattering\n\n\u2191 RBE\n\n\u2191 OER\n\n\u2193 Secondary neutrons\n\n\nHelium ions versus carbon ions:\n\u2193 Fragmentation tail\n\n\u2193 Costs"}
{"_id": "Radiology$$$4732161c-aaab-4a6d-8671-65d60fbf99f8", "text": "Helium ions versus Protons:\n\u2193 Lateral scattering\n\n\u2191 RBE\n\n\u2191 OER\n\n\u2193 Secondary neutrons"}
{"_id": "Radiology$$$f6f9d4a5-ea60-47f7-bc50-b86ee9448e19", "text": "Particles used for therapy need to have sufficient energy to penetrate the patient\u2019s body to the desired depth, i.e., several hundred MeV/u. At therapy centers, the acceleration is done by the use of circular accelerators, which can be divided into two types, the cyclotron and the synchrotron. Another way of accelerating particles is through the use of high-frequency linear accelerators, so-called LINACS, which at the moment are getting more and more in the focus. The different accelerator types are summarized in Table 6.11."}
{"_id": "Radiology$$$b07293c2-a761-44f1-ae5f-9665e10cfa2e", "text": "A classical cyclotron consists of a large electromagnet with hollow, D-shaped electrodes, called Dees in-between. The Dees are separated by a small gap, which is the acceleration region of the cyclotron. The electromagnet has a constant magnetic field perpendicular to the plane of the movement of the particles. The electrodes induce a radiofrequency electric field, which is changing polarization in resonance with the particle movement. The particles are injected in the middle of the gap. In this gap, the ions are accelerated the first time, upon entering the first Dee there is no electric acceleration field, keeping the particle at constant velocity. Within the electrode, the magnetic field bends the particle due to the Lorentz force and brings it on a circular path with radius\n\n (6.8)with m0 the mass, v the velocity, q the charge of the particle, and B the magnetic field of the electromagnet. After a half circle, the particle enters the acceleration gap and is accelerated until the second Dee is entered, where again a half circle is formed, which has a larger radius but is traveled within the same time. Acceleration only happens if the frequency f of the electric field, the so-called cyclotron frequency, is adapted to the time, the particle needs to traverse the Dee and therefore to the charge q and the mass m of the particle and the magnetic field B:\n\n (6.9)but stays constant in time. This process happens until the radius corresponds to the extraction radius R and the particle is extracted with an energy of\n\n (6.10)Classical cyclotrons are using iron magnets which limit the magnetic field to 1\u20132\u00a0T, if superconducting magnets are used, the magnetic field can be increased, and therefore the size of the cyclotron decreased. This kind of cyclotron only works for non-relativistic particles with velocities v\u00a0\u226a\u00a0c. For higher energies and thus higher velocities, the time for the half circle is not constant anymore. Therefore, they get asynchronous to the constant acceleration frequency. For relativistic particles, the mass m is no longer constant but increases by the factor\n\n (6.11)The cyclotron frequency is now dependent on particle velocity\n\n (6.12)This limits the maximum energies achievable using classical cyclotrons to, e.g., approx. 20 MeV for protons, which is much smaller than the needed energies for particle therapy. This problem is overcome by two new types: the synchrocyclotron and the isochronous cyclotron. As the synchrocyclotron has a very low duty cycle, it is not usable for particle therapy."}
{"_id": "Radiology$$$95ae8ee5-b9f4-43d7-83ed-de14f0acf9f9", "text": "The isochronous cyclotron makes use of a non-constant magnetic field. Here the magnetic field gets larger by the factor \u03b3 with increasing radius to increase the Lorentz force and balance the mass increase, resulting again in a constant travel time. This increase in magnetic field leads to a defocusing of the beam, which is compensated by alternating-gradient (also called strong) focusing. Technically it is realized by changing the magnet design, into the so-called hill-valley design, in so-called sector cyclotrons. This design results in regions with higher and lower magnetic fields as shown in Fig. 6.30b. At the transition between hill and valley, the magnetic field is bent and a defocusing (valley to hill) and focusing effect (hill to valley) can be achieved. Using this design acceleration to clinical relevant energies for protons is achievable. Furthermore using the isochronous mode together with superconducting magnets allows for small cyclotron sizes of only a few meters diameter. These properties make the isochronous cyclotron the most popular accelerator for proton therapy.\n\n2 diagrams. Diagram A displays the top view and side view of a classical cyclotron. Diagram B exhibits the hill-valley magnet design that connects the higher and lower magnetic fields.\n\nFig. 6.30\n(a) Principle of a classical cyclotron. (b) Hill-valley magnet design"}
{"_id": "Radiology$$$e6a27cc9-8b27-4f7c-8bee-d090b2942ca6", "text": "2 diagrams. Diagram A displays the top view and side view of a classical cyclotron. Diagram B exhibits the hill-valley magnet design that connects the higher and lower magnetic fields."}
{"_id": "Radiology$$$9e8669e7-9286-4fa8-bafb-3f692a652438", "text": "A classical synchrotron consists of an injector, a set of bending and focusing magnets, guiding the particle on a circular track and linear acceleration tracks without magnetic field in between and an extractor as shown in Fig. 6.31a. The injector is basically a linear pre-accelerator, which injects the particles in the ring with a certain energy and a set of inflection magnets which initially bend the particles into the acceleration tube. In contrast to the cyclotron where the particle track is spiral, the particle track stays circular in the synchrotron at all times. To achieve a circular particle track, dipole bending magnets, which bend the particles to stay in the circle, are placed all along the cyclotron. The magnetic field needs to be increased in synchronization with increasing energy and therefore velocity of the accelerated particle, to keep the particles on track. The particles are accelerated close to the speed of light; therefore, the processes happen in the relativistic regime. In the synchrotron, the following requirement, due to the Lorentz force, has to be fulfilled at all times:\n\n (6.13)One can see that the magnetic field has to be increased proportionally to the increased velocity and therefore energy of the particles. Furthermore, quadrupole and even higher order magnets are necessary to focus the particle beam within the vacuum acceleration tube. The quadrupole magnets are able to spatially focus the beam and therefore work as a lens. In contrast to optical lenses, magnetic lenses only focus in one direction and even worse defocuses in the other direction. Therefore magnetic lenses always come in units of pairs, one focusing the x-direction and the other the y-direction. The higher order magnets are able to correct even the smallest aberrations and therefore ensure that the beam keeps on track. Modern synchrotrons also take advantage of the strong focusing to further reduce beam diameter, as in the isochronous cyclotron. The energy of the particles is increased in the linear acceleration tracks, where high-frequency electric fields are applied in cavity resonators, which again have to be synchronized with the velocity of the particles. Both magnetic field strength and phase of the electric field have to be adapted to the particle\u2019s energy in each circle. The vacuum chamber for particles in a synchrotron can, due to the circular path, be a thin torus rather than a disk as it is for cyclotrons, which allows a more cost-efficient construction. The last part is the extractor, which consist of sets of dipole magnets which extract the particles once the desired energy is reached. The synchrotron by design can only operate in a quite slow pulsed mode, but has the advantage that the energy can be easily varied pulse by pulse. Synchrotrons are mainly used when different particle types (protons, carbon ions, and others) are used in the same facility, as the magnet tuning allows flexibility to flexibly change the accelerated ions, which is not possible in cyclotrons (Box 6.21).\n\n2 diagrams. Diagram A exhibits the circular synchrotron principle which includes extraction magnets, particle beam, acceleration cavity, injector, inflector, bending magnets, and focussing magnets. Diagram B displays the dipole magnets and the x and y-focused quadrupole magnets.\n\nFig. 6.31\n(a) Principle of a synchrotron. (b) A positively charged beam coming from the front is deflected by Dipole magnets and focused by quadrupole magnets"}
{"_id": "Radiology$$$b6c52c10-a788-465e-9dd6-7eab5715e832", "text": "2 diagrams. Diagram A exhibits the circular synchrotron principle which includes extraction magnets, particle beam, acceleration cavity, injector, inflector, bending magnets, and focussing magnets. Diagram B displays the dipole magnets and the x and y-focused quadrupole magnets."}
{"_id": "Radiology$$$f9c90ba2-1b47-4621-b814-739d6c58e5d9", "text": "Cyclotrons consist of a big magnet and two, complex shaped electrodes.\n\nCompact design of asynchronous cyclotrons allows for small sizes of a few meters diameter.\n\nAsynchronous cyclotrons most popular accelerator for proton therapy.\n\nSynchrotrons consist of a set of bending and focusing magnets and field free drift tracks, which are arranged in a circle.\n\nSynchrotrons can accelerate different particle types (protons, helium, carbon, and also heavier ions) with the same design."}
{"_id": "Radiology$$$a470d3c2-86ef-4100-a006-8408564a6e2d", "text": "Cyclotrons consist of a big magnet and two, complex shaped electrodes."}
{"_id": "Radiology$$$fd0d2c6f-cf5f-4d7b-95de-d9a548ac403a", "text": "Compact design of asynchronous cyclotrons allows for small sizes of a few meters diameter."}
{"_id": "Radiology$$$5488262d-2aa6-4cb5-b984-db1fb1afe6f4", "text": "Synchrotrons consist of a set of bending and focusing magnets and field free drift tracks, which are arranged in a circle."}
{"_id": "Radiology$$$f02ee241-7934-4029-b95d-14854f6806fb", "text": "Synchrotrons can accelerate different particle types (protons, helium, carbon, and also heavier ions) with the same design."}
{"_id": "Radiology$$$53af4341-aaea-4089-9f92-976029438efb", "text": "A high-frequency linear accelerator (LINAC) represents a complementary type of accelerator compared to cyclotron and synchrotron. It is based on the same principle as the modern clinical LINACs for X-ray therapy, as commonly used worldwide to accelerate electrons to high energies and stimulate them to emit X-rays at several MeV energies. Due to the light weight of the electrons, these accelerators can be very compact and directly mounted on the application gantry. For particles such as protons and heavier ions in contrast, more complex technological developments are necessary. Although already proposed in the 1990s, the technology for particle LINACs still is in its infancy, with only a few projects worldwide [209, 210]. Radiofrequency LINACs are based on the principle to accelerate a bunch of particles in cavity resonators as shown in Fig. 6.32a. The particles are synchronized to the applied alternating electric field. They are accelerated when they are in the acceleration space. When the field commutes, the particles are shielded in a field free drift space. The shielding also serves as electrodes for the electric field. When the particles enter the next acceleration space, due to alternation of field again see an acceleration electric field. This process is continued until the final energy is reached. Particle LINACs in the so-called all-linac approach consist of different types of acceleration cavities shown in Fig. 6.32b, after the ion source, each suited for a different particle energy range. For energies up to ~5\u00a0MeV, a radiofrequency quadrupole (RFQ) is used for acceleration. For energies between 5 and 70\u00a0MeV, the acceleration is performed in a SCDTL (side-coupled drift tube LINAC), followed by the coupled cavity LINAC (CCL) up to the maximum energies of ~250 MeV. The acceleration is performed in an electric field in which the resonators are oscillating with 3 GHz allowing for high electric fields and a shrink the system length to approximate of ~30\u00a0m, which can be fit into a clinical building. The RFQ is a quadrupole electromagnet, which is oscillating with a 3 GHz radiofrequency. Special longitudinal design of the electrodes makes it possible to push the particle beam through the RFQ and therefore accelerate it. Furthermore, the RFQ bunches the particle beam so that it fits the needs of the SCDTL and CCL structures, which can only accelerate a bunch of particles. The SCDTL accelerates the beam in the mid energy range 5 and 70 MeV. The SCDTL structure as shown in Fig. 6.32c consists of a huge cavity resonator where drift tubes are mounted. In the cavity, the alternating electric field is built and the tubes serve as field free drift space. The length of the drift tube must be synchronized to the velocity of the particles, so that the particles only see the acceleration of the oscillating field. The length of the ith tube is:\n\n (6.14)with\n\n (6.15)describing the velocity v of the particle in units of velocity of light c and \u03bbRF being the wavelength of the oscillating field. For a 3 GHz radiofrequency, the wavelength is\n\n (6.16)For an acceleration between 5 MeV (\u03b2\u00a0=\u00a00.1) and 70 MeV (\u03b2\u00a0=\u00a00.36), this results in a drift tube length of 1\u20133.6 cm. For higher energies, a coupled cavity LINAC (CCL) system is used (Fig. 6.32d). The design of the structure is different compared to SCDTL. Here the field is coupled in through a cavity, which makes them more efficient for higher particle velocities. The manufacturing of SCDTL and CCL structures is quite complicated as material defects such as welding seams or supernatant material will disturb the electric field. New production techniques such as 3D metal printing will offer possibilities of high precision manufacturing of such structures.\n\nDiagram A depicts field free drift space and acceleration denoted by leftward arrows in the linear acceleration principle. Diagram B exhibits the proton L I N A C system which includes ion source and R F Q which has low energy, and S C D T L structures with mid energy among others. Diagram C indicates a field free drift space and acceleration cavity in a side-coupled drift tube structure. Diagram D displays coupling cavity, and others in a coupled cavity structure.\n\nFig. 6.32\n(a) Linear acceleration principle. (b) A proton LINAC system. (c) Principle of a side-coupled drift tube LINAC (SCDTL) structure (cut through). (d) Principle of a coupled cavity LINAC structure (cut through)"}
{"_id": "Radiology$$$dac81871-d96e-4230-9379-a6bd0820148c", "text": "Diagram A depicts field free drift space and acceleration denoted by leftward arrows in the linear acceleration principle. Diagram B exhibits the proton L I N A C system which includes ion source and R F Q which has low energy, and S C D T L structures with mid energy among others. Diagram C indicates a field free drift space and acceleration cavity in a side-coupled drift tube structure. Diagram D displays coupling cavity, and others in a coupled cavity structure."}
{"_id": "Radiology$$$89a520dc-3a07-423a-b2ae-8390baba46d5", "text": "High-frequency LINACs for particle therapy are an emerging technology.\n\nComplex cavities accelerate beams with a GHz frequency.\n\nCavity size has to be precisely aligned with particle velocity."}
{"_id": "Radiology$$$d167fff1-69c9-44db-ad65-dc78829d628d", "text": "After the accelerator, the particle beam needs to be guided to the patient. For beam guiding as in the acceleration process of the synchrotron, sets of magnets are used. Dipole magnets are used for bending the beam, whereas quadrupole magnets are used to keep the beam on track in the vacuum tube. Before the patient also beam diagnostics, such as a dosimetry chamber is placed. A quite important step is also the beam shaping, which defines the energy and size of the beam. In most centers, pencil beam scanning is used, which allows to get rid of a collimator close to the patient and therefore reduce unwanted exposure of the patient with neutrons coming from the collimator. The energy selection can be done away from the patient, and it must only be guaranteed that the beam has a defined profile modern therapy centers mostly rely on the application of radiation from different angles, which makes it necessary to move the beam around the patient. This is done by the use of so-called gantries, which are rotatable. The beam is deflected on the gantry and then can be delivered at a defined position. In particle therapy, due to the velocity of the particles and their rigidity, i.e., the resistance of a particle to be bent by a magnetic field, huge and especially heavy magnets must be used, which make gantries quite large and heavy. A conventional proton gantry is in the order of 150\u00a0t with a size of several meters, whereas for carbon ions it can be up to 600\u2013700\u00a0t (Box 6.22)."}
{"_id": "Radiology$$$7b1c191d-2977-452c-905c-225eb70b6bb1", "text": "Nano-objects exhibit different physical and chemical properties compared to the related bulk materials due to a high surface-to-volume ratio, a metric that decreases with the size of the object.\n\nThe surface of nanoparticles can be functionalized to actively target cancer cells opening avenues for a use in nanomedicine field. Recognition and clearance of the nano-objects from the bloodstream by the reticuloendothelial system (i.e., resident macrophages in liver, spleen, lungs) remain the main challenge.\n\nNanoparticles have the potential to be used to efficiently and specifically deliver drugs to the tumor, to produce heat in hyperthermia therapy, and to sensitize cancer cells to radiotherapy.\n\nTranslation of nanoparticles to the clinic remains poor due to hurdles related to their large-scale manufacturing and toxicity studies."}
{"_id": "Radiology$$$ff75051b-3445-47f4-bf42-eaa08bf89b6e", "text": "Nano-objects exhibit different physical and chemical properties compared to the related bulk materials due to a high surface-to-volume ratio, a metric that decreases with the size of the object."}
{"_id": "Radiology$$$1fd176ed-3a1a-49d7-9c27-1d3fb7340e7b", "text": "The surface of nanoparticles can be functionalized to actively target cancer cells opening avenues for a use in nanomedicine field. Recognition and clearance of the nano-objects from the bloodstream by the reticuloendothelial system (i.e., resident macrophages in liver, spleen, lungs) remain the main challenge."}
{"_id": "Radiology$$$e07b24d8-8b04-419d-9f19-ccf389d4fdd5", "text": "Nanoparticles have the potential to be used to efficiently and specifically deliver drugs to the tumor, to produce heat in hyperthermia therapy, and to sensitize cancer cells to radiotherapy."}
{"_id": "Radiology$$$035066d3-5e3f-44ad-b0c5-d934905261c4", "text": "Translation of nanoparticles to the clinic remains poor due to hurdles related to their large-scale manufacturing and toxicity studies."}
{"_id": "Radiology$$$ee5cb384-1a46-4c44-a4b6-e0e7180ae666", "text": "In the last few decades, the use of nanomaterials in medicine has attracted increased interest. A nanoparticle is a particle with at least one of its external dimensions in the size range of 1\u2013100 nm. Due to this small size, nanoparticles exhibit physical, chemical, and optical properties that significantly differ from those of their bulk material, which makes them emerge as promising tools to improve the efficacy of cancer diagnosis and therapy. This section describes how nanoparticles have the potential to contribute to certain cancer therapies that are discussed in Sects. 6.4 and 6.5, including the delivery of chemotherapeutic drugs, targeted therapy, hyperthermia, and RT (Box 6.23)."}
{"_id": "Radiology$$$0c07d0c6-7166-4dee-8c18-5df856bb2c08", "text": "Nanoparticles can typically be classified based upon their material (organic or inorganic), shape, surface, or size (Fig. 6.33). As such, a broad and versatile spectrum of nanoparticles exists. Organic nanoparticles include liposomes, polymeric nanoparticles, dendrimers, and micelles. On the other hand, examples of inorganic nanoparticles are metallic nanoparticles, magnetic nanoparticles, silica nanoparticles, carbon-based nanoparticles, and quantum dots. The type of nanoparticle to use depends on its application in medicine.\n\nA diagram displays the surface with charge and functionalization, material, size, and shape of a nanoparticle and its applications that include drug delivery, hyperthermia, and radiosensitization.\n\nFig. 6.33\nThe versatility of nanoparticles and their potential applications in cancer therapy"}
{"_id": "Radiology$$$b2aa1552-8864-4c85-b798-569c58f0c1e5", "text": "A diagram displays the surface with charge and functionalization, material, size, and shape of a nanoparticle and its applications that include drug delivery, hyperthermia, and radiosensitization."}
{"_id": "Radiology$$$82e7c13f-b69c-4373-97c4-5e6b2dc96a43", "text": "A major challenge in nanomedicine is the immediate and inevitable \u201cmasking\u201d of nanoparticles by proteins, lipids, carbohydrates, and nucleic acids once the nanoparticles are introduced into the blood circulation, forming a \u201cbiocorona.\u201d Subsequently, the adsorbed surface proteins are recognized by the abundant phagocytic cells in the liver and the spleen, causing the rapid trapping and removal of nanoparticles from the bloodstream. A limited blood circulation time prevents nanoparticles from reaching the tumor cells. In order to improve the biocompatibility, solubility, and stability of the nanoparticles in physiological media, the surface of nanoparticles is usually coated with polymers, generating an electrostatic repulsion and/or a physical barrier between the nanoparticles. Depending on the applied coating, the net surface charge of the nanoparticle can be positive, negative, or neutral, which strongly influences the biological fate and effects of the nanoparticles. One of the most commonly used polymers for nanoparticle coating is polyethylene glycol (PEG), which reduces the biocorona formation by neutralizing the nanoparticle surface charge and giving the nanoparticle a \u201cstealth\u201d character. This delays their recognition and subsequent sequestration of the nanoparticles by the reticuloendothelial system (RES), prolonging the blood circulation time."}
{"_id": "Radiology$$$acf4980e-23ef-4cb5-a1cd-374642617f62", "text": "An important physical property of nanoparticles is the large surface area-to-volume ratio. When the size of the nanoparticles decreases, a larger proportion of their atoms or molecules are displayed on the particle\u2019s surface, rather than in the particle\u2019s core, increasing the surface area-to-volume ratio. This ratio decreases with the size of nanoparticles modifying their physical and chemical properties compared to bulk materials. Furthermore, the large surface area-to-volume ratio facilitates the functionalization of the nanoparticle surface with multiple moieties, supporting their multifunctional applications in cancer diagnosis and therapy, which is discussed in more detail below."}
{"_id": "Radiology$$$48c90aa4-7708-4718-ba10-5722bf38c4e8", "text": "In order to use nanoparticles in cancer remediation applications, nanoparticles need to reach and accumulate in the tumor tissue. Rapidly growing tumors stimulate the formation of new blood vessels to supply the tumor cells with a sufficient amount of oxygen and nutrients. The newly formed tumor vasculature is usually characterized by the presence of abnormal, leaky, and immature blood vessels, which are poorly aligned with a defective endothelium. Consequently, nano-sized particles can efficiently pass through inter-endothelial gaps and accumulate in the tumor. Furthermore, the decreased level of lymphatic drainage promotes the nanoparticle tumor retention. This \u201cpassive\u201d process is known as the enhanced permeability and retention (EPR) effect. Importantly, the efficacy of the EPR effect is limited due to the heterogeneity of the vascular structure within the tumor, at different tumor stages and between different tumor types. Furthermore, despite the success of the EPR effect in preclinical tumor models, the efficacy and clinical translation of cancer nanomedicine remain poor, indicating that the EPR effect is less reliable in human tumors. In fact, research demonstrated that extravasation of nanoparticles into the tumor via active trans-endothelial transport pathways occurs more frequently than passive diffusion and thus should not be underestimated [211]."}
{"_id": "Radiology$$$87bb66f3-58ce-4b34-ba65-e954f014510b", "text": "A strategy to complement the EPR effect and to improve the tumor accumulation efficiency of nanoparticles is the functionalization of the nanoparticle surface with cancer-targeting ligands. Cancer-targeting ligands are often specific for factors that are unique or upregulated in cancer cells and that are mostly involved in processes such as tumor progression, invasion, metastasis, and angiogenesis. In general, these targeting ligands can be categorized in five main classes: small molecules, peptides, protein domains, antibodies, and nucleic-acid based aptamers. Examples of cancer-specific targeting ligands are folic acid (FA) (essential for DNA synthesis), cyclic arginine-glycine-aspartic acid (cRGD) peptide (a cell adhesion motif with a high affinity for \u03b1\u03b2-integrins), and targeting ligands that can bind to membrane receptors, such as EGFR or VEGFR. Thanks to the large surface area-to-volume ratio of nanoparticles, multiple targeting molecules can be conjugated to the nanoparticles, which enables multivalent interaction with membrane receptors, increasing the tumor uptake and the intratumoral retention time."}
{"_id": "Radiology$$$c2217a0f-43b5-440b-bb5e-4d54264f8233", "text": "Nanoparticles can be used as promising tools to enhance the efficiency of multiple anticancer therapies, including the delivery of chemotherapeutic drugs, hyperthermal therapy, and RT."}
{"_id": "Radiology$$$e019c229-2404-4a21-b06d-420a5d586834", "text": "The conventional chemotherapeutic treatment strategies have certain drawbacks linked to the systemic administration and nonspecific distribution of the drugs through the body. This can, for instance, result in limited accessibility of the drug to the tumor, requiring high therapeutic doses and causing off-target toxicity due to damage to healthy cells. Besides, cancers can develop resistance to chemotherapeutic drugs, which is an important factor in treatment failure. Nanoparticles have the potential to improve these aspects by acting as drug delivery systems (DDS). In fact, nanoparticles can efficiently hold a massive payload of the drug, improving the solubility and stability of the drug in the blood circulation. In addition, they enable targeted delivery of the drug to the tumor sites and promote transport across membranes. Altogether, nanoparticle-based drug delivery has the potential to enhance the efficacy of the chemotherapeutic treatment, while minimizing the side effects. Furthermore, in order to counteract multidrug resistance, nanoparticles can be used to deliver multiple therapeutic agents, including chemo-sensitizers, small interfering RNA, microRNA, enhancing antitumor effects."}
{"_id": "Radiology$$$3303f251-83b4-43d5-aa78-9a2abe581008", "text": "Therapeutic agents can typically be loaded on nanoparticles through physical packaging, covalent binding, or electrostatic complexation. Lipid-based nanoparticles, such as liposomes, consisting out of a double lipid layer are the most popular structures in nanoparticle-based drug delivery thanks to their excellent biocompatibility and biodegradability. Furthermore, they can transport both hydrophilic and hydrophobic drugs, encapsulated in the aqueous core and the bilayer membrane, respectively. Other organic nanoplatforms used for drug delivery include polymers, micelles, and dendrimers. On the other hand, inorganic nanoparticles such as carbon-based nanotubes, gold nanoparticles, silica nanoparticles, and iron oxide nanoparticles are also used as drug delivery systems because of their advanced multi-functionality, excellent stability, high drug payload, and unique surface properties."}
{"_id": "Radiology$$$e20cec4b-2329-4f12-a7a5-dbc95c48e8e5", "text": "To improve the precision of drug delivery, it is possible to engineer a cancer-targeted, stimulus-sensitive DDS, which releases the drug at the tumor site in a controlled and sustained manner upon encountering an endogenous or exogenous trigger, without affecting the regions near the tumor site. The tumor microenvironment features conditions that substantially differ from those in normal tissues, such as an acidic pH, high enzyme levels of matrix metalloproteinases (MMPs) and proteases, hypoxia, metabolic shift to anaerobic glycolysis, and a high redox activity. These endogenous stimuli can induce nanoparticle degradation and subsequent drug release. The development of nanocarriers sensitive for exogenous stimuli such as near infrared light, heat or sound waves enables an \u201con-demand\u201d drug delivery that is tightly controlled from outside the body [212]."}
{"_id": "Radiology$$$33482051-f50a-4f61-8ad8-04b2e87681d5", "text": "As mentioned in a previous section, hyperthermia can help in tumor control thanks to its tumor vasculature effect. Briefly, hyperthermia triggers vasodilation. In healthy vasculature, it helps to efficiently dissipate the heat and avoid tissue damage. However, in the aberrant organization and structure of tumor vasculature, it initially increases the blood flow and oxygen supply to the tumor tissue until the heat accumulated in the tissue reaches 42\u00a0\u00b0C triggering the collapse of tumor blood vessels that promotes cancer cell death. Therefore, it is important to localize hyperthermia to the tumor tissue while avoiding prolonged exposure of healthy cells to elevated temperatures."}
{"_id": "Radiology$$$1a315a6f-60e8-4b51-b943-1e348781439f", "text": "Interestingly, the increase in tumor blood flow induced by hyperthermia can be used to sensitize cancer cells and to enhance the delivery of drugs improving the efficacy of chemotherapy and RT, respectively. Nanoparticles have unique properties, which enables them to efficiently convert incident energy into heat. For instance, alternating magnetic fields activate magnetic nanoparticles, such as iron oxide nanoparticles, stimulating heat production. On the other hand, plasmonic nanoparticles, such as gold nanoparticles, typically hold a unique optical characteristic called the surface plasmon resonance (SPR). This phenomenon implies the interaction of light of a specific wavelength with the free electrons on the surface of the nanoparticle, resulting in the absorbance and scattering of light, and the generation of heat [213]. Finally, carbon nanotubes absorb electromagnetic radiation over an extremely broad frequency spectrum, ranging from near infrared light to radiofrequency waves. The absorbance of electromagnetic energy induces electron excitation and relaxation within the nanoparticle, causing heat production. The ability to target and accumulate nanoparticles in the tumor tissue allows the nanoparticle-mediated heat generation to be localized at the tumor site."}
{"_id": "Radiology$$$4610ece5-f312-4b92-af36-f9210eebcd7a", "text": "In 2004, it was demonstrated that gold nano-objects injected in tumors can enhance the effect of radiation by improving tumor control in mice treated with kilovoltage X-rays. Since this pioneering work, extensive experimental validations were performed evidencing the potential of a large series of metal-based nanoparticles as radiosensitizer at preclinical level. However, the mechanism(s) of action, a complex mixture between physical, chemical, and biological contributions is still under debate [214]. Physical contribution resides in their ability to increase the dose deposited (radioenhancement effect) via the emission of secondary Auger and photoelectrons following the interaction with IR. The capacity of nanoparticles to increase radiolysis processes leading to a higher oxidative stress in cellular systems constitutes a chemical contribution to the mechanism of action. Finally, the biological effect is based on cell detoxification and DNA repair system impairment, enabling to potentiate the effect of irradiation (radiosensitization effect) [215, 216]."}
{"_id": "Radiology$$$6ba5ecb8-5b26-4c0e-a3f7-d9826a538b7e", "text": "Researchers designed complex and multimodal nanoplatforms enabling the simultaneous use of nano-objects for diagnostic and therapeutic applications. These nano-objects are called \u201ctheranostics\u201d agents. They enable a non-invasive and real-time tracking of the in vivo nanomaterial distribution and facilitate the dose and toxicity management, as discussed previously, fine-tuning the patient-specific treatment protocol [217]. Superparamagnetic iron oxide nanoparticles (SPIONs) is one interesting example of theranostic agent. While it has been used for years as contrast agents in MRI, enabling to increase the quality of images used for diagnostics (with higher spatial resolution), these nanoparticles have recently shown radiosensitizing properties. The presence of these nano-objects within the tumor allows to better define the area to treat and to increase the efficiency of the treatment. These SPIONs can also be coupled to chemotherapeutic drugs, such as doxorubicin, further increasing their therapeutic impact."}
{"_id": "Radiology$$$160d8b3b-a104-4ebe-b5d2-56266384ddc1", "text": "Currently, only a relatively small amount of nano-objects are FDA approved for cancer treatment, since the translation toward clinics is an expensive and time-consuming process that is associated with two main challenges [218]:\nLarge-Scale Manufacture\nTo enable large clinical trials, drugs have to be produced on a large scale. The Good Manufacturing Practices (GMP) of nanoparticle technology is characterized by a high complexity compared to conventional formulation technologies that usually contain free drug dispersed in a given medium. Indeed, the efficacy of nano-objects is determined by optimal parameters that should be preserved during the scaling-up process. Therefore, nanoparticles have to be manufactured with proper quality standards and with a strict batch-to-batch reproducibility to ensure product specification. Finally, they have to be stable during long-duration storage ensuring the product quality at the time of clinical administration.\n\nExtensive Toxicity Studies\nBefore a drug candidate can be tested in humans, its safety profile must be proven in animal models. These preliminary tests allow a thorough understanding of its pharmacokinetics and toxicity as well as the establishment of safe limits for further clinical trials.\nPreclinical in vivo studies have demonstrated nano-object accumulation in liver and spleen for several months post intravenous injection, raising the question of long-term toxicity for which time-consuming approaches are needed. These toxicological studies are governed by specific rules and regulations of Good Laboratory Practice (GLP), a quality system ensuring the uniformity, consistency, reproducibility, and reliability of non-clinical safety tests. Nevertheless, the current regulatory approaches used for the toxicological assessment of conventional drugs may not be appropriate to fully assess the toxicity of nanomaterials requiring the development of new specific approaches."}
{"_id": "Radiology$$$1e317f7d-8d65-49fe-af4a-03cfd96ce7b0", "text": "To enable large clinical trials, drugs have to be produced on a large scale. The Good Manufacturing Practices (GMP) of nanoparticle technology is characterized by a high complexity compared to conventional formulation technologies that usually contain free drug dispersed in a given medium. Indeed, the efficacy of nano-objects is determined by optimal parameters that should be preserved during the scaling-up process. Therefore, nanoparticles have to be manufactured with proper quality standards and with a strict batch-to-batch reproducibility to ensure product specification. Finally, they have to be stable during long-duration storage ensuring the product quality at the time of clinical administration."}
{"_id": "Radiology$$$45d709be-9a31-4525-964a-f314299863af", "text": "Before a drug candidate can be tested in humans, its safety profile must be proven in animal models. These preliminary tests allow a thorough understanding of its pharmacokinetics and toxicity as well as the establishment of safe limits for further clinical trials."}
{"_id": "Radiology$$$cb6bb366-09a4-4384-b768-8d25e1689e8f", "text": "Preclinical in vivo studies have demonstrated nano-object accumulation in liver and spleen for several months post intravenous injection, raising the question of long-term toxicity for which time-consuming approaches are needed. These toxicological studies are governed by specific rules and regulations of Good Laboratory Practice (GLP), a quality system ensuring the uniformity, consistency, reproducibility, and reliability of non-clinical safety tests. Nevertheless, the current regulatory approaches used for the toxicological assessment of conventional drugs may not be appropriate to fully assess the toxicity of nanomaterials requiring the development of new specific approaches."}
{"_id": "Radiology$$$0cf6aaca-5d1d-4928-b3ca-6a2c1680bda1", "text": "Although often used interchangeably, there is a fundamental difference between second and secondary cancers. Second cancer is a more general name for any tumor occurring in patients who have been treated earlier for a first cancer, while the development of a secondary cancer can be ascribed to the treatment for the first cancer. This is not uncommon and should be discussed as part of the process of taking informed consent when explaining the treatment with chemotherapy or RT."}
{"_id": "Radiology$$$3e07f2b4-de05-417d-996b-ec7cf43cb54d", "text": "The risk of developing a secondary malignancy following RT depends on:\nThe organs irradiated\n\nThe age at treatment, with younger patients having an increased risk compared to a teenager or adult\n\nThe total dose of radiation received\n\nThe time from treatment\n\nThe prior use of alkylating agent chemotherapy\n\nUnderlying genetic predisposition"}
{"_id": "Radiology$$$f0d06b50-c36d-4ed9-9dca-7ccfa150e4a5", "text": "The age at treatment, with younger patients having an increased risk compared to a teenager or adult"}
{"_id": "Radiology$$$35543e7e-5e0c-4501-95a5-1c3d9c044b7a", "text": "The risk of developing a secondary tumor is cumulative and increasing over time. However, as age increases, the risk relative to the normal population decreases as cancer becomes more common in the general population as well."}
{"_id": "Radiology$$$30b2b245-7ccf-40bb-8b9e-ded478cfa8f9", "text": "Well-known examples are breast cancer, meningiomas, thyroid cancer, and sarcomas. There is an increased risk of development of breast cancer in girls treated for Hodgkin lymphoma under 16 years of age, with a 20% cumulative incidence of breast cancer by the age of 45 [219]. Girls treated with whole lung RT for Wilms tumor are also at risk of breast cancer. There is a well-documented increased incidence of meningiomas associated with cranial RT, with young age at time of RT and time from treatment associated with higher risk. An excess of thyroid cancer and bone and soft tissue sarcoma are also seen in relation to previous RT [220]."}
{"_id": "Radiology$$$c6fe7b5e-de92-4d0e-9d16-bed939e0c5a9", "text": "There have been concerns about the \u201clow-dose bath\u201d effect of modern RT techniques such as intensity modulated radiotherapy or arc therapy (IMRT/IMAT) increasing the risk of secondary cancers, compared with simple conformal RT. However, IMRT results in greater conformality and reduces the non-target high dose volume. This may offset the increased volume of normal tissue receiving low-dose irradiation. As of today, the feared increase in secondary cancers has not been proven. A major advantage of proton beam RT is the expected reduced risk of secondary malignancy."}
{"_id": "Radiology$$$5401898b-c612-4750-93f9-d12bcf75be12", "text": "Molecular RT may lead to an increased risk of secondary leukemias and cancers, both from the general effects of irradiation of the whole body, and from organ-specific dose, e.g., thyroid uptake of free radioiodine in meta-iodobenzylguanidine (mIBG) therapy, despite the use of thyroid blockade."}
{"_id": "Radiology$$$74f72f83-36d0-43ce-b7d0-7bceabd37445", "text": "RT is not alone in causing cancer. Chemotherapy, particularly alkylating agents, may predispose to the development of myelodysplasia, secondary leukemias, and other malignancies. Chemotherapy and RT may be synergistic in this regard."}
{"_id": "Radiology$$$10088bc5-fee0-4317-8b6c-53954c4915fa", "text": "Predisposing genetic factors such as retinoblastoma, Li\u2013Fraumeni syndrome, or neurofibromatosis type 1 (NF1) also increase the risk of induction of secondary, but also second, malignancies."}
{"_id": "Radiology$$$62c3ef20-2a20-407d-ad8c-e3e877142308", "text": "The risk is also related to the underlying cancer, with an increase seen after treatment for Hodgkin lymphoma and sarcoma."}
{"_id": "Radiology$$$e4a3f3f8-b70f-49cb-a9d2-2a4f59ebd029", "text": "Finally, lifestyle factors contribute to the risk, hence the importance of emphasizing healthy living choices, for example, smoking cessation, normal body weight, and good intake of fruit and vegetables, in survivors to try to mitigate this where possible."}
{"_id": "Radiology$$$b0dfdea8-5bba-473d-8c22-a85d96beeba1", "text": "Q1.\nWhich statement is true? The Continuous Hyperfractionated Accelerated RadioTherapy (CHART) irradiation protocol is characterized by:(a)\nA fraction size <2 Gy.\n\u00a0(b)\nReduced overall treatment time compared with conventional fractionation.\n\u00a0(c)\nIrradiation is continued during the weekend.\n\u00a0(d)\na, b, and c are all correct.\n\u00a0\n\u00a0Q2.\nWhy is hyperfractionation potentially beneficial when it comes to late normal tissue sparing relative to conventional fractionation?(a)\nThe \u03b1/\u03b2 ratio is high.\n\u00a0(b)\nThe repair of sublethal damage is very effective.\n\u00a0(c)\nThe fraction size <2 Gy.\n\u00a0(d)\nThe number of fractions is larger.\n\u00a0\n\u00a0Q3.\nOn the basis of radiobiological aspects, what would be the optimal number of fractions in a hypofractionated treatment regimen?\n\u00a0Q4.\nWhich of the following is not true about Stereotactic Body Radiation Therapy (SBRT)(a)\nIn SBRT a high dose per fraction is used.\n\u00a0(b)\nSBRT has high conformality.\n\u00a0(c)\nSBRT has a large margin for the beam penumbra.\n\u00a0(d)\nIn SBRT image guidance is required for geometric verification of targets.\n\u00a0\n\u00a0Q5.\nPlease indicate which of the following statements is wrong when it comes to the SBRT treatment planning.(a)\nThe dose is prescribed to lower isodose lines.\n\u00a0(b)\nA homogeneous dose distribution is seen.\n\u00a0(c)\nThere is a sharp dose falloff outside target volume.\n\u00a0(d)\nAn isotropic grid size of 2 mm or finer is recommended for dose calculation.\n\u00a0\n\u00a0Q6.\nBelow are some statements related to how targeted therapy may sensitize tumors to radiation therapy (RT). Please indicate which statements are correct or wrong:(a)\nInhibition of the DNA repair enzyme PARP1 with small molecules is a possible RT sensitizer for all types of tumors.\n\u00a0(b)\nTo increase the function of Bcl-2 is a RT sensitizing strategy.\n\u00a0(c)\nInhibitors toward EGFR is a promising RT sensibilization option for some tumors.\n\u00a0(d)\nReverting hypoxia is a way for RT sensitization.\n\u00a0\n\u00a0Q7.\nPlease name a key reason why RT can be combined with some immune therapies?\n\u00a0Q8.\nHyperthermia has been shown to increase the effect of radiation therapy. Describe a DNA repair pathway that hyperthermia can inhibit.\n\u00a0Q9.\nName an advantage and a disadvantage of photon spatially fractionated radiation therapy (SFRT), proton minibeam radiotherapy (pMBRT) and ion MBRT?\n\u00a0Q10.\nGive an example of a vectorized radiopharmaceutical used in the clinic and outline how it works.\n\u00a0Q11.\nHelium ions are good candidates in RT of tumors. What makes them good candidates?(a)\nHelium ions produce more secondary neutrons compared to protons.\n\u00a0(b)\nHelium ions produce more nuclear fragments compared to carbon ions.\n\u00a0(c)\nHelium ions have higher radiobiological effect (RBE) compared to protons.\n\u00a0(d)\nHelium ions have lower oxygen enhancement ratio (OER) compared to protons."}
{"_id": "Radiology$$$1151b7ee-1b33-43f4-b84b-89bd84a18726", "text": "Which statement is true? The Continuous Hyperfractionated Accelerated RadioTherapy (CHART) irradiation protocol is characterized by:(a)\nA fraction size <2 Gy.\n\u00a0(b)\nReduced overall treatment time compared with conventional fractionation.\n\u00a0(c)\nIrradiation is continued during the weekend.\n\u00a0(d)\na, b, and c are all correct."}
{"_id": "Radiology$$$bcac4d91-11af-4290-af01-8d7a527b59ec", "text": "Why is hyperfractionation potentially beneficial when it comes to late normal tissue sparing relative to conventional fractionation?(a)\nThe \u03b1/\u03b2 ratio is high.\n\u00a0(b)\nThe repair of sublethal damage is very effective.\n\u00a0(c)\nThe fraction size <2 Gy.\n\u00a0(d)\nThe number of fractions is larger."}
{"_id": "Radiology$$$1739109c-c4cc-41c8-9866-2c654e6e7c0e", "text": "On the basis of radiobiological aspects, what would be the optimal number of fractions in a hypofractionated treatment regimen?"}
{"_id": "Radiology$$$d506af86-d942-4492-bdbb-da704f4deb1d", "text": "Which of the following is not true about Stereotactic Body Radiation Therapy (SBRT)(a)\nIn SBRT a high dose per fraction is used.\n\u00a0(b)\nSBRT has high conformality.\n\u00a0(c)\nSBRT has a large margin for the beam penumbra.\n\u00a0(d)\nIn SBRT image guidance is required for geometric verification of targets."}
{"_id": "Radiology$$$31eb710c-a483-40ca-9f17-5b2d9f00df20", "text": "In SBRT image guidance is required for geometric verification of targets."}
{"_id": "Radiology$$$35d9c010-8e1e-4554-b33d-e2d8bc30de77", "text": "Please indicate which of the following statements is wrong when it comes to the SBRT treatment planning.(a)\nThe dose is prescribed to lower isodose lines.\n\u00a0(b)\nA homogeneous dose distribution is seen.\n\u00a0(c)\nThere is a sharp dose falloff outside target volume.\n\u00a0(d)\nAn isotropic grid size of 2 mm or finer is recommended for dose calculation."}
{"_id": "Radiology$$$9b0346b7-3e29-4d6a-9ace-60e9b909c766", "text": "An isotropic grid size of 2 mm or finer is recommended for dose calculation."}
{"_id": "Radiology$$$7b3dbc44-909b-448d-aa28-0acff283c170", "text": "Below are some statements related to how targeted therapy may sensitize tumors to radiation therapy (RT). Please indicate which statements are correct or wrong:(a)\nInhibition of the DNA repair enzyme PARP1 with small molecules is a possible RT sensitizer for all types of tumors.\n\u00a0(b)\nTo increase the function of Bcl-2 is a RT sensitizing strategy.\n\u00a0(c)\nInhibitors toward EGFR is a promising RT sensibilization option for some tumors.\n\u00a0(d)\nReverting hypoxia is a way for RT sensitization."}
{"_id": "Radiology$$$9076c0f1-25bd-4a1d-a838-6b984fe327a6", "text": "Inhibition of the DNA repair enzyme PARP1 with small molecules is a possible RT sensitizer for all types of tumors."}
{"_id": "Radiology$$$46a3d6e2-216e-45d6-971a-fa34445b678f", "text": "To increase the function of Bcl-2 is a RT sensitizing strategy."}
{"_id": "Radiology$$$626ff6a0-b58a-41db-84d0-23cd25d8456f", "text": "Inhibitors toward EGFR is a promising RT sensibilization option for some tumors."}
{"_id": "Radiology$$$2adb6bc3-207a-4cc6-9ea9-5b0c6b799d72", "text": "Please name a key reason why RT can be combined with some immune therapies?"}
{"_id": "Radiology$$$4b206111-54fd-4384-a3a0-3a18ff9ac4cc", "text": "Hyperthermia has been shown to increase the effect of radiation therapy. Describe a DNA repair pathway that hyperthermia can inhibit."}
{"_id": "Radiology$$$76395f52-30bf-4a12-951c-d55b45924f9a", "text": "Name an advantage and a disadvantage of photon spatially fractionated radiation therapy (SFRT), proton minibeam radiotherapy (pMBRT) and ion MBRT?"}
{"_id": "Radiology$$$c338cd53-7dae-4abc-a6fa-3a045124454c", "text": "Give an example of a vectorized radiopharmaceutical used in the clinic and outline how it works."}
{"_id": "Radiology$$$c6191b89-06de-426e-a457-1f37aa40e254", "text": "Helium ions are good candidates in RT of tumors. What makes them good candidates?(a)\nHelium ions produce more secondary neutrons compared to protons.\n\u00a0(b)\nHelium ions produce more nuclear fragments compared to carbon ions.\n\u00a0(c)\nHelium ions have higher radiobiological effect (RBE) compared to protons.\n\u00a0(d)\nHelium ions have lower oxygen enhancement ratio (OER) compared to protons."}
{"_id": "Radiology$$$a5b1404b-bb07-4c0a-bea1-fc72d2f15004", "text": "Helium ions have lower oxygen enhancement ratio (OER) compared to protons."}
{"_id": "Radiology$$$431e27c4-4465-4e4b-9abd-429acc2d7bff", "text": "SQ1.\nAlternative (d). All statements (a, b, c) about the CHART irradiation protocol are correct. It involves a fraction size of <2 Gy and treatments are given during weekends giving a reduced treatment time compared to a conventional fractionation scheme.\n\u00a0SQ2.\nAlternative (c). The fraction size <2 Gy.\n\u00a0SQ3.\nTaking the normal tissue dose-volume constraints into account and considering, e.g., the kinetics of reoxygenation, the activation of the immune system and the abscopal effect, a number of six to eight medium sized fractions spaced 72\u00a0h might be optimal regarding tumor control. However, this is still a point of debate.\n\u00a0SQ4.\nAlternative (c). In SBRT, small or no margin is given for beam penumbra to improve sharp dose falloff.\n\u00a0SQ5.\nAlternative (b). SBRT treatment plans have a heterogenous dose distribution.\n\u00a0SQ6.\n(a). The statement is wrong. PARP1 is primarily a target in tumors that have mutations in BRCA1/BRAC2 or have a \u201cBRACAness\u201d phenotype. Such tumors lack functional DNA repair via HR and hence blocking PARP can impair repair of RT-induced DNA DSB. This is called synthetic lethality. PARP inhibition can also be applied for tumors with impairment in ATM or ATR. (b). The statement is wrong. Bcl-2 is an anti-apoptotic protein. Its activity/expression needs to be inhibited in order for RT to more prominently trigger cell death. (c). The statement is correct. EGFR inhibitors work in EGFR-mutant tumors, i.e., NSCLC or in tumors over-expressing EGFR. (d). The statement is correct. Tumor hypoxia can be attacked for RT sensitization purpose in several different ways.\n\u00a0SQ7.\nSince radiotherapy (RT) does exert both, immune stimulatory and immune suppressive effects, immune therapies aim to switch off the immune suppressive effects of RT or to boost the immune activating ones can be applied. This may result in effective local and systemic antitumor immune responses.\n\u00a0SQ8.\nHyperthermia can temporarily downregulate the BRCA2 protein, thereby blocking the homologous recombination.\n\u00a0SQ9.\n\u00a0\nPhoton SFRT\n\nProton MBRT\n\nIon MBRT\n\nAdvantage\n\nEasy implementation in clinic\n\nHomogeneous tumor irradiation already from one direction\n\n(Almost) no widening on the way to the tumor\n\nDisadvantage\n\nLow PVDR compared to MBRT\n\nWidening of the beams on the way to the tumor\n\nTechnically challenging as interlacing necessary for homogeneous tumor irradiation\n\n\u00a0SQ10.\nExamples of vectorized radionuclide therapy are 177Lu-PSMA-617 for the treatment of prostate cancer, 177Lu-NeoB for the treatment of solid metastatic tumors, 177Lu-DOTATATE for the treatment of neuroendocrine tumors, and 90Y-ibritumomab tiuxetan (Zevalin\u00ae) for the treatment of CD20-positive Non-Hodgkin lymphoma. Brief description of the principle: A radiopharmaceutical comprises a targeting moiety, which targets a specific molecule expressed on certain cells, and a radionuclide, which emits IR. By linking the targeting moiety to the radionuclide, molecules (e.g., somatostatin receptors, PSMA, CD20, etc.) that are highly expressed on the target tissue can be targeted to treat disease. Thus, the targeting moiety ensures specific delivery of toxic IR to the targeted cells which ensures treatment of the tumor disease, while causing minimal damage to surrounding healthy tissues.\n\u00a0SQ11.\nAlternative (c). Helium ions have higher RBE compared to protons."}
{"_id": "Radiology$$$081a399a-82a1-49fa-98b1-c0ddbbab4654", "text": "Alternative (d). All statements (a, b, c) about the CHART irradiation protocol are correct. It involves a fraction size of <2 Gy and treatments are given during weekends giving a reduced treatment time compared to a conventional fractionation scheme."}
{"_id": "Radiology$$$6031938c-ce8a-449a-840d-1b467a7123f1", "text": "Alternative (c). The fraction size <2 Gy."}
{"_id": "Radiology$$$c4913d32-274b-43e2-97a4-458d85b0d38b", "text": "Taking the normal tissue dose-volume constraints into account and considering, e.g., the kinetics of reoxygenation, the activation of the immune system and the abscopal effect, a number of six to eight medium sized fractions spaced 72\u00a0h might be optimal regarding tumor control. However, this is still a point of debate."}
{"_id": "Radiology$$$0c0103c2-cc68-4878-9656-83dab89036b3", "text": "Alternative (c). In SBRT, small or no margin is given for beam penumbra to improve sharp dose falloff."}
{"_id": "Radiology$$$877c62c8-3903-48d4-a019-41f942af589f", "text": "Alternative (b). SBRT treatment plans have a heterogenous dose distribution."}
{"_id": "Radiology$$$46a35052-1f71-4369-b05b-ac8522a7d5b5", "text": "(a). The statement is wrong. PARP1 is primarily a target in tumors that have mutations in BRCA1/BRAC2 or have a \u201cBRACAness\u201d phenotype. Such tumors lack functional DNA repair via HR and hence blocking PARP can impair repair of RT-induced DNA DSB. This is called synthetic lethality. PARP inhibition can also be applied for tumors with impairment in ATM or ATR. (b). The statement is wrong. Bcl-2 is an anti-apoptotic protein. Its activity/expression needs to be inhibited in order for RT to more prominently trigger cell death. (c). The statement is correct. EGFR inhibitors work in EGFR-mutant tumors, i.e., NSCLC or in tumors over-expressing EGFR. (d). The statement is correct. Tumor hypoxia can be attacked for RT sensitization purpose in several different ways."}
{"_id": "Radiology$$$ad980796-ebae-42f0-898a-e19757db38f0", "text": "Since radiotherapy (RT) does exert both, immune stimulatory and immune suppressive effects, immune therapies aim to switch off the immune suppressive effects of RT or to boost the immune activating ones can be applied. This may result in effective local and systemic antitumor immune responses."}
{"_id": "Radiology$$$b824124d-6f39-4dd6-8ac8-8b0db3c30805", "text": "Hyperthermia can temporarily downregulate the BRCA2 protein, thereby blocking the homologous recombination."}
{"_id": "Radiology$$$d1a6ab89-aa16-4695-bb1d-2e08d06f9a89", "text": "Photon SFRT\n\nProton MBRT\n\nIon MBRT\n\nAdvantage\n\nEasy implementation in clinic\n\nHomogeneous tumor irradiation already from one direction\n\n(Almost) no widening on the way to the tumor\n\nDisadvantage\n\nLow PVDR compared to MBRT\n\nWidening of the beams on the way to the tumor\n\nTechnically challenging as interlacing necessary for homogeneous tumor irradiation"}
{"_id": "Radiology$$$b1250780-9370-4bad-a297-579547ec0b11", "text": "Examples of vectorized radionuclide therapy are 177Lu-PSMA-617 for the treatment of prostate cancer, 177Lu-NeoB for the treatment of solid metastatic tumors, 177Lu-DOTATATE for the treatment of neuroendocrine tumors, and 90Y-ibritumomab tiuxetan (Zevalin\u00ae) for the treatment of CD20-positive Non-Hodgkin lymphoma. Brief description of the principle: A radiopharmaceutical comprises a targeting moiety, which targets a specific molecule expressed on certain cells, and a radionuclide, which emits IR. By linking the targeting moiety to the radionuclide, molecules (e.g., somatostatin receptors, PSMA, CD20, etc.) that are highly expressed on the target tissue can be targeted to treat disease. Thus, the targeting moiety ensures specific delivery of toxic IR to the targeted cells which ensures treatment of the tumor disease, while causing minimal damage to surrounding healthy tissues."}
{"_id": "Radiology$$$753b9f20-3809-4244-b96c-2532f15f7833", "text": "Alternative (c). Helium ions have higher RBE compared to protons."}
{"_id": "Radiology$$$ce558108-cf10-44ea-a951-8a29fdb9e262", "text": "The term \u201cradiosensitivity\u201d is one of the most extensively used words in radiobiology. It was described as radiation-induced tissue reactions (e.g., skin is radiosensitive) in the first decade of the nineteenth century [1]. Since 1930s, with the first Congresses of Radiology, the term \u201cradiosensitivity\u201d was also used as a synonym of radiation-induced cancers (e.g., thyroid is a radiosensitive organ) and progressively was used for radiation-induced cataracts (e.g., eyes are radiosensitive [2]). All these different uses lead to an actual confusion and notably raise legal issues since radiation-induced cancers, cataracts, or skin burns do not correspond to the same level of clinical injuries [3]."}
{"_id": "Radiology$$$291a7afc-8f1a-4529-a969-6f44a6bef2d8", "text": "To avoid these confusions, a possible approach is to consider all the major clinical features of the response to radiation by using unequivocal terms that could be indifferently applied to the individual, tissue, cellular, or molecular scales. To consolidate this approach, it is important to document the individual response to radiation through a complete knowledge of its different features. For example, it is noteworthy that ataxia telangiectasia (AT), caused by homozygous mutations of the AT mutated (ATM) gene resulting in aberrant ATM protein, is associated with post-RTfatal reactions and high risk of leukemia [4], while Li Fraumeni\u2019s syndrome is associated with cancer proneness but not with significant post-RT adverse tissue reactions [5]. Conversely, Cockayne\u2019s syndrome is associated with significant tissue radiosensitivity but no cancer proneness [6]."}
{"_id": "Radiology$$$1854b9d6-ae61-4177-9e7e-9db83076643d", "text": "Hence, the following definition has been therefore proposed in literature [7] and summarized in Table 7.1.Table 7.1\nSummary of the terms\u2014radiosensitivity, radiosusceptibility, and radioresistance\n\nRadiosensitivity\n\nRadiosensitivity refers to adverse healthy tissue reactions like burns, dermatitis, rectitis, etc., that is, any reaction led by radiation-induced cell death that may be generally accompanied by inflammation.\n\nRadiosensitivity also refers to the inherent response of tumor/cancer cells to radiation which can be measured by the reduction of the volume, the extent of regression, rapidity of response, and response durability that are also linked to radiation-induced cell death.\n\nThe degree of radiosensitivity depends on the combination of various genetic traits, interaction with each other, ability to repair damage, hypoxia, cell cycle position, growth fraction, hormonal balance, immune system, and various environmental factors.\n\nThe probable cause of radiosensitivity may be an insufficient repair of the radiation-damaged DNA generally due to defective DNA damage signaling and/or repair mechanism.\n\nRadiosusceptibility\n\nThe proneness to radiation-induced cancers generally linked to radiation-induced cell transformation and mis-repaired DNA damage.\n\nIt is also an important issue for both low- and high-dose radiation exposures to an individual who exhibits higher cancer risk spontaneously.\n\nDifferences in radiosusceptibility between individuals, or groups, may relate to genetic constitution, but also to other characteristics such as age at exposure, health status and comorbidity, epigenetic factors, lifestyle, and co-exposures to other stressors.\n\nRadiodegeneration\n\nThe term is to describe any aspects of IR responses (non-cancer effects) attributable to mechanisms related to accelerated aging.\n\nRadioresistance\n\nRadioresistance describes a normal response to IR at any level; whether molecular, cellular, tissular, and clinical.\n\nIn terms of radiosensitivity, radioresistance is the synonym of absence of any adverse tissue reactions and of a normal DNA damage repair (rate and efficiency).\n\nIn terms of radiosusceptibility, radioresistance is synonymous with a low risk of radiation-induced cancer.\n\nIn terms of radiodegeneration, radioresistance is synonymous with a low risk of radiation-induced aging."}
{"_id": "Radiology$$$500119ab-47a5-446e-a335-d0be8666b874", "text": "\u201cRadiosensitivity\u201d is the proneness to radiation-induced adverse tissue events that are considered as non-cancer effects attributable to cell death. Radiosensitivity is generally correlated with unrepaired DNA damage and observed in response to high doses of radiation [8] (Box 7.1).\n\n\u201cRadiosusceptibility\u201d is the proneness to radiation-induced cancers which are non-toxic effects attributable to cell transformation and/or genomic instability (in part correlated with DNA misrepair). Since IR is considered to be a carcinogenic agent, radiosusceptibility is distinctly and strongly linked to susceptibility to spontaneous cancer induction. The term \u201cradiosusceptibility\u201d was proposed due to its similarities with \u201ccancer susceptibility,\u201d extensively used in the ICRP (International Commission on Radiological Protection) reports and since it introduces the notions of stochastic events [9].\n\n\u201cRadiodegeneration\u201d responses are non-cancer effects attributable to mechanisms which are related to accelerated aging and often correlated with unrepaired DNA damage that is tolerated by and accumulated in cells [9]. Radiodegeneration responses cannot be considered like radiosensitivity responses as defined above since their incidence rates, the types of cellular death, and the genes involved are different."}
{"_id": "Radiology$$$736c4aeb-1c4d-4ec0-bad8-de8470b29f2d", "text": "\u201cRadiosensitivity\u201d is the proneness to radiation-induced adverse tissue events that are considered as non-cancer effects attributable to cell death. Radiosensitivity is generally correlated with unrepaired DNA damage and observed in response to high doses of radiation [8] (Box 7.1)."}
{"_id": "Radiology$$$0125c6d6-0496-4f1f-8db7-7b78d680e380", "text": "\u201cRadiosusceptibility\u201d is the proneness to radiation-induced cancers which are non-toxic effects attributable to cell transformation and/or genomic instability (in part correlated with DNA misrepair). Since IR is considered to be a carcinogenic agent, radiosusceptibility is distinctly and strongly linked to susceptibility to spontaneous cancer induction. The term \u201cradiosusceptibility\u201d was proposed due to its similarities with \u201ccancer susceptibility,\u201d extensively used in the ICRP (International Commission on Radiological Protection) reports and since it introduces the notions of stochastic events [9]."}
{"_id": "Radiology$$$3e5119ce-2ae9-4d01-967c-d64cbcdc8790", "text": "\u201cRadiodegeneration\u201d responses are non-cancer effects attributable to mechanisms which are related to accelerated aging and often correlated with unrepaired DNA damage that is tolerated by and accumulated in cells [9]. Radiodegeneration responses cannot be considered like radiosensitivity responses as defined above since their incidence rates, the types of cellular death, and the genes involved are different."}
{"_id": "Radiology$$$134cfc0a-76ce-4f60-b951-470cde8cbd22", "text": "Radiosensitivity differs throughout the cell cycle with, in general, G1 phase taking an intermediate position, and late S phase being most radioresistant.\n\nThe greater proportion of repair by HR than by NHEJ in late S phase may explain the resistance of late S phase cells.\n\nChromatin compaction and poor repair competence (reduced enzyme access) could explain the high radiosensitivity in G2/M."}
{"_id": "Radiology$$$672d6459-185e-44d5-aa75-03ae31ae331b", "text": "Radiosensitivity differs throughout the cell cycle with, in general, G1 phase taking an intermediate position, and late S phase being most radioresistant."}
{"_id": "Radiology$$$bf0053ac-971c-4009-a071-e466cf3139b5", "text": "The greater proportion of repair by HR than by NHEJ in late S phase may explain the resistance of late S phase cells."}
{"_id": "Radiology$$$abbf8bd5-6631-42a9-94c2-fef905c09603", "text": "Chromatin compaction and poor repair competence (reduced enzyme access) could explain the high radiosensitivity in G2/M."}
{"_id": "Radiology$$$ab38143d-d015-4298-bee2-b258f06050f4", "text": "A biomarker is an objective feature with one or more defined characteristics which indicate specific normal biological and pathological processes, or responses to an exposure or to therapeutic interventions. To date, radiation biomarkers are primarily identified in blood or saliva and are measurable indicators that reflect an interaction between a biological system and one or more environmental agents (chemical, physical, or biological). Biomarkers provide crucial information on the complex molecular cascade of events and their mechanisms underlying the pathological conditions or pharmacological responses to a therapeutic intervention."}
{"_id": "Radiology$$$8df698d4-30d8-4c27-9a95-bad54cefa930", "text": "Biomarkers can be used to assess various different types of biological characteristics or parameters. These include genetic sequences, receptor expression patterns, radiographic or other imaging-based measurements, blood composition, electrocardiographic parameters, or organ function. Since biomarkers are quantifiable, they can be used to characterize the response to direct or indirect IR exposure, to select radiation dose, and to assess the potential safety issues related to dose administration. A large number of such biomarkers have been developed over the years; the characteristics of the different classes of radiation biomarkers will be reviewed in Sect. 7.2.2."}
{"_id": "Radiology$$$253af1fc-f372-4e28-bfd9-7777d67a79bd", "text": "Although the definitions, nature, and use of biomarkers are multiple and rapidly evolving with the sophisticated\u2014omics technologies, they must be evaluated in terms of their ability to address etiology and genetic susceptibility, predict and quantify dose of exposure. There are certain properties which are desirable when linking a biomarker with an exposure, e.g., IR. These include high specificity and sensitivity, known variability in the general population, should give reproducible results when assessed and multiplexing of analyses to allow for screening purposes. Some additional desirable characteristics of an ideal biomarker can be listed for use in large scale molecular epidemiological studies: (a) Early expressivity; (b) Linear relationship across time; (c) Strong correlation with a health effect; (d) Reproducible between laboratories; (e) Biologically plausible; (f) Inexpensive and feasible for sample collection; (g) Consistency (the same exposure will produce the same concentration of the biomarker every time)."}
{"_id": "Radiology$$$98d8aa3c-4bbf-4b07-a164-877525c272f4", "text": "Radiation biology research has identified several approaches, especially the \u201comics\u201d fields, as promising avenues for the development of suitable biomarkers of high sensitivity and specificity for radiation exposure. Radiation epidemiology biomarkers should preferably be specific to radiation and independent of other environmental exposures such as tobacco or cigarette smoke. Such a biomarker would simplify analysis and help to substantiate radiation causality. Though biological biomarker often lack specificity, they can still be informative in predicting the development of radiation-induced disease if such exposures are additive or interactive. Multi-biomarker approaches should be particularly useful in epidemiological studies, both for (1) assessing exposure\u2013response relationships and how they vary with individual susceptibility and (2) to understand better disease mechanisms and the interplay of different possible pathways."}
{"_id": "Radiology$$$d0095be6-1e6a-4700-ae26-2f1efc2dfb91", "text": "Contrariwise, carefully planned molecular epidemiological studies are crucial for the validation and verification of biomarkers, to determine their specificity and sensitivity as well as factors that might influence them (e.g., age, sex, smoking status, environmental agents, chronic conditions such as inflammation or individual sensitivity) [10]."}
{"_id": "Radiology$$$d754f1bb-b005-4e58-a2a4-6d7fbe740eb0", "text": "The ultimate goal of using biomarkers in molecular epidemiological studies is to be able to predict health risk. The types of biomarkers mentioned in Table 7.2 hold substantial prospective in epidemiological studies; however, there are a number of key questions to be considered which are generic to their application. Among these are: \u201cWhat to measure?\u201d \u201cWhere to measure?\u201d and \u201cWhen to measure?\u201dTable 7.2\nClassification of biomarkers based on temporal parameters\n\nBiomarkers of exposure\n\n\u2022\u2003Available at some point after exposure.\n\u2022\u2003Suitable for estimating the dose received and identifying human internal exposure to environmental and occupational chemicals/radiation by using novel techniques and approaches.\n\u2022\u2003Biomarkers of this category can have potential for use in radiation oncology to provide information on the probable outcome of RT.\n\u2022\u2003Cytogenetic biomarkers are the best dosimetry biomarkers of radiation exposure as they show a high degree of specificity and sensitivity.\n\u2022\u2003Emerging biomarkers related to alterations in transcriptional profiles can have potential as biomarkersBiomarkers of exposure [11].\n\nBiomarkers of susceptibility\n\n\u2022\u2003Available before, during, or after exposure.\n\u2022\u2003Provide key information which reflect intrinsic characteristics toward adverse effects of an exposure and thus predict an increased risk of radiation-induced health effects.\n\u2022\u2003Appropriate to provide meticulous knowledge of the exposure-risk relationship, and variability of risks between individuals of identical or different population/subgroups.\n\u2022\u2003Genetic variants (polymorphism) and/or metabolic phenotypes associated with cancer predisposition may prove to be useful biomarkers of susceptibility.\n\u2022\u2003Cytogenetic endpoints (e.g., the G2 assay) are of interest as biomarkers of susceptibility.\n\nBiomarkers of late effects\n\n\u2022\u2003Suitable for assessing a long-time health effects post exposure, even before clinical detection of radiation induced disease or death.\n\u2022\u2003Cytogenetic assays emphasize some potential as biomarkers of late effects of radiation exposure to predict the risk of RT side effects.\n\u2022\u2003Transcriptional biomarkers can be employed to identify either pathways or gene expression signatures predictive of susceptibility and late health effects.\n\nBiomarkers of persistent effects\n\n\u2022\u2003Applicable to assess radiation effects present a long period of time after exposure.\n\u2022\u2003Biomarkers of exposure and effects may potentially be used to identify individuals at higher risk of development of cancer.\n\u2022\u2003Chiefly an aspirational category on the basis of current science."}
{"_id": "Radiology$$$e56e406f-c3fd-45d3-8a3a-e97f6f51b2f2", "text": "Determining if a biomarker is a good biomarker (the characteristics to determine an ideal biomarker are outlined in Fig. 7.1) for molecular epidemiological studies is complex because this relies on a number of different concepts associated with the radiation exposure and otherwise, which\u00a0will very much depend on the biological samples such as cells (buccal cells, fibroblasts, hair follicle cells, etc.), blood, saliva, urine, tooth, hair, nail which can be collected non-invasively at different time points post IR exposure to study biological effects.\n\nAn illustration of characteristics of an ideal biomarker. For molecular epidemiological studies: validity of the assay and marker, suitability of the marker and assay, invasiveness, and acceptability. General: Ease, cost, interindividual variation, speed, background, and radiation specificity.\n\nFig. 7.1\nCharacteristics to determine an ideal biomarker. An ideal biomarker for molecular epidemiological studies (top) and general considerations of a good biomarker (bottom)"}
{"_id": "Radiology$$$5938bd65-5450-4896-840c-5f689a89496f", "text": "An illustration of characteristics of an ideal biomarker. For molecular epidemiological studies: validity of the assay and marker, suitability of the marker and assay, invasiveness, and acceptability. General: Ease, cost, interindividual variation, speed, background, and radiation specificity."}
{"_id": "Radiology$$$87b71ce9-927f-49a2-b56d-3c11b867d1e1", "text": "There is a great interest in developing new biomarkers for radiation exposure, which could be used in large molecular epidemiological studies in order to correlate estimated doses received by individuals and health effects using high-throughput technologies, i.e., \u201comics.\u201d In these instances, biomarkers can provide a measure of external exposure as well as internal absorption of radioactive material and can thus be markers of internal dose as well. However, factors other than the exposure may influence biomarker expression, and thus there may not always be a simple relationship between external exposure and internal dose. For example, DNA or protein adducts may be applicable as markers of other processes such as absorption, distribution, metabolism, and DNA repair, as well as of exogenous exposure. As a result, the measured internal radiation doses (biomarkers) will be an amalgam of exposure and these variables."}
{"_id": "Radiology$$$91ad08ab-ed90-4e10-9252-ee9c3fdadedb", "text": "In a nutshell, reliable radiation biomarkers databases can be shaped by integrating the information from radiation genomics, metabolomics, and proteomic analysis in order to expand the scientific frontiers on predicting and/or monitoring radiation exposure-associated effects. Such protocols along with more sophisticated technologies are probably vital for the development of personalized medicine and will undoubtedly prove highly useful to bring a new horizon of therapeutic possibilities [12] (Box 7.2)."}
{"_id": "Radiology$$$71dfff61-d1ce-4bbf-887f-1e04127ebba9", "text": "Biomarkers and/or biological dosimeters are essential for predicting and/or monitoring radiation exposure-associated effects, quantifying the exposure, estimating absorbed radiation dose in certain accidental situations or a suspected radiation overexposure.\n\nRadiation epidemiology biomarkers should be specific to radiation and independent of other factors that might influence them (such as age, chronic conditions, smoking, tobacco, or individual sensitivity).\n\nIdentifying biomarkers of IR exposure employs a multi-parametric approach to achieve an accurate dose and risk estimation."}
{"_id": "Radiology$$$ef0e3d6e-0cde-47e0-8720-cc55a9d2696b", "text": "Biomarkers and/or biological dosimeters are essential for predicting and/or monitoring radiation exposure-associated effects, quantifying the exposure, estimating absorbed radiation dose in certain accidental situations or a suspected radiation overexposure."}
{"_id": "Radiology$$$00eb272f-91c2-4b22-8987-3fd98415bd7d", "text": "Radiation epidemiology biomarkers should be specific to radiation and independent of other factors that might influence them (such as age, chronic conditions, smoking, tobacco, or individual sensitivity)."}
{"_id": "Radiology$$$e688aa5e-014a-4a41-84af-9b2300953558", "text": "Identifying biomarkers of IR exposure employs a multi-parametric approach to achieve an accurate dose and risk estimation."}
{"_id": "Radiology$$$3f0914a0-61ff-41f4-bd6b-5172c69185ea", "text": "Several biological responses can act as potential biomarkers for IR exposure. They are linked to cellular or physiological mechanisms which have been shown to change soon after radiation exposure. The use of various \u201comic\u201d technologies together with hypothesis-driven approaches may be highly useful to measure radiation biomarkers in a biological system. Some biomarkers could be used as response markers or as surrogate endpoints to predict radiation side effects. The expression levels of many biomarkers can be expected to be correlated with each other and so could be classified in multiple categories, such as\nPhosphorylated histone H2AX\u00a0(\u03b3-H2AX) acts as protein biomarker for radiation exposure but is useful as a DNA damage marker; suggesting a close one-to-one relationship between initial as well as residual radiation-induced DNA DSBs and \u03b3-H2AX foci.\n\n8-oxo-dG acts as a marker of nucleotide damage but is strongly associated as a maker of oxidative DNA damage suggesting it is produced abundantly in DNA exposed to free radicals and reactive oxygen species (ROS).\n\nPhosphoproteomic profiling insights into processes influenced by epigenetic modifications, but also uncovers signaling pathways."}
{"_id": "Radiology$$$c1a2bf55-40fc-4fe5-ab9a-48d11a29eb69", "text": "Phosphorylated histone H2AX\u00a0(\u03b3-H2AX) acts as protein biomarker for radiation exposure but is useful as a DNA damage marker; suggesting a close one-to-one relationship between initial as well as residual radiation-induced DNA DSBs and \u03b3-H2AX foci."}
{"_id": "Radiology$$$c8f7c78c-0b1e-4424-8aca-0eb18e7a391b", "text": "8-oxo-dG acts as a marker of nucleotide damage but is strongly associated as a maker of oxidative DNA damage suggesting it is produced abundantly in DNA exposed to free radicals and reactive oxygen species (ROS)."}
{"_id": "Radiology$$$e74b1815-197a-4775-b73d-66707fc01936", "text": "Phosphoproteomic profiling insights into processes influenced by epigenetic modifications, but also uncovers signaling pathways."}
{"_id": "Radiology$$$fe68773f-d14e-41d3-8f5d-3fed266dec82", "text": "These biomarkers can be organized in categories such as (a) cytogenetic; (b) nucleotide pool damage and DNA damage; (c) germline inherited mutations or variants; (d) induced mutations; (e) transcriptional and translational changes; (f) epigenetic modifications; (g) lipid peroxidation; (h) others, including biophysical markers (Fig. 7.2).\n\nAn illustration of the types of radiation biomarkers. The types are cytogenetics, nucleotide pool damage and D N A damage, germline inherited mutations or variants, induced mutations, transcriptional and translational changes, epigenetic modifications, lipid peroxidation, biophysical, and others.\n\nFig. 7.2\nBiological classification of radiation biomarkers. (Reproduced with permission, with some modification (changed layout and some content), from [10]; licensed under CC BY-NC-ND 3.0)"}
{"_id": "Radiology$$$b537fde3-541d-4d29-87b6-3d6f5dfb2327", "text": "An illustration of the types of radiation biomarkers. The types are cytogenetics, nucleotide pool damage and D N A damage, germline inherited mutations or variants, induced mutations, transcriptional and translational changes, epigenetic modifications, lipid peroxidation, biophysical, and others."}
{"_id": "Radiology$$$2a20c78f-f251-44a2-a49c-697e02b8866e", "text": "Biomarkers of radiation exposure are further discussed in Chaps. 2, 3, and 8."}
{"_id": "Radiology$$$d12e3d97-1085-4601-91e9-49fbbdaaffb6", "text": "Over the past decades, the definition and classification of the different types of biomarkers have varied slightly, depending on the biomedical field considered. Biomarkers are an important aspect of radiation countermeasure development and can be used as a trigger for intervention as well as in selecting a radiation dose and treatment regimen in humans, e.g., in the context of RT of cancer ([13] and as further discussed here\u00a0in Chap. 7 and in Chap. 8). Biomarkers can also provide information on potential modifying/confounding factors to allow an assessment of biological interactions. Pernot et al. [10], Hall et al. [14] classified biomarkers into four broad categories, based on their temporal parameters Table 7.2."}
{"_id": "Radiology$$$cc5d6178-b6b8-4adb-828f-fb6fa6852cba", "text": "One should be cognizant of the fact that overlap does exist between these different types of biomarkers. Taken together, these attributes enable a better understanding of exposure and its effect on biological pathways across different forms of exposure, health changes, disease headway; providing more meaningful comprehensive risk assessment (Fig. 7.3). This classification is acceptable not only with respect to the timing of processes that can be measured with these biomarkers, but also in considering the most adequate designs and sampling procedures in molecular epidemiological studies (Box 7.3).\n\nAn illustration of the progression of different biomarkers over time when there is a low dose ionizing radiation exposure. Exposure: Increases and decreases. Susceptibility: Remains constant. Late effects: Increases. Persistent effect: Remains constant through stages.\n\nFig. 7.3\nTimeline of radiation-induced disease progressions and relation with different types of radiation biomarkers. (Reproduced with permission, with some modification (changed color and layout), from [10]; licensed under CC BY-NC-ND 3.0)"}
{"_id": "Radiology$$$2cc793c0-833d-4101-8250-0935685a7855", "text": "An illustration of the progression of different biomarkers over time when there is a low dose ionizing radiation exposure. Exposure: Increases and decreases. Susceptibility: Remains constant. Late effects: Increases. Persistent effect: Remains constant through stages."}
{"_id": "Radiology$$$7ec8d484-bf30-41a9-8c15-e8b15a7c4a56", "text": "Biomarkers of exposure are available at some point after exposure and are suitable for estimating the dose received.\n\nBiomarkers of susceptibility can be available before, during, or after exposure and can predict an increased risk of radiation effects.\n\nBiomarkers of late effects can be used to assess health effects that are present a long time after exposure before clinical detection of the radiation induced disease or death.\n\nBiomarkers of persistent effects allow the assessment of radiation effects present a long period of time after exposure."}
{"_id": "Radiology$$$1e9d604b-c4e5-4575-ada9-608c1ae1b430", "text": "Biomarkers of exposure are available at some point after exposure and are suitable for estimating the dose received."}
{"_id": "Radiology$$$ccd42cc7-897f-410f-826c-36abefb43792", "text": "Biomarkers of susceptibility can be available before, during, or after exposure and can predict an increased risk of radiation effects."}
{"_id": "Radiology$$$e18c31a7-a50a-4004-975e-6b34e8d7b138", "text": "Biomarkers of late effects can be used to assess health effects that are present a long time after exposure before clinical detection of the radiation induced disease or death."}
{"_id": "Radiology$$$b875135e-e069-4632-a370-6eb286636c65", "text": "Biomarkers of persistent effects allow the assessment of radiation effects present a long period of time after exposure."}
{"_id": "Radiology$$$27462fdf-80b3-4acd-9a48-c3bf1142599f", "text": "Not only since the \u201cage of OMICS,\u201d it is well known that the collection of samples from patients and healthy volunteers is essential for future research [15]. Especially in radiation research, the collection of biological samples represents a significant part of translational research, since, especially in studies on radiation protection, the collected biological samples represent an essential parameter for analysis of (historic) radiation exposure [14]. Also, in therapeutic trials, the sampling of tissues and body fluids has an immense impact on the search, discovery, and validation of novel biomarkers supporting the pathological diagnosis as well as for the determination of therapy toxicity and/or outcome [15, 16]. The collected samples may safely expand the possibilities of the entire analytical process within prospective and retrospective trials in radiation science. However, the collection and storage of biological samples should always be done within a quality-controlled manner [17]. In contrast to tissue sampling, the sampling of body fluids also has the big advantage, that these samples are nearly always available or easy to access like vein puncture. In addition, the sampling of blood can be done mostly together with clinical mandatory blood draws, minimizing the burden of the patient/donor, and enhancing the amount of time points of sampling as well as it also increases the donor\u2019s acceptance of giving blood for research. Since the collection of samples at biobanks accelerate the process of transferring scientific knowledge into therapeutic application, it should be the duty of clinical researchers adding translational programs with sample collection to the prospective clinical trials. In our hands, the sampling and analysis of immunological parameters lead to predictive biomarkers supporting the pathological diagnosis and therapeutic intervention and helping radiation treatment in precision medicine [16, 18]."}
{"_id": "Radiology$$$d082ce9b-724c-4439-be6f-199ea8ac6999", "text": "The sampling, the processing, as well as the storage have to be done in a quality-controlled manner as outlined before by Winter and colleagues [19] or at the respective international biobank consortia like the European, Middle Eastern and African Society for Biopreservation and Biobanking (ESBB), or the European research infrastructure for biobanking (BBMRI-ERIC; [20]). There are another three very important things to keep in mind when collecting samples for later analysis: The best collections are almost worthless if they are not connected with clinical, radiation exposure, and patients/donor data. Along with this, the informed consent of the donor should allow use of the samples for the respective analyses even when the samples will be given for, e.g., \u201cOMICS\u201d analysis to a cooperation partner or to the statistician who performs the analysis of the data. Lastly, a biobank is a living \u201cthing\u201d which should be used for research and not as a secure vault to store samples for eternity. Taken together, it should be the duty of research on humans to collect and store samples for further analyses, but also processing and storage should be carried out in accordance with applicable regulations and standards. This is the only way to ensure that the samples do not suffer any loss of value and are available for later applications."}
{"_id": "Radiology$$$671de681-a16a-44a2-8a46-71726164e65f", "text": "Tissue reactions induced by IR are the result of different types of cell death (mitotic death, apoptosis, autophagy, senescence, etc.). Loss of clonogenicity (and not physical disappearance or metabolic shutdown) appeared to be common to all types of cell death."}
{"_id": "Radiology$$$5d848dbf-cb78-4b4f-b4f7-016985ec89d3", "text": "In 1957, Puck and Markus proposed to use clonogenic assays (or colony method) to quantify cellular radiosensitivity [21] (Fig. 7.4). The assay is based on the ability of an individual tumor cell to grow into a colony after exposure to various doses of radiation given the surviving fraction (SF) at each dose. The fraction of cells surviving after 2 Gy (SF2) has been demonstrated to be a robust predictor for radiation sensitivity but colony formation can take 7\u201314\u00a0days. Several predictive tests have been proposed to approach clonogenic survival but with a suboptimal statistical power.\n\nAn illustration of eight steps in the clonogenic assay. 1. Collect patient tumor material. 2. Obtain single cell suspension. 3. Seed cells into plate wells. 4. Irradiate cells. 5. Wait 1 to 3 weeks for results. 6. Stain cells. 7. Manually enumerate colonies. 8. Calculate survival fraction.\n\nFig. 7.4\nBrief overview of the original clonogenic assay"}
{"_id": "Radiology$$$ef598f2c-7627-45d4-9036-c41d26aae088", "text": "An illustration of eight steps in the clonogenic assay. 1. Collect patient tumor material. 2. Obtain single cell suspension. 3. Seed cells into plate wells. 4. Irradiate cells. 5. Wait 1 to 3 weeks for results. 6. Stain cells. 7. Manually enumerate colonies. 8. Calculate survival fraction."}
{"_id": "Radiology$$$4d68a2b0-ae4b-47e0-823b-efdb2e217740", "text": "The original clonogenic assay can be performed in two different ways (1) irradiation after plating or (2) plating after irradiation. The first is usually carried out to investigate intrinsic radiosensitivity to varying modalities (types) of treatment, and the second allows for the assessment of reproductive ability. The irradiation after plating method is presented in Fig. 7.4 as it is usually used in radiobiological studies. Further details on the clonogenic assay can be seen in Chap. 3."}
{"_id": "Radiology$$$ea8c410f-c920-49f0-8af0-0fd0f1e9881f", "text": "Several techniques continue to rely on cell culture:\nThe level of radiation-induced micronuclei\u00a0(MN) has been quantitatively correlated with radiosensitivity since the 1960s thanks to a simple and robust protocol consisting of blocking the process of cytokinesis by drugs such as cytochalasin B [22].\n\nThe premature chromosome condensation (PCC) assay consists in making chromosome fragments appear more quickly by fusing the tested cell with a cell in mitosis. The heterokaryon thus formed allows the exchange of mitotic factors in the cell into G0/G1 and then produces premature condensation of the chromatin [23].\n\nThe enumeration of chromosomal aberrations by fluorescence in situ hybridization technique."}
{"_id": "Radiology$$$393bef69-3c18-4471-a6c2-af60cd364587", "text": "The level of radiation-induced micronuclei\u00a0(MN) has been quantitatively correlated with radiosensitivity since the 1960s thanks to a simple and robust protocol consisting of blocking the process of cytokinesis by drugs such as cytochalasin B [22]."}
{"_id": "Radiology$$$ccfe580a-b294-4307-8dd4-baeb34e9cb31", "text": "The premature chromosome condensation (PCC) assay consists in making chromosome fragments appear more quickly by fusing the tested cell with a cell in mitosis. The heterokaryon thus formed allows the exchange of mitotic factors in the cell into G0/G1 and then produces premature condensation of the chromatin [23]."}
{"_id": "Radiology$$$e0eb4ce5-6aaa-411c-809d-f31d47501061", "text": "The enumeration of chromosomal aberrations by fluorescence in situ hybridization technique."}
{"_id": "Radiology$$$39989bb9-a825-4a5d-aa9f-73bc22875676", "text": "It made sense to focus on the molecular mechanisms of the cellular response to radio-induced damage to DNA and in particular to DNA repair, since a quantitative link between unrepaired Double-Strand Breaks (DSB), chromosomal breaks, and radiation-induced clonogenic cell death was demonstrated [24]. Moreover, the vast majority of genetic syndromes associated with individual radiosensitivity are linked to mutations in genes involved in radiation-induced DSB signaling or repair. DSB measurement techniques were investigated with some confusion on their specificity and instead reflected other types of damage [7]. The first techniques for measuring DSB were based on discriminating radiation-induced DNA fragments based on their size. This was particularly the case with sedimentation in sucrose gradients, neutral elution, and pulsed-field electrophoresis. Such a principle has the advantage of measuring the repair of DSBs independently of any molecular repair pathways regardless of the post-irradiation time. On the other hand, these techniques do not make it possible to assess the quality of the repair, that is to say whether it is faithful or at fault."}
{"_id": "Radiology$$$52a9678d-5ffa-4dc5-a2f7-e755c5fa654c", "text": "The halo technique consists, using fluorescent intercalators, in quantifying such an increase in the nucleus. The comet technique combines electrophoresis and the halo technique, both applied individually to each cell. Data from the comet technique are usually given in the form of the product of the increase in the size of the nucleus (comet head) times the distance that DNA fragments migrate (comet tail) [25]."}
{"_id": "Radiology$$$c5762bc5-deed-4713-94a1-17bc323c830c", "text": "From 2003, with indirect immunofluorescence, it became possible to follow precisely and in real time in the nucleus and for a wide dose spectrum, the kinetics of appearance/disappearance of DNA repair proteins (foci). A correlation between SF2 and the rate of unrepaired DSB 24\u00a0h after 2 Gy (\u03b3-H2AX marker) could be demonstrated\u2014constituting a functional repair test [26]. A second marker significantly increased the performance of the test\u2014based on the speed of nuclearization and the functionality of the pATM protein in the nucleus [8]."}
{"_id": "Radiology$$$aa6950aa-a2e9-4daa-b301-2ebcc0275188", "text": "Genome-wide association (GWAS)\u00a0studies have been widely used to identify associations between commonly occurring variations in DNA sequence, such as single nucleotide polymorphisms (SNP) and human traits such as individual radiosensitivity [27]. A few SNP as well as mitochondrial haplogroups have been reported."}
{"_id": "Radiology$$$fe717e6a-abf0-41b6-aea4-ef60796ef041", "text": "The interest in the predictive power of the transcriptome began in the early 2000s and in vitro transcriptomic signatures for individual radiosensitivity then emerged. The identified predictive genes were associated with cellular functions such as TGF\u03b2 pathway, particularly extracellular matrix remodeling, apoptosis, proliferation, and ROS\u00a0scavenging [28, 29] (Table 7.3).Table 7.3\nReported gene expression signatures for individual radiosensitivity\n\nPublication\n\nRS patients\n\nRR patients\n\nRadiation scheme\n\nSelected differentially expressed genes\n\nAssay used for gene selection\n\nQuarmby et al. [28]\n\n3\n\n3\n\nNot irradiated\n\nFMLP-R-I, TNF\u03b1, NGFR, EPHB2, PDGFB, NTRK1, LFNG, DDR1; IFNGR1\n\nCytokine array\n\nAlsner et al. [30]\n\n22\n\n4\n\n3\u00a0\u00d7\u00a03.5 Gy over 3\u00a0days, RNA extracted 2\u00a0h after last irradiation\n\nCDC6, CDON, CXCL12, FAP, FBLN2, LMNB2, LUM, MT1X, MXRA5, SLC1A3, SOD2, SOD3, WISP2\n\n15K cDNA microarray\n\nR\u00f8dningen et al. [31]\n\n10\n\n4\n\n3\u00a0\u00d7\u00a03.5 Gy over 3\u00a0days, RNA extracted 2\u00a0h after last irradiation\n\nPLAGL1, CCND2, CDC6, DEGS1, CDON, CXCL12, MXRA5, LUM, MT1X, MT1F, MT1H, C1S, NF1, ARID5B, SCL1A3, TM4SF10, MGC33894, ZDHHC5/MFGE8\n\n15K cDNA microarray\n\nForrester et al. [32]\n\n6\n\n8\n\nNot irradiated\n\nFBN2, FST, GPRC5B, NOTCH3, PLCB1, DPT, DDIT4L, SGCG\n\nGeneChip Human Exon 1.0 ST Array"}
{"_id": "Radiology$$$c4907c56-6b5f-411f-a139-6698cf05f27a", "text": "Epigenetic modifications include histone modifications such as acetylations and methylations, DNA methylation, particularly on CpG island, non-coding RNAs, and three-dimensional chromatin organization. As this a relatively new field, only few studies have been conducted on the epigenetic regulations of skin fibrosis, mainly on miRNAs [32, 33]."}
{"_id": "Radiology$$$38c73319-c759-4bdd-99a1-85a07ba78084", "text": "Ozsahin et al. [34] developed a rapid radiosensitivity test (<24\u00a0h) based on lymphocyte apoptosis, a biological response developing 6\u201372\u00a0h after irradiation. The authors showed that low Radio-Induced Lymphocytic Apoptosis (RILA) was significantly correlated with late grade \u22652 tissue toxicities."}
{"_id": "Radiology$$$e47f3fe6-6276-4e8e-ac26-5364dcd6f3c6", "text": "In recent years, the identification of routinely available blood and clinical markers that may help to predict the response to immune therapies alone and in multimodal settings including RT has been in focus of scientists of several disciplines and clinicians [35, 36]. Here, immune markers of the peripheral blood are key factors, since they circulate in the body and enter several tissues in response to disease, therapy, and stressors such as radiation. Stress and immune parameters should jointly be considered, and a differentiation between primary radiation signatures and consecutive systemic immune biosignatures is challenging, but anyhow interconnected [37, 38]. Notably, single immune parameters are insufficient, but rather immune profiles that reflect the complexity of the immune system and the manifold interactions of its cellular and soluble components [16, 39]."}
{"_id": "Radiology$$$eb341af6-4546-48e0-aa77-dcd214755c85", "text": "Tumor response to RT is a multi-faceted metric of outcomes after radiotherapeutic treatment, often observed through biopsy of the tumor or liquid biopsy. There is currently no universal definition of tumor response, but it can generally be considered as any favorable response of the tumor to therapy. Tumor biopsies may aid in the development of personalized patient treatment regimens by providing molecular and structural material for use in developing metrics capable of identifying who will or who will not favorably respond to RT. For patients who do not respond favorably to treatment, they can be offered another more effective avenue of treatment, sparing them from treatment toxicity."}
{"_id": "Radiology$$$04df11d7-0145-4f65-935e-95a6ab1dc0d0", "text": "Identifying treatment-resistant phenotypes/genotypes and therapeutic targets that may influence tumor response is at the center of current radiation biology research. Robust, patient-specific, and predictive biomarkers are critical to assess tumor response to improve patient treatment and outcomes. There is an unmet clinical need to identify translational biomarkers that allow for tailor-made and optimized patient-specific treatment. Patient tumor samples such as tissue and liquid biopsies along with varying modalities of analysis that can be performed to identify predictive biomarkers of RT treatment response will be discussed in this subsection (Figs. 7.5 and 7.6).\n\nAn illustration of different modalities of analysis. When the patient tumor sample is collected, the three modalities of analysis, namely P D Xs, P D Os, and I H C are used. P D Xs and P D Os are patient-derived 3 D models.\n\nFig. 7.5\nPatient tissue biopsy sample types and different modalities of analysis that can be performed to identify predictive biomarkers of RT treatment response\n\n\nAn illustration of four analysis methods of the sample obtained by liquid biopsy. The methods are transmission electron microscopy, size exclusion chromatography, western blot, and polymerase chain reaction.\n\nFig. 7.6\nSchematic of clinically informative elements obtained by liquid biopsy and various analysis methods. (Reproduced with permission from [40])"}
{"_id": "Radiology$$$bf2fc558-e6cb-4e1b-8682-cda18e759a1f", "text": "An illustration of different modalities of analysis. When the patient tumor sample is collected, the three modalities of analysis, namely P D Xs, P D Os, and I H C are used. P D Xs and P D Os are patient-derived 3 D models."}
{"_id": "Radiology$$$56de3269-795c-4c6d-8d6f-7eaf0194f816", "text": "An illustration of four analysis methods of the sample obtained by liquid biopsy. The methods are transmission electron microscopy, size exclusion chromatography, western blot, and polymerase chain reaction."}
{"_id": "Radiology$$$f9982cd9-64da-4f3f-85d9-1cad76015867", "text": "Tissue biopsies are the current gold standard for profiling tumors and can provide both key pathological and molecular information [41]. Numerous studies have investigated the potential of tumor tissue biopsies to predict the biological behavior of tumors, before and during RT, which could highlight the modes of biological action toward radioresistance. Examples of studies are provided in Table 7.4.Table 7.4\nExamples of studies that have used tumor biopsies to predict response to RT.\n\nResearch team\n\nTechnique\n\nTissue type\n\nMain outcome\n\nPollack et al. [42]\n\nTissue biopsy\u2014IHC\n\nProstate cancer\n\nKi67, a marker of cellular proliferation, and apoptotic proteins bcl2 and bax are independently associated with BCDF.\n\nWilkins et al. [43]\n\nTissue biopsy\u2014IHC\n\nProstate cancer\n\nKi67 is an independent prognostic factor for BCDF.\n\nDriehuis et al. [44]\n\nPDOs\u2014Next generation sequencing and dose response kill curve\n\nHNSCC\n\nA patient with a prolonged response to RT had an organoid line with the highest sensitivity to RT.\nRelapsed patients post-RT also had the most resistant organoid lines.\n\nYao et al. [45]\n\nPDOs\u2014Whole-exome sequencing and organoid size\n\nLocally advanced rectal cancer\n\nThe PDOs matched the clinical outcomes of the patient with a 85% match ratio (n\u00a0=\u00a080).\n\nAbbreviations: IHC immunohistochemistry, PDOs patient tumor tissue-derived organoids, HNSCC head and neck squamous cell carcinoma, BCDF biochemical or clinical disease failure, RT radiotherapy"}
{"_id": "Radiology$$$9bafc35a-7f60-425e-8994-356ce30433c3", "text": "Immunohistochemistry (IHC) is a low-cost technique used by pathologists that involves staining fresh, frozen, or paraffin-embedded tissue and is widely applied\u00a0in a clinical diagnostic setting. IHC has been used to identify predictive tissue biomarkers for RT response and include markers related to cell proliferation; ki67 and PKA (protein kinase), cell cycle checkpoint; p53 and p16, apoptosis; bcl2 and bax, growth factor receptors; EGFR (epidermal growth factor receptor) and finally, hypoxia; HIF1\u03b1 (hypoxia-inducible factor 1-alpha (e.g., [42])). IHC facilitates the direct assessment of antigen expression in tissues through enzyme-conjugated antibodies. Initially, IHC was designed to classify the cellular origin of a tumor but with enzyme-conjugated antibodies and paraffin embedding, IHC is also capable of assessing treatment efficacy and is useful for tumor subtyping as well as in predicting patient response to RT. However, IHC is prone to pre-analytical subjectivity, operator subjectivity, and limited to known proteins [46]. Patient-derived 3D models can also be used to assess tumor response to RT and will be discussed in the following section."}
{"_id": "Radiology$$$317d3fbf-9149-499b-bbad-94fbc4cd6d4d", "text": "In the last decade, patient-derived organoids\u00a0(PDOs) have provided novel models for preclinical and translational research for assessing tumor response toward personalization of treatment. Organoids have the potential to be used as predictors for patient treatment response due to their ability to reflect the biological characteristics of primary tumors, i.e., intra-tumor heterogeneity, genotype, and phenotype [47] as well as the tumor microenvironment [48]. Compared to 2D models, PDOs possess improved cell morphology, differentiation, and viability, rendering them more relevant to the in vivo context [49]. Assays that can be performed on organoids include genomic profiling, survival assays, flow cytometric analysis, immunofluorescent, and histological staining. The main limitations associated with organoids include their high cost both in an economic and time-input sense [50]."}
{"_id": "Radiology$$$ae570d23-4756-4b40-a143-61a429f236a0", "text": "PDXs are mouse models that are widely used in modern cancer research and are proving to be another useful platform in the development of personalized medicine strategies due to an improved relationship with the context in vivo. PDXs also demonstrate similar susceptibility to anti-cancer therapies, they closely resemble patient tumor features, have similar histological and molecular characteristics, and can be cultured long-term in vitro [51, 52]. The tumor material to be used in PDXs is derived from fresh tumor tissue collected from a patient during surgery. Small tumor pieces are then implanted into severely immunodeficient or humanized mice. Although PDXs are a promising tool for translational research, they are difficult to apply as tumors may not grow or metastasize. Other disadvantages include the long process required to establish a model which requires significant involvement by pathologists, sampling and representational issues due to tumor heterogeneity, the overall economic cost of their development, their inability to evaluate the involvement of the immune system ex vivo, the potential for grafts to be rejected (\u201cengraftment rate\u201d), and the required use of regulated and approved animal facilities [53]."}
{"_id": "Radiology$$$7dc4156e-5d6a-497c-a3dc-e66dce35c8e0", "text": "PDX models have been used to investigate biomarkers of RT response with the aim of stratifying patients based on risk and facilitating the individualization of treatment, as exemplified\u00a0recently in PDX models of glioblastoma. The CHGA and MAPK8 gene signatures have been associated with increased survival in patients with glioblastoma who have received RT [54]. As the use of PDXs to reliably predict clinical activity of treatment options is still in its infancy, it is currently unknown whether these models can be used to guide individual treatment strategies in a time frame that is useful for a patient. Future technological advancements may accelerate their involvement clinically."}
{"_id": "Radiology$$$04d2bf42-01ea-430c-8a22-2c6d20d21602", "text": "The invasive nature of tumor sample acquisition lends to many of the limitations associated with this sample type, including\u00a0being painful and difficult to collect, time-taxing,\u00a0having limited repeatability\u00a0due to localized sampling of tissue. In addition\u00a0serial assessments are often\u00a0limited, and this diagnostic approach\u00a0requires expert pathologists for evaluation, with the potential to introduce new risks to patients. Importantly\u00a0a tumor may not be fully represented by a single tissue biopsy due to tumor heterogeneity\u00a0which potentially adversely affects the accuracy of the test. Lastly, if the condition of a patient has worsened, the acquisition of tissue biopsy is not feasible [55, 56]."}
{"_id": "Radiology$$$af381800-50a9-49cc-ae1e-468fff263004", "text": "As the collection of tissue biopsies from patients often introduces unnecessary risks to the patient, there has been a recent increase in the focus on safer and less invasive sample collection methods, including via liquid biopsies. Liquid biopsies are generally a rich source of tumor-specific biomarkers, providing a temporal snapshot of the genomic character of a tumor, and can help overcome the complication of intra-tumor heterogeneity [56]. However, there are several limitations associated with liquid biopsies, including the lack of standardization of methodologies and inadequate technical/clinical validation for routine clinical utility [57]."}
{"_id": "Radiology$$$be2c00ac-7c3e-46f9-9f00-bc3c12c89ee2", "text": "It is known that intra-tumoral components are released into the bloodstream, urine, cerebrospinal fluids, pleural fluid, and so on, and that each contains information relating to tumor-specific material [58]. Blood is the most widely investigated liquid biopsy and where intra-tumoral components such as circulating tumor cells, circulating cell-free DNA, and extracellular vesicles\u00a0(EVs) can be found [59]. These are the most investigated of the intra-tumoral components and will be discussed in this subsection (Fig. 7.6). Other intra-tumor components include circulating RNA, circulating proteins, and tumor-educated platelets; however, they will not be discussed in this subsection. Due to recent technological advances, these circulating biomarkers can be detected and researchers have identified them as a novel and promising avenue for stratifying patients based on risk and identifying patients who may be radiosensitive or possess radioresistant disease."}
{"_id": "Radiology$$$9c3576a5-ae11-46da-bb6f-cdf810ac4b8a", "text": "CTCs have recently been discovered to be potential biomarkers for predicting tumor response to RT. A recent study by Qian et al. [60] demonstrated that nasopharyngeal patients with a complete response to concurrent chemoradiotherapy exhibited decreased CTC levels when compared to patients with a partial response. CTCs enter the bloodstream or lymphatic system and are disseminated throughout the body as they are released from primary, metastatic, or recurrent tumors. Metastatic tumors in distant locations can also form through CTCs that evade immune cell recognition [61]. These cells are rare, and the proportion present in peripheral blood is quite low when compared to white and red blood cells [62]. Molecular heterogeneity and the low concentration of CTCs in peripheral blood lead to multiple limitations in terms of their isolation, enumeration, and detection [63]. Current platforms to isolate and analyze CTCs are based on distinguishing features between CTCs and white and red blood cells such as morphology, biophysical and biomechanical properties along with modification, synthesis, regulation, and concentration of protein [64]. CTC isolation/enrichment platforms include microfiltration devices and dielectrophoretic field flow fractionation (DEP). CTC recognition platforms can be split into two groups: (1) label independent and (2) label dependent. The former includes PARSORTIX and CytoTrack. The latter includes iCHIP, CTC-Chip, and CELLSEARCH [64]. CELLSEARCH is an FDA-approved platform and is based on the expression of cell surface markers such as epithelial cell adhesion molecule (EpCAM), cluster of differentiation (CD)45\u00a0(CD45), cytokeratins 8, 18, and/or 19 [65]. This platform uses antibodies against these cell surface markers conjugated with magnetic nanoparticles or immobilized on microfluidic chips."}
{"_id": "Radiology$$$76252390-0be4-4ebf-9bf5-1d022568ba45", "text": "EVs can be isolated from a wide range of body fluids, such as bile, cerebrospinal fluid, saliva, breast milk, urine, blood, and amniotic fluid. Various cell-derived membrane structures are collectively termed EVs and include exosomes, microvesicles, and apoptotic bodies [66]. Exosomes are ideal candidates to study response to RT because radiation not only alters exosome manufacturing, but also affects their molecular cargo [67]. However, investigating the role of exosomes in radiosensitivity is a relatively novel approach, and studies currently are limited to in vitro studies that require translation  in vivo to broaden our understanding of the mechanisms behind the development of radioresistance."}
{"_id": "Radiology$$$0a64c07c-9582-449f-86ef-63fe0991b81e", "text": "Current exosome isolation methods include immunoaffinity capture, ultracentrifugation, density gradient centrifugation, size exclusion chromatography, and exosome precipitation, while characterization methods include western blotting, ELISA, and transmission electron microscopy [68]. The disadvantages associated with these techniques currently make them unsuitable for clinical utility. These include (1) the large amount of starting sample and costly instrumentation that is required for analysis and (2) the labor- and time-intensive nature of the procedures required for sample isolation."}
{"_id": "Radiology$$$62977bed-d919-4a2a-89a4-0647a13276b4", "text": "cfDNA is reported to be found in elevated levels in cancer patients when compared to healthy individuals [69]. Usually, cfDNA is found in fragments ranging from 120 to 220 base pairs (or multiples thereof) [70]. The mechanisms responsible for the release of cfDNA into the bloodstream are not fully understood, but it is thought that it may be facilitated via apoptosis, necrosis, senescence, and actively through cell secretion [71]. In the blood, cfDNA is mostly nucleosome associated, and the tumor derived element in cancer patients is circulating tumor DNA (ctDNA) where concentrations of ctDNA have a linear relationship with tumor size and metastasis [72, 73]. Disease stage will also influence ctDNA concentration with late-stage disease associated with higher levels than early-stage disease [74]."}
{"_id": "Radiology$$$5614cf98-59f5-4400-af9d-3ceaf09ae375", "text": "ctDNA is more fragmented than cfDNA ranging from 100 to 200 base pairs and exists at much lower concentrations [75]. Detectable alterations that are tumor relevant include mutations, chromosomal rearrangements, copy number aberrations, methylation, DNA fragment lengths, tumor gene expression, and the presence of viral sequences (in tumors associated with oncogenic viruses) [73]. In patients with advanced stage nasopharyngeal carcinoma, plasma Epstein\u2013Barr virus DNA load at the midpoint of RT is associated with a worse clinical outcome [76]. Detectable circulating HPV-DNA at the end of chemoradiation is associated with lower progression-free survival in HPV+ cervical cancer patients [77]. Somatic mutations in ATM, a DNA repair gene, can determine exceptional responses to RT in patients with head and neck squamous cell carcinoma, endometrial cancer, and lung cancer [78]. Several methods have been developed to extract and sequence ctDNA. These methods include, but are not limited to:1.\nPolymerase chain reaction (PCR)-based techniques: BEAMing PCR (beads, emulsion, amplification, and magnetics), droplet digital PCR (ddPCR), and real-time quantitative PCR (qPCR).\n\u00a02.\nTumor-informed sequencing approaches: cancer personalized profiling by deep sequencing (CAPP-Seq), Signatera, and targeted digital sequencing (TARDIS)."}
{"_id": "Radiology$$$a0f4187c-f6d5-4285-9b99-0ed090899e12", "text": "Polymerase chain reaction (PCR)-based techniques: BEAMing PCR (beads, emulsion, amplification, and magnetics), droplet digital PCR (ddPCR), and real-time quantitative PCR (qPCR)."}
{"_id": "Radiology$$$b8e14f8e-ebf5-4442-bf3a-e574afe4d793", "text": "Tumor-informed sequencing approaches: cancer personalized profiling by deep sequencing (CAPP-Seq), Signatera, and targeted digital sequencing (TARDIS)."}
{"_id": "Radiology$$$38eb384c-af80-4d3b-b07b-52584a20f639", "text": "Drawbacks associated with some of these techniques include that only one or a small number of mutations can be investigated at a time, a large amount of blood is needed to identify a small number of mutations due to low concentrations of ctDNA in the blood, and prior knowledge related to the tumor must be acquired before analysis, which usually requires invasive sample collection [79]. Next generation sequencing-based techniques include whole-exome sequencing (WES) and whole-genome sequencing (WGS) are also used for ctDNA analysis and limitations related to these techniques include that a large initial concentration of ctDNA is required and low sensitivity has previously been reported for WGS [80]. Examples of studies exploring these circulatory biomarkers can be found in Table 7.5.Table 7.5\nExamples of studies that have utilized biomarkers from liquid biopsies to predict tumor response to RT (see the referenced publications for the full study details, including RT regime)\n\nResearch team\n\nBiomarker\n\nMethodology\n\nStudy population\n\nMain outcome\n\nSun et al. [81]\n\nCTCs\n\nFluorescence microscopy\n\nLocally advanced colorectal patients (n\u00a0=\u00a0115)\n\nBaseline CTC counts of biological responders were significantly elevated when compared to non-responders\n\nJeong et al. [82]\n\nctDNA\n\nHybrid capture-based approach (Capp-Seq)\n\nNon-small cell lung cancer (n\u00a0=\u00a044)\n\nKEAP1 mutations in the NRF2 pathway; present in plasma baseline samples, promoted radiosensitivity and prediction of the rate of local failure post-treatment\n\nSalami et al. [83]\n\nCTCs\n\nEpic Sciences CTC platform\n\nPatients with high-risk localized prostate cancer (n\u00a0=\u00a019)\n\nHigher number of baseline CTCs associated with BCR after therapy\n\nLiang et al. [84]\n\nEBV ctDNA\n\nRT-qPCR\n\nPatients with nasopharyngeal carcinoma (n\u00a0=\u00a0940)\n\nIMRT of CC patients with elevated baseline levels of EBV ctDNA (>4000 copies/mL) demonstrated greater disease-free survival and distant metastasis-free survival compared to IMRT patients\n\nDai et al. [85]\n\nExosomes\n\nCCK-8, invasion, and apoptosis assay\n\nGBM cell lines\n\nExosomes originating from long non-coding RNA AHIF overexpressing GBM cells enhanced radioresistance, viability, and invasion\n\nTang et al. [86]\n\nExosomes\n\nmiRNA technology\n\nNon-small cell human lung cancer cells\n\nRadiation-induced miR-208a enhanced proliferation and decreased cell apoptosis through activation of p21 of the AKT/mTOR pathway\n\nAbbreviations: SABR stereotactic ablative radiotherapy, RT radiotherapy, KEAP1 Kelch-like ECH associated protein 1, NRF2 nuclear factor-erythroid factor 2-related factor, ADT androgen deprivation therapy, BCR biochemical recurrence, EBV Epstein-Barr virus,\u00a0GBM glioblastoma, RT-qPCR real-time quantitative polymerase chain reaction, IMRT intensity modulated radiotherapy, CC concurrent chemotherapy, HGM human glioblastoma multiforme, AHIF antisense hypoxia-inducible factor, CCK-8 cell counting kit-8, miR-208a microRNA-208, AKT protein kinase B, mTOR mechanistic target of rapamycin"}
{"_id": "Radiology$$$f5038a87-7e1b-45d0-b48b-d5768b40f4c2", "text": "Further studies are needed to elucidate the role of biomarkers in predicting tumor response to RT as currently there are limited studies that investigate their potential. Furthermore, biomarker identification is in its infancy, with liquid biopsies and 3D patient-derived models providing an enormous opportunity to further advance precision medicine. The limitations associated with these techniques may be mitigated in the coming years through technological advancements that allow the creation of more specific and sensitive assays. Along with harmonization and standardization of methodologies, the techniques mentioned in this section may move from a translational phase to routine clinical use. It can be expected that research on liquid biopsies and patient-derived 3D models will only grow in the coming years, and with this comes the potential to revolutionize patient care and treatment."}
{"_id": "Radiology$$$ee8b1346-8d5d-460f-8704-9711a29e8af6", "text": "The radiosensitivity of normal cells, tissues, and tumors varies considerably between patients. There is variability in the patient\u2019s response to RT, and most patients experience few or no side effects during or after treatment. However, due to this variability, many patients will receive suboptimal treatment dosing due to current dose thresholds being applied as a protective measure against toxicity events in radiosensitive patients. For patients who will develop side effects, a small number of these may develop more extreme side effects. Extreme side effects related to late radiation toxicity can be irreversible and life-threatening and greatly affect the quality of life of a patient. Identifying patients who possess intrinsic radiosensitivity prior to starting treatment would be clinically beneficial, as RT could do more harm than good in this small subset of patients. Identifying potential predictive biomarkers of normal tissue response to RT has been the focus of intense research within the clinical radiobiology arena over the years. Numerous attempts have been made by various research groups to develop an assay capable of predicting radiosensitivity, yet to date, no biomarkers to predict radiosensitivity are in clinical use. Assays have been developed with the aim of studying and predicting radiosensitivity in normal tissues and tumors. However, current developed methods have produced conflicting results and come with many limitations that make them impractical for clinical use (Table 7.6).Table 7.6\nExamples of studies using traditional and emerging techniques to assess radiosensitivity\n\nAssay\n\nSample type\n\nResearch team\n\nStudy outcome\n\nClonogenic assay\n\nEGFR mutant (n\u00a0=\u00a06) and wild-type (n\u00a0=\u00a09) NSCLC cell lines\n\nAnakura et al. [87]\n\nCompared to wild-type cell lines, EGFR mutant lines demonstrate to be significantly more radiosensitive to low-dose and low fraction-sized irradiation (2 and 4\u00a0Gy).\n\nClonogenic assay\n\nHNSCC patients (n\u00a0=\u00a038)\n\nStausb\u00f8l-Gr\u00f8n and Overgaard [88]\n\nLoco-regional tumor control was not correlated with SF2 after exposure to 62\u201368 Gy.\n\nMTT assay\n\nRadioresistance EAC cell line\n\nMekkawy et al. [89]\n\nThe EAC cell line can be radiosensitized if incubated with bromelain prior to irradiation. Bromelain may have clinical application in protecting normal tissues from damage.\n\nCBMNcyt\n\nPBLCs of LARC patients (n\u00a0=\u00a0134)\n\nDr\u00f6ge et al. [90]\n\nCytogenetic damage of lymphocytes is not a predictor of the outcome of RCT (50.4\u00a0Gy) outcome in LARC patients.\n\nG2\u00a0MN assay\n\nPBLCs from 18 BRCA2 mutation carriers, BRCA1 (n\u00a0=\u00a09) and BRCA2 (n\u00a0=\u00a08) families that do not exhibit the familial mutation (non-carriers) and healthy volunteers (n\u00a0=\u00a018)\n\nBaert et al. [91]\n\nIncreased radiosensitivity in carriers of the BRAC2 mutation compared to healthy volunteers after exposure to 2 Gy irradiation.\n\n\u03b3-H2AX DNA damage assay\n\nLymphocytes from prostate cancer patients (n\u00a0=\u00a050)\n\nPinkawa et al. [92]\n\nNo correlation was found between the development of toxicity and the number of \u03b3-H2AX foci was found.\n\n\u03b3-H2AX DNA damage assay\n\nPBMCs of NSCLC patients (n\u00a0=\u00a038)\n\nLobachevsky et al. [93]\n\nPatients with compromised DNA repair had an elevated risk of developing toxicity.\n\nFTIR spectroscopy\n\nPlasma from prostate cancer patients (n\u00a0=\u00a053)\n\nMedipally et al. [94]\n\nVariations in FTIR spectral signatures related to lipids, proteins, nucleic acids, and amide I/II when comparing late toxicity grade 2+ patients with toxicity grade 1.\n\nRaman spectroscopy\n\nLymphocytes from prostate cancer patients (n\u00a0=\u00a042)\n\nCullen et al. [95]\n\nVariations in Raman spectral signatures related to Amide III, lipids, proteins, and DNA when comparing late toxicity grade 2+ patients with toxicity grade 1.\n\nAbbreviations: EGFR epidermal growth factor receptor, HNSCC head and neck squamous carcinoma, EAC Ehrlich ascites carcinoma, CBNMcyt cytokinesis block micronucleus cytome, PBLCs peripheral blood lymphocytes, LARC locally advanced rectal cancer patients, RCT radiochemotherapy, BRAC breast cancer gene, PBMCs peripheral blood mononuclear cells, NSCLC non-small cell lung carcinoma"}
{"_id": "Radiology$$$470f56fa-c914-4c91-9d24-2cf490427a4a", "text": "Cell viability assays are used predominantly to study cell response by measuring cell survival and proliferation after exposure to cytotoxic compounds. However, they are also extensively used in radiobiology studies. Clonogenic and MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays are well-known assays for assessing in vitro radiosensitivity. The clonogenic assay is currently the gold standard for determining cellular radiosensitivity [96]. Further details on this assay can be found in Chaps. 3 and 7."}
{"_id": "Radiology$$$18342a8d-af34-4a72-bfa6-1c2ebe3b104a", "text": "Early clonogenic studies provided evidence that in patients with cervical cancer and breast carcinoma, SF2 correlates with radiotherapeutic outcome [97, 98]. On the contrary, other early clonogenic studies have not found a correlation between SF2 and radiotherapeutic outcomes in head and neck cancer and multiforme glioblastoma multiforme [88, 99]."}
{"_id": "Radiology$$$0bdcedf4-9155-4df0-a33b-035a6a9afbc7", "text": "Numerous disadvantages are associated with the clonogenic assay, i.e., invasive sample acquisition, observer subjectivity through manual counting, merging of colonies that grow close together, long wait time for results as post-irradiation colonies can form 1\u20133\u00a0weeks later, labor intensive and technically difficult to perform [100\u2013102]. As results from the clonogenic assay have a slow turn-around time, receiving results quite some time after sample collection/analysis would be of very little benefit to the patient, and it is clear that more efficient, rapid, and high-throughput methods need to be developed."}
{"_id": "Radiology$$$b0498d88-7bf6-4d20-9478-e238f1cdad7c", "text": "Plate-based cellular viability assays using tetrazolium salts such as MTT have also been used to assess radiosensitivity and can determine cell growth after irradiation [103]."}
{"_id": "Radiology$$$61560ffc-bd9c-405d-8ee0-bb43eaac95fb", "text": "Mitochondrial enzymes within metabolically active cells reduce the yellow MTT to water-insoluble purple formazan crystals. The amount of formazan crystals formed is directly proportional to the number of viable cells present in the sample, and this allows for the determination of viable cells through absorbance measurements obtained via a spectrometer at 492 nm ([103]; also discussed in Chap. 2). Buch et al. [103] also demonstrated that MTT performs similarly to the clonogenic assay when assessing the survival of irradiated human NSCLC and human glioblastoma cell lines. Compared to the clonogenic assay, the MTT assay is technically easier to perform and provides rapid results [104]. Rai et al. [105] also found that the MTT assay underestimated radiation induced cellular growth inhibition in numerous cell lines by comparing MTT values with cell numbers."}
{"_id": "Radiology$$$e888bafb-5d3d-4428-85e1-d03164dd78c9", "text": "The MTT assay also has multiple disadvantages that make this assay unsuitable for routine clinical use, including:"}
{"_id": "Radiology$$$e81b9eac-b624-467a-a39a-14d895996e4a", "text": "1.\nLack of specificity since tetrazolium reductions also reflect cell metabolism and not just cell proliferation.\n\u00a02.\nInterference from reducing compounds.\n\u00a03.\nAdditionally, excessive direct light exposure of reagents and higher pH of culture medium can lead to sporadic reduction of tetrazolium salts resulting in raised background absorbance values.\n\u00a04.\nMTT is cytotoxic and has been reported to inhibit cellular respiration leading to apoptosis [106\u2013108]."}
{"_id": "Radiology$$$15c6b72d-85dc-4b70-a9b4-7090e680fc0d", "text": "Lack of specificity since tetrazolium reductions also reflect cell metabolism and not just cell proliferation."}
{"_id": "Radiology$$$640e12c6-59fa-438d-a141-2065118cb14d", "text": "Additionally, excessive direct light exposure of reagents and higher pH of culture medium can lead to sporadic reduction of tetrazolium salts resulting in raised background absorbance values."}
{"_id": "Radiology$$$d29ec180-35c8-4ad2-9b1a-e2fb14de769f", "text": "MTT is cytotoxic and has been reported to inhibit cellular respiration leading to apoptosis [106\u2013108]."}
{"_id": "Radiology$$$7f245fb1-f173-43f6-8aa1-2ac9c5c6f34f", "text": "These assays are used to identify chemicals and physical agents with genotoxic potential including irradiation."}
{"_id": "Radiology$$$c43df484-0e97-4aa4-90e4-ccdb958d4b9e", "text": "During mitosis, MN are extranuclear bodies that are separated from the nucleus and contain defective chromosome fragments produced from DNA breakage and/or full chromosomes produced by interference of the mitotic machinery. MN and the micronucleus assay are discussed in detail in Chap. 3."}
{"_id": "Radiology$$$3c943fdf-e7d1-4f12-89a1-819cf6ebec7c", "text": "An early MN study carried out by Rached et al. [109] in the late 90s demonstrated that the MN assay had no predictive power for normal tissue reactions to irradiation. In this study, no variations in MN scores were observed between patients of various cancers who did or did not develop severe acute toxicities. Another study performed by Batar et al. [110] did not reveal any significant differences in MN scores between breast cancer patients who did or did not develop acute toxicities. However, a more recent study found a statistically significant difference in MN frequency per 1000 binucleated lymphocytes from patients who developed late cutaneous toxicity grade \u22653 when compared to grade \u22642 when irradiated with 10 Gy. Limitations of the MN assay include poor reproducibility due to high intra-individual variation and inter-laboratory variability, under certain conditions pseudo-\u00a0MN can occur, and different types of chromosomal aberrations cannot be distinguished by micronuclei alone [111\u2013113]."}
{"_id": "Radiology$$$a93e21f0-d960-4429-8e82-26095711956f", "text": "The \u03b3-H2AX foci assay has also been explored as a prognostic technique for radiosensitivity. Please refer to Chap. 3, Sect. 3.\u200b6 (Cytogenetics and DNA Damage Measurements for Assessments of Radiation Effects) for more information. More recently, this assay was used to predict radiosensitivity in patients with oral squamous cell carcinoma and human colorectal cell lines [114, 115]. Other studies have also shown that \u03b3-H2AX foci enumeration is not an ideal method for the prediction of acute and late toxicity development in prostate cancer, breast cancer, and rectal carcinoma [92, 116, 117]. On the contrary, other studies have used the \u03b3-H2AX foci assay to identify patients at risk of developing radiation-induced toxicity in patients with lung cancer and breast cancer [93, 118]. These conflicting results on the fitness-of-use of \u03b3-H2AX to predict intrinsic radiosensitivity further reinforce the idea that a novel method of analysis that can produce accurate and reproducible results needs to be developed. Disadvantages related to this assay include poor predictive performance and observer objectivity if \u03b3-H2AX foci are enumerated by eye, and this is a fastidious and time-taxing process [119]. Inter-laboratory variations are also produced by this assay where significant variation in manually scored \u03b3-H2AX foci yields obtained from irradiated lymphocytes has been observed [120]."}
{"_id": "Radiology$$$80043eeb-3396-45be-9c97-ed1e972d6736", "text": "The previously mentioned assays have limited clinical use due to their significant shortcomings, and a more practical approach needs to be developed to further investigate intrinsic radiosensitivity as a predictor of radiotherapeutic outcome."}
{"_id": "Radiology$$$7176cde0-a79f-4554-ad6b-1b0d33519b41", "text": "Novel approaches to identify potential predictive biomarkers for radiosensitivity include Raman and Fourier transform infrared (FTIR) spectroscopic analysis of biofluids and cells. These techniques fall under the vibrational spectroscopy umbrella and are based on the transitions between quantized vibrational energy states of molecules due to the interaction between the sample and electromagnetic radiation [121]. Both techniques have numerous advantages over the previously mentioned predictive assays including minimal sample preparation and minimally invasive sample collection, speed, ease, and cost of analysis; they also allow for non-destructive and label-free analysis of a sample [121]."}
{"_id": "Radiology$$$af2f81b5-d540-40a8-9936-f30866760138", "text": "Each technique provides a biochemical fingerprint of a sample. Researchers in biomedical fields tend to focus on the range from 400 to 4000 cm\u22121 and, in particular, the fingerprint region from 600 to 1800 cm\u22121, as vibrations in these spectral regions produce refined bands and rich biochemical information related to disease prognostics and diagnostics. A major disadvantage of IR spectroscopy is the interference of water, which can overshadow crucial biochemical information [122]. However, Raman spectroscopy has a weak water signal and minimal water interference, making it ideal for the analysis of biological materials [123]."}
{"_id": "Radiology$$$64c9c902-711f-411f-9997-fd4f1d53398c", "text": "FTIR and Raman spectroscopy have recently been shown to be capable of discriminating patients on radiotherapeutic response [94, 95]. Both studies were successful in identifying variations in spectral intensities between patients with late toxicity grade 0\u20131 and grade 2+ with a high degree of sensitivity and specificity."}
{"_id": "Radiology$$$9926cf4c-509c-4b56-9a98-3a0d0f9caeab", "text": "Current research from the same group involving Raman spectroscopy includes the analysis of biofluids and lymphocytes for the prediction of late normal tissue toxicity in high-risk localized prostate cancer patients and HPV+ head and neck cancer patients. Vibrational spectroscopy is far from being translated into the clinic, as currently there are no standardized protocols regarding the handling, storage, and preparation of samples to facilitate uniform spectroscopic analysis. However, researchers active in this area are currently investigating this to provide optimal protocols that will generate accurate and reproducible results [124, 125] (Fig. 7.7).\n\nAn illustration of the basic schematic of a Raman spectrometer. Incident beam strikes the target. The scattered beams are anti-Stokes scattering, Stokes-scattering, and Rayleigh scattering. A graph is obtained from the scattered beams.\n\nFig. 7.7\nBasic schematic of a Raman spectrometer"}
{"_id": "Radiology$$$f8490b25-a9b5-4fd6-957e-d93d3fa0d978", "text": "An illustration of the basic schematic of a Raman spectrometer. Incident beam strikes the target. The scattered beams are anti-Stokes scattering, Stokes-scattering, and Rayleigh scattering. A graph is obtained from the scattered beams."}
{"_id": "Radiology$$$9812bca4-c75e-42e3-90de-7f318375b30d", "text": "Raman spectroscopy is based on the inelastic scattering of light and scattering occurs when a sample is probed by a monochromatic light source. Most of the scattered light will be Rayleigh scattered where the laser photons\u00a0will neither gain nor lose vibrational energy and will have the same energy as the incident light. Rayleigh scattering is also known as the elastic scattering of light and provides no information about molecular vibrational transitions [124]. A small fraction of light (approximately 1 in 107 photons) is scattered at optical frequencies different from that of the incident light [125]. The Raman effect occurs when light probes a molecule and interacts with the electrons of the molecular bonds and the scattered light vibrational energy is not equal to that of the incident light. This process leaves the molecule in an altered vibrational state. Other light scattering processes take place with Rayleigh scattering, i.e., Raman scattering, and two forms exist: stokes (dashed arrow) and anti-stokes. Anti-Stokes scattering\u00a0occurs when atoms or molecules lose energy during the transition from higher to lower vibrational energy states. Stokes scattering occurs when the atoms or molecules relax into a high vibrational excited state from the ground virtual state, resulting in a vibrational energy level higher than that of the incident light [124]. The Stokes scattered light\u00a0will enter the Raman spectrometer and by a series of optics and mirrors will be directed to a monochromator. The collected light will be analyzed by the spectrometer and displayed as a Raman spectrum on a computer."}
{"_id": "Radiology$$$d280255e-7db7-471e-97a9-3542d15e5da6", "text": "RT is a mainstay in cancer therapy, and due to recent technological advances, therapeutic efficacy has improved over the years. However identification of patients at risk of toxicity, as well as those who are\u00a0radiosensitive or radioresistant\u00a0remains a research challenge, which, if successful, could save patients from unnecessary treatment and avoid normal tissue toxicity and potentially result in improved tumor control. Numerous studies have attempted to identify a robust predictive biomarker of patient response to RT. Although the results of the studies have been promising, to date\u00a0no biomarkers have been validated or translated successfully into the clinic. The assays mentioned here are not an exhaustive list of those currently being used for research purposes to study radiosensitivity (Box 7.4)."}
{"_id": "Radiology$$$a0d859fd-b764-4e9b-9ad8-c91ed7692081", "text": "There is patient variability in response to RT with most patients experiencing few or no side effects during or post-treatment.\n\nA small subset of patients may experience life changing and deliberating toxicities.\n\nCurrently, no biomarker is in use in the clinic today to predict normal tissue toxicity.\n\nDisadvantages of conventional radiobiological assays deem them unsuitable for translation into the clinic.\n\nNovel methods such as vibrational spectroscopy demonstrate great potential in the hunt for a predictive biomarker."}
{"_id": "Radiology$$$64a9986d-4fc7-4256-bd41-96ce1d339dfc", "text": "There is patient variability in response to RT with most patients experiencing few or no side effects during or post-treatment."}
{"_id": "Radiology$$$21a5af13-533b-4a4b-9875-7b0d426307c0", "text": "A small subset of patients may experience life changing and deliberating toxicities."}
{"_id": "Radiology$$$235d56f1-5c23-4b78-acb3-96ad7870e135", "text": "Currently, no biomarker is in use in the clinic today to predict normal tissue toxicity."}
{"_id": "Radiology$$$79a96ae4-e945-408a-882b-2c39465f5fb1", "text": "Disadvantages of conventional radiobiological assays deem them unsuitable for translation into the clinic."}
{"_id": "Radiology$$$0c21f47e-3b1c-4806-a6f8-3b47ed0853e0", "text": "Novel methods such as vibrational spectroscopy demonstrate great potential in the hunt for a predictive biomarker."}
{"_id": "Radiology$$$e547b6f3-2eae-4bee-a4f8-476875c5e8e3", "text": "The G2 chromosomal radiosensitivity assay (also known as G2 assay) is a method that illustrates the existence of enhanced radiosensitivity and cancer predisposition based on the chromatid aberrations after G2-phase irradiation. For the evaluation of the individual radiosensitivity with this technique, peripheral blood lymphocytes are irradiated in vitro in their G2-phase of the cell cycle, incubated to allow repair of DNA damage, and blocked in mitosis by the use of colcemid, so that the chromatid aberrations can be observed and quantified. A high yield of chromatid breaks can indicate high radiosensitivity. This methodology has a major advantage as it enables a time-efficient individual radiosensitivity assessment."}
{"_id": "Radiology$$$49d4f050-0258-4153-ba4c-7b4fb0d0505a", "text": "The original G2 assay was developed by Sanford et al. [126]. However, a significant problem of this method was the high variability in radiation-induced damage observed in different samples even from the same donor. In addition, there was often an overlap between the G2 chromatid aberration yield in lymphocytes from healthy donors and cancer patients. Following further development, Terzoudi et al. [127, 128] proposed the use of caffeine in order to induce G2/M checkpoint abrogation, simulating this way the high radiosensitivity of AT patients. AT cells are known to have a defective G2/M checkpoint arrest and therefore AT patients are highly radiosensitive. With the use of caffeine, it was feasible to express the individual radiosensitivity in relation to the high radiosensitivity level observed in AT patients (Figs. 7.8 and 7.9). This protocol has a great advantage that it minimizes the effects of laboratory specific parameters and makes the inter-laboratory comparison feasible by enabling an ameliorated intra-experimental and inter-laboratory reproducibility. More recently, efforts have been realized for further optimization of the G2 assay by using other DNA Damage Response (DDR) and G2-checkpoint inhibitors\u2014than caffeine\u2014such as ATR- or ATM/ATR inhibitors (e.g., VE-821 and UCN-1). Of these inhibitors, VE-821 has been proven effective in a rapid radiosensitivity assessment of different cell lines as well as normal tissue and primary tumor cells [129].\n\nAn illustration of a cluster of chromosomes. Some have broken chromatids, while arrows point from one pair of chromosomes to the other. \n\nFig. 7.8\nG2 chromosomal radiosensitivity assay. Chromatid breaks after 1 Gy of \u03b3-irradiation as visualized at a metaphase peripheral blood lymphocyte from a healthy donor where four chromatid breaks are observed. (Reproduced with permission from [128])\n\n\nAn illustration of a cluster of chromosomes, some with broken chromatids. \n\nFig. 7.9\nG2 chromosomal radiosensitivity assay. Chromatid breaks after 1 Gy of \u03b3-irradiation as visualized at a metaphase peripheral blood lymphocyte after applying G2-checkpoint abrogation by means of caffeine where 13 chromatid breaks are visualized. (Reproduced with permission from [128])"}
{"_id": "Radiology$$$edc05255-58df-4f82-88f2-d1a93ae7252e", "text": "An illustration of a cluster of chromosomes. Some have broken chromatids, while arrows point from one pair of chromosomes to the other."}
{"_id": "Radiology$$$c33d61ac-3c24-4935-b747-5d2f513c79ae", "text": "An illustration of a cluster of chromosomes, some with broken chromatids."}
{"_id": "Radiology$$$21fef5c7-42f2-495b-acc0-b53bd1ee17a4", "text": "Age at the time of radiation exposure is a key factor contributing for radiation-induced health effects, namely cancer. In a general way, it is accepted that individuals exposed at early ages are the most radiosensitive, whereas the latency period from primary damage to outbreak into cancer is longer. Then, radiation sensitivity decreases until maturity and increases again at older ages [130, 131]. In addition, considering that both cancer incidence and mortality rates increase with age, a model of radiation-induced cancer must also include the attained age. Attained age is defined as the sum of the age of the person at the time of radiation exposure and the period elapsed since the radiation exposure (\u201cattained age\u201d\u00a0=\u00a0\u201cage-at-exposure\u201d\u00a0+\u00a0\u201ctime since exposure\u201d) [132]."}
{"_id": "Radiology$$$21157423-507c-4d97-ba26-c10dff8bb0e2", "text": "Age-time patterns may also be represented as the \u201ctime since exposure,\u201d corresponding to the \u201cattained age\u201d subtracting the \u201cage-at-exposure.\u201d For example, the cancer risk for someone with an age at exposure of 15\u00a0years and observed at an attained age of 40\u00a0years (time since exposure of 25\u00a0years) will be different from the risk for someone exposed at the same age but observed at an attained age of 79\u00a0years (time since exposure of 64\u00a0years) [132]."}
{"_id": "Radiology$$$d47517d5-b8f1-406d-a90f-d67804e4e885", "text": "The understanding of the age-related alterations that may compromise individuals\u2019 health after exposure to IR is increasingly relevant, along with the elucidation of the biological mechanisms underlying the aging-radiation exposure association. The fact that life expectancy of the worldwide population is steadily rising emphasizes the urgent need for a better understanding of the relationship between aging and sensitivity to radiation, which impacts radiation protection in clinical practice [130]."}
{"_id": "Radiology$$$1a058032-5c0a-4653-a2c5-0650bb71a6d7", "text": "Epidemiological studies developed in the Life Span Study (LSS)\u00a0cohort of the Japanese atomic bomb survivors have provided valuable data on the relationship between the age at the time of exposure and oncogenic risks. The most standard models for radiation sensitivity, based on the measure of carcinogenic events, predict that the relative risks decrease monotonically with the increase of age at exposure, at all ages. However, new epidemiological data suggest that risks differ by age at the time of radiation exposure and by type of cancer (Fig. 7.10) [130].\n\nA line graph of relative susceptibility of cancers over time. Leukemia and cancer of brain, skin, and thyroid peaks at birth and reduces by childhood. Breast and uterine cancers peak at puberty. Most solid cancers reduce over time. Lung cancer increases. Cancer of colon, liver, and bladder reduce.\n\nFig. 7.10\nSchematic representation of the relationship between the relative susceptibility and the age at exposure. (Reproduced with permission from [133])"}
{"_id": "Radiology$$$13fe1bb8-db5c-4494-96ae-69885c4ad739", "text": "A line graph of relative susceptibility of cancers over time. Leukemia and cancer of brain, skin, and thyroid peaks at birth and reduces by childhood. Breast and uterine cancers peak at puberty. Most solid cancers reduce over time. Lung cancer increases. Cancer of colon, liver, and bladder reduce."}
{"_id": "Radiology$$$1fae3d44-c9f3-4f3d-a413-97334fbd260e", "text": "Data from the LSS cohort of the Japanese atomic bomb survivors showed that the excess relative risks (ERRs) of developing cancer following radiation exposure were higher during childhood and progressively decreased as a function of age until ages of 30\u201340\u00a0years old. However, for ages of exposure higher than 40, the ERR of developing solid cancer increased again. Thus, a bimodal distribution of radiation-induced cancer risks is associated with different biological processes. The greater susceptibility of children to radiation carcinogenesis is thought to be associated with three mechanisms: (1) long latency period between the primary injury and the cancer onset, that make children more likely to experience the long-term consequences, such as cancer; (2) faster radionuclides accumulation in growing bones compared to bones of an adult; (3) high frequency of cell division (as the one occurring in a growing organism) may allow an impairment of the radiation-induced DNA damage repair mechanisms. At a cellular level, this high radiosensitivity of children may be also related with the initiation of malignant processes due to the larger number of stem cells that can derive into cancer cells in younger people compared with aged ones. On the other hand, the radiation risks for individuals exposed at later ages are related to the age-related deterioration of cell functions, which can be responsible for an augmented susceptibility for oncogenic transformation [130, 131, 134]."}
{"_id": "Radiology$$$c4d6a4cd-6c52-4fc2-898b-a262cc437b1d", "text": "The results of surveys targeting atomic bomb survivors also showed that the periods that relate to high radiation sensitivity vary according to the type of cancer. For individuals exposed while they were young, the risks of thyroid and stomach cancers and solid cancer as a whole are higher, while individuals exposed during puberty have an increased risk of breast cancer and people with 40\u00a0years old or older have increased risk of lung cancer [135, 136]."}
{"_id": "Radiology$$$2466669c-34fd-4f91-9626-1025593e175a", "text": "The higher radiosensitivity of individuals exposed at early ages is likely to have a long-term biological counterpart in their organisms. The mechanistic interplay between age and radiosensitivity is thought to be influenced by age-related cellular changes, such as impaired DNA damage repair, telomere erosion and accelerated cellular senescence, augmented susceptibility of cells to oxidative stress and inflammation, and radiation-induced epigenetic alterations (Fig. 7.11) [130, 131].\n\nAn illustration of the mechanistic interplay between age and radiosensitivity for impaired D N A damage repair, telomeres attrition, oxidative stress, and epigenetic alterations in young and aged cells. \n\nFig. 7.11\nAge-related cellular changes that may influence radiosensitivity and their mechanistic interplay. Compared to young cells, aged cells present increased impaired DNA damage repair, telomeres attrition, increased oxidative stress, and additional epigenetic alterations"}
{"_id": "Radiology$$$46430658-2f53-4e30-b171-ea7309243b3b", "text": "An illustration of the mechanistic interplay between age and radiosensitivity for impaired D N A damage repair, telomeres attrition, oxidative stress, and epigenetic alterations in young and aged cells."}
{"_id": "Radiology$$$076a39ba-19e8-4671-b512-bc0fc21c9445", "text": "Aged cells show a decline in the efficiency of the DNA damage response (DD) after radiation-induced DNA DSBs. The DDR should begin with the recruitment of proteins involved in both nonhomologous end joining (NHEJ) and homologous recombination (HR) repair pathways (see Chap. 3). Aged cells present several defects in these repair pathways such as delayed DDR kinetics, poor repair efficiency, and compromised repair due to chromatin reorganization as a result of aging. Thus, the aging process entails a disturbed nuclear organization that may compromise the recruitment of DDR proteins to the site, where they are needed, the nucleus. Irradiating aged cells will increase the damages in an already dysfunctional repair system, leading to irreversible damages. These damages are usually persistent and appear in a chronic mode increasing the damage burden in cells and tissues. Such accumulated damages can trigger enhanced inflammatory and immune system responses often leading to pathophysiological conditions like autoimmune disease and sensitivity to radiation and other types of environmental stresses [130, 137, 138]."}
{"_id": "Radiology$$$2088ada1-f0c8-4e4d-838f-de3600498f46", "text": "Previous studies showed that telomere shortening relates to increased radiosensitivity. When aged cells escape from replicative senescence (a state of permanent growth arrest induced when shortened telomere length is attained), telomeres keep getting shorter, originating a greater number of uncapped chromosomes available to rearrangements. This loss of telomere integrity leads to an increase of genomic instability, which can initiate a carcinogenic process [130, 131]."}
{"_id": "Radiology$$$03b91f45-152c-46c3-ad8e-80be90e5e94f", "text": "Although there is some controversy about the causal relation between oxidative stress and an aged phenotype, it is known that aged cells have higher ROS levels production and a compromised antioxidant machinery compared with younger cells. This progressive loss of the pro-oxidant/antioxidant equilibrium compromises both cellular structures and homeostasis of aged cells. Exposing these aged cells to IR will unequivocally overload the antioxidant system, making them more susceptible to the IR-induced cell damages [139]."}
{"_id": "Radiology$$$ce8b51c8-0581-4ee0-816c-a6a11ec7918f", "text": "Radiation-induced oxidative stress can drive epigenetic alterations, such as (1) DNA hypomethylation through 8-OHdG methylation inhibition or DNA demethylation processes, (2) DNA hypermethylation through DNA methyltransferase up-regulation or DNA methylation catalysis, (3) histone modifications, and (4) miRNA expression. On the other hand, cumulative epigenetic alterations can also occur upon aging. Although this topic must be further explored, it seems to be a relation between epigenetic alterations and age-dependent radiosensitivity [131]."}
{"_id": "Radiology$$$682ce856-3a34-489a-8e1e-9c2f0cf3edd0", "text": "In children/adolescents/young adults, RT remains essential for the curative treatment of brain tumors, Hodgkin lymphomas\u00a0(HL), acute leukemias, Ewing and soft tissue sarcomas, neuroblastomas, nephroblastomas, or high-risk retinoblastomas. Life expectancy is long for the 80% of children/adolescents who are likely to be cured. The incidence of acute post-radiation complications, especially late, and proportional to the dose delivered may exceed that in adults. In fact, the cumulative incidence of overall iatrogenic sequelae 30\u00a0years after the end of treatment reaches more than 70% in this population compared to 15% maximum in the adult population after a median 3\u20135\u00a0years of follow-up. This late toxicity can lead to sometimes lethal sequelae with a major socio-economic impact (e.g., educational problems, parental mobilization, difficulties in entering the workforce, hospitalizations and costly symptomatic treatments and impoverishment, etc.). Along with high cure rates in this population, radiation-induced cancers appear with a probabilistic distribution (20-year cumulative incidence of secondary malignancies 3%)\u2014but the incidence of which increases with the dose delivered and the duration of follow-up. Also note, however, that risk of secondary cancers increases in cancer patients who have not had prior radiation treatment as well as those who had chemotherapy [140, 141]. Differences are observed in the long-term, site-specific patterns of excess radiation inducing second malignancies between survivors of childhood cancer and adult-onset cancer, in terms of second malignancies histologic distribution, magnitude of risk, latency period, associated risk factors (genetic predisposition, environmental exposures, hormonal factors, and immune function) [142, 143]."}
{"_id": "Radiology$$$adeed8e8-d955-4040-9368-65fb24458141", "text": "On the other hand, RT is essential in the multidisciplinary management of the majority of cancer types in elderly patients, where it sometimes is considered as the first treatment option, often hypofractionated, and in others, as an alternative to surgery and/or chemotherapy."}
{"_id": "Radiology$$$d9fd8ff4-2b48-4a11-b5b9-b8e352f3a0d1", "text": "In adults and the elderly, self-sustaining inflammation, fibrosis/atrophy, microcirculatory abnormalities are more readily associated with radiation-induced sequelae. In addition, in children, the manifestation of radiation-induced sequelae involves abnormalities in tissue maturation, delays (or even cessation) of growth of irradiated tissues\u2014resulting in additional hypoplasia and/or hypofunction [144]."}
{"_id": "Radiology$$$32e5ff87-1784-47e5-9ff9-b1a8b1722b3f", "text": "In adults, the distribution of individual radiosensitivity follows a Gaussian curve, and the toxicity observed in 5% of the most radiosensitive individuals is at the origin of dose recommendations to be applied to organs at risk in any patient in daily RT practice. There are many reasons to believe that this is not the case with children and seniors, with likely great variability with age. This is especially true if one consider all the changes in metabolic functions throughout growth and/or due to additional comorbidities, variations in tumor death, and tissue healing pathways with age and tumor predispositions associated with childhood cancer involving DNA repair pathways (assuming that this trait correlates with individual radiosensitivity)."}
{"_id": "Radiology$$$ba97edba-b28e-41ca-a8cf-3d78fc87a0af", "text": "Differences in organ development and tissue repair in children and adults have a significant effect on the expression of radiation injury. In many tissues, organ development is supported by cell proliferation from the prenatal period. During the development of each tissue, pluripotent embryonic stem cells differentiate into different unipotent lineages that will participate in mature tissue homeostasis. Some stem cells remain\u2014ensuring self-renewal within the tissue. Thus, these two mechanisms are involved in growth as well as in tissue repair and regeneration. As the tissue matures, each organ thus contains a mosaic of dividing cells that are at rest either transiently or permanently. During childhood and adolescence, body tissues follow different growth patterns with their own kinetics. Not surprisingly, the rapid growth of normal tissues also seems to coincide with increased tissue radiosensitivity and, consequently, with a higher susceptibility to radiation-induced neoplasia. Overall, neurocognitive effects, development of muscles, and growth of bones are all sensitive to the age at treatment. For example, the intelligence quotient (IQ)\u00a0deteriorates more in children irradiated on the brain before the age of 5 years compared to older children [145]."}
{"_id": "Radiology$$$8db3c64e-5df0-4bec-bd50-feb0ce89139a", "text": "In contrast, in the elderly, the cells of the proliferative compartment move toward a permanent state of rest or senescence. This aging process becomes critical after injury because, although senescent cells are capable of metabolic functions, they lose their proliferative capacity after stress such as radiation. Therefore, late effects in the elderly population can be seen as the result of an interaction between their diminishing ability of cells to repair themselves after injury and their natural tendency to progress to a state of senescence, which itself can be accelerated by irradiation."}
{"_id": "Radiology$$$7e4e19c5-d832-4a8d-8216-9ff29b68b1e8", "text": "Only very rare cases of children have been studied for their individual radiosensitivity. Three genetic syndromes have formally been associated with RT-induced fatal non-cancer adverse tissue events:  AT (homozygous ATM mutations), LIG4 syndrome (homozygous LIG4 mutations), Nijmegen\u2019s syndrome (homozygous NBS1 mutations)\u2014all characterized by the impairment in DSB repair and signaling pathways (see detailed information in Sect. 7.8). Noticeably, some syndromes also confer an increased individual cancer predisposition. Some cases of significant radiosensitivity with mutations of genes whose function was not expected in the radiation response have to be stressed\u2014involving cytoplasmic functions or cell scaffold and membrane organization (for example, Huntingdon disease, Usher syndrome; [146])."}
{"_id": "Radiology$$$7edfbde9-54f2-477b-bca3-bad7673a9126", "text": "The individual radiosensitivity in children/adolescents and elderly is thus so far mainly unknown, and clinical trials are pending using individual radiosensitivity assays and very long-term observational studies (Box 7.5)."}
{"_id": "Radiology$$$12190ffe-f113-4b14-a9a2-1e9e5d266e76", "text": "Age at time of radiation exposure is a key factor contributing to radiation-induced health effects.\n\nNew epidemiological data suggest that risk of developing cancer differs by age at the time of radiation exposure as well as by type of cancer.\n\nCellular and molecular changes related to aging influence radiosensitivity.\n\nDifferences in organ development and tissue repair in children and adults have a significant effect on the expression of radiation injury."}
{"_id": "Radiology$$$b3b38df9-2003-4aeb-89ea-6a6b0d1202b2", "text": "Age at time of radiation exposure is a key factor contributing to radiation-induced health effects."}
{"_id": "Radiology$$$32572654-7a4b-4758-a941-d4207315950d", "text": "New epidemiological data suggest that risk of developing cancer differs by age at the time of radiation exposure as well as by type of cancer."}
{"_id": "Radiology$$$697c37d6-726c-4a7b-9157-b4999de588e8", "text": "Differences in organ development and tissue repair in children and adults have a significant effect on the expression of radiation injury."}
{"_id": "Radiology$$$118aa40b-8f57-42bb-acc6-00800b00ac4e", "text": "The different individual radiosensitivity may be affected by genetic and individual factors as well as by lifestyle factors. One of the individual factors that have been associated with radiation sensitivity is biological sex."}
{"_id": "Radiology$$$96791d74-5a1d-4613-9b14-48b70ed6d67e", "text": "The different radiosensitivity and radiosusceptibility for each sex could be due to biological factors. The human sex is determined by the sex chromosomes, namely by Y and X chromosomes. Whereas females have two X chromosomes, males have one Y and one X chromosome. These two sex chromosomes differ in terms of length, structures, and in the number and types of genes. Thus the X chromosome is approximately 160 Mb with more than 1000 genes while the Y chromosome is approximately 65 Mb with only 100 genes. The Y-specific genes are expressed mostly in testicular tissue with the SRY gene being the most important for determining male sex [147, 148]."}
{"_id": "Radiology$$$7e803fd7-90c6-4b5f-9cc4-176711ab8fff", "text": "Gene mutations or defects in gene expression of sex chromosomes dominantly affect the X chromosome and could be responsible for the death of the zygote and, consequently, decrease female birth. It also is hypothesized that differences in biological sex-related radiation responses could be due to immunological and hormonal differences apart from epigenetic and genetic factors. The mechanism underlying biological sex-related radiation sensitivity is still not clear and needs to be studied in more detail. Until now, it is known that the cellular response to radiation is highly complex and involves several processes like alterations in gene expression, signal transduction, repair process, and cell proliferation and death which could vary with sex."}
{"_id": "Radiology$$$222e1bf3-ae02-4384-b7e0-4fc6d94078ff", "text": "Most of the data used for improving the knowledge on radiation-induced health effects and radioprotection was gained from the atomic bomb survivors in Hiroshima and Nagasaki (in Japan) and Chernobyl (in Ukraine). Also, the development of other epidemiological and cohort studies to evaluate the effects of radiation on the population exposed to high-dose levels due to medical reasons, radiation accidents, or from natural sources, contributed to the effects documented till now, as summarized in Figs. 7.12 and 7.13. The use of cancer risk models allows to predict the excess relative risk (ERR), i.e., the proportional increase in risk over the background absolute risk, and the excess absolute risk (EAR) of cancer, i.e., the additional risk above the background absolute risk, of cancer as a consequence of radiation exposure [134].\n\nAn illustration of the health risks to different radiation exposures in males and females. The different exposures in increasing order of risk are occupational exposure, A-bomb survivors, and Chernobyl disaster. The health risks are listed under each exposure for males and females.\n\nFig. 7.12\nSummary of biological sex-dependent health risks induced by radiation exposure. (Reproduced with permission from [149])\n\n\nAn illustration of the most common radiation-exposure associated morbidities in males and females, along with their details.\n\nFig. 7.13\nSummary of most common morbidities induced by radiation exposure for each biological sex. (Reproduced with permission from [149])"}
{"_id": "Radiology$$$572b8950-fc6e-41f5-8477-fce8bd9c7754", "text": "An illustration of the health risks to different radiation exposures in males and females. The different exposures in increasing order of risk are occupational exposure, A-bomb survivors, and Chernobyl disaster. The health risks are listed under each exposure for males and females."}
{"_id": "Radiology$$$3654db6c-4f03-4582-90ac-13bad4cc01d8", "text": "An illustration of the most common radiation-exposure associated morbidities in males and females, along with their details."}
{"_id": "Radiology$$$c6a403e1-a1fb-4f63-863f-62352ce7700c", "text": "The analyses of the several investigations done since 1945, based on data from Hiroshima and Nagasaki A-bomb survivors, revealed a higher incidence of cancer with elevated rated of leukemia, breast cancer, thyroid carcinoma, stomach and lung cancers, with risk for solid cancers varying with sex (Table 7.7). Related to radiation-induced lung cancer (LC), an increased radiation risk was evidenced and it is nearly four times greater for females than males [150]. Furthermore, a report on mortality from a follow-up from 1950 to 1997 showed that only ERR of cancer is far higher for females than males, without significance for EAR [134] (UNSCEAR 2000).Table 7.7\nValues for excessive relative risk per Sv (ERR/Sv) obtained from A-bomb survivors data for age at exposure of 30\u00a0years (UNSCEAR 2000)\n\nCancer type\n\nMales\n\nFemales\n\nFemale/male ratio\n\nAll solid cancer\n\n0.38\n\n0.79\n\n2.1\n\nLung\n\n0.50\n\n2.18\n\n4.3\n\nEsophagus\n\n0.41\n\n0.84\n\n2.1\n\nStomach\n\n0.29\n\n0.60\n\n2.1\n\nColon\n\n0.46\n\n0.95\n\n2.1\n\nLiver\n\n0.58\n\n0.58\n\n1.0\n\nBladder\n\n1.18\n\n0.98\n\n0.8\n\nBreast\n\n0\n\n1.55\n\n\u2013\n\nOther cancer\n\n0.47\n\n0.28\n\n0.6"}
{"_id": "Radiology$$$6d001b5f-f5c0-4902-86ba-a38781175c9b", "text": "Reports and studies based on the nuclear catastrophe in Chernobyl in 1986, where the population was exposed mostly to iodineIodine-131, showed an increased incidence of a range of cancers. Apart from the incidence of the same types of cancers report from A-bomb survivors (Table 7.7), there was also an increase in the incidence of bladder cancer and renal-cell carcinoma. There are still new cases of non-hematological cancers detected every year, so it is too early to present the final reports. The development of various radiation-related health problems in people living in the contaminated territories of Ukraine, Russia, and Belarus were more evident in women, inclusively by affecting their reproductive abilities and leading to an increase in the number of spontaneous miscarriages, mostly of the female fetus. Moreover, in Ukraine, the development of thyroid cancer was seen 2.5 times more often in females than in males who lived in contaminated territories [149, 151]."}
{"_id": "Radiology$$$13aa068d-7206-462e-837b-90bf33faf2d3", "text": "Data from the most recent nuclear accident in Fukushima is not yet enough to reach conclusions. Although the residing population was immediately evacuated from the most contaminated area, in the most affected areas that were not evacuated, average doses to adults in the first year were estimated to be <4\u00a0mSv, so discernable increases in related cancers are not expected (UNSCEAR 2021)."}
{"_id": "Radiology$$$46c96ed9-62a3-4dc8-b0c6-7f6dc66ae353", "text": "Studies from health care workers exposed to IR strongly indicate that occupational exposure leads to increased rates of IR-related cancers. Although these outcomes are associated with dose and also are age dependent, little attention has been given to biological sex [149]."}
{"_id": "Radiology$$$4e09332c-c7ef-4815-9cc7-b98384b9d998", "text": "A study carried out in Mayak workers about LC mortality revealed that ERR is four times higher for females than males, but the EAR is 0.43 less in the same comparison. Related to other cancers, the ERRs per Gy is also higher in females than males for lung, liver, and bone cancers. Moreover, a cohort study from Sweden, Denmark, and the USA about the carcinogenic effects of long-term internal exposure to alpha-particles radionuclides showed no significant differences between sex for solid cancer. The reduction of the female birth rate was also reported for the population living close to nuclear power plants or affected by nuclear testing [147, 149]."}
{"_id": "Radiology$$$d1487dd3-77b6-4ca6-a577-ce558b904762", "text": "Thus, the epidemiological studies presenting separated risk coefficients for females and males do not present a consensus about sex-related radiation sensitivity. Although the studies from A-bomb survivors demonstrated higher ERR values for women than for men for all solid cancers, the corresponding EAR values are similar for males and females when sex-specific organs are not considered. The data collected from the radiation-induced occurrence of the same cancer type in different cohorts is also inconsistent. Although all these differences, the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) concludes that the EAR and ERR for total solid tumors are around two times higher in women than men, varying with site and organs, but for leukemia, no sex differences were observed [147, 149]."}
{"_id": "Radiology$$$d8acfe03-30f6-4066-8fa6-6f59ea784d86", "text": "Several experiments were carried out in animal models to provide clear information about the relationship between biological sex and radiation sensitivity as well as to confirm and expand the evidence obtained from epidemiological studies. Also, cell models were created from peripheral blood samples from healthy donors, cell lines, or primary cultures from organs of interest. These studies made it possible to study in depth the molecular mechanism inherent to sex differences in radiation sensitivity, namely to access cellular responses to IR, whole-genome screening for gene expression, and analyses of epigenetic regulatory mechanisms [147]."}
{"_id": "Radiology$$$9bac354a-eb4c-48d1-a3b1-5b0a72b53893", "text": "The data obtained through the analyses of gene expression as well as from epidemiological studies showed no correlations among the sex-specific expressed genes and corresponding cellular phenotypes. Nevertheless, a much higher incidence of thymic lymphoma and osteosarcoma have been found in female mice after treatment with 227Th than in male mice. Most recently, it was reported bystander effects in the non-radiated spleen of mice and rats varying according to the sex-specific differences. A sex-specific activation of distinct pathways was also suggested in mice, in response to whole-body irradiation as well as different tissues and organs irradiations with acute and chronic low doses [147, 149]."}
{"_id": "Radiology$$$670029bd-fc4a-46b4-bd34-9a5652b64505", "text": "The differences in radiosensitivity of males and females could be due to biological factors.\n\nUNSCEAR concludes that the EAR and ERR for solid tumors are around two times higher in females than in males.\n\nThe identification of biological sex-related radiosensitivity will contribute to personalized dose and fractionation for RT as well as for radiation protection.\n\nCurrently, the annual dose limits for occupational exposures recommended by ICRP do not recognize sex."}
{"_id": "Radiology$$$691997ac-b528-47f6-b3e6-a3b260050a68", "text": "The differences in radiosensitivity of males and females could be due to biological factors."}
{"_id": "Radiology$$$b0b32756-91a6-47f5-bcd2-0f707b43c79e", "text": "UNSCEAR concludes that the EAR and ERR for solid tumors are around two times higher in females than in males."}
{"_id": "Radiology$$$dfd5c21f-7318-4a47-b22b-934f94bc4016", "text": "The identification of biological sex-related radiosensitivity will contribute to personalized dose and fractionation for RT as well as for radiation protection."}
{"_id": "Radiology$$$4e9fb08d-0bbb-4a97-901a-f23f84c5259e", "text": "Currently, the annual dose limits for occupational exposures recommended by ICRP do not recognize sex."}
{"_id": "Radiology$$$d16aae0f-bb7b-4558-ae2e-55cb65237839", "text": "The severity of tissue reactions observed in cancer patients exposed to the same dose of IR during RT is assigned to differences in individual radiosensitivity [152]. It is generally believed that individual radiosensitivity is genetically determined based on the existence of certain hereditary diseases that we detailed more in Chap. 3. Moreover, the response to RT could also be influenced by other facts than the biological and physiological differences between males and females in organs and tissues, such as lifestyle, i.e., be sex related (Box 7.6)."}
{"_id": "Radiology$$$7f3c199b-a67a-40c6-83bb-18c51136cdd6", "text": "There was evidence that females when exposed to the same whole-body exposure dose of IR have a greater risk of cancer than males [153]. Moreover, radiogenomic research has brought evidence that individual polymorphisms are correlated with treatment response with significant differences between females and males. However, the few available findings do not allow any conclusions to be drawn about sex-specific differences in radiation sensitivity, mostly because there are no studies that present enough data to support these hypotheses, without other confounding factors, or whose focus is specifically on sex [154]. So, the inclusion of biological sex or even gender as a variable in future randomized control trials or cohort studies will be crucial. The identification of the individual radiosensitivity of each patient will allow a personalized dose adjustment for RT as well as to use the values to improve the protection of occupationally exposed persons."}
{"_id": "Radiology$$$0d20c7be-08ef-4209-8526-c0e0e1cafb68", "text": "Regarding fractionation, high total doses delivered at a high-dose rate, in fractions, at appropriate intervals showed a lesser genetic effect in both males and females than the same dose delivered in a single fraction. It was also reported that the magnitude of its reduction is the same as the low dose rate effect."}
{"_id": "Radiology$$$fe90ed79-0ad3-439f-94b3-aa8a610d1850", "text": "Since its foundation, the International Commission on Radiological Protection (ICRP) has issued recommendations and guidelines related to the use of IR, based on the most recent scientific evidence and experience obtained through the years of implementation of the system of radiation protection. Until now, the annual dose limit for occupational exposure recommended by ICRP is not based on individual characteristics, such as biological sex or gender. Although the inclusion of these characteristics will increase the complexity of the model, it would be a critical step to overcome the actual generalized system used for determining the proper radiation protection for each specific case [134]."}
{"_id": "Radiology$$$2899c4ca-cf46-44f2-9807-94630e049011", "text": "Two radiation research projects, Multidisciplinary European Low Dose Initiative (MELODI, https://\u200bmelodi-online.\u200beu/\u200b) and European Alliance Medical Radiation Protection Research (EURAMED, https://\u200bwww.\u200beuramed.\u200beu/\u200b), have been working on this topic defining the individual differences in radiation sensitivity as a key research priority."}
{"_id": "Radiology$$$e15c2c4c-6dcc-43e0-8303-504c3d5a0ce4", "text": "Ataxia Telangiectasia (AT) is an autosomal recessive neurodegenerative disease that is caused by mutations in AT mutated (ATM) gene. A-T was first described by Sillaba and Henner in 1926, however, its phenotypic spectrum was only expanded after the description of the ATM gene in 1995. A-T has a worldwide estimated prevalence of 1:40,000 to 1:100,000 and is related with a poor prognosis and a short life span, being chronic pulmonary diseases and malignancy the A-T-related most common causes of death [155, 156].\n\nAn illustration of four D N A lesions, their treatment pathways, and their syndromes. The lesions are as follows: Single-strand break, single-base damage, bully lesions and crosslinks, base mismatch, and double-strand break, or D S B.\n\nFig. 7.14\nOverview of DNA damage and repair pathways and most common genetic disorders"}
{"_id": "Radiology$$$5561dcc9-60c9-4c76-87a2-1250bae8fef6", "text": "An illustration of four D N A lesions, their treatment pathways, and their syndromes. The lesions are as follows: Single-strand break, single-base damage, bully lesions and crosslinks, base mismatch, and double-strand break, or D S B."}
{"_id": "Radiology$$$f1112cf6-29bc-4bff-a60f-f59182863d01", "text": "As the main known gene related to A-T clinical phenotype, ATM gene contains 66 exons and encodes the ATM protein, one of the three members of the PI3K-like family. ATM protein plays a pivotal role in the activation of cellular signaling pathways upon DSBs, apoptosis, and genotoxic stresses, such as IR. It functions essentially in the nuclear compartment; however, it is known that ATM is also present as a soluble protein in the cytoplasm [157]. In the nucleus, as part of DNA damage response upon DNA DSBs or oxidative stress, ATM is activated leading to a phosphorylation cascade of several target substrates involved in DNA repair, chromatin remodeling, cell cycle checkpoint, and transcription, namely P53 (S15), CHK2 (T68), and MDM2 (S395). In the cytoplasm, it is thought to be responsible for the functions of peroxisomes and mitochondria upon oxidative stress stimuli, as well as regulating angiogenesis, glucose metabolism, and telomere processing [155, 158]."}
{"_id": "Radiology$$$add37a5f-26f7-4a14-b6d7-e1442f5675bd", "text": "A-T is a complex multisystem disorder characterized by a phenotypic heterogeneity, since patients show a broad range of clinical manifestations, including progressive cerebellar degeneration, immunodeficiency, oculocutaneous telangiectasia, increased metabolic diseases, radiosensitivity, and cancer predisposition. Other abnormalities can also be manifestations of A-T, such as dystonia, chorea, athetosis, tremor, and parkinsonism. Clinical heterogeneity of A-T can be assigned to different types of mutations that cause an impaired ATM protein expression or affect its function in different ways. Clinical and preclinical studies revealed that the presence of inactive ATM is more cancer prone and lethal than null ATM [156, 157]. A-T patients show potentially a 10\u201325% increased risk of developing cancer, due to their immunodeficiency. In childhood, the most common types of malignancy are leukemia and lymphoma, while adults may also develop different solid tumors, namely breast, gastric, liver, parotid gland, and esophageal carcinomas. It is described that heterozygous ATM mutations lead to an increased risk of 5.1 for the development of breast cancer, compared to the general population; while ATM monoallelic defects are associated with an estimated relative risk of ~3%. Although there are some controversy on the association between ATM mutations and breast cancer susceptibility, cancer screening guidelines are being developed for ATM-mutated carriers [155]."}
{"_id": "Radiology$$$06b56fac-19e0-45e5-bbfa-922866c6f095", "text": "The first association between the A-T caused by ATM homozygous mutations and its higher human radiosensitivity was made in 1975. This hypothesis has been clearly strengthened over the years by the fact that several studies reported lower SF2 (survival fraction at 2\u00a0Gy) in ATM-mutated cells compared to other radiosensitive cases, reinforcing its higher radiosensitivity. These cells are inclusively characterized as hyper-radiosensitive (SF2 ranging from 1% to 10%). In a mechanistic point of view, it is proposed that ATM protein may act upstream of the molecular process of radiation response, namely upstream of the predominant DSB repair pathway, NHEJ. Although it is not yet fully understood which of the ATM functions has the biggest influence on radiosensitivity, the hyper-radiosensitivity of ATM-mutated cells is mainly explained by the deficient recognition of DSBs by NHEJ, as a consequence of the absence of an ATM kinase activity in the nucleus [158]."}
{"_id": "Radiology$$$e5399cd9-73cc-4f27-bee1-f5b35d18e1a9", "text": "DNA ligase IV deficiency or Ligase 4 (or LIG4) syndrome is an extremely rare autosomal recessive disease caused by mutations in DNA ligase IV. LIG4 was the first radiosensitive-severe combined immunodeficiency (RS-SCID) disorder to be described and belongs to the group of hereditary disorders associated with impaired DNA damage response mechanisms. Only few cases were recognized with LIG4 worldwide, the reason why its prevalence is difficult to estimate [159]."}
{"_id": "Radiology$$$e0817b01-85e9-4991-9a60-1b3328ab5972", "text": "The LIG4 gene encodes a key component of the major DSB repair machinery, the NHEJ pathway. This pathway constitutes a multistep process that involves several proteins, such as Ku 70/80, DNA-PKcs, XRCC4, and DNA ligase IV, among others ([160]; see also Chap. 3). DNA ligase IV is an ATP-dependent ligase IV involved in the final step of NHEJ. It forms a complex with XRCC4 and then interacts with DNA-PKcs and XLF to rejoin a pair of DNA ends. DNA ligase IV also develops an important role in the production of T and B lymphocytes receptors, being recruited to repair programmed DNA DSB induced during lymphocyte receptor development [160]."}
{"_id": "Radiology$$$bde7baa6-fdbe-4854-9abc-cb4ae54097b0", "text": "All mutations of LIG4 gene identified in patients are located near its active site and are typically hypomorphic. This means they are not fully inactivating, since they do not affect ligase expression and maintain a residual but impaired activity of the enzyme (5\u201310% compared to the wild-type) [159, 160]."}
{"_id": "Radiology$$$0b3a0799-9118-453a-825b-b6e254b67905", "text": "Clinically and morphologically, LIG4 syndrome is characterized by microcephaly, unusual facial features, growth retardation, and skin anomalies. Patients also manifest acute radiosensitivity, immunodeficiency, and bone marrow abnormalities. Some clinical phenotypes of LIG4 syndrome overlap with other genetic syndromes, like Seckel syndrome, NBS, and FA. Although the incidence of this disorder is very low, some patients were reported with malignancy, mainly lymphoma [7, 160]."}
{"_id": "Radiology$$$f5ddfb10-a9ac-439e-abfa-939820ddbb3f", "text": "The LIG4 syndrome is also considered a hyper-radiosensitive condition, which is caused by the loss of DNA ligase IV function and consequent impaired NHEJ activity, with a gross DSB repair defect. The first patient described with LIG4 syndrome developed acute lymphoblastic leukemia at age 14. The patient dramatically over-responded to cranial RT and died from radiation morbidity. Subsequent studies revealed a homozygous mutation in DNA ligase IV, which is located near the ATP binding site and is thought to hamper the formation of DNA ligase IV-adenylate complex, reducing its activity to ~10%. This post-RT fatal reaction made this genetic syndrome to be associated with hyper-radiosensitivity [7, 159]."}
{"_id": "Radiology$$$9a2e4209-1b7a-4d9b-a335-fa43f9e72264", "text": "Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disease mainly characterized by presenting microcephaly at birth, stunted growth, immunodeficiency, and high predisposition to cancer, without the manifestation of ataxia. NBS was first described in 1979 in a 10-year-old Dutch boy and, then, was formally reported in 1981 when a brother of the boy presented similar clinical features. NBS is estimated to have a prevalence at 1:100,000 live births worldwide, being most common in Eastern Europe [161]. NBS is a consequence of mutations in the NBS1 gene, also named NBN, on chromosome 8q21. It was determined a Slavic founder mutation, considering that most of the individuals with this syndrome are from Slavic regions and carry the same deleterious deletion, c.657del5. Eleven NBS-causing mutations have been identified, all of them in exons 6\u201310 of the NBS gene [162]."}
{"_id": "Radiology$$$ff3d9cb3-2145-4248-a183-7a94b9eb552a", "text": "The NBN gene encodes a 754 amino acid protein named Nibrin (NBN), p95 or nbs1. Nibrin is part of the MRN (Mre11/Rad50/Nibrin) complex involved in the repair of DNA DSB, as well as in immune gene rearrangements, maintenance of telomeres, and meiotic recombination. When exposed to DNA damaging agents, the MRN complex is activated by ATM phosphorylation and localized to DNA damage sites forming protein foci at DNA breaks. Consequently, mutations in this NBN gene lead to impaired translocation of the Nibrin protein into the MRN complex impairing subsequent repair of the DNA DSB lesion [162]."}
{"_id": "Radiology$$$84859028-b495-478e-8e3e-ff2159c857a3", "text": "The diagnosis of this syndrome is based on the identification of the main clinical manifestations and posterior confirmation by genetic analysis. The previous knowledge of disease-causing mutation in both alleles of the NBN gene allows the realization of prenatal molecular genetic diagnosis. NBS patients have a high predisposition to develop malignancies, being the syndrome with highest cancer incidence among all chromosomal instability syndromes. Till now, no specific therapies are defined, and the prognosis for NBN patients with malignancies is still poor [162]."}
{"_id": "Radiology$$$d75fae7f-8ff7-41af-951b-e1ddbf014b7f", "text": "The first documented case of radiation sensitivity observed in an NBS patient involved a 3-year-old microcephalic boy with medulloblastoma. Also, several in vitro studies have shown that NBS cells present high sensitivity to IR and radioresistant DNA synthesis. Thus, the NBS patients face several challenges in treating their presented malignancies, such as cancer, due to the limitation of using RT. In fact, considering the defective DNA repair system, the exposure of these individuals to radiation should be minimized and avoided when possible [161]."}
{"_id": "Radiology$$$0caeaaa7-7f02-4e3d-a9ef-ab8984f152fb", "text": "Xeroderma Pigmentosum (XP) is a rare hereditary autosomal recessive disorder with an incident rate of 1:250,000 in North America, and 1:1,000,000 in Europe, affecting both sexes equally [163]. XP is clinically characterized by the presence of pain induced by UV exposure, skin dryness, progressive pigmentary alterations, xerosis, several types of skin lesions and damage, and high incidence of malignant tumors affecting skin, head, and neck. In fact, acute severe sunburns are present in 50% of XP patients as a consequence of the hypersensitivity to sunlight. Some patients also showed neurological disorders and ophthalmologic degeneration [164, 165]. XP is caused by defects in seven complementation groups (XPA to XPG) which play a role in  NER systems. XPC and XPA are the most prevalent in Southern Europe and North Africa. XPC is caused by mutation in the gene XPC, which contains 16 exons and is located in chromosome 3 (3p25), encoding for xeroderma pigmentosum group C (XPC) protein. The most frequent mutation in the XPC gene is a 2\u00a0bp deletion, c.1643_1644delTG, p.Val548AlafsX25 [164]."}
{"_id": "Radiology$$$9370f69c-8be8-47a0-b45d-2176aa17731a", "text": "XPC is a protein with several functions in the NER system to repair DNA damage by recognizing the damaged bases and forming a stable complex with UV excision repair protein RAD23 (\u201cHR23B\u201d) protein needed for the recruitment of other actors involved in the removal of bulky DNA adducts. Mutation in these genes leads to an irreparable DNA damage that confers hypersensitivity to radiation to these patients, including UV exposure, and predisposition to develop malignancies [163, 164]."}
{"_id": "Radiology$$$6a65c8f2-038f-4966-be18-e0e220477272", "text": "XP patients have 10,000-fold more probability in developing skin cancer than the general population. No cure is yet available for XP patients, so they need to be completely protected and isolated from any source of UV radiation. Although there is a correlation between XP syndrome and hypersensitivity to UV radiation, there are only few reports presenting the effects of using radiation therapy in XP patients with malignancies. Most of those reports did not show acute or chronic complication after treatment, probably due to the action of other repair pathways, such as NHEJ or HR instead of NER. However, there have been reported preclinical studies showing that some variants of XP could be more susceptible to IR and it is recommended that all XP patients should be classified before starting radiation therapy [166]."}
{"_id": "Radiology$$$4d1c0145-b542-474f-9ceb-7122a99d8992", "text": "Fanconi anemia (FA) was firstly described by Guido Fanconi in 1927, a pediatrician who reported three children, brothers, with specific features: short stature, physical abnormalities, and anemia [167]. Defined as a rare genetic disease, FA is caused by pathogenic variants in at least 23 genes: FANCA, FANCB, FANCC, FANCD1/BRCA2, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ/BRIP, FANC, FANCM, FANCN/PALB2, FANCO/RAD51C, FANCP/SLX4, FANCQ/ERCC4, FANCR/RAD51, FANCS/BRCA1, FANCT/UBE2T, FANCU/XRCC2, FANCV/REV7, FANCW/RFWD3, and FANCY/FAP100. All these genes play a critical role in DNA repair and genomic instability and can be organized in different complexes [168]. Classified as an inherited bone marrow failure syndrome, FA is the most common genetic cause of aplastic anemia and, besides that related to hematologic malignancies, is one of the most common genetic causes with a ratio of males to females 1.2:1 [169]. Concerning heritability, FA can be inherited in an autosomal recessive manner, an autosomal dominant manner (RAD51-related FA), or an X-linked manner (FANCB-related FA) [170]."}
{"_id": "Radiology$$$693cd81b-0b5e-4744-9451-81d29fab0d43", "text": "This syndrome of impaired DNA repair and genomic instability, defined as complex and heterogeneous, is based on different mutations. FA patient cells are unable to perform different functions, namely repair DNA interstrand crosslinks, NER, translesion synthesis, and HR, inhibiting DNA replication and transcription, important cellular processes [171]. Related to IR, DNA damage and in particular DSB are the main alterations caused, with it reported that hypersensitivity to IR on FA mutation carriers translated not only into deterministic effects but also into stochastic effects [169]."}
{"_id": "Radiology$$$2e76cbb7-3daa-48fb-94e0-4737f64cbc2a", "text": "FA is diagnosed at the median age of 7\u00a0years although symptomatic and asymptomatic family members have been described from birth to >50\u00a0years of age [172]. This syndrome is classified as multisystem disease, characterized by clinical features such as congenital malformations (short stature, skeletal malformations of the lower and/or upper limbs, abnormal skin pigmentation, microcephaly, and genitourinary tract and ophthalmic alterations), progressive bone marrow failure with pancytopenia presentation, typically presents in the first decade, often initiated with thrombocytopenia or leukopenia, and increased probability of hematologic (myelodysplastic syndrome or acute myeloid leukemia) and solid malignancies (head and neck, skin, and genitourinary tract; [170])."}
{"_id": "Radiology$$$9aafabcc-e481-4598-a7ad-e0a2dd9e5fa7", "text": "Hereditary Breast and Ovarian Cancer (HBOC) syndrome was first reported by the French physician Pierre Paul Broca, in 1866, when observed a greater predisposition to cancer in his wife\u2019s family. This syndrome is an autosomal dominant disease, mostly caused by germline deleterious mutations in Breast Cancer gene 1 (BRCA1) and Breast Cancer gene 2 (BRCA2). The exact cancer risks depend on the type of pathogenic variant, being this syndrome mainly characterized by an increased predisposition to different types of cancer. These mutations affect all ethnic groups and races: in the general population, mutations in BRCA1 and BRCA2 genes are estimated to have a frequency between 1:400 and 1:500. However, in Ashkenazy Jewish people, the frequency of causal variants is higher: 1:40 [173, 174]."}
{"_id": "Radiology$$$82ed2845-fdb0-4d06-a8a9-c217a9348db3", "text": "HBOC is mostly a consequence of mutations in BRCA1 gene, located in chromosome 17, and BRCA2 gene, located in chromosome 13. However, only 25% of cases are associated with these two genes. Therefore, other genes are associated with this syndrome and, currently, more than 25 genes have been associated, such as Checkpoint Kinase 2 (CHEK2) gene, AT Mutated (ATM) gene, and Partner And Localizer Of BRCA2 (PALB2) gene. Most of them encode proteins that, in conjunction with BRCA1 and BRCA2 genes, act on genome maintenance pathways. More than 1600 mutations in BRCA1 gene and more than 1800 in BRCA2 gene associated with tumor susceptibility have been described [173, 175]."}
{"_id": "Radiology$$$e5550975-9dff-4b90-800d-9cbd2d7884ef", "text": "BRCA1 and BRCA2 genes are tumor suppressor genes with a crucial role in the cell, since they encode proteins that repair DNA DSB through HR\u00a0recombination, allowing the maintenance of genomic stability and tumor suppression. When exposed to IR, these proteins are activated, localize DNA damage, and repair it. In this way, mutations in these genes lead to an inefficient repair mechanism and to an increase in genomic instability, increasing the probability of cancer development [176]."}
{"_id": "Radiology$$$b7b588f7-11a7-4b97-af44-f31ab78914ac", "text": "The diagnosis of HBOC associated with mutations in BRCA genes is based on the identification of pathogenic variants in these genes through molecular genetic tests. HBOC patients have a high predisposition to develop different types of cancers, some of which at an earlier stage, such as breast cancer (in both sex) and ovarian cancer. Additionally, HBOC is also associated with an increased risk of developing prostate cancer, melanoma, and pancreatic cancer although to a lesser degree. Until the moment, there are no specific therapies defined, so early diagnosis in carriers of pathogenic variants in the BRCA1 and BRCA2 genes is crucial to apply effective surveillance and prophylaxis measures [173]."}
{"_id": "Radiology$$$728b75b9-851c-455a-a0f6-c7d65ee9d0e9", "text": "Since the twentieth century, several studies have been carried out to understand whether individuals with mutations in the BRCA genes are more sensitive to IR, trying to understand the role of exposure to IR in patients with HBOC and whether there are differences in the ability to repair of DNA damage between carriers and non-carriers of mutations in these genes. Although some studies show an association between the exposure of individuals with the syndrome to diagnostic doses and the development of cancer [177, 178], other studies fail to show any association [91, 179]. Thus, it is crucial to carry out more specific studies to obtain clear and objective conclusions in relation to this subject."}
{"_id": "Radiology$$$ad3d136d-19e1-4a06-b67a-bce8c1a04c44", "text": "Biological markers of changes in the body in response to radiation have long been used to assess radiation dose and exposure circumstances (see Chaps. 3 and 8). In recent years, with advances in technology and the sophistication of the markers, the potential to use biomarkers of the body\u2019s response to radiation and other stressors to help predict treatment outcome and indeed to tailor treatments has begun to be explored [180]."}
{"_id": "Radiology$$$d6c82b30-8d6b-4525-998d-541384beadbd", "text": "Development, validation, and implementation of biomarkers are not a simple process (see Chap. 3). Firstly because our bodies are hugely complex systems relying on hundreds of thousands of changing and interacting processes at any one moment, many of which have associated measurable changes, there are a huge number of potential biomarkers based on the body\u2019s complex response to IR confounded by a large number of other internal and external factors. Secondly, and just as importantly, there is huge variation in interindividual responses for most biomarkers. One recent study, for example, identified 40 blood-based biomarkers which could provide informative data on carbon metabolism, vitamin status, inflammation, and endothelial and renal function in cancer-free older adults alone [181]. Harlid et al. [182] also outlined the large number of potential biomarkers for risk predictive and diagnostic biomarkers for colorectal cancers, in a recent systematic review. In terms of molecular radiation epidemiology, a very large number of potential biomarkers have been identified, but despite a very large amount of work in this area, only one biomarker (based on transcriptional changes) has been identified as suitable to pursue now [14]. Furthermore, the practicalities of development of protocols and standard operating procedures for clinical use are also a barrier to implementation [183]."}
{"_id": "Radiology$$$914cf085-e6be-49c6-9a57-0a5bc685056b", "text": "However, in wider clinical practice as well as for radiation medicine, biomarkers to support personalized intervention are in development and in some cases, already in use. For example, Karschnia et al. [184] reported improved survival in patients with advanced cancers of the central nervous system, following application of systemic targeted immunotherapeutic agents. Connor et al. [185] showed how implementation of novel image-based biomarkers to support RT has improved patient-specific therapy outcomes for glioma patients."}
{"_id": "Radiology$$$68f0ac16-dc89-4d40-8309-1ed6506473bd", "text": "Going forward, despite the fact that the mechanisms of radiation resistance are still not well understood, use of miRNA in prostate cancer has shown promise. For example, Soares et al. [186] found 23 miRNAs which were involved in genetic regulation of prostate cancer cell response to RT. In the lung, Leiser et al. [187] recently demonstrated the potential utility of caveolin-1 (a membrane protein highly expressed in radiation resistant lung cancer cells) as a prognostic biomarker for response to treatment with radiation as well as for tumor progression, in support of precision medicine. And for cancers of the liver, De la Pinta [188] recently identified a number of candidate biomarkers of radiation response and toxicity and highlighted how close this field in particular is to use of such techniques to support personalized radiation medicine."}
{"_id": "Radiology$$$732faff9-b5df-4dd3-804e-cc2e7198fcf9", "text": "Indeed, use of large scale \u201comics\u201d data together with machine learning or other artificial intelligence approaches has opened up a number of avenues of research. For example, Manem [189] compared five different machine learning based approaches in two existing radiogenomics datasets and found a large number of biomarkers associated with statistically significant pathways of response associated with surviving fractions of cells. New techniques in cellular barcoding are also proving incredibly interesting, with Wursthorn et al. [190], for example, recently demonstrating the use of this technique for assessing clonogenic survival in response to radiation and quantification of radiosensitivity as well as the contribution of stochastic and deterministic processes. Major bioinformatics studies can help in the identification of gene signatures as biomarkers\u00a0for predicting normal tissue radiosensitivity.\u00a0A key challenge is still the need for large scale, independent, validation of biomarkers in prediagnostic studies [182] as well as biomarker-driven randomized controlled trials [191].\u00a0Nevertheless, given the recent advances, use of radiation biomarkers to support precision radiation medicine is an exciting field in which large leaps forward are expected in a relatively short timescale."}
{"_id": "Radiology$$$fcaadd84-7671-410c-9c34-2df81ba08c1e", "text": "Q1.\nCite a genetic syndrome associated with both radiosensitivity and radiosusceptibility.\n\u00a0Q2.\nCite a genetic syndrome associated with radiosusceptibility, but not radiosensitivity.\n\u00a0Q3.\nWhat is described as the attained age in relation to radiosensitivity?(a)\nThe age from birth to death\n\u00a0(b)\nThe sum of the age at exposure and time since exposure\n\u00a0(c)\nThe age between onset of cancer diagnosis and end of treatment\n\u00a0(d)\nThe sum of the age at exposure and time of exposure\n\u00a0\n\u00a0Q4.\nWhat are the three mechanisms associated with the greater susceptibility of children to radiation carcinogenesis?\n\u00a0Q5.\nWhich of the following sentences are true or false?(a)\nAged cells may have a compromised repair due to chromatin reorganization.\n\u00a0(b)\nSenescence in older cells can be accelerated by irradiation.\n\u00a0(c)\nAbnormalities in tissue maturation is often seen as radiation-induced sequelae in adults.\n\u00a0\n\u00a0Q6.\nIs the radiation sensitivity higher for males or females?\n\u00a0Q7.\nWhy is sex important to consider in context of radiation therapy?\n\u00a0Q8.\nWhy is sex not yet included in the ICRP recommendations?\n\u00a0Q9.\nWhy is it necessary to identify biomarkers to predict the response of the tumor to radiation therapy?\n\u00a0Q10.\nWhat circulatory biomarkers are of current interest in the field of radiation oncology?\n\u00a0Q11.\nWhy are liquid biopsies rapidly being adopted into translational research?\n\u00a0Q12.\nWhat is the current gold standard for assessing radiosensitivity?\n\u00a0Q13.\nWhat advantages do vibrational spectroscopic techniques have over conventional radiobiological assays?\n\u00a0Q14.\nIf normal tissue toxicity determines the total dose to be delivered to a patient, what outcome will this have on their treatment?"}
{"_id": "Radiology$$$b1a6097b-4074-473a-9885-5f7d80a7f4a9", "text": "What is described as the attained age in relation to radiosensitivity?(a)\nThe age from birth to death\n\u00a0(b)\nThe sum of the age at exposure and time since exposure\n\u00a0(c)\nThe age between onset of cancer diagnosis and end of treatment\n\u00a0(d)\nThe sum of the age at exposure and time of exposure"}
{"_id": "Radiology$$$dd11a993-aaf2-4d99-81b1-aadea452adbe", "text": "The sum of the age at exposure and time since exposure"}
{"_id": "Radiology$$$60054f91-e5a1-417a-ac8f-85812aeacf43", "text": "The age between onset of cancer diagnosis and end of treatment"}
{"_id": "Radiology$$$216229eb-9681-4250-b2c0-f2948eae7084", "text": "The sum of the age at exposure and time of exposure"}
{"_id": "Radiology$$$a82d9a54-7a64-462f-a62d-34689290ab50", "text": "What are the three mechanisms associated with the greater susceptibility of children to radiation carcinogenesis?"}
{"_id": "Radiology$$$43439d2e-2f43-4e21-ba2e-1084c5750b21", "text": "Which of the following sentences are true or false?(a)\nAged cells may have a compromised repair due to chromatin reorganization.\n\u00a0(b)\nSenescence in older cells can be accelerated by irradiation.\n\u00a0(c)\nAbnormalities in tissue maturation is often seen as radiation-induced sequelae in adults."}
{"_id": "Radiology$$$19f74719-55be-4bbe-9b27-a90a6b6b7b4e", "text": "Aged cells may have a compromised repair due to chromatin reorganization."}
{"_id": "Radiology$$$db149a83-059b-43a6-86c0-819d1a2dfc4f", "text": "Abnormalities in tissue maturation is often seen as radiation-induced sequelae in adults."}
{"_id": "Radiology$$$bd528267-3422-4466-8405-7384f7654f0b", "text": "Why is sex important to consider in context of radiation therapy?"}
{"_id": "Radiology$$$72f5a33f-077c-4eaf-aa05-99845ae4967b", "text": "Why is it necessary to identify biomarkers to predict the response of the tumor to radiation therapy?"}
{"_id": "Radiology$$$676f68ca-5d3e-4775-bd7b-e38322e88345", "text": "What circulatory biomarkers are of current interest in the field of radiation oncology?"}
{"_id": "Radiology$$$d2a66e85-3dc7-44ee-bffb-d98310f402fa", "text": "What advantages do vibrational spectroscopic techniques have over conventional radiobiological assays?"}
{"_id": "Radiology$$$3bd3ed08-2749-4667-ae6a-f955d47fa65d", "text": "If normal tissue toxicity determines the total dose to be delivered to a patient, what outcome will this have on their treatment?"}
{"_id": "Radiology$$$e6604d51-248b-43a3-8d2f-9261a6da5695", "text": "SQ1.\nAtaxia telangiectasia (AT) caused by homozygous ATM mutations is associated with fatal tissue reactions post-RT and high cancer proneness after exposure to radiation.\n\u00a0SQ2.\nLi-Fraumeni\u2019s syndrome (LFS) caused by heterozygous p53 mutations is associated with high cancer proneness after an exposure to radiation but LFS patients do not show adverse tissue reactions post-RT.\n\u00a0SQ3.\nAlternative (b) is correct. (The sum of the age at exposure and time since exposure).\n\u00a0SQ4.\nLong latency period between injury and cancer onset; faster radionuclides accumulation in growing bones; high frequency of cell division.\n\u00a0SQ5.\n(a) true, (b) true, (c) false.\n\u00a0SQ6.\nFemales.\n\u00a0SQ7.\nConsideration of the individual radiosensitivity of each patient will allow a personalized dose and fractionation adjustment for RT.\n\u00a0SQ8.\nDue to the lack of scientific evidence to support the establishment of different annual dose limitations based on sex, as well as the complex social and societal issues associated with potential implementation of sex specific dose limits.\n\u00a0SQ9.\nIdentifying biomarkers of tumor response will allow stratification of patients based on risk and identifying patients who may not respond favorably to treatment. In turn, this will provide tailored and optimized treatment for patients.\n\u00a0SQ10.\nCirculating tumor cells, circulating free DNA, and EVs.\n\u00a0SQ11.\nLiquid biopsies overcome many limitations associated with tumor biopsies, such as minimally invasive sample acquisition, easy repeatability, lower cost, and a rich source of tumor-specific biomarkers.\n\u00a0SQ12.\nThe clonogenic assay is still the current gold standard for studying radiosensitivity.\n\u00a0SQ13.\nVibrational techniques involve minimally invasive sample collection, non-destructive, label free measurement of cells, and results can be produced in a short time frame.\n\u00a0SQ14.\nPatients who are radiosensitive and undergo RT are at a higher risk of developing severe toxicity, and to circumvent this, the doses delivered to these patients will be at a lower dose than is necessary for adequate tumor control and a positive outcome of treatment."}
{"_id": "Radiology$$$cb77acff-735a-4623-bb73-b06f3f3567c5", "text": "Ataxia telangiectasia (AT) caused by homozygous ATM mutations is associated with fatal tissue reactions post-RT and high cancer proneness after exposure to radiation."}
{"_id": "Radiology$$$b16ec76c-4bba-4174-8532-c10b45176728", "text": "Li-Fraumeni\u2019s syndrome (LFS) caused by heterozygous p53 mutations is associated with high cancer proneness after an exposure to radiation but LFS patients do not show adverse tissue reactions post-RT."}
{"_id": "Radiology$$$4961ae87-d98c-4002-8608-1bd094dd2ede", "text": "Alternative (b) is correct. (The sum of the age at exposure and time since exposure)."}
{"_id": "Radiology$$$b3d8c952-6dd5-4e46-923e-c3d32f51090f", "text": "Long latency period between injury and cancer onset; faster radionuclides accumulation in growing bones; high frequency of cell division."}
{"_id": "Radiology$$$0065779d-51eb-4706-a6ec-2a18a19bad32", "text": "Consideration of the individual radiosensitivity of each patient will allow a personalized dose and fractionation adjustment for RT."}
{"_id": "Radiology$$$d3e14ed8-331c-44ab-9ad0-8683c9bb42dd", "text": "Due to the lack of scientific evidence to support the establishment of different annual dose limitations based on sex, as well as the complex social and societal issues associated with potential implementation of sex specific dose limits."}
{"_id": "Radiology$$$b0679a95-c281-4528-b1ea-002293dcbb0b", "text": "Identifying biomarkers of tumor response will allow stratification of patients based on risk and identifying patients who may not respond favorably to treatment. In turn, this will provide tailored and optimized treatment for patients."}
{"_id": "Radiology$$$dc41bd32-c3bc-49f2-82a0-a507518e8e78", "text": "Liquid biopsies overcome many limitations associated with tumor biopsies, such as minimally invasive sample acquisition, easy repeatability, lower cost, and a rich source of tumor-specific biomarkers."}
{"_id": "Radiology$$$08f3183e-936b-486b-887c-1c04a99c9d9d", "text": "The clonogenic assay is still the current gold standard for studying radiosensitivity."}
{"_id": "Radiology$$$b5714ee7-97e1-4bbb-ab38-7a8f4e6a3fbe", "text": "Vibrational techniques involve minimally invasive sample collection, non-destructive, label free measurement of cells, and results can be produced in a short time frame."}
{"_id": "Radiology$$$cf2df184-8cc0-449e-bd73-403f83d069a8", "text": "Patients who are radiosensitive and undergo RT are at a higher risk of developing severe toxicity, and to circumvent this, the doses delivered to these patients will be at a lower dose than is necessary for adequate tumor control and a positive outcome of treatment."}
{"_id": "Radiology$$$519344cb-f011-47c7-b4a7-8f6d30215d4a", "text": "Individuals can be exposed to ionizing radiation in many accidental or intended situations with different ranges of dose, dose rate, and radiation quality. Human exposures can occur directly from external radiation sources or through either internal or external contamination with radioactive materials/substances. In certain circumstances, external radiation exposure may occur concomitantly with external or internal contamination (Fig. 8.1). While the radiation dose from external exposure or internal contamination could be substantial, health risk from external contamination is highly dependent on the penetrating ability of the radionuclide. Since alpha particles can be effectively blocked by a piece of paper or by the upper layer of the skin, risk of external contamination by alpha particles is expected to be negligible. Most external contamination can be eliminated either by cleansing and/or by removing contaminated clothes.\n\nAn illustration of the exposure and contamination scenarios of radiation. In external exposure, radiation passes through the body and causes damage. In external contamination, the radiation damages the surface of the body. In the internal contamination, the radiation is incorporated into the body.\n\nFig. 8.1\nExternal exposure and contamination"}
{"_id": "Radiology$$$178ae6aa-27ac-466e-ad4d-763b8ad1f120", "text": "An illustration of the exposure and contamination scenarios of radiation. In external exposure, radiation passes through the body and causes damage. In external contamination, the radiation damages the surface of the body. In the internal contamination, the radiation is incorporated into the body."}
{"_id": "Radiology$$$124cf7b1-0822-4ee9-9b60-3f0e682ec0a1", "text": "The following section lists the types of exposure scenarios with specific examples."}
{"_id": "Radiology$$$6e4eaa03-2bc8-4d31-afca-a3688ac3e073", "text": "Aside from radiation oncology, which has been well described in Chap. 6, medical exposures can occur from diagnostic and therapeutic procedures other than cancer treatment. These procedures can cause exposures to the patient but also exposure in utero to the embryo or fetus. Worldwide medical exposures account for almost 20% of the average human exposure from all the sources [1]."}
{"_id": "Radiology$$$67488abf-a71a-4802-b0be-e77a90ddb62b", "text": "Doses from diagnostic radiology procedures range from very low doses in dental radiography to higher doses from computed tomography or fluoroscopy procedures. In general, radiation doses from diagnostic procedures tend to be low and are therefore unlikely to cause deterministic effects (discussed in Sects. 2.\u200b7.\u200b2 and 8.2), but especially repeated fluoroscopy-guided procedures like angioplasty may result in substantial skin dose to the patients (see also Sect. 8.1.6). Table 8.1 lists the effective doses (see definition in Sect. 8.7) associated with each of the commonly used diagnostic procedures, but these doses can vary among different countries. The total number of these procedures conducted worldwide to date, is around 4 billion (2.6 billion for radiography, 1.1 billion for dental radiography and 400 million for CT) and the number has been steadily increasing over the past 25\u00a0years, especially for CT [2].Table 8.1\nExamples of each type of diagnostic procedures and their typical doses (reproduced with permission from [2])\n\nExamination type\n\nTypical effective dose (mSv)a\n\nDental radiography\n\nIntraoral\n\n0.006\n\nPanoramic\n\n0.024\n\nProjection radiography\n\nHead (skull and facial bones)\n\n0.076\n\nChest (thoracic spine)\n\n0.45\n\nMammography\n\n0.22\n\nLumbar spine\n\n1.0\n\nPelvis and hips (bone)\n\n0.49\n\nLimbs and joints\n\n0.02\n\nWhole spine (trunk)\n\n1.5\n\nRadiography and fluoroscopy\n\nGastrointestinal tract\n\n3.4\n\nCardiac angiography\n\n7.0\n\nPelvic angiography\n\n3.2\n\nUrogenital tract\n\n2.4\n\nComputed tomography\n\nHead (skull and facial bones)\n\n1.5\n\nNeck (soft tissues)\n\n2.8\n\na ICRP 60 tissue weighting factors were applied for the effective dose determination [3]"}
{"_id": "Radiology$$$639d9e98-f2da-4e5e-a310-f808d4313b74", "text": "There have been many instances of therapeutic exposures unrelated to cancer treatment in the past including patients treated with radiation for ankylosing spondylitis (total body dose of 0.86\u20134.62\u00a0Gy) to relieve pain and children treated for tinea capitis (ringworm of the scalp) with a brain dose ranging from 0.75 to 1.7 Gy. There is evidence of increased cancers in these populations [4, 5] and alternative treatments have now been adopted that do not involve radiation. Presently, radiotherapy is used in procedures such as to treat benign tumors, pain relief for arthritis, arteriovenous malformations as shown in Fig. 8.2 [6]. These procedures deliver a range of doses from 5 to 60 Gy which can be delivered in single or multiple fractions.\n\nA cyclic chart of the percent for non-malignant conditions. Keloid, 78. Graves' orbitopathy, 69. Heterotopic bone formation, 61. Desmoid and aggressive fibromatosis, 54. Pterygium and Arteriovenous malformation, 41. Histiocytosis, 38. Arthrosis, 37. Nasopharyngeal angiofibroma, 33. Tendinitis, 32.\n\nFig. 8.2\nNon-malignant conditions most commonly treated with radiation therapy as a percentage of all international radiotherapy institutes surveyed (n\u00a0=\u00a0508). (Data extracted with permission from [6])"}
{"_id": "Radiology$$$4f9bceef-e18f-48f2-b279-93734f6bdf24", "text": "A cyclic chart of the percent for non-malignant conditions. Keloid, 78. Graves' orbitopathy, 69. Heterotopic bone formation, 61. Desmoid and aggressive fibromatosis, 54. Pterygium and Arteriovenous malformation, 41. Histiocytosis, 38. Arthrosis, 37. Nasopharyngeal angiofibroma, 33. Tendinitis, 32."}
{"_id": "Radiology$$$b5efd631-2deb-4257-9ef5-2a18d166c3ac", "text": "Radiation exposures can occur in many occupational settings with the highest average effective doses reported in the nuclear sector although this shows a steadily decreasing trend due to increased knowledge about the effects of radiation and better radiation protection practices over the past decades. Figure 8.3 shows data for the occupational exposures over a 27-year period. The average effective dose per worker is the highest in the nuclear sector. Due to the high number of workers in the medical field (~7500 in 2002) compared to the nuclear sector (~660 in 2002) and the industrial sector (~850 in 2002), collective exposures are the highest in the medical field, followed by those working in nuclear power and industrial uses of radiation.\n\n2 grouped bar graphs of annual effective dose and collective effective dose versus years. The values are plotted for industrial, medical, military, nuclear, and other. 1. Nuclear has the highest value from 1975 to 1979 at 4.4. 2. The medical has the highest value from 1995 to 2002 at 3500.\n\nFig. 8.3\nData for estimated occupational exposures from 1975 to 2002. (Reproduced with permission from [1, 7])"}
{"_id": "Radiology$$$2a2062aa-2990-4354-bbf1-6bb86f484bf4", "text": "2 grouped bar graphs of annual effective dose and collective effective dose versus years. The values are plotted for industrial, medical, military, nuclear, and other. 1. Nuclear has the highest value from 1975 to 1979 at 4.4. 2. The medical has the highest value from 1995 to 2002 at 3500."}
{"_id": "Radiology$$$3db048eb-54d4-4b66-b292-7a7d20800ddd", "text": "Out of all the occupational exposures, the medical profession makes up the single largest group of workers exposed in the workplace. This group encompasses nurses, doctors, technicians, and other support workers. The procedures mostly comprise diagnostic imaging and radiation therapy, which have been increasing yearly as technology develops and the benefits become more widespread. Table 8.2 shows some of the specific medical professions with the highest average exposures based on dosimeter readings, in Canada. These values will vary from country to country but are similar in countries with comparable level of health care.Table 8.2\nSelection of the highest exposed medical occupations of monitored workers (reproduced with permission from [8])\n\nOccupation\n\nAve dose (mSv/year) (2008)\n\nMean effective dose (mSv/year) (2016)\n\nNuclear medicine technologist\n\n1.56\n\n1.23\n\nDiagnostic radiologist\n\n0.44\n\n0.17\n\nMedical radiation technologist\n\n0.10\n\n0.11\n\nMedical physicist\n\n0.03\n\n0.05\n\nRadiation therapist\n\n0.05\n\n0.04\n\nDental assistant\n\n0.01\n\n0.01\n\nAll medical professions\n\n0.08\n\n0.07"}
{"_id": "Radiology$$$e5dd05bc-a739-43fd-8276-7d09e8cf1c1f", "text": "Occupational dose in diagnostic radiology is quite variable due to the wide range of technologies available. For example, most CT technologists have no measurable dose while the individual effective dose for interventional procedures such as vascular surgery supported by fluoroscopy is significant and medical doctors performing these procedures are the most occupationally exposed group from diagnostic radiation. Depending on the procedure, the occupational dose can range from 0.008\u20132\u00a0mSv per interventional procedure. Diagnostic radiation is also frequently used in dental clinics; therefore, the number of devices and workers exposed is extremely large. The average annual effective dose in dental radiology has been decreasing over the last few decades from 0.32\u00a0mSv in the late 1970s to 0.06\u00a0Sv in the early 1990s due to improved equipment [1]"}
{"_id": "Radiology$$$add1a19a-7efa-405f-ab2f-842d5a55c2c2", "text": "Nuclear medicine involves the use of radionuclides, particularly 99mTc, to investigate physiological process and organ function. Occupational exposures result from personnel having to be in close contact with patients when injecting them and while positioning them during which time they can be exposed to gamma radiation emitted by the radionuclides. Preparation of the radionuclides can also result in high exposures with annual doses up to 5\u00a0mSv and doses to the hands and fingers up to 500\u00a0mSv. There are several other nuclear medicine techniques with different exposures such as positron emission tomography using 18F labeled fluorodeoxyglucose and thyroid treatment with 131I to name a few. Worldwide, the annual collective effective dose is on the order of 85 man Sv and had been increasing over the years with increasing number of workers in this field. However, the annual collective dose is no longer increasing [1] since the 1980s as the average annual effective dose was reduced from 1\u00a0mSv down to about 0.75\u00a0mSv."}
{"_id": "Radiology$$$da05c159-ab77-440c-8b16-b760879e9c6b", "text": "Radiotherapy for treating malignant disease delivers the highest dose to the patient; however, occupational doses in this setting remain very low. These procedures have been well described in Chap. 5. The collective annual dose in radiotherapists has decreased substantially since the 1970s despite the increase in workers in this field. This is due to a large drop in the annual average effective dose per worker."}
{"_id": "Radiology$$$42d659cd-a1d6-46d1-b1c5-dd71b15dd744", "text": "Workers throughout the nuclear fuel cycle are exposed to ionizing radiation, from mining, through milling, enrichment, fuel fabrication, reactor operation, and reprocessing [1]. This group of workers is most closely monitored for their radiation exposure. As there are more workers in mining and reactor operation, the collective effective dose is the highest in this group. The average annual effective dose for nuclear workers has also been decreasing steadily since the mid-1970s from 4.1 to 1.0\u00a0mSv currently, and the collective effective dose has decreased since the 1980s from 2500 to 800 man Sv (Fig. 8.4). These reductions are due to implementation of ALARA programs that have improved plant designs, implemented upgrades, and improved operational procedures [1].\n\n3 grouped bar graphs of annual effective dose and collective effective dose versus practice. 1. The milling has the highest value from 1975 to 1979. 2. The mining has the highest value from 1980 to 1984. 3. The reactor operation has the highest value from 1990 to 1994. Values are estimated.\n\n\nFig. 8.4\nGlobal trends in the number of monitored workers, and in collective effective doses and effective doses to workers for different practices of the nuclear fuel cycle. (Reproduced with permission from [1])"}
{"_id": "Radiology$$$fba5d5fb-6c23-4714-873a-996d2f5ebcd7", "text": "3 grouped bar graphs of annual effective dose and collective effective dose versus practice. 1. The milling has the highest value from 1975 to 1979. 2. The mining has the highest value from 1980 to 1984. 3. The reactor operation has the highest value from 1990 to 1994. Values are estimated."}
{"_id": "Radiology$$$d53b51be-f9fe-4259-bbeb-5627483a7490", "text": "Industrial radiography is a non-destructive method used to look at defects in materials such as welded pipeline and castings. This can involve the use of X-rays or gamma ray sources sealed in capsules (e.g., 60Co and 192Ir). Radiation penetrates the object being examined and exposes a detection system behind the object. The devices used are designed to protect the operator and annual effective doses to the workers under normal use are less than 0.5\u00a0mSv."}
{"_id": "Radiology$$$4a7c39be-ae5c-423f-8d5c-0dea52ca7d56", "text": "Most military exposures results from the fabrication and testing of nuclear weapons, the use of nuclear energy on naval vessels, and the use of ionizing radiation for activities similar to those used in civilian applications (e.g., research, transport, and non-destructive testing). Data from the USA indicates that the average annual effective dose in monitored military individuals form all military activities is on the order of a few tens of mSv. There has, however, been a substantial decrease in the average collective doses since the 1970s where annual effective doses to monitor military workers were as high as 1\u00a0mSv [1]."}
{"_id": "Radiology$$$38b85d62-9c91-4769-b121-aba5ab6bd07a", "text": "Enhanced levels of natural radiation are found in several occupational settings. Because the radiation is naturally occurring, workers are not routinely monitored so exposure levels are not well known. Miners make up a large group of these occupational exposures and their estimated collective dose is about 30,000 man Sv [9]. Air crew make up another group of workers exposed to naturally occurring radiation and have been identified as one of the most highly exposed professional groups with exposure levels of 3\u20138\u00a0\u03bcSv/h during the flight depending on latitude and altitude. Worldwide, the estimated collective effective dose to aircrew is about 900 man Sv. Overall, there are about 13 million workers worldwide exposed to natural sources of radiation with an estimated average effective dose of 2.9\u00a0mSv and an estimated collective effective dose of 37,260 man Sv. This average effective dose from natural exposures is not decreasing as much as with man-made exposures, however, as the number of workers is increasing, the collective dose has been rising between the early 1990s and early 2000s [9]."}
{"_id": "Radiology$$$3cc7ddbc-ad80-46ad-af9a-dd8455f8e76a", "text": "In addition to those mentioned above, there are a number of other professions where radiation might be involved. These include, but are not limited to, research in academic institutions, management of spent radioactive sources and transport of radioactive material. Academic institutions make up 92% for the monitored workers in this category and about 87% of the collective dose. Overall, the average annual effective dose for all monitored workers in this category is less than 1\u00a0mSv and doses, decreasing from 0.5 to 0.1\u00a0mSv between 1975 and 2004 [9]."}
{"_id": "Radiology$$$f26bd9a9-f594-4a7d-acff-34235ba586db", "text": "Unintended exposures in medicine are defined as exposures that differ significantly from the exposure intended for the given purpose and are considered medical errors. These events can include operator errors, equipment failures, and other mishaps with consequences that can range from less to more severe. Events can occur with both diagnostic and therapeutic procedures and may also result in unintended doses to an embryo or fetus. The most serious overexposures can result in doses to the skin that are high enough to cause tissue reactions. These typically arise from CT and interventional fluoroscopy procedures, most notably from perfusion studies [10]."}
{"_id": "Radiology$$$ec11a7ef-d99e-483f-8637-beaf876b7fd4", "text": "Despite the adoption of safety measures to reduce the risk of accidents at Nuclear Power Plants (NPPs), there have been several accidents as well as near misses with varying degrees of impact and radiation exposure to workers and the general population [11]. These accidents are characterized by the release of large amounts of radionuclides with relatively short half-lives [12]. Three such past incidents of high impact are Three Mile Island in 1979 [13], Chernobyl in 1986 [14], and Fukushima in 2011 [15]. Accidents in NPPs can result in high doses to a small population of clean-up workers (e.g., Chernobyl) as well as small doses to a large population living in the vicinity of the NPP (e.g., Fukushima). These NPP accidents, along with other accidents, can be rated according to the International Nuclear Event scale (INES) based on severity and impact of the incident (Fig. 8.5). Accidents can also occur during the transportation of nuclear waste by road or rail with the primary concern of exposure for this waste being 137Cs, a \u03b3-emitter. Although the fuel is well packaged during shipment, the amount of radioactive material may be on the order of PBq per shipment container, so any dispersal would be catastrophic. In general, occupational exposures tend to be low doses and low-dose rates.\n\nA pyramid chart exhibits the 8 layers, from 0 to 7 of N P Ps accidents with its events. It includes below scale, anomaly, incident, serious incident, accident with local consequences, with wider consequences, serious accident, and major accident.\n\nFig. 8.5\nInternational Nuclear Event scale based on severity and impact of the incident"}
{"_id": "Radiology$$$e589a595-ad96-49fb-ba84-912df587b560", "text": "A pyramid chart exhibits the 8 layers, from 0 to 7 of N P Ps accidents with its events. It includes below scale, anomaly, incident, serious incident, accident with local consequences, with wider consequences, serious accident, and major accident."}
{"_id": "Radiology$$$86c5c00b-e9ba-4387-bcff-6a95806ef3a9", "text": "During industrial radiography, accidents can occur multiple ways: loss of control of the source of radiation, damage to the source, direct contact with the source or improper use of shielding [16]. Even when operating procedures are correctly followed, dose rates close to the source can be very high causing overexposures in a matter of seconds. Table 8.3 lists a few examples of accidents due to inadequate regulatory control, failure to follow operational procedures, inadequate training, inadequate maintenance, and human error.Table 8.3\nSelected accidents in industrial radiography\n\nYear\n\nPrimary cause\n\nExposed population\n\nSource/activity\n\nScenario\n\nDose to exposed population\n\nReference\n\n1989\n\nInadequate regulatory control\n\nGeneral public\n\n192Ir/260 GBq\n\nSource not removed prior to transportation\n\nPublic <5\u00a0mSv\nDriver\u20140.31\u00a0Sv\n\nUSNRC [17]\n\n1992\n\nFailure to follow operational procedures\n\nOperator\n\nVarious sealed sources\n\nUnsafe operations with radiographic sources\n\nLifetime 10\u00a0Sv whole body, >100\u00a0Sv to hand\n\nLloyd et al. [18]\n\n1969\n\nInadequate training, insufficient supervision\n\nOperator\n\n192Ir/900 GBq\n\nShutter of source left open during transportation\n\n450\u00a0mSv whole body, 2.14\u00a0Sv to left hip\n\nHarisson et al. [19]\n\n1993\n\nInadequate maintenance\n\nOperator\n\n192Ir/3600 GBq\n\nMissing roll pins to secure camera lock\n\n6\u00a0mSv whole body, 19\u00a0Sv to fingers\n\nUSNRC [20]\n\n1996\n\nHuman error\n\nOperator\n\nX-ray\n\nWrong cable connected to control panel causing wrong X-ray unit to be activated\n\n600 and 160\u00a0mSv to each of two operators\n\nWheelton [21]"}
{"_id": "Radiology$$$792f20e7-42f1-4457-8cf8-718a1ea157dd", "text": "An orphaned source is a self-contained radioactive source that is no longer under proper regulatory control. These sources can come from both therapeutic and industrial radiation machines and can have activities in the TBq range. As long as they remain sealed, they do not cause contamination but when opened can cause high doses and extreme health effects and even death, due to their high activity such as occurred in Thailand in 2000 [22]. Their containment can also become compromised, spreading radioactive material over large areas as occurred in Goiania, Brazil in 1987 [23]."}
{"_id": "Radiology$$$af582690-f1b9-498c-abaf-bea1d5b253cb", "text": "The health consequences after an accidental exposure to radiation will depend on the exposure scenario. Although there is a long list of attacks that could involve radiation, the following three are considered the most probable."}
{"_id": "Radiology$$$89eee7c4-473a-4300-9b43-630f489834ff", "text": "INDs incorporate nuclear material that can produce nuclear explosions. This can cause extensive blast (mechanical), thermal, and radiation injuries with large numbers of fatalities and casualties as well as high doses of radiation to potentially large numbers of individuals, when detonated at or close to a major city. The radiation injury can be a result of the prompt radiation within minutes near the epicenter of the explosion that is predominantly from \u03b3-rays and neutrons. Delayed exposures can result from fallout that is produced by fission products and neutron-induced radionuclides and are dispersed downwind from the epicenter. Finally, ground shine can result from the deposition of radionuclides on the ground of the fallout area that is highly dependent on the wind direction and speed (Fig. 8.6). INDs are considered highly unlikely but possible to be used; hence, it is necessary to be prepared for such events. The result of such an event would be catastrophic. Thousands of people could be killed by the blast and heat, hundreds to thousands could be killed or made ill by radiation effects, and thousands could have an increased long-term risk of leukemia or solid cancer. Furthermore, the psychological and infrastructure effects would also be enormous [24].\n\nA graph plots the kilometers from ground zone with the radioactive fallout pattern. It has 4 concentric circles with their centers at 0. The first circle denotes ground zero, the second one denotes dangerous fallout, the third one denotes moderate damage, and the outer circle denotes light damage.\n\nFig. 8.6\nApproximate prompt and delayed (fallout) effects from a 10-kT detonation. (Reproduced with permission from Lawrence Livermore National Laboratory)"}
{"_id": "Radiology$$$aa586bca-b744-4f19-a18b-bfc2dde92e82", "text": "A graph plots the kilometers from ground zone with the radioactive fallout pattern. It has 4 concentric circles with their centers at 0. The first circle denotes ground zero, the second one denotes dangerous fallout, the third one denotes moderate damage, and the outer circle denotes light damage."}
{"_id": "Radiology$$$c2f80a56-b7a5-47aa-b9c7-d33a64bc535a", "text": "The population that has had the greatest impact on risk assessment is the A-bomb survivors. A large population of Japanese were exposed in 1945 during an atomic bomb attack in both Hiroshima and Nagasaki. This cohort comprises the Life Span Study (LSS) that includes 94,000 in-city subjects of all ages and sex with dose estimates ranging up to 4\u00a0Sv.\u00a0There has been a long-term follow-up on this cohort, allowing for high quality mortality and cancer incidence data [25]. The majority of survivors were exposed to doses less than 0.1\u00a0Sv and, therefore, provide excellent data in the dose range of interest for radiation protection. This cohort also provided data on in utero and early childhood exposures [26]."}
{"_id": "Radiology$$$b85e9fbd-dc18-47c8-bd22-c3d6002fec09", "text": "RDDs use explosives or mechanical devices to distribute radiological material resulting in radioactive contamination. This is considered a more likely scenario than an IND. With RDDs, a relatively small area would be affected and radiation exposures could take the form of both internal and external contamination; however, exposures are expected to be lower than medically significant. Most likely, a small number of individuals will be contaminated with radioactive material."}
{"_id": "Radiology$$$a12895e1-afbc-4c9d-9c02-2f5228e171b9", "text": "REDs involve hidden sealed sources designed to expose people to significant doses without their knowledge and without causing contamination. They are usually hidden in a busy public location, such as under a seat on a bus or in a sports stadium and could remain undetected for long periods. Individuals who come close to these sources can receive significant localized doses but numbers of highly exposed individual are anticipated to be low."}
{"_id": "Radiology$$$c98bf6d6-4985-477f-ab1d-1ac89a200e69", "text": "It is generally accepted that the developing embryo and fetus are more radiosensitive than children or adults. In common with other health effects, at low doses (<100\u00a0mGy), stochastic risk is the main driver to protect the fetus (see Chap. 1). Deterministic effects or tissue reactions\u2014mainly central nervous system effects and congenital malformations\u2014are reported for higher doses; however, the evidence is somewhat sparse."}
{"_id": "Radiology$$$9b0c08eb-b974-4f68-975b-26873922885e", "text": "Evidence for fetal radiation effects comes mostly from animal studies performed with high doses of in utero radiation. Evidence is limited from the larger scale population exposures such as those of the A-bomb survivors, as well as from other small-scale accidents, and medical uses of radiation (e.g., Gilbert [26]). The relevant animal data suggest thresholds for non-cancer effects including small fetal size, microcephaly, and intellectual disability (see also Sect. 2.\u200b7.\u200b2). However, due to interspecies differences and different selection pressures, it is impossible to draw conclusions pertaining to the levels of such effects in human studies. As such, in order to draw conclusions for radiation protection purposes at least, epidemiological studies are more reliable."}
{"_id": "Radiology$$$9cd42f00-dc75-4a83-ab16-faccaa53a47a", "text": "The human data, however, are limited. There is only one epidemiological study that has been able to provide evidence of brain damage in humans following in utero exposure. From about 10,000 woman who were pregnant at the time of the atomic bombs at Hiroshima and Nagasaki, the children of about 1700 of them have been followed into adulthood. The study identified 27 children with severe \u201cmental retardation\u201d (now more commonly termed intellectual disability), 30 children with small head size without apparent intellectual effects, 24 children who suffered from seizures which appear to have no clinically identifiable precipitating cause, and a larger group of children with reduced intelligence (IQ) scores or with lower than expected scholastic achievement in school, compared to the unexposed population."}
{"_id": "Radiology$$$48000e43-edc8-4ce8-ad95-6fcff0d07096", "text": "While the sample sizes were small and hence the uncertainties were large, the key finding\u2014still much quoted today\u2014was that neurocognitive effects were only observed for those exposed for doses >~0.5\u00a0Gy, and only during the 8\u201315 post-conception period, corresponding to the key period of neurogenesis and neuronal migration [27\u201329]."}
{"_id": "Radiology$$$e0dbbb2f-851e-40f8-885d-617e4326bcc7", "text": "For earlier stages of embryogenesis, there is some evidence that preimplantation exposure to doses below 100\u00a0mGy may lead to miscarriage. During the major period of organogenesis, approximately 2\u201315\u00a0weeks post-conception, exposures on the order of 0.25 Gy may lead to smaller head sizes and the associated reduction in intellect, with this period also being particularly sensitive for induction of cancer. Post 15\u00a0weeks, the threshold for increased risk of cancer would appear to be on the order of 100\u00a0mGy, and the threshold for severe intellectual disability is still ~500\u00a0mGy (Fig. 8.7).\n\nA comparison of the possible deterministic effects of radiation with days post conception for pre, implantation, major organogenesis, and fetal growth. 4 curves for prenatal death, neuropathology, malformations, and growth retardation risk factors follow a small peak and a decreasing trend.\n\nFig. 8.7\nRelationship between ionizing radiation induced tissue effects and fetal/embryo stage of development. (Reproduced with permission from [30])"}
{"_id": "Radiology$$$306140b8-b6b0-49c5-aa82-819d8f718b0e", "text": "A comparison of the possible deterministic effects of radiation with days post conception for pre, implantation, major organogenesis, and fetal growth. 4 curves for prenatal death, neuropathology, malformations, and growth retardation risk factors follow a small peak and a decreasing trend."}
{"_id": "Radiology$$$5e01d2b9-468a-479e-bcf8-17f799c075b8", "text": "In 2001, UNSCEAR concluded there was no definite adverse pregnancy outcomes (malformations, stillbirths, premature births) related to the exposure from the Chernobyl accident. However, in more recent years, there is evidence that 131I internalized by pregnant women following Chernobyl crossed the placenta and resulted in thyroid cancer in their children. Children born to Chernobyl 131I exposed individuals also had dose-dependent longer gestational periods, smaller head, and chest sizes, but normal birth weights. While stunted cerebral growth during critical periods of neurogenesis accounts for microcephaly and the related developmental effects, the biological mechanisms behind the effect on gestational period is still largely unknown [7]."}
{"_id": "Radiology$$$5312f6a1-3d7f-4739-bcb7-d2affe8bbdb9", "text": "Fetal death following exposure in utero appears only to occur following doses >2\u00a0Gy; however, most of the evidence for this still comes from animal studies. There is also limited evidence linking fetal radon exposure to increased risk of disease. For example, excess brain cancer has been observed in children born to pregnant women drinking water with high levels of radon [31]."}
{"_id": "Radiology$$$a7482b46-7858-4d6a-806f-ffc114b78b5e", "text": "In terms of cancer risk, there is a clear link between doses received in utero and childhood and adult cancers, including childhood leukemia. In the A-bomb survivors exposed in utero, the most recent evidence using individual estimates of mother\u2019s weighted absorbed uterine dose supports a continued increased risk of solid cancer mortality in females but, not in males. As with the previous data, the effects of radiation on non-cancer disease mortality in this cohort appeared to be mediated through small head size and low birth weight, but also parental survival status. The most recent data suggest that the excess risk of childhood cancer (up to 15\u00a0years of age) is on the order of 6% per Gy, with approximately half of the cases being fatal. These data are summarized in Table 8.4.Table 8.4\nHealth effects as a function of gestational age for humans (reproduced with permission from [29])\n\nGestational age\n\nWeeks post-conception\n\nFetal dose, Gy\n\nEffects observed\n\nPreimplantation\n\n0\u20132\n\n0.05\u20130.10\n\nPrenatal death (animal data)\n\nMajor organogenesis\n\n1\u20138\n2\u201315\n\n0.20\u20130.25\n\nGrowth restriction\nSmall head size, intellectual deficit\nSensitive for cancer induction\n\nRapid neuronal development and migration\n\n8\u201315\n\n>0.1\n\nSmall head size, seizure risk, reduction in IQ (~25 points/Gy)\n\nPost organogenesis\n\n15-full term\n\n>0.1\n>0.5\n\nIncreased cancer risk\nSevere mental disability (16\u201325\u00a0weeks in particular)"}
{"_id": "Radiology$$$aacd4b2f-84a5-48b7-a88c-8fbee804f7ac", "text": "It is worth noting that on the basis of the current (albeit limited) evidence, for occupational radiation protection purposes in the UK as in many other countries, the unborn fetus is treated as a member of the public, hence the effective dose limit is 1\u00a0mSv/year."}
{"_id": "Radiology$$$63369c9d-03f5-4d52-b6ff-1d23d3a0f7e8", "text": "Mutations occur naturally in somatic and germ cells potentially leading to cancers and heritable genetic diseases, respectively. In 1927, Muller and colleagues initially showed the mutagenic effects of X-rays in Drosophila, which were rapidly followed by similar findings reported for other radiation types and organisms. These experimental animal data established the concept of genetic damage-inducing effects of radiation. However, concerns appeared about these genetic effects in large numbers of people, especially after the exposure of people to the detonation of atomic bombs. The UNSCEAR and the BEIR committees decided to follow the potential heritable effects of radiation in the exposed Japanese population, even if other environmental factors can interfere. Indeed, the goal pursued by both committees is to predict additional risk of genetic diseases in humans exposed to radiation. However, no association between radiation exposure and the occurrence of hereditable effects has been observed in humans to date [7]. Like cancers, genetically, diseases such as hemophilia, color-blindness, and congenital abnormalities do not arise specifically from ionizing radiation, but also occur spontaneously or due to other environmental and/or genotoxic factors without any specific clinical appearance."}
{"_id": "Radiology$$$c7193e19-70cd-43dc-a52f-c0a89eac2d04", "text": "The concept of \u201cradiation inducible genetic diseases\u201d relies on different parameters. Indeed, every cell contains genetic material in the form of DNA, and mutations observed in DNA may lead to a genetic disease such as malformations, metabolic disorders, or immune deficiencies. Sometimes, however, when mutations are induced in gonads or germ cells (oocytes or sperm or their precursors) of an exposed individual, hereditable effects occur in their offspring. To induce a genetically abnormal offspring, the mutation must successfully pass through many cell divisions to form a viable live-born infant. Further, to be of genetic significance, gonadal exposure must occur before or during the person\u2019s reproductive period. It gives rise to the concept of genetically significant dose. Thus exposure to, for example, a post-menopausal woman, or someone who never intends to have children, carries no associated \u201cheritable\u201d risk [7, 32]."}
{"_id": "Radiology$$$7486c925-7e68-4834-b754-b754a4b2e5a4", "text": "It is important to note that ionizing radiation does not produce new types of genetic diseases or new unique mutations but is assumed to increase the incidence of the same mutations that occur spontaneously. It increases the incidence of the spectrum of known diseases in the population. Hence, it is important, as far as possible, to have a good understanding of the background risks. There are very little direct human data on radiation-induced genetic disease. Pieces of evidence appeared for the heritable genetic effects of radiation almost entirely from animal experiments initially performed at Oak Ridge National Laboratory through the mega mouse project (7 million mice studied to determine specific locus mutation rates in the mice). Animal experiments have led to the development of relevant concepts including the doubling dose, i.e., the dose required to double the background frequency of genetic conditions detectable in the newborn population [33]. This project leads to five main conclusions: (1) a significant factor of about 35 for the radiosensitivity of different mutations; (2) a dose rate effect with fewer mutations induced by chronic exposure compared with acute ones; (3) an exquisite radiosensitivity of the oocytes; (4) reduction of the genetics effects of a given dose when there was a time interval between exposure and conceptions; (5) differences between male and female mice but with a doubling dose on the order of 1 Gy for protracted exposures. Given that conclusions on the background frequency, life span, selection pressures, and spectrum of genetic disease in the laboratory mouse are very different from humans, caution must be applied in using these data for human radiation protection purposes. Nevertheless, such data are important."}
{"_id": "Radiology$$$0ef1f79a-ec77-4089-bd45-a091665c01a8", "text": "Estimates then need to be made for the mutational component of classes of human genetic diseases and clearly, this is considerably different between dominant gene disorders and multifactorial conditions. The selection pressures on mutations being lost by death during embryo/fetus development also need to be assessed. Finally, an assessment of the transmissibility of abnormalities through further generations needs to be made [7]."}
{"_id": "Radiology$$$783fc18e-83bc-4029-9a6a-63970d792f07", "text": "Evolution depends on the existence of mutations, with beneficial mutations conferring an advantage. However, their random nature ensures that the vast majority of mutations are harmful. Alterations can concern genes or point mutations to the DNA code and chromosomal aberrations."}
{"_id": "Radiology$$$fcafd237-359f-4dfb-9249-fb11dd076b8c", "text": "Diseases caused by mutations in single genes are known as Mendelian diseases. The majority (67%) are caused predominantly by point mutations (base-pair changes in the DNA), followed at 22% by both point mutations and DNA deletions within genes, and by intragenic deletions and large deletions at 13%. They are divided into autosomal dominant, autosomal recessive, and X-linked depending on the chromosomal location and the phenotype resulting from the transmission."}
{"_id": "Radiology$$$98b65d48-f3ed-430f-a05c-7d8f69e7eec2", "text": "Autosomal dominant: Dominant conditions are where even in the heterozygote state (a person inheriting one mutant and one normal gene) the abnormality is seen in the individual. Their effects in the homozygote (double dose of the mutant gene) are usually more severe, if not lethal. They are expressed in the first generation after its occurrence. An example of a dominant gene condition is Huntingdon\u2019s chorea (HC), which is characterized by nerve cell damage and changes in physical, emotional, and mental state. HC is caused by a faulty gene on chromosome 4. Other examples include achondroplasia, neurofibromatosis, Marfan syndrome, or myotonic dystrophy.\n\nAutosomal recessive: Usually, this condition requires homozygosity, which means two mutant genes at the same locus, to produce the trait disease. The mutant gene must be inherited from each parent. Recessive disorders are usually rare, as the mutation would need to be inherited from both parents. However, some recessive genes even when present in a single dose, i.e., heterozygote accompanied by a dominant normal gene do still confer slight deleterious effects. An example of a recessive gene disorder is cystic fibrosis, which is caused by mutations on a gene located on chromosome 7. Other examples include phenylketonuria, hemochromatosis, Bloom\u2019s syndrome, and ataxia-telangiectasia.\n\nX-linked: Disorders involve genes located on the X chromosome. A large proportion of mutations that are inherited are related to the X chromosome. Since there is only one X chromosome in males, mutant genes here act as dominant genes in males who suffer whereas they are masked in the female with two X chromosomes who act as carriers. Mutations in these genes will exert their effect in females only when present in homozygotes and therefore appear as a recessive condition. Half the male offspring of a carrier mother will suffer and half her female offspring will be carriers. Examples of sex-linked conditions are color-blindness and hemophilia."}
{"_id": "Radiology$$$304151ec-b11e-4e76-97c8-ab081b868213", "text": "Autosomal dominant: Dominant conditions are where even in the heterozygote state (a person inheriting one mutant and one normal gene) the abnormality is seen in the individual. Their effects in the homozygote (double dose of the mutant gene) are usually more severe, if not lethal. They are expressed in the first generation after its occurrence. An example of a dominant gene condition is Huntingdon\u2019s chorea (HC), which is characterized by nerve cell damage and changes in physical, emotional, and mental state. HC is caused by a faulty gene on chromosome 4. Other examples include achondroplasia, neurofibromatosis, Marfan syndrome, or myotonic dystrophy."}
{"_id": "Radiology$$$363b06ed-e227-4037-bb49-ee66f624e5ec", "text": "Autosomal recessive: Usually, this condition requires homozygosity, which means two mutant genes at the same locus, to produce the trait disease. The mutant gene must be inherited from each parent. Recessive disorders are usually rare, as the mutation would need to be inherited from both parents. However, some recessive genes even when present in a single dose, i.e., heterozygote accompanied by a dominant normal gene do still confer slight deleterious effects. An example of a recessive gene disorder is cystic fibrosis, which is caused by mutations on a gene located on chromosome 7. Other examples include phenylketonuria, hemochromatosis, Bloom\u2019s syndrome, and ataxia-telangiectasia."}
{"_id": "Radiology$$$e389d71f-ef91-4d2e-8c5c-aefe2a514047", "text": "X-linked: Disorders involve genes located on the X chromosome. A large proportion of mutations that are inherited are related to the X chromosome. Since there is only one X chromosome in males, mutant genes here act as dominant genes in males who suffer whereas they are masked in the female with two X chromosomes who act as carriers. Mutations in these genes will exert their effect in females only when present in homozygotes and therefore appear as a recessive condition. Half the male offspring of a carrier mother will suffer and half her female offspring will be carriers. Examples of sex-linked conditions are color-blindness and hemophilia."}
{"_id": "Radiology$$$fcb73dac-20dd-4fbc-9991-240c4971ee9b", "text": "Chromosome aberrations are generally structural or numerical alterations that are microscopically visible/detectable (Fig. 8.8) and efficiently caused by radiation. Many chromosomal abnormalities are not compatible with life and are lost as spontaneous abortions. They correspond to 40% of spontaneous abortions and 6% of stillbirths. However, there are exceptions, and the evidence suggests that abnormalities of the sex chromosomes do tend to be transmitted. Examples include Downs syndrome, which is a trisomy of chromosome 21, as well as Turner\u2019s syndrome, which is a monosomy of chromosome X. Turner\u2019s syndrome individuals are, however, sterile. It is also interesting to note that the X chromosome is dominant, but (a single gene on) the Y chromosome determines sex.\n\n2 microscopic images of the chromosomes. A has several dicentric and tricentric chromosomes, while b has radiation-induced chromosomes.\n\nFig. 8.8\nExamples metaphase spreads with (a) dicentrics tri-centrics and several fragments and (b) with a translocation. These aberrations result from the fusion of sections of broken chromosomes"}
{"_id": "Radiology$$$afd376c3-74d9-431b-8a08-11da2a69d203", "text": "2 microscopic images of the chromosomes. A has several dicentric and tricentric chromosomes, while b has radiation-induced chromosomes."}
{"_id": "Radiology$$$30d04a39-4240-43c8-943b-fe73388f8c41", "text": "Multifactorial diseases are an additional class of effect, which combine heritable aspects (genetic components) in addition to influence from environmental factors. Their transmission patterns do not fit Mendelian transmission and the interrelated concepts of genetic susceptibility and risk factors are more appropriate to talk about these multifactorial diseases. Chronic conditions which arise later in life, for example, type II diabetes, tend to occur after an individual has already had children. However, in such cases, individuals may inherit predisposition but may never suffer from the disease. Multifactorial diseases also include congenital abnormalities which are present at birth. An example is cleft lip and palate where most sufferers are missing a part of chromosome 22\u2014this abnormality can be inherited but in most cases the cause of the deletion is unknown."}
{"_id": "Radiology$$$d0fe016c-ee10-449e-a743-0903d6c9ccc2", "text": "Furthermore, epigenetic changes are now considered for their involvement in radiation-induced heritable disease. These changes involve molecular modifications such as DNA methylation or changes in the chromatin packaging of DNA by post-translational histone modifications that can modulate gene expression without any DNA sequence alterations. Exposure to environmental factors at prenatal and early postnatal stages can alter the epigenetic programming thereby increasing the risk of developing the disease later."}
{"_id": "Radiology$$$debdcd8b-7824-45dd-9ca2-ec77be76a5e5", "text": "Additionally, expression of the imprinted gene in the current generation depends more and more on the environment experienced by the previous generation. Only one parental allele with the other allele silenced can lead to a non-Mendelian germline inherited form of gene regulation (heritable DNA methylation and histone modification) (Box 8.1)."}
{"_id": "Radiology$$$ee1ff737-1af5-46b0-9289-890092aca725", "text": "Gene mutations are molecular, sub-microscopic, changes affecting the functionality of one or more gene-specific loci.\n\nThere are three classes of Mendelian type gene mutations, where genes are inherited from each parent.\n\nOther parameters such environment may lead to radiation-induced genetic heritable diseases."}
{"_id": "Radiology$$$f1ffab6b-c857-4e88-876e-e1ada5e36f1f", "text": "Gene mutations are molecular, sub-microscopic, changes affecting the functionality of one or more gene-specific loci."}
{"_id": "Radiology$$$712f67f4-77d6-4e76-ae00-0ec4c7eb0480", "text": "There are three classes of Mendelian type gene mutations, where genes are inherited from each parent."}
{"_id": "Radiology$$$df357985-dac9-45e9-9834-c599f57824bc", "text": "Other parameters such environment may lead to radiation-induced genetic heritable diseases."}
{"_id": "Radiology$$$e247bb6d-030c-468f-a9c5-3d0aa7c18606", "text": "The assessment of radiation risks in progeny for heritable effects is thus a complex task. However, this has been done by UNSCEAR and ICRP reports [7, 32]. It is important to note that the data used to make the risk calculations are uncertain, with several assumptions, hence the ranges. From these data, the ICRP assumes that the exposure to radiation of a parent to a single gonadal dose of 1 Gy is responsible for 1 additional severe disease caused by radiation-induced mutations in 500 births, with a genetic risk that may last for up to 2 generations. With chronic exposure of gonad to 1\u00a0Gy, this proportion reaches 1 for 100 births, and heritable effects may persist for several generations. In this report, the total risk for genetic diseases estimated was about 3000 to 4700 cases per million first-generation progeny per Gy. The outcome of the risk calculations, in the form of risks per Gy per million live-born children, are given in Table 8.5.Table 8.5\nGenetic risk from one-generation exposure to low LET low-dose or chronic irradiation with assumed doubling dose of 1 Gy (reproduced with permission from [7])\n\nDisease class\n\nBaseline frequency, per 106 live births\n\nRisk per Gy per 106 progeny in the\n\nFirst generation\n\nSecond generationa\n\nMendelian\n\n\u2003Autosomal dominant and X-linked\n\u2003Autosomal recessive\n\n16,500\n7500\n\n~750\u20131500\n0\n\n~500\u20131000\n0\n\nChromosomal\n\n4000\n\nb\n\nb\n\nMultifactorial\n\n\u2003Chronic\n\u2003Congenital\n\u2003Total\n\n650,000c\n60,000\n738,000\n\n~250\u20131200\n~2000d\n~3000\u20134700\n\n~250\u20131200\n400\u20131000e\n1150\u20133200\n\nTotal risk per Gy (expressed as % of baseline)\n\u00a0\n~0.41 to 0.64\n\n0.16 to 0.43\n\na Risk to second generation is lower than that in the first because of the assumption that radiation exposure occurred in one generation only; the risk will progressively decrease with time (in generations)\nb Assumed to be subsumed in part under the risk of autosomal dominant and X-linked diseases and in part under that of congenital abnormalities\nc Frequency in the population\nd Estimate obtained using mouse data on developmental abnormalities and not with the doubling-dose method\ne Under the assumption that the selection coefficient is 0.2\u20130.5"}
{"_id": "Radiology$$$56fad951-bcc0-4be4-b908-487624bfd1fa", "text": "For risk estimation, the effects of high-dose irradiations have to be investigated in animal experiments. The effects of low radiation doses on humans, which are difficult to measure unequivocally, have to be inferred from these results. How these data are applied in radiation protection is then the responsibility of ICRP, who averages and combines the risks in Table 8.6 to generate a single risk estimate for all the genetic effects, for both the reproductive and total populations.Table 8.6\nPercentage risk per Gy for the reproductive and total population and up to two generations when the population sustains radiation exposure generation after generation (reproduced with permission from [34])\n\nDisease class\n\nReproductive population\n\nTotal population\n\nRange\n\nAverage\n\nAverage\n\nMendelian diseases\n\n0.13\u20130.25\n\n0.19\n\n0.08\n\nChronic diseases\n\n0.03\u20130.12\n\n0.08\n\n0.03\n\nCongenital abnormalities\n\n0.24\u20130.30\n\n0.27\n\n0.11\n\nTotal for all classes\n\u00a0\n0.54\n\n0.22"}
{"_id": "Radiology$$$7abac5e0-ed47-4efc-972f-33ecf842399a", "text": "In this case, ICRP assumes that people on average live to age 75 years and cease breeding by age 30 years. The genetically significant dose is therefore 40% (30/75) of the total population dose. For radiation workers, who ICRP assumes to begin working at 18 years and finish having children by age 30, the work-specific heritable risk is further reduced, as illustrated in Table 8.7.Table 8.7\nICRP recommended genetic risk coefficients for low dose or low-dose-rate low-LET radiation (reproduced with permission from [34])\n\nGroup\n\n10\u22122\u00a0Sv\u22121\n\nWhole population\n\n0.2\n\nRadiation workers\n\n0.1"}
{"_id": "Radiology$$$3b1c8a9b-c4fc-4927-97f7-6edb7efb9291", "text": "Cataract is the most common cause of blindness worldwide World Health Organization (WHO). There are three types of cataracts: nuclear cataract, which is characterized by hardening and opacification of the lens nucleus; cortical opacities, which are initiated at the lens cortices and which then form characteristic \u201cspokes\u201d pointed towards the center of the lens, and posterior subcapsular cataract, which develops on the capsule, at the posterior pole of the lens. The subcapsular cataracts are most readily associated in the epidemiological literature with radiation [32] (Fig. 8.9).\n\n3 illustrations. A exhibits the lens structure with the effects of radiation induced cataract. B. 2 eyeball structures. 1 with proper focus of light into the retina and the other with improper focus of light due to cataract. C has the posterior view of a healthy and cataractous lens.\n\nFig. 8.9\nProtein fiber and cellular organization within the lens. (a) The lens is formed from a single cell layer of lens epithelial cells (LECs) that covers the anterior portion of the lens. The cells in the central region are mostly quiescent; meanwhile the proliferating cells are largely confined to the germinative zone (GZ) in the equator of the lens. After division, LECs migrate to the transitional zone (TZ), situated immediately adjacent to the GZ and most distal to the anterior pole. In the TZ, LECs begin differentiation to form lens fiber cells (LFCs) that comprise the bulk of the lens mass. They enter the body of the lens via the meridional rows (MRs), adopting a hexagonal cross-sectional profile, offset from their immediate neighbors by a half cell width to deliver the most efficient cell\u2013cell packing arrangement that is perpetuated into the lens body as LECs continue their differentiation and maturation process into LFCs. (b) The lens sits in the anterior portion of the eye where it focuses light onto the retina to create a sharp image (top). However, when a cataract develops, the transmission of light is either blocked or not focused correctly (bottom), creating a distorted image. (c) Example of lens fiber sutures as viewed from the posterior pole of the lens in the healthy lens compared to a nuclear cataract, similar to that represented in (b). (Reproduced with permission from [35])"}
{"_id": "Radiology$$$5a075100-e486-49f0-8171-856f412fd308", "text": "3 illustrations. A exhibits the lens structure with the effects of radiation induced cataract. B. 2 eyeball structures. 1 with proper focus of light into the retina and the other with improper focus of light due to cataract. C has the posterior view of a healthy and cataractous lens."}
{"_id": "Radiology$$$9c9082e5-df33-4aab-80f2-f816dcd960ba", "text": "Until relatively recently, it was thought that radiation cataract was a \u201cdeterministic\u201d effect, now more commonly termed tissue reaction, with a threshold for acute exposures of approximately 2 Gy and a potentially much higher threshold for chronic or protracted exposures. However, in recent years it has become apparent that the latency period for radiation cataract may be many tens of years, and thus the threshold is likely to be much lower than previously thought, with the best current estimate based on the weight of epidemiological or population-based evidence that the current threshold is on the order of 0.5 Gy. However, there is some emerging evidence which suggests that radiation cataract may indeed be more stochastic in nature [32]. From the public health perspective, the high-dose response to radiation cataract is relatively clear from many years of animal studies and the smaller number of epidemiological studies reviewed in ICRP [32], and there are a number of methods of characterization and detection of cataract."}
{"_id": "Radiology$$$789c8857-80bf-44c4-83ef-42e10fd625af", "text": "While the mechanistic data on radiation cataract remains relatively sparse compared to, say, cancer, a number of publications have looked into the radiobiological basis of cataract. In brief, the structure, function and physiology of the lens are relatively well understood, as are the processes of lens cell fiber differentiation from the lens epithelial \u201cstem\u201d cell layer to the functional and carefully organized lens fiber cells which allow the passage and alignment of light for effective vision [35] (Fig. 8.10). Radiation is thought to act on several different stages of this carefully balanced process, from initial oxidative stress leading to genetic (DNA) damage, the effects on the transcriptional responses in epithelial cells (and, interesting, there is evidence that genes involved have some connections with tumor forming processes), through to morphological changes apparent in the misalignment of mature fiber cells which leads to opacification and functional cataract.\n\n2 illustrations of a human and animal lens demonstrate how the passage and ionizing radiation mechanisms are carried out for effective vision. It includes lens biology with oxidative stress, D N A damage, post translational changes, morphology, altered signaling, and non-targeted effects.\n\nFig. 8.10\nMechanisms of ionizing radiation response observed in human and animal lens epithelial cells or cell lines. Cx connexin, ECM extracellular matrix, FGF fibroblast growth factor, IR ionizing radiation, LEC lens epithelial cell. (Reproduced with permission from [35])"}
{"_id": "Radiology$$$a0e841fd-6e58-4bc9-a112-c77a6705159b", "text": "2 illustrations of a human and animal lens demonstrate how the passage and ionizing radiation mechanisms are carried out for effective vision. It includes lens biology with oxidative stress, D N A damage, post translational changes, morphology, altered signaling, and non-targeted effects."}
{"_id": "Radiology$$$b98fabfb-3111-4a5c-aeeb-96ae40364eb1", "text": "Recent work using animal models has highlighted the importance of the early phase DNA damage, proliferative, biochemical and proteomic/lipidomic responses, as well as the clear influence of genotype and pathways of response, age at exposure, sex, dose, and dose rate [36]."}
{"_id": "Radiology$$$13ad950f-8072-471d-a0f5-901c9477476b", "text": "Further work is still needed, particularly in relation to the mechanisms of higher RBE or LET radiation for cataract. However, at the time of publication, current understanding is that radiation cataract is still best characterized for radiation protection purposes as a tissue reaction, but that low-dose chronic exposure can contribute to the \u201ccataractogenic load\u201d of the combined genetic and environmental factors which ultimately determines whether individuals develop cataract or not [37] (Fig. 8.11).\n\n3 diagrams illustrate the cataract latency and load. a. An evolution of the aging lens from age 0 to 80. P C R ranges from 0 to 30, while age-related cataract ranges from 40 to 80. B exhibits the effect of age-related cataract without exposure. C exhibits the I R induced cataract with exposure.\n\nFig. 8.11\nThe latency of cataract and Lifelong Cataractogenic Load. (a) Timeline for lens aging. (b) Accumulated cataract load without exposure to ionzing radiation. (c) Accumulated cataract load after exposure to ionizing radiation (Reproduced with permission from [37])"}
{"_id": "Radiology$$$0ff60a3c-9100-4b62-8ca4-8da73af2575c", "text": "3 diagrams illustrate the cataract latency and load. a. An evolution of the aging lens from age 0 to 80. P C R ranges from 0 to 30, while age-related cataract ranges from 40 to 80. B exhibits the effect of age-related cataract without exposure. C exhibits the I R induced cataract with exposure."}
{"_id": "Radiology$$$91ab5d06-5017-4e5d-ab13-c2e8c3d0f347", "text": "In addition to the acute effects on the vascular system, ionizing radiation can in the long-term influence development of cardiovascular diseases (CVD) and metabolic effects which are major risk factors for diseases of the circulatory system. This section therefore considers a number of different diseases, including atherosclerosis which can cause ischemic heart disease and cerebrovascular disease, and which can lead to acute myocardial infarction and stroke."}
{"_id": "Radiology$$$7874aaef-14e2-40dc-8ed0-cd8ebe07ca24", "text": "The effects of ionizing radiation on the circulatory system is something which has long been researched, but only within the last 10\u00a0years or so has the weight of evidence been such that it is possible to consider taking account of the radiation effects as part of the system of radiation protection [38]. Currently, circulatory disease is considered a \u201cdeterministic effect\u201d or tissue reaction, with a threshold on the order of 0.5\u00a0Gy, and with a long latency period."}
{"_id": "Radiology$$$f7b7f725-ce99-4ef9-8002-9459aebf6b07", "text": "Most of the epidemiological evidence comes from exposures of medically (therapeutically or diagnostically) exposed individuals, with some data from occupational or environmentally exposed cohorts (reviewed in [39, 40]). Medical exposure to ionizing radiation during radiotherapy of thoracic tumors, such as breast cancer, Hodgkin\u2019s lymphoma and lung cancer, can involve some incidental radiation exposure to the cardiovascular system, resulting in cardiovascular complications. This is especially an issue for women with left-sided breast cancer due to the higher cumulative dose received by the heart, which is estimated to be approximately 6.6\u00a0Gy, compared to 2.9 Gy in women with right-sided breast cancer [41]. Cardiovascular disorders due to ionizing radiation are usually not seen until 10\u201315\u00a0years after exposure. However, asymptomatic abnormalities may develop much earlier. This long asymptomatic period may be a reason why the radiation sensitivity of the heart has formerly been underestimated. Recently, advancements in radiotherapy and heart-sparing techniques, including target-specific dose-delivery, deep inspiration breath hold and patient prone position setup, have resulted in decreasing the mean heart exposure dose from 4.6 Gy in 2014 to 2.6 Gy in 2017, as reported from 99 worldwide studies [42]. Despite that, the mean heart radiation doses remain relatively high and late cardiovascular complications continue to occur. The late-onset aspect of ionizing radiation-induced cardiotoxicity represents a diagnostic challenge to timely initiation of radioprotective therapy. Currently, there are some efforts paid to identify early biomarkers of radiation-induced cardiotoxicity, which may help in screening patients at risk for developing cardiovascular complications after radiotherapy, thus countermeasures and early medical intervention might be applied to prevent further cardiac toxicity [43]. Furthermore, research is exploring radioprotective agents which interfere with one or more of the identified pathophysiological mechanisms of ionizing radiation-induced cardiotoxicity."}
{"_id": "Radiology$$$2acaef6b-23cb-4d7d-9ff9-60749ee1ea65", "text": "Mechanistically, as with cataract, the high-dose effects are relatively clear, based on, for example, oxidative stress, DNA damage and enhanced adhesion of endothelial cells\u2014the genomic and proteomic basis of which is also under investigation. The lower dose studies are much less common; however, lifestyle factors and genetic susceptibility are undoubtedly confounders of development of circulatory system diseases, and indeed most of the mechanistic work carried out to date has focused on the genetic basis of development. Genome wide and targeted studies have identified, for example, the involvement of a number of genes of interest associated with inflammation, differentiation, proliferation, and apoptosis, among other processes which ionizing radiation is already known to impact. In addition, there are a number of biological dynamic models for cardiovascular disease (the topics in this paragraph reviewed in Tapio et al. [40])."}
{"_id": "Radiology$$$02890eca-f6d3-435e-8d1a-a1a92f7ebe8f", "text": "The most recent epidemiological evidence demonstrates increases in the probability of occurrence of these effects with dose, with no increase in severity; these are classical characteristics of stochastic radiation effects. However, the mechanisms are still highly unclear, and the low-dose effects, as well as the impact of dose rate, remain less studied [39, 40]. Recently, an adverse outcome pathway, an approach helps to assemble current knowledge on well-accepted critical events linked to disease progression, has been proposed for radiation-induced cardiotoxicity, which may help in structuring and simplification of the available mechanistic information and can facilitate predictive interpretations, beyond cellular or animal models, at the human population level (Fig. 8.12). This approach assists as well in identifying critical knowledge gaps for future research on radiation-induced cardiotoxicity, such as the need for an experimental model to understand low doses of radiation exposure and the need to understand epigenetic effects induced by radiation in the cardiovascular system [44].\n\nA schematic diagram of the cross-section of a human heart. It lists the respective cell types, key events, and adverse outcomes that lead to cardiovascular diseases.\n\nFig. 8.12\nProposed cell types in the heart, key events and adverse outcomes that may contribute to cardiovascular disease. Not all potential cell types and key events are listed and some of the key events listed may be common across the different cell types. ECM extracellular matrix, MCP-1 monocyte chemoattractant protein-1, NO nitric oxide, PPAR alpha peroxisome proliferator-activated receptor (PPAR)-alpha, ROS reactive oxygen species. (Reproduced with permission from [44])"}
{"_id": "Radiology$$$deef0f9c-848e-4d7d-816a-e372835b6f26", "text": "A schematic diagram of the cross-section of a human heart. It lists the respective cell types, key events, and adverse outcomes that lead to cardiovascular diseases."}
{"_id": "Radiology$$$3499b25b-e536-45ff-ae1d-8c5426258c02", "text": "Radon and thoron are natural radioactive noble gases resulting from the decay of uranium and thorium, which leak from the soil in concentrations that depend on local geological conditions. Radon and thoron are chemically inert and electrically neutral, so at physiological temperatures there are no chemical interactions [45]."}
{"_id": "Radiology$$$29b37df8-ff87-47cd-af26-89e32090d8ac", "text": "There are several natural isotopes of radon and thoron, originating from different series, as can be seen in Table 8.8 [46]Table 8.8\nNatural isotopes of radon and thoron (based on [46])\n\nSeries\n\nNuclide\n\nDecay mode\n\nT1/2\n\nUranium\n\n234Th\n\nBeta-\n\n24.10 days\n\n230Th\n\nAlpha\n\n7.54\u00a0\u00d7\u00a0104 years\n\n222Rn\n\nAlpha\n\n3.8235 days\n\n218Rn\n\nAlpha\n\n35\u00a0ms\n\nThorium\n\n232Th\n\nAlpha\n\n1.405\u00a0\u00d7\u00a01010 years\n\n228Th\n\nAlpha\n\n1.9116 years\n\n220Rn\n\nAlpha\n\n55.6\u00a0s\n\nActinium\n\n231Th\n\nBeta-\n\n25.52\u00a0h\n\n227Th\n\nAlpha\n\n18.68 days\n\n219Rn\n\nAlpha\n\n3.96\u00a0s\n\nNeptunium\n\n229Th\n\nAlpha\n\n7340 years\n\n217Rn\n\nAlpha\n\n540\u00a0\u03bcs"}
{"_id": "Radiology$$$ce143edf-2d05-4076-9172-f0aa3a334801", "text": "In the open air, the concentration of radon and thoron is normally very low, but being gases, they tend to accumulate in non-ventilated areas (WHO). In buildings constructed on soils that are rich in elements of the radioactive families mentioned above, their release causes them to accumulate inside houses. The pressure difference between the subsoil and the interior of the dwellings also favors this accumulation, due to diffusion."}
{"_id": "Radiology$$$12e58689-a6ce-4ea9-9ec2-5b024b24dd6f", "text": "Figure 8.13 shows the arithmetic mean of the annual indoor radon concentration per grid cell (10\u00a0km\u00a0\u00d7\u00a010\u00a0km) in ground floor rooms in some European countries.\n\nAn European map of radon with the distribution of 8 arithmetic means and 2 other features. The radon concentrations are spread throughout the country.\n\nFig. 8.13\nEuropean Indoor Radon Map: annual indoor radon concentration expressed as arithmetic means per 10\u00a0km\u00a0\u00d7\u00a010 km grid cells in ground-floor rooms. (Data received until December 2021 included; Reproduced with permission from European Commission. Joint Research Centre, EC-JRC, REM 2021)"}
{"_id": "Radiology$$$ca8b9af3-85db-4886-bc88-1b23f6486d4f", "text": "An European map of radon with the distribution of 8 arithmetic means and 2 other features. The radon concentrations are spread throughout the country."}
{"_id": "Radiology$$$460e4fe9-8ffd-4e52-9c4c-0d7be66a9e6e", "text": "As all radon and thoron isotopes are radioactive gases, after being released into the ambient air, they accumulate indoors and disintegrate into various unstable daughter nuclides. After decay in air, these radionuclides aggregate with other gases and water vapor, forming aerosols with diameters of 0.5\u20135\u00a0nm, which are easily inhaled, travel through the conducting airways and reach the alveoli of the lungs [47, 48]. However, as the airways are saturated with water vapor, the hydration of aerosols allows their diameter to increase up to about 10 times [49]."}
{"_id": "Radiology$$$6697cfdf-5578-45a7-970f-01fd9f656346", "text": "Once inhaled, the decay process occurs predominantly in the lungs. The main biological incorporation pathway is by inhalation of radioactive aerosols. Alpha emissions are the biggest contributors to the absorbed dose (about 90%) while beta and gamma emissions contribute only about 10% [47, 50\u201352]. Considering the aerosol dynamics, they are deposited according to three physical mechanisms: inertial impaction, sedimentation, and diffusion. Also taking into account the length, diameter and bifurcation angle of the airways, as well as the diameter of aerosols, deposition varies along the respiratory tract. Particles with larger diameters (2\u201350\u00a0\u03bcm) are deposited by inertial impaction in the nasopharynx, larynx, trachea and bronchi up to the third division. For particles with intermediate diameters (100\u00a0nm\u201310\u00a0\u03bcm) sedimentation is the main mechanism of deposition and occurs mainly in the lower respiratory tract, also in the bronchioles and even alveoli. For particles with diameters less than 200\u00a0nm, Brownian diffusion predominates and occurs in the alveoli, where gas exchange takes place [47\u201349]. Additionally, the multiple divisions of the airways and the consequent turbulence generated determine a non-homogeneous deposition pattern [47, 53]."}
{"_id": "Radiology$$$efe02027-4ecf-463a-9477-cf57bc6336f8", "text": "Considering the different radiosensitivity of regions of the respiratory tract in which the mucosal and basal bronchial epithelial cells are particularly radiosensitive [54] as well as the multiple divisions of the conduction airways, the largest dose is deposited in the bifurcation of the trachea [47, 55]."}
{"_id": "Radiology$$$296aa244-2aaa-48d6-b36e-66455f38bd76", "text": "Radon, thoron and their respective decay products emit alpha particles, beta- and gamma radiation, as mentioned above and the carcinogenic effect of these radionuclides is associated with the emitted ionizing radiation that can, directly or indirectly, damage DNA [56, 57]. This DNA damage causes mutations that can lead to carcinogenesis, resulting in the development of malignant tumors."}
{"_id": "Radiology$$$7cd92991-fdc5-448c-8ab9-ba1a57c0f763", "text": "The correlation of radon with the incidence of lung cancer has been unquestionably proven by extensive epidemiological studies (BEIR VI). However, it is not excluded that it can also cause kidney cancer, melanoma, hematologic cancers, primary brain tumors, and even stomach, liver and pancreas cancers [56, 58\u201360]. However, given the low penetration of radon further than the respiratory system, the association with non-respiratory diseases is not proven [56]."}
{"_id": "Radiology$$$2c280a2d-65e0-4cc8-bd63-f4d903c24086", "text": "Epidemiological studies on chronic radon exposure show that the estimated risk of carcinogenesis is related to the subject\u2019s concentrations, exposure time, and age [47]. Concerning lung cancer and radon concentration, there appears to be an increased risk of 16% per 100\u00a0Bq/m3 [45, 47, 61]. With respect to mortality, there is a non-threshold linear correlation with exposure. If we add smoking to radioactive exposure, the risk of lung cancer increases even further [47, 61]. With regard to primary malignant brain tumors, there appears to be a positive correlation between chronic radon exposure and mortality [58, 61]. The same seems to be the case for non-cancer situations such as Alzheimer\u2019s and Parkinson\u2019s diseases, without, however, understanding the pathophysiological mechanisms [60]. There is a similar correlation for chronic radon exposure and incidence of chronic myeloid and lymphocytic leukemia and, in the case of children, with acute myeloid leukemia [45, 47, 61]."}
{"_id": "Radiology$$$c69935f7-90e5-4808-8c68-e1eb675c625b", "text": "Latency times are highly variable between irradiation and the development of malignant tumors. Thus, for leukemia the times range from 5 to 7\u00a0years, while for solid tumors they are much longer, ranging from 10 to 60\u00a0years [45, 47, 61] (Box 8.2)."}
{"_id": "Radiology$$$f914ae4c-1980-46cc-b0f5-4ad57b05f7b6", "text": "Radon and thoron are noble radioactive gases\n\nThere are several isotopes of radon and thoron\n\nThe decay process occurs in the lungs due to inhalation\n\nThere is carcinogenic risk associated to chronic radon exposure"}
{"_id": "Radiology$$$bf4e4335-e60a-4939-93ee-6ba02964fa84", "text": "Depending on the amount of energy deposited, the absorbed dose, as well as the radiation quality, significant whole-body or partial-body exposure to ionizing radiation may lead to acute clinical radiation effects resulting in an Acute Radiation Syndrome (ARS). This may be followed by Delayed Effects of Acute Radiation Exposure (DEARE) that take months and years to develop [62, 63]."}
{"_id": "Radiology$$$4f00896b-0689-4591-b9bc-2ffb65517990", "text": "Many aspects have to be considered regarding the diagnosis and management of radiation exposure. Regarding latency of occurrence, acute and chronic effects can be distinguished. The acute effects may require prompt diagnosis and immediate therapeutic intervention."}
{"_id": "Radiology$$$24ca5b4f-39e4-4efd-a152-4fd6088e1187", "text": "Considering the pathophysiological mechanisms, the effects can be distinguished as either deterministic or stochastic (see also Sect. 2.\u200b7.\u200b2). Deterministic effects are caused by radiation exposure exceeding a certain level (threshold) and are more severe with increasing dose. After whole-body irradiation, different categories of clinical syndromes can develop, usually depending on the absorbed dose: nausea, vomiting, diarrhea (NVD) syndrome (1\u20132\u00a0Gy), hematopoietic syndrome (2\u20136\u00a0Gy), gastrointestinal syndrome (>6\u00a0Gy) and central nervous syndrome/neurovascular syndrome (10\u201320\u00a0Gy); after local irradiation of the gonads, permanent sterility (0.1\u20136\u00a0Gy), of the eye opacity of lens (0.5\u00a0Gy), of the skin erythema (3\u20136\u00a0Gy) and hair loss (4\u00a0Gy) may develop [32, 34]. Clinical dosimetry based on the individual patient\u2019s clinical signs and symptoms is important to define the severity of radiation exposure."}
{"_id": "Radiology$$$f7ae621d-ba2f-4d6f-b5bb-28a320af3eef", "text": "For stochastic effects, no threshold value is assumed, the probability of occurrence increases with radiation dose and even very low-dose exposure effects cannot be completely excluded [62]."}
{"_id": "Radiology$$$552fc86d-08e8-4fb2-8bba-b486d365d6a3", "text": "In case of radionuclide contamination, establishing the presence of external contamination is very important since decontamination should be performed as soon as possible keeping people, equipment, and facilities safe in the process. However, urgent medical treatment has the highest priority as lifesaving always comes first. Luke-warm water and mild soaps should be used for the first line of decontamination. Reduction to background or at most 3\u00d7 background dose should be aimed for. In case of residual contamination, peeling products can be used to remove contamination adherent to the skin. If measurements indicate persistent contamination, the presence of radioactive particles in the skin (like shrapnel, requiring surgical removal) or internal contamination should be suspected."}
{"_id": "Radiology$$$b30d82c8-dbf9-47c8-a59a-50baed55c57d", "text": "In case of radionuclide ingestion and/or inhalation, identification of the radionuclide is crucial to select the appropriate decorporation therapy. Decorporation therapy must be carried out as fast as possible in order to reduce radiation dose absorption, since pharmaceuticals are often most effective if given immediately or within 2\u00a0h after ingestion or inhalation. This can be achieved by using blocking agents, diluting agents, chelating agents or enhanced de-corporation drugs like Prussian blue, Zn-DTPA, Ca-DTPA and ammonium chloride [62, 64]. Physical decorporation measures such as gastric lavage for ingested radioactive substances (if applied within 2\u00a0h of ingestion) and bronchoalveolar lavage for large amounts of insoluble inhaled radionuclides could also be used [65]."}
{"_id": "Radiology$$$01c6acc6-24a7-42a2-bf9b-c84b8e3f7f53", "text": "Acute radiation syndrome (ARS) develops when whole- or partial-body radiation exposure exceeds a certain dose, partially depending on individual radiosensitivity and radiation damage repair mechanisms. ARS is usually assumed to occur with whole-body doses above 0.5\u20131 Gy if given with high-dose rate [32, 66, 67]."}
{"_id": "Radiology$$$6a116ee9-dc59-4baa-9fb9-d953d72746b0", "text": "The deposition of energy at the molecular and cellular level leads to physico-chemical-biological consequences already described in the previous chapters."}
{"_id": "Radiology$$$9f5518f5-0979-41e4-b9e1-5c85fbca9b2a", "text": "The clinical evolution of the acute radiation syndrome is sequential and its canonical evolution begins with prodromes, followed by the latent state, the state of manifest illness, and ends with the state of recovery or death [32, 62, 68]."}
{"_id": "Radiology$$$9f78096b-9231-48ed-a4a5-a1750f4c9273", "text": "In the prodromal state, the exposed person has non-specific symptoms, which is easily confused with a flu-like syndrome. Anorexia, nausea, vomiting, diarrhea and, eventually, erythema are frequent symptoms. The fluid loss that is caused by diarrhea may be accompanied by fever, hypotension, and headache, depending on its intensity [62, 68, 69]. Given the non-specific nature of these symptoms and signs, exposure to radiation may not be the first clinical hypothesis, which makes the information about the circumstances and awareness for radiological incidents very important. Prodromal symptoms and signs can appear at doses as low as 0.5\u00a0Gy, depending on individual radiosensitivity [62, 68]. This state lasts from a few minutes to a few days, depending on the dose: the higher the dose, the shorter the duration of this state. Except for people with increased radiosensitivity, the prodromal state may be absent or mild for whole-body doses of 1 Gy or less. If signs and symptoms appear within the first 2\u00a0h, this usually means an exposure dose greater than 2 Gy. In this case, the symptoms are predominantly gastrointestinal, and the patients may survive if adequately treated. At doses greater than 10\u00a0Gy, severe symptoms will develop, often within 5\u201315 min after exposure, predominantly cerebrovascular. A severe prodromal phase usually has a poor clinical prognosis that can lead to death [67, 69, 70]."}
{"_id": "Radiology$$$50c82f72-7836-4b74-a815-8982f55a2f2b", "text": "Doses that are associated with prodromal symptoms and signs in approximately 50% of irradiated people are given in Table 8.9.Table 8.9\nDoses that are associated with prodromal symptoms and signs (reproduced with permission from [32, 68])\n\nDose (Gy)\n\nSymptoms and signs\n\n1\u20132\n\nAnorexia\n\n1\u20132\n\nNausea\n\n1\u20132\n\nVomiting\n\n2\u20136\n\nDiarrhea\n\n>6\n\nFever\n\n>8\n\nConsciousness changes"}
{"_id": "Radiology$$$20acb2ae-ac97-4c44-be3b-1f882d99ec19", "text": "The aforementioned prodromal symptomatology, which appears at doses lower than 0.5 Gy up to about 3\u00a0Gy, seems to be dependent on damage of the cell membrane, with the consequent release of inflammatory molecules from the destroyed cells and to be mediated by the parasympathetic system [32]."}
{"_id": "Radiology$$$38ba9215-b8c5-4834-9966-757e308d5125", "text": "The second phase of ARS is called the latent phase. In this phase, symptoms and signs diminish and may even disappear, in such a way that the patient feels better and appears to be recovered. In fact, injuries are developing, but the activated repair mechanisms can lead to complete (disappearance of symptoms and signs) or incomplete repair of the damage (reduction of symptoms and signs). The duration of the latent phase, which can vary from minutes to weeks, is also inversely related to the dose, that is, the higher the dose, the shorter its duration. Despite the absence of symptoms, it is in the latent phase that the most important consequences of exposure to radiation occur, leading to its effects, which are manifested in the manifest illness phase [69, 70]."}
{"_id": "Radiology$$$dee9d434-73d4-4ced-8f64-6c6cfcb5dc17", "text": "If repair mechanisms are inefficient, the latent phase progresses to the next phase, the manifest illness phase. The absence of the latent phase, i.e., if the patient goes directly from the prodromal phase to the manifest illness phase, is an indicator that the dose was very high. In the manifest illness phase, there are specific symptoms and signs, depending on the organ or system mainly affected. However, there may be a mixture of symptoms and signs coming from different systems, which makes the diagnosis more complex. Also in this phase, the signs and symptoms, as well as the duration, are dose dependent, that is, the higher the dose, the earlier the symptomatology starts and the shorter the phase lasts, which can be from minutes to weeks [32, 66, 69, 70]."}
{"_id": "Radiology$$$5038c46c-16a6-4d01-9dfe-fb270752b7f2", "text": "In this state specific syndromes are described, commonly classified as the hematological, gastrointestinal, and neurovascular syndromes, depending on dose (Table 8.10). In addition to these syndromes, skin lesions and lung toxicity may also develop (Fig. 8.14).Table 8.10\nAcute radiation syndromes\n\u00a0\nHematopoietic syndrome\n\nGastrointestinal syndrome\n\nNeurovascular syndrome\n\nTarget organ\n\nBone marrow\n\nSmall intestine\n\nBrain\n\nThreshold\n\n1 Gy\n\n5 Gy\n\n20 Gy\n\nLatency time\n\n2\u20133 weeks\n\n3\u20135\u00a0days\n\n30\u00a0min\u20133\u00a0h\n\nDeath\n\n\u22652 Gy\n\n10 Gy\n\n50 Gy\n\nTime of death\n\n3\u20138 weeks\n\n3\u201314\u00a0days\n\nUp to 2\u00a0days\n\nCharacteristic signs and symptoms\n\nGeneral malaise, fever, dyspnea, fatigue, anemia, leukopenia, thrombopenia, purpura\n\nGeneral malaise, anorexia, nausea, vomiting, diarrhea, GI changes, fever, dehydration, electrolyte loss, circulatory collapse\n\nLethargy, tremors, convulsions, ataxia, coma\n\n\nA flow diagram exhibits the phases of the clinical evolution of acute radiation syndrome. The phases are promodal, latent, illness, and recovery or death. The illness includes hematopoietic, neurovascular, gastrointestinal, cutaneous, and pulmonary effects.\n\nFig. 8.14\nScheme showing the phases sequence of the Acute Radiation Syndromes and examples of symptoms"}
{"_id": "Radiology$$$a077c94f-433c-4496-9bd5-17b8567f23c5", "text": "A flow diagram exhibits the phases of the clinical evolution of acute radiation syndrome. The phases are promodal, latent, illness, and recovery or death. The illness includes hematopoietic, neurovascular, gastrointestinal, cutaneous, and pulmonary effects."}
{"_id": "Radiology$$$f59c8eac-b61a-4595-9906-f217a06342b9", "text": "The hematological or hematopoietic syndrome has as its target organs the hematopoietic organs, with special emphasis on the bone marrow. Generally speaking, the hematopoietic syndrome can develop from 1 Gy and the latency time varies from 2 to 3\u00a0weeks. Before a generalized failure of the hematopoietic system occurs, the progenitor cells of all linages have to be irreversibly damaged, which can happen with doses of at least 2 Gy. Without treatment, death may occur 3\u20138\u00a0weeks after exposure."}
{"_id": "Radiology$$$ce90d775-cc16-427f-bde1-649ca7e7432b", "text": "The characteristic signs and symptoms of this syndrome include general malaise, anemia, leukopenia and thrombocytopenia. The decrease in the number of circulating blood cells determines secondary symptoms such as dyspnea, asthenia, hypoxia, fever and purpura. If death occurs, it is mainly due to infections and/or hemorrhage [32, 66, 69, 70]. Treatment requires the use of cytokines, growth factors, antiemetics, antimicrobial agents (antibiotics, antifungals, antivirals), analgesics and in some cases anxiolytics can also be useful. Allogeneic stem cell transplantations should only be performed in specific circumstances (homogeneous whole-body dose, availability of perfectly HLA-matched stem cells)."}
{"_id": "Radiology$$$c071fce7-53a7-4529-b29b-99cbd0b9076a", "text": "If the radiation dose is higher, symptoms corresponding to the involvement of cells of the gastrointestinal system (gastrointestinal syndrome) appear, specifically the cells of the intestinal villi that are found in the mucosa of the small intestine. This syndrome can appear from a dose of 5 Gy with a latency time of 3\u20135\u00a0days. Complete loss of intestinal mucosa occurs at doses above 10 Gy and will be fatal within 3\u201314\u00a0days."}
{"_id": "Radiology$$$55a5b937-12bb-4f2f-a9b9-5f24dd3efb63", "text": "The characteristic signs and symptoms of this syndrome include general malaise, anorexia, nausea, vomiting, diarrhea, fever, dehydration, electrolyte loss and circulatory collapse, leading to death within a few days [32, 66, 69, 70]. Treatment requires adequate fluid administration, parenteral nutrition, growth factors, antiemetics, antimicrobial agents (antibiotics, antifungals, antivirals) and analgesics."}
{"_id": "Radiology$$$1c682fce-1b5b-4faf-844f-6de9a22d67e2", "text": "For higher doses of ionizing radiation, the neurovascular system is involved (neurovascular syndrome) appears, where glial cells may be damaged with doses of 1\u20136\u00a0Gy, lesions of the endothelial cells of the cerebral vessels that occur with doses of 10\u201320\u00a0Gy, or white matter necrosis that appears with doses in the order of 40 Gy or even demyelination that occurs with doses around 60 Gy. This damage will lead to signs and symptoms including lethargy, tremors, convulsions, ataxia, pre-coma and coma, leading to death within hours."}
{"_id": "Radiology$$$44dee129-09f5-47a0-90ad-aa593303ecf9", "text": "This neurovascular syndrome can develop from a dose of 20 Gy with a latency time of 30 min to 3\u00a0h. Death occurs within 2\u00a0days after doses above 50 Gy [32, 66, 69, 70]. Treatment is usually only symptomatic with analgesics and sedatives."}
{"_id": "Radiology$$$eeb0d21c-5f10-4cd7-944f-c440670436c0", "text": "In addition to this syndromes, other important changes can occur in other organs, in response to exposure to ionizing radiation. One of these organs is the skin with the consequent cutaneous effects. Cutaneous effects are deterministic that only appear above a certain threshold dose. The first changes appear in the hair follicles at doses above 0.75 Gy. With higher doses other lesions appear. We can approximately summarize that epilation appears with doses of around 3\u00a0Gy, erythema with doses of around 6\u00a0Gy, desquamation with doses of 10\u00a0Gy, which appears associated with edema, meaning transepithelial lesion, with doses of 20 Gy."}
{"_id": "Radiology$$$0674881e-4352-45ac-9344-a761263a1ebc", "text": "Pulmonary effects, which appear over a huge range of doses (from about 5 Gy to doses as high as 50\u00a0Gy), are strongly dependent on the great vascular richness of the lung. In this context, we must mention the endothelial cells of the small pulmonary vessels, as well as the type II pneumocytes, alveolar cells that secrete surfactant, whose injury has enormous pulmonary functional repercussions. The pulmonary interstitium is also of special importance, as it responds with an intense inflammatory process to exposure to ionizing radiation, called radiation pneumonitis. This inevitably progresses to pulmonary fibrosis with big clinical impact."}
{"_id": "Radiology$$$4292145d-d062-485c-b2c7-39b60465e522", "text": "As mentioned, the manifest illness phase has variable duration and can progress to the phase of death or recovery, depending on dose, dose rate and target organs. The recovery phase is associated with lower doses at which hematopoietic and/or gastrointestinal syndromes occur, especially if adequate medical treatment is carried out. If doses are high enough to induce neurovascular syndrome, the likely outcome is death. In this situation, death occurs few hours after irradiation and predominantly results from systemic vascular effects associated with multi-organ failure [70, 71]."}
{"_id": "Radiology$$$aaefae23-2d11-48bc-87ef-2d79ddcf67cd", "text": "Delayed effects of acute radiation exposure (DEARE) occur when there has been recovery after exposure, that is, when doses were lower, and hematologic and/or gastrointestinal syndromes were developed, after having been subjected to adequate medical treatment."}
{"_id": "Radiology$$$e34a51a6-85cb-46e5-ae18-775088ec85a1", "text": "The delayed manifestations of these syndromes lose their acute expression and are associated with signs and symptoms that show the repercussion in various organs such as the lung, heart, kidney, central nervous system, beyond the bone marrow and gastrointestinal system, the target organs. Evolution results in the progressive failure of the organs involved, until death occurs. Given these characteristics, medical treatment is indicated with radioprotective drugs and/or radiomitigators of the effects of radiation which must be administered as soon as possible after the acute irradiation. This approach has the double goal of reducing the severity of the initial damage and the late onset-pathology [71, 72]."}
{"_id": "Radiology$$$d02457c2-41bb-4fe7-b64c-0eec258b6209", "text": "The concept of lethal dose (LD) is a pharmacological concept that can be applied to the consequences of exposure to ionizing radiation and is defined as the amount of dose of radiation that kills elements of an irradiated population. This broad concept can be further specified if we consider the dose that kills 50% of an irradiated population, which is called the median lethal dose (LD50) [70, 73]."}
{"_id": "Radiology$$$554de0e2-cbf2-486c-ba42-77b045d8be56", "text": "The characteristics of the biological effects of radiation, namely the duration of latency time, associated with the great individual variability led to the refinement of this concept. Thus, there is often referred the LD50/30 (dose that kills 50% of the irradiated population in 30\u00a0days) or LD50/60 (dose that kills 50% of the irradiated population in 60\u00a0days). The LD50/60 for a healthy adult range between 2.5 and 3\u00a0Gy, while the LD50/30 ranges between 2.5 and 4.5 Gy. These values assume whole-body irradiation and the natural history of the disease, that is, the non-use of medical care, and are based on data from the survivors of Hiroshima and Nagasaki [34, 66, 74]. Although the LD50/30 and LD50/60 are similar concepts, they provide complementary and very important indications. In the case of somatic effects, the LD50/60 informs that if a survival for more than 60\u00a0days after an irradiation occurs, the recovery is expected."}
{"_id": "Radiology$$$bb062b0d-68d4-4d37-8ee6-bc67829b1863", "text": "For bone marrow, the LD50/60 ranges from approximately 3.5 to 4.5\u00a0Gy, however with supportive medical care, such as blood transfusions associated with antibiotic therapy, it can change to values between 5 and 6 Gy. With more robust treatments, such as the administration of hematopoietic growth factors, values from 6 to 8 Gy can be achieved [66] (Box 8.3)."}
{"_id": "Radiology$$$913a1b11-4fdb-48cc-a00e-28ff8923dfab", "text": "Acute radiation syndromes appear after whole-body irradiation\n\nAfter an irradiation, the biological consequences appear following four stages: Prodromal, latent state, manifest illness state, and of recovery or death state\n\nWhen recovery occurs, delayed effects of acute radiation exposure can manifest\n\nLD50 is the dose that kills 50% of the irradiated population after 30 days (LD50/30 or 60 days (LD50/60)"}
{"_id": "Radiology$$$8bf4ba77-39f1-4c38-a1aa-6ce7d3b12340", "text": "After an irradiation, the biological consequences appear following four stages: Prodromal, latent state, manifest illness state, and of recovery or death state"}
{"_id": "Radiology$$$5ce5f972-68d4-42d5-a0fc-b041f7649bf8", "text": "When recovery occurs, delayed effects of acute radiation exposure can manifest"}
{"_id": "Radiology$$$6283d8c5-a17b-4e1a-adcf-639b58fed227", "text": "LD50 is the dose that kills 50% of the irradiated population after 30 days (LD50/30 or 60 days (LD50/60)"}
{"_id": "Radiology$$$2f106830-61d8-47ee-adeb-449ddceeb72c", "text": "When individuals are exposed to ionizing radiation in an accidental scenario, there is an urgent need to categorize exposed individuals not only in terms of the urgency of their need for treatment, but also in relation to ionizing radiation exposure. In general, radiation accidents lead to external radiation exposure and/or external or internal contamination with radionuclides. Exposures in situations requiring triage tend to be acute, but chronic exposures also need to be considered. Further exposure or contamination can be approximately homogeneous or highly heterogeneous. Hence the available tools and processes need to be flexible and sufficient to allow appropriate triage in a variety of potential situations. This section considers in the need for initial triage including decontamination, specific considerations related to radiological triage, as well as the need for late follow-up. Communication to the public is also a topic of importance, not covered in detail here, but with further information in the TMT Handbook [75]."}
{"_id": "Radiology$$$6490ee9f-2206-44f6-9ae9-9e906da4a15c", "text": "In general, triage is used to screen the patients with severe injuries after a mass incident, including chemical, biological, radiological, nuclear, or explosive events (CBRNE). The first step during triage is to classify the affected person according to the type and severity of the suffered injuries, accurately assessing prognosis and survival expectancy, and to minimize the consequences of the event through the timely administration of first aid and/or treatment. After a catastrophic event the affected individuals can suffer from severe injuries, including tissue or bone trauma, thermal and/or chemical damage, in addition to ionizing radiation [75, 76]."}
{"_id": "Radiology$$$d20453a0-d722-4f84-b07e-1ceb6962ad7a", "text": "Initial triage should be swift, simple, and based on universal guidelines, especially because it is often performed in a danger zone within the vicinity of the accident; further, triage will be initially based on the immediate threats to life and not on radioactive exposure and/or contamination. This cannot be understated; primary medical attention will always be aimed at dealing with immediate life-threatening conditions. The primary aim is to determine the transport priority of the victims to the hospital, screening the wounded in the area for later medical attention (Table 8.11). However, the classification of the injured and affected victims should be continuously re-evaluated, as the victims\u2019 condition can change very quickly. There are several types of triages, for example, SALT (Sort, Assess, Lifesaving Interventions, Treatment/Transport); START (Simple Triage and Rapid Treatment\u2014Adult), and JumpSTART (Simple Triage and Rapid Treatment\u2014Children). These systems have four main color-coded categories [75, 78].Table 8.11\nClassification of victims of the radiation accident based on initial triage (e.g., START) [77] (reproduced with permission from the USDHHS Radiation Emergency Medical Management, https://\u200bchemm.\u200bhss.\u200bgov)\n\nTriage categories\n\nColor\n\nFirst aid\n\nSorting victims\u2019 priority\n\nTransport priority\n\nImmediate/priority 1 (P1)\n\nRed color tag\n\nImmediate urgent first aid and priority transport\n\nThird\n\nFirst\n\nDelayed/priority 2 (P2)\n\nYellow color tag\n\nDelayed urgent first aid and transport after P1\n\nFourth\n\nSecond\n\nWalking wounded/minor/priority 3 (P3)\n\nGreen color tag\n\nMinor/minimal first aid, separate departure from the zone or with mutual assistance\n\nFirst\n\nThird\n\nDeceased/expectant/priority 4 (P4)\n\nBlack color tag\n\nDead/deceased, injuries incompatible with life, shall be marked and left at the site of the finding for later recovery of the body if at all possible\n\nSecond\n\nFourth"}
{"_id": "Radiology$$$60b8793e-7a71-46ab-b693-819ee0f00570", "text": "If people are exposed to radioactive material, they are swiftly screened in the triage by the first responders at the scene of the accident, i.e., paramedics, to assess the condition of the victims (Table 8.12). The aim of the triage system is to identify the victims with severe trauma and provide first aid and evacuation. The trauma triage system has three category priorities (P1\u2013P3) (Table 8.13).Table 8.12\nClassification of externally irradiated individuals according to the received dose (reproduced with permission from [75])\n\nRadiation dose (Gy)\n\nPriority\n\nLess than 2\n\nP3\n\n2\u20136\n\nP2, eventually P1 if they are also injured\n\n6\u201310\n\nMore than 10\n\nP4\nTable 8.13\nClassification of victims of the radiation accident based on trauma triage (reproduced with permission from [75])\n\nCategory/priority\n\nFirst aid\n\nVictim classification (SOP)\n\nCategory/priority 1 (P1)\n\nFor severely injured victims in need of immediate first aid and evacuation\n\nRemoval from the accident site in the first place\n\nCategory/priority 2 (P2)\n\nFor less severe injured victims in need of evacuation into the hospital, with a delay of up to 12\u00a0h\n\nRemoval from the accident site in the second place\n\nCategory/priority 3 (P3)\n\nFor victims with minor injuries who can depart the zone of the accident on their own, wait several hours for medical treatment, or go home to return to the triage on the following day\n\nRemoval from the accident site in the third place"}
{"_id": "Radiology$$$97130ae5-898c-49d7-b910-d3af54666aed", "text": "Victims with trauma injuries should be identified first and medical attention for them is a priority (Fig. 8.15); however, if ionizing radiation exposure is an issue for both victim and first responder then the former must be moved from the area to reduce the dose rate. Contamination with radioactive material, both external and internal, is to be expected in these incidents, especially after an explosion. All the victims in the categories P1, P2 and P3 may be contaminated with radioactive material; therefore, triage for these individuals should be different. The victims sorted into category 1 are immediately transported to the hospital without prior decontamination, thus the medical staff has to be made aware of this fact. Serious injury is to be expected if the victims are sorted into category 2, although their evacuation can be delayed and thus decontamination should be performed before transport to the hospital, otherwise the hospital staff should be informed that decontamination has not taken place. The victims sorted into category 3 should be decontaminated at the site of the accident or given information on how self-decontamination should be performed and sent home. Decontamination for these victims is not performed at the hospital and medical treatment has lower priority than for category 1 and 2 victims (Table 8.14) [75, 79, 80]. It should also be noted that non-surviving victims of the mass biological, chemical, radiological or nuclear event are a potential and hazardous source of ionizing radiation.\n\nA flow diagram exhibits the steps to identify the trauma injuries. 1. Check for a physical injury. If not, exit trauma triage. 2. If yes, proceed with P 1 and go to the hospital. If not, proceed with P 2, followed by decontamination near the site. 3. Radiological triage at the hospital.\n\nFig. 8.15\nSchema for trauma triage. (Reproduced with permission from [75])\nTable 8.14\nInjury priority and decontamination (reproduced with permission from [75])\n\nPriority\n\nUrgent medical attention\n\nDecontamination\n\nPriority 1 (P1)\n\nImminent death if immediate medical attention is not administered\n\nResuscitation and stabilization have priority over decontamination\n\nPriority 2 (P2)\n\nAcute surgery necessary within 2\u20134\u00a0h after injury\n\nDecontamination has priority if stabilization is not possible due to the nature of the injury\n\nPriority 3 (P3)\n\nMedical attention can be delayed for more than 4\u00a0h\n\nDecontamination has priority"}
{"_id": "Radiology$$$3ee367dd-9ba5-41cb-be9c-27b6a7e16833", "text": "A flow diagram exhibits the steps to identify the trauma injuries. 1. Check for a physical injury. If not, exit trauma triage. 2. If yes, proceed with P 1 and go to the hospital. If not, proceed with P 2, followed by decontamination near the site. 3. Radiological triage at the hospital."}
{"_id": "Radiology$$$ca59ab36-f5f6-428a-85a4-ebbbf29dc80c", "text": "Following initial triage for trauma as described above, Category 2 and 3 victims should be monitored and further evaluated in the next steps of triage, comprising information about location at the time of the accident and/or radiological analysis based on clinical signs and symptoms to identify individuals who may have received doses high enough to cause deterministic effects."}
{"_id": "Radiology$$$8d2caa58-2ab1-4097-b4b3-f930a4d06f67", "text": "As much information as possible should be collected regarding the type and energy or activity of the source and the dispersal of the radiation within the environment contributing to exposure/contamination. Regarding individual information, considerations include the time of direct contact or distance from the source when in proximity, whether the exposure took place within an enclosed or open environment, whether or not the individual was within the line of sight of the source, and if the source was mobile. Such information is needed for all potential points of exposure and can then be used to help prioritize individuals for treatment as described in more detail in the TMT Handbook [75]. In addition, such information can contribute to modelling of radiation exposure at the individual or population level, as considered in Chap. 4."}
{"_id": "Radiology$$$9a9078ee-3c00-4089-9d28-883a27ec14cc", "text": "Section 8.4.2 describes the prodromal clinical signs and symptoms associated with approximate (>60%) whole-body ionizing radiation exposure, which can be used to estimate the radiation dose and the potential severity of ARS for Category 2 and 3 patients, as well as for any individuals identified through the location analysis to have doses high enough to potentially cause deterministic effects (Fig. 8.16). These individuals should be monitored for onset of nausea and vomiting, diarrhea and/or erythema.\n\nA line graph plots time and patient percent versus dose. The line for time begins at (2, 4.6), decreases gradually, and ends at (10, 0.8). The patient line begins at (2, 36), increases gradually, and ends at (10, 99). Values are estimated.\n\nFig. 8.16\nRelationship between time to onset of vomiting and dose between 2 and 10 Gy. (Reproduced with permission from [75])"}
{"_id": "Radiology$$$101e6b98-d6c1-4b9f-a0e3-871618804248", "text": "A line graph plots time and patient percent versus dose. The line for time begins at (2, 4.6), decreases gradually, and ends at (10, 0.8). The patient line begins at (2, 36), increases gradually, and ends at (10, 99). Values are estimated."}
{"_id": "Radiology$$$130b3c1c-c948-4fb9-aebc-bc58285e797e", "text": "In addition, differential blood cell counts should be taken, according to Fig. 8.17, at 8\u00a0h intervals on the first day and 12\u00a0h intervals on the second day, with decisions regarding later intervals to be taken according to the indicated severity of the complete blood count (CBC) suppression, the number of potentially exposed individuals and the available capacity. Where CBC indicates that significant doses have been received, or significant effects are expected, chromosome aberration analysis should be carried out to obtain a more concrete individual estimate of dose, as detailed in Sect. 8.6.\n\nA multi-line graph plots lymphocytes versus time. The y-axis ranges from 0 to 3000, and the x-axis ranges from 0 to 2. The values are plotted for normal, moderate, severe, and critical injuries. 4 lines follow a decreasing trend.\n\nFig. 8.17\nLymphocyte depletion with dose and time post exposure, following whole-body doses exceeding 1 Gy. (Reproduced with permission from [75])"}
{"_id": "Radiology$$$389c579f-548d-467b-82b2-2a74b5a6696a", "text": "A multi-line graph plots lymphocytes versus time. The y-axis ranges from 0 to 3000, and the x-axis ranges from 0 to 2. The values are plotted for normal, moderate, severe, and critical injuries. 4 lines follow a decreasing trend."}
{"_id": "Radiology$$$79f6e249-8ad0-4a05-a4a8-1bbab45b3ef1", "text": "The next step in cases of internal contamination should be the swift assessment and sorting of the affected persons, mostly because decontamination efficiency decreases with time. Cases of internal contamination are recognized through a radiation survey, which can detect significant residual and localized (e.g., lungs, thyroid) or distant (e.g., urine, blood, smears, feces) radioactivity [81]. The initial monitoring of internal contamination victims cannot be done without special equipment, such as whole-body counters or thyroid uptake systems [82]. According to the TMT Handbook, the first set of actions during radioactive emergencies should be as follows:1.\nFocus on life-threatening conditions, control of vital functions and hemorrhage, and transfer to emergency medical care facilities.\n\u00a02.\nPerform external contamination monitoring and decontamination, if external contamination is detected.\n\u00a03.\nLower the risk of internal contamination and initial monitoring level of internal contamination for further treatment and prevent further contamination.\n\u00a04.\nBased on the initial monitoring, early clinical judgement should be based on the risks and benefits of treatment of internal contamination by radionuclides. Medical professionals will determine if medical treatments are needed [75]."}
{"_id": "Radiology$$$e731c59d-880f-432c-9f4c-317df59a2358", "text": "Focus on life-threatening conditions, control of vital functions and hemorrhage, and transfer to emergency medical care facilities."}
{"_id": "Radiology$$$e25ef63f-5de7-4434-906f-193d3f865c24", "text": "Perform external contamination monitoring and decontamination, if external contamination is detected."}
{"_id": "Radiology$$$b9bafc4b-a693-4324-a6dc-fdc5be116c8d", "text": "Lower the risk of internal contamination and initial monitoring level of internal contamination for further treatment and prevent further contamination."}
{"_id": "Radiology$$$d1211904-7f83-4600-99a4-cb5a3f81826c", "text": "Based on the initial monitoring, early clinical judgement should be based on the risks and benefits of treatment of internal contamination by radionuclides. Medical professionals will determine if medical treatments are needed [75]."}
{"_id": "Radiology$$$4307c3ed-efee-445e-99cc-9fab249e9f2c", "text": "Internal contamination does not cause immediately serious or acute effects nor does it present a time-limiting life-threatening condition before the appropriate lifesaving and decontamination measures can be performed. Having said that, some radionuclides, such as 210Po or 137Cs, can cause massive internal damage or acute radiation syndrome within a few days after contamination [79, 83]."}
{"_id": "Radiology$$$8a8a6a51-9e55-4c12-b273-70a78d150d57", "text": "The victims should ideally have been externally decontaminated by the time of arrival at the medical facilities; if such is not the case the medical staff should be made aware about their condition and take the appropriate measures. The decontamination treatment of internally contaminated victims should start as soon as possible, especially if there is a risk of deterministic effects; however, accident history and dose estimation should be carefully considered (Table 8.15). The effectiveness of the treatment is determined by the early administration of radionuclide counteragents and the first aid provided, even if radioactive contamination is only suspected. The treatment administered should remove the contaminating radionuclides from the human body using chemical or biological agents, which may reduce their absorption, prevent their incorporation and internal deposition (e.g., chelating agents), or promote their elimination or excretion (e.g., lavage of the oral cavity, nose, conjunctival sac, stomach, use of laxatives or diuretics). In this regard, most methods of treatment for internal contamination with radionuclides include isotope blocking, dilution, or displacement, and the use of ion exchange resins, and ion mobilization or chelation (Table 8.16) [24].Table 8.15\nAction levels for treatment of radionuclide contamination (reproduced with permission from [75])\n\nAssessed committed effective dose (mSv)\n\nRecommended action\n\n<1\n\nAppropriate for public reassurance that doses pose a minimum risk to health. No treatment.\n\n1\u201320\n\nMore accurate dose assessment is required. Treatment should not be considered.\n\n20\u2013200\n\nMore accurate dose assessment is required. Treatment is subject to medical judgement. Although clinical effects are unlikely to occur, the potential efficacy of extended or protracted treatment should be considered.\n\n>200\n\nTreatment should be considered. However, psychological factors and potential efficacy of extended or protracted treatment should be considered.\nTable 8.16\nSelected radionuclides and radiation countermeasures for treatment (reproduced with permission from [84])\n\nRadionuclide\n\nTreatment\n\nDose\n\nEffect\n\nIodine\n\nPotassium iodide (KI)\n\n130\u00a0mg/day (pill) for 7\u00a0days\n\nBlocking agent\n\nPlutonium\nYttrium\n\nDTPA (diethylene-triamine penta-acetic acid)\n\n1\u00a0g calcium DTPA in 500\u00a0mL i.v. for 60 min\n\nChelating agent\n\nUranium\n\nSodium bicarbonate\n\nSlow i.v. infusion by NaHCO3 solution (250\u00a0mL)\n\nAlkalization of urine\n\nCesium, rubidium, thallium\n\nPrussian blue\n\n3\u00a0g in 100\u2013200\u00a0mL H2O orally three times per day\n\nMobilization decreases  gastrointestinal tract uptake, absorption\n\nRadium, strontium\n\nBaSO4\nSodium alginate\n\n100\u00a0g in 250\u00a0mL H2O This is the dose for BaSO4. For Sodium alginate it is\n5\u00a0g orally twice daily\n\nReduction/inhibition of absorption\n\nTritium\n\nH2O\n\nDrinking 6\u201312\u00a0L/day\n\nFacilitates excretion\n\nLead, copper, polonium\n\nd-penicillamine dimercaptopropanol\n\n1\u00a0g i.v./day or 0.9\u00a0g orally/4\u20136\u00a0h\n\nChelating agent"}
{"_id": "Radiology$$$b969390d-0903-4ead-98e1-04c0925ec72e", "text": "The measures for internal decontamination are not used to treat acute radiation injury, but the main aim is to reduce the risk of stochastic effects like tumors induced by radiation in organs or tissues where radionuclides were incorporated."}
{"_id": "Radiology$$$fe0637c8-d3c4-4853-be06-1e698a18df63", "text": "Long-term medical monitoring should be carried out for the patients suffering from the clinical symptoms of acute radiation syndrome or local radiation injuries; however, asymptomatic patients should also be included in long-term follow-up as well as those for which there is only a presumed ionizing radiation exposure."}
{"_id": "Radiology$$$21f513c4-c00c-444d-9e21-0ed3caf0e80c", "text": "The patients with clear clinical symptoms should be scheduled for long-term follow-up to prevent, control, and care for the health consequences of ionizing radiation exposure. The long-term follow-up means that the patients will be checked in regular appointments in specialized clinical departments over a 5-year period to monitor any risk factors, health outcomes, or both. The long-term follow-up does not always have the same scenario and it is different on a case-by-case basis, mostly based on the development of symptoms of acute radiation syndrome and received dose of radiation. As an example, the logical first step for affected person is to contact and inform the primary care physician about the radiation exposure incident and plan a follow-up program with the physician and the specialists at various departments in the hospital (e.g., hematology, radiotherapy, psychology, internal medicine) if needed. If the affected patient recovers from the hematological consequences of acute radiation syndrome, a hematological examination should be conducted every 3 months during the first year and a routine medical examination once a year. Annual examinations at the ophthalmological clinic are also recommended for monitoring cataract incidence, if any. In addition, medical consultation should be offered to exposed victims for mental and reproductive health as and when needed [75]. The benefit of this long-term medical monitoring is the identification of radiation symptoms, and though it may sound daunting this follow-up does not differ much from that performed for other clinical conditions. It must be noted that those patients without symptoms could have the greatest benefit from long-term medical monitoring. This monitoring provides the capacity to classify the individuals at greater risk; further, it also enables the proper evaluation of diseases that may be found in the population at risk. Although it may be inconvenient for asymptomatic patients, long-term medical monitoring may help in early diagnosis and treatment of serious radiation-related illnesses, thus minimizing morbidity and mortality rates. Persons who have been exposed to low doses of ionizing radiation during a radiation emergency, who have not experienced ARS or other immediate symptoms associated with radiation exposure, should also be included in long-term follow-up and monitoring mostly to dismiss the existence of radiation effects or to monitor ionizing radiation exposure related illnesses, which often come in the form of cancer. In addition, the long-term follow-up may also provide the affected patients with mental health support and reproductive health consulting."}
{"_id": "Radiology$$$5fe9dd7b-e9fa-440e-852e-06fc04841d20", "text": "Taken together, the long-term follow-up and medical monitoring of the persons affected by radiation emergencies can provide new epidemiological data since medical follow-up data for potential stochastic effects such as cancer are sparse. However, social, economic, legal, and psychological aspects should be considered in the follow-up and monitoring of these patients [75]. The epidemiological follow-up determines two groups, i.e., exposed and unexposed to radiation, and registers any difference in the health outcome. How this will be done will depend on the exposure scenario. The typical outcome in radiation epidemiology is represented by a greater incidence of cancer or mortality related to radiation. The most precise and conclusive parameter in an epidemiological study is mortality due to clear and obvious occurrence, supported by the records available worldwide. Also, epidemiological follow-up studies should include non-malignant morbidities and mortality, which are known parameters collected from A-bomb survivors\u2019 life span studies. However, it has to be mentioned that this is not always the main interest of epidemiological follow-up of health outcomes. In many cases there is an interest in diseases that can affect quality of life, such as nonfatal diseases, for example, tissue degenerative diseases [75, 85] (Box 8.4)."}
{"_id": "Radiology$$$adf18eee-0ff3-426d-b068-3c65ea2d9ec9", "text": "Initial triage for trauma, the victims should be monitored and further evaluated in the next step of triage, comprising information about location at the time of the accident and/or radiological analysis based on clinical signs and symptoms.\n\nInternal contamination should be the swift assessment and sorting of the affected person, mostly because decontamination efficiency is often hindered by time delays.\n\nCases of internal contamination are recognized through a radiation survey, which can detect significant residual.\n\nInternal contamination does not cause immediately serious or acute manifestations nor does it present a time-limiting life-threatening condition.\n\nThe treatment administered should remove the contaminating radionuclides from the human body through chemical or biological agents."}
{"_id": "Radiology$$$f33ac14a-2217-4a11-bf45-969085f54aa9", "text": "Initial triage for trauma, the victims should be monitored and further evaluated in the next step of triage, comprising information about location at the time of the accident and/or radiological analysis based on clinical signs and symptoms."}
{"_id": "Radiology$$$8b7f7ec5-9152-4575-80c9-1a2482efc14c", "text": "Internal contamination should be the swift assessment and sorting of the affected person, mostly because decontamination efficiency is often hindered by time delays."}
{"_id": "Radiology$$$7def1784-9e7b-45da-a721-909574d2c2f1", "text": "Cases of internal contamination are recognized through a radiation survey, which can detect significant residual."}
{"_id": "Radiology$$$55e6eab5-8be2-4c28-b58f-ff18e8a8d010", "text": "Internal contamination does not cause immediately serious or acute manifestations nor does it present a time-limiting life-threatening condition."}
{"_id": "Radiology$$$2d99b0c0-ef00-4548-9380-b8f7e1536717", "text": "The treatment administered should remove the contaminating radionuclides from the human body through chemical or biological agents."}
{"_id": "Radiology$$$6a455017-17b2-4247-90c8-c4728bc15656", "text": "Biological dosimetry is an internationally accepted method for the detection and quantification of presumed/suspected exposures to ionizing radiation in humans. On the basis of biomarkers in the peripheral blood, the amount of ionizing radiation to which an individual has been exposed can be determined and estimated. Biological dosimetry can be used in addition to physical dosimetry or as a distinct method for dose reconstruction. The traditionally used, well-established cytogenetic assays are predominantly based on induction and misrepair of radiation induced DNA double strand breaks. The analyses are performed in lymphocytes of the peripheral blood, as these circulate throughout the body, and they are normally in the G0/G1 stage of the cell cycle. Since lymphocytes are not cycling, they need to be stimulated to proliferate during in vitro cell culturing. There are several essential requirements for biological parameters to be meaningful dosimeters: Low background level, clear dose effect relationship for different radiation qualities and dose rates, specificity to ionizing radiation, non-invasive sample collection, fast availability of dose estimation, good reproducibility, as well as comparability of in vitro and in vivo results to set up a calibration curve [86]."}
{"_id": "Radiology$$$3e1655c5-e508-45cc-aa20-20d432c6caaa", "text": "The analysis of dicentric chromosomes (dic) (Fig. 8.18) with or without the inclusion of centric rings in lymphocytes of the peripheral blood is a well-established method for dose reconstruction after an acute exposure to ionizing radiation and therefore, considered as the \u201cgold standard\u201d in biological dosimetry [87]. After blood collection, lymphocytes are cultured at 37\u00a0\u00b0C for 48\u00a0h and stimulated to enter mitosis by using specific mitogens. During mitosis, chromosomes condense and become visible by light microscopy and dicentric chromosomes can be quantified. In Fig. 8.18 the formation of dicentric chromosomes is schematically presented (a) and a Giemsa stained metaphase cell is shown in (b) with a dicentric chromosomes and an accompanying fragment (ace). The dicentric chromosomes fulfill the essential requirements of a suitable biomarker for the detection of exposure to ionizing radiation. In particular, dicentric chromosomes are almost exclusively caused by ionizing radiation [88]. In healthy, non-exposed individuals, dicentric chromosomes rarely occur spontaneously and the background rate is about 0.5\u20131 dicentric chromosome in 1000 cells [89]. Therefore, the method has a good sensitivity. The lowest detectable dose of a homogeneous acute whole-body irradiation with low-LET (linear energy transfer) radiation is about 100\u00a0mGy when 500\u20131000 cells are evaluated [90]. It is well accepted that a comparable number of chromosomes damaged per dose unit is induced for both high- and low-LET radiation in vitro and in vivo [91] enabling dose estimation on the basis of in vitro calibration curves. The dose effect relationship can be modeled by a linear-quadratic curve (Y\u00a0=\u00a0c\u00a0+\u00a0\u03b1D\u00a0+\u00a0\u03b2D2) for up to 5 Gy of low-LET radiation and by a linear model (Y\u00a0=\u00a0c\u00a0+\u00a0\u03b1D) for high-LET (alpha or neutron) radiation [92]. In addition, based on the analysis of dicentric chromosomes, a distinction can be made between homogeneous and inhomogeneous or between high- and low-LET exposures [89]. The mean lifetime of lymphocytes with dicentric chromosomes in the peripheral blood is between 0.6 and 3\u00a0years [93], and this is largely influenced by both the absorbed radiation dose (low or high) and inter-individual variation in lymphocyte turnover rate [88]. The decline of dicentric chromosome bearing lymphocytes can occur either by cell death or by dilution of damaged lymphocytes with the fresh population of lymphocytes over long periods of post radiation exposure. Therefore, in the case of radiation exposure that occurred a long time ago or was protracted, i.e., over a longer period of irradiation at a low-dose rate, appropriate adjustments must be made to avoid underestimation of the dose. Chromosome analysis is considered as a very labor-intensive method requiring well-trained staff to perform the analyses [94]. To increase the throughput of the method for a large-scale accident with a large number of potentially exposed individuals, different approaches have been developed. Scoring 50 cells or 30 dicentrics has been accepted as sufficient in triage scoring to identify those who need immediate medical support [95]. Software-based automated scoring systems for the rapid detection of dicentric chromosomes have been developed and successfully applied in various studies (e.g. [96]). Recent advances in using imaging flow cytometry to identify dicentric chromosomes have demonstrated the feasibility, however, there is still much room for improvement [97]. Also automated robotically based high-throughput platform (RABiT, Rapid automated Biodosimetry Tool) has been designed to enhance the capacity of dicentric chromosome analysis [98].\n\n2 schematic diagrams. a. It demonstrates how the dicentric chromosomes are formed from the normal chromosomes via radiation-induced breaks. Acentric fragments are also formed. b. A structure of several chromosomes and fragments with dicentric and acentric.\n\nFig. 8.18\n(a) Schematic representation of the formation of a dicentric chromosome (dic) after exposure to ionizing radiation with the formation of a chromosome fragment without centromere (ace). (b) Giemsa stained metaphase spread of a human peripheral blood lymphocyte with a dic and ace"}
{"_id": "Radiology$$$5adc5ae2-72a0-4354-af9b-5331f00a3139", "text": "2 schematic diagrams. a. It demonstrates how the dicentric chromosomes are formed from the normal chromosomes via radiation-induced breaks. Acentric fragments are also formed. b. A structure of several chromosomes and fragments with dicentric and acentric."}
{"_id": "Radiology$$$df5d1aeb-684e-4d0f-9856-1983be88e72d", "text": "The analysis of micronuclei (MN) in binucleated (BN) cells of peripheral blood lymphocytes is an alternative cytogenetic technique used in biological dosimetry (Fig. 8.19). The assay originally developed by Fenech and Morley in 1985 restricted MN scoring to first division cells after inhibition of cytokinesis (cytoplasmic division) by cytochalasin B [99]. Micronuclei (MN) are small extranuclear bodies resulting from chromosome fragments or whole chromosomes that are excluded from mitotic spindle and therefore not included in the main daughter nuclei during cell division. Due to an elevated spontaneous frequency of micronuclei (0\u201340 MN/1000 BN cells) relative to dicentric chromosomes [89], the lowest detectable radiation dose of a homogeneous acute whole-body irradiation with low-LET based on micronuclei analysis is about 200\u2013300\u00a0mGy when 500\u20131000 BN cells are analyzed [88]. The application of Fluorescence in situ hybridization (FISH) using a human pancentromeric probe can help in determining the origin of MN based on the presence (presumably whole chromosomes) and absence (chromosome fragments) of centromeric signal. It is well demonstrated that most radiation-induced MN are centromere negative [100]. Therefore, the sensitivity of the MN assay can be increased in the low-dose range by this method [101]. MN are less radiation specific than dicentric chromosomes and show greater variability both inter- and intra-individually. The rate of MN is influenced by age, sex, and lifestyle as well as exposure to other environmental mutagens [102]. The advantage of the method is the simple and quick evaluation, enabling relatively rapid training of inexperienced persons [103]. Various automated systems are available for MN analysis based on microscopy [104] or flow cytometry methods [105]. Furthermore, a high throughput and miniaturized version of the CBMN assay for accelerated sample processing has been described [106]. Several studies have confirmed the reliability of the automated MN assay for high-throughput population triage [107].\n\n4 micrographs of binucleated cells. 1 has a cell with no micronuclei, 2 has a cell with 1 micronucleus, 3 has a cell with 2 micronuclei, and 4 has a cell with 4 micronuclei.\n\nFig. 8.19\nPresentation of binucleated cells including 0, 1, 2 or 4 micronuclei"}
{"_id": "Radiology$$$252bd3a7-d83e-4d73-acdf-d4c078efe74c", "text": "4 micrographs of binucleated cells. 1 has a cell with no micronuclei, 2 has a cell with 1 micronucleus, 3 has a cell with 2 micronuclei, and 4 has a cell with 4 micronuclei."}
{"_id": "Radiology$$$dcf0c83a-7b15-48f0-a0f9-b77b22886094", "text": "Fluorescence in situ hybridization (FISH) techniques have been in use for a number of years to identify translocations for the purpose of retrospective radiation dose assessment of radiation exposed victims [108] (Fig. 8.20). The technique relies on the use of chromosome-specific libraries of fluorescent probes to paint chromosomes in blood lymphocytes, in order to quantify the frequency of chromosome exchanges. In the simplest form of the assay, a cocktail of DNA probes for three human chromosomes labeled with a single fluorophore is used to estimate \u201cgenome equivalent\u201d number of translocations based on the percentage of chromosomal material represented by the stained chromosomes. Typically, a cocktail of DNA probes for three human chromosomes covers at least 20% or more of the human genome. As translocations are not radiation specific and are predominantly stable within the genome, the expected background number of translocations [109] must then be subtracted from the observed number in the suspected irradiated sample. The genome equivalent rate of translocations is then translated to radiation dose by reference to a pre-determined dose response curve. The relative stability of translocations does, however, mean the assay can be used many years post exposure.\n\nA schematic diagram and a radiograph. a. It demonstrates how chromosomal translocation is formed from the normal chromosomes via radiation-induced breaks. b has radiated chromosomes, and the bright and dark shades have arrows.\n\nFig. 8.20\n(a) Schematic representation of the formation of a symmetrical translocation after radiation induced chromosomal breaks. (b) FISH painted metaphase spread of a human peripheral blood lymphocyte with translocations indicated by the arrows"}
{"_id": "Radiology$$$aad904eb-c4c6-4b7e-bb65-a7a94a128a05", "text": "A schematic diagram and a radiograph. a. It demonstrates how chromosomal translocation is formed from the normal chromosomes via radiation-induced breaks. b has radiated chromosomes, and the bright and dark shades have arrows."}
{"_id": "Radiology$$$bc28f291-1439-4bc2-a620-9da8531c76ea", "text": "In addition to this single color painting, genome wide analysis, known as M-FISH (which does not require adjustment for genome equivalent damage), allows the detection of all simple interchromosomal exchanges as well as complex rearrangements involving multiple breakpoints in several chromosomes. Use of chromosome specific multicolor band probe (mBAND) facilitates the assessment of intra-chromosomal rearrangements such as pericentric and paracentric inversions."}
{"_id": "Radiology$$$c68b5970-bb2a-4e97-adcc-1917f3fceaa5", "text": "The FISH translocation assay has most commonly been used to estimate radiation doses following external radiation exposures [108]. As above, this technique is relevant for dose assessment at post-exposure time periods of days up to many years post exposure, however, does not work well for partial-body exposure."}
{"_id": "Radiology$$$7d9f0fa7-ea56-4ac7-9996-ccfde0268ed9", "text": "The detection limit for FISH for uniform whole-body external low-LET exposures is on the order of 250\u00a0mGy, however, this varies depending on a number of factors, including the number of cells scored, age and smoking status (because translocations are not radiation specific), as well as length of time post exposure [109]. These issues, together with the length of time needed to culture the cells in order to visualize the aberrations, are the main limitations of the assay. Automation of FISH analysis is under development, but is not yet in common use."}
{"_id": "Radiology$$$2254a501-d7bf-452e-8318-e0b8018e2ad8", "text": "Lymphocytes are sensitive to radiation and therefore use of both DCA and CBMN for exposure doses higher than 4 Gy is somewhat problematic. Especially in radiation accidents involving high doses of radiation, the premature chromosome condensation (PCC) assay can be of use in the quantification of radiation-induced chromosomal aberrations directly on unstimulated interphase blood lymphocytes [89]. Specifically, PCC induction in G0 lymphocytes isolated from whole human blood is mainly achieved by means of their fusion to Chinese hamster ovary (CHO) mitotic cells using the chemical polyethylene glycol (PEG) as a kind of fusogen [110]. PCC can also be induced in G2 cells by phosphatase inhibitors such as okadaic acid or calyculin A. Unlike cell fusion of unstimulated G0 lymphocytes, chemically induced PCC method requires stimulation of lymphocytes for one cell division because these chemicals induce premature condensation of G2 cells after DNA replication. The PCC method is suitable for the analysis of ring chromosomes, especially at higher doses [111]. To quantify radiation-induced chromosomal aberrations in G0-phase lymphocytes using the fusion PCC-assay, the total number of single chromatid PCC elements per cell in the exposed lymphocytes is recorded (Fig. 8.21a) and the yield of radiation-induced excess PCC fragments is estimated by subtracting the number of 46 PCC elements expected to be scored in non-irradiated lymphocytes (Fig. 8.21b). The dose assessment is based on a dose-response calibration curve generated by in vitro irradiation of unstimulated blood lymphocytes. These curves have a linear shape and the residual yield of excess fragments depends on the time elapsed for repair between the irradiation and the cell fusion Especially in radiation accidents where high doses are received the premature chromosome condensation (PCC) assay enables quantification of radiation-induced chromosomal aberrations directly on unstimulated interphase blood lymphocytes [89].\n\n2 schematic representations of the chromosome irradiated with and without gamma rays. A has several chromosomes and 14 P C C fragments. They are small or tiny. B has chromosomes and 46 single chromatid P C C fragments.\n\nFig. 8.21\n(a) Prematurely condensed single chromatid chromosomes following gamma irradiation to 4 Gy as visualized using the PCC assay and lymphocyte fusion to a mitotic CHO cell. Fourteen excess PCC fragments can be scored (shown by arrows). (b) Non-irradiated G0-lymphocyte PCCs demonstrating 46 single chromatid PCC elements. (Reproduced with permission from [112])"}
{"_id": "Radiology$$$89e08a32-9dd1-4dc8-b6c2-815354898c37", "text": "2 schematic representations of the chromosome irradiated with and without gamma rays. A has several chromosomes and 14 P C C fragments. They are small or tiny. B has chromosomes and 46 single chromatid P C C fragments."}
{"_id": "Radiology$$$62299627-a008-422c-88e4-78bf79e6e287", "text": "Overall, the fusion PCC assay allows rapid assessment of the radiation dose, even within 3\u00a0h post irradiation, and can successfully distinguish between whole- and partial-body exposures [113]. Furthermore, when the PCC-assay is combined with the fluorescence in situ hybridization (FISH) technique, inter- and intra-chromosomal rearrangements can be analyzed directly in G0 lymphocytes for radiation biodosimetry purposes and retrospective assessment of radiation-induced effects [114]. Finally, a quick, automatable, and minimally invasive micro-PCC assay was recently proposed for rapid individualized risk assessments in large-scale radiological emergencies [115]. However, the PCC assay requires the availability of either fresh or frozen mitotic cells [116] and expertise in cell fusion procedures and analysis of lymphocyte prematurely condensed chromosomes. Due to these limitations, the test is still not widespread."}
{"_id": "Radiology$$$7a04257b-efd7-4fcf-8ca2-59d919b7a9dc", "text": "The radiation-induced gamma-H2AX foci assay can be used to detect and quantify DNA double strand breaks indirectly using a phospho-specific antibody for the histone variant H2AX [30] (Fig. 8.22). In addition, the potential for rapid, high throughput, batch processing [117, 118] makes the foci assay ideal for early triage categorization to quickly identify patients who may be at risk of developing acute radiation syndrome and help prioritize the more established biodosimetry methods such as the dicentric assay.\n\nA schematic diagram and a microscopic image. a. It demonstrates how the phosphorylation of H 2 A X is formed at the damaged side from the normal D N A via double-strand breaks. B has non-irradiated and irradiated cells, with dots throughout the cell upon irradiation.\n\nFig. 8.22\n(a) Schematic representation of the formation of gamma-H2AX foci. Following radiation-induced DNA breakage, the free DNA ends are labeled by the phosphorylation of H2AX, which can be visualized and quantified using immunofluorescence antibodies. (b) Gamma-H2AX foci in human blood lymphocytes following exposure to 0 or 1 Gy X-rays following a post-exposure incubation for 1\u00a0h (40\u00d7 magnification fluorescence microscopy images showing gamma-H2AX foci in green and DNA counterstain in blue)"}
{"_id": "Radiology$$$5d52fb92-e137-47ad-b223-cad103aa7043", "text": "A schematic diagram and a microscopic image. a. It demonstrates how the phosphorylation of H 2 A X is formed at the damaged side from the normal D N A via double-strand breaks. B has non-irradiated and irradiated cells, with dots throughout the cell upon irradiation."}
{"_id": "Radiology$$$a8918e7d-389a-4ecc-993f-c2adae8803da", "text": "The advantage of the gamma-H2AX assay is that a dose estimate, based on foci levels in peripheral blood lymphocytes, can be given within 5\u00a0h from the receipt of a blood sample [117]. Background levels of mean foci per cell are low, ~0.3 or less [119] and gamma-H2AX foci increase linearly with dose. However, foci loss follows the time course of DNA double strand break repair [120] and the time between radiation exposure and blood sampling greatly effects the observed yield of foci. To enable reliable exposure assessment, calibration curves for different post-exposure time points are essential [121]. The rapid loss of gamma-H2AX foci requires a blood sample to be taken within 1\u20132\u00a0days after a radiation exposure with the minimum detectable dose increasing from a ~\u00a01\u00a0mGy [122] for a sample taken within 1\u00a0h after exposure to ~0.5 Gy for a lag time of 2\u00a0days between exposure and sampling [123]. Use of two separate foci biomarkers, for example, gamma-H2AX and 53BP1 with dual-color immunostaining, could enhance the sensitivity for low-dose exposure by only scoring foci that coincide, so reducing the influence of staining artefacts [123]. Manual scoring of gamma-H2AX foci is the preferred method, as it gives smaller uncertainties in the dose estimate than automated scoring techniques [124] or flow cytometry [123]. However, gamma-H2AX flow cytometry imaging has the potential to be a very rapid, high throughput tool suitable for analyzing large numbers of samples [125]. The data analysis of foci counts for calibration curve fitting, estimating doses and calculating confidence intervals can be performed in the same manner as conventional chromosome dosimetry. Some evidence suggests the distribution of gamma-H2AX is Poisson among the scored cells and can be used to estimate partial-body exposure using the methods developed for the dicentric assay, although over-dispersion has been observed in other data sets [124]."}
{"_id": "Radiology$$$2f84ba13-1e32-4de8-9f06-0591e5ee9bf1", "text": "Radiation quality, time, and dose-dependent changes in gamma-H2AX foci numbers need to be considered when converting foci yields into dose estimates. The rapid loss of foci following irradiation and other assay methodology influencing factors (e.g., sample shipment conditions, staining reproducibility), suggests that currently gamma-H2AX-based dose estimation may be associated with large uncertainties; especially if the exact time between exposure and blood sampling is unknown. Given this, the assays main function is that of a qualitative indicator of exposure as opposed to a precise dosimetry tool."}
{"_id": "Radiology$$$35409a6b-a783-4009-90a4-2a45e18810d6", "text": "One relatively new method for biological dosimetry is the analysis of changes in gene expression. In response to exposure to ionizing radiation, cells activate multiple transduction pathways to activate cell cycle arrest and induce DNA repair mechanisms in order to prevent the cell from apoptosis. These radiation-responsive alterations in the transcriptome can be quantified by molecular analysis, which lately have been exploited for biological dosimetry [126]. Global discovery platforms are initially used to search for appropriate marker genes that are useful for biodosimetric applications. The expression values need to be measurable in a relevant dose range and exhibit a linear dose-response relationship such that the level for the respective gene can be assigned to a specific radiation dose. Those studies focus mainly on human peripheral lymphocytes, which are also the material of choice for classical biodosimetry methods due to their sensitivity and specificity to ionizing radiation and the possibility of minimally invasive collection. The gene response can be monitored either by quantitative real-time polymerase chain reaction (qRT-PCR), which accurately quantifies single genes, or by microarrays that can show a global scale analysis [127]. Using ex vivo irradiated lymphocytes the sensitivity and linear dose dependency of this assay was assumed to be 100\u00a0mGy up to 5 Gy whole-body irradiation [128]."}
{"_id": "Radiology$$$f0c35bc4-6b52-4958-baa5-da6c7f4f5e15", "text": "Currently, the use of gene expression analysis in dosimetry is still experimental. Several genes have already emerged as useful biomarkers, with ferredoxin reductase (FDRX) being the most promising one [129]. Due to the activation of a very complex molecular reaction by ionizing radiation, estimation of the dose based on single changes in gene expression is not optimal. Therefore, the use of multiple panels of radiation-sensitive genes is more promising to improve the accuracy of the estimation [87]. Currently, many researchers are working on the definition of such a gene signature in order to apply gene expression for biological dosimetry. There are also some studies that have identified genes for specific ARS effects [130]."}
{"_id": "Radiology$$$babb015c-2a3c-4505-9a80-0787fc4fbba0", "text": "The advantage of gene expression-based over other biodosimetric methods is rapid radiation dose estimation and high sample throughput, which is particularly advantageous for large populations. However, due to the dynamics of gene expression, dose estimation is only possible in a relatively short time frame after exposure. In addition, the influence of health status, age, and sex on changes in radiation-induced gene expression is known, and thus there is a need to develop individualized gene expression-based dosimetry models for different population subgroups. So far, it has also not fully been clarified how to infer from changes in gene expression to different radiation qualities and more complex exposure scenarios such as detection of partial-body irradiation. Although there is currently no universal standardization of gene expression analysis for biological dosimetry available, research is on going and the analysis of gene profiles seems to hold great potential to support the individual dose estimation especially in large-scale radiation accidents (Box 8.5)."}
{"_id": "Radiology$$$a67afa28-d4c3-41f9-805f-f75a0ac7c65f", "text": "In biological dosimetry biomarkers are used to verify exposure to ionizing radiation and to estimate the absorbed dose.\n\nThe analysis of dicentric chromosomes is considered as \u201cgold standard\u201d in biological dosimetry after an acute radiation exposure.\n\nAccording to the radiation scenario other cytogenetic methods are available (CBMN, FISH; PCC).\n\nRelatively new methods on the molecular level are gamma-H2AX foci assay and analysis of changes in the gene expression."}
{"_id": "Radiology$$$cd12560c-f2a8-45d5-aaf9-1023c6534122", "text": "In biological dosimetry biomarkers are used to verify exposure to ionizing radiation and to estimate the absorbed dose."}
{"_id": "Radiology$$$58f412b9-af63-4ad8-8930-ebd259d59115", "text": "The analysis of dicentric chromosomes is considered as \u201cgold standard\u201d in biological dosimetry after an acute radiation exposure."}
{"_id": "Radiology$$$c5a12903-4a83-49db-90c5-029ebc4df15e", "text": "According to the radiation scenario other cytogenetic methods are available (CBMN, FISH; PCC)."}
{"_id": "Radiology$$$1a080e5e-6fa4-4823-a848-ca114e0d5591", "text": "Relatively new methods on the molecular level are gamma-H2AX foci assay and analysis of changes in the gene expression."}
{"_id": "Radiology$$$d486c4f8-9b84-4a7f-830c-ecb02b416eb5", "text": "Since the discovery and the rapid introduction and exploitation of ionizing radiation in medicine, technology and industry, the limited knowledge about the detrimental health effects of radiation led to the exposure of many individuals to high doses, and subsequently to various radiation exposure related health effects such as cancer [131, 132]."}
{"_id": "Radiology$$$8ddbd9ba-c0a8-466b-89c3-cc956625ad09", "text": "Guidelines for radiation protection purposes started as early as the 1890s with more detailed dose limits being released as more research was being published. However, as the detrimental effects of radiation became more known, and more research was being published about its negative side effects, the need for a cohesive set of guidelines and regulations became more apparent. At the second International Congress of Radiology, held in Stockholm in 1928, a new unit was proposed for quantifying ionizing radiation, specifically for the purpose of radiation protection. The unit was named R\u00f6ntgen, after the discoverer of X-rays. It was also during this congress that the International X-Ray and Radium Protection Committee (IXRPC) was founded, which would later be known as the Commission for Radiation Protection (ICRP). The first dose limit recommendation by the IXRPC came in 1934. These stated that a person in normal health can tolerate 0.2 roentgens of X-rays per day. This would correspond to approximately an annual effective dose of 500\u00a0mSv; a dose 25 times higher than the current annual dose limit for occupational workers. No dose limit recommendation was given for \u03b3-rays at this point."}
{"_id": "Radiology$$$1455cd28-b89b-48ed-b271-65691484d2e5", "text": "Separate from the IXRPC, a document was published in the 1930s, outlining many protective methods and techniques to shield from the harmful effects of radiation. This report was commissioned by what would later become the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR). The comments on permissible dose were vague, however. In the following years, several recommendations were being made by various bodies. Around this time, terminology also began changing, and the previously used \u201ctolerance dose\u201d was changed to \u201cmaximum permissible dose.\u201d In 1946, the US advisory Committee was re-established as the National Council on Radiation Protection and Measurements (NCRP) and amended their initial recommendations to now allow a maximum permissible dose of 0.05 Roentgen/day, expressed at that time as 0.3 Roentgen/week [133]. This reduction was largely due to the growing evidence of the hereditary harm of radiation. This new guideline was also echoed by the ICRP in 1950, when they also proposed a weekly maximum permissible dose of 0.3 Roentgen. The reduction from their previous 1934 recommendations of 0.2 Roentgen/day corresponded to 1 Roentgen/week, which was then seen as being too close to the threshold of adverse effects [134]."}
{"_id": "Radiology$$$04be7483-60bc-4fba-a25d-584200d5d37d", "text": "The first publication by the ICRP came in 1955; here a clear distinction was made between the levels allowed for public and occupational exposure, public exposure allowance was reduced by a factor of 10 from what was allowed for occupational exposure. Recommendations on permissible doses were given for various organs. New units were also introduced, with the rad (now corresponding to 0.01\u00a0Gy) being used for absorbed dose, and rem as the RBE weighted unit (corresponding today to 0.01\u00a0Sv) [135]. In 1958, the ICRP published what is now known as \u201cPublication 1\u201d. The concept of a weekly dose limit was abandoned, and the new annual occupational dose limit was 5\u00a0rem, with a public limit of 0.5\u00a0rem/year (50 and 5\u00a0mSv respectively) [136]."}
{"_id": "Radiology$$$2120afbf-3ac2-40d9-b9d8-65de2eb23376", "text": "Changes to terminology and units were revised once again in 1977, in publication 26. The Sievert replaced the rem, and effective dose equivalent was introduced. More thought was also being placed on cost benefit assessment and the concept of radiation health detriment was introduced. Three general rules for the use of radiation were also introduced, justification, optimization and individual dose limitation. The term maximum permissible dose was replaced by dose limit; however, no changes were made to the guidelines, a dose limit of 50\u00a0mSv remained for occupational workers, with a public dose limit of 5\u00a0mSv [137]. In 1991, publication 60 reduced the occupational dose limit from 50\u00a0mSv to 20\u00a0mSv/year, averaged over 5\u00a0years. Public exposure was now limited to 1\u00a0mSv, with higher exposer levels being permissible as long as the annual average over a span of 5\u00a0years did not exceed 1\u00a0mSv. A radiation weighting factor was introduced, and the measure of dose equivalent was replaced by quantity equivalent dose. As there were now also tissue weighting factors for many more organs, effective dose equivalent was also replaced by the term effective dose [3]. The latest recommendations were issued in 2007 (publication 103) updating consolidating and developing additional guidance on the protection from radiation sources. One of the main characteristics of publication 103, is that it evolves from the previous process-based protection approach (practices and interventions) to an approach based on the exposure situation (planned emergency and existing exposure situations). The radiation and tissue weighting factors, effective dose and detriment are updated based on the most recent scientific data available. Finally, ICRP 103 focuses also on the radiological protection of the environment [34]."}
{"_id": "Radiology$$$288eca8b-3684-4cfc-b2b4-ec46ca7f0b93", "text": "Ionizing radiation can have severe damaging effects in the human body. These harmful effects can be classified into two general categories: the deterministic effects and the stochastic effects. The deterministic effects are due to the killing or malfunction of cells after exposure to high radiation doses. The stochastic effects refer to either cancer or hereditary effects due to mutations of somatic cells or germ cells respectively."}
{"_id": "Radiology$$$e61f24d5-fc84-4bc1-9579-1edc5c3a7247", "text": "The deterministic effects are manifested when the dose exceeds the dose threshold for a given effect [85]. These effects appear mostly after high irradiation doses. These thresholds are essential in preventing risk of morbidity in specific cell populations and overall mortality [32]. Tissues generally have different threshold dose baselines for these deterministic effects which depend on the radiosensitivity of the cells and the functional reserve of the tissue."}
{"_id": "Radiology$$$2f63c340-5cc2-46b6-8477-6d8803428778", "text": "Depending on the absorbed dose and the type and energy of the radiation source, the equivalent dose (HT, mSv) for individual organs can be calculated. Equivalent dose (HT) is the absorbed dose, in tissue or organ T weighted for the type and quality of radiation R."}
{"_id": "Radiology$$$e0eb206f-e09f-4de4-a6cf-d8c8889651b1", "text": "(8.1)where DT,R is the absorbed dose averaged over tissue or organ T, due to radiation R and wR is the radiation weighting factor. wR is a dimensionless factor that correlates with the biological effectiveness of radiations of different qualities. The values wR as these are presented in ICRP 103 are shown in Table 8.17.Table 8.17\nRadiation weighting factors, as defined in the ICRP 103. All values relate to the radiation incident on the body or, for internal sources, emitted from the source (reproduced with permission from [34])\n\nRadiation type\n\nwR\n\nPhotons\nElectrons and muons\nProtons and charged ions\nAlpha particles, fission fragments, heavy ions\nNeutrons, En\u00a0<\u00a01 MeV\nNeutrons, 1\u00a0MeV\u00a0\u2264\u00a0En\u00a0\u2264\u00a050 MeV\nNeutrons En\u00a0>\u00a050 MeV\n\n1\n1\n2\n20"}
{"_id": "Radiology$$$297eae38-4ab8-43cd-adc1-b70ccc43772e", "text": "When the radiation field is composed of types and energies with different values of wR, the total equivalent dose, HT, is given by:\n\n (8.2)"}
{"_id": "Radiology$$$e1b38032-6a9e-4ad6-bc12-890f911b5548", "text": "The stochastic effects are characterized for not having a known threshold and include cancer and hereditary disorders. The stochastic effects can represent a serious risk even at low doses of ionizing radiation, especially if the dose exceeds 100\u00a0mSv. The risk of induction represents the value of the effective dose absorbed in the whole organism. The effective dose is related to the health status detriment caused by stochastic effects. Because the tissues differ in their sensitivity to radiation, a tissue weighting factor (wT) has been determined. wT is the factor by which the equivalent dose in a tissue or organ T is weighted to represent the relative contribution of that tissue or organ to the total health detriment resulting from uniform irradiation of the body [34]. It is weighted such that \n\n."}
{"_id": "Radiology$$$f5eda708-b883-4b61-8ac1-408c627c026d", "text": "The effective dose (E) can be calculated as the sum of the weighted equivalent doses in all the tissues and organs of the body from internal and external exposure. It is defined by:"}
{"_id": "Radiology$$$b5ec655d-a61e-46a9-a814-b637557ce7e5", "text": "(8.3)where DT,R is the absorbed dose averaged over tissue or organ T, due to radiation R, wR is the radiation weighting factor and wT is the tissue weighting factor for tissue or organ T (Table 8.18).Table 8.18\nTissue weighting factor (wT) values (reproduced with permission from [34])\n\nTissue\n\nwT\n\n\u03a3wT\n\nBone-marrow (red), colon, lung, stomach, breast, remainder tissuesa (nominal wT applied to the average dose to 14 tissues)\n\n0.12\n\n0.72\n\nGonads\n\n0.08\n\n0.08\n\nBladder, esophagus, liver, thyroid\n\n0.04\n\n0.16\n\nBone surface, brain, salivary glands, skin\n\n0.01\n\n0.04\n\na Remainder tissues (14 in total): adrenals, extrathoracic (ET) region, gall bladder, heart, kidneys, lymphatic nodes, muscle, oral mucosa, pancreas, prostate, small intestine, spleen, thymus, uterus/cervix"}
{"_id": "Radiology$$$b6a93e03-d06a-4749-933b-a86ca8b57c26", "text": "The effects of ionizing radiation, mostly as a health hazard, have been studied for several decades. In this regard, the term nominal cancer risk coefficients has been introduced. These coefficients define the incidence probability of stochastic effects per radiation dose. The nominal risk coefficients depend on age, sex, averaged lifetime risk, among other radiobiological factors. In the twentieth century the nominal risk coefficient for cancer risk after exposure to ionizing radiation was estimated in 5.5% and 4.1% per Sievert (Sv) for the general population and for adult workers, respectively. The nominal risk for heredity damage was estimated in 0.2% and 0.1% per Sievert (Sv) for the general population and for adult workers, respectively (Table 8.19).Table 8.19\nNominal risk coefficients for cancer and hereditary effects (10\u22122\u00a0Sv\u22121) (reproduced with permission from [34])\n\nExposed population\n\nCancer\n\nHereditary effects\n\nTotal\n\nGeneral\nWorkers\n\n5.5\n4.1\n\n0.2\n0.1\n\n5.7\n4.2"}
{"_id": "Radiology$$$d37c73cd-8b4e-4f94-88ba-242f23024f6b", "text": "As previously mentioned, people are exposed to ionizing radiation from natural and artificial sources throughout their life. Which is why dose limits were implemented, seeking to prevent deterministic effects or to reduce the risk of stochastic effects. These dose limits are applicable only for situations of planned exposure and doses above the normal natural background radiation. However, these dose limits are not applied in the medical field so as to not hamper the effectiveness of diagnosis or treatment. Dose limits are applied into two main groups of exposed individuals: (1) occupationally exposed and (2) public (Table 8.20) [85]. Dose limits are strongly regulated to ensure that no one is exposed to an excessive amount of radiation in either normal or planned situations.Table 8.20\nRecommended dose limits in planned exposure situations (reproduced with permission from [34])\n\nType of limit\n\nOccupational\n\nPublic\n\nEffective dose\n\n20\u00a0mSv/yeara,b\n\n1\u00a0mSv in a yearc\n\nAnnual equivalent dose in\n\nLens of the eye\n\n20 mSv/yeara,d\n\n15\u00a0mSv\n\nSkin (averaged over 1 cm2\u00a0of skin)\n\n500\u00a0mSv\n\n50\u00a0mSv\n\nHands and feet\n\n500\u00a0mSv\n\n\u2013\n\na 100\u00a0mSv in 5\u00a0years (averaged over 5 consecutive years), with no single year exceeding 50\u00a0mSv\nb After a worker declares a pregnancy, the dose to the embryo/fetus should not exceed about 1\u00a0mSv during the remainder of the pregnancy\nc Value applies to the average value over a period of 5\u00a0years\nd Revised value by ICRP Statement on tissue reactions in ICRP publication 118 [32]"}
{"_id": "Radiology$$$5b7419ed-7a75-408d-83e0-a661579d3314", "text": "Q1.\nWhen radon is inhaled the largest dose is found at the level of the(a)\nMouth\n\u00a0(b)\nBronchial wall\n\u00a0(c)\nBifurcation of the trachea\n\u00a0(d)\nAlveoli\n\u00a0\n\u00a0Q2.\nWhen is the initial triage used?\n\u00a0Q3.\nHow many categories of priority are used in initial triage?\n\u00a0Q4.\nWhat methods of treatment are used for internal contamination with radionuclides?\n\u00a0Q5.\nIn hematopoietic syndrome the death is mainly due to(a)\nAnemia\n\u00a0(b)\nDyspnea\n\u00a0(c)\nHemorrhage and infection\n\u00a0(d)\nThrombopenia\n\u00a0\n\u00a0Q6.\nIn gastrointestinal syndrome the death is mainly due to(a)\nAnemia\n\u00a0(b)\nFever\n\u00a0(c)\nVomiting\n\u00a0(d)\nCirculatory collapse\n\u00a0\n\u00a0Q7.\nThe LD50 for humans is about without medial support measures is(a)\n1 Gy\n\u00a0(b)\n4 Gy\n\u00a0(c)\n10 Gy\n\u00a0(d)\n50 Gy\n\u00a0\n\u00a0Q8.\nDiscuss the most appropriate biodosimetric assay(s) for use in a suspected cases of radiation exposure which occurred approximately?\n\u00a0(a)\n12\u00a0h ago\n\u00a0(b)\n1\u00a0month ago\n\u00a0(c)\n1\u00a0year ago"}
{"_id": "Radiology$$$ae80e816-7e3d-464d-ad3e-3f98d93d60e4", "text": "When radon is inhaled the largest dose is found at the level of the(a)\nMouth\n\u00a0(b)\nBronchial wall\n\u00a0(c)\nBifurcation of the trachea\n\u00a0(d)\nAlveoli"}
{"_id": "Radiology$$$09221e68-f790-4e1f-8443-ffef1a6fd0b7", "text": "What methods of treatment are used for internal contamination with radionuclides?"}
{"_id": "Radiology$$$d2ec7414-fb8f-4e96-9477-fb3ee4e1c80a", "text": "In hematopoietic syndrome the death is mainly due to(a)\nAnemia\n\u00a0(b)\nDyspnea\n\u00a0(c)\nHemorrhage and infection\n\u00a0(d)\nThrombopenia"}
{"_id": "Radiology$$$3e06a256-9bdf-4ac5-918e-f715b21abf12", "text": "In gastrointestinal syndrome the death is mainly due to(a)\nAnemia\n\u00a0(b)\nFever\n\u00a0(c)\nVomiting\n\u00a0(d)\nCirculatory collapse"}
{"_id": "Radiology$$$c3229da6-9af0-49fd-b99b-932fd0f735cb", "text": "The LD50 for humans is about without medial support measures is(a)\n1 Gy\n\u00a0(b)\n4 Gy\n\u00a0(c)\n10 Gy\n\u00a0(d)\n50 Gy"}
{"_id": "Radiology$$$1f288d1f-e8aa-4478-8dfe-bf0b9797d2b4", "text": "Discuss the most appropriate biodosimetric assay(s) for use in a suspected cases of radiation exposure which occurred approximately?"}
{"_id": "Radiology$$$020a5458-aecb-4c83-9d28-193ef568f30f", "text": "SQ1.\nc\n\u00a0SQ2.\nInitial triage is used to screen the patients with severe injuries after a mass biological, chemical, radiological or nuclear event.\n\u00a0SQ3.\nFour categories of priority.\n\u00a0SQ4.\nIsotope blocking, dilution, or displacement, and the use of ion exchange resins, and ion mobilization or chelation.\n\u00a0SQ5.\nc\n\u00a0SQ6.\nd\n\u00a0SQ7.\nb\n\u00a0SQ8.\nThe data in Sect. 8.6\u00a0should be referred to in order to formulate a full answer, based on the scenario of exposure. However, the short answers are: (a) gamma-H2AX and dicentric assays; (b) dicentric or CBMN assays; (c) FISH translocation assay."}
{"_id": "Radiology$$$5da1b1a2-22a3-4188-a49d-250093f267c8", "text": "Initial triage is used to screen the patients with severe injuries after a mass biological, chemical, radiological or nuclear event."}
{"_id": "Radiology$$$fa37197b-bdce-4a12-82f0-6e60e18ae5ec", "text": "Isotope blocking, dilution, or displacement, and the use of ion exchange resins, and ion mobilization or chelation."}
{"_id": "Radiology$$$9fe4981b-061d-45a8-88df-2e76e3e12111", "text": "The data in Sect. 8.6\u00a0should be referred to in order to formulate a full answer, based on the scenario of exposure. However, the short answers are: (a) gamma-H2AX and dicentric assays; (b) dicentric or CBMN assays; (c) FISH translocation assay."}
{"_id": "Radiology$$$168b1124-e08c-44ce-9703-528b2d8230a1", "text": "Environmental radiobiology refers to the study of the effects of radiation on ecosystems and species that are part of various habitats, collectively known as \u201cthe environment.\u201d The discipline is part of Radioecology which is a broad area of research, covering the transfer, uptake and effects of radionuclides in the environment. Radioecology includes, for example, the speciation of radionuclides in environmental media, the transfer of radionuclides through the different environmental compartments and exposure of wildlife to ionizing radiation and its consequences. While this chapter focuses predominantly on the biological and ecological impacts of radiation on non-human species\u2014since transfer is a key aspect of wildlife dosimetry\u2014the environmental behavior of key radionuclides is briefly covered in Sect. 9.2."}
{"_id": "Radiology$$$e13623be-6043-4ef8-9307-a7c5028dda3c", "text": "It is important to understand that the basic mechanisms that lead to effects in humans, discussed in earlier chapters, also occur in non-human biota, but the effects of concern lie at higher levels of organization, such as the population or ecosystem. For example, a harmful mutations induced by radiation exposure may lead to cancer on humans, but in the environment, where the sustainability of the population is a critical endpoint, low levels of carcinogenic mutations are unlikely to impact the overall population. This means that the tools and techniques needed to document and evaluate radiobiological effects in natural populations, and ultimately in ecosystems, are much more complex to those used in human radiobiology."}
{"_id": "Radiology$$$44d363ec-627c-4dad-be5d-cfafa5f86b1d", "text": "A key issue is the importance and the difficulty of conducting good experiments in field situations, particularly at environmentally relevant concentrations and with proper controls. Single species studies in the laboratory have an important role in determining high and low dose effects, understanding mechanisms and testing resistance. But results can be misleading if they are extrapolated to environmental conditions, with lower doses, chronic exposures, and a variety of confounding factors such as genetics, age, life stage, predation, availability of resources, as well as the interaction with other stressors and difficulties to make a proper dosimetry [1]."}
{"_id": "Radiology$$$0c772fdc-8597-4c92-8001-bcc22ab9963e", "text": "Another important issue is how to measure impacts on ecosystems. Several robust biomarkers are available to determine impacts at the level of the gene, cell, tissue, organ, and organism. These are discussed in Sects. 9.3 and 9.4 of this chapter. Population level markers are also available including population numbers, mortality and morbidity, fecundity and population growth rate, but at the level of the ecosystem, the complexity makes it very difficult to assess ecosystem health following radiation exposure, including effects on functions and services. The importance of legacy sites is discussed in Sect. 9.4, as natural labs like, for example, \u201cRadioecological observatories\u201d (https://\u200bradioecology-exchange.\u200borg/\u200bcontent/\u200bradioecological-observatories) where all the mechanisms of effect from populations to ecosystems can be deeply studied. Other approaches include measurements of biodiversity index and the use of drone technologies to monitor ecosystem change at the gross level, for example, forest cover and diversity, lake eutrophication, or extreme habitat change."}
{"_id": "Radiology$$$b1e53240-6bd0-428e-b72e-3f21a93c9bdc", "text": "Transfer of anthropogenic radionuclides through food chains has been studied since the time of atmospheric weapons testing and has been supported by data from nuclear power generation and accidents, as well as studies of the behavior of naturally occurring radionuclides (NORs). While there is a wealth of data on the transfer of radionuclides through human food chains, there has been less focus on wildlife and especially organisms that are not common sources of food for humans such as insects and invertebrates. While much of the focus in studying the environmental impacts of radiation has been on the uncertainties in effects measurement, it is important to stress that there are also uncertainties in dosimetry, and especially from internal radionuclides. Hence, knowledge of the factors influencing the behavior of radionuclides in the environment will be fundamental to support dosimetry and exposure assessments. This includes information on the behavior of naturally occurring radionuclides, which is needed both to calculate background doses to organisms, and thus put anthropocentric exposures into perspective, as well as to assess doses in areas with enhanced levels of natural radioactivity."}
{"_id": "Radiology$$$59d7879e-470f-48cf-be8e-b837e0a3e4da", "text": "Naturally occurring radionuclides (NORs) include the radionuclides 14C, 3H, and 40K and also radionuclides that arise from three decay chains: the uranium (238U), the thorium (232Th), and the actinium (235U) decay chains [2] (Figs. 9.1 and 9.2). When they are contained in or released from processing materials they are defined as NORM [3]. Uranium and thorium are both metals belonging to the heavy actinide series, giving rise to long and complex decay chains that contain important radionuclides in the context of environmental radiation exposure (Fig. 9.1). Key radionuclides include isotopes of radon (222Rn with a half-life of 3.8\u00a0days; 220Rn with a half-life of 55\u00a0s), radium (226Ra half-life of 1602\u00a0years, 223Ra half-live of 11.43\u00a0days; 228Ra with a half-life of 5.7\u00a0days), and polonium (210Po with a half-live of 138\u00a0days, 216Po with a half-life of 0.145\u00a0s, and 212Po with a half-life of 299 ns). Compared to typical exposures from accidents such as Chernobyl and Fukushima, which are predominantly beta and gamma-emitting radionuclides, NORM exposures are often characterized by high levels of alpha emitters.\n\n3 decay chains with alpha and beta decays of Uranium, U 238, Actinium, U 235, and Thorium, T h 232.\n\nFig. 9.1\nUranium (including uranium 238U and actinium 235U) and thorium decay chains\n\n\nAn illustration of the natural radionuclides on building materials, groundwater and surface water, soil, and rock.\n\nFig. 9.2\nNatural radionuclides distribution in different environmental compartments"}
{"_id": "Radiology$$$b89d602c-b782-433c-b82b-1e7809e984db", "text": "3 decay chains with alpha and beta decays of Uranium, U 238, Actinium, U 235, and Thorium, T h 232."}
{"_id": "Radiology$$$3e77120d-2c8c-4588-830e-7853efbc0424", "text": "An illustration of the natural radionuclides on building materials, groundwater and surface water, soil, and rock."}
{"_id": "Radiology$$$abc9c3c0-94fa-4e51-97f4-741c56904118", "text": "Radionuclides in the environment can be distributed through the Earth\u2019s atmosphere, hydrosphere, and lithosphere (Fig. 9.2). The behavior and fate of radionuclides in the environment depend on physical and chemical properties of radionuclides, the location and the type of emission source, and the environmental conditions [4]. Radionuclides undergo chemical reactions that affect their distribution and retention time. Organisms interact with the nonliving environment and can be exposed to the radionuclides. In order to estimate the doses received by an organism, the activity concentration of radionuclides in the organism\u2019s habitat is calculated."}
{"_id": "Radiology$$$25bb8943-8161-403f-86bb-90248763aa2e", "text": "The natural environment is a highly complex system in which elements flow and circulate through the spheres of the Earth. To simplify the study of radionuclides, the environment can be divided compartments such as air, surface and groundwater, sediment, soil, and biota. Compartments are usually chosen so that they are distinguishable by spatial boundaries [5]. In each compartment, there are certain processes that have the greatest influence on behavior, so simplifications are made by only taking into account the key interactions that are important to consider for the radionuclide in question. As such, an environmental compartment can be chosen so that it is a volume of medium within which it is assumed that system parameters are constant and chemical concentrations do not vary spatially [6]. For example, in the air compartment, the aerosol formation and particle deposition process of emitted radioactive iodine (e.g., 131I) are key processes to consider, while in the soil compartment, the association with organic matter has been considered the process that determines the largest share of the fate of iodine. Assumptions can be made so that only the key reactions and dynamics are taken into account."}
{"_id": "Radiology$$$fcfbdaee-096c-4866-851f-288e599dea60", "text": "In general, the first step in studying the behavior of the radionuclide in the environment is to obtain knowledge of the location and properties of the emission source. Knowing where the radionuclides come from and in what form they occur can already reveal much information about where the radionuclides will be transported to. For example, the radioactive uranium released from nuclear explosions may end up in very different locations than uranium in nuclear waste dumped into the sea or uranium brought to the surface during the mining of uranium-bearing ores [7]. In addition to the location, the type of emission source should be considered. Anthropogenic emissions of radionuclides result from human activities. These radionuclides are released into the environment at a certain point in time. Unlike anthropogenic emission sources, natural emission sources from the subsurface have been present since the creation of the Earth. Uranium and thorium ores, for example, can be considered as diffuse sources of radionuclides in the Earth\u2019s crust. If groundwater near a uranium deposit flows in a particular direction toward areas where drinking water is extracted, it may behave as a point source. Anthropogenic radionuclide sources, such as nuclear weapon tests and nuclear power plant accidents, release radionuclides at high temperatures and pressures in a certain area over a relatively short period of time and can therefore, be considered a point source. Depending on the weather conditions, the radionuclides can be further dispersed as clouds, with the emission spreading diffusely rather than being a point source. Other point sources, such as the emission of nuclear waste dumped in the ocean, release radionuclides diffusely over a large waterbody. Radionuclides that are dispersed without a specific point of discharge and over a long period of time may be considered as a diffuse source. Agricultural practices, for example, often require high levels of fertilizers, which end up in water bodies through various diffuse processes. Phosphate rock in fertilizers can contain small amounts of naturally occurring radionuclides such as uranium, thorium, and radium. Human activities can enhance the release of radionuclides."}
{"_id": "Radiology$$$31e24ecc-9ad8-49b7-9b0d-51c1bd6875ff", "text": "The study of the fate of radionuclides is complicated by the property of radioactive decay. Radioactive decay changes the type of radionuclide, thereby altering its physicochemical properties and potentially altering the fate of the entity. That is, when a radionuclide decays, the daughter element often has very different chemical properties than the parent element [8]. If the parent element is a solid and its daughter is a gas, the parent may partition into other compartments, such as air or water. For example, in the natural uranium (238U) decay series, radon (222Rn) is formed after the decay of radium (226Ra). Radium is an alkaline metal that can be present in a mineral structure within the parent rock or in the pore water as an ionic salt, while radon is an inert gas. If the released radon is captured in a closed space such as the basement of a building or a cave, it can be inhaled by an organism. The gaseous 222Rn decays further releasing alpha and beta particles and eventually decays into stable solid 206Pb. The latter is a metal chemically toxic for organisms. When radionuclides are the stressors of concern, both chemical- and radiation-induced effects on organisms are expected."}
{"_id": "Radiology$$$0a58cab0-94bb-4451-8c11-574a3bc60b76", "text": "Once the radionuclide is emitted, its chemical speciation determines how the radionuclide reacts with components in the environment. It is important to keep in mind that radionuclides are not only physical entities, but also have chemical characteristics [9]. For a more detailed discussion of the importance of the chemical characteristics of radionuclides, the reader is referred to the text by Whicker and Schultz [10]. Radionuclides can occur in various chemical forms or species that have different mobility. The following examples of species are for thorium (Th). Radionuclides such as Th can occur in elemental form (e.g., Th0), but these are very rare in the environment. They can be present as free ions in water (e.g., Th4+). However, dissolved Th is almost always complexed in natural water [11]. Free ions can be bound to inorganic or organic molecules in either the solid or dissolved phases, such as thorium hydroxyl complexes Th(OH)40, Th(OH)3+, Th(OH)22+, ThOH3+, Th(SO4)2+, Th(HPO4)32\u2212, Th-oxalate and Th-EDTA complexes. Radionuclides can also be components of a mineral, such as thorianite (ThO2), and thorite (ThSiO4). The thermodynamic properties of various species can be used to compute liquid-solid equilibria relations. These theoretical calculations reveal much about the possible conditions for and the extent of mobility of radionuclides [11]. The thermochemical data and adsorption results from laboratory experiments help to explain the behavior of radionuclides, such as Th in natural waters, sediments, and wastes."}
{"_id": "Radiology$$$a4164424-63fe-434f-a108-bfb1fb6308bd", "text": "In general, the total sum of chemical species can be expressed as [9]:\n\n (9.1)where (MS) is the total sum of species present; (M)n+/\u2212 the element present as positively or negatively charged free ion (n+/\u2212); (MmLm)n+/\u2212 an element complexed by any kind of ligand, L, such as an oxide, organic, or any other form, negatively or positively charged; (MmA) an element adsorbed onto a surface or trapped in a crystal lattice, or in an amorphous structure, A; m is the number of M or L molecules in the complex; and n+/\u2212 is the number of charges."}
{"_id": "Radiology$$$75afbb45-4915-486b-a3e7-592878ffbcd5", "text": "The fraction of the different chemical species in this formula, that are present in the environment, will depend on the source of the radionuclide and the physicochemical conditions of its surroundings. Parameters such as pH, redox state, ionic strength and the presence of complexing ligands will influence the proportions of each chemical species present."}
{"_id": "Radiology$$$4669c044-6822-4fbb-b862-904c276f065f", "text": "Some chemical species of radionuclides undergo chemical reactions that influence their mobility or retention. The main chemical reactions determining speciation are adsorption and desorption processes, ion exchange and dissolution reactions, precipitation and co-precipitation, complexation to inorganic and organic ligands [12] and redox reactions. For a detailed explanation of the mechanisms of these reactions, please refer to a course on aquatic chemistry such as Langmuir [8] or Sparks [13]."}
{"_id": "Radiology$$$e043cc52-bbb1-45a7-be3c-6751e4b87766", "text": "Of particular interest when studying the behavior of radionuclides are the chemical reactions at the solid\u2013water interface, such as complexation with ligands and adsorption to mineral surfaces. These reactions will largely determine whether the radionuclide is mobile and potentially available for the biota to take up. A dissolved species can associate with an ion or molecule ligand and form a complex [8]. For example, Th is a complex-forming actinide metal for which the chemical speciation of the cation changes with the pH. The multivalent Th cations tend to form strong hydroxyl (OH) complexes. Only in acid waters, the OH concentration is low enough so that competition with ligands is minimal. In these conditions, it is easier for ligands to displace OH and complex it. Complexation with carbonates, humic materials, or other ligands increases the solubility of the Th species and thus the mobility in the environment. An adsorbed species can associate with charged surfaces or broken bonds of minerals. For example, Th adsorbs onto clays, oxides and organic matter in soils and sediments. The adsorption of Th increases if the pH increases from acid to neutral conditions [11]. Sorption processes increase the retardation of Th and thus decrease its mobility in the environment. In general, Th in the soil compartment will remain strongly adsorbed onto soil constituents so that contamination of groundwater through the transport of Th from soil to groundwater will not occur in most soils [14]. Certain microorganisms (Pseudomonas aeruginosa) present in soils may enhance the dissolution of Th by producing chelating agents that can form soluble complexes with this radionuclide [15]. This is not the only way for microorganisms to influence the speciation and mobility of radionuclides. They can also, for example, change their redox state, immobilize them by processes such as biosorption, biomineralization, and precipitation [16]. In the water compartment, soluble Th ions will hydrolyze at a neutral pH forming complexes with OH. The Th-hydroxyl complexes can in turn be absorbed on suspended particles in the water. Although dissolved Th tends to form strong complexes, facilitating its transport, Th concentrations in natural waters\u2014with pH between 5 and 9\u2014remain limited by the scarcity of the element, small solution rates and insolubility of Th-bearing minerals [11]. In groundwaters at mining facilities, Th concentrations may be higher due to the more acidic conditions which cause the leaching of Th."}
{"_id": "Radiology$$$be524532-b7b3-4570-ac39-938bee881e6f", "text": "A common approach to quantify the mobility and availability of radionuclides in the environment is to estimate the ratio between the activity concentrations of the radionuclide in two chosen compartments or trophic levels [9, 17]. The radionuclide retention on the solid phase is estimated by determining a partitioning coefficient. The coefficient describes the partitioning of a radionuclide between the solid and aqueous phases and takes no explicit account of sorption mechanisms [18]. It is assumed that an equilibrium exists between the dissolved and sorbed amount of radionuclides and that exchange is reversible [19]. This simplification relates the concentration of a radionuclide in water to the amount of radionuclide adsorbed:\n\nwhere Maq and Mads are the aqueous and adsorbed species, respectively."}
{"_id": "Radiology$$$940c0322-e5ec-49dd-9e3a-119b38f5d656", "text": "A solid-liquid distribution coefficient (Kd) is derived from the ratio of radionuclide concentrations in the solid phase to that in solution and is calculated as:\n\n (9.2)where Aint is the initial radionuclide activity (Bq), Aeq is the equilibrated radionuclide activity (Bq) in the aqueous phase, V is the volume of the liquid phase (L), and m is the mass of solid phase (kg)."}
{"_id": "Radiology$$$a168df9c-6e01-4449-843c-c4797a8cf8f9", "text": "The adsorption of radionuclides onto soil particles is often expressed as a Kd value. The Kd is determined by adding a known amount of sorbent (i.e., clay, oxide, soil) to a solution with an initial radionuclide concentration, and after equilibration and phase separation (e.g., by ultracentrifugation or a dialysis membrane), radionuclide concentration in the aqueous phase at equilibrium is measured."}
{"_id": "Radiology$$$9a2c06fc-475b-4632-a288-7ccdfd45d95f", "text": "In case of radiocesium (e.g., 134Cs and 137Cs), for example, the CsKd value is obtained by the ratio of the total radiocesium activity concentration in the solid phase and in liquid phase after a chosen time of contact between the two phases. The experimental design must be carefully thought out, as parameters such as contact time, radionuclide concentration, solid to liquid volume, and the ion composition of the aquatic phase affect the Kd value. Radiocesium dissolves well in water, so that radiocesium exists in the aqueous phase only as a free ionic species. Only one metal species of Cs should be considered, which simplifies the study of adsorption equilibria. Moreover, radiocesium cations can be directly adsorbed from solution by an organism, because the cations have no tendency to form soluble complexed species [20]. Thus, the CsKd value can be determined in a relatively simple manner and it can provide useful information about the radiocesium accessible to the organism for uptake [18]."}
{"_id": "Radiology$$$da33f8b8-43aa-4daa-8626-96b3cd1de9b2", "text": "However, caution must be taken in interpreting a Kd value, as it may change over time [18]. On the one hand, the Kd changes in a short term, because an equilibrium is not always reached instantaneously, as for example for radioactive isotopes of iron [21]. On the other hand, the Kd changes in long term, because adsorbed radionuclides, such as 137Cs, can migrate deeper into structures of minerals so that it is no longer available and becomes fixed. Kd values are often determined by short-term laboratory experiments lasting several hours or days. However, Kd values can also be determined in the field, where the results depend on the time elapsed since the contamination occurred and this gives a more reliable picture of the long-term fate of the radionuclides. The time effect was studied in a laboratory study [22] with soils showing that CsKd values of mineral soils with 5% clay minerals can increase from 30\u00a0to 1000\u00a0L/kg in 40\u00a0days and 200\u00a0to 5000\u00a0L/kg in 415\u00a0days for peaty soils with 10% clay minerals. In this example, the CsKd of the mineral soil increases by a factor of 30 over a relatively short period of time, and the CsKd of an organic soil increases accordingly but over a much longer period of time. Laboratory results of CsKd values can only partly explain the reduction in Cs soil-to-plant transfer in the field. A study after the Chernobyl accident [23] shows that 137Cs soil-to-plant concentration ratios, that were initially elevated, were reduced by more than 50 times in the following years. This trend was explained by an initial step of radionuclide release from fuel particles into soil aqueous phase, followed by a reduced transfer attributed to the progressive fixation of 137Cs by soil minerals, referred to as \u201caging effect\u201d that makes 137Cs gradually less available for uptake by the plant."}
{"_id": "Radiology$$$73575cab-8173-4ab8-a962-cbaf9f69299f", "text": "In many cases, the factors that influence the transfer of radionuclides to biota are similar for humans and include soil and water chemistry, speciation of radionuclides, as well as biokinetics (biological and ecological half-lives) and interactions between radionuclides and stable elements. For example, the soil-to-plant transfer of 137Cs, is influenced by clay content and K levels in the soil, and radiostrontium (90Sr) by Ca levels. Another example, is the uptake of U to fish and other aquatic organisms, that is are dependent on pH and carbonate concentrations, which change the availability and complexation of this element [24]. In contrast to Cs, radionuclides such as U exist as several species in the environment. The bioavailability of different U species in soil to ryegrass was studied in a laboratory pot experiment [25], which showed that speciation has an important influence on the uptake of U by grass. From the results, it was concluded that the uranyl-cation (UO22+) and uranyl-carbonate complexes (e.g., UO2CO3(aq), UO2(CO3)34\u2013 and (UO2)2CO3(OH)3\u2013) together with uranyl-phosphate (UO2PO4\u2013) are the forms that are most readily taken up by ryegrass and thus are more bioavailable compared to other uranyl-phosphate complexes (e.g., UO2HPO4) and the hydroxy- (e.g., UO2(OH)2(aq) and UO2OH+) and sulfate-complexes (e.g., UO2SO4(aq) and UO2(SO4)2\u2013). As demonstrated in the previous examples, some species are not available for uptake by biota. Hence, a value other than the total concentration in the compartment should be used to estimate the bioavailability of a given radionuclide and, the exposure of biota through ingestion of radionuclides should only be estimated from the activity concentrations of the bioavailable species [17]."}
{"_id": "Radiology$$$f75648ff-5721-4ae2-9ad1-5433cafd4819", "text": "Internal exposure and toxic effects of radionuclides require that an organism takes up the radionuclide, and for chemically available species to be taken up by biota, the radionuclide must be able to cross cell membranes [26]. To investigate whether this exposure will occur through ingestion, it is important to know whether this contaminant is a source for ingestion by biota. A radionuclide\u2019s potential for biota uptake in soil and sediments is defined by its bioavailability or bioaccessibility. There is a slight difference between the bioavailability and bioaccessibility of pollutants in sediment and soil. This difference has implications for the design of experimental set-ups, but also for the interpretation of results. The bioaccessible fraction is the species in the environment, which are available to cross an organism\u2019s membrane if the organism has access to the radionuclide in the longer term [26]. The bioavailable fraction is freely available to cross an organism\u2019s membrane from the medium the organism inhabits at a given time. For example, technetium (Tc) may be highly mobile in aqueous solution at oxidation state +7 (i.e., Tc(VII)), but strongly absorbed and retarded in the subsurface at oxidation state +4 (i.e., Tc(IV)) [27]. Technetium is used in nuclear medicine for diagnosis and is emitted in the environment from the nuclear fuel cycle. Technetium exists primarily in two stable oxidation states as Tc(VII) or as Tc(IV), and the two species can have a different fate when released to the environment. While TcO4\u2212 in solution is bioavailable, TcO2\u00b7nH2O is expected to be adsorbed at low concentrations and precipitated at high concentrations. The species TcO2\u00b7nH2O can become available for uptake when oxidized by air and is thus bioaccessible."}
{"_id": "Radiology$$$be9eb698-c643-4104-9f7c-64227d08e3af", "text": "Besides the speciation of radionuclides, the extent to which radionuclides can be transferred to different compartments is influenced by competition between ions. On the one hand, stable isotopes of the radionuclides may compete for adsorption to the solid phase or uptake by biota. For example, radionuclides such as 3H, 40K, 48Ca, 54Mn, 60Co, 65Zn, and 131I, are isotopes of essential biological nutrients [10]. Therefore, their uptake and retention characteristics are largely controlled by the flux of these essential nutrients through biological processes. On the other hand, elements that are chemically similar to the radionuclides may compete. Certain radionuclides behave in the environment in a similar way to essential elements for biota, due to their chemical properties. For example, 137Cs and 90Sr have similar chemical properties and follow the same transfer and cycling processes in the environment as the macronutrients potassium (K) and calcium (Ca), respectively. The tendency of these radionuclides to accumulate in the biota is reduced if there is an abundance of the analogous element in the environment [10]. Conversely, the accumulation of the radionuclide in the biota increases when there is a scarcity of the analogue element. For example, low concentrations of K and Ca in the soil can result in increased uptake of radionuclides by plants, as they find it more difficult to discriminate between nutrients and radionuclides under these stressful conditions [20]. As mentioned earlier, the long-term bioavailability of 137Cs and many other radionuclides depend heavily upon ecosystem characteristics, and in particular, soil properties [10]. Soils and sediments of high clay content can effectively immobilize 137Cs by chemical binding. In such systems, the soil acts like a sink for 137Cs and in time very little of the nuclide is available for biological incorporation. Other systems have sandy soils with a low cation exchange capacity, and larger quantities of 137Cs can be recycled through the biota of such systems for long periods of time [9]."}
{"_id": "Radiology$$$3949a269-780f-4368-ad0e-88f0d45aa9b7", "text": "In summary, depending on their speciation, radionuclides can be transferred in the biosphere from the emission source to different compartments until they reach an equilibrium or final sink, or they can be recycled within the environment."}
{"_id": "Radiology$$$f3ff7757-1bc2-474c-86bd-eb92040c04d5", "text": "Information on the uptake of radionuclides to biota is vital for calculating dose to the organisms, since both external and internal irradiation contributes to exposure. Soil and sediment dwelling organisms often have high external dose rates by virtue of their habitat, but also internal exposure from ingested radionuclides. Many field studies on radiation effects in wildlife are flawed due to underestimation of the internal dose, reporting only ambient air dose rates [28]. This is particularly important for \u2329- (e.g., Ra) and \u00ae-emitting (e.g., Sr) radionuclides, for which internal exposure is the greatest contributor to dose, but also internal contributions from radiocesium or radium, for example, can make a significant contribution to the overall dose."}
{"_id": "Radiology$$$950b661c-9214-470d-a9e8-7e9566493542", "text": "There are a number of programs available for estimating the dose to biota. These are usually based on rather simplistic geometry and homogeneous internal distribution, but the basic principles are similar to those used for human dosimetry. They can also be adapted to give organ specific doses. For example, the ERICA Assessment Tool can calculate doses to a wide range of reference animals and plants, as well as user constructed organisms (see Box 9.1)."}
{"_id": "Radiology$$$6fee2d19-4c8c-4526-84c2-61a71f7f944f", "text": "The ERICA Assessment Tool is a free to download, computer software system for assessing the risks of ionizing radiation to terrestrial, freshwater and marine biota (https://\u200berica-tool.\u200bcom/\u200b). The system is based on the three tier ERICA Integrated Approach that was originally developed as part of the ERICA EURATOM project [29] (see also https://\u200bwiki.\u200bceh.\u200bac.\u200buk/\u200bdisplay/\u200brpemain/\u200bERICA)."}
{"_id": "Radiology$$$75e65305-ce6a-4629-92c9-42563ae66bad", "text": "The ERICA Tool includes various components, all of which are linked to internationally recognized programs and databases. These include\nModelling transfer of radionuclides through the environment: links to IAEA Wildlife Transfer Database (WTD) and IAEA handbooks [30]; https://\u200bwww.\u200bwildlifetransfer\u200bdatabase.\u200borg/\u200b.\n\nMethodology for estimating dose rates to biota from internal and external distributions of radionuclides: ICRP biota DC software version 1.5.1 for the calculation of dose conversion coefficients (DCC) [31].\n\nRisk characterization in order to evaluate the significance of the dose rates received by organisms, including comparison with background radiation doses, screening values [32], Environmental Media Concentration Limits (EMCL) [33], derived consideration reference levels (DCRL) and biological effects (FREDERICA database, https://\u200bwww.\u200bfrederica-online.\u200borg/\u200bmainpage.\u200basp)."}
{"_id": "Radiology$$$b737af30-74c5-40a3-8275-fe372d581923", "text": "Modelling transfer of radionuclides through the environment: links to IAEA Wildlife Transfer Database (WTD) and IAEA handbooks [30]; https://\u200bwww.\u200bwildlifetransfer\u200bdatabase.\u200borg/\u200b."}
{"_id": "Radiology$$$f7054656-cac0-49d2-a7e0-6a522ad29e45", "text": "Methodology for estimating dose rates to biota from internal and external distributions of radionuclides: ICRP biota DC software version 1.5.1 for the calculation of dose conversion coefficients (DCC) [31]."}
{"_id": "Radiology$$$5c46237b-e40b-412e-b099-ef934230372d", "text": "Risk characterization in order to evaluate the significance of the dose rates received by organisms, including comparison with background radiation doses, screening values [32], Environmental Media Concentration Limits (EMCL) [33], derived consideration reference levels (DCRL) and biological effects (FREDERICA database, https://\u200bwww.\u200bfrederica-online.\u200borg/\u200bmainpage.\u200basp)."}
{"_id": "Radiology$$$9a8b2746-4887-4015-9413-59efde95a3f9", "text": "The tool contains data on concentration ratios and DCC for all radionuclides in publication 107 [34], and in addition to a selection of pre-created reference organisms, allows users to create their own assessment organism."}
{"_id": "Radiology$$$29d68e37-7315-48dc-a866-572946acca5b", "text": "The ERICA tool has been updated since its original release, and the current version, ERICA Tool 2.0 (beta version released in November 2021\u2014https://\u200berica-tool.\u200bcom/\u200bthe-erica-assessment-tool-has-been-updated-to-version-2-0/\u200b) includes updates on concentration ratios, as well as new approaches for calculation of dose contribution from short-lived progeny, noble gases radon and thoron [35\u201337]."}
{"_id": "Radiology$$$03c0029e-90ea-4c5b-97b5-a617a2ac7b3a", "text": "Internal and external exposures are determined from specific dose conversion factors (DCC) combined with using field measurements of concentration activities or default concentration ratios (CR). The CR represents the activity concentration of radionuclides in biota (fresh and dry weight in animals and plants, respectively) and the activity concentration in soil (dry weight, upper 10\u00a0cm), water, or air for a given radionuclide [38]. The tool also allows the calculated exposures to be compared to background radiation or screening values."}
{"_id": "Radiology$$$0149afe8-a364-4c51-9f51-97f746456dd2", "text": "The calculation of external dose rates takes account of the occupancy of the organism (i.e., percentage of time spent in, on, or above soil, sediment, or water) and is determined by:"}
{"_id": "Radiology$$$00165d0d-40d6-4cd7-ac66-acf0c9a44159", "text": "DR\u2014dose rate (Gy/unit of time)\n\nDCC\u2014dose conversion coefficient\n\nCmedia (Bq/kg or Bq/L)"}
{"_id": "Radiology$$$cb88ffc4-d560-4641-bd09-93346cb2ee1e", "text": "Internal doses\n\n\nDR\u2014dose rate (Gy/unit of time)\n\nDCC\u2014dose conversion coefficient\n\nCorganism (Bq/kg)"}
{"_id": "Radiology$$$0a2e9793-5e7b-4f16-8d76-51a1eb5a7c85", "text": "There are several other simplifications to the approach, including assumptions on habitat ranges and feeding habits of biota [38]. CR are lacking for many organisms and radionuclides; however, the tool provides default CR based on available data and assumptions (e.g., similar taxonomy or chemical behavior to other organisms or radionuclides)."}
{"_id": "Radiology$$$3786e5bc-da66-4d40-97f1-3b9ae847d760", "text": "Uncertainties in dose estimates can be reduced if field measurements are available, but determination of internal concentrations of radionuclides can also be challenging, as organisms may be too small for direct radiochemical analyses, or it can be difficult to distinguish between radionuclides internalized in animal tissues, from those adsorbed to the body segment or cuticle. Efforts have been made to compare ERICA default CRs with field measurements at Chernobyl, showing a relatively good agreement between the CR values calculated for many organisms [39]. However, it was concluded that such similarity may have resulted from the broad range of estimated CR values available [40]."}
{"_id": "Radiology$$$3e00efab-bc72-4dcf-a970-a66f54d73310", "text": "In soil, Beaugelin-Seiller [41] concluded that DCC values are highly dependent on factors such as the porosity and soil water content, the body size of the organisms within other factors. For \u00ae-emitters, the difference in DCC values recorded reached a factor of 3, between dry and saturated soil conditions. The calculation of doses in organisms under exposures to NORM is also highly dependent on assumptions of equilibrium that must be made for several radionuclides from the 238U decay series [42]. Usually a 100% equilibrium is assumed, although different equilibrium percentages are also accepted for radon, as it can escape to the atmosphere."}
{"_id": "Radiology$$$18d38309-2d55-47d4-b7ab-0a34a57d16e7", "text": "The positioning of organisms in the trophic chains and the composition of their diets may be determinant for the magnitude of exposures. In a coastal sand dune system, under a long-term contamination through atmospheric deposition and sea-to-land transfer of radionuclides at Sellafield nuclear reprocessing site (West Cumbria, England), Wood and collaborators [43] recorded high activity concentrations of 137Cs, 238Pu, 239+240Pu, and 241Am in soil detritivorous (e.g., Collembola and Isopoda) when compared with predators (e.g., Coleoptera larvae). Within the same trophic level, these authors also found significant differences in the whole-body activity concentrations of different invertebrate groups. Size also influences the internal doses to organisms. Dose calculations for two benthic invertebrates, the larval midge Chironomus tetans and the amphipod Hyalella azteca, based on estimations from NORM activity concentrations in sediments impacted by uranium mining demonstrated that the smaller amphipod, received a greater dose of alpha irradiation. This reflected the high content of ingested radionuclides within the gastrointestinal tract and that as diameter of the gastrointestinal tube decreases, the assessment factor (AF) for ingested alpha-emitters increases, as more alpha-particles are expected to reach the tissues of the organisms [42]. Therefore, it was suggested that the contribution of sediment within the gastrointestinal tract for the calculation of internal doses must be considered, and not only the activity concentrations of radionuclides recorded in external sediments."}
{"_id": "Radiology$$$c022727b-4a58-4ffb-bacd-2a02e62743c2", "text": "In the case of accidents, there is also a need to account for historical dose and radionuclide decay, since observed effects may be a legacy of high levels of exposure after the accident. These high exposures can also be a source of confounding factors, since the initial damage may lead to indirect ecosystem changes (such as the replacement of pine trees by less sensitive species) [44]. While much of the focus in studying the environmental impacts of radiation has been on the uncertainties in effects measurement, it is important to stress that there are also uncertainties in dosimetry."}
{"_id": "Radiology$$$6464cef5-2282-4de0-a81b-13f212fb46f6", "text": "Following the discovery of X-rays by Wilhelm Roentgen in 1895 and of radioactivity by Henri Becquerel in 1896, studies on its effects started immediately. The detonation of the atomic bombs over Hiroshima and Nagasaki in 1945 raised the concern about the health impacts of radioactive contamination and the behavior of radionuclides in the environment [45]. Therefore, a great number of studies using a variety of plants and animals have been performed since then."}
{"_id": "Radiology$$$815b688e-b67a-45fc-bece-d6c66a7d59bd", "text": "The first harmful effects caused by the exposure to ionizing radiation occur at the molecular and cellular level. If these effects are severe enough, they can impact tissues, organs, individual organisms, populations, and entire communities. However, even though an individual organism may suffer from severe damage at the molecular and cellular level, it does not necessarily mean that entire populations and communities will be affected [46]. It seems that individual organisms are able to sustain a certain level of effects before they are reflected at a population level [46]. However, when an effect is seen at the population level or at higher levels of organization (i.e., communities or ecosystems), it means that effects at individual organisms are expected to be occurring (Fig. 9.3) [45].\n\nAn infographic of environmental ionizing radiation exposure and effects. It includes the list of most frequent radiation types and exposure for gamma and particulate radiations of beta and alpha particles, and lethal, immune, molecular, reproduction, and genetic effects.\n\nFig. 9.3\nExposure and effects of different radiation types on organisms"}
{"_id": "Radiology$$$ea40bb61-816b-4884-847a-0bfe1e0a47d0", "text": "An infographic of environmental ionizing radiation exposure and effects. It includes the list of most frequent radiation types and exposure for gamma and particulate radiations of beta and alpha particles, and lethal, immune, molecular, reproduction, and genetic effects."}
{"_id": "Radiology$$$68a58b47-17cc-49f8-8bfd-abe195bf0a18", "text": "There can be two types of effects caused by ionizing radiation. They can be stochastic or non-stochastic (deterministic). Stochastic effects are effects that occur by chance and the higher the dose the higher the probability of its occurrence. However, the severity of those effects is not dependent on radiation dose. The main stochastic effects related to ionizing radiation exposure are cancer and genetic damage/alterations (i.e., mutations) [47]. For non-human biota, stochastic effects that occur at germinal cells will be the ones that will have a higher impact, as they will have a higher probability of being inherited and, therefore, of affecting the next generations, impacting populations and communities [47]. Deterministic effects depend on time of exposure, doses and type of radiation. They are adverse tissue reactions that result from the damage or killing of many cells in an organ or tissue. The severity of these effects increases with dose when radiation levels reach a threshold, below which harmful effects to tissues/organs do not occur. The deterministic effects that are most important at a population level are mortality (which affects density, age distribution, and death rate), fertility (birth rate) and fecundity (which affects birth rate, age distribution, size of the population) [45] (Fig. 9.3). As for other stressors (i.e., chemicals), exposure to ionizing radiation can be acute or chronic. Acute exposures are short-term exposures to relatively high doses of radiation that usually last minutes or hours. Chronic exposures are long-term exposures or lifetime exposures to usually low doses of ionizing radiation. Doses in acute exposures are often reported as total absorbed doses, whereas for chronic exposures doses are often reported as dose rates (i.e., mGy/day, Gy/year, or mGy/h) [46, 48]. For a given dose of ionizing radiation, acute exposure induces higher injury than chronic exposure [46]. The higher the dose the lower the ability of cells to correctly and rapidly repair the damage and also the lower the ability of healthy cells to divide and regenerate the damaged tissue [46]. Depending on the dose received by cells or organisms, several types of effects can occur, namely genetic damage, DNA lesions that can induce teratogenic effects (malformations) on embryos when occurring in germinal cells (i.e., gametes), cell transformation in somatic cells and cell death (Fig. 9.3). In some cases, DNA damage can be so severe that it becomes incompatible with the survival of the cell or of the entire organism. Depending on the kind of cells that are affected (germ cell or somatic cells), there can be different consequences. Severe damage (i.e., DNA double strand breaks, gross mutation like duplications, deletions, translocations, and chromosome gain or loss) will cause cell death potentially leading to the death of the organism or, for example, to its sterility if it occurs in germ cells (Fig. 9.3). If the damage is not enough to cause cell death, it can cause cell transformation and cancer in somatic cells or it can affect the fitness of the organisms and entire populations if it affects germ cells. Mutations can cause a reduction in the production of viable embryos or viable gametes and also, they can be passed and accumulated throughout generations reducing the population\u2019s fitness. Therefore, DNA alterations can have an important impact on fertility and fecundity and consequently in reproduction [46]."}
{"_id": "Radiology$$$0663efe2-f2a6-4db9-8126-42df7b3f5deb", "text": "Also, there can be effects on the homeostasis of organisms (Fig. 9.3), namely depression of the immune system, alterations in normal metabolism, oxidative stress, and disturbances in the endocrine system [49]. The majority of the studies performed so far are focused on the determination of the acute effects of high doses of radiation, and only few studies are focused on chronic exposures to low doses of ionizing radiation."}
{"_id": "Radiology$$$b5cc2c05-9926-484c-9270-bd676104d0ea", "text": "The younger the organisms (namely fetuses and embryos) the more sensitive they are to the deleterious effects of radiation exposure. This is due to the higher sensitivity of cells that frequently undergo mitosis (which occurs frequently in young organisms for each tissue/organ as it is part of the growing process). Also, tissues/organs that have the ability to regenerate or that are constantly producing new cells like the hepatic tissue, the skin, the bone marrow, germinal cells, and gut lining are more sensitive to radiation (Fig. 9.3). The higher the cell division rate in an organism the more sensitive it will be to radiation\u2019s harmful effects."}
{"_id": "Radiology$$$97ddb25f-d77c-45a7-be78-2bd82c2c6777", "text": "Regarding the sensitivity of parameters like mortality and reproduction, in general the reproductive capacity is a more sensitive parameter to the effects of radiation exposure both for terrestrial and aquatic invertebrates and vertebrates, than life expectancy (mortality) [45]. Negative effects on reproduction rate can occur at less than 10% of the radiation dose required to induce direct mortality in mammals [45]."}
{"_id": "Radiology$$$dbdee415-5eb0-49f6-a3e2-667716dad281", "text": "All organisms evolved in the presence of radiation, being cosmic radiation or natural radiation emitted by NORs present in the earth crust [50]. The studies performed so far, on the effects of ionizing radiation, showed that there is a considerable variation in the response of organisms from the same or different species, due to intra- and interspecies variability in sensitivity. In general, it is widely accepted that mammals are the most sensitive organisms, followed by birds, fish, and reptiles and that invertebrates and other less complex organisms have the highest radiation resistance (Fig. 9.4) [46, 50]. However, it has to be noted that most of the knowledge gathered so far comes from laboratory exposures of specific strains of these organisms and that results may differ significantly from what happens to their wild counterparts.\n\nA phylogeny chart of the approximate acute lethal dose ranges varying between 10 superscript 0 and 10 superscript 4 for the corresponding taxonomic groups of viruses, mollusks, protozoa, bacteria, moss, insects, crustaceans, reptiles, amphibians, fish, higher plants, birds, and mammals.\n\nFig. 9.4\nSchematic representation of overall sensitivities of different taxa to acute gamma radiation exposure. (Reproduced with permission of UNSCEAR, adapted from UNSCEAR 2008 report, Annex E)"}
{"_id": "Radiology$$$de10ae32-a305-45f6-b030-87385a42fbc9", "text": "A phylogeny chart of the approximate acute lethal dose ranges varying between 10 superscript 0 and 10 superscript 4 for the corresponding taxonomic groups of viruses, mollusks, protozoa, bacteria, moss, insects, crustaceans, reptiles, amphibians, fish, higher plants, birds, and mammals."}
{"_id": "Radiology$$$60259e71-ea67-483b-b85c-e077ce61e4e6", "text": "The majority of the existing studies on the effects of ionizing radiation in cells are focused on DNA as the main target, making it clear that there is a cause-effect relationship between DNA damage with cytotoxicity and mutagenicity associated with ionizing radiation exposure. However, the cascade of molecular effects that lead to the induction of biological effects in exposed organisms is complex and involves, firstly, the interaction of radiation with water molecules and structural and functional biological molecules inside the cells. This interaction will induce the formation of ions, radical species, and excited molecules that will move from the site where they were formed to other cell compartments, causing damage to other biological molecules. This will trigger several signaling cascades, activating cell responses that will change the normal metabolic state of the cell, including changes in gene expression, enzyme recruitment and activities, DNA methylation patterns, and other stress-induced signaling events. When DNA is damaged, the cell cycle is interrupted allowing for DNA integrity check. DNA can be damaged directly through direct ionization or indirectly through the attack of free radicals that are formed when radiation interacts with water molecules of the cell [51]. Given the high content of water in cells, IR interacts with water in a process called radiolysis, generating free radicals as H\u2219 or OH\u2219, which trigger a cascade of events giving rise to other ROS as hydrogen peroxide and the superoxide anion [52] and references quoted. If not neutralized these products may diffuse within cells, as well as between cells, affecting other biomolecules such as DNA, proteins, and lipids, both in target and non-target cells (i.e., cells not directly irradiated) [53, 54]. Regarding DNA, ROS may oxidize bases or cause single and double strand breaks (SSB and DSB) [55]. Also, post-irradiation DNA lesions can be formed as a consequence of the attempt of the cell to repair sugar and base residues, which can be converted to SSBs (Single Strand Breaks) and DSBs (Double Strand Breaks) [51]. If DNA is correctly repaired, the cell will continue its cycle normally, if not, the cell can undergo transformation as mutations and chromosome aberrations may occur or if the damage is too severe, programmed cell death (apoptosis) will occur. The repairability of the damage and the repair accuracy will depend on damage severity and complexity. Low LET (beta particles, gamma and X-rays) and high LET (alpha particles and neutrons) radiation exposure can cause several types of DNA damage that are usually repairable, like SSBs, abasic and apurinic and apyrimidinic sites and DSBs (Fig. 9.5). However, the fraction of irreparable DNA damage depends strongly on LET. High and low LET radiation exposure can cause complex DNA damage, but this type of damage is more frequently associated with high LET radiation. Complex DNA damage is composed by closely spaced DNA lesions that form clusters [51]. Clusters contain two or more DNA lesions of the same or different origins, close to each other and on opposite strands (bistranded lesions). These lesions can be DSBs or non-DSBs oxidative clustered DNA lesions like SSBs, oxidized base lesions, and oxidized apurinic/apyrimidinic sites (AP sites) [51] (Fig. 9.5). These clustered lesions have a high mutagenic and carcinogenic potential since they are considered repair-resistant or even unrepairable due to the relative inefficiency of DNA repair systems to process such closely spaced and complex lesions. As there are several DNA repair systems in the cells and each of them is specialized in the processing of specific lesions, when several types of lesions are closely spaced in the DNA molecule, the different repair systems cannot act properly, retarding the repair and often generating other lesions. High LET radiation is mostly associated with the generation of DSB\u2019s clustered DNA lesions and low LET radiation to non-DSB\u2019s oxidative clustered DNA lesions [51], but this is not completely clear and needs further studies. High LET radiation is also associated with increased frequency of chromosome aberrations, and also to a high frequency of unrejoined DSBs and consequently with a higher cell killing efficiency, as unrejoined DSBs are a cause of cell death.\n\nAn illustration of the comparison of low and high L E T radiation D N A damage distributions where photons or beta particles are random in low radiation and alpha particles are concentrated in high radiation.\n\nFig. 9.5\nHigh and low LET radiation DNA damage effects"}
{"_id": "Radiology$$$37b5a435-3121-4fa4-9aca-611c520841d6", "text": "An illustration of the comparison of low and high L E T radiation D N A damage distributions where photons or beta particles are random in low radiation and alpha particles are concentrated in high radiation."}
{"_id": "Radiology$$$46040386-e5dc-43f5-b154-4d7578cc8404", "text": "Microorganisms, including fungi, can be seen as good indicators of the ecosystem\u2019s \u201chealth.\u201d They include ubiquitous and taxonomically diverse microorganisms that play important key roles on diverse ecosystems\u2019 function. Specifically, with regard to radiation, microorganisms play a very important role in the health of these systems and in their cleaning and decontamination."}
{"_id": "Radiology$$$8ceb9bdc-7583-4dcd-877a-18821add362f", "text": "Microorganisms play a key role in the biogeochemical cycle of elements. In soils, they are important for organic matter turnover and maintenance of soil structure and fertility. As such, changes in the structure of microbial communities, by either metals or radionuclides, can have indirect effects on the above processes. Prokaryotes (bacteria and Archaea) have dominated a large part of the history of our planet, occupying virtually every \u201cinhabitable\u201d niche on earth. To be able to do that they have adapted to withstand large ranges in: (1) temperature, e.g., the hot temperatures found in hot springs and fumaroles, and the contrasting cold temperatures found on sea ice and polar regions, (2) pressure, e.g., deep sea, (3) salinity, e.g., hypersaline lakes, (4) pH, e.g., acid mine drainage sites, and (5) radiation, e.g., naturally occurring (deserts and high mountains, mining sites) and from nuclear contaminated sites [56]. Microorganisms that have adapted to such environments are referred to as extremophiles or polyextremophile (the latter being capable of withstanding different extreme conditions simultaneously), and these conditions are a requirement for their normal metabolic and biochemical operation. Most of these microorganisms belong to the domains Bacteria and Archaea although some fungal species have also been described. To survive these harsh conditions, extremophiles produce various primary and secondary metabolites, such as extremolytes, enzymes, and pigments [57]. Extremolytes, for example, are known to protect extremophiles cell structures and macromolecules from their harsh environments by forming protective water layers (e.g., ectoine), which is a co-solvent that shields proteins and cell membranes from UV light, heat, and dryness [58] around them or acting as chemical scavengers (e.g., carotenoids), protecting cells and their structures from UV radiation and oxidative stress [58]. Ultimately, the exceptional properties of these biomolecules find possible applications in various industrial sectors, in human healthcare, and well-being [59]."}
{"_id": "Radiology$$$d19841fc-81b5-437b-bce9-2d42f0bad750", "text": "With regard to radioactively contaminated sites, microorganisms play an essential role on the mobility, toxicity, and distribution of radionuclides, through processes that include reduction, uptake, and accumulation by the cells, biosorption, and biomineralization with phosphates and carbonates [16]."}
{"_id": "Radiology$$$db4b002e-e283-4de9-a25b-4cc3c3f8c716", "text": "Culture dependent and culture-independent approaches have shown the effects of long-term exposure to metals or radionuclides on individual species and on microbial communities. In addition, they have allowed those specific genes and cell functions mostly affected by radiation and metals to be identified, thus contributing to a better understanding of the molecular mechanisms behind microbial metal/radioresistance. Furthermore, the acquisition of genetic determinants by horizontal gene transfer contributes to shape microorganisms and microbial communities occupying these sites. More recently, refined metagenomic approaches focusing on prokaryotic communities have been employed and are expected to shed more light on the cells\u2019 strategies to overcome radiation stress to remain operational."}
{"_id": "Radiology$$$0c8764d7-12c8-41ee-8d63-7313bf9e0a49", "text": "The following section addresses in more detail some of the mechanisms that contribute to the survival and maintenance of microorganisms in these environments. We will end by referring to the impact of more recent methodologies, such as metagenomics and other omics technologies, and their contribution to clarify aspects such as the impact of these contaminants on the microorganisms and communities that exist in these sites."}
{"_id": "Radiology$$$515c117d-e0c5-4080-ad75-d03baf1903ae", "text": "It has been reported that when radiosensitive microorganisms are subjected to multiple high IR exposures, their resistance increases [60]. This was recently demonstrated by experimental evolution, where populations of Escherichia coli very resistant to IR were generated in the laboratory, after 100 selection cycles, and to which the dose needed to kill 99% of the population increased from 750 Gy to about 3000 Gy [61]. Likewise, radioresistant species can become even more resistant with repeated exposure [62]. This \u201cmemory\u201d adaptation is associated with smooth genetic alterations that affect DNA repair and metabolic functions. During this process of adaptation, other physiological characteristics of the microorganisms are profoundly affected as, for example, growth which is slowed down, because the microorganism must direct its energies to other processes, such as effectively repairing the damaged DNA."}
{"_id": "Radiology$$$81f7492c-8ee7-4b40-9be5-31106c2213de", "text": "The association between genome size and radiosensitivity between taxa has long been suggested. For instance, for the same chronic exposure to IR, fungi, for which genome sizes range between 12 and 20 Mbp, suffer more DSBs per unit time than bacteria with their smaller genomes (3\u20136 Mbp). However, this is not true for Shewanella oneidensis and Deinococcus radiodurans whose genomes are practically the same size, but while the former is killed after exposure to a radiation dose causing one DSB, the latter manages to recover from hundreds of DSBs. This is probably due to the fact that D. radiodurans has up to ten identical copies of its genome per cell and uses this genetic information to repair its DNA. In addition, there is also evidence for the interference of non-enzymatic antioxidants such as manganese complexes, which protect proteins from IR-induced oxidation, facilitating the maintenance of cell homeostasis and DNA repair. Although in many radioresistant bacteria and yeasts, the most common DNA DSB repair pathway is similar to homologous recombination (HR),1 in fungi, non-homologous end joining (NHEJ)2 is the preferred, as in other eukaryotes, despite being error-inducing. Melanin pigments also seem to be involved in protection against multiple stressors, including IR as it can act as an oxygen radical scavenger [62]."}
{"_id": "Radiology$$$e7e82824-7e56-44c7-a1f2-b00d21c21670", "text": "Radioresistant microbial extremophiles have developed strategies to survive and withstand dose rates that to the majority of organisms, including humans, would result in acute health effects [63]. It is believed that radioresistant microorganisms possess highly efficient processes to repair DNA damage. However, it has recently been demonstrated that the repair mechanisms and the proteins involved are common to those found in radiation sensitive microorganisms [64]."}
{"_id": "Radiology$$$81a3776f-df1f-439b-ac16-5dc2edda4a17", "text": "The genus Deinococcus is probably the most well studied and characterized and there is a great deal of information, to what its radioresistance is concerned. Metabolically active Deinococci vegetative cells can tolerate chronic radiation levels of more than 100\u00a0Gy/h, whereas other bacteria, Archaea, and fungi can be resistant to several kGy of acute IR. D. radiodurans exhibits resistance to acute IR up to 15\u00a0kGy, to 60\u00a0Gy/h of chronic radiation, and also to high levels of resistance to UV-C irradiation (100\u2013295\u00a0nm), desiccation and oxidative stress. Thus, regarding the example of Deinococcus radiodurans, it can be argued that it efficiently and rapidly repairs DNA damage caused by IR. A number of genes have been identified whose expression is activated after irradiation, namely those encoding proteins associated with (1) efficient DNA repair, (2) protection against oxidation and (3) DNA supercoiling, which helps to maintain DNA integrity after irradiation [65]. More recently, it was demonstrated that in this organism, the adaptation to dryness and desiccation is at the basis of its radioresistance [64]."}
{"_id": "Radiology$$$ccb7e164-72b0-4602-ae0d-7ea10efbdb99", "text": "Nonetheless, it has been reported that Deinococcus\u2019 ability to repair DNA damage results from a selective pressure other than ionizing radiation, because there are no terrestrial environments subjected to the levels of radiation it tolerates. Still, the information gathered, albeit with some degree of uncertainty, has contributed to a better understanding of the mechanisms of radioresistance in other organisms, making this an excellent model organism to unravel these mechanisms [66]."}
{"_id": "Radiology$$$77671dff-98f5-4e3c-84ac-b02fbdeaa201", "text": "Studies have shown that the DNA repair systems used by D. radiodurans are less complex than those of radiation sensitive bacteria, namely Bacillus subtilis, a spore-former species and Escherichia coli. Transcriptomics studies revealed that in response to \u03b3-radiation, specific genes involved in damage response are activated (ddrA, ddrB, and irrE (pprI)). PprI, for instance, regulates the expression of the recombinase recA and pprA, which is a protein involved in DNA ligation that is essential for the radiation resistance exhibited by D. radiodurans. Strains lacking pprI show impaired genome recovery [66]. Another important DNA repair system involves the synthesis of long and single-stranded overhangs, a process referred to as \u201cExtended Synthesis-Dependent Strand Annealing\u201d (ESDSA).3 The process allows the reconstruction of a functional genome from the chromosome fragments produced by the exposure to radiation. Accordingly, the process is used by the RecFOR pathway to repair DNA double strand breaks. To support these observations, strains mutated in the genes involved in the RecFOR pathway are susceptible to \u03b3-radiation [67]."}
{"_id": "Radiology$$$a7731b11-452b-4fa4-984a-d80b7693bafa", "text": "Laboratory experiments with Escherichia coli, and other mesophilic bacteria, have shown that these may become resistant to the chronic exposure to IR just by adding Mn2+ and orthophosphate to its growth medium, which spontaneously form potent Mn-antioxidant complexes. Another important factor associated with radioresistance is cell density. For example, in D. radiodurans high cell concentrations seem to exert a protective effect against a radiation dose of 67\u00a0Gy/h [60]. Still, further and more complete studies are required until we know all the phenomena that contribute to the radioresistance exhibited by microorganisms. One thing is certain, it results from the interplay of several factors."}
{"_id": "Radiology$$$036ff377-8438-4b49-96a4-6f15d4c702f5", "text": "Undoubtedly, multi-omics approaches (genomics, transcriptomics, proteomics, and metabolomics) will shed light and will further contribute to our understanding of the mechanisms involved in microbial radioresistance and detoxification. In order to contribute to a better understanding of the mechanisms involved in uranium resistance/tolerance, a recent high-throughput proteogenomic study was applied to bacteria of the genus Microbacterium, isolated from Chernobyl U contaminated soils and from natural U rich soils. The approach allowed the identification of proteins involved in membrane transport (e.g., ABC transporters and efflux pumps), phosphate (e.g., phosphatases involved in biomineralization) and iron metabolism (e.g., siderophores), in addition to a large percentage of proteins of unknown function, which reveals the complexity of this mechanism [68]. Still, in another study carried out with a member of the genus Geobacter exposed to 100 \u03bcM\u00a0U, proteins involved in DNA protection, in efflux pumps of the RND family and in oxidative stress responses (e.g., SOD and superoxide reductase), were also identified. Exploring these recent approaches will certainly allow us to gain knowledge that will contribute to clarify this complex intricate process. Furthermore, they will allow the selection for the best microorganism(s) with the potential to clean-up these contaminated sites by more eco-friendly processes. So far, in addition to the above study, genomic approaches proved useful in the identification of key genes and their respective products, encoded in the genomes of microorganisms resistant/tolerant to radionuclides/metals and which are, therefore, involved in the detoxification of this contaminants. With this approach, U-resistant bacteria of the genus Burkholderia and fungi of the genus Penicillium have been identified. Transcriptomics studies, by giving access to the analysis of gene expression and regulation, have gained relevance in the area of bioremediation. The information gathered from this comprehensive analysis, and also from future studies employing these methodologies, will surely shed light on the mechanisms of microbial resistance/tolerance to radionuclides/metals, while helping in the identification and selection of microorganisms that can be employed for bioremediation purposes of radionuclide/metals contaminated sites [69]."}
{"_id": "Radiology$$$9c4e9d8f-4725-4047-a1e3-9f43f4b8fcd5", "text": "Unlike most laboratory studies, environmental exposure to radionuclides, (e.g., NORM sites and nuclear power plant accident sites), includes different radiation types (\u03b1 and \u03b2, as well as \u03b3) combined with many other stressors (e.g., temperature, nutrients, toxic chemicals like metals, etc.) over long periods. Thus, in polyextremophiles, the response to the adaptation/resistance should be broader and involve an intricate crosstalk between the different cellular processes [70]."}
{"_id": "Radiology$$$e58ff563-8108-42a8-839e-9283da1b0bd6", "text": "Culture-independent field studies have shown that radionuclide contaminated environments host a wide diversity of bacteria and that radionuclides strongly impact community function and structure. Recently, a metagenomics approach carried out in surface soil samples from Chernobyl and Fukushima, over a gradient of radionuclide concentrations (137Cs 1680\u20140.4 and 90Sr 209.1\u20141.9\u00a0kBq/kg), revealed that samples clustered according to the level of radiological contamination, irrespective of the collection site [71]. Nonetheless, a lower microbiota diversity was found in Chernobyl samples, which was expected as Chernobyl soils are more contaminated. The following were reported to be the most common phyla: Proteobacteria, Acidobacteria and Actinobacteria. Furthermore, as expected, the functions encoded by the genes identified seem to be related with stress, metal and radiation tolerance. For instance, genes involved in decontamination, DNA repair, information storage and processing, cellular processes and signaling and metabolism. A comprehensive listing of the function of the genes responsive to this type of contaminants has been recently reviewed by Hoyos-Hernandez and co-workers [71]."}
{"_id": "Radiology$$$491f7a5a-fac7-4ee9-8548-a02cf5166440", "text": "A similar approach was employed in a study performed by Theodorakopoulos and colleagues [72], in Chernobyl, which demonstrated the high diversity of bacteria in those contaminated sites. The same authors isolated cultivable bacteria of the genus Microbacterium that were employed in laboratory exposure studies, contributing to a better understanding of the mechanisms of tolerance to radionuclides/metals in those bacteria. The identified mechanisms involve biosorption, efflux and biomineralization [68]."}
{"_id": "Radiology$$$05211dc7-224e-4930-be46-41ae91bb4999", "text": "Although further studies are required to better understand how radiological contamination exerts a selective pressure and how it shapes the structure of the microbial community, the sensitivity of the various organisms to radioactive contamination under environmental conditions generally exceeds the sensitivity of the same organisms to experimental laboratory exposures [62]. It is clear though that communities from soils of these contaminated sites have functional profiles that allow them to deal with this type of radiological and chemical contamination. Furthermore, these environments constitute a genetic pool from which the phylogenetic affiliation of cultivable and non-cultivable microorganisms can be determined, thus allowing the identification of new genes involved in the resistance to these contaminants, in addition to further contributing to clarify those mechanisms."}
{"_id": "Radiology$$$d78eab80-ed35-4efa-9eb5-b56166aabc01", "text": "Plants are sessile organisms that cannot leave the surrounding environment if the ecological factors are not suitable for their growth. Thus, under unfavorable circumstances, plants have only the choice to perish or adapt to changing environments. The extreme physiological plasticity of plants allowed their diffusion in all ecosystems of the Earth and today we may have a comprehensive vision of the multitude of adaptations carried out by these organisms in diverse places. Indeed, plants such as other living organisms can adapt to cyclical natural disturbances over time, developing the capacity for endurance (resistance) and self-repair (resilience) in different ecosystems."}
{"_id": "Radiology$$$dda1637d-8bc8-4b4a-9e07-27861b3bcb91", "text": "Laboratory and field studies showed that ionizing radiation may exert different effects on plant metabolism, growth and reproduction, depending on plant developmental stage at the time of exposure, plant physiological and morphological traits, as well as genetic characteristics [73, 74]. Moreover, depending on the dose or radiation type (low or high-LET), ionizing radiation induces detrimental outcomes at high doses, harmful consequences at intermediate levels and stimulatory effects at low doses."}
{"_id": "Radiology$$$d1066eef-9f21-454e-9d18-aefa2bfa2b8b", "text": "In some cases, ionizing radiation exposure increases embryo lethality, induces dwarf architecture and modifies floral elements [74] and literature herein. Other studies indicated that some irradiated crops showed a taller architecture, increased yields and reproductive success and the ability to endure water shortage [75, 76]. As for many other organisms, within plant cells, the nucleus is considered the primary site of injury by ionizing radiation, which is responsible for random DNA damage and generates different kinds of mutations, such as deletions, base substitutions and chromosomal alteration [74, 77]. There is a direct relationship between the radiosensitivity of a plant and the average volume occupied by a chromosome in the cell nucleus. If the chromosome volume is large, the plant will be more sensitive and, therefore, the dose of ionizing radiation causing severe damages is less. Hence, polyploid species exhibit a minor sensitivity to radiation damage because gene redundancy protects polyploidy from the deleterious effect of mutations [78]. Besides plant cells, it is noteworthy that ionizing radiation may have different impacts on organs and tissues. Generally, more complex tissue architecture is less sensitive to damage; thus, young tissues are more vulnerable than old [73, 79]. At functional level, many studies have evidenced that radiation is dangerous for the photosynthetic apparatus. Generally, a decline of photosynthesis often implicates damage to photosystem II (PSII) and in particular to D1 protein, implicated in the right functioning of photosynthetic electron transport. Together with the impairment of PSII, a significant decrease of photosynthetic pigments and enzymes of the carbon assimilation cycle was also detected [73]."}
{"_id": "Radiology$$$721e4254-c7a5-4360-bcb6-a9b9e2f0c284", "text": "The majority of information on the impacts of radioactivity on plants comes from studies carried out by scientists after the nuclear disasters of Chernobyl (Ukraine) in 1986 and Fukushima (Japan) in 2011 [80]."}
{"_id": "Radiology$$$e3a441c4-e968-46f9-b7dc-2b1101d30cb2", "text": "Since 1986 the Chernobyl red forest has represented a living laboratory for biologists to study for long-lasting plant behavior in response to acute and chronic radioactive contamination. The name \u201cRed Forest\u201d comes from the ginger-brown color of the pine trees as a result of the high radiation levels immediately after the explosion of the nuclear plant. Studies continued in the post-accident period and enlarged the knowledge on the effects of acute and chronic radiation on plants [81]. Generally different plant species show diverse sensitivity to radiation, being shrubs more resilient than conifers. The sensitivity of the pine compared to other tree species was most apparent in the Chernobyl exclusion zone and trees showed dramatic alterations in the morphology of trunks and branches, indicating damage at meristems level [82]. Following the Fukushima accident, despite the much lower exposure levels, Japanese red pine (Pinus densiflora Siebold & Zucc.) and Japanese fir (Abies firma Siebold & Zucc.) species showed developmental anomalies similar to those observed in Chernobyl [83, 84]. However, it is uncertain if the aberrations observed in Chernobyl are due to direct effects of radiation on the trees or multiple stresses due to biotic and other abiotic factors."}
{"_id": "Radiology$$$51e9ceed-efb8-42c1-a123-c9c59f677c04", "text": "It is noteworthy that the quantity of radionuclides absorbed by plants depends on their phenological stage and growth status which, in turn, varies with the pedo-climatic conditions and cultivation factors. Once deposited on the vegetation and in particular on the leaf surface, the radioisotopes are absorbed through stomata and then transported to the other organs including fruits, thus possibly entering the food chain through edible leaves and fruits [85]."}
{"_id": "Radiology$$$7bc65a12-d4b4-427f-b2ec-9b328e36e547", "text": "Today the Red Forest remains one of the most contaminated sites globally, and the surrounding forest area also represents an area of active research and scientific interest because of the return of wildlife in the exclusion zone. Here, the understory vegetation and deciduous (silver birch) trees have reappeared, but radioactive dust still remains stored in plant biomass and soil, for the very slow matter cycle."}
{"_id": "Radiology$$$90fff831-10d5-4789-8eb1-e3700eed2e94", "text": "The occurrence of revegetation has proven to be remarkably resilient to the intense radiation around the nuclear disaster zone. The exclusion zone is now dominated by grasslands and shrublands, while the most representative trees are Scots pine and silver birch Betula pendula [74] and literature herein."}
{"_id": "Radiology$$$c1814971-3fcb-4920-a390-fbfa568296c2", "text": "Recent studies suggest that plants subjected to not-lethal doses of ionizing radiation show an increased resistance to other environmental stresses. Two strategies have been hypothesized, namely the production of ROS-mediated cell signaling and/or a boost of secondary metabolites [86]."}
{"_id": "Radiology$$$2e161e02-b97f-4573-85b9-db95258a47b2", "text": "The resilience to radiation in plants of the Chernobyl exclusion zone and from most contaminated sites at Fukushima is due to different mechanisms to protect the genetic material, improving the plant radioresistance [80]. Generally, plants are more radioresistant than animals because they present integrated adaptation mechanisms at genetic, anatomical, and physiological levels."}
{"_id": "Radiology$$$99c16535-099b-480c-873a-17deed394c89", "text": "At genetic level, mechanisms include the regulation of expression of some genes encoding for radical scavenging and DNA-repair enzymes, homologous and non-homologous recombination, and the activation of scavengers. The higher stability induced by polyploidy, typical among plant kingdom, enhances radioresistance thanks to the presence of several copies of the same genes, which may serve as additional wild type copies in the case of radiation-induced injuries [87]. At the structural and metabolism level, plant cells present some traits such as thickened cell walls, cuticles, pubescence, increased deposition of phenolic compounds around membranes [88, 89]. At the anatomical level, complex tissue organization is associated with high resistance to mutagenic effects and the capability to adopt repair mechanisms."}
{"_id": "Radiology$$$2898a490-4ae7-40cc-8a5b-14008e60ac82", "text": "Non-lethal doses of ionizing radiation may also induce hormesis improving plant defense against stressors, through the stimulation of the production of antioxidant enzymes (SOD, CAT, APX) or morpho-anatomical and photosynthetic changes that favor plant growth and metabolism [74, 90, 91]."}
{"_id": "Radiology$$$56d8e2b1-09e3-4dde-ad96-6abe24c1c6a0", "text": "Radiation-induced hormesis is still an unclear phenomenon in plants because it strongly depends on species intrinsic characteristics. At present, further studies are in progress to understand if it is a sort of compensation to irradiation damage or a transitory change, not enough to induce permanent injuries."}
{"_id": "Radiology$$$060182fe-53ae-4090-b619-89c6f694587a", "text": "Invertebrates have been considered a relevant group of organisms for studying the effects of ionizing radiation, both focusing on mechanisms of action and on previewing impacts in natural communities. Several reasons can be enumerated for choosing aquatic and terrestrial invertebrates as model organisms for IR studies, namely:1.\nThey have long served for providing insights into fundamental mechanisms of development, biomedical research (e.g., neurobiology, basic physiology, genetics, immunology, cancer biology), species diversification and genome evolution (e.g., Drosophila melanogaster, Caenorhabditis elegans; planarians and crustaceans) [92\u201395]; for studying the effects of ionizing radiation in neuronal function [96] and as model organisms in radiation hormesis studies [97].\n\u00a02.\nDue to their important role in food webs, transferring carbon from producers to higher trophic levels (i.e., cladocerans, copepods), as detritivores contributing for degradation of organic matter through comminution (e.g., oligochaetes) and turnover of microbial communities (i.e., bacterivorous nematodes).\n\u00a03.\nThe role of some species as ecosystem engineers dynamically working the structure of soils and sediments (i.e. oligochaetes, polychaetes, ants) and the contribution for other soil and sediment functions.\n\u00a04.\nThe sensitivity and the ease of culture for some invertebrate species under laboratory conditions, as well as proliferation, producing a great number of individuals for testing in complex experimental designs and without tight regulatory requirements."}
{"_id": "Radiology$$$66734d58-dafe-47e6-9771-16610965d5e4", "text": "They have long served for providing insights into fundamental mechanisms of development, biomedical research (e.g., neurobiology, basic physiology, genetics, immunology, cancer biology), species diversification and genome evolution (e.g., Drosophila melanogaster, Caenorhabditis elegans; planarians and crustaceans) [92\u201395]; for studying the effects of ionizing radiation in neuronal function [96] and as model organisms in radiation hormesis studies [97]."}
{"_id": "Radiology$$$50707db4-f74d-4c0a-ae06-1818d272f26d", "text": "Due to their important role in food webs, transferring carbon from producers to higher trophic levels (i.e., cladocerans, copepods), as detritivores contributing for degradation of organic matter through comminution (e.g., oligochaetes) and turnover of microbial communities (i.e., bacterivorous nematodes)."}
{"_id": "Radiology$$$28318448-afb9-4eea-8885-058ed29ecc45", "text": "The role of some species as ecosystem engineers dynamically working the structure of soils and sediments (i.e. oligochaetes, polychaetes, ants) and the contribution for other soil and sediment functions."}
{"_id": "Radiology$$$68b13291-c22d-4ba9-9b2a-ddfaa6ee40a6", "text": "The sensitivity and the ease of culture for some invertebrate species under laboratory conditions, as well as proliferation, producing a great number of individuals for testing in complex experimental designs and without tight regulatory requirements."}
{"_id": "Radiology$$$8eb4eab5-403c-427f-9daa-019de44308a2", "text": "Aquatic invertebrates as benthic organisms and invertebrates living burrowed in soils or dwelling at the surface are among the group of organisms that may receive the highest radiation doses, since these environmental compartments are relevant environmental sinks of radionuclides. The mechanisms of action and the subsequent effects of ionizing radiation in invertebrates have been addressed mainly since the seventies, with a limited number of species, through laboratorial exposures to gamma radiation of single species, frequently at high-dose rates, with few environmental relevance for chronic exposure scenarios [98]. Real conditions include exposures to industrial radionuclides in areas affected by nuclear accidents, nuclear power plants, or in nuclear test sites, as well as through exposures to natural occurring radionuclides (NORs), as those found in uranium mining areas. In the later areas, the effects of radionuclides, mainly alpha-emitters, cannot be distinguished from that of metals, also present at high levels in the affected environmental matrices. The same difficulty exists in areas of nuclear accidents as the Chernobyl exclusion zone, where the release of different artificial radionuclides has occurred, although data available for activity concentrations in biota are almost limited to 90Sr, 137Cs, and some few other radionuclides [38]."}
{"_id": "Radiology$$$6ab8e046-db5f-4730-afaa-c25cea546c3b", "text": "Invertebrates are among the least sensitive organisms to ionizing radiation [62, 99]. Cassidy and co-authors [100] suggested that the reasons for these differences in sensitivity, between organisms of different taxonomic groups, may  include differences in DNA content, DNA repairing processes, and kinetics of cell cycle, within other aspects. The doses able to cause mortality or decrease life span are species dependent and frequently very high: as for example above 1000 Gy for Caenorhabditis elegans [101]. However, differences in sensitivity of different life stages were also reported (i.e., Johnson and Hartman [101]), with reproduction effects being seen at much lower doses (i.e., 4 mG/h for earthworm)."}
{"_id": "Radiology$$$1f3df812-ebd7-45a0-96a3-328704670aef", "text": "Ionizing radiation hormesis has been reported in a number of studies with invertebrates (dipterans, coleoptera), exposed to low doses from different sources (X-ray, gamma radiation, 137Cs) (see review by Vaiserman et al. [97]). Reduced mortality rates and long-life spans were highly dependent on the exposure conditions [102], for example, life-extended effects were only observed in house flies (Musca domestica) reared in groups, and thus under high locomotor activity and exposed to a 10 Gy dose. Several hypotheses were then postulated and tested to unveil the factors responsible for modulating radiation hormesis, using Drosophila melanogaster, as model species, as for example:  increased IR resistance, IR-induced sterility in females, apoptosis induction and changes in DNA repair genes and life-stage differential sensitivity were some of the proposals [97] and references quoted herein. X-ray irradiation of D. melanogaster eggs with 0.75\u00a0Gy, decreased the amount of DNA segments, by cleavage of S1 nuclease sensitive sites (<3\u00a0kb), resulting in a great DNA stability, changing the repair and/or transcription processes and thus affecting lifespan and the resistance of adults to IR [103]. Based on all the studies conducted, the radiation hormesis model proposes that the exposure to low doses of IR could induce several adaptive responses, which in turn will prevent environmental-induced health effects [97]."}
{"_id": "Radiology$$$c5645d6b-5fd5-4335-8538-873717fc1cc5", "text": "At the cellular level, oxidative stress and the activation of oxidative stress-response mechanisms have been reported as the major indirect consequences of exposures to IR of aquatic and terrestrial invertebrates. Won and Lee [104] observed a significant increase in the activation of several enzymes, as for example, superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) and glutathione-S-transferase (GST) in the marine copepod Paracyclopina nana, exposed to gamma radiation doses equal or greater than 10 Gy (at a dose rate of 2\u00a0Gy/min). However, in this study, no data from additional molecular parameters, as those related with DNA damage or lipid peroxidation were provided, preventing us to infer if the activation of these enzymes was sufficient or not to prevent cellular damages. A dose-dependent increase in ROS was also recorded in another marine invertebrate species, as for example, the copepod Tigriopus japonicus and the rotifer Brachionus koreanus, for a range of concentrations from 50 to 200 Gy (irradiated at a dose rate of 2\u00a0Gy/min) [105, 106]. Concomitantly, the antioxidant response system was activated, and GST and GR activities were significantly increased for the copepod, while for the rotifer the same was recorded for the activity of GST. A cellular and lipid peroxidation (LPO)-related ROS was dose-dependent overproduction was also recorded in the freshwater cladoceran Daphnia magna after 8-day exposure to a dose rate of 100\u00a0mGy/h of gamma radiation. The overproduction of mitochondrial ROS was significantly enhanced at 40 and 100\u00a0mGy/h [1]. Dose rates of the same order of magnitude (10.7 and 42.9\u00a0mGy/h) were also able to cause lipid peroxidation in daphnids, after both 24 and 48\u00a0h of exposure. However, at the highest dose rate tested (106\u00a0mGy/h), the same effect was only registered after 48\u00a0h of exposure [55]. This observation, which was consistent with other studies (i.e., Fuller et al. [107]), gave rise to the hypothesis that ROS may also act as a signaling molecule, requiring a certain level within the cell to activate antioxidant defense mechanisms. Neutral lipid catabolism was also observed in the nematode C. elegans independently of the different doses and dose rates tested (7 and 52\u00a0mGy/h), and this effect was associated with a reduced longevity, as lipid homeostasis is responsible for endocrine signaling of longevity [108]. In fact, the up-regulation of different hormone receptors in daphnids was suggested as a signal of disruption of normal endocrine functions in response to IR exposure [1]."}
{"_id": "Radiology$$$ed742155-89ed-4e87-ac06-8e2058643e55", "text": "Regarding the interaction of ROS with proteins, Won and Lee [104] registered an upregulation of the hsp gene in the copepod P. nana, which was interpreted as being related with a possible response to protect key proteins (probably those involved in DNA repair signaling pathways) through the synthesis of chaperones.4 In the cascade of events promoted by ionizing radiation, Song and co-authors [1] recorded an enhanced expression of the Ube2 gene in D. magna, involved in the degradation of proteins, suggesting the activation of a mechanism responsible for the elimination of proteins damaged by ROS. A highly efficient antioxidant protection system may not be able to protect DNA from damage but it can delay protein carbonylation.5 Therefore, protecting cellular components involved in the repair of DNA double-strand breaks (DSB) was proposed as a main factor to explain the resistance of bdelloid rotifers to ionizing radiation [109]."}
{"_id": "Radiology$$$3d60905f-8607-41a5-b215-65eb5c73554a", "text": "DNA damage is a frequently reported effect in invertebrates exposed to IR from different sources. These damages can be either caused indirectly, mediated by ROS, or by direct deposition of radiation energy in DNA [1, 104]. In response to DNA damage, the expression of genes related with DNA repair systems (e.g., p53, RAD50, Mre11 coding for the DSB repair protein, Ku70, Ku80, and DNA-PK) was recorded in different invertebrate species, frequently with a non-monotonic response, but always with a significant and differential expression at low and higher dose rates (at 4, 100, and 200 mG/h) [1, 55, 104, 106]. In summary, genes involved in nucleotide excision, base excision, homologous recombinant, and non-homologous recombination repair pathways have been found to be all involved in the response of cells to IR. At high IR dose/dose rates, ROS may also induce DNA methylation,6 leading to the accumulation of damages, by silencing some genes. Song et al. [1] recorded an enhanced expression of DNA (cytosine-5)-methyltransferase 1 (Dnmt1), DNA cytosine-5 methyltransferase 3A2 (Dnmt3a2) genes, involved in maintenance of DNA methylation and in de novo DNA methylation, respectively, in D. magna."}
{"_id": "Radiology$$$686e5cf3-7d43-484f-9ba1-17e3a0fe3470", "text": "The disruption of energy metabolism under the exposure to IR is another reported effect at the cellular level, once again in different invertebrate species [1, 55]. Direct interference with proteins of the electron transport chain, mitochondria ultrastructural changes caused by ROS and modulation of oxidative phosphorylation are within some of the mechanisms proposed, based on observations made in D. magna exposed to gamma radiation [55]. Genes encoding NADH dehydrogenase (Nd), succinate dehydrogenase subunit A (SdhA) of complex II, different cytochrome oxidase subunits (COX1, COX2, and COX3), cytochrome c oxidase copper chaperone (COX17) of complex IV and ATP synthase subunit mitochondrial (sun) of complex 4 were some of the genes involved in the electron transport chain found to be suppressed by gamma radiation [55]. At the end of the cascade of events triggered by gamma-radiation, the regulation of different apoptotic signaling pathways was observed in freshwater Cladocera, in parallel with DNA damage and regulation of repair mechanisms, cell cycle disruption and mitochondrial dysfunction [1, 55]. Although not significant, an increasing trend in apoptotic cell death with increasing dose rates of radiation was recorded in crustaceans, namely daphnids and in the Norway lobster (Nephrops norvegicus) cell cultures exposed to 60Co gamma-radiation [110]. Apoptosis is a downstream event, to oxidative stress and DNA damage occurrences, that is activated to eliminate damaged cells in an ultimate effort for protecting organisms."}
{"_id": "Radiology$$$35aba2b5-b716-4cf4-ac28-7bc30c142513", "text": "The effects of ionizing radiation at the population level are poorly documented and it has been demonstrated that equal levels of effect at similar individual endpoints (e.g., growth or reproduction) may have different impacts on population dynamics [111]. Furthermore, it is still difficult to link the results of biomarkers of oxidative stress and genotoxic damage with phenotypic consequences (changes in morphology, growth, reproductive output, and viability of offspring) [112]. Data available allowed a tentative hierarchization of individual endpoints based on their radiosensitivity: mutation\u00a0>\u00a0reproduction\u00a0> morbidity and mortality [113]. One step forward, modeling population responses it was shown that they differed depending on the affected individual reproduction endpoint (juvenile or adult survival, delay in maturity, or reduction in fecundity) [114]. Hatching was shown to be the most sensitive endpoint to chronic exposures to gamma radiation for aquatic invertebrates (EDR107 of 830\u00a0mGy/h for the polychaete worm Neanthes arenaceodentata) and fecundity for terrestrial invertebrates (EDR10 of 2600\u00a0mGy/h for Porcellio scaber). These species displayed similar EDR10 values for individual and population level endpoints (net reproduction rate). This was observed for the species that had a particularly sensitive individual endpoint."}
{"_id": "Radiology$$$8b8e801c-92e9-4ab7-b987-579f3093747b", "text": "The most concerning consequences of genotoxicity, that may support inferences about potential effects on natural populations, are those that affect the reproductive fitness of organisms. Reproduction has shown to be the most sensitive parameter in invertebrates (collembolans, worms, tardigrades, chironomids, and polychaetes) exposed to IR, when compared with survival or other endpoints at the individual level [109, 115\u2013120]. It was suggested that the decrease in fecundity is not caused by the number of DNA DSB, but by the inactivation of the DNA repair systems [109]. In fact the incomparable ability of bdelloid rotifers to remain fertile, after extensive DNA damage, was attributed to high efficiency of repair systems and to mechanisms that protect proteins of these repair systems [121]. These authors also associated the resistance to ionizing radiation of these organisms with their resistance to desiccation resulting from their adaptation to ephemeral ponds. Desiccation, similarly to radiation, increases ROS production and DNA breakage."}
{"_id": "Radiology$$$2f396b4c-894f-4701-a41c-c935622fa192", "text": "Harrison et al. [112, 122], also working with the polychaeta N. arenaceodentata, hypothesized that chromosomal aberrations caused by gamma radiation doses of 2.0 and 4.0 Gy were responsible for gametal cell death and subsequent decreases in brood sizes of this species. In opposition, under laboratory conditions, significant effects were recorded in sperm quality, but not on sperm numbers, of males of the crustacean Echinogammarus marinus chronically exposed to doses rates of 1 and 10\u00a0mGy/day provided by the betta emitter 32P, for two weeks. Significant DNA damage was recorded in spermatozoa cells only at the highest dose rate. Furthermore, only a weak correlation was found between sperm quality parameters, fecundity, and embryo parameters analyzed [107]. Effects on ovary structure and oocyte development were also reported in the freshwater cladoceran D. magna in response to exposure to 1 and 100\u00a0mGy/h gamma radiation, dose rates."}
{"_id": "Radiology$$$c1e7a07c-dc25-4f48-8f2f-b329cff92d1b", "text": "Another possible cause of reproduction impairment in invertebrates, under exposure to ionizing radiation, may be related with the allocation of energy to molecular response mechanisms (e.g., activation of antioxidant defense system, DNA repair mechanisms) rather than to reproduction, with consequences on the fecundity of organisms [117]."}
{"_id": "Radiology$$$76fec444-48a3-4788-bade-e203ce8e8936", "text": "An ED508 for reproduction of 21.9\u00a0Gy, one order of magnitude lower than that recorded for growth (144\u00a0Gy) was found for the collembolan Folsomia candida, under exposure to 137Cs gamma radiation at a constant dose rate of 8.3\u00a0Gy/min. Song et al. [1] also observed a non-monotonic reduction in the total number of offspring of the cladocera D. magna, concomitantly with no effects on survival, molting or ovulation frequency (at dose rates of 1 and 100\u00a0mGy/h). At the lowest dose, the effect on the cumulative reproduction output was mainly associated with an increase in the number of days needed to deliver four broods, while at the highest dose rate, the reproductive cycles were accelerated but the size of the broods was reduced. A similar observation was made by Parisot et al. [123] in the same organisms exposed to dose rates of 0.07\u201335.4\u00a0mGy/h of gamma-radiation, for 23\u00a0days. The same non-monotonic response was recorded D. magna representing 38 different genotypes collected in lakes located inside the Chernobyl exclusion zone with a range of dose rates between 0.1 and 181.2\u00a0mGy/h."}
{"_id": "Radiology$$$59d57226-24ff-4385-be3a-742edc8e0db1", "text": "In a study conducted by Alonzo and collaborators [111], the freshwater species D. magna and the terrestrial earthworm Eisenia fetida, two species with different life history strategies (short lived/parthenogenic versus more long-term life/sexually reproducing hermaphrodite, respectively) were selected: (1) to model population growth in response to individual effects caused by the exposure to IR and (2) to investigate populations susceptibility using two different models to take into account single generation and multiple generation exposures. It was shown that in daphnids, the population growth was 1.5-fold more sensitive to changes in fecundity than in mortality. Daphnids population growth was also highly affected by delays in reproduction. Earthworms\u2019 population growth was more sensitive to delays in reproduction, while effects in fecundity and mortality have a similar and lower impact on populations. Despite the different life strategies, the intrinsic rates of population increase were equivalent for both species, because the greater reproductive rate of daphnids is compensated by a shorter life span relative to earthworms."}
{"_id": "Radiology$$$4cb31b12-76cf-4304-881e-270ff87f309a", "text": "After disturbances of great magnitude, the recovery of natural populations of cladocera may rely on the banks of resting eggs in the sediments of lentic systems. These resting eggs if irradiated may have its performance compromised, affecting the dynamic of the natural populations. Zadereev et al. [124] observed that although doses up to 100 Gy (variable dose rates) did not affect the survival and hatching of resting eggs of Moina macrocopa, the size and the structure of populations initiated from resting eggs exposed to this highest dose of gamma-radiation, were affected. Therefore, subsequent effects on the dynamic of the populations of this cladocera may be expected in lakes with highly contaminated sediments."}
{"_id": "Radiology$$$99fe3a41-9da8-4ed4-8765-477e0ff80d61", "text": "Under a real scenario of radionuclides contamination, no correlation was found between different reproduction endpoints (proportion of breeding females, fecundity, brood mass, maternal body mass) of the crustacean Asellus aquaticus, sampled at different lakes in the Chernobyl affected area, with the gradient of dose rates between 0.064 and 27.1\u00a0mGy/h registered at these ecosystems [107]. Also, upscaling to populations and communities, Murphy et al. [125] focused on the diversity of littoral macroinvertebrates communities at eight natural lakes in Belarus, with a range of external dose rates from 0.066 to 10.22\u00a0mGy/h once again did not find any correlation between population endpoints (abundance, taxon richness, Shannon-Wiener diversity index, and the Berger-Parker dominance index) and the range of external dose rates registered in the sampled lakes. This study suggested that the IR dose rates recorded had no detectable effects on the littoral macroinvertebrate communities of these lakes."}
{"_id": "Radiology$$$4350c426-1d89-405a-ae82-4764cc2a44e8", "text": "Impacts on natural populations of invertebrates may be also caused by other mechanisms rather than those affecting gamete production, eggs viability, fecundity, or reproduction delays. For example, the exposure of fourth-instar nymphs to IR from a 137Cs source up to doses of 12 Gy (at a dose rate of 0.25\u00a0Gy/min) has shown to affect the acoustic signaling of male crickets (Acheta domesticus) and subsequently their ability to find mates, due to morphological changes in their wings [126]. In fact, few is known about other direct and indirect effects that may affect the fitness individuals, its biotic relationships, and subsequently the dynamics of natural populations and communities at IR contaminated scenarios, rather than those effects identified based on commonly used biomarkers. The complexity of the biotic interactions, as well as the role of dominant abiotic factors determines the type and the impact of the indirect effects on ecosystems, whose responses can be unpredictable [98]. In a birch forest in South Urals, the contamination of litter with 90Sr (doses reaching up 70\u00a0Gy) compromised the development of pupae of tachinid flies (Tachinid sp.). This accounted for an increased survival of the host caterpillars of the gypsy moth (Lymantria dispar dispar L.) with increasing IR levels [127] in Geras\u2019kin [98]. M\u00f8ller et al. [128] also linked the reduction in the set of fruits produced by trees and bushes, at the Chernobyl exclusion zone with the local reduction of pollinator insects. The role of other biotic factors in the radiosensitivity of invertebrates also needs to be investigated, as it may be relevant under specific environmental or industrial scenarios. It was shown that the ability of marine mussels (Mytilus galloprovincialis) to respond to genotoxic induced effects by tritiated water, released by cooling operations of nuclear power plants, was limited by enhanced temperatures [129]."}
{"_id": "Radiology$$$4a55ac8d-a9a4-4c07-8d8b-1bcc88dac5dc", "text": "Invertebrates also have a key role in several ecosystem functions, as, for example, the degradation of wood, organic matter, and nutrients recycling. Mousseau et al. [130] conducted a study in forest areas within the Chernobyl exclusion zone, at different distances of the nuclear plant and with levels of background radiation differing by several orders of magnitude (range 0.09\u2013240.25\u00a0mSv/h). A significant effect of background radiation in the mass loss of litter bags buried in the surface of the forest soils was registered. The mass loss of litter bags from the sites with high levels of background IR was 40% lower than that recorded at the sites with lower levels of radiation. However, no significant influence of the mesh size of litter bags was found, suggesting that decrease in the decomposition of litter at that site was not only caused by impacts on soil invertebrates\u2019 communities, but also on soil microbiome. Soil invertebrates\u2019 assemblages from pit falls and wood slices from the same area showed that the abundance of taxonomic groups displayed a different relationship with background radiation and with wood contamination with radionuclides, being positively, negatively, or not affected at all [131, 132]. This was consistent with a previous observation of a general loss of diversity in sub-surface and flying invertebrates with increasing concentration activities of 90Sr and 137Cs in the litter of forest sites within the Chernobyl exclusion zone [133], as well as by the apparent decrease in the feeding activity of these organisms measured by the bait-lamina test.9 However, such changes were not followed by changes in total biomass of organisms. These results suggest that chronic environmental exposures to IR may exert their effects on natural communities, through structure and functional diversity simplification, with possible impacts on ecosystem\u2019s functions."}
{"_id": "Radiology$$$4aa7a19d-6dd9-4329-abb5-49bf19647b65", "text": "In a first attempt to estimate risk limits for chronic g-radiation exposures, predicted no effect dose rates (PNEDR) of 10\u00a0mGy/h (0.24\u00a0mGy/day) for freshwater ecosystems and of 67\u00a0mGy/h (1.61\u00a0mGy/day) for terrestrial ecosystems were obtained, using assessment factors and species sensitivity distribution methods, respectively. The estimated values were found to be highly protective as they were about \u00d750 to \u00d7100 times higher than the upper bound of the range of natural background concentrations and of the lower dose rates causing effects at contaminated sites [134]. Later, and by applying an assessment factor (AF) of 3 to the HDR510 estimated for invertebrates, a PNEDR of 170\u00a0mGy/h for IR was obtained. However, and considering that no sufficient data was available for applying probabilistic methods to estimate PNEDR for specific groups of organisms or for environmental compartments, Garnier-Laplace et al. [135] derived a generic HDR5 from a species sensitivity distribution using data from controlled laboratorial chronic exposures to low dose rates of gamma-radiation, and applied an AF of 5, obtaining a PNEDR of 1.5 mG/h which was considered to be protective for the conditions found at Chernobyl exclusion zone."}
{"_id": "Radiology$$$d3077313-6be8-43f7-8700-2f11bae55726", "text": "Among all the vertebrates, mammals are organisms on which the effects of radiation exposure were most extensively studied in radiobiological experiments. Negative effects on these organisms, due to radiation exposure at high doses (i.e., 10\u201350\u00a0Gy), are primarily due to effects at the hematopoietic system and the gastro-intestinal mucosa [45, 46]. The time needed for death to occur varies widely within species. The dose of radiation needed to cause lethality, due to gastro-intestinal syndrome, to 50% of the exposed organisms (LD50) is approximately as follows for dog\u20148\u00a0Gy, mouse\u201412\u00a0Gy, rat\u201411\u00a0Gy, and rhesus monkey\u20149 Gy [46]. However, these values were estimated for particular species of these organisms, so there can be wide variations for other species. These variations are normally related with specific intestinal morphologies, which are related to diet (i.e., herbivores, carnivores, and omnivores). Regarding bone marrow damage, the weight of the animals receiving the dose appears to have a significant role in the bone marrow radioresistance, being weight inversely proportional to radiation sensitivity, as LD50 values are greater for smaller mammals (6\u201310 Gy approximately) than for larger ones (1.2\u20133.9\u00a0Gy). A reduction in life span is also related to the type of radiation to which animals are exposed, being high LET radiation more effective than low LET radiation. Also, acute exposures are substantially more effective by a factor of 7 in causing mortality than chronic exposures [46]. Significant life span shortening occurred in dogs and mice exposed to low LET radiation (gamma radiation) at dose rates between 100 and 1000\u00a0mGy/h and the same happened for mice exposed to neutrons (high LET radiation) at the same dose rates [136]. In general, a significant reduction in life span of several mammal species was observed at dose rates higher than 1000\u00a0mGy/h [50, 136, 137]. Chronic exposures of less than 100\u00a0mGy/h have a low probability of inducing significant effects on most terrestrial organisms [45, 46, 136]. Particularly, a dose rate of less than 40\u00a0mGy/h has a low probability of inducing effects on the fertility, fecundity, and the production of viable offspring of a mammalian population [45]. This is true for low LET radiation, however for high LET radiation, this dose rate value is lower, as this type of radiation has a much higher relative biological effectiveness (RBE) [45]. An experiment performed in mice irradiated with neutrons, at dose rates lower than 100\u00a0mGy/h for at least 475\u00a0days, led to a significant increase of mortality in mice in comparison with the control [136]."}
{"_id": "Radiology$$$df8c31c2-1f43-4aa2-932d-6826cfb9ed54", "text": "Reproduction is a more radiosensitive parameter than mortality, and effects of radiation may appear at radiation levels that apparently do not induce other observable responses. The magnitude of the effects depended also on the developmental stage in which the animal was irradiated [136]. A good example are mice, as the LD50 occurs at a radiation dose approximately between 6 and 10\u00a0Gy; however, at a radiation dose of 0.08\u00a0Gy, the production of oocytes was reduced to 50% in newborn mice (the most radiosensitive stage in mice) [45, 46]. However, this does not necessarily mean that there will be a decline in fecundity, since mice produce much more oocytes than the amount effectively used for reproduction, but there could be a reduction in the offspring [46]. In adult males, fertility is temporarily impaired after a 10 Gy exposure; however, in young mice (3\u20135\u00a0days old), it can cause permanent sterility. Mice in the second week after birth are also especially sensitive to the detrimental effects of radiation on reproduction [136]. The differences between males and females are mostly a consequence of the differences in the gametogenesis process. There are also differences between species, being mice one of the least radioresistant. Chronic irradiation affects mainly the time needed for oogonial cell division and the size of stem cell pool [46]. In males, the spermatogenic process is maintained, although at lower levels than unexposed organisms [46]."}
{"_id": "Radiology$$$a44aa53a-ec7d-4f48-a0d9-7a80d4e8bb20", "text": "The developing embryo is particularly sensitive to radiation, due to the high number of cells proliferating, reducing fecundity and postnatal survival, potentially influencing population size [46]. Acute radiation exposure, before the implantation of the embryo, causes its early death and can also cause post implantation and postnatal death [46]. This has a good correlation with the occurrence of DNA damage in the form of chromosome aberrations in the blastomeres (cells that result from the cleavage during the early development of the embryo) [46]. Radiosensitivity is strongly influenced by cell cycle stages and mitotic cycle in the very early developmental stages [46]. During organogenesis, the most typical response to acute radiation is the occurrence of malformations (teratogenic effects), which can occur during embryonic and fetal growth and may or may not be fatal. The occurrence of teratogenic effects in a particular organ is related to a high level of cell proliferation in the precursor tissue [46]. Although this has been observed for the several species studied (mouse, hamster, cattle, pig, monkey rabbit, etc.), the responses to specific radiation doses will depend on the species and on its developmental stage at the time of exposure [46]. There are not many studies on the effects of chronic radiation exposure during organogenesis, however a study performed on mice showed doses of 0.01\u00a0Gy/day in pregnant mice 6\u20139\u00a0days after conception induce a significant impairment of the offspring\u2019s learning ability [46]. Also, dose rates of 420\u00a0mGy/h reduced neonatal brain weight, with unknown effect at the functional and behavioral levels [45]."}
{"_id": "Radiology$$$5dccdbbc-56a9-41bc-9aa6-ddcd2dbcc29a", "text": "A direct relationship between DNA damage and radiation dose is expected at high doses of radiation; however below 100\u00a0mGy, it is not clear. In reindeer, a tenfold increase in the number of chromosome aberrations was observed at dose rates between 100 and 1000\u00a0mGy/h [136]. For rodent species acutely exposed to low LET radiation, mutations in the form of reciprocal translocations (exchange of DNA between homologous chromosomes) occur in stem cell spermatogonia when organisms are exposed to between 0.01 and 0.03 Gy at total doses from 3 Gy [46]. High LET radiation exposure (in the form of alpha particles emitted by 239Pu), delivered at a dose rate of 36\u00a0mGy/h significantly increased the occurrence of translocations and acentric fragments (chromosome fragments without a centromere) in spermatogonia and spermatocytes, respectively [46]. In primates, the dose interval is 0.01\u20130.078 Gy at doses from 1 Gy [46]. Translocations, ring chromosomes (aberrant chromosomes whose ends were broken and then fused together to form a ring) and dicentric chromosomes (the result of two broken chromosomes that fused together) are used for radiation dosimetry in human and non-human biota for a long time, as their frequency increases with radiation dose [138]. In rodents, this is more easily seen at total absorbed doses higher than 0.5\u00a0Gy, suggesting that their use as a biomarker of radiation exposure is more effective at high dose exposure than at low doses (below 100\u00a0mGy). Regarding carcinogenicity, there is a wide variation in the sensitivity for tumor formation among tissues and species. The induction of cancer, even at high radiation exposure doses (>100\u00a0mGy) will also vary according to the age of exposure. Dogs exposed to doses higher than 7 Gy showed soft tissue cancers when exposed in utero but not when exposed as young adults [46]. In rodent species, there were limited carcinogenic effects on animals that were exposed to doses between 0.1 and 1 Gy [138]."}
{"_id": "Radiology$$$5d82cb6a-7705-4e56-a7a8-9ec6316d317d", "text": "The effects of radiation exposure in birds are apparently similar to the ones observed in small mammals [45]. The LD50 for wild birds is in the same range as small mammals (5\u201312\u00a0Gy). For poultry, the LD50 determined experimentally for mortality is of 7\u201311 Gy in 3\u20134-day-old individuals when irradiation lasts for less than 1\u00a0h and of 12\u201320 Gy when irradiated for 24\u00a0h. Egg production is affected in white leghorn chicken at a total absorbed dose of 4\u20138 Gy and at higher doses, effects are more severe and long lasting [45]. A limited number of experiments performed in artificially incubated chicken embryos showed a LD50 of 12\u201313\u00a0Gy, which apparently indicates a higher radioresistance than adults [46]. In white leghorn chickens, eggs hatchability is affected at a total absorbed dose of 8\u00a0Gy, but the progeny is unaffected [48]. The International Commission on Radiation Protection also reported dose ranges for which long-term effects on developing embryos were reported (100\u20131000 mGy/day), reduced reproductive success (1\u201310 mGy/day) and increased morbidity (10\u2013100\u00a0mGy/day) [139]. Recently, it was reported a decrease in species abundance at a dose range of (from 0.3 to 97 \u03bcGy/h) in the Fukushima exclusion zone, which is consistent with the dose ranges reported for increased morbidity and decreased reproductive success [140]. The existing knowledge on DNA damage/alterations on birds exposed to ionizing radiation results from the evaluation of effects of radioactive environmental contamination resulting from the Fukushima and Chernobyl accidents [141]."}
{"_id": "Radiology$$$31fefffb-034e-40bb-8129-a50674d00afd", "text": "The information gathered so far for reptiles and amphibians suggest that their radiosensitivity is similar to that of mammals and birds. The LD50 values recorded for frogs, salamanders, turtles and snakes vary between 2 and 24 Gy [46]. The main cause of death identified was damage to the hematopoietic system [46]. In two separate experiments performed on lizards, two very different LD50 doses ranges were obtained (10\u201312\u00a0and 17\u201322\u00a0Gy). The possible reasons for this marked difference are associated with the fact that these values may vary according to radiation type and quality, the dose rate to which the organisms were exposed and their maintenance conditions at the laboratory [46]. An acute exposure to 50 Gy caused temporary sterility in males, but recovery was well in process after 48\u00a0days post irradiation and irradiation of gonads in males and females to an absorbed dose of 4.5 Gy leads to a substantial decrease in the production of offspring [46]."}
{"_id": "Radiology$$$9de39ae6-5a2f-4170-85b5-1135d001dc70", "text": "Regarding amphibians, different life stages showed different radiosensitivities. For adult toads, the LD50 value is of 24\u00a0Gy, for juveniles it is of 10 Gy and for tadpoles it is of 17 Gy [46, 139]. The life stage more sensitive to radiation exposure was the fertilized egg with an LD50/40 (LD50 after 40\u00a0days of exposure) of 0.6 Gy [33]. There is evidence that the exposure of male toads to 3\u201320 Gy caused a reduced survival and increased induction of abnormalities to the offspring [46, 139]. Although these LD50 values for amphibians seem slightly higher than the ones recorded for mammals, time after exposure optimal for the recording of LD50 values seem to be an important factor [33]. Reptiles and amphibians are poikilothermic organisms; therefore, their metabolism is quite variable and different from mammals and birds [33]. A study performed on 4 species of amphibians showed that if the assay period was extended a decrease in the LD50 to values that ranged between 0.8 and 7 Gy would be recorded [33]."}
{"_id": "Radiology$$$fee41c2f-869f-4f96-9627-6d0ecf870a9e", "text": "Chronic irradiation exposure (5.5\u00a0years duration) of common side blotched lizard, western whiptail, long nosed leopard lizard and long nosed lizard showed that at ranges from 285 to 570 \u03bcGy/h, radiation exposure caused lack of reproduction, female ovaries regression and some degree of male sterilization [46]."}
{"_id": "Radiology$$$e568d6ac-ffb5-4f3e-b62f-7b370f48c050", "text": "Regarding the induction of DNA damage, it was observed by Ulsh and co-authors [142] that the exposure of turtles from the species Trachemys scripta to 0\u20138 Gy 137Cs gamma radiation, given at a dose rate of 0.55\u00a0Gy/h induced the occurrence of significant levels of chromosome translocations in lymphocytes. Studies on the induction of DNA alterations in amphibians and reptiles have been performed in Fukushima and Chernobyl exclusion zones, as well as in areas contaminated with NORM."}
{"_id": "Radiology$$$b51a94af-1fed-4b68-aa10-35eae0bff2d0", "text": "Among non-mammalian aquatic organisms, fish are the most sensitive to the exposure to ionizing radiation [45, 46]. Although these organisms are also poikilothermic (as amphibians and reptiles), and therefore, apparently more radioresistant than mammals, there is a substantial overlap in radiosensitivities [46]. Until now, there is no substantial data on effects of ionizing radiation on marine mammals, however, there is no reason to believe that their radiosensitivity is substantially different from that of terrestrial mammals. Data on acute exposures exist mainly for bony and freshwater fishes, with a small number of studies on cartilaginous and marine and anadromous species."}
{"_id": "Radiology$$$741ebbe0-1152-4b10-bff3-d2c92c71140d", "text": "The LD50 determined for six marine species after 40\u201350\u00a0days of exposure was of 9\u201323 Gy [46, 139]. Fish developing embryos are, however, more sensitive than adults, as for silver salmon their LD50 after 50\u00a0days of exposure is of 0.30 Gy at hatching and 0.16 Gy at a post-hatching larval stage of 90\u00a0days [46]. A study performed on sharks (Triakis scyllium and Heterodontus japonicus) exposed to 20 Gy showed that mortality occurred after 20\u00a0days of exposure, due to hematopoietic and gastrointestinal damage [33]. This suggests that the radiosensitivity of cartilaginous fish may be similar to that of teleost fish."}
{"_id": "Radiology$$$5fc0fca7-e68c-46a9-8d98-8c3cf678764c", "text": "Regarding reproduction, an acute exposure to 10 Gy reduced the total number of germ cells at all developmental stages of medaka fish (Oryzias latipes) [46]. A similar radiosensitivity was found in rainbow trout, with an induction of more than 50% sterility in organisms exposed late in embryonic development [46]. This leads to the conclusion that as in mammals, the newly hatched fry and the primordial gonads in fish embryos are more sensitive to the acute radiation exposure than in adult fish [46]. Irradiation of mature medaka fish at acute doses of 5\u201310 Gy only induced temporary sterility, being completely recovered at 60\u00a0days after irradiation [46]. On the other hand, chronic irradiation of males from the fish species Ameca splendens for 5.4\u00a0days at a dose rate from 137Cs gamma rays of 7300\u00a0mGy/h disrupted spermatogenesis and render the animals sterile at an accumulated dose of 9.7 Gy (8\u00a0weeks of exposure) [46]. There was 60\u201370% recovery, 236\u00a0days after irradiation [46]. Another freshwater fish, the guppy (Poecilia reticulata), when exposed to gamma dose rates from 1700 to 13,000\u00a0mGy/h showed a significant reduction in fecundity, but no negative effects on survival and sex ratio, as well as no significant higher incidence of abnormalities in the offspring were observed [33, 136]. The marine fishes Pleuronectes platessa and the eelpout (Zoarces viviparus) exposed to 240 and 2000\u00a0mGy/h gamma radiation, respectively, showed a significant reduction of testes when compared to the control [136]."}
{"_id": "Radiology$$$34bc873f-4af7-45da-8170-ab0667d68e24", "text": "There are some findings also on the effects of the exposure to ionizing radiation in the immune system of these organisms. A significant reduction in the humoral immune response in the rainbow trout (Oncorhynchus mykiss) exposed to tritium beta-particles for 20\u00a0days at a dose rate as low as 8.3\u201383\u00a0mGy/h during embryogenesis was evidenced through a reduction in antibody titer following a specific challenge [46]."}
{"_id": "Radiology$$$98846c60-d655-4fff-b3ed-26e66a7d72a9", "text": "Regarding DNA damage there are very few studies on which some conclusion can be taken on this matter. On a study on medaka fish, at larval stages, there was a significant induction of vertebral anomalies after irradiation at dose rates from 137Cs gamma rays higher than 18,000\u00a0mGy/h and also to beta particles from 3H at dose rates higher than 35,000\u00a0mGy/h [46]. There is also a report on the occurrence of minor morphological abnormalities in the operculum of salmons exposed to a gamma radiation dose rate of 200\u00a0mGy/h that may affect latter survival [136]."}
{"_id": "Radiology$$$39e5837c-27b0-41fc-b97d-c14065c37fcd", "text": "Anthropogenic activities of concern related to the environmental release of natural uranium isotopes (mainly 238U and 235U) and other radionuclides from their decay chains, namely 226Ra and 223Ra, 222Rn, and 210Po, include mainly the production of phosphate fertilizers, uranium mining and milling and the incorrect disposal of tailings, uranium conversion and enrichment, the production of uranium fuel, production of coal, oil and gas, extraction of rare earths, extraction and purification of water, extraction of minerals for building materials and the generation of geothermal energy [3, 143]. All of these industrial activities increase the concentration of these elements in all environmental matrices, thereby posing a risk to human and non-human biota as many of them have not been regulated for NORM release [3, 143]. Another important issue is the fact that the contaminated areas that result from these anthropogenic activities do not only present high levels of certain natural radionuclides, like 226Ra, 222Rn, and 210Po but also other important stressors, namely metals like manganese, zinc, iron, aluminum, etc. [143]. These are usually multiple exposure scenarios, which contain several kinds of contaminants that may act synergistically and increase the risk of the occurrence of biological effects on human and non-human biota and even of modifying the susceptibility of cells/organisms to the biological effects of ionizing radiation exposure [144]."}
{"_id": "Radiology$$$a93d194f-f015-4038-ac60-4703ebd9437d", "text": "The accumulation of small amounts of radionuclides and metal over long periods is translated in chronic exposure to radiation. Naturally contaminated sites harbor a diversity of microbial species that become resistant or tolerant to these contaminants by bioaccumulating radionuclides and metals either by biosorption to their cell surfaces and biomolecules or by internalization into their cells. Briefly, under environmental conditions, chronic IR effects are very complex, particularly when compared to those from laboratory exposures because (1) radiation emitted by the different radionuclides present has different biological effects, (2) radiation from the same location is absorbed differently by different microorganisms, (3) abiotic factors (e.g., temperature, nutrients, pH, other stressors) are present and can interfere with radiation, (4) cooperation/interaction between microbial communities, including diversity and/or abundance can all be modulated by radiation [62]. Regarding uranium, probably the most well studied radionuclide, and for which a lot of information is available, interaction with microbial cells involving solubility by biomineralization (bioprecipitation) depends on all the above factors and also on the presence of affinity groups generated by microorganisms\u2019 cell metabolism, like hydroxides, phosphates, and carbonates. Uranium toxicity is both chemical and radiological. In the environment, uranium exists in its reduced insoluble form U(IV), and/or the oxidized form U(VI), which is soluble and toxic. Microorganisms interact with uranium by changing its redox state, aerobically, through oxidation (biolixiviation), or anaerobically by reduction. In order to do that, microorganisms need to be highly tolerant to uranium and to radiation. Other processes of microbial interaction with metals, involve biosorption, where contaminants passively concentrate through binding to cell structure constituents (e.g., lipopolysaccharides, teichoic acids, peptidoglycan), and biomineralization, which leads to the formation of biominerals using organic phosphate sources and phosphatases."}
{"_id": "Radiology$$$fe2f6e93-d37d-427b-841e-7e9880fc82d8", "text": "Unless disturbance occurs, NORM sites have a characteristic microbiome, which is specific for a given site, but may share common microbial genera and species, regardless of location and/or chemical contamination. It includes nitrate-reducing bacteria that tolerate acidic and low-nutrient conditions, while being highly resistant to metals. Members of the Proteobacteria (Alpha-, Beta-, Delta- and Gamma- proteobacteria), Acidobacteria, Actinobacteria, Bacteroidetes, and Firmicutes are generally associated with uranium transformation and are therefore found in these environments. Most represented bacterial genus include Geobacter, Thiobacillus, Arthrobacter, Bacillus, Actinobacteria, Desulfovibrio, and Microbacterium. Most of the studies are focused on bacteria and bacterial communities. Although little information exists regarding fungi, they are particularly resistant to radiation and thus play a role in the process of detoxification of radionuclides. For instance, an isolate of the genus Paecilomyces, was found to detoxify U(VI) through bioprecipitation of the metal, and the reduction was promoted by phosphate. Also, the yeast S. cerevisiae was able to reduce U(VI) toxicity by biomineralization [60]."}
{"_id": "Radiology$$$7ec204e1-dbc3-4ec4-8c30-2bd6fb072831", "text": "Accordingly, the survival, abundance, and maintenance of a given species or community diversity depend on its adaptability to the existing conditions. Furthermore, several studies suggest that in those radionuclide-rich natural sites, resistance to high levels of chronic IR may occur among taxa that tolerate a wide range of environmental conditions and, therefore, have an advantage over other more sensitive species [62]."}
{"_id": "Radiology$$$3a00ee19-eca3-4ba5-aa2e-890c679883c2", "text": "There have been some studies in aquatic organisms, namely in Daphnia magna, Daphnia longispina, and Moinodaphnia macleayi at NORM sites [145, 146]. When testing several percentages of a uranium mine effluent containing metals and radionuclides from 238U and 235U decay chains, the Antunes et al. [145] study recorded an EC5011 for daphnids immobilization at 50.4% for D. magna and at 28.4% for D. longispina, showing that D. magna was less sensitive than D. longispina. However, regarding fertility, D. magna was more sensitive than D. longispina, as this last species did not show significant effects in the offspring produced at effluent concentrations lower than 30.38%. Regarding M. macleayi, when a natural population of these organisms, living adjacent to a uranium mine in Australia, was challenged with a concentration of uranium ranging from 0 to 700\u00a0\u03bcg/L, it was shown that this population comparing to other populations tested, was the one that presented the highest sensitivity as it evidenced the lowest NOECs and LOECs.12 It was shown that although this population lived in a water containing already considerable amounts of uranium, there was no tolerance to higher levels of uranium, when compared to the other tested populations. This probably shows that it was an already very stressed population that suffered \u201cgenetic erosion\u201d [147] and because of that, it had lower capacity to deal with additional stresses, such as a single high dose of uranium."}
{"_id": "Radiology$$$f7de3289-b217-45da-8470-ac130795a5fe", "text": "When D. magna was exposed to uranium and to a uranium mine effluent [148, 149], significant genotoxic effects (DNA strand breaks) were detected in neonates and <5\u00a0days old daphnids after exposure to 55.3\u00a0\u03bcg/L of uranium and 2% of a uranium mine effluent. Moreover, in this same study, bystander effects, in the form of DNA damage, were detected in unexposed organisms when placed in contact with organisms directly exposed to uranium and to uranium mine effluent. In another paper [149], published by the same authors, on a transgenerational study performed on D. magna exposed to the same concentrations of uranium and uranium mine effluent as the study previously referred, it was observed that DNA damage was transmitted only to the first broods of the exposed organisms. By the third brood, DNA damage was no longer detected. This study showed that although short-term exposure to low concentrations of uranium and uranium mine effluent induces DNA damage to exposed organisms, it seems that it was not enough to significantly affect life history traits of D. magna populations in a long-term scenario. Nevertheless, the interpretation of these results is limited to the response observed for the endpoints here analyzed (DNA strand breaks). As such, other endpoints for genotoxicity assessment (i.e., mutation detection) and also the analyses of the epigenome of these organisms should be performed, as these molecular changes do not reflect a loss of DNA\u2019s structural integrity [149]."}
{"_id": "Radiology$$$f814c25c-926c-41ba-9bd6-779bc2043868", "text": "As for terrestrial invertebrates, most of the studies conducted so far were on the annelid Eisenia andrei [150\u2013155]. Gene expression alterations were reported in earthworms exposed to sludge from a uranium mine decantation pond. These genes were mainly related with metabolism, oxidoreductase activity, redox homeostasis, and response to chemical stimulus and stress [152]. In these studies, the occurrence of DNA damage in the form of DNA strand breaks and changes in cell\u2019s DNA content in exposed organisms was also detected. Alterations in earthworm\u2019s immune system were also reported, in terms of the frequency of each cell compartment, as it was observed a decrease in the number of effector cells (amebocytes) and an increase of the cells responsible for the maintenance of the organism\u2019s homeostasis (eleocytes) [153, 154]. In parallel with a significant bioaccumulation of metals and radionuclides from uranium\u2019s decay chain (238U, 234U, 235U, 226Ra, 230Th, and 210Pb), it was also observed a significant decrease in earthworms\u2019 biomass, a reproduction inhibition, and significant histological alterations, namely in earthworm\u2019s body wall (epidermis, circular, and longitudinal muscles) and gastrointestinal tract (chloragogenous tissue and intestinal epithelium) [153\u2013155]."}
{"_id": "Radiology$$$d1cbdc2d-e973-496e-9ebe-fd7de7f62923", "text": "Under a real scenario of contamination, all of these effects may explain the lower biodiversity of soils contaminated with NORM, and the subsequent loss of their functions, if the contamination is perceived by the organisms. By using an avoidance assay (a standard ecotoxicological assay), to study earthworms\u2019 behavioral responses to soils collected in a uranium mine area, it was shown that earthworms actively avoided several contaminated soils. Earthworm\u2019s avoidance responses allowed it to discriminate highly to moderately toxic soils. On the other hand, on another study published by the same authors, using the analyses of oxidative stress enzymatic biomarkers (catalase, glutathione peroxidase) and lipid peroxidation biomarkers (through the quantification of thiobarbituric acid reactive substances), in earthworms exposed to soils nearby a uranium mine, showed no response for none of the biomarkers analyzed [150]."}
{"_id": "Radiology$$$0a2bd7be-eb5e-4595-a834-8d5d54043843", "text": "Although there have been a wide number of studies performed on the effects of gamma radiation exposure on vertebrates, very few were performed so far for NORM exposure. Regarding aquatic vertebrates, fish have been the most used model organisms. On a study performed in former uranium mines from the Limousin region of France, where Rutilus rutilus specimens were caged on a pond contaminated with NORM and metals, immune, oxidative stress, biotransformation, neurotoxicity, and physiological parameters were measured [156]. The results obtained showed a stimulation of the immune parameters, the occurrence of oxidative stress and a decrease of acetyl choline esterase-AChE in the fish caged in the contaminated pond [156]. Zebrafish (Danio rerio) specimens exposed to uranium mill tailings leaching solution also showed alterations for the oxidative stress biomarkers used (superoxide dismutase\u2014SOD, catalase\u2014CAT, malondialdehyde\u2014MDA and Na+\u2013K+\u2013ATPase) but specially for Na+\u2013K+\u2013ATPase and also evidenced that the organs most susceptible to oxidative stress were the gills [157]. In another study performed on a uranium milling operation in Northern Saskatchewan, Canada, Pimephales promelas specimens (adults and 5-day-old larvae) were exposed to contaminated water and contaminated sediment [158]. Results indicated effects on reproduction (reduced hatching) and larvae development (increase of skeletal deformities) and an increase in metal body burdens. However, the effects detected on the offspring, when considering the increase in egg production, were not significant in the level of deformities between treatments [158]. The effects on reproduction on the same species have already been observed under an exposure to effluent waters also from a uranium mining site in Saskatchewan, Canada. A significant decrease in eggs hatching time and hatching success was registered when early life stages of fathead minnows were exposed [159]. Nevertheless, metals and radionuclides are not the only stressor responsible for the effects caused by effluent waters from NORM sites. Louren\u00e7o et al. [160] performed an exposure of zebrafish eggs to a uranium mine effluent, barium chloride-treated mine effluent, and settling ponds sludge elutriates and showed that pH of the mine effluent strongly affected hatching success. After eliminating the effect of pH, this study also showed some teratogenicity associated with the uranium mine effluent, the occurrence of DNA damage, mainly associated with the exposure to treated mine effluent and sludge elutriates and mild effects on growth observed mainly on embryos exposed to the mine effluent and sludge elutriates. This study showed that the use of the Fish Embryo Toxicity Test (FET) test is suitable to test uranium mining wastes to determine and discriminate the risk of discharge. It also showed that the inclusion of the evaluation of genotoxicity endpoints in the FET test prevented the underestimation of risks, when only looking at chemical and radiological benchmark values defined by national and international directives, for the determination of risks, due to the chemical complexity of these wastes."}
{"_id": "Radiology$$$75bbc219-f85e-4f21-ad4a-2ade17980d30", "text": "On what concerns amphibians, there are very few studies on these organisms as well. Marques and co-authors performed very important studies on amphibians, namely Pelophylax perezi exposed to NORM in situ. They have studied both tadpoles and adults and they have analyzed several endpoints, such as growth, survival, oxidative stress biomarkers (catalase, glutathione peroxidase, glutathione reductase, and lipid peroxidation through thiobarbituric acid reactive species (TBARS) quantification), gene expression alterations, histopathological changes, erythrocytic nuclear abnormalities and micronuclei, on organisms exposed to a uranium mine effluent in Portugal [161\u2013165]. A study performed on 2008, on larvae and eggs [165] exposed to a uranium mine effluent, showed a decrease in larvae body length as well as a decrease in stimulus reactions, an increase in pigmentation along with tail deformities and metals bioaccumulation. The in situ exposure of tadpoles of the same species showed decreased survival and growth, a higher glutathione peroxidase activity and an increased lipid peroxidation [164] in organisms exposed in the mine effluent pond, when compared with organisms from a control pond. Although there may have been the influence of NORM and metals exposure, the studies also evidenced the effects of effluent\u2019s acidity (typically seen in metal mining contexts), mainly in the growth and survival parameters and also in metal\u2019s uptake. Another study, performed by the same authors [163], on adults living on the same uranium mine pond, analyzed gene expression changes using a technique called Suppressive Subtractive Hybridization (SSH). Significant changes in the expression levels of genes that play an important role in protecting cells against oxidative stress were shown, evidencing once again that oxidative stress response is very important in protecting cells and in maintaining DNA integrity on organisms exposed to NORMs and metals. Another study performed by this team on Pelophylax perezi adults inhabiting a uranium mining pond [162], showed significant metals bioaccumulation in the liver and the kidneys. Significant histopathological alterations in the liver, the lungs and in the kidneys, mainly in the form of a slight increase in melanomacrophagic centers, a dilatation of the renal tubules, a discrete thickening along with a slight hyperplasia of the alveolar septa and a slight hypoplasia of the goblet cells, were observed. The same animals living in the mine pond also displayed a significantly higher number of erythrocytic abnormalities (micronuclei and notched, kidney and lobed shaped nuclei) as well as a significantly lower frequency of immature erythrocytes. Both observations led to the belief that the removal and replacement of abnormal blood cells might be compromised."}
{"_id": "Radiology$$$12dd57ac-74ad-47ca-a81b-6b14a16147f7", "text": "There are a few studies published on the uptake of NORM by mammals that were performed mainly on former uranium mining areas, but very few examined the effects of that exposure. A study performed by Cleveland et al. [166] analyzed NORM uptake and histopathological alterations in liver and kidneys of rodents (Peromyscus maniculatus and P. boylii) inhabiting former uranium mines and observed that rodents bioaccumulated elements from 238U decay chain but without exceeding literature-based effects thresholds for small rodents. The authors also observed that there were some minor lesions in the tissues (liver and kidneys) analyzed that could not, however, be attributed to U mining activities. Louren\u00e7o and co-authors [167], captured mice (Apodemus sylvaticus) on the surroundings of a former uranium mining site and on a control area. DNA damage and bioaccumulation of metals and radionuclides were assessed, as well as the expression and the presence of single nucleotide polymorphisms on tumor suppressor genes. Results showed that cadmium and uranium were significantly bioaccumulated by exposed organisms. Organisms living in the former uranium mining area also evidenced significantly higher levels of DNA damage when compared with control organisms and also a higher expression of TP53 tumor suppressor gene and the presence of single nucleotide polymorphisms in Rb tumor suppressor gene. These effects can cause a disturbance in the genetic material of exposed organisms causing genetic instability and changes in the genetic pool of the population, potentially affecting the population\u2019s fitness and stability. However, they cannot be attributed to any of the stressors in particular. It is known that uranium is genotoxic due to its chemical and radiological properties. Nevertheless, other metals present in uranium ore have shown greater genotoxic properties [151]."}
{"_id": "Radiology$$$1997bbca-7610-452f-a9a1-b6c15eb10efe", "text": "As for plants, there are a few studies already performed using soil/sludge or plant species collected directly from radium production industry storage sites, uranium rich regions, but mainly uranium mining sites and uranium milling tailings, that showed NORM bioaccumulation [168\u2013180]. However, very few assessed the effects of that bioaccumulation. On a study performed by Evseeva et al. [170], Vicia cracca populations, inhabiting areas contaminated with uranium mill tailings and radium production wastes, were sampled and analyzed for the presence of chromosome aberrations, frequency of embryonic lethal mutations, seed germination and survival rate of seed sprouts. Results showed an increased frequency of embryonic lethal mutations, decreased seed germination, increased chromosome aberration counts and decreased survival rate of seed sprouts. The same authors [171], used Allium cepa specimens to determine the genotoxicity of an effluent from a radium production storage facility, through chromosome aberrations counting. Results showed a significant increase in chromosome aberration counts in the roots of exposed plants. Two studies [168, 179] using soils contaminated with metals and radionuclides from Portuguese former uranium mines were performed using Lactuca sativa and Zea mays as test species to determine the eco (through growth inhibition) and genotoxicity (mutation analysis through the Ames test) of amended and unamended mine soils. Studies showed genotoxicity of the unamended soils containing the highest levels of metals and radionuclides, a significant decrease in Lactuca sativa biomass and also a significant bioaccumulation of these elements. The soil amendment methodology used in these studies significantly decreased the levels of metals and radionuclides in soils leachates and the soil available fraction."}
{"_id": "Radiology$$$635d6cec-76e1-4f0a-873c-e70f7d4d6316", "text": "Q1.\nWhat is the relationship between life stage and an organism\u2019s radiosensitivity?\n\u00a0Q2.\nPlease indicate which is the most radiosensitive parameter: mortality or reproduction?\n\u00a0Q3.\nPlease indicate the most important non-stochastic effects induced by organisms exposure to ionizing radiation at a population level.\n\u00a0Q4.\nWhich kind of exposure is more effective in causing organisms mortality?\n\u00a0Q5.\nRegarding radioactive contamination, what information can be retrieved from the omics approaches? What can be the contribution of those studies for future remediation of radiologically contaminated sites?\n\u00a0Q6.\nWhat are the main traits conferring radioresistance to plants compared to animals?\n\u00a0Q7.\nWhat does \u201chormesis\u201d in plants mean?"}
{"_id": "Radiology$$$e5d20008-fe97-4e16-8ca3-db6d03c6f6e2", "text": "What is the relationship between life stage and an organism\u2019s radiosensitivity?"}
{"_id": "Radiology$$$1598ad8e-bf72-4ff3-9270-d82c3fa1705d", "text": "Please indicate which is the most radiosensitive parameter: mortality or reproduction?"}
{"_id": "Radiology$$$393d9bce-e390-414f-a7fb-7e0e8804684a", "text": "Please indicate the most important non-stochastic effects induced by organisms exposure to ionizing radiation at a population level."}
{"_id": "Radiology$$$5b08d293-ec34-4981-a1a9-8cb448a59f9f", "text": "Which kind of exposure is more effective in causing organisms mortality?"}
{"_id": "Radiology$$$28488146-d815-4bde-911e-6bec287803ef", "text": "Regarding radioactive contamination, what information can be retrieved from the omics approaches? What can be the contribution of those studies for future remediation of radiologically contaminated sites?"}
{"_id": "Radiology$$$17d64dc3-a6b9-4864-ac82-c005a59ba157", "text": "What are the main traits conferring radioresistance to plants compared to animals?"}
{"_id": "Radiology$$$674dfad9-4bef-47be-a521-e6c6583715d0", "text": "SQ1.\nThe younger the organisms, the more sensitive they are to the deleterious effects of radiation exposure.\n\u00a0SQ2.\nReproduction and reproductive capacity is a more sensitive parameter to the effects of radiation exposure both for terrestrial and aquatic invertebrates and vertebrates, than mortality.\n\u00a0SQ3.\nThe non-stochastic effects that are most important at a population level are mortality, fertility, and fecundity.\n\u00a0SQ4.\nAcute exposures to high doses of ionizing radiation are more effective in inducing higher injury than chronic exposures to low doses of ionizing radiation. The higher the dose the lower the ability of cells to divide and regenerate the damaged tissue which translates into a higher probability for organisms mortality.\n\u00a0SQ5.\nThe application of multiomics approaches, namely genomics, proteomics, metabolomics, and transcriptomics, has gained relevance in many different fields. These high-throughput techniques allow an analysis of the total set of molecules (DNA, proteins, and other metabolites) in a biological sample. Therefore, the integrated data have revolutionized biology and have contributed to advancing our understanding of different biological processes.\nGenome sequencing, comparative genomics, and proteomics have allowed the identification of microbial essential genes (key players) that encode biomolecules, mainly proteins, involved in biological processes, including those involved in detoxification of radionuclides and metals. Furthermore, metagenomics approaches directed to the microbial communities of these contaminated environments allow for the identification, and characterization, of microorganisms with relevant functions in the bioremediation/decontamination processes. It is therefore expected that these broader approaches will contribute even more to the identification of microorganisms and to the elucidation of the metabolic pathways and key genes involved in those processes that may be further applied in the bioremediation/decontamination of these sites.\n\u00a0SQ6.\nThe elevated radioresistance of plants compared to animals relies on differences in cell structure and metabolism. Plant cells present some traits such as thickened cell walls, cuticles, hairs (pubescence), phenolic compounds, and often polyploidy.\n\u00a0SQ7.\nLow doses of ionizing radiation induce positive outcomes in plants such as increasing growth and production of secondary metabolites engaged in the antioxidant defenses."}
{"_id": "Radiology$$$3b34b9a1-26f3-4b65-ab63-d0f9190648bc", "text": "The younger the organisms, the more sensitive they are to the deleterious effects of radiation exposure."}
{"_id": "Radiology$$$8e3e2bdb-2eb3-4126-98d8-25fe84bee714", "text": "Reproduction and reproductive capacity is a more sensitive parameter to the effects of radiation exposure both for terrestrial and aquatic invertebrates and vertebrates, than mortality."}
{"_id": "Radiology$$$0c4f7266-6e41-4135-91c0-164c025274f7", "text": "The non-stochastic effects that are most important at a population level are mortality, fertility, and fecundity."}
{"_id": "Radiology$$$c6fb40e9-2e3c-40e2-b9b6-8ce720dc3a95", "text": "Acute exposures to high doses of ionizing radiation are more effective in inducing higher injury than chronic exposures to low doses of ionizing radiation. The higher the dose the lower the ability of cells to divide and regenerate the damaged tissue which translates into a higher probability for organisms mortality."}
{"_id": "Radiology$$$807b24d7-a1ce-4dd0-a01d-50f105fcc629", "text": "The application of multiomics approaches, namely genomics, proteomics, metabolomics, and transcriptomics, has gained relevance in many different fields. These high-throughput techniques allow an analysis of the total set of molecules (DNA, proteins, and other metabolites) in a biological sample. Therefore, the integrated data have revolutionized biology and have contributed to advancing our understanding of different biological processes."}
{"_id": "Radiology$$$7d5fee01-9636-44b3-976c-0c5d30b1a13c", "text": "Genome sequencing, comparative genomics, and proteomics have allowed the identification of microbial essential genes (key players) that encode biomolecules, mainly proteins, involved in biological processes, including those involved in detoxification of radionuclides and metals. Furthermore, metagenomics approaches directed to the microbial communities of these contaminated environments allow for the identification, and characterization, of microorganisms with relevant functions in the bioremediation/decontamination processes. It is therefore expected that these broader approaches will contribute even more to the identification of microorganisms and to the elucidation of the metabolic pathways and key genes involved in those processes that may be further applied in the bioremediation/decontamination of these sites."}
{"_id": "Radiology$$$bb60f1bf-dbd3-4e89-be2c-d6ff93c9e66e", "text": "The elevated radioresistance of plants compared to animals relies on differences in cell structure and metabolism. Plant cells present some traits such as thickened cell walls, cuticles, hairs (pubescence), phenolic compounds, and often polyploidy."}
{"_id": "Radiology$$$a22377ad-1323-44cb-b7f2-b26e509676cf", "text": "Low doses of ionizing radiation induce positive outcomes in plants such as increasing growth and production of secondary metabolites engaged in the antioxidant defenses."}
{"_id": "Radiology$$$f1e616e5-0866-47ff-9e4d-2db87c8ad763", "text": "Experiments in space provided us with new insights into radiation biology. This chapter is organized as follows. First, we present a historical overview of the field that can be traced to the first experiments at the Eiffel tower. Then, we overview the space radiation environment and mathematical models used to describe it. Later in this chapter, we present a macroscopic picture of health effects in humans (observed or anticipated in the space environment). Afterward, we turn to a microscopic level and describe biomolecular changes introduced by space radiation. Then, we describe experimental evidence obtained from models\u2014small animals, plants, eukaryotic cells, and extremophiles (organisms living under conditions extreme from a human point of view). Finally, we present an overview of ground-based facilities mimicking the space environment."}
{"_id": "Radiology$$$3f1c0346-5b65-4455-8856-634bbd1021d3", "text": "Human space travels were very early the concerns of a number of scientists like Johannes Kepler who warned that extraterrestrial trips would require ships fit to withstand the breezes of heaven [1]. The development of electroscopes manufactured by Pierre Curie made the assessment of local currents possible due to any particle crossing the two metallic plates [2]. The Italian physicist Domenico Pacini suggested in 1910 that the background noise measured with the Curie electroscopes was caused by radiation emitted from the Earth ground [3]. By performing some experiments with the Curie electroscope at the Eiffel tower, Theodor Wulf, a Jesuit priest, demonstrated that half of the radiation emitted by the Earth ground disappears at a height of 300 m. When the technology of balloons was safe, Victor Hess observed that the ionization density of the atmosphere progressively decreases up to 1000 m, but increases above 1800 m, suggesting the existence of two components of natural radiation: one from the Earth ground, the other from space, \u201ccosmic rays\u201d [4]. In 1936, Hess was awarded the Nobel Prize in physics for his discoveries [5]."}
{"_id": "Radiology$$$28b60087-5786-4f5c-b3bc-aba916dcd723", "text": "Between the 1930s and the 1940s, there were considerable advances in the technology of particle counters and in the knowledge of particle physics; thanks to balloon experiments, new clues were brought to support that cosmic rays consist of very energetic (108\u20131020 eV) particles. Furthermore, data hinted an unexpectedly high proportion of the iron-associated elements in the galactic cosmic radiation (GCR). The latter observation led to the hypothesis of the nucleosynthesis origin of cosmic rays [3]. Figure 10.1 shows the advances in space radiation biology since that period.\n\nA timeline from the 1930s to 2010s depicts significant milestones achieved in space radiobiology, advances in radiobiology, main human missions, and advances in physics.\n\nFig. 10.1\nSynopsis of advances in space radiation biology. The continuous increase of space mission duration up to 400 days is illustrated by the grey line on the left. For Mercury, Gemini, Apollo, Salyut, Skylab, and Mir missions, the maximum dose values are given as red dots [6]. ALTEA anomalous long-term effects on astronauts, FISH fluorescence in situ hybridization, HPRT hypoxanthine guanine phosphoribosyl transferase, ISS International Space Station, LNT linear no-threshold, NLT nonlinear threshold, PCC premature chromosome condensation, SilEye silicon eye. (Reprinted with permission from Maalouf  et al. [6])"}
{"_id": "Radiology$$$b23619a1-8a6b-44ad-846f-2efec2c43239", "text": "A timeline from the 1930s to 2010s depicts significant milestones achieved in space radiobiology, advances in radiobiology, main human missions, and advances in physics."}
{"_id": "Radiology$$$dff79018-77ff-4bcc-a5ba-81edf53847fe", "text": "The pioneer works of William Gilbert, Carl Friedrich Gauss, and Henri Poincar\u00e9 about magnetism suggested that charged particles may be influenced by the Earth\u2019s magnetism and that a ring current should exist around the Earth. At the end of the 1950s and overall in the 1960s, the number of artificial satellites increased drastically and permitted to verify these hypotheses. In 1958, James Van Allen and Louis A. Frank pointed out the existence of the Earth\u2019s radiation belt, based on data collected by the Explorer I and Pioneer IV satellites. Protons and electrons were found to be the major constituents of the Van Allen belt [7, 8]. In the same decade, Mariner II provided important data about the solar wind that permitted to document our knowledge on the radiation component from our Sun [9]."}
{"_id": "Radiology$$$7bcfd451-6feb-4baf-b7fa-11d61767ca21", "text": "During short-term (less than 2 weeks) missions in the 1960s at low Earth orbit (LEO), astronauts were exposed to several mGy at an average dose rate of about 0.17 \u03bcGy/min (245 \u03bcGy/mission day). This dose was delivered discontinuously as (1) the inner and outer zones of the Van Allen radiation belt contain protons and electrons of differing energy spectra that result in different secondary particles at dose rates different and energies; (2) the South Atlantic Anomaly (SAA), the area where the inner Van Allen radiation belt is the closest to the Earth surface, leading to an impressive flux of protons and electrons is passed about 15 times a day; here the dose rate can increase sixfold resulting in a significant contribution to the radiation exposure; and (3) unpredicted solar particle events (SPE) can increase the total dose, while the protection in LEO is still sufficient to prevent life-threatening acute radiation syndrome (see Sect. 10.6.2.1)."}
{"_id": "Radiology$$$473d4fc6-23f1-410d-9d51-97ffc619363d", "text": "The characterization of individual heavy cosmic particles of high-energy and high atomic number\u2014Z\u2014(HZE) was performed with different physical radiation detectors (nuclear emulsions, plastics, silver chloride (AgCl) crystals, and lithium fluoride (LiF) thermoluminescence dosimeters) for the first time in space in the Biostack experiments flown aboard Apollo 16 and 17 (see Sect. 10.5). In parallel, their biological effects were examined in different biological objects such as bacterial spores, protozoa cysts, plant seeds, shrimp eggs, and insect eggs investigating various radiobiological end-points [10]."}
{"_id": "Radiology$$$d42e12dc-42bc-4773-99a7-dc904550ff65", "text": "Examples of short-term experiments of up to 2 weeks in LEO combining radiation dosimetry and biological investigations were loaded on Space Shuttles (e.g., STS 9, 42, 45, 65), on free-flying satellites (e.g., LDEF, EURECA, BIOPAN 1\u20136) and on the MIR space station (Perseus mission). Later on, similar long-term experiments were performed on the International Space Station (ISS) (EXPOSE-E, -R, -R2) [11, 12]."}
{"_id": "Radiology$$$0b5955ea-770d-4b8b-b48e-5ff196f65a84", "text": "\u201cCytogenetics observations revealed for the first time the major biological consequences of an exposure to space radiation: the yield of chromosome breaks seemed to increase after flight, but statistical significance was still needed (see Sect. 10.4.2.2). Data from eye flashes and helmets (see Sect. 10.4.2.3) suggested the existence of a certain \u201chidden part\u201d of the heavy ions\u2019 component, probably due to secondary particles generated by the interaction of very high-energy particles with metallic materials. The contribution of these heavy ions to the total dose of radiation remained unknown at the end of the 1960s\u201d [6]."}
{"_id": "Radiology$$$05c1e9f7-143e-4def-ba7b-22b613320f1a", "text": "Space experiments in combination with ground-based research (see Sect. 10.10) enabled a better understanding of the effects of space radiation and microgravity on human cells, microbes, and other biological models such as the roles of different complementary DNA repair mechanisms, the reactive oxygen species detoxification system and the intracellular accumulation of compatible solutes summarized, e.g., in Senatore et al. [13]. The modern picture of the space radiation dosimetry and its effects on human cells may be summarized as following [6]:1.\nThe energy spectrum of space particles and the dose spacecraft crews are exposed to can be quantified precisely by active and passive dosimetry. The dose delivered by secondary particles and countermeasures to reduce it require further investigations into the interaction of space radiation with a diversity of materials and in a complex spacecraft geometry.\n\u00a02.\nEpidemiological studies for estimating hazards due to space radiation exposure are hampered by the small astronaut population, the individual radiation susceptibility, and radiation exposure history of each astronaut. International collaboration integrating different astronaut cohorts may help in overcoming these restrictions.\n\u00a03.\n\u201cCytogenetic data undoubtedly revealed that space radiation exposure produces significant damage in cells. However, our knowledge of the basic mechanisms specific to heavy ion and low-dose and repeated exposures, and of adaptive responses is still incomplete. Furthermore, experiments about genomic instability and delayed mutagenesis may help in quantifying the risk of potential space radiation-induced cancer. The application of new radiobiological techniques may help in progressing in this field.\u201d"}
{"_id": "Radiology$$$c78609a7-d9ac-47d5-b25f-eb5bea275041", "text": "The energy spectrum of space particles and the dose spacecraft crews are exposed to can be quantified precisely by active and passive dosimetry. The dose delivered by secondary particles and countermeasures to reduce it require further investigations into the interaction of space radiation with a diversity of materials and in a complex spacecraft geometry."}
{"_id": "Radiology$$$702a0b43-b04d-4125-bf52-f1db0e747ccc", "text": "Epidemiological studies for estimating hazards due to space radiation exposure are hampered by the small astronaut population, the individual radiation susceptibility, and radiation exposure history of each astronaut. International collaboration integrating different astronaut cohorts may help in overcoming these restrictions."}
{"_id": "Radiology$$$d8d6f4b3-0d34-46ed-a435-a1eec06bdac1", "text": "\u201cCytogenetic data undoubtedly revealed that space radiation exposure produces significant damage in cells. However, our knowledge of the basic mechanisms specific to heavy ion and low-dose and repeated exposures, and of adaptive responses is still incomplete. Furthermore, experiments about genomic instability and delayed mutagenesis may help in quantifying the risk of potential space radiation-induced cancer. The application of new radiobiological techniques may help in progressing in this field.\u201d"}
{"_id": "Radiology$$$f3c0c22c-0c02-43a4-a33d-f0bf1fb05104", "text": "Space is permeated with radiation, both electromagnetic radiation and particles with mass. Electromagnetic radiation in space spans many wavelengths, from long wavelength radio waves to very short-wavelength gamma rays. Gamma rays, X-rays, and some far/extreme ultraviolet (UV) waves, which can be generated for example during some transient events on the Sun [14], are actually ionizing radiation. The wavelengths of UV, X-, and gamma rays are all shorter than those of visible light. The majority of these rays are absorbed by the Earth\u2019s atmosphere. The extraterrestrial solar UV radiation ranges from vacuum UV (wavelength <200 nm) to UVA (320\u2013400 nm). The ozone layer absorbs some, but not all, of these types of UV radiation: UVA is not absorbed by the ozone layer, UVB (wavelength: 290\u2013320 nm) is mostly absorbed by the ozone layer, but some does reach the Earth\u2019s surface, while UVC (wavelength: 100\u2013290 nm) is completely absorbed by the ozone layer and atmosphere. Overall, the electromagnetic radiation reaching the Earth\u2019s surface encompasses radio waves, some microwaves, some infrared light, UVB and UVA radiation, and visible light. Of the light that reaches Earth\u2019s surface, infrared radiation makes up 49.4% while visible light provides 42.3%. UV radiation makes up just over 8% of the total solar radiation. UVA and UVB radiation contribute not only to premature aging of the skin but also to some serious health effects such as skin cancer, cataracts, and suppression of the immune system."}
{"_id": "Radiology$$$525e2160-0ffe-45f6-9355-4d3750f03f7b", "text": "Generally however the expression \u201cspace radiation\u201d mainly refers to radiation consisting of particles with a mass. There are three main radiation populations in space: galactic cosmic rays (intra- and extragalactic; GCR), solar radiation (including both the Solar Energetic Particles, SEP, and solar wind), and trapped radiation. A schematic representation of these radiation types and the environment which they can influence is given in Fig. 10.2.\n\nAn illustration depicts the effect of solar energetic particles, galactic cosmic rays, solar wind, magnetosphere, Van Allen belt, trapped and secondary particles on a spacecraft and an astronaut.\n\nFig. 10.2\nRadiation environment during a space mission. (Image courtesy by ESA and reprinted from Chancellor et al. [15] with permission under Creative Commons Attribution-NonCommercial-NoDerivatives License: http://\u200bcreativecommons.\u200borg/\u200blicenses/\u200bby-nc-nd/\u200b4.\u200b0/\u200b)"}
{"_id": "Radiology$$$6ebcf1ed-6891-4176-8ad4-cfcc1c61972a", "text": "An illustration depicts the effect of solar energetic particles, galactic cosmic rays, solar wind, magnetosphere, Van Allen belt, trapped and secondary particles on a spacecraft and an astronaut."}
{"_id": "Radiology$$$a5cb9187-8cff-400f-ba8f-6b0300f5259c", "text": "GCRs are constantly present highly energetic radiation in space. Their intensity is slowly varying and low with a few particles per second traversing an area of a cm2 to a m2 or more. They are nearly isotropic, meaning that they impinge from all directions. They originate from outside the heliosphere, most likely from deep space high-energy phenomena [16], such as supernova shock waves throughout the Galaxy, and also possibly from stellar wind termination shocks, pulsars, or other more exotic objects. They are composed of 98% baryons, of which 87% protons (hydrogen ions), 12% helium ions (\u03b1-particles), and 1\u20132% high-energy and highly charged ions, called High charge Z and Energy (HZE) particles, and 1% electrons and positrons [17]. HZE comprises ions from Z = 3 (Li) to Z = 28 (Ni). The most common elements are C, O, Mg, Si, and Fe ions (Fig. 10.3). Ions heavier than Ni can be encountered, yet these are very rare.\n\nA double line graph of relative abundances versus atomic number Z plots the curves of solar system and G C R for the following elements. H, H e, B e, C, N e, S i, A r, T i, F e, and Z n.\n\nFig. 10.3\nGCR composition, as based on data from NASA\u2019s Advanced Composition Explorer (ACE) spacecraft. (Reprinted with permission from http://\u200bwww.\u200bsrl.\u200bcaltech.\u200bedu/\u200bACE/\u200bACENews/\u200bACENews83.\u200bhtml)"}
{"_id": "Radiology$$$6610e20f-fc39-4e26-bb3e-6f064b3a8e02", "text": "A double line graph of relative abundances versus atomic number Z plots the curves of solar system and G C R for the following elements. H, H e, B e, C, N e, S i, A r, T i, F e, and Z n."}
{"_id": "Radiology$$$c0fcd39d-a85a-4dae-af78-5076feadfd77", "text": "The spectrum of the GCRs is influenced by periodical, long-term, and short-term effects. Also, the Sun\u2019s behavior is periodical and follows an 11-year cycle which affects the interplanetary medium. The increased solar and heliospheric magnetic fields during the maximum phase of the solar cycle partially shield the solar system and decrease the low-energy portion of the GCRs flux, by preventing it from entering the inner heliosphere [18], while at solar minimum the reduced interplanetary magnetic field strength implies a more intense GCRs population [19]. The GCR flux is thus inversely proportional to the solar activity and decreases by a factor of 2\u20134 when moving from solar minimum to solar maximum, depending on the depth of the solar minimum and the intensity of the solar maximum [20, 21]."}
{"_id": "Radiology$$$4a6935c6-2fb2-4b0b-8be4-4c4ecdce13c8", "text": "The modulation of the GCR flux for different ions is reported for the period of solar maximum and minimum. In the short term, GCRs can also be reduced by intense release of high-energy particles (mostly protons) during transient solar eruptions [22] (see Sect. 10.3.1.2). The energy spectrum of GCRs covers a huge range of energies: it commences at about 107\u2013108\u00a0electron volt (eV) (10\u2013100 MeV), and the most energetic cosmic rays reach up to 1020 eV (Fig. 10.4). A prominent feature is a so-called knee, with an energy of about 2.7\u20133.1 PeV (PeV = 1015\u00a0eV). This energy originated from the diffusive shock acceleration from the Galactic supernova remnants. The so-called anide or ankle, with an energy of about 5\u00a0\u00d7\u00a01018 eV, is another characteristic of the energy spectrum. It is believed to mark the lower end of the energy of ultra-high energy GCRs, those that originate from extragalactic sources [24].\n\nA graph of flux versus energy plots the following data points. 1 particle per meter squared per second. Knee, 1 particle per meter squared per year. Anide, 1 particle per kilometer squared per year.\n\nFig. 10.4\nGCR overall average fluxes versus energy. (Data from Beatty et al. [23])"}
{"_id": "Radiology$$$84a4faea-8a03-464e-8ab3-5404788dc901", "text": "A graph of flux versus energy plots the following data points. 1 particle per meter squared per second. Knee, 1 particle per meter squared per year. Anide, 1 particle per kilometer squared per year."}
{"_id": "Radiology$$$d77403ff-3abf-463f-8c2e-ccbe3c5f3ab4", "text": "When traversing Earth\u2019s atmosphere, GCRs induce nuclear-electromagnetic-muon cascade reactions resulting in ionization of atmospheric molecules and generation of secondary particles [25, 26]. A small fraction of the initial primary particles, together with secondary particles of sufficient energy, reaches the ground. The maximum in secondary particle energy release (Pf\u00f6tzer maximum) occurs at altitudes of 15\u201326 km depending on latitude and solar activity level. The radiation reaching the Earth\u2019s surface has levels similar to other low levels of radiation that humans are frequently exposed to. The average yearly exposure of a person is around 3.5 millisieverts (mSv). About half of this dose can be attributed to artificial sources (X-ray, computer tomography (CT) scan, mammography), while the other half originates from natural sources, including around 10% from cosmic radiation."}
{"_id": "Radiology$$$f16803c2-8805-4889-95e9-bded67a16c1d", "text": "SEPs originate from transient events on the Sun and come as massive injections of mostly protons and electrons (and to lesser extent helium (~4%) and heavier ions), with typical energies from ten to hundreds of MeV [27]. These transient events are Sun eruptions such as flares and Coronal Mass Ejections (CMEs). Characteristically, a flare lasts only minutes to hours and is the result of an explosive energy release from the Sun\u2019s coronal magnetic field. Also, the electromagnetic flux increases, particularly in the short-wavelength (Extreme ultraviolet\u2014XUV, gamma ray) range, and also in the radio regime. Usually originating in active regions, CMEs are large-scale plasma-magnetic structures with high speeds (up to thousands of km/s) associated with prominence eruptions and flares."}
{"_id": "Radiology$$$78880427-4974-43d3-84db-86a2baafaa50", "text": "The likelihood of CME events increases with the power and size of the related flare event, although not all CMEs are associated with flares. Such events extend from several hours to a few days, and they have a higher likelihood of occurring during solar maximum. The level of the Sun\u2019s activity is fairly described by the number of sunspots, which provides an indication of the phases of the cycle. The number of spots increases toward the solar maximum, while during solar minimum the Sun\u2019s surface is almost spotless. Nevertheless, such SEPs events are hardly predictable and can also occur during solar minimum. Examples of an active region, an initial flare, and then a prominent eruption initiating a CME is shown for the 28/10/2003 event as part of the \u201cHalloween Storms of 2003\u201d in Fig. 10.5, with the related sudden increase in proton flux as detected by the Geostationary Operational Environmental Satellite (GOES) satellite (Fig. 10.6a). Examples of fluences (integral of the flux over the period of the event) related to major SEP events are shown in Fig. 10.6b.\n\nFour photographs taken by SOHO satellite on 28 10 2003 depict Halloween Storms of 2003. Agile areas, sun spot, huge bubbles of coronal plasma threaded by magnetic field lines ejected from the sun.\n\nFig. 10.5\nThe active regions (upper left), solar flare (upper right), and coronal mass ejections (CME, lower left and right) of the 28/10/2003 event captured by the Solar and Heliospheric Observatory (SOHO) satellite. The CME was imaged by the Large Angle and Spectrometric COronagraph (LASCO) instrument by blocking the light from the solar disk. (Courtesy of SOHO/EIT and SOHO/LASCO consortium. SOHO is a project of international cooperation between ESA and NASA)\n\n\nLine graph a of particles versus universal time plots five minute data of G O E S proton flux. Line graph b of integral fluence versus proton kinetic energy plots the curves for 1956 to 1989.\n\nFig. 10.6\n(a) Proton flux between 28 and 31 October 2003. The 5-min averaged integral proton flux for energy thresholds of >10 (red line), >50 (blue line), and >100 MeV (green line) was measured by the primary Geostationary Operational Environmental Satellite (GOES) satellite of the Space Weather Prediction Center (SWPC). CO Colorado, MeV Mega electron volt, NOAA National Oceanic and Atmospheric Administration, s second, sr steradian, UTC Coordinated Universal Time. Reprinted with permission under terms of the Creative Commons Attribution License [28]. (b) Distribution in the energy of proton fluences for major past SEPs events (free space). (Reprinted with permission from: The space radiation environment: an introduction. Schimmerling W. https://\u200bthree-jsc.\u200bnasa.\u200bgov/\u200bconcepts/\u200bSpaceRadiationEn\u200bviron.\u200bpdf. Date posted: 2-5-2011)"}
{"_id": "Radiology$$$8f8e3d49-a1d8-4ef7-b5df-2d0d5f45c1f2", "text": "Four photographs taken by SOHO satellite on 28 10 2003 depict Halloween Storms of 2003. Agile areas, sun spot, huge bubbles of coronal plasma threaded by magnetic field lines ejected from the sun."}
{"_id": "Radiology$$$5aad0e25-7f46-498d-8c04-71f7ff9d36a2", "text": "Line graph a of particles versus universal time plots five minute data of G O E S proton flux. Line graph b of integral fluence versus proton kinetic energy plots the curves for 1956 to 1989."}
{"_id": "Radiology$$$fc46c13c-b7a3-419b-81b2-d21f93bc32c2", "text": "A classification exists between Impulsive SEP events, which are short (\u22641 day), numerous (~1000/year in periods of high activity), and of low intensity, and gradual events, which are long (several days at energies of a few MeV/nucleon), rather rare (a few tens per year), characterized by orders of magnitude higher protons fluences than impulsive events and ascribed to acceleration by CME-driven shocks as they propagate through the heliosphere. There is however some debate about the role played by \u201cflare acceleration\u201d in these events [29, 30]."}
{"_id": "Radiology$$$fefc50f4-fccf-4cbf-84aa-f5a5ccad641d", "text": "Contrary to GCRs, SEP events can be considered mostly inducing deterministic effects (Sects. 10.4.2 and 10.6.2). Deterministic effects are those certainly occurring once a specific threshold dose has been overpassed. The high-intensity SEP flux can significantly increase the absorbed dose to astronauts, for example, during extravehicular activities (EVA) at the ISS, or eventually, if the event is characterized by a \u201chard\u201d spectrum with a strong high-energy component, also during both interplanetary mission or missions on thin atmosphere such as Mars. Acute radiation syndrome (ARS), sickness, or, in extreme cases, death after a lethal dose can occur [31]."}
{"_id": "Radiology$$$9dcabf5e-b00b-4084-89d4-ede77c53e91c", "text": "A comparison between GCR and SPE can be found in Table 10.1 (adapted from NASA Space Flight Human System Standards\u2014NASA Standard 3001).Table 10.1\nComparison of GCR and SPE\n\u00a0\nGCR\n\nSPE\n\nSpatial distribution\n\nIsotropic beyond terrestrial influence (no preferred direction of arrival)\n\nNon-isotropic at onset, later becoming diffused through the solar system\n\nComposition\n\nProtons (~87%) and helium ions (~12%) with the remainder consisting of HZE (1\u20132%)\n\nMostly protons\n\nTemporal variations\n\nChronic\n\nAcute\n\nEnergy\n\nExtending to at least 1017 eV in some cases (much greater maximum than solar particles)\n\nAbout 1010 eV highest recorded\n\nOrigin\n\nTheories only; supernova explosions, neutron stars, pulsars, or other sources\n\nActive regions of flares on the Sun, CMEs\n\nFlux density\n\nRelatively low: about 2 particles/cm2/s of all energies\n\nVery high: may be as high as 106 particles/cm2/s\n\nBiological effects\n\nPrimarily genotoxic and mutagenic with some vital cell destruction\n\nPrimarily acute damages, possible sudden illness, incapacitation, or death\n\nAdapted from https://\u200bmsis.\u200bjsc.\u200bnasa.\u200bgov/\u200bsections/\u200bsection05.\u200bhtm#_\u200b5.\u200b7_\u200bRADIATION"}
{"_id": "Radiology$$$7fad6e32-4673-4785-957c-9c7bd145a831", "text": "The solar wind is a continuous flow of plasma from the Sun\u2019s corona, mainly consisting of protons, electrons with a small percentage of He ions, with kinetic energies between 0.5 and 10 keV. There are also some trace amounts of heavy ions and atomic nuclei such as C, N, O, Ne, Mg, Si, S, and Fe. Their energy results from the high temperature of the Sun\u2019s corona and allows them to escape the Sun\u2019s gravity. The flux of the solar wind varies over time, solar longitude and latitude, together with its temperature, density, and speed. At distances of more than a few solar radii from the Sun, the solar wind reaches supersonic speeds of 250\u2013750 km/s [32]. At much greater distances, about 75\u201390 astronomical units (1 au is the distance Sun-Earth), the so-called \u201ctermination shock,\u201d interactions of the local interstellar medium with the solar wind slow it down to subsonic speed."}
{"_id": "Radiology$$$ead7f958-69ea-484d-a4ef-9c4b1d4f71e7", "text": "There are different classes of solar wind [30]:(a)\nThe long-lived solar wind high-speed streams, representatives of the inactive or \u201cquiet\u201d Sun. Sources for such streams are coronal holes usually located above inactive parts of the Sun, where \u201copen\u201d magnetic field lines prevail, e.g., around activity minima at the polar caps;\n\u00a0(b)\nA slow wind stream from more active near-equatorial regions on the Sun, often associated with \u201cclosed\u201d magnetic structures. Sharp boundaries exist between these two solar wind streams (in longitude as well as in latitude), and their main properties differ significantly according to the location and magnetic properties at the source;\n\u00a0(c)\nAnother slow solar wind stream emerging during high solar activity, from active regions distributed over large parts of the Sun, in a highly turbulent state. It is highly variable and usually contains a significant fraction (about 4%) of alpha particles;\n\u00a0(d)\nThe solar wind disturbances superimposed on the ambient solar wind in case of CMEs. They exhibit unusually high percentages of alpha particles (up to about 30%)."}
{"_id": "Radiology$$$624fe9ca-a0ee-4ced-aebc-5cc6a0f9c3c0", "text": "The long-lived solar wind high-speed streams, representatives of the inactive or \u201cquiet\u201d Sun. Sources for such streams are coronal holes usually located above inactive parts of the Sun, where \u201copen\u201d magnetic field lines prevail, e.g., around activity minima at the polar caps;"}
{"_id": "Radiology$$$3b596694-6d2c-4147-9ee9-a62f32307e24", "text": "A slow wind stream from more active near-equatorial regions on the Sun, often associated with \u201cclosed\u201d magnetic structures. Sharp boundaries exist between these two solar wind streams (in longitude as well as in latitude), and their main properties differ significantly according to the location and magnetic properties at the source;"}
{"_id": "Radiology$$$30befc1a-17fb-4419-95a8-0ea1905c97c1", "text": "Another slow solar wind stream emerging during high solar activity, from active regions distributed over large parts of the Sun, in a highly turbulent state. It is highly variable and usually contains a significant fraction (about 4%) of alpha particles;"}
{"_id": "Radiology$$$3eafb95c-8a5a-4d97-ac16-af2c4977bd10", "text": "The solar wind disturbances superimposed on the ambient solar wind in case of CMEs. They exhibit unusually high percentages of alpha particles (up to about 30%)."}
{"_id": "Radiology$$$fff0048b-476a-48e2-b0b6-a33352a95a43", "text": "The Earth\u2019s magnetosphere deflects the solar wind, causing most of the solar wind to flow around and beyond us. Nevertheless, a small number of particles from the solar wind reach the upper atmosphere and ionosphere. This may produce phenomena such as aurora and geomagnetic storms, the latter occurring when large inflation of the magnetosphere, due to an increased pressure of the contained plasma, distorts the geomagnetic field."}
{"_id": "Radiology$$$68d610ba-5cc7-45f2-817b-7b4e1615cc9c", "text": "In space missions, the solar wind has no impact on astronauts, as it is efficiently stopped by the spacecraft shielding and also by appropriate astronaut suits, because of the small range in a matter of the low speed-solar wind particles. However, if not appropriately shielded, the solar wind particles may affect the human body during eventual EVAs in deep space or on the surface of airless bodies, such as the Moon."}
{"_id": "Radiology$$$a7ea45c0-6ebe-475d-9b9e-79046326a428", "text": "Trapped radiation particles are produced mainly by the interaction of GCRs and SEPs with the Earth\u2019s atmosphere and are trapped by its magnetic field into the Van Allen radiation belts. These comprise:(a)\nA stable inner belt of trapped protons and electrons with energies between some keV and 100 MeV that is centered at a height between 300 and 1000 km above the Earth and reaches up to a height of around 10,000 km.\n\u00a0(b)\nA less stable outer electron belt, comprising mainly high-energy (0.1\u201310 MeV) electrons and which extends from an altitude of about 10,000\u201340,000 km (see Fig. 10.7 for a schematic representation).\n\u00a0\n\nA schematic diagram depicts the earth\u2019s vertical rotational axis, angled magnetic axis, inner radiation belt, and outer radiation belt.\n\nFig. 10.7\nRadiation belts of the Earth. (Figure from Van Allen radiation belt. Reprinted with permission from Wikipedia. Author Booyabazooka at English Wikipedia, https://\u200bcommons.\u200bwikimedia.\u200borg/\u200bwiki/\u200bFile:\u200bVan_\u200bAllen_\u200bradiation_\u200bbelt.\u200bsvg)"}
{"_id": "Radiology$$$a60a6566-aabe-4937-9852-066999363587", "text": "A stable inner belt of trapped protons and electrons with energies between some keV and 100 MeV that is centered at a height between 300 and 1000 km above the Earth and reaches up to a height of around 10,000 km."}
{"_id": "Radiology$$$ffaeced0-bbb3-41ea-a608-357d44062649", "text": "A less stable outer electron belt, comprising mainly high-energy (0.1\u201310 MeV) electrons and which extends from an altitude of about 10,000\u201340,000 km (see Fig. 10.7 for a schematic representation)."}
{"_id": "Radiology$$$2661953b-e0b1-4d0f-9627-18c496944dee", "text": "A schematic diagram depicts the earth\u2019s vertical rotational axis, angled magnetic axis, inner radiation belt, and outer radiation belt."}
{"_id": "Radiology$$$54284da3-43ac-40be-8ea0-aeae32a64e7b", "text": "In the radiation belts, the energetic particles move along Earth\u2019s magnetic field lines, via the combination of three types of motion: a fast rotation (or \u201cgyration\u201d) around magnetic field lines, typically thousands of times each second; a back-and-forth bouncing along the stronger magnetic fields in the northern and southern hemispheres, typically lasting 1/10 s; a slow drift around the magnetic axis of the Earth (the drift is eastward for electrons and westwards for ions), such drift is from the current field line to its neighbor, with the particle keeping roughly the same distance from the axis. A typical time to complete a full circle around the Earth is a few minutes."}
{"_id": "Radiology$$$eb261b7c-8a19-4b89-9f20-52560c795224", "text": "In the area above the southeastern part of South America and the South Atlantic, the inner radiation belt approaches the surface of Earth down to a few hundreds of kilometers (South Atlantic Anomaly, SAA). This is caused by the tilt and shift of the axis of the dipole-like magnetic field of the Earth with respect to its axis of rotation [33]. The dip of magnetic lines leads to an increased particle flux within this region."}
{"_id": "Radiology$$$aa78a30e-5216-439c-af47-e53295c56ad3", "text": "The dose rate experienced by the astronauts on the ISS has a considerable contribution from trapped protons in the inner Van Allen belt because the ISS orbit with an altitude of about 400 km passes through this belt at the SAA (roughly 50% of the total dose rate) [34]."}
{"_id": "Radiology$$$5019e76b-270e-4db6-b9d7-bbb49dd37f55", "text": "A low Earth orbit (LEO) is an Earth-centered orbit close to our planet with an altitude ranging from 160 to 2000 km. Thus, the ISS, which flies at an altitude of around 400 km, is also in such an orbit, with an orbital inclination (the tilt of the orbital plane with respect to the equatorial plane, which helps to understand an orbit\u2019s orientation with respect to the equator) of 51.6\u00b0 and an orbiting period of 90\u201393 min. Consequently, in 24 h the ISS makes 16 orbits of Earth and travels through 16 sunrises and sunsets. The environment of these altitudes is extreme and characterized by microgravity, high vacuum, meteoroids, extremes of temperature, ionospheric plasma, space debris, and UV as well as ionizing radiations."}
{"_id": "Radiology$$$0643b8a3-ab0d-49f6-8177-199b7c68ec6a", "text": "The radiation sources are GCR, trapped radiation, and SEP events. The GCR environment accounts for about 50% of the total dose rate, the other 50% being induced by trapped protons of the inner belt, the only component of the inner belts that reaches energies and intensities to be important for effects on astronauts inside the ISS [35]. Other orbits, such as Medium Earth Orbits (2000\u201335,786 km), Geostationary orbits (35,786 km), and High Earth Orbits (over 35.786 km), are exposed to different sub-components of the trapped radiation, some may not pose any danger. On board the ISS, astronauts encounter SPE events as a transient increase in dose rates. As mentioned above, the GCR flux is modulated by the solar cycle. At the ISS altitude, the GCR flux is also modified by the geomagnetic field, besides the modulation due to the solar activity. This field removes particles with lower energies (~few GeV/nucleon), but particles of higher energies are unaffected [36]. At low altitudes, the trapped radiation is also modulated by solar activity: at solar maximum, because of the increase in UV radiation, the upper atmosphere expands, leading to the loss of trapped protons at low altitudes. Furthermore, the inner radiation belt is mainly filled by decaying neutrons created by incoming GCR particles and the GCR flux is inversely proportional to solar activity [37]. Therefore, at solar maximum, a lower proton flux is present, leading to a smaller radiation hazard compared to the solar minimum [36, 38]."}
{"_id": "Radiology$$$d0961775-9200-4612-94a5-ad29fe8e204d", "text": "The interaction of energetic protons and HZE nuclei with spacecraft structures produces an additional intravehicular radiation field. This secondary radiation includes mainly, protons, neutrons, photons (X-rays and gamma rays), leptons (e.g., electrons and positrons), mesons (e.g., charged pions) and a great number of lighter and heavier nuclear isotopes (ions) [39, 40]. This happens in LEO and is of high concern in particular for the deep Space phase of a mission (see below), as the spacecraft would not be protected by the Earth\u2019s atmosphere and magnetic field."}
{"_id": "Radiology$$$a88d53d8-e92f-4e9b-a39e-0b1bb9eb525a", "text": "Radiation challenges for astronautic missions beyond LEO, such as travel to the Moon or Mars, come from SEP events, GCR and intravehicular secondary radiation (Fig. 10.2). The solar wind particles, also constantly present in deep Space, do not contribute to the radiation dose induced in crews inside a spacecraft, as they are efficiently stopped even by thin shielding thicknesses."}
{"_id": "Radiology$$$9e03abe2-1501-453b-815e-a19286231ff8", "text": "Similar to the case of the LEO scenario, most GCRs are not efficiently stopped by regular depths of spacecraft shielding. The intravehicular radiation field is constituted by the ensemble of secondary radiation mentioned above. Adding more shielding would increase to a considerable extent the weight at launch and would not reduce the GCR-induced absorbed dose to zero. As the only modulation of GCR in deep space is provided by the shielding of the heliospheric field during solar maximum, the idea of carrying out missions to Mars during solar maximum has been considered a viable option. If one considers that during a 180-day trip at the solar maximum peak a crew would also likely receive a total SEP-contributed dose equivalent, a round trip to Mars would result in a total dose equivalent of 560 \u00b1180 mSv,1 higher than the estimation based on the data from the Radiation Assessment Detector (RAD) onboard the Mars Science Laboratory NASA mission [41] which was on cruise during solar minimum [42]. The above estimate for the radiation exposure is substantially lower than the accepted safe upper limit for 30\u201360-years old nonsmoking females and males (above 1500 mSv\u2014see Fig. 10.8). However, inaccuracy and limitations of the models and unpredictability of SEP events must be considered.\n\nA scale of radiation in millisievert for different medical procedures, space missions, celestial body, general population, and NASA astronaut limits.\n\nFig. 10.8\nRelative radiation exposure of varying duration during medical procedures (green), specific space missions (purple), and on various celestial bodies (blue). The astronaut yearly and career limits are given in red boxes. For comparison, some facts on radiation exposure of the general population and occupational exposure limits (US) are indicated (gold). (Reprinted with permission from Iosim et al. [43])"}
{"_id": "Radiology$$$c03063c3-d0b0-4a90-ac73-9d490aeffcb8", "text": "A scale of radiation in millisievert for different medical procedures, space missions, celestial body, general population, and NASA astronaut limits."}
{"_id": "Radiology$$$9783f6ff-2dcf-442a-9e4f-cb69652c3277", "text": "The Moon is about 380,000 km away from Earth and is the next endeavor for space missions beyond LEO. Although some areas of the Moon have a weak magnetic field, the Moon does not have a global magnetic field like on Earth and no atmosphere. Consequently, its surface is not shielded from radiation. The solar wind particles get stopped in the first millimeters or, maximally, centimeters of the lunar regolith, while GCR and SEP can impact the lunar surface also resulting in the production of backscattered secondary particles. The total amount of radiation that astronauts will be exposed to is influenced strongly by solar activity, their whereabouts on the Moon surface with respect to local magnetic fields, and the type and amount of radiation shielding used in spacecraft, Moon vehicles, and habitats. Recently, the Lunar Lander Neutrons and Dosimetry experiment aboard China\u2019s Chang\u2019E 4 lander revealed that radiation levels on the Moon\u2019s surface are 200\u20131000 times more than that on Earth\u2019s surface and 2.6 times more than what astronauts onboard the ISS are exposed to Zhang et al. [44]. Efficiency of the radiation shielding by lava tubes on the Moon appears promising to reduce the dose rates considerably [45]."}
{"_id": "Radiology$$$965cace1-7ba2-4c47-aa95-3385f6f29113", "text": "Mars does not possess a global magnetic field, and it has only a thin atmosphere with its surface pressure less than 1% of that at Earth\u2019s surface. Therefore, high-energy GCRs can reach the surface, although still a considerable portion of them will induce hadronic-electromagnetic-muon cascades in the atmosphere, causing fragmentation/spallation and ionization showers of downward secondaries. All these particles can then induce further reactions in the planet\u2019s regolith, which generate a backscattered, albedo radiation component, giving overall complex spectra including both primaries and (downward and upward) secondaries at the surface [46\u201348]."}
{"_id": "Radiology$$$daed7f3e-303d-422b-9f20-feb6ed64c9de", "text": "SEP events can increase the dose rate and dose equivalent at the Martian surface and constitute a danger for EVA on Mars. Only protons impinging the top of the atmosphere with energy above ~200 MeV do actually reach the ground, and thus SEPs events with high flux contribution at high energy constitute the biggest hazard for explorers on Mars if they are not in a habitat or otherwise sufficiently shielded. For the solar wind, despite the thin character of Mars\u2019 atmosphere, the upper layers of the latter are able to stop such radiation. Underground solutions for Mars habitats, shielded from the radiation by the regolith, are being investigated [49]."}
{"_id": "Radiology$$$1a15fca1-2490-41a7-91ed-5e74e4524539", "text": "Overall, to contextualize radiation doses in space, a comparison of these doses to doses received during medical interventions is shown in Fig. 10.8. It is important to emphasize that being exposed to a hefty radiation dose within a short time (minutes to hours) will be more health-threatening than the same dosage over a longer duration of months of years. Yet, although the health effects of acute radiation exposure are well studied, less is known about the effects of chronic exposure."}
{"_id": "Radiology$$$7c15f2bd-52c1-4534-a3a7-9e94c93b26ed", "text": "Ionizing radiation exposure is one of the most critical health risks for astronauts. Inside the ISS, astronauts are exposed to an effective dose rate of the order of 20 \u03bcSv/h, which is about 100 times higher than on the Earth\u2019s surface. Beyond LEO in deep space, the protection of the Earth\u2019s atmosphere and magnetic field disappears, leading to an effective dose rate of the order of 75 \u03bcSv/h. Also, on the surface of the Moon or Mars, there is only limited protection and astronauts are exposed to respectively about 30 and 25 \u03bcSv/h. It is estimated that astronauts will accumulate during a Mars mission a total effective dose of the order of 1 Sv, leading to an extra risk for cancer of the order of a few percent up to more than 10% depending on sex and age [50]. Furthermore, on their way through deep space or on the surface of the Moon or Mars, astronauts can receive such high doses during intense solar storms that immediate health effects or even a deadly outcome are possible (see Sect. 10.4.2). Therefore, it is clear that astronauts need to be protected against ionizing radiation in space."}
{"_id": "Radiology$$$3a7cfc3a-953e-4eed-b66b-4ce9dfbe640c", "text": "The only technology that can currently be used in practice to reduce the radiation level in spacecraft is to use shielding materials for stopping part of the radiation. The heavy ion impinging on the shielding material is the projectile, and the shielding material is the target. A multitude of interactions can occur when the projectile hits the target, including fragmentation of the projectile or target. For comparison of different materials, the area density as mass per unit area in g/cm2 is used (for example, an 1 cm thick plate of Al with the density of 2.7 g/cm3 has an area density of 2.7 g/cm2). In current spacecraft, one makes most use of constructive materials such as aluminum. Unfortunately, such materials are not the most efficient for radiation shielding in space (see Chap. 4). The interaction of energetic GCRs with heavier elements such as aluminum results in the breakup of these heavier elements and the creation of secondary cosmic radiation such as energetic heavy ions and neutrons. Therefore, when using aluminum for shielding, the effective dose rate first increases as function of the shielding thickness before it starts to decrease and this decrease is quite flat as attenuation of heavy ions is nearly in balance with the build-up of light particles (Fig. 10.9 Left).\n\nTwo line graphs of dose equivalent rate versus depth plot G C R and Van Allen trapped protons, for aluminum, water, polyethylene, and liquid hydrogen.\n\nFig. 10.9\nCalculated dose equivalent rate in LEO (51.6\u00b0 inclination, 390 km altitude) as a function of shielding thickness given as area density for different shielding materials: (left) GCR, (right) Van Allen trapped protons. (Data used with permission from Dietze et al. [37])"}
{"_id": "Radiology$$$589d01cd-f463-447d-a857-2eb4af1614b2", "text": "Two line graphs of dose equivalent rate versus depth plot G C R and Van Allen trapped protons, for aluminum, water, polyethylene, and liquid hydrogen."}
{"_id": "Radiology$$$7f8e1816-40af-4085-9ad6-57f8aeebde1e", "text": "Materials consisting of lighter elements such as hydrogen have a higher stopping power per unit of mass for charged radiation particles as they attenuate their fluence via projectile fragmentation. They also minimize the build-up of neutrons and other target fragments. Radiation protection of astronauts can thus be further optimized by making use of lighter shielding materials or, for instance, also by making strategic use of the necessary stock of water as additional shielding. Figure 10.9 shows the calculated dose equivalent rate for a LEO orbit similar to that of ISS (51.6\u00b0 inclination, 390 km altitude) as a function of shielding thickness for different shielding materials. At standard temperature and pressure, based on a density of 1000 kg/m3, the water column required to reach an area density of 20 g/cm2 would have a height of 20 cm. For 20 g/cm2 aluminum, a material thickness of 7.4 cm is derived from the density at room temperature of 2.7 g/cm3. At the same area density of 20 g/cm2, the shielding effect of water is much more pronounced than the one of aluminum. The thickness of the two materials is different, but they would contribute to the same extent to the mass budget of the spacecraft which is critical for leaving the Earth surface during launch. The left and right plots show the results for respectively GCRs and Van Allen protons. These plots clearly show that hydrogenous materials are much more efficient for radiation shielding in space."}
{"_id": "Radiology$$$ecf1600e-d479-4faf-a20d-f9349260e5af", "text": "In spacecraft it is unfortunately not possible to reduce the effective dose rate to the dose rate on Earth\u2019s surface. With limited shielding, a large part of the energetic protons and electrons from SEPs and the Van Allen protons can be stopped. However, GCRs have such high energies that about 1000 g/cm2 of shielding is required to reduce the effective dose rate to the level on Earth\u2019s surface. Due to mass constraints in spacecraft, only shielding of the order of a few 10 g/cm2 is possible. In spacecraft, astronauts can thus be protected against sudden very high and potentially deadly doses from solar storms, but they will be unavoidably chronically exposed to the ever-present GCRs leading to an increased risk for late effects."}
{"_id": "Radiology$$$67853e00-8d9d-45be-9fab-9f5b9a3daba2", "text": "It is clear that with current technology additional radiation exposure in spacecraft is unavoidable. However, for future manned missions to the Moon or Mars during which astronauts will stay on the surface for a longer time it will be necessary to strongly reduce their radiation exposure during their stay. This is possible because on the surface of the Moon or Mars, we can make use of the present soil material to provide adequate shielding. A few meters of soil material should suffice to reduce the effective dose rate level to similar levels as on Earth\u2019s surface. This can be done by building igloos or by living in caves or lava tubes."}
{"_id": "Radiology$$$bef92367-c5be-4059-905f-4ee9d59d5b63", "text": "Besides shielding by using materials to block the radiation, it is in principle also possible to make use of strong electromagnetic field for shielding. Several research groups are investigating this possibility. However, the required mass and energy consumption of such systems makes the concept practically impossible with current technology (Box 10.1)."}
{"_id": "Radiology$$$2fdcdb10-29fe-4770-b195-5487710a966c", "text": "(a)\nGCRs are the constantly present highly energetic radiation in space, they are mostly constituted by protons, with a smaller contribution from alpha particles and HZE particles. They generate particle showers in the atmosphere, although a small portion of direct GCRs can eventually reach the ground.\n\u00a0(b)\nSEP events are more probable during solar maximum, but they can actually also occur during solar minimum.\n\u00a0(c)\nTrapped radiation is constituted by GCRs and solar protons trapped in the Van Allen belts. Trapped radiation is a concern for ISS-like missions, especially because of the flux accumulated during different orbits in the SAA, or also missions on other orbits crossing one or the other belt."}
{"_id": "Radiology$$$3d9301ca-a46a-44fe-9678-26982ccf1b80", "text": "GCRs are the constantly present highly energetic radiation in space, they are mostly constituted by protons, with a smaller contribution from alpha particles and HZE particles. They generate particle showers in the atmosphere, although a small portion of direct GCRs can eventually reach the ground."}
{"_id": "Radiology$$$a0a1c1cc-db1f-4e6f-9296-6a07df1ed9a7", "text": "SEP events are more probable during solar maximum, but they can actually also occur during solar minimum."}
{"_id": "Radiology$$$1a424c5c-25c7-423d-be9f-2f8b13e9680c", "text": "Trapped radiation is constituted by GCRs and solar protons trapped in the Van Allen belts. Trapped radiation is a concern for ISS-like missions, especially because of the flux accumulated during different orbits in the SAA, or also missions on other orbits crossing one or the other belt."}
{"_id": "Radiology$$$994cff55-9c64-4c75-9004-b9484dcc6e48", "text": "The modeling of the radiation environment at or inside a spacecraft, at different altitudes in the atmosphere or at the surface/subsurface of a planet, a moon, or a small body allows to obtain the relevant dosimetric quantities for the assessment of the health risks incurred by humans due to radiation [51\u201353], as well as to estimate the half-lives of biomolecules in search-for-life studies [54, 55]."}
{"_id": "Radiology$$$ad8b07be-5e14-4bd0-a1dc-c725eb128074", "text": "The transport of radiation through matter is described by the time-independent Linear Boltzmann Transport Equation, which allows to treat atomic and nuclear collisions. The Boltzmann transport equation (10.1) describes the flux ni(r, E, \u03a9, t) of several types of particles i, possessing different energies E, and moving in different directions \u03a9 by considering the particle balance in a small volume V. It thus gives the average space-time distribution of the expected energy-momentum behavior of the particle beam, transported and scattered across the target, where each interaction is characterized by its own differential cross-section \n\n. The Boltzmann equation reads as follows:\n\n (10.1)"}
{"_id": "Radiology$$$6a60cbfb-bac1-4d97-a966-d42aace79b08", "text": "In this equation:\nthe first term is the time-dependent flux change, due to particles escaping from the system boundaries, or disappearing by an absorption reaction or radioactive decay;\n\non the right-hand side, the unscattered term represents the flux change due to translation without change of energy and direction (free flight);\n\nthe particles scattered out are those exiting a \u201ccell\u201d (a unit volume in the phase space, the latter comprising both space and time variables);\n\nthe particles scattered in are those entering a \u201ccell\u201d from a \u201ccell\u201d at a previous point in the phase space;\n\nthe production of secondaries represents the effect of collisions;\n\nthe source term can be external (e.g., a particle beam irradiating the target volume), or internal (e.g., neutrons from fission reactions in the volume)."}
{"_id": "Radiology$$$36906875-84a4-4cf6-b2c6-ae1b29637a88", "text": "the first term is the time-dependent flux change, due to particles escaping from the system boundaries, or disappearing by an absorption reaction or radioactive decay;"}
{"_id": "Radiology$$$6d3c2cdb-7098-465e-b605-23d128c0b1af", "text": "on the right-hand side, the unscattered term represents the flux change due to translation without change of energy and direction (free flight);"}
{"_id": "Radiology$$$681570df-b9b8-4ea3-b58d-d585c1bf6ac7", "text": "the particles scattered out are those exiting a \u201ccell\u201d (a unit volume in the phase space, the latter comprising both space and time variables);"}
{"_id": "Radiology$$$3c810804-d846-4b20-971a-db682c23b340", "text": "the particles scattered in are those entering a \u201ccell\u201d from a \u201ccell\u201d at a previous point in the phase space;"}
{"_id": "Radiology$$$4d44e970-72ee-4b18-99f8-131310a6e04a", "text": "the source term can be external (e.g., a particle beam irradiating the target volume), or internal (e.g., neutrons from fission reactions in the volume)."}
{"_id": "Radiology$$$4b464411-bce2-41d2-9ae5-f12e7f0410d9", "text": "In particular for high-energy particles, the number of interactions that must be described in order to find the solution to this equation is daunting, including ionization, excitation, spallation/fission/fragmentation, production of positron-emitting nuclei, and de-excitation through gamma rays. A solution to the problem can be attained via two different approaches:1.\nDeterministic methods. These are deterministic approaches based on approximations to the Boltzmann equation and often on the reduction to a 1D problem via the use of the straight-ahead approximation, according to which the secondary particles from nucleon-nucleus collisions are emitted in the direction of the incident nucleon [37]. They rely on models for the relevant quantities in the transport calculation and use the continuous slowing down approximation (CSDA). Deterministic codes such as NASA\u2019s HZETRN [56] and BRYNTRN [57] follow such an approach and require relatively low computational resources to perform calculations and the calculation time is relatively short. This is due to the fact that deterministic codes do not consider all products of reactions and neglect their correlation, e.g., the coefficients used in the Boltzmann equation are related to relatively simple one-particle quantities. Thus, correlations on event-by-event basis are not considered and particle scattering at an angle is ignored [58]. Last, such methods can only be applied to restricted geometries and restricted interaction models.\n\u00a02.\nMonte Carlo method. Monte Carlo (MC) is a stochastic method, exploiting random numbers to (a) \u201cgenerate\u201d an initial particles\u2019 \u201ccocktail\u201d; (b) track them in arbitrary geometries; (c) accumulate the contribution of each track to a statistical estimator of the desired physical observables [59]. Step-by-step particles\u2019 transport is simulated according to the statistical model of their interactions. Quantities (such as step lengths, event type, energy losses, and deflections) are sampled via generation of random values according to a given probability distribution. Indeed, in MC codes, the MC method deals with sampling from suitable stochastic distributions, with large samplings allowing to solve the integrations of multidimensional integrals."}
{"_id": "Radiology$$$51d6ed89-01ac-46f2-985b-cbd096577b6a", "text": "Deterministic methods. These are deterministic approaches based on approximations to the Boltzmann equation and often on the reduction to a 1D problem via the use of the straight-ahead approximation, according to which the secondary particles from nucleon-nucleus collisions are emitted in the direction of the incident nucleon [37]. They rely on models for the relevant quantities in the transport calculation and use the continuous slowing down approximation (CSDA). Deterministic codes such as NASA\u2019s HZETRN [56] and BRYNTRN [57] follow such an approach and require relatively low computational resources to perform calculations and the calculation time is relatively short. This is due to the fact that deterministic codes do not consider all products of reactions and neglect their correlation, e.g., the coefficients used in the Boltzmann equation are related to relatively simple one-particle quantities. Thus, correlations on event-by-event basis are not considered and particle scattering at an angle is ignored [58]. Last, such methods can only be applied to restricted geometries and restricted interaction models."}
{"_id": "Radiology$$$e83ac2b9-9356-4f47-84e3-1449a3d065fd", "text": "Monte Carlo method. Monte Carlo (MC) is a stochastic method, exploiting random numbers to (a) \u201cgenerate\u201d an initial particles\u2019 \u201ccocktail\u201d; (b) track them in arbitrary geometries; (c) accumulate the contribution of each track to a statistical estimator of the desired physical observables [59]. Step-by-step particles\u2019 transport is simulated according to the statistical model of their interactions. Quantities (such as step lengths, event type, energy losses, and deflections) are sampled via generation of random values according to a given probability distribution. Indeed, in MC codes, the MC method deals with sampling from suitable stochastic distributions, with large samplings allowing to solve the integrations of multidimensional integrals."}
{"_id": "Radiology$$$c2b85511-5227-46ea-9fc6-94f5dcba01d4", "text": "In the context of space environment, the main interest is in high-energy particles whose scattering is generally low-angle. Therefore, it is reasonable to approximate multiple scatterings by a single continuous step, taking into account overall energy loss and direction change. This approach is known as the condensed-history technique. For example, ionization and excitation energy losses are described as continuous processes, i.e., they are continuously distributed along a particle step, if the loss is lower than a chosen threshold, together with their fluctuations."}
{"_id": "Radiology$$$fa4a9b9d-932f-4906-bd05-6dab9aec6b8b", "text": "Several MC codes are used nowadays throughout the world, such as Geant4 [60], FLUKA [61], and PHITS [62]. MC codes provide a detailed treatment of the three-dimensional transport of ions and neutral particles (see Chap. 4)."}
{"_id": "Radiology$$$eb7014c6-61f6-4f95-919b-8fc159286ffd", "text": "An overview of the different steps for calculation of the radiation environment of a celestial body is given in Fig. 10.10.\n\nA flowchart depicts primary particles in deep space plus atmosphere and regolith model lead to particle transport and surface particle spectra of G C Rs and S E Ps.\n\nFig. 10.10\nScheme for Monte Carlo (MC) calculations of the radiation environment at a planet/celestial body, here in particular Mars. GCRs galactic cosmic rays, SEPs solar energetic particles, p+ protons, He2+ ions helium ions"}
{"_id": "Radiology$$$f6d5b0a6-5892-4ef5-85cb-5fb50d18e358", "text": "A flowchart depicts primary particles in deep space plus atmosphere and regolith model lead to particle transport and surface particle spectra of G C Rs and S E Ps."}
{"_id": "Radiology$$$70ee3b37-e7be-4b0d-8fa8-e1706a33cf01", "text": "The input spectrum for GCRs can be chosen among different existing models that account for the variations of GCR particle fluxes due to variations in solar activity and in the large-scale heliospheric magnetic field throughout the solar cycle. The ISO 15390 model (ISO-15390 2004) [63] accounts for solar cycle variations in the GCR intensities on the basis of 12-month averages of the sunspot number. Changes in the large-scale heliospheric magnetic field are usually taken proportional to the corresponding changes in the Sun\u2019s magnetic field, considering also solar cycle. More accurate models describe the spectra of GCR beyond the heliospheric modulation region. The CREME96 [64] and its updated version CREME2009 (https://\u200bcreme.\u200bisde.\u200bvanderbilt.\u200bedu/\u200b) are based on a semi-empirical model [65] where the particle spectrum is calculated as a product of a function describing the LIS and a function describing the modulation according to solar activity. GCR particle spectra are described in the energy range from 10 to 105 MeV/nucleon, from H up to Ni nuclei from the year 1760 to present. The Badhwar\u2013O\u2019Neill 2010 (BON2010) [66] uses, instead of an empirical description of the modulated GCR."}
{"_id": "Radiology$$$fb24f21a-eb13-44bc-8dbb-0d7a46991aeb", "text": "As in the CREME model, a physical approach to describe the GCR propagation in the heliosphere due to diffusion, convection, and adiabatic deceleration. The BON2010 model exploits data from the International Sunspot Number (ISN) and considers time lag of GCR flux relative to the solar activity. The ISN is calibrated with GCR measurements from the Advanced Composition Explorer (ACE) and the Interplanetary Monitoring Platform-8 (IMP-8). The Burger-Usoskin model [67] is limited to GCR He and H ions assuming a constant ratio of the two types of ions. The reconstruction of the modulation parameter is based on neutron monitor count rates. The DLR model by Matthia et al. [68] describes the GCRs spectra of nuclei based on a single parameter, which is derived from measurements of the ACE spacecraft and from Oulu neutron monitor count rates for different solar modulation conditions."}
{"_id": "Radiology$$$e2955562-295a-41af-8518-66da0f72d50e", "text": "SEP proton spectra are often considered from historical events, then parameterized by double power law fits in kinetic energy to event-accumulated integral fluence measured by the Geostationary Operational Environment Satellites and/or ground-based neutron monitor data [69]."}
{"_id": "Radiology$$$4d765fd4-636a-449a-87f9-d18a3e328e13", "text": "Input spectra for both GCR and SEP events can often be retrieved via user-friendly tools, such as the SPENVIS online tool (https://\u200bwww.\u200bspenvis.\u200boma.\u200bbe/\u200b) that is actually a collection of modules that allow for calculations of the radiation environment and radiation-induced effects via MC simulations in Geant4, or the On-Line Tool for the Assessment of Radiation in Space (OLTARIS) which operates on top of the deterministic code HZETRN (https://\u200boltaris.\u200bnasa.\u200bgov/\u200b)."}
{"_id": "Radiology$$$71f7d6c8-c813-4aa1-bba1-3ecc10e37c8b", "text": "For Earth, more than 99.99% of its atmosphere\u2019s mass is contained in the lower atmospheric layers below about 100 km. This region is mainly composed of N2, O2, and Ar which account for about 75%, 23%, and 1.3% by mass, respectively. The exact mass fraction of each constituent depends on the altitude. The water content in the atmosphere is highly variable but small, with the hydrogen fraction only reaching the order of 10\u20135% even in cloudy conditions [70]. Composition, density, temperature, and pressure vertical profiles can be obtained, for example, from the empirical atmospheric model 1 NRLMSISE-00 [71], which includes total mass density from satellite accelerometers and from orbit determination covering 1981\u20131997. For Mars, vertical profiles for pressure, density, temperature, and chemical composition of the atmosphere are often constructed exploting databases like MCD (Mars Climate Database http://\u200bwww-mars.\u200blmd.\u200bjussieu.\u200bfr) [46, 49]. Data can be extracted for specific locations, a specific day/night time, and season. The surface elevation and topology are extracted from the Mars Orbiter Laser Altimeter (MOLA) aboard Mars Global Surveyor. The fields (temperature, wind, density, pressure, radiative fluxes, etc.) are stored on a 5\u00b0\u00a0\u00d7\u00a05\u00b0, longitude-latitude grid from the surface to 120 km (and above) are averaged and stored 12 times a day, for 12 Martian \u201cseasons.\u201d"}
{"_id": "Radiology$$$e065cfc8-7208-4af3-b369-683ba347dcda", "text": "For Earth, the soil is often considered to consist of 50%Vol solids (of which 75%Vol SiO2 and 25%Vol Al2O3) and a scalable amount of H2O. Studies show that the neutron environment strongly depends on soil moisture (and air humidity) [72]. The composition of the surface and subsurface of Mars can either be chosen to model specific scenarios, for example, a default basaltic composition (SiO2 51.2%, Fe2O3 9.3%, H2O 7.4%) [73] or more/less hydrated compositions to study the possibility of underground shielding habitats [49], or it can be taken from data from the Gamma Ray Spectrometer aboard Mars Odyssey [46]. The dosimetric quantities at the Martian surface do not depend strongly on the regolith composition, although some differences due to hydration and Fe-content can affect neutrons and gamma rays spectra [49]."}
{"_id": "Radiology$$$a9a3f090-9ccd-4a0e-b92e-fab1ee989684", "text": "MC particle transport codes strongly rely on the availability of physics models and database of cross sections. A schematic view of the downward and upward main particles that need to be considered is shown in Fig. 10.11. In the open source Geant4 code [60], hadronic models are: (1) data-driven, which mainly deals with the detailed transport of low-energy neutrons and isotope production, (2) parametrized models which include fission, capture, elastic, and inelastic scattering reactions; (3) theoretical models for high energies, above several 10\u2013100 MeV, where experimental cross-section data are scarce. For electromagnetic physics, the basic processes for electrons, positrons, photons, and ions, such as Compton scattering, photoelectric effect, pair production, muon-pair production for photons, ionization, \u03b4-electron production, Bremsstrahlung, \u010cerenkov radiation, and annihilation, are considered. Additionally, processes involving the atomic shell structure such as Rayleigh scattering are also considered. Special process classes handle muon interactions like Bremsstrahlung, capture, and annihilation. Multiple scattering models provide corrections for path lengths and lateral displacements of multiple scattered charged particles. In order to decrease the computational time and resources, a certain production cutoff in the range is set for electrons, positrons, and photons, which is translated to energy below which the particle then loses its remaining kinetic energy continuously along the track and no secondary particles are produced.\n\nA diagram depicts two different downpours of primary particles, such as proton, neutron, electron, and gamma rays.\n\nFig. 10.11\nSchematic view of the particle showers (main particles are plotted here) generated in the downward propagation of primary GCRs particles through the Martian atmosphere and of the backscattered particles [74]"}
{"_id": "Radiology$$$543efb43-132e-4f93-b7c4-8c7643691afe", "text": "A diagram depicts two different downpours of primary particles, such as proton, neutron, electron, and gamma rays."}
{"_id": "Radiology$$$2e924853-40e2-47bc-99e5-a0bcb1c2693a", "text": "In principle, the proper approach to calculate the absorbed dose and dose equivalent rates is to use. Such standardized phantom has been defined by the International Commission on Radiation Units (ICRU) and it is given by the ICRU sphere, a 30 cm-diameter sphere with a density of 1 g/cm3 and a mass composition of 76.2% O, 11.1% C, 10.1% H, and 2.6% N, which reflects the composition of tissue. Still, in recent times more human-like phantoms have been used [75]. However, such complexity is not always necessary, and sometimes other spheres of water or water slabs have been used [76]."}
{"_id": "Radiology$$$75d6bc82-92de-4492-b1ff-049de1fc244b", "text": "Apart from running the MC (or deterministic) codes in standalone mode, several tools such as the previously mentioned SPENVIS online system (https://\u200bwww.\u200bspenvis.\u200boma.\u200bbe/\u200b), OLTARIS (https://\u200boltaris.\u200bnasa.\u200bgov/\u200b), and the EXPACS/PARMA code (https://\u200bphits.\u200bjaea.\u200bgo.\u200bjp/\u200bexpacs/\u200b) based on PHITS can be used to run a combination of the steps described above, resulting in a punctual estimation of doses at a specific location on a body or altitude in an atmosphere or in radiation maps covering several regions."}
{"_id": "Radiology$$$a94f1774-0f6d-469b-90fc-56f4a530f272", "text": "For human exploration of Mars and other bodies, the quantities of interest are the absorbed dose corrected by the relative biological effectiveness (RBE) factor (to estimate the risk for acute effects or death due to high doses for Solar Energetic Particle events) and the Effective Dose and Dose Equivalent to respectively estimate the risks to long-term effects induced by exposure to GCRs and to compare with measurements from radiation detectors. Space Agencies implement the ALARA principle [77] which ensures that mission operations are designed to keep the radiation risks as low as reasonably achievable. Although the different agencies use common limits for deterministic effects on the ISS, different career radiation exposure limits (for stochastic effects) for astronauts in LEO missions exist and no specific limits for interplanetary missions are issued (only those for LEO exist)."}
{"_id": "Radiology$$$08779b70-99d4-4fd1-8ee9-fa401eb1898a", "text": "Harmonization of risk models requires improvements in modeling radiation sources, in the accuracy of radiation transport codes, and the development of new realistic quality factors based on the features of the variegated radiation field in Space."}
{"_id": "Radiology$$$537fe4a2-2426-466c-9182-7531b34725f7", "text": "As already mentioned in Chap. 2, the approach commonly used for estimating risk from high linear energy transfer (high-LET) radiations is based on multiplying the induced absorbed dose (in units of gray) by a so-called quality factor, or RBE factor (always greater than one, usually below 20) representing the enhancement of effectiveness of the high-LET radiation. Such increased effectiveness comes from available evidence on the RBE of the radiations from both laboratory and theoretical studies (Sects. 10.4 and 10.5). As previously shown, RBE varies with LET. It depends also on other factors and may be different, e.g., for particular chromosome aberrations, mutations, or different tumor types. Also, RBE may vary in different biological systems. Furthermore, low-LET dose response is usually nonlinear while high-LET response tends to be more linear."}
{"_id": "Radiology$$$4134daba-4ad4-4724-b1aa-0621e4cab076", "text": "However, for radiation protection purposes, the use of RBE for low-dose exposure to radiation with different LET was superseded by the adoption of radiation weighting factor, wR, by the International Commission on Radiological Protection (ICRP) [78], to convert absorbed dose (measured in Gy) to equivalent dose (measured in Sv) in a tissue and to effective dose (measured also in Sv) in the body. ICRP recommends wR = 1 for photons of all energies, electrons, and leptons. The value wR = 2 is recommended for protons and charged pions, and wR = 20 for \u03b1-particles, heavy charged particles, and fission fragments [78] (see Table 10.2). However, the adoption of specific values for such weighting factors, based on the judgment from the available data on RBE, was accompanied by a recognition of the simplistic description and of the limited accuracy that the systematic application of this set of values for wR would have brought. Thus, quality factors, Q(LET), defined as a continuous function of the LET of the radiation, were later introduced in order to give broadly similar results for measured radiation fields [78] (see Table 10.2). Such quality factors are nowadays used in the risk assessment model by the European Space Agency and were also used in the previous risk assessment model by NASA.Table 10.2\nRadiation weighting factors and quality factors\n\nRadiation type\n\nRadiation weighting factor (wR)\n\nQuality factor (Q(LET))\n\nPhotons\n\n1\n\u00a0\nElectrons and muons\n\n1\n\u00a0\nProtons and charged pions\n\n2\n\u00a0\nAlpha particles, fission fragments, heavy ions\n\n20\n\u00a0\nNeutrons\n\nA continuous function of neutron energy\n\u00a0\n\u2003For LET\u00a0<\u00a010 keV/\u03bcm\n\u2003For 10\u00a0\u2264\u00a0LET\u00a0\u2264\u00a0100 keV/\u03bcm\n\u2003For LET\u00a0>\u00a0100 keV/\u03bcm\n\n1\nQ\u00a0=\u00a00.32L\u20132.2\nQ\u00a0=\u00a0300L\u20131/2"}
{"_id": "Radiology$$$49d2b855-6037-465a-8033-b67cb5fde6e0", "text": "Nevertheless, this specification of Q in terms of the LET alone suffers from the limitations already highlighted in Chap. 1, about the fact that the sole LET cannot fully describe the effectiveness of radiation in inducing biological damage. Indeed, even simply from the perspectives of the first-stage radiation-induced effects, without mentioning the complex dependencies of the RBE on phenomena related to the chemical and biological steps, it remains the fact particles with different charge and different velocity may have the same LET and still inducing different final biological effects. The variation in the effectiveness of radiation in inducing different final biological effects has thus its root in the differences in track structures between particles that have the same LET but different charge and velocity, as highlighted in Chap. 1. Differences can be particularly large for the HZE particles encountered in space, methods used on Earth are inadequate for space travel, as, among other reasons, the ICRP radiation quality description does not represent HZE radiobiology correctly."}
{"_id": "Radiology$$$1d3d19b7-1cc5-4ac6-9553-0147789c2fb1", "text": "The key difference between (a) the quality factor used by NASA [79] for the projection of risk from space exposures and (b) the quality factor recommended by the ICRP (Q(LET)) for operational radiation protection on Earth is consideration of track structure (Box 10.2)."}
{"_id": "Radiology$$$fc6fd729-b913-4274-9e93-899f55c803dc", "text": "(a)\nThe Boltzmann equation describes the transport of radiation in matter; it can be solved via analytical (deterministic) or via numerical (Monte Carlo) methods.\n\u00a0(b)\nThe different steps for setting up a calculation of the radiation environment are input radiation spectra, definition of the parameters describing the atmosphere, with dependence on the altitude, definition of the regolith composition, definition of the physics model to be used according to the different energy ranges, definition of the target where the scoring of the absorbed dose will be done."}
{"_id": "Radiology$$$2aae50f6-594d-40cd-8ba7-5746cf53298c", "text": "The Boltzmann equation describes the transport of radiation in matter; it can be solved via analytical (deterministic) or via numerical (Monte Carlo) methods."}
{"_id": "Radiology$$$0666f3ab-b08a-404d-a27a-48e66c8d1527", "text": "The different steps for setting up a calculation of the radiation environment are input radiation spectra, definition of the parameters describing the atmosphere, with dependence on the altitude, definition of the regolith composition, definition of the physics model to be used according to the different energy ranges, definition of the target where the scoring of the absorbed dose will be done."}
{"_id": "Radiology$$$3355d94a-416e-4fdd-8740-0297c23946dd", "text": "The space environment is hostile to the health of astronauts in several ways. The confinement in the restricted space of spacecraft for shorter or longer periods exposes the crew to sometimes severe behavioral problems. Microgravity can lead to osteoporosis, a modification of the electrolyte compartments, sarcopenia, cardiac arrhythmias, dysthemeral rhythm disorganization, vestibular deconditioning, relative immunosuppression, and postural hypotension on return [80]. Finally, the space radiation environment is very different and much more hostile than that encountered on Earth. Add a temperature amplitude of 300 \u00b0C on the spacecraft\u2019s surface and the almost absolute vacuum conditions that astronauts must consider during extravehicular excursions. Finally, let us point out the disturbances secondary to the return to the ground: neurological, vestibular, cardiovascular reconditioning, etc."}
{"_id": "Radiology$$$99a33dd0-1d3e-419f-988a-105429bfe3b6", "text": "The constant flux of galactic cosmic rays (GCR) causes astronauts\u2019 chronic low-dose whole-body exposure during space missions. The primary GCR particles interact with the spacecraft hull, so that astronauts are\u2014like patients\u2014exposed to secondary radiation from nuclear interactions between the incident radiation and the shielding of the spacecraft. Due to mass limitations for launching spacecraft, complete shielding of GCR is not feasible. Compared to an astronaut suit for extravehicular activities, the shielding of the spacecraft by aluminum and other materials strongly reduces the skin dose and also, but to a much lower extent, the whole-body dose. On the microscopic level, due to the physical characteristics of particle radiation, very high doses can be reached, leading to permanent damage (see Sect. 10.4)."}
{"_id": "Radiology$$$6c58deb1-a678-48b4-9806-f2b294bcc860", "text": "In LEO, traversal of the SAA of the inner radiation belt contributes to the accumulated dose during, e.g., a mission on the ISS. Human phantom experiments on the ISS (MATROSHKA experiment series) allowed the quantification of the effective dose rate which was 690\u2013720 \u03bcSv/day during extravehicular activities and lower inside the ISS amounting to 550\u2013570 \u03bcSv/day [81, 82]. Therefore, astronauts accumulate effective doses of around 100 mSv during a 6-months ISS mission. The variations of the accumulated dose depend on solar activity and the flight altitude of ISS, with higher doses during lower solar activity and increasing flight altitude. For a 1000-day Mars mission, a total effective dose of galactic cosmic radiation of about 1 Sv is expected [83, 84], which is quite considerable and exceeds terrestrial lifetime radiation exposure limits, which amount to 400 mSv in the European Union. Risks of cancer and degenerative diseases are associated with this chronic GCR exposure (Fig. 10.12).\n\nA diagram of an astronaut lists the radiogenic acute effects in central nervous system, immune system, and skin, and chronic effects in central nervous system, eye, and overall risk.\n\nFig. 10.12\nPossible health effects of space radiation exposure"}
{"_id": "Radiology$$$3309026b-a28e-4b90-bf23-7f3dc3b646d6", "text": "A diagram of an astronaut lists the radiogenic acute effects in central nervous system, immune system, and skin, and chronic effects in central nervous system, eye, and overall risk."}
{"_id": "Radiology$$$39150b10-b041-42e6-baaa-80d3bdc129c1", "text": "Solar Particle Events (SPE) emanating from the Sun (Sect. 10.3.1.2) result in increased proton fluxes that may reach the spacecraft or a celestial body surface. In LEO, protection by the Earth\u2019s magnetic field is still sufficient to protect from deadly SPE, but in free space or on planets or moons without magnetic field and atmosphere, high doses might be accumulated within hours or days in situations of insufficient shielding, e.g., in a spacesuit. Above a certain threshold, acute effects will occur (Fig. 10.12). In contrast to GCR, shielding of SPE protons is feasible in special compartments of the spacecraft, which can be surrounded by more material. Astronauts can protect themselves from an SPE in such a radiation shelter until the proton flux normalizes."}
{"_id": "Radiology$$$7b268ce0-b8cf-4e68-934d-489501820756", "text": "Deterministic effects appear for acute global exposures classified as medium, high, and very high (0.2 to more than 10 Sv) by UNSCEAR [85]."}
{"_id": "Radiology$$$371ad6df-7652-4f7d-8c61-2243bd3d71d6", "text": "Under exceptional conditions of insufficient shielding during spaceflight, the exposure to mostly protons during a large solar particle event (SPE), the whole-body dose can reach several Gy or the skin dose even tens of Gy and thereby cause the acute radiation syndrome (ARS, see Chap. 2, Sect. 2.\u200b7.\u200b2). Such situations in the event of a solar flare of exceptional intensity can occur in LEO in areas of weakness of the Van Allen belts, extravehicular exit, and exit on extraterrestrial soil in a spacesuit or an insufficiently shielded vehicle. The total dose is delivered over a short period of time: generally, instantaneously but by definition over less than 4 days."}
{"_id": "Radiology$$$7515663d-ead8-43d5-85af-20df2b5c3470", "text": "The acute effects affect rapidly renewing tissues which are particularly radiosensitive (bone marrow, digestive epithelium, germ cells, skin). The classic \u201cradiation sickness\u201d or prodromal syndrome (headache, dizziness, nausea, bone marrow hypoplasia) occurs for an exposure of 0.5\u20131 Gy. A dose of 3\u20134 Gy kills 50% of exposed individuals in 1 month [86]. Unlike the desired partial exposure of patients undergoing radiotherapy, solar flares are unpredictable, which seriously complicates mission planning for astronauts."}
{"_id": "Radiology$$$297b6ae1-e5f7-4f30-8dca-6d33fe028006", "text": "For several decades, NASA has collected data concerning acute and chronic morbidity and mortality in US astronauts in the NASA\u2019s Longitudinal Study of Astronaut Health [87]. One main aim is to determine whether astronauts\u2019 occupational space radiation exposure is associated with an increased risk of cancer or other diseases. The cohort is made up of 312 astronauts selected by NASA since 1959. Employees at the NASA Johnson Space Center in Houston, Texas, served as the control group. In January 2003, just before the explosion of the Columbia shuttle, 29 deaths (9.3%) were counted in the group of astronauts versus 17 (1.8%) in the control group. Note 20 accidental deaths among astronauts (versus 2 in the matched group). No other cause reached the threshold of significance."}
{"_id": "Radiology$$$73a0a488-7810-4b23-a5f0-210209fa5b2f", "text": "Compared to the control group at matched age, astronauts had a higher specific mortality rate (SMR) from cancer. This difference was not significant. However, both groups had a lower specific mortality rate than the general population. Fourteen cases of cancer have been described in astronauts (not counting 33 cases of non-melanoma skin cancer), which represents a relative risk of 1.59 compared to the Air Force pairings but of 0.54 compared to the cohort of NCI (general population), which ultimately remains insignificant. A later study found that standardized mortality rates for astronauts were significantly below US white male population rates [88]."}
{"_id": "Radiology$$$59e2cd36-7150-4a10-b260-1f2db2c79866", "text": "During a Mars exploration mission, each cell nucleus of an astronaut would be crossed by a proton or a secondary electron every 2 days, and by a heavier ion every month [89]. Due to their strong ionizing power, these ions appear to be the main vector of carcinogenic risk despite their low fluence."}
{"_id": "Radiology$$$0bde036d-bd52-4614-92c9-71f4d1caa136", "text": "The interval between irradiation and tumor appearance has been shown in rats to be shortened compared to conventional radiation [90, 91]; fewer events would be needed in the promotion of carcinogenesis induced by high-LET particles. Particle mass, energy, and charge can influence the cancer risk of an HZE particle."}
{"_id": "Radiology$$$c4219ce9-f39e-4794-b11a-e7f6c6dd4bb6", "text": "The linear no-threshold (LNT) model used to predict the risk of cancer mortality in astronauts sent on interplanetary missions relies on data from atomic bomb survivors extrapolated to this particular population, to these types of particles, and to the dose rates encountered in the space environment. Though nearly universally used by public bodies to assess cancer risk, LNT is far from being a scientific consensus and its application for low dose rates is rather controversial\u2014see Chap. 2. For cancer risk estimation, age at exposure, attained age, sex- and tissue-specific mortality and incidence, and latency has to be considered. Also, an important question is whether the additional cancer risk induced by space radiation exposure is independent of other cancerogenic events (excess absolute risk, EAR), or whether the risk depends on other cancer risks (excess relative risk, ERR)."}
{"_id": "Radiology$$$a04c9ea0-8de5-4817-8873-b02cb58fb858", "text": "Table 10.3 summarizes the LNT-estimated carcinogenic risk under different exposure conditions. The confidence interval includes epidemiological, physical, and biological uncertainties. The maximum acceptable risk for an astronaut dying from cancer is typically set at 3% [50].Table 10.3\nDoses and LNT-based estimates for cancer mortality risk following space missions\n\u00a0\nAbsorbed dose (Gy)\n\nEffective dose (Sv)\n\nRisk of death by cancer (%) [IC95%]\n\nMale 40 y.o.\n\nFemale 40 y.o.\n\nMoon Mission (180 days)\n\n0.06\n\n0.17\n\n0.68 [0.20\u20132.40]\n\n0.82 [0.24\u20133.00]\n\nMars Orbit Mission (600 days)\n\n0.37\n\n1.03\n\n4.00 [1.00\u201313.50]\n\n4.90 [1.40\u201316.20]\n\nMars Mission (1000 days)\n\n0.42\n\n1.07\n\n4.20 [1.30\u201313.60]\n\n5.10 [1.60\u201316.40]"}
{"_id": "Radiology$$$c4a39228-ae16-4b18-9dbf-30408cc81030", "text": "Besides the calculated increased cancer risk for astronauts, cataracts might be triggered or promoted by space radiation exposure. Astronauts exposed to a dose of more than 8 mSv exhibit earlier and more frequent cataracts (in a study that identified 295 astronauts paired with as many US Air Force pilots) [92]."}
{"_id": "Radiology$$$2ca5dd5b-f830-4a21-b028-81cbf0cd757b", "text": "Due to the densely distributed ionizations around a heavy ion\u2019s path through a cell nucleus, severe DNA damage (Sect. 10.5.3) possibly leading to chromosomal aberrations (Sect. 10.5.2) can be induced. Therefore, chromosome damage induced in vivo was identified early as a sensitive biodosimeter [93, 94] that integrates radiation exposure in quality and quantity and also the individual radiosensitivity [95]. Peripheral blood lymphocytes are accessible by venipuncture and the chromosomal aberration test can be performed with these cells before and after flight."}
{"_id": "Radiology$$$9bb3bfc8-ef5e-43ff-83d3-4853c7219ffc", "text": "In order to determine the effects of space radiation on astronauts, chromosomal aberrations were quantified already in Gemini astronauts before and after the spaceflight [96]. In some astronauts, a small increase was observed after the flight which did not correlate with flight duration (1\u201314 days), extravehicular activities, or diagnostic radioisotope injections [96]. Missions with a duration of up to 3 weeks did not result in an increase of the aberrations above background; after missions of 6 months or longer, a rise was clearly observed [95, 97\u2013104], but dose estimation based on the cytogenetic analysis varied strongly [95]. Here, the inter-individual variability of the translocations\u2019 half-life in peripheral blood lymphocytes has to be considered [105]. Also, the basal aberration frequency and the reaction toward ionizing radiation varies from individual to individual [106\u2013108]. Furthermore, the effects of multiple space missions might not be additive [109, 110]. Prediction of dicentrics frequencies for a Mars mission assume values 10\u201340\u00d7 above background in peripheral lymphocytes [111]."}
{"_id": "Radiology$$$a0bde527-30b1-46e0-badd-b2e396eea9d7", "text": "For detection of reciprocal translocations, multicolor fluorescence in situ hybridization (mFISH) was first applied to members of the Mir-18 crew [112]. In search of a specific marker of heavy ion exposure, complex chromosome interchanges were suggested and analyzed in blood lymphocytes of astronauts [113, 114]. High-resolution multicolor banding (mBAND) of chromosome 5 can visualize intrachromosomal exchanges\u2014long-term missions to the ISS did not increase this parameter [115]. Such inversions were only recently found in three astronauts during a 6-months ISS mission [116]. Complex chromosomal rearrangements occur very rarely in astronauts therefore their use as biomarker is limited [93]. Over the years, different cytogenetic or chromosomal signatures that allow reconstruction of absorbed dose and radiation quality were suggested, such as insertions [117], inversions [118], and complex chromosome interchanges, but up to now, no consensus for a biomarker of exposure to high-LET radiation has been reached [119] (see Sect. 8.\u200b7)."}
{"_id": "Radiology$$$cb781c34-3bf2-43f2-8a19-0a1892ed2cb9", "text": "The relevance of the telomere elongation that was first observed during the 1-year ISS mission and its fast shortening after return to Earth [120], which was now also found during 6-months missions [116], for assessment of space radiation risk is currently unclear. The telomere changes are considered as an integrative biomarker for effects of the spaceflight environment [121]."}
{"_id": "Radiology$$$8224ae45-d344-4c07-92f6-be6183e1c44a", "text": "Before the first human went to space, in 1952, Professor Cornelius A. Tobias made the famous prediction that cosmic radiation can cause unusual light sensations by interaction with the visual system. The Apollo-11 astronaut Edwin (Buzz) Aldrin was first reported to have perceived light flashes during the Moon mission [122]. This initiated a series of investigations already during the following Apollo missions [123], and later on Mir, Skylab, Apollo-Soyuz Test Project (ASTP), Shuttle missions, and on the ISS. They started with observation sessions and nuclear emulsion plates (Apollo light flash moving emulsion detector, ALFMED). The observations were later combined with sophisticated particle detectors in the Silicon Eye (SilEye-1 and -2) experiments on Mir [124], and Alteino-SilEye-3 and Anomalous Long-Term Effects on Astronauts (ALTEA) experiments on ISS, which included also an electroencephalograph."}
{"_id": "Radiology$$$b3aa31f2-b16d-4901-ae7d-8828ebf6577a", "text": "The observations of the Apollo astronauts resulted in an average event rate of one light flash event in ~3 min [123]. In LEO, when passing through the SAA, the light flash rates are very high [125], and outside the SAA, light flash frequency is higher in the polar parts of the orbit than in equatorial latitudes [126]. The number of light flashes perceived in LEO varies on average between one every minute up to one every 7 min on Mir [127] or every 20 min [128, 129] dependent on the orbital height, the inclination, the shielding of the spacecraft and solar activity [130]."}
{"_id": "Radiology$$$95395a51-5f6a-4aad-904d-824548a1e6b6", "text": "So, in conclusion, contrarily to the usual statement that we have no senses to perceive ionizing radiation, when closing their eyes, most space travelers can \u201csee\u201d the exposure to galactic cosmic rays and trapped radiation as mostly colorless light flashes or phosphenes in the form of spots, stars, streaks, or diffuse clouds of light [125]. About 15\u201320 min of dark adaptation is required [123] so that they are usually perceived before falling asleep."}
{"_id": "Radiology$$$529326a3-22af-438a-90d7-f911b2a58554", "text": "This light flash phenomenon is explained by a visual sensation that is produced by the interaction of highly energetic heavy ions with the retina of the eye [131, 132] or possibly with visual centers in the brain or the optic nerve after penetration of the spacecraft walls and the eye or head. The interaction might be direct or indirect via Cherenkov radiation in vitreous humor which is emitted as light when the charged particle passes through it with a velocity higher than the speed of light in the vitreous humor [133]. The probability of a heavy ion to cause a light flash has been estimated to be around 1%\u2014with increasing probability with increasing LET\u2014and for protons to be below 0.001% in LEO [127]. A deleterious effect of the flashes on vision is not suspected, but some astronauts report that their sleep was disturbed by light flashes."}
{"_id": "Radiology$$$1dbc0df8-73f7-4ac1-984a-a714ceab4738", "text": "Ionizing radiation, which exists primarily in the form of high-energy, charged particles make up space radiation. The radiation environment in space is characterized by a high complexity due to different sources and a higher number of particle species, and a broad energy range. Galactic cosmic radiation (GCR), solar particle events (SPE), and, in LEO, trapped radiation are the naturally occurring sources of space radiation."}
{"_id": "Radiology$$$0e8dccdc-8119-4307-a733-1c87f41d8f43", "text": "The exposure to GCR occurs at a low dose rate on the organismal level, but strong cellular effects might be triggered in case of a \u201chit\u201d by an energetic particle, especially high Z and high energy (HZE) particles or heavy ions. HZE particles make up only 1% of GCR therefore only small hit frequencies are expected in the human body that could be responsible for late effects [134]. First evidence of biological effects of HZE particles was found in mice after a high-altitude balloon flight when the coat of black mice locally turned grey [135]. Single particle effects on different dormant biological systems under spaceflight conditions were proven by means of the Biostack experiments on the Apollo-16 and -17 missions [10, 136]. In this experimental system, biological systems and detector foils were stacked onto each other to allow assignment of heavy ion hits to the biological systems. Heavy ion hits were detected in plastic foils (cellulose nitrate, polycarbonate), silver chloride crystals, and nuclear emulsions. The biological systems were immobilized on the foils with water-soluble polyvinyl alcohol and included Bacillus subtilis spores, seeds of the thale cress Arabidopsis thaliana, roots of the field bean Vicia faba, eggs of the brine shrimp Artemia salina, insect eggs (stick insect, Carausius morosus and rice weevil, Tribolium confusum), and protozoa cysts (Colpoda cucullus). The outgrowth of B. subtilis after germination was significantly reduced after an HZE particle hit [137, 138]. During the development of brine shrimp eggs that were hit by a single particle, abnormalities appeared at the extremities, the thorax, and the abdomen [139] and the eggs showed the most sensitive reaction toward HZE particles compared to the other biological systems in Biostack [137, 140]. Developmental abnormalities were also found in hit insect eggs [141]. The total dose for the Biostack experiments was quite low (5.8\u20137.5\u00a0mGy), and ~0.03 mGy was allocated to the HZE particles, whereby it has to be considered that the local dose in a hit cell can be much higher than the total dose."}
{"_id": "Radiology$$$737837fe-7b63-455b-adbd-e9641563e0d4", "text": "These experiments were continued in LEO using the Free Flyer Biostack Experiment (LDEF\u2014Long Duration Exposure Facility) [142], EURECA\u2014European Retrievable Carrier [143\u2013146], and the biosatellites COSMOS 1887 and 2004 [147, 148] and refined, so that synergistic effects of HZE particle hits and microgravity in the developmental disorders of C. morosus were revealed."}
{"_id": "Radiology$$$6b815fa8-2679-4820-9c16-d1c1541d124e", "text": "These intriguing results showing strong deleterious effects of single particle traversals and even an enhancement by other spaceflight environmental effects initiated a multitude of biological experiments in space and at heavy ion accelerators (see Sect. 10.9) in order to quantify the biological effectiveness of HZE particles, to understand the underlying mechanisms and to develop countermeasures. A variety of experimental models are used for these experiments (see Sects. 10.5\u201310.7, and 10.8.2). The uncertainties in risk assessment for cancer and non-cancer effects in the central nervous system and other organ systems for astronauts are still unacceptably high therefore further investigations into the biological effects of HZE particles are necessary. The experimental approaches shown in Box 10.3 below take the low dose rate but strong biological effects in case of a particle hit into account."}
{"_id": "Radiology$$$45147f08-572a-4298-8336-f2dc1026c058", "text": "Natural GCR exposure\nCorrelation of biological effects with single particle hits by combination of biological model and detector foil, e.g., Biostack; can be combined with 1xg reference centrifuge to determine contribution microgravity effects\n\nCorrelation of light flashes with HZE particles that traverse astronauts\u2019 eyes\n\nDose accumulation over weeks or months by storing dormant or freeze-dried or deep-frozen cells or small organisms in space, subsequent reactivation and measurement of radiation damage or response\n\nDetermination of spaceflight effects by exposure of, e.g., fruit flies, rodents, or other organisms on satellites or high-altitude balloons\nExposure to selected HZE particles\nExposure of a variety of biological systems at heavy ion accelerators or microbeam facilities to selected heavy ions (singe particle at defined energy or mixture of particles of defined energies) and analysis of the biological response"}
{"_id": "Radiology$$$c826359f-26f8-4354-a9b3-4abe7cb23b2e", "text": "Correlation of biological effects with single particle hits by combination of biological model and detector foil, e.g., Biostack; can be combined with 1xg reference centrifuge to determine contribution microgravity effects"}
{"_id": "Radiology$$$e8258bee-5ee3-401d-b46c-d3ed70e7e234", "text": "Correlation of light flashes with HZE particles that traverse astronauts\u2019 eyes"}
{"_id": "Radiology$$$faffbfe4-138a-4066-ab20-7bb061acbc29", "text": "Dose accumulation over weeks or months by storing dormant or freeze-dried or deep-frozen cells or small organisms in space, subsequent reactivation and measurement of radiation damage or response"}
{"_id": "Radiology$$$96b57a39-58d8-4b16-91ed-ff8cebc639e0", "text": "Determination of spaceflight effects by exposure of, e.g., fruit flies, rodents, or other organisms on satellites or high-altitude balloons"}
{"_id": "Radiology$$$401394f5-07a7-4b9d-b7b6-16a10ea1930d", "text": "Exposure of a variety of biological systems at heavy ion accelerators or microbeam facilities to selected heavy ions (singe particle at defined energy or mixture of particles of defined energies) and analysis of the biological response"}
{"_id": "Radiology$$$198aa42a-9ced-456f-bfbd-f25aef33deb5", "text": "As described in Chap. 2, radiation quality is an important factor influencing the cell death response. It can affect the extent and mode of cell death. A stronger cell killing of human cells by alpha particles with an LET up to 100 keV/\u03bcm was already observed in the 1960s [149], indicating an RBE for cell killing up to 7. Since then, survival data after heavy ion exposure were collected for many mammalian cell types including primary cells and tumor cell lines using the colony forming ability (CFA) test which is described in Chap. 2. This was less driven by space radiation research but by tumor therapy research to identify suitable ions and to determine the cell killing RBE for treatment planning. The shoulder observed in the dose response curves for cell killing by low-LET radiation disappears in high-LET survival curves, resulting in purely exponential dose\u2013effect relationships and indicating the lack of repair capacity after heavy ion exposure [150] (Fig. 10.13).\n\nA double line graph of surviving fraction versus dose in gray units plots the fast and slow declining curves for high L E T radiation and low L E T radiation, respectively.\n\nFig. 10.13\nSurvival of mammalian cells after exposure to low linear energy transfer (LET) and high-LET radiation. Low-LET radiation includes photons, electrons, positrons, protons, and more. High-LET radiation encompasses heavy ions, and, depending on energy, also He ions and neutrons"}
{"_id": "Radiology$$$16d79c07-1cbc-47b0-8d65-eca82c400557", "text": "A double line graph of surviving fraction versus dose in gray units plots the fast and slow declining curves for high L E T radiation and low L E T radiation, respectively."}
{"_id": "Radiology$$$9808bc76-ee1d-4de8-a6d1-009f97187db7", "text": "Clonogenic cell survival data for more than 1100 experiments comparing the effects of ion irradiation to photon irradiation are available in a database established by the GSI biophysics group [151]. The database is called Particle Irradiation Data Ensemble (PIDE, www.\u200bgsi.\u200bde/\u200bbio-pide). The maximal RBE for cell killing (10% survival level) was observed in the LET range of 100\u2013200 keV/\u03bcm with values of 2\u20137 [151]. This large variation in RBE is explained by the influence of particle species and energy in addition to LET, of cell type and other experimental factors. At LETs above ~200 keV/\u03bcm, more energy is deposited in a cell traversed by a particle than is required to kill the cell and more hits per cell cannot produce more cell death as any hit will kill the cell, resulting in a decrease of RBE that is called \u201coverkill effect.\u201d"}
{"_id": "Radiology$$$8e6b8102-d11f-4e36-851d-e6b14dc0f229", "text": "The clonogenic survival data integrate cell death by various modes such as mitotic catastrophe, apoptosis, necrosis, autophagy, and other mechanisms (see Chap. 2) and permanent cell cycle arrest, possibly accompanied by cellular senescence. As for low-LET radiation, it depends on the cell or tissue type whether a cell population is prone to ionizing radiation-induced apoptosis [152]. Apoptosis might occur at higher rates after high-LET radiation exposure compared to low-LET irradiation with a maximum at a LET of ~100 keV/\u03bcm [153]."}
{"_id": "Radiology$$$48ae1c5c-529d-49ba-a052-02d9c8dbd701", "text": "The consequences of heavy ion-induced cell death for the organism can be that transformation of a heavily damaged cell is prevented thereby protecting from cancer. This effect also limits the number of cells with mutations (see Sect. 10.5.4) or chromosomal aberrations at a LET >200 keV/\u03bcm (see Sect. 10.5.2) and cellular transformation (see Sect. 10.5.5). On the other hand, deleterious effects might occur such as depletion of stem cell pools or loss of terminally differentiated cells with no or low regeneration potential that might affect the functionality of a tissue or organ."}
{"_id": "Radiology$$$e508c22c-1a6a-4817-95f2-0f496a9430ba", "text": "For some microorganisms, growth and viability were measured during space missions. A 14-days exposure of Escherichia coli on the Space Shuttle or 140-d exposure on Mir did not result in any differences in viability and mutations frequencies in comparison to ground controls [154, 155]\u2014the same was the case in Saccharomyces cerevisiae [156]. Using repair-deficient E. coli mutants, DNA polymerase, and 3\u2032\u21925\u2032 exonuclease were identified as the most important enzymes for GCR-induced DNA damage in E. coli [157]. Also, the slime mold Dictyostelium discoideum did not grow differently and did not show differences in the mutation frequency in the spores during a 7-days Shuttle flight [158, 159], but the number of spores per fruiting body was reduced [160]."}
{"_id": "Radiology$$$bba0cf94-dd20-44c6-8022-ab13e94e9960", "text": "Chromosomal aberrations are alterations in DNA structure that become microscopically visible after following a chromosome staining protocol [161] (see Chap. 2). They can result from mis-rejoining of DNA ends from ionizing radiation-induced DNA double strand breaks (DSB), from lack of repair leading to terminal deletions and incomplete exchanges or from chromosome mis-segregation [162, 163]. They are exquisitely and quantitatively sensitive to ionizing radiation. Symmetrical resolution of the DNA DSB can lead to chromosomal interchanges resulting in translocations which are usually nonlethal. Asymmetrical resolution produces among other dicentrics (chromosomes with two centromeres) and acentric fragments, mostly contained within micronuclei; also, during the repair process, DNA sections can be lost, producing a deletion [164]. Ionizing radiation can also induce quadriradials (U-type by asymmetrical resolution, X-type by symmetrical resolution). Complex and asymmetric aberrations such as dicentrics usually lead to cell death (lethal aberrations) [163]."}
{"_id": "Radiology$$$e0b308bc-5f4a-4fcc-9e6c-28b0047d0618", "text": "They are determined during metaphase or by chemically induced Premature Chromosome Condensation (PCC, see Chap. 2) during interphase [165], usually in lymphocytes or fibroblasts, providing data on a cell-by-cell basis. Their dose\u2013response relationship follows a curvature. While dicentrics and acentric fragments can be detected with a GIEMSA staining, mFISH is required for interchromosomal translocations and mBAND for intrachromosomal translocations (see Sect. 10.3.4). Inversions can be detected by Directional Genomic Hybridization (dGH) [166]."}
{"_id": "Radiology$$$7b38917d-0e7c-4fe1-965c-e679906975f6", "text": "Chromosomal aberrations are of high interest in space radiation biology as they are an early-stage effect and regarded as a surrogate endpoint for cancer risk as many human cancers are linked to them and all \u201cclastogens2\u201d are both mutagenic and carcinogenic."}
{"_id": "Radiology$$$60a49f7a-3bb4-4f9a-93fa-0aba94dbf98e", "text": "For carcinogenesis, the surviving cells with chromosomal aberrations are relevant. The fraction of these cells depends on LET, track structure, and fractionation (Box 10.4)."}
{"_id": "Radiology$$$bf949a4d-3cb1-44e0-a650-0bf7cd1efda1", "text": "Dose rate\n\nFractionation\n\nLinear energy transfer (LET)\n\nTrack structure\n\nCell nuclear geometry (e.g., spherical or flat)"}
{"_id": "Radiology$$$640b5463-96b4-44a1-b7eb-6e1196151d49", "text": "Cell nuclear geometry (e.g., spherical or flat)"}
{"_id": "Radiology$$$f7428117-a82b-4f35-a9a1-089718832686", "text": "HZE particles have a very high efficiency in inducing chromosomal aberrations\u2014the RBE in comparison to low-LET radiation was estimated to reach 30\u201335 during interphase [163, 167, 168]. Furthermore, high-LET \u03b1-particles at low fluences (1 track per cell nucleus) were more efficient in inducing complex aberrations in human peripheral blood lymphocytes than X-rays [117]. Complex chromosome aberrations are defined as aberrations that involve three or more breaks in at least two chromosomes. Here, the particle track structure comes into play [169]. Delta rays move out of the primary particle track, producing further ionizations that can induce damage. This damage might interact with other breaks generated by either a separate track or delta rays emanating from it (intratrack action). The range of the delta rays is proportional to the specific energy of its corresponding primary particle. Higher energy particles would have a greater chance of track interaction than their lower energy counterparts because of the longer range of the delta rays where breaks can be close in space and time at high doses and dose rates as they are produced by multiple tracks (intertrack action). The breakpoints induced by delta rays add up to those produced in the primary particle track. Hence, the number of exchange breakpoints and their spatial arrangement are important determinants for the formation of complex exchanges. For example, the number of breakpoints per cell was higher for 56Fe ions (1.1 GeV/n) and \u03b1-particles (0.9 MeV/n) in comparison to 137Cs \u03b3-rays. In spherical cell nuclei, one particle traversal is sufficient to produce two breakpoints, e.g., in a lymphocyte [170, 171]. In summary, HZE particles produce more breakpoints per track and more highly complex exchanges compared to low-LET radiation [118] (Fig. 10.14). These complex aberrations partly disappear between the first and second cell division after radiation exposure, but some are transmissible and might be stable through several cell generations.\n\nA diagram of a cell depicts a prominent nucleus with nucleolus, chromatin, and nuclear membrane. The passage of F e 56 ion depicts many breaches in the chromatin material.\n\nFig. 10.14\nAs a heavy ion travels through a mammalian cell nucleus, a multiple of ionizations is produced, damaging a chromosome arranged in its nuclear territory several times. Delta rays emanating from the primary track can induce further damage. Therefore, traversal of high-LET radiation through a cell nucleus can produce many breakpoints in chromosomes"}
{"_id": "Radiology$$$8e0d4e2d-323e-4628-89d1-6158d075a02a", "text": "A diagram of a cell depicts a prominent nucleus with nucleolus, chromatin, and nuclear membrane. The passage of F e 56 ion depicts many breaches in the chromatin material."}
{"_id": "Radiology$$$a2d379fd-27d2-485d-8289-76337bfb8b85", "text": "As other radiation qualities, protons, \u03b1-particles, and HZE particles can induce various types of DNA damage by direct ionization or indirectly through radiolysis of intracellular water (see Chap. 2). Among base damage, loss of bases, DNA-DNA and DNA-protein crosslinks, single strand breaks (SSBs), and double strand breaks (DSBs), DNA DSBs are the most severe DNA lesion. Unrepaired DNA DSBs are at the center of biological effects such as cell killing and chromosomal aberrations and are trailblazers of the majority of early and late effects induced by ionizing radiation exposure [163, 172, 173]."}
{"_id": "Radiology$$$546bf827-d7f5-4a86-8239-4cf40676b90a", "text": "What makes particle radiation special is the multitude of ionizations localized along the particle\u2019s path through the cell. The spatial distribution of direct DNA damage differs strongly for low- and high-LET radiation, with a diffuse distribution for the former and clusters for the latter. Such clusters of different damage (base lesions, abasic sites, SSB, DSB, etc.) within a few helical turns of DNA are called complex DNA damage (Fig. 10.15) (formerly: multiply damaged sites or clustered DNA damage) [164, 174, 175].\n\nA diagram of double helical structure of D N A depicts a few ionizing events in the passage of electron with low L E T and many ionizing events in the passage of alpha particles with high L E T.\n\nFig. 10.15\nComparison of ionizations (grey dots) in a DNA molecule that are induced by electrons as an example of low-LET radiation and by a high-LET \u03b1-particle. The ionizations produced by the \u03b1-particle are located densely along the track, with some secondary electrons (\u03b4 rays) generated while traversing the cell. This spatial distribution goes along with a higher probability of simultaneously breaking both DNA strands thereby producing a double strand break (DSB), and also further damage to bases and single strand breaks (SSB) in close proximity which is then called complex DNA damage"}
{"_id": "Radiology$$$6778ad00-f3d4-4f98-806f-e7423a1914fb", "text": "A diagram of double helical structure of D N A depicts a few ionizing events in the passage of electron with low L E T and many ionizing events in the passage of alpha particles with high L E T."}
{"_id": "Radiology$$$8dccc3f3-d51a-4d68-8788-b4fd802805b0", "text": "Although the contribution of direct action to the biological effectiveness of high-LET radiation is larger than indirect action [176], reactive oxygen species (ROS) generated by radiolysis can also play a part in the overall radiation effects. As the lifetime and diffusion range of ROS are small, only radicals produced in DNA\u2019s vicinity are relevant for DNA damage induction and increase in its complexity. With increasing LET, the contribution of direct effects rises, and the indirect effects drop. Low-LET radiation and endogenous ROS rarely induce complex DNA damage [163]."}
{"_id": "Radiology$$$fe04ece7-9fa2-4ec5-a5c8-9a80322ab9c5", "text": "The detection of GCR-induced DNA damage succeeded in HeLa cells during the Shuttle and Mir missions [177\u2013179]. In human lymphoblastoid cells that were stored at \u201380\u00a0\u00b0C for several months on ISS\u2014in total 134 days at an average dose rate of 0.7\u00a0mSv/day, one particle track per 100 cells was detected by means of immunofluorescence staining of \u03b3H2AX after return to the ground (see below) [180]. Such tracks were also observed in human fibroblasts that were cultivated for 14 days on the ISS [181]."}
{"_id": "Radiology$$$70c80c18-95df-4707-b5ad-ab9223ee0adb", "text": "Various DNA damage repair pathways ensure genome integrity and stability in uni- and multicellular organisms. The current understanding is that multiple repair pathways have to be coordinated to repair complex DNA damage making it very challenging, that short fragments might be lost during repair and that multiple breakpoints in the DNA ribose-phosphate backbone can favor complex genomic rearrangements [164, 182]. The damage might still persist at DNA replication because of repair delays that were observed after HZE particle exposure. If repair of complex lesions is completed, its fidelity might be lower when compared to simple DNA damage [183\u2013185]. After 56Fe ion (1 GeV/n) exposure, 14% of the damage remained unrepaired compared to 5% after \u03b3-ray or \u03b1-particle exposure [171]. In vivo, persistent DNA DSBs were found even 1 month after exposure to iron ions [186]. Growth arrest, cell death, or senescence are possible consequences of such unrepaired DNA damage [164], while mutations and chromosomal aberrations are key steps in cellular transformation and tumorigenesis."}
{"_id": "Radiology$$$36bae1ae-316d-4651-a381-0845d63b3072", "text": "DSBs are mainly repaired by nonhomologous end joining (NHEJ) and homologous recombination (HR) in eukaryotes (see Chap. 2). DNA DSB repair follows biphasic kinetics with a faster velocity in the beginning and lower speed at later timepoints. The phosphorylated form of the histone variant H2AX (\u03b3H2AX) [187, 188] as a marker of DNA DSB is often applied to microscopically visualize DSB induced by high-LET radiation exposure, sometimes in combination with antibodies binding to 53BP1 or other DSB repair proteins or to oxidative base damage [189]. After immunofluorescence staining, fluorescent foci indicate \u03b3H2AX and 53BP1 accumulation around DNA DSB. Ground-based experiments performed at heavy ion accelerators allow quantification of DNA damage induction and DNA repair by one ion with a specific energy or, since lately, several ion species with specific energies hitting the cells from one direction (see Sect. 10.10.4). They are usually performed additionally with low-LET radiation for comparison."}
{"_id": "Radiology$$$221c795a-c301-48b1-8417-9c38f92ed6c8", "text": "For example, in human fibroblasts, repair of DSB induced by carbon ions was slower than those induced by proton or helium ion irradiation and the size of the repair foci increased with increasing LET [190]. Larger repair foci that persist longer are a common finding when exposure to heavy ions and X-rays are compared [191, 192]. One day after exposure to 1 GeV/n iron ions, 30\u201340% of the 53BP1 and \u03b3H2AX foci still remained indicating the extent of residual damage [193]. The slow repair kinetics and incompleteness of repair of DNA damage induced by high-LET radiation [190, 191, 194] are consistent findings of experiments with mammalian cells at heavy ion accelerators. Also, there are some hints that high-LET radiation inhibits c-NHEJ and shifts toward error-prone alternative nonhomologous end joining repair and microhomology-mediated end joining, resulting in a lowered fidelity of repair for days or weeks [195]. Other studies have shown that the repair of complex DNA requires DNA resection for processing at the DNA ends in G1 and G2 cells and forces the pathway choice toward resection-dependent HR [196, 197]."}
{"_id": "Radiology$$$fd74b2c3-a793-4f95-b061-b6f86256efd3", "text": "As mentioned above, to repair complex DNA damage, other repair pathways might be involved such as base excision repair (BER) and/or nucleotide excision repair NER [198]. Oxidative base damage such as 8-oxoguanine can be restituted by BER starting with damage recognition and removal by a DNA glycosylase and final steps by polymerase and ligase proteins [172]. NER is responsible for the repair of larger helix-distorting lesions."}
{"_id": "Radiology$$$47c00281-b412-45a6-8e5b-310d38a59962", "text": "In summary, DNA damage complexity increases with increasing LET, resulting in less effective DNA repair, a higher rate of residual lesions, genomic instability, and enhanced cell killing [174]."}
{"_id": "Radiology$$$d3554379-8af5-42be-b223-5377ae88cd65", "text": "The results of the Biostack experiments raised the question of whether microgravity or other spaceflight environmental factors affect DNA repair processes, as explained hereinafter. The advanced Biostack experiments included an inflight 1g control on a centrifuge, allowing the separation of effects of microgravity and of all other environmental factors. In this experiment, eggs of the stick insect Carausius morosus were exposed in space and the HZE particle hits were traced back to the eggs by means of particle track detector foils. Back on Earth, the insects were allowed to hatch. When the eggs were hit by an HZE particle under microgravity, more abnormalities were observed compared to hits during centrifugation at 1g, indicating additive or even synergistic damaging effects of cosmic radiation and microgravity [144]."}
{"_id": "Radiology$$$beddddff-9218-4d21-b9c9-70c5257229e0", "text": "Therefore, DNA repair and radiation response under microgravity were examined in further spaceflight experiments using a 1g centrifuge inflight control and in ground-based simulation using clinostats or random positioning machines. For determining subtle differences in DNA repair capacity or kinetics, a high level of DNA damage has to be induced. For this purpose, the dose rates of GCR in LEO on the Space Shuttle or on ISS are too low; therefore, DNA damage has to be induced by irradiation on ground in a metabolically inactive state, by irradiation in space using an artificial radiation source brought in LEO or by incubation with chemicals. When radiation damage was already induced on ground using a radiation source, cooled cells were brought to space and activated there to repair their DNA under microgravity [199, 200]. Alternatively, DNA DSB were induced by bleomycin [201] or restriction enzymes [202] during spaceflight. Often, no or only small interactions were found [203, 204]. In yeast however DNA DSB repair was delayed under microgravity, suggesting additive effects of radiation and microgravity [205, 206]. In human fibroblasts and Bacillus subtilis, microgravity did not influence the repair of DNA SSB and DSB [200, 207]. Also, ligase activity [204] and DNA replication [208] were not affected. The expression of genes involved in the DNA damage response was altered under microgravity [209\u2013211]. Besides these gene expression changes, a growth-stimulating effect of microgravity was observed in many ground-based and space experiments that might contribute to the microgravity effects on the DNA damage response [209]. In ground-based experiments, limitations of various microgravity simulators have to be considered [212], especially the generation of shear forces [213] as possible confounders. For microorganisms, such as bacteria, it has also to be considered whether they are motile because of, e.g., flagella or not, and the effect of microgravity can be most likely attributed to changes in the medium surrounding the microbes [214]."}
{"_id": "Radiology$$$7cd93827-fbf3-44db-b7b8-fb22239d7d7c", "text": "Animal experiments addressing the question of DNA repair under spaceflight conditions are scarce. After a 14-day spaceflight, the level of the tumor suppressor p53, which acts as a transcription factor in the DNA damage response, was increased in the muscle of mice compared to ground control mice [179]. Experiments with the nematode Caenorhabditis elegans during the Shenzhou-8 mission revealed changes in the expression of four microRNAs and of 4.2% of the genes involved in the DNA damage response after 16.5 days of microgravity when compared to the inflight 1g control [215]. Hindlimb unloading is used in rodent models to simulate on ground the head-ward fluid shift that occurs in microgravity. After 21 days of hindlimb unloading and low-dose irradiation of mice, some genes involved in DNA repair, chromatin organization, and cell cycle were differentially expressed in the spleen compared to control mice [216]."}
{"_id": "Radiology$$$e7e36b94-5141-4a1e-8fb4-f469f56100ab", "text": "Space experiments are the only way to unambiguously identify the effects of real microgravity on biological systems, here the enzymatic repair of radiation-induced DNA damages. The opportunities to perform experiments with actively metabolizing organisms in space are rare and usually have a long lead time from the acceptance of an experiment proposal to the execution of the experiment in space."}
{"_id": "Radiology$$$e25009c6-af68-4a1c-8215-839efe2b5052", "text": "The Biolab facility in the Columbus module of the ISS provides many possibilities for biological experiments on microorganisms, cells, tissue cultures, small plants, and small invertebrates in LEO (https://\u200bwww.\u200besa.\u200bint/\u200bScience_\u200bExploration/\u200bHuman_\u200band_\u200bRobotic_\u200bExploration/\u200bColumbus/\u200bBiolab). However, experiments on the ISS are subjected to limitations such as up- and download mass, up- and download temperature conditions, availability of a suitable facility in space, data downlink, number of sample replicates, appropriate control experiments in space and on ground. The Biolab facility will be used for LUX-in-Space (ESA AO LSRA-2014-026, Team Coordinator: P. Rettberg), the first space experiment where the whole series of events from DNA damage induction in metabolically active cells to the different steps of enzymatic repair reactions will take place in real microgravity and the repair kinetics will be monitored by optical measurements in situ. The effects of microgravity will be clearly separated from other spaceflight factors by comparison with parallel samples on an onboard 1g centrifuge in the Biolab facility and in a parallel ground control experiment with identical samples in flight-identical hardware. Due to safety issues, ESA decided to apply UV radiation for DNA damage induction. It causes defined types of DNA damage, e.g., cyclobutane pyrimidine dimers, which are among those also induced by ionizing radiation. Bacteria serve as model organisms possessing the same type of nucleotide excision repair as all other living organisms including humans. The capability of bacterial cells to counteract radiation damage by activating genes involved in DNA repair will be assessed using a bioluminescent reporter gene operon under the control of the SOS regulon, known as the SOS LUX assay. The DNA repair kinetics will be followed by bioluminescence and optical density measurements. For the space experiment, TripleLux Part C preparatory work was already performed successfully to adapt the SOS LUX assay to the space conditions provided by the Biolab facility on the ISS. This experiment was canceled later by ESA due to a lack of available resources at that time and it is a predecessor of LUX-in-Space [217, 218]. The launch of LUX-in-Space is scheduled for 2023/2024."}
{"_id": "Radiology$$$e22c6234-dbc5-4dfa-96ce-5146c654fb8b", "text": "Biosentinel will be the first deep-space experiment investigating the repair of DNA damage induced by space radiation (Principal Investigator: Sharmila Bhattacharya). It is a further development of NASA\u2019s biological CubeSats, small satellites with different payloads that were already flown successfully in LEO. Biosentinel will first follow a trajectory of cis-lunar flyby and, for 6\u201312 months, enter a heliocentric orbit. The organism under investigation is the budding yeast Saccharomyces cerevisiae. These eukaryotic cells are robust, desiccation resistant, were already flown in space before, and have similarities to cells of higher organisms such as humans. Cells from a radiation-resistant yeast wildtype strain and a radiation-sensitive \u0394rad51D mutant will be uploaded in a dry form. After different periods of time, during which the cells will accumulate radiation-induced DNA damage, the cells will be activated by the addition of nutrient medium and their growth and metabolic activity will be measured optically. In parallel, another Biosentinel payload will be flown in the ISS, in addition to the corresponding ground reference experiment. The launch is scheduled for 2022 as a secondary payload of NASA\u2019s Artemis-1 mission [219, 220]."}
{"_id": "Radiology$$$3e085886-c287-47ac-9b67-0bd417aaece9", "text": "Mutations as a deleterious outcome of erroneous repair of space radiation-induced DNA damage are of special interest in radiation risk assessment as they can initiate the multi-step carcinogenic process [163, 182] and they can be responsible for genetic effects in the offspring if they occur in the germline. Mutations can be detected in cells that survived irradiation and are, as chromosomal aberrations, late endpoints of radiation-induced DNA damage. For improving space radiation risk assessment, the dependence of mutation induction by radiation of different linear energy transfer (LET) was examined in different biological systems: Mutation induction by heavy ions was determined in many organisms including bacteria (E. coli, B. subtilis), yeast (S. cerevisiae), Neurospora, Drosophila, C. elegans, M. musculus, plants, and mammalian cell systems including human fibroblasts and lymphoid cells. These were mostly ground-based experiments at heavy ion accelerators."}
{"_id": "Radiology$$$1b1b8433-ab4e-47e1-810e-206a3fe4667d", "text": "The hypoxanthine guanine phosphoribosyl transferase (HPRT, EC 2.4.2.8) gene (mutations on the single copy X-chromosome in male-derived cells) in human diploid fibroblasts was used in early studies of LET dependency of mutation induction. A maximum of around 7 times more mutations compared to low-LET radiation was observed for helium ions or heavier ions with a LET of 100\u2013300 keV/\u03bcm [221]. The number of mutations per single track through a mammalian cell nucleus increases with LET, reaching saturation at around 100 keV/\u03bcm [222]. The induction of mutations in the X-linked HPRT locus in Chinese hamster cells by accelerated heavy ions reached a local maximum in the LET range of 80\u2013100 keV/\u03bcm [223]."}
{"_id": "Radiology$$$34d0e415-c9d0-42cc-90c2-9b33c5bddedb", "text": "Studies on mutation induction in autosomes became possible by means of AL human-hamster hybrid cells having one copy of human chromosome 11. In these hybrid cells, neutrons of various energies were more efficient in inducing mutations in the a1 locus on chromosome 11 compared to gamma rays; the RBE reached up to 30 at the 0.1% survival level [224]. The autosomal thymidine kinase gene (TK1) locus in human cells allowed investigation of the loss of heterozygosity (LOH) which can occur via deletion or allelic recombination and it revealed a higher peak of mutations at a lower LET (~50\u2013100 keV/\u03bcm) compared to the HPRT mutations (up to 15\u00d7 compared to ~5\u00d7). As for other biological endpoints, LET is not the only determinant of the biological efficiency of an HZE particle. The track structure means the energy deposition pattern varies for different ion species of the same LET. Such an effect of ion species was observed for mutation induction at the HPRT locus in human fibroblast-like cells\u2014the RBE for mutation induction determined in this system was between 3.6 and 7 for carbon and neon ion beams in the LET range of 60\u2013120 keV/\u03bcm compared to 137Cs gamma rays [225]."}
{"_id": "Radiology$$$482957f5-77d1-4b76-8b4f-0fbe761810bf", "text": "Besides mutations observed in the direct hit cells, bystander mutagenesis can contribute to the overall mutation rate after particle exposure as it was observed, for example, after alpha particle exposure [226]."}
{"_id": "Radiology$$$34f9b941-b235-4354-92dc-ca4a95784144", "text": "An experiment on the ISS designed to detect mutations in human cells that were induced by natural galactic rays made use of the frozen storage as described in Sect. 10.5.3. Frozen human lymphoblastoid TK6 cells were stored for 134 days in the Kibo module of the ISS and accumulated a dose of 72 mSv. After analysis on ground, a tendency for higher mutation frequency at the TK locus was observed in the flight samples compared to ground control [227]. Earlier experiments on Mir for 40 days with a model system based on Saccharomyces cerevisiae and Escherichia coli also revealed two to threefold higher mutation frequencies in some flight samples compared to ground samples, with a predominance of large deletions that might be caused by high-LET radiation [228]."}
{"_id": "Radiology$$$1ec2ab4e-d76b-4334-ba24-5f1e9f14f1d6", "text": "If mutations occur in tumor suppressor genes and inactivating them, or proto-oncogenes and activating them, cells can be transformed and lose growth control including anchorage-dependent growth. It can be seen as a surrogate marker for the carcinogenic potential of a radiation quality in question. Transformation can only occur in cells that survived the radiation exposure. In vitro, transformation of mammalian cells is determined by their ability to grow anchorage independently in soft agar. The soft agar test was applied to different cell types after exposure to HZE particles at heavy ion accelerators in order to determine their potential for transformation, usually in comparison to low-LET radiation."}
{"_id": "Radiology$$$1ba1cfb9-9e37-49c2-851f-d1ec50cac900", "text": "Already in the 1980s, it was shown that HZE particles are more effective in transforming mammalian cells than low-LET radiation: In mouse embryonic cells (C3H10T1/2), the effectivity of transformation increased up to 10 with a LET ~200 keV/\u03bcm [229] while Hei et al. observed a plateau at LETs of 80\u2013120 keV/\u03bcm [230]. In Golden hamster embryo cells, 14N ions (LET 530 keV/\u03bcm) and 4He ions (36 and 77 keV/\u03bcm) were ~3\u00d7 more effective in inducing cellular transformation than gamma or X-rays [231]. Later, a maximal RBE for neoplastic transformation was found at a LET of ~100 keV/\u03bcm, reaching a maximum of seven [232]. In human bronchial epithelial cells, iron and silicon ions (LET 151 and 44 keV/\u03bcm, respectively) were more efficient in inducing transformation than gamma rays from a 137Cs source especially when these cells were oncogenically progressed by stable transfection of mutant oncogenes [233]."}
{"_id": "Radiology$$$721f0bf1-25d5-4637-b48f-1559bac78079", "text": "Cell cycle arrests play a central role in the DNA damage response of dividing cells. Before the cell enters the next cell cycle phase, e.g., from G1 to S phase or from S to G2/M phase, they allow repair of damaged DNA (Chap. 2). They can therefore protect from cell death, mutations or chromosomal aberrations. Concerning the special radiation qualities present in space that are prone to induce complex DNA damage which might persist longer, stronger, or longer cell cycle arrests might be induced in comparison to low-LET radiation. Early experiments observing mitotic delay by time-lapse microscopic cinematography already gave hints that accelerated neon ions produce a stronger delay compared to Co-60 gamma rays [234]. High-LET radiation produces stronger and more persistent blocks in the G2 phase of the cell cycle than low-LET radiation [235]. In synchronous V79 Chinese hamster cells, the cell cycle delays per particle traversal increased with increasing LET and were primarily due to blocks in S and G2/M phase of the cell cycle [236]. Permanent arrest in the G1 phase can also be induced by high-LET radiation [237]. The relative biological efficiency of heavy charged particles with a LET in the range of 100\u2013330 keV/\u03bcm for inducing cell division delays was 3.3\u20134.4 [236] and the percentage of mitotic cells as indication of an arrest at the early G2/M checkpoint decreased with increasing LET [238]. The cell cycle regulating protein p21 (CDKN1A) accumulates in nuclear foci rapidly after heavy ion exposure of fibroblasts [239]. Besides this, expression levels of cell cycle regulatory proteins might be affected to a higher extent by high-LET radiation compared to low-LET radiation [237], for example, after iron ion exposure p21 expression was much higher compared to gamma rays and persisted 10 days after irradiation [193]."}
{"_id": "Radiology$$$a9f03479-2746-4efa-b394-7bf3791e98d3", "text": "Similar to studies with low-LET radiation, gene expression studies after high-LET radiation developed from a focus on single genes (mRNA and protein level by Northern Blot, RT-PCR, real-time RT-qPCR, Western Blot) to arrays of multiple genes, microarrays [240] and detection of the levels of all mRNAs present in cell populations or even single cells by RNA sequencing. After exposure to ionizing radiation, signal transduction pathways can result in the activation of transcription factors. These transcription factors bind to binding sites in their target genes\u2019 promoters which are specific for them (usually short palindromic DNA motifs) [241]. Also, besides promoter or enhancer activation via transcription factor binding, epigenetic mechanisms can be responsible for (persistent) gene expression changes and are therefore the focus of mechanistic research (see Sect. 10.5.9)."}
{"_id": "Radiology$$$080f40a1-5086-485e-b37e-d939090bde03", "text": "In addition to spaceflight experiments, a huge amount of gene expression data from ground-based exposure to neutrons, protons, and different heavy ions for different experimental model systems exists. NASA GeneLab (https://\u200bgenelab.\u200bnasa.\u200bgov/\u200b) offers a repository for space-related omics data, among others transcriptomics and proteomics from experiments with model organisms, cells, cell lines, and tissues. Currently, a comprehensive picture of gene expression changes is difficult to paint due to the multiple influencing factors that range from the model system (e.g., gut epithelial cells and human bronchial epithelial cells, tissue, animal model) to the methods, cell cycle phase, radiation qualities, doses, kinetics of exposure, timepoint after exposure, and additional spaceflight environmental factors (such as simulation of microgravity effects by hindlimb unloading). The interpretation of the data is complicated by the fact that in the majority of the heavy ion accelerator experiments, the dose is acutely applied within minutes, while exposure during long-term space missions is protracted over several months."}
{"_id": "Radiology$$$b0466bae-6525-4d96-9581-77e16ffcb693", "text": "The emerging view is that heavy ions, especially iron ions are capable to induce a stress response persisting for several weeks in addition to an early transient response. This early response can encompass p38MAPK and TP53 activation and expression of its target genes, whereby the cell cycle regulator gene CDKN1A can also be expressed TP53-independently. In tissues, long-term changes in the expression of genes involved in inflammatory and free-radical scavenging pathways occur after iron ion exposure and these changes involve transcription factors such as signal transducer and activator of transcription 3 (STAT3), GATA binding protein 4 (GATA4), Nuclear Factor \u03baB (NF-\u03baB) and nuclear factor of activated T cells 4 (NFATc4) [242]. In human cells, NF-\u03baB was strongly activated by heavy ions, its activation depended on LET [243] and the expression of several chemo- and cytokines was increased [244]."}
{"_id": "Radiology$$$5d883642-c875-45b6-9cbf-75c55c78570b", "text": "HZE particles are potent inducers of senescence, more potent than gamma rays. Senescence-associated changes in the tumor microenvironment may induce invasion and stemness of tumor cells. Senolytics can be applied to eliminate senescent cells and thereby deplete senescent stromal cells with tumor supportive roles. Shortening of telomeric sequences can lead to telomere fusions and contributes the chromosome instability after heavy ion exposure [245]. Furthermore, accumulation of short telomeres eventually triggers apoptosis or senescence. Unlike normal somatic cells, germline, stem, and tumor cells avoid the latter through a high expression of telomerase. Due to natural telomere shortening during cell division, telomere length is highly linked to aging [246]. Considering the environmental radiation exposure during spaceflight, with higher levels of HZE particles compared to on Earth, NASA investigated the effect of spaceflight on telomere length in the twin study. The twin study examined molecular- and physiological differences of twin astronauts, one spending a year onboard the ISS and the other on Earth [120]. Telomere lengths of peripheral blood mononuclear cells (PBMCs), collected from peripheral blood samples taken preflight from both twins were of similar length. However, during spaceflight, the space twin\u2019s telomere length increased significantly, while the Earth twin\u2019s telomers remained stable during the study. Once returning to Earth, the increased telomere length diminished within 48 h and the number of short telomeres increased compared to preflight [116]. While an unexpected finding, increased telomere length has recently been associated with other biological functions such as DNA damage response, cell cycle kinetics, and mitochondrial stress [247]. Indeed, chromosome aberrations (inversions and translocations) were more frequent during spaceflight and inversion frequencies of the space twin remained elevated postflight, consistent with ionizing radiation exposure inflight. Furthermore, DNA damage repair pathways were upregulated in several circulating immune cells, suggesting increased genomic instability due to ionizing radiation during spaceflight [121]. Similar results (increased telomere length and chromosomal aberrations) were also seen in astronauts during a 6-month spaceflight mission. While telomerase activity likely is responsible for the increased telomere length inflight, the actual contributing mechanism is still unknown. However, astronauts returning from 1 year and 6 month missions showed elevated telomerase activity upon return to Earth [116]."}
{"_id": "Radiology$$$c90bed28-7210-46b7-8de7-5f2dcba40590", "text": "Persistent gene expression and functional changes induced by space radiation exposure could be caused by changes in the epigenome. Changes in the DNA methylation profile and in the histone code encompassing methylation and acetylation of histones could therefore contribute to high-LET carcinogenesis and degenerative diseases and could represent possible prophylactic or therapeutic targets."}
{"_id": "Radiology$$$e14b5cf6-1d22-488d-9d44-9dac016250d3", "text": "For example, in immortalized human bronchial epithelial cells, hypermethylation at CpG sites occurred early after Fe-56 ion exposure and persisted a long time [248]. Long-term epigenetic reprogramming after such exposure was also observed in hematopoietic progenitor and stem cells [249]."}
{"_id": "Radiology$$$08f24a5e-fb12-4300-8865-2c01763c8a00", "text": "High levels of DNA methylating enzymes were also found in the hippocampus of Si-28 ion irradiated mice that developed cognitive impairment [250]."}
{"_id": "Radiology$$$bb71b610-cad6-4cf5-aa21-8eff8b3eaaf7", "text": "In addition to heavy ion exposure experiments, combined exposure to simulated microgravity and chronic low-dose irradiation or spaceflight experiments using small animals or cell cultures and astronaut data reveal alterations in the methylome and histone modification status after combined exposure to spaceflight environmental factors such as microgravity and space radiation. The lasting imprint of high-LET radiation exposure on the epigenome might allow monitoring the cumulative biological impact of space radiation exposure [248]."}
{"_id": "Radiology$$$30642b50-a3d8-4b18-a49e-bebfbfa9a09b", "text": "The use of small animal models in research is debatable, but still essential to provide general information on cellular and molecular mechanisms, to develop new drugs and treatments. They are mainly used in fundamental scientific research, for the advancement and development of new diagnostic tests and treatment for diseases, for education of researchers as well as in safety assessments of drugs and chemicals."}
{"_id": "Radiology$$$2ffbea1d-c49c-440d-9878-173a4d3bde4b", "text": "Animals are a useful research subject for a variety of reasons. Only in living organisms, it is possible to study complex physiological processes. Furthermore, the environment of the experiment can be perfectly controlled (e.g., diet, light, housing, etc.). Also, they have a shorter life cycle so studies can be conducted throughout a whole lifespan or across generations. Animals are biologically very similar to humans and often suffer from similar health problems. In fact, mice share more than 85% of protein-encoding genes with humans\u2014Why Mouse Matters, from the National Human Genome Research Institute (https://\u200bwww.\u200bgenome.\u200bgov/\u200b10001345/\u200bimportance-of-mouse-genome)."}
{"_id": "Radiology$$$be80e0c0-ceb4-43d6-8715-43099b503d52", "text": "Animal experiments can cause harm to the animal thus ethical review processes have been established around the world [251]. With respect to this, the 3R\u00b4s principle by [252] ensure the reduction of animal numbers, refining the test methods to lower the harm to the animal to a minimum and replace animal experiments with alternative methods, when possible (Box 10.5)."}
{"_id": "Radiology$$$a34a2040-ded8-42ad-939e-017fe78ae8c2", "text": "The aim of the principle is to improve the treatment of laboratory animals and at the same time advance the quality of scientific studies.\nReplacement: Includes methods that avoid or replace the use of animals such as computer/mathematical models (in silico), cell culture models (in vitro), or relative replacement (e.g., invertebrates, such as fruit flies and nematode worms).\n\nReduction: With improved experimental design, modern imaging, or sharing data and resources, the total number of animals needed can be minimized.\n\nRefinement: Modification in the experiment, which minimize pain, suffering, and distress and allow general improvement of animal welfare (e.g., improvement in the research animal housing conditions, analgesia, and anesthesia for pain relief)."}
{"_id": "Radiology$$$d37415cd-6b1a-4755-8806-89d9a0fdff3c", "text": "Replacement: Includes methods that avoid or replace the use of animals such as computer/mathematical models (in silico), cell culture models (in vitro), or relative replacement (e.g., invertebrates, such as fruit flies and nematode worms)."}
{"_id": "Radiology$$$0ecad9d4-bf12-4e75-b0f6-76e6ace48dbc", "text": "Reduction: With improved experimental design, modern imaging, or sharing data and resources, the total number of animals needed can be minimized."}
{"_id": "Radiology$$$742e881a-1799-41c3-a5f4-0bcf3923cf47", "text": "Refinement: Modification in the experiment, which minimize pain, suffering, and distress and allow general improvement of animal welfare (e.g., improvement in the research animal housing conditions, analgesia, and anesthesia for pain relief)."}
{"_id": "Radiology$$$9d575ceb-62e4-43fc-8ec1-377b84708fc5", "text": "The animals that are most used for terrestrial research are mice, fish, and rats. Since the beginning of space exploration also animals have been used in space programs. Similarly, to how microgravity and cosmic radiation can affect human health, animals are also affected. This is why during an early space mission, at the beginning of 1940, animals were used to investigate various biological processes and the effects of space flights on living organisms. On the 20th of February 1947 the first living organism, fruit flies, were sent to space with the V2 rocket. The dog Laika was the most famous and first mammal which was sent to an orbital spaceflight around the Earth (Fig. 10.16) onboard of the Soviet Spacecraft Sputnik 2 on 3rd November 1957 [253]. Since then, a variety of animals have been sent into space including rodents, ants, cats, monkeys, spiders, and jellyfishe. Nowadays the effect of space conditions on animals, including microgravity and radiation, can also be studied to a certain degree on Earth with the help of clinostats, particle accelerator, and X-ray machines. However, all factors of the complex space environment cannot be simulated simultaneously on Earth.\n\nA photograph of Laika, a Soviet space dog who was one of the first animals in space and the first to orbit the Earth.\n\nFig. 10.16\nOn 3 November 1957 Laika was the first living mammal that was sent to space onboard the satellite Sputnik 2"}
{"_id": "Radiology$$$abd6c1d6-4360-47a1-8bf8-12a94246f1c9", "text": "A photograph of Laika, a Soviet space dog who was one of the first animals in space and the first to orbit the Earth."}
{"_id": "Radiology$$$a57a1660-c856-4c29-a9af-2a3a660426c9", "text": "In case of a large SPE and insufficient shielding, the acute radiation syndrome (ARS, see Chap. 2) might be induced, endangering astronauts\u2019 health and mission success. To understand the pathogenesis of ARS induced by protons and develop therapeutic approaches for space missions, experiments with different animal models including rodents, minipigs, and non-human primates were performed. Whole-body doses up to 2 Gy are expected when astronauts are exposed to large SPE in free space with insufficient shielding. In this dose range, effects on the immune system (see Sect. 10.6.2.3) dominate the syndrome. As the skin dose can be 5\u201310 higher, the skin might be damaged (see Sect. 10.6.2.2)."}
{"_id": "Radiology$$$2c04a7db-7ba4-49b7-84e9-6d91f1c3f099", "text": "Forming the barrier between the outside environment and the inside of the body, the skin is a vital organ. Different skin layers provide the skin with tensile strength and keep a proper barrier function to prevent body water loss, regulate the immune defense and temperature, and protect against ultraviolet damage. The outermost layer, the epidermis, is built mostly out of layers of keratinocytes that differentiate and migrate toward the skin surface. A balance between the proliferation of keratinocytes and shedding of dead cells at the surface of the skin regulates the thickness of the epidermal layer. Below the epidermis lays the dermal skin layer which is mostly composed of connective tissue. Skin\u2019s tensile strength and elasticity are provided by Collagen type I and III, and elastic fibers. Fibroblasts are the major provider synthesizing these proteins. Furthermore, they play a major part in skin wound healing by migrating to the side of the wound, recruiting other cells, and remodeling the extracellular matrix (ECM) to restore the injured skin [254]."}
{"_id": "Radiology$$$29e956a6-7a76-4f7d-926d-396ea8221638", "text": "The skin receives greatest dose and greatest number of stopping particles, particularly during solar flares [255]. SPE events during EVA could lead to higher skin dose than to internal organs. Furthermore, simulations of SPEs has shown that the total skin dose for astronauts performing EVAs is estimated to be up to 32 Gy (for SPE simulation of August 1972) [31]."}
{"_id": "Radiology$$$682d80ff-9b3a-4fef-bd4a-6554a063bd0d", "text": "Radiation-induced skin injuries can be distinguished by several phases depending on the condition of exposure [256]. Early skin reaction is shown by erythema within a few hours after irradiation. After several weeks, inflammatory damage, erythema, loss of epidermal cells, moist desquamation, hyperpigmentation, edema/hyper-proliferation, and epilation can be observed. Late effects can develop after several months and include dermal atrophy, necrosis, and problems related to the deterioration of the skin vasculature. Skin problems, such as burns and slower wound healing, combined with a deprived immune system increase the risk of infections and hinder recovery from ARS [31]."}
{"_id": "Radiology$$$1d33f1a0-3080-44d5-ab77-23aad985e36a", "text": "Because of morphological similarities between (mini) pigs and human skin, these animals have been widely used to better understand the skin reaction to ionizing radiation. Furthermore, rodent models such as mouse, rat, or guinea pig have also been studied for ionizing radiation effects on skin."}
{"_id": "Radiology$$$ca73cb96-b4d4-451f-8705-3cd20708d6f5", "text": "Using porcine models, researchers have been able to indicate skin toxicity after exposure to a simulated SPE radiation resembling the energy and fluence profile of a SPE documented in 1989 [257]. Hyperpigmentation of minipig irradiated skin was observed 7 days after irradiation and lasted throughout the entire observation period. These observations were supported by an increase in melanin deposition found in the stratum granulosum. Further observations of increased proliferation, parakeratosis (an accelerated keratinocytic turnover) and increased amount of melanophages, are thought to be an indication of an inflammatory skin response after irradiation."}
{"_id": "Radiology$$$c09c532d-ff53-4ce5-aaf7-03bdf53115c9", "text": "Other studies exposed minipigs to doses ranging from 5 to 25 Gy of electrons [258]. In agreement with previous mentioned study, a dose-dependent hyperpigmentation of the skin was observed as well as an increase in melanin deposition. Furthermore, in the highest dose exposed group of 25 Gy, skin wounds and ulcers developed 19 days after irradiation on body parts that received the highest dose (tail, ears, and legs). In addition, hair loss in the form of alopecia was observed along the dorsum of these pigs."}
{"_id": "Radiology$$$30177fd0-4a05-4363-9815-5eadff15e009", "text": "Low dose rate exposure of skin to low doses of photons, seem to mostly induce oxidative stress and ECM alterations as observed in a mouse model [259]. Skin gene expression changes related to oxidative stress and extracellular matrix (ECM) have been found after whole-body \u03b3-ray exposure. At low dose rates, genes involved in the formation of reactive oxygen species (ROS) were significantly upregulated at doses of 0.25 Gy. Furthermore, dose rate effects were also found in ECM gene expression profiles. Enhanced expression of genes encoding ECM structural components were found after low dose rate exposure."}
{"_id": "Radiology$$$12766018-7b46-43cf-adff-e67b5d005b38", "text": "The immune system consists of a variety of cells, processes, and chemicals that combine efforts to protect the body from foreign microbes, viruses, cancer cells, and toxins [260]."}
{"_id": "Radiology$$$88e0658c-c670-44c3-8355-2bf324bf2a5f", "text": "Dysfunction of the human immune system has been shown during [261] and even after space flight [262]. Among the causes of this immune dysfunction, an altered distribution of the cellular components and altered cytokine profiles [263], as well as cytoskeleton alterations and gene expression dysregulation [264] has been shown in many immune cells. When human lymphocytes are subjected to simulated cosmic radiation in vitro they show chromosomal damage, depending on the type of radiation shielding."}
{"_id": "Radiology$$$bcc9b0bd-9758-4d5d-825a-030160c2882f", "text": "The adverse effects of space radiation on the immune system is one of the major concerns for space flight. The vast majority of the cellular components that constitute the immune system are highly sensitive to ionizing radiation [265]. It is still not clear if space radiation has a synergistic effect in combination with microgravity, principally in long duration missions and in the context of the immune system."}
{"_id": "Radiology$$$2410567a-fe56-41e7-b1e5-74e7e2fa1da1", "text": "As mentioned, in vitro models have been widely used for studying the effects of space radiation on several cellular types. However, the complexity of most systems\u2014such as the case of the immune system\u2014require approaches that will better mimic physiologic conditions, either in ground-based studies or inflight campaigns. Several animal models that recreate some of the conditions of space flight have been developed for use on Earth. For immunology studies, murine models remain one of the most commonly used small animal model in space radiobiology. Rats exposed to 56-Fe (5\u00a0GeV/n) to total doses of 0, 1, 2, and 4 Gy showed a decrease in their lymphocytes, particularly B cells. In another study, mice were irradiated with total (single) doses of 0, 0.5, 2, and 3 Gy with 56-Fe ions. Red blood cell (RBC) counts diminished proportionally to the dose. All three major types of leukocytes also decreased [266]."}
{"_id": "Radiology$$$36f813e6-867a-4a1a-9243-c431c5f2b8d3", "text": "Sanzari et al. [267] directed a series of radiation experiments using Yucatan minipigs. The animals were exposed to beams comprised of Solar Particle Events (SPE)-like protons, 155 MeV, and electrons, 6 and 12 MeV, with dose profiles that mimic SPE radiation. Their findings suggest that, based on the magnitude of the decrease and the time required to reach the lowest leukocyte counts after irradiation, the proton SPE radiation had more impact on the count than electron SPE radiation, with lymphocytes being the most sensitive type of leukocytes. After proton SPE radiation at skin doses >5 Gy, certain populations of leukocytes (neutrophils) had lasting effects following the irradiation (up to 90 days) [267]."}
{"_id": "Radiology$$$a75b475f-fffd-42d4-8515-a234d343cc83", "text": "For studying the intricate function of the immune system and how it responds to acute exposures of space radiation, small animal models are essential since they can showcase the network of phenomena. Adding up to the already challenging task of pinpointing the alterations occurring in the irradiated immune system we must find a way of adding the following to the equation: isolation, altered circadian rhythms, psychologic stress, and, of course, altered gravity levels."}
{"_id": "Radiology$$$4830af2c-233e-439e-b889-33eae8d27574", "text": "Chronic and late effects of space radiation exposure encompass increased cancer risk, early cataract formation, and a possibly increased risk for degenerative diseases of several organ systems such as the cardiovascular and the central nervous system)."}
{"_id": "Radiology$$$4a78a970-0667-4275-a903-3549aa81ccb7", "text": "Animal models of cancer induction by space radiation play a crucial role in the determination of the radiation risk associated with a space mission."}
{"_id": "Radiology$$$246a8f41-7808-4d0c-8067-485716cdf01d", "text": "Firstly, they provide with information about the RBE of different space radiation components such as HZE particles for cancer induction in different organs when compared to a low-LET radiation quality, such as gamma rays or X-rays. The Radiation Quality Factor is derived from the RBE data for cancer induction by HZE particles to scale from gamma radiation to the mixed field of GCR in space radiation cancer risk models. If the RBE is above 1, a higher cancer risk can be assumed for space radiation compared to well-known terrestrial low-LET radiation qualities."}
{"_id": "Radiology$$$010dee52-7f1e-4977-a507-7ffa489167b0", "text": "Secondly, experiments with high and low dose rates are the basis to estimate the dose and dose rate effectiveness factor (DDREF) to scale from acute to chronic radiation exposure and thereby account for dose rate effects. As animal experiments with exposure at low dose rates are rarely feasible at heavy ion accelerators because of restricted beam time access, dose-rate effect experiments were performed so far at neutron facilities."}
{"_id": "Radiology$$$f5219aae-aa8f-4169-b192-7e7d4b696a58", "text": "Furthermore, animal models give insight into the mechanisms of cancerogenesis by HZE particle exposure, e.g., the role of non-targeted effects, and thereby allow to identify potential molecular targets for effective countermeasures (Box 10.6)."}
{"_id": "Radiology$$$217940d1-5185-4a14-99e2-5d24be7db6cf", "text": "Inbred mouse strains are produced by at least 20 generations of brother-sister mating and they are traceable to a single founding pair. The individuals of an inbred strain are genetically nearly identical to each other and experimental results are highly reproducible. Examples: CBA mouse (cross of Bagg albino and DBA), C57BL/6 mouse (with black coat), BALB/c (Bagg albino) mouse.\n\nOutbred strains provide genetic diversity and are effectively wildtype in nature with as little inbreeding as possible.\n\nMating of at least two strains led to the generation of the first filial generation (F1) hybrid mice."}
{"_id": "Radiology$$$a2bf65ae-35a3-4882-b01c-d7b61017cdaf", "text": "Inbred mouse strains are produced by at least 20 generations of brother-sister mating and they are traceable to a single founding pair. The individuals of an inbred strain are genetically nearly identical to each other and experimental results are highly reproducible. Examples: CBA mouse (cross of Bagg albino and DBA), C57BL/6 mouse (with black coat), BALB/c (Bagg albino) mouse."}
{"_id": "Radiology$$$1f235eab-783b-42ef-a7c8-0befb0f65593", "text": "Outbred strains provide genetic diversity and are effectively wildtype in nature with as little inbreeding as possible."}
{"_id": "Radiology$$$16b0f480-4f30-4abb-b778-1311f29ea048", "text": "Mating of at least two strains led to the generation of the first filial generation (F1) hybrid mice."}
{"_id": "Radiology$$$cc21bd11-b080-432a-b1bd-de21f29c405c", "text": "The first animal experiment with HZE particles to determine cancer induction by single ion exposure used mice and focused on the induction of tumors of the exocrine Harderian gland which is located between eye and ear [268\u2013271]. In these experiments, tumor prevalence was determined by sacrificing mice at a predetermined timepoint after exposure and the number of mice with tumors was counted or the number of tumors per mouse was counted. As this gland does not exist in humans, other animal models were developed and applied. Two different approaches predominate: either wildtype rodents, e.g., inbred, F1 hybrid, or outbred mice, or genetically altered rodent models are exposed to HZE particles at a heavy ion accelerator. Multiparent outbreeding strategies can reduce the strong effects of the genetic background that limit gene-environment interactions in studies with inbred, genetically homogeneous animals [272]. To consider sex-specific cancer types, optimally, both sexes are included [272]. After whole-body irradiation of wild-type rodents, they were followed up over the lifespan of the animals for tumor induction. Alternatively, rats were followed up by palpation until first tumor (time-to-cancer incidence), with an additional follow-up until death. After necropsy, histology was performed to determine the number and types of cancer, e.g., mammary tumors [273, 274]. Here, high numbers of animals are required to detect the increase of cancer incidence above the background cancer rates."}
{"_id": "Radiology$$$3578eb8e-9efb-4d0d-84c8-79f8439d8d6a", "text": "Therefore, genetically altered mouse models were developed in order to lower the number of mice and to mimic a specific cancer induction and promotion pathway, mostly for lung, gastrointestinal [275, 276] or liver cancer (hepatocellular carcinoma) [277, 278]. Using a genetically radio-sensitized model implies an assumption about the mechanisms of radiation-induced cancerogenesis\u2014genetically engineered mice carry some, but not all mutations, needed to generate cancer. The rationale behind this approach is to consider somatic mutations in cancer genes such as NOTCH1 and TP53 that might be already present in astronauts when they depart for their first space missions as the number of mutations in the epithelium increases with age [279]."}
{"_id": "Radiology$$$96904d0f-d56f-4d61-9d27-6fef9a9fee60", "text": "In risk models, development of leukemia (leukemogenesis) and induction of solid tumors are considered separately because of different latency periods after radiation exposure and dose\u2013response relationships. Leukemogenesis is highly relevant for space missions because of its short latency in humans. The CBA mouse strain is susceptible to radiation-induced acute myeloid leukemia (AML) [280] which is explained by a deletion in chromosome 2 (PU.1) that can occur 1 month after irradiation. A point mutation in the second copy of the PU.1 gene causes a differentiation block in the myeloid cells which favor autocrine growth stimulation. In this model, the RBE of iron ions for induction of AML was 1, meaning that the risk of AML induction by high-LET iron ions and low-LET radiation is comparable. As only surviving cells can be transformed into a cancer cell, a higher mutation and chromosomal aberration rate induced by HZE particles can be compensated by cell death from collateral damage after an HZE ion traversed a myeloid cell [277]. RBE for other cancer types can be much different as the effectiveness of HZE ions in inducing a specific cancer type depends on the mechanism responsible for the tumorigenesis in that particular cancer. For example, in the same mouse strain that was used for the AML studies, hepatocellular carcinoma (HCC) was induced by HZE particles with an RBE of up to 74 [278]."}
{"_id": "Radiology$$$0d009a2e-ab09-4c13-8df6-de2b0b3ea77c", "text": "Concerning solid tumors, a special focus in the studies so far was to evaluate the stage of tumors that can be induced by HZE particles and on detailed studies on lung cancer, gastrointestinal cancer, and brain tumors (Box 10.7)."}
{"_id": "Radiology$$$63d82b16-0142-4bde-90c4-caf61c0b4fa0", "text": "Pituitary adenoma, osteosarcoma, Harderian gland tumor, soft tissue sarcoma, thyroid adenoma, ovarian Granulosa cell tumor, mammary adenocarcinoma, histiocytic sarcoma, hemangiosarcoma, hepatocellular carcinoma (HCC), pulmonary adenocarcinoma, small cell lung cancer, myeloid leukemia, (thymic) lymphoma (T cell, B cell), brain tumors, e.g., gliomas [272]."}
{"_id": "Radiology$$$118356ed-65f6-4de0-9e74-85368505326a", "text": "The lung has the highest susceptibility to radiation-induced carcinoma incidence and mortality, based on analysis of human populations exposed to radiation (Life Span Study of atomic bomb survivors). A minimum of five genetic changes convert immortalized human lung epithelial cells to malignant tumors. For lung carcinogenesis, BALB/cByJ or C57/BL6 mice or the K-rasLA1 mouse model [281] were used. In C57/BL6 mice, lung tumors occurred in irradiated mice but not in controls and all were adenocarcinomas, with no significant differences between males and females and for dose fractionation (dividing a radiation dose into multiple fractions, see Chap. 4) versus single dose were found. Incidence of lung tumors was higher in high-LET-irradiated mice than in X-ray-irradiated mice, with an RBE above 6 for all investigated HZE particles (Fe, Si, and O ions) [282]."}
{"_id": "Radiology$$$4538e5fd-7dd3-429f-b76c-22a1b7428e7b", "text": "In the pathogenesis of gastrointestinal tumors, for instance, colorectal cancer and hepatocellular carcinoma (HCC), inflammation plays a crucial role. Animal experiments revealed that heavy ion radiation triggers a pro-inflammatory state which can be associated with late colonic tumors. Furthermore, premalignant polyps with mutations in the Adenomatous polyposis coli (APC) gene could be already present in middle-aged astronauts. In the small intestine, the formation of a few polyps and later adenomas and even adenocarcinomas can result from truncation of the APC gene at codon 1638 [283]. Therefore, a mouse model with a chain-terminating mutation by a mutation to a stop codon or a frameshift (see Chap. 4) in one allele of the APC gene was developed for colon cancer research (Apc1638N/+). APC mutant mouse models show a good correlation with carcinogens implicated in human colorectal cancer. Delayed genomic instability in APC1638N/+ mice paves the way to gastrointestinal tumorigenesis. In this model, no evidence for dose-rate effects with HZE particle exposure was found [275], indicating that the carcinogenic potential of HZE particles is independent of the dose rate."}
{"_id": "Radiology$$$6941167e-0814-4f42-ab47-f65734274dbd", "text": "Also, genetically altered mouse models for the formation of brain tumors are used in space radiation research as already experiments from the 1970s indicated that charged particles can induce glioblastomas: Monkeys (Macaca mulatta) irradiated with high-energy protons (55 MeV, penetration depth ~2.5 cm) surviving 2 years or longer developed glioblastomas [284]. Here, the focus is on the loss of tumor suppressors such as cyclin dependent kinase inhibitor 2A (Cdkn2a or Ink4-Arf), phosphatase and tensin homolog (Pten), and TP53 in astrocytes and on oncogene activation (e.g., epidermal growth factor receptor variant III, EGFRvIII) after irradiation. Iron and silicon ions were much more potent tumor inducers in \u201cpreinitiated\u201d astrocytes than gamma rays [285]."}
{"_id": "Radiology$$$eda92651-4aaa-4a12-be42-03fe9911375f", "text": "The animal studies with single beam irradiations show that the efficiency of HZE particles to induce cancer is related to ion energy, LET with a peak RBE below 100 keV/\u03bcm, sex of the animals, and depends on the tumor type [275]. The RBE for cancer induction was recently determined to range from 5 to 16 [286], representing a snapshot that will be further updated as not all available data were included. Currently, based on the results of single beam irradiations, multiple beam experiments with up to 33 ion beams are performed at the NASA Space Radiation Laboratory (NSRL) using the GCR simulator in order to understand whether the effects of the different GCR components act in an additive or even in a synergistic manner in cancer induction."}
{"_id": "Radiology$$$a06bd11f-d3ce-40a2-b46f-8d1f7fbb2459", "text": "According to recent epidemiological evidence, radiation-induced cataract (see Chap. 2) occurs with a threshold absorbed dose of 0.5 Gy (0\u20131 Gy) of sparsely ionizing radiation, meaning that a cataract can arise after any ionizing radiation dose no matter how low if the remaining lifespan is long enough for its appearance. The 1 Sv GCR dose to be expected for a 1000-day Mars mission [83, 84] means that even the upper limit of the cataract-induction threshold dose confidence interval will be reached during a human Mars exploration mission. In astronauts, epidemiological data suggest a higher risk for the development of cataracts in case of missions in LEO with high inclination [287]."}
{"_id": "Radiology$$$acfacc57-ed51-486a-89e8-b812733286f5", "text": "Due to its germinative zone in the lens epithelium, the eye lens is a radiation-sensitive organ. These cells are actively proliferating during lifetime and finally differentiate into transparent lens fibers. In case cells are damaged, they cannot be eliminated from the lens which is covered by a capsule and not vascularized. Exposure of the eye lens to ionization radiation is thought to result in sub-capsular cortical lens opacification via various steps, starting with genetic damage of lens epithelial cells via changes in cell cycle control, apoptosis, differentiation, or other pathways controlling lens fiber cells\u2019 differentiation, and cellular disorganization."}
{"_id": "Radiology$$$aca601ee-32c1-4c53-a599-c4a2055195a7", "text": "Due to higher local dose and different patterns of cellular energy deposition from high-LET components of GCR, higher efficiency in the induction of lens-damaging effects is assumed than for low-LET radiation. Therefore, animal experiments were mostly performed to determine the RBE of HZE particles to induce lens opacification and to detect possible dose rate effects. In rats, the RBE reached 50\u2013100 for HZE particles within LET above 80 keV/\u03bcm [288] and fractionation of exposure did not reduce the cataractogenic effect [289]. Neutrons as secondary particles occurring in spacecraft and on planetary or moon surfaces had also a high RBE for cataract-induction in rats [290]."}
{"_id": "Radiology$$$1ae1db29-d463-41f7-87cd-a6e96def74f1", "text": "To determine the role of genetic predispositions, mice that are heterozygous for Ataxia telangiectasia mutated protein (ATM) were exposed to HZE particles and cataract formation was followed. ATM plays a central role in the DNA damage response (DDR). Heterozygosity for the ATM gene predisposes carriers for early onset time and progression of cataracts even without exposure to ionizing radiation [291]. Also after gamma ray and 1 GeV/n iron ion exposure, cataracts appear earlier in ATM heterozygous animals compared to wild-type mice and the RBE for HZE particle induced cataract formation ranged from 4 to 200, whereby the highest values were found for the lowest dose (10 mGy) and RBE decreases with increasing dose [292, 293]. In conclusion, HZE particles present in GCR and neutrons as part of the secondary radiation field are highly cataractogenic and the mechanisms such as long-term changes in gene expression, complex DNA damage, and chromosomal aberrations in eye lens epithelial cells (LECs) are still under investigation."}
{"_id": "Radiology$$$9f286a99-41c5-4c82-86aa-b7498596cfb5", "text": "Exposure to space hazards, including microgravity and heavy ion exposure can cause harmful effects on the cardiovascular system during spaceflight. Upon entering microgravity, cephalad fluid shifts cause increased stroke volume and cardiac output. Furthermore, the cephalad fluid shift is also hypothesized to cause visual impairments due to increased cranial pressure [294]. During flight, mean arterial pressure is decreased, together with central venous pressure. Furthermore, decreased systemic vascular resistance, results from increased cardiac output, systemic arterial vasodilation, and decreased arterial pressure [295]. Other effects of microgravity exposure include hypovolemia, cardiac arrhythmia, cardiac atrophy, and orthostatic intolerance. Believed to be caused by fluid shifts and movement of interstitial water from the legs to the head, the fluid reduction and eventually hypovolemia results in a reduced number of red blood cells [296]. Moreover, cardiac atrophy occurs as a result of decreased metabolic demand and oxygen uptake during microgravity conditions. Together, cardiac deconditioning, i.e., hypovolemia, cardiac atrophy, and decreased cardiac output, causes a decreased exercise capacity and orthostatic intolerance post-flight [297]."}
{"_id": "Radiology$$$6456949a-7971-4f0c-b7d7-b8a7fda93ac2", "text": "While effects related to microgravity exposure during spaceflight are fairly well-known (albeit underexplored), impacts of the cardiovascular system from space radiation and heavy ion exposure during spaceflight are less known. Furthermore, studies from space analogs focusing on radiation effects have shown several effects on the cardiovascular system. Mice exposed to heavy ions show myocardial remodeling, resulting in hypertrophy and cardiac fibrosis [186]. Additionally, accelerated development of atherosclerosis has been found in mice after heavy ion exposure. Leading to a greater prevalence of myocardial infarction [298]. Both in vivo and in vitro models during space flight as well as using space analogs have been used to investigate underlying mechanisms of space-induced CVD. Important mechanisms include endothelial dysfunction, cellular apoptosis, cellular senescence, inflammation, and reactive oxygen species production [297]."}
{"_id": "Radiology$$$2615f062-ced3-4c45-9cc1-454df0f69f8c", "text": "Exposure to heavy ion, especially during long-term space mission, can also affect the central nervous system (CNS). The CNS is part of the nervous system and is composed of the brain and the spinal cord. It is responsible for perceiving any exterior information, transmitting, and subsequently processing it. Responsible for signal transmission are neurons, whereas glial cells (oligodendrocytes, microglia, or astrocytes) have diverse function such as the trophic support of neurons. As neurons are terminally differentiated and have a very restricted regeneration potential, damaged cells will usually not be replaced and thus damage might accumulate over months or years."}
{"_id": "Radiology$$$8c637ebc-ddb1-4aa9-a276-55ed18d681ae", "text": "Acute CNS effects of ionizing radiation exposure are only observed after exposure to very high doses and can be expected in spaceflight only during very large Solar Particle Events (SPE) in case of insufficient shielding. Thus, for more than 20 years, possible effects of chronic low-dose exposure of the CNS to galactic cosmic rays (GCR) are discussed and a decrease in CNS performance of astronauts is suspected, which was also further evidenced in animal studies [299, 300]. Normally rodent animal experiments are performed at heavy ion accelerators simulating space radiation at doses below 1 Gy in a relatively short time, revealing impairment in cognitive performance, reduction of dendrites, reduced neurogenesis, and increased neuroinflammation [301\u2013303]. As these effects can be seen even months after irradiation, late effects are possible even after exposure to lower doses [304]."}
{"_id": "Radiology$$$66e6c99a-492f-4151-a36e-387cbe539abb", "text": "Whereby it has to be considered that in these heavy ion accelerator experiments, the dose can only be applied in a short time, and prolonged exposure over several weeks or months mimicking the real situation in spaceflight is not often possible. With the use of new, low dose rate neutron irradiation facilities, it is now possible to expose rodents to a chronic low-dose as expected during space flights [305]. Also, mice that were irradiated with this chronic neutron irradiation (for 6 months) resulted in diminished hippocampal neuron excitability, a region which is essential for memory and learning, and disrupted hippocampal and cortical long-term potentiation. In addition, mice showed severe impairments in memory and learning tasks as well as distress behaviors [305]."}
{"_id": "Radiology$$$749db627-0df9-4639-9daa-1fe6c15a7337", "text": "One limit of experiments at the accelerator is that only radiation exposure of a few single radiation types can be studied, while in space, radiation exposure consists of a complex radiation mixture. It is still unclear if humans\u2019 brains are affected to the same extent, but chronic low-dose radiation may cause problems for astronauts regarding decision-making processes or performance [306] (Box 10.8)."}
{"_id": "Radiology$$$f8b9b931-807b-4f7b-90c0-296ca791ac2e", "text": "Since their discovery by Antonie van Leeuwenhoek in 1702, bdelloid rotifers and tardigrades have remained intriguing organisms. Their tolerance to desiccation at any stage of their life and their ability to survive a variety of stresses (e.g., low and high temperatures, absence of oxygen, vacuum, high level of ionizing radiation, etc.), makes them good candidates to study extreme resistance mechanisms in the context of space research. Tardigrades have a long history of space astrobiology experiments being among the first animals exposed to space vacuum and radiation. Recent experiments performed onboard of the ISS used bdelloid rotifers and tardigrades to study the adaptation to microgravity and cosmic radiation during spaceflight."}
{"_id": "Radiology$$$e50ed76c-7b2b-4b86-8352-98e282f4e7a1", "text": "Bdelloid rotifers (Fig. 10.17) and tardigrades (Fig. 10.18) are among the smallest animals on Earth: most species are less than 1mm in size and contain ~1000 cells. Despite their small size, these animals have complete nervous, muscular, digestive, excretory, and reproductive systems. Mainly living in semi-terrestrial environments, such as lichens and mosses, most (but not all) bdelloid and tardigrade species are able to enter and survive complete desiccation (see Box 10.9 for definition) at any stage of their life cycle.\n\nTwo photographs of Adineta vaga depict the difference in the size and shape of its hydrated and desiccated forms. Egg production occurs in the hydrated form.\n\nFig. 10.17\nOverview of the bdelloid rotifer Adineta vaga life cycle. Bdelloid rotifers live in limno-terrestrial habitats like mosses and lichens. Adapted to these environments, they can be desiccated at any stage of their life cycles including egg stage. When they are exposed to desiccation, adults adopt a \u201ctun\u201d shape allowing optimal desiccation resistance. Adineta vaga is about 200\u2013250 \u03bcm long. (Credits B. Hespeels)\n\n\nA set of 5 micrographs depicts the structural features of Echiniscus testudo, Paramacrobiotus areolatus, and the eggs of Macrobiotus kamilae and Paramacrobiotus areolatus.\n\nFig. 10.18\nMorphology of adult tardigrades and eggs. (a, b) Lateral and dorsal views of Echiniscus testudo. (c) Dorsal view of Paramacrobiotus areolatus. (d, e) Global morphology of eggs laid by Macrobiotus kamilae and P. areolatus. Pictures were captured using scanning electron microscopy. (Illustration kindly provided by Daniel Stec and reprinted with his permission)"}
{"_id": "Radiology$$$bcdc2b92-eeac-4bfa-bd40-871bdcaf150a", "text": "Two photographs of Adineta vaga depict the difference in the size and shape of its hydrated and desiccated forms. Egg production occurs in the hydrated form."}
{"_id": "Radiology$$$68987b83-f02f-451f-bdaa-9007af1bbcd5", "text": "A set of 5 micrographs depicts the structural features of Echiniscus testudo, Paramacrobiotus areolatus, and the eggs of Macrobiotus kamilae and Paramacrobiotus areolatus."}
{"_id": "Radiology$$$660a3bac-ea45-4162-b425-26bb470ef409", "text": "When water starts to evaporate, these animals begin to contract their muscles and their body to adopt a \u201ctun\u201d shape allowing an optimal desiccation resistance [307\u2013310]. This proper contraction of the body, followed by a specific organization of internal structures is a key step in enabling a successful recovery of desiccated animals after rehydration [308, 309]. The desiccation resistance and recovery rate vary between species [311\u2013314]. The survival rate depends on the length of the desiccation period, the relative humidity, temperature, and animal age. Tardigrades desiccated over 10\u201320 years, within dry mosses stored at room temperature, were successfully rehydrated confirming their desiccation resistance for periods [315] [316]. While being frozen, these animals were shown to survive over 30 years of desiccation [317]. Bdelloid rotifers have also been shown to survive long periods of desiccation, up to 9 years [318]. As for tardigrades, cold temperatures seem to extend the capacity of desiccated bdelloids to cope with the long duration of metabolic arrest. In a recent publication by Shmakova et al. bdelloid rotifer specimens were recovered from frozen permafrost soil 24,000 years old [319]. If no data are still available for tardigrades, studying old permafrost samples may reveal other records of small animals\u2019 life preservation. For example, some nematodes were described to successfully recover after melting from 30 to 40,000 years old samples [320]."}
{"_id": "Radiology$$$5fd50111-f26e-44ce-805c-ea248448867a", "text": "Desiccation tolerance must be differentiated from drought tolerance. Many organisms are able to tolerate drought as a reduction in water availability in the environment for longer or shorter times. However, a reduced number is able to survive a loss of 90% or more of their body water content. Complete desiccation is reached when the water content decreases below 10% of the dried mass, not enough to form a monolayer around macromolecules, preventing enzymatic reactions and therefore metabolism."}
{"_id": "Radiology$$$34bc4728-4954-4812-b222-72ded7d1577c", "text": "Mostly found in habitats where physical parameters can change unpredictably, tardigrades and bdelloid rotifers were described to be able to cope with a wide range of physical extremes besides desiccation and freezing, such as UV radiation, high temperatures (exceeding 100 \u00b0C for a few minutes), high pressure or deep space vacuum [317, 321\u2013327]."}
{"_id": "Radiology$$$30d76740-6f5f-4045-ad56-fb123ae92e66", "text": "Among others, bdelloid rotifers and tardigrades were described to be highly resistant to low- and high-LET [328] radiation. In 2008, it was demonstrated for the first time that two bdelloid rotifer species, A. vaga and Philodina roseola, were resistant to ionizing radiation while being hydrated, surviving up to 1200 Gy of gamma radiation with fecundity (i.e., the total number of daughters produced by irradiated animals) and fertility (i.e., the capacity to produce at least one daughter) showing a dose response [329]. Later, it was demonstrated that desiccated bdelloid rotifers survive doses >5000 Gy of X-ray and proton radiation. These levels of radiation exposure were contrasting the Lethal Dose 50 (LD50) (i.e., dose required to kill 50% of the irradiated population) of mammalian cells which range from 2 to 6 Gy after X-ray irradiation. Similarly, desiccation-resistant tardigrades were described to survive high dose of X-ray and gamma ray (LD50 ranging between 3000 and 6000 Gy) (reviewed in [322]). Unexpectedly, radio-resistance of hydrated and desiccated tardigrades appeared to be more tolerant to high-LET radiation. For example [330], LD50 of the eutardigrade Richtersius coronifer was approx. 10,000 Gy. A major difference in comparison with bdelloid rotifers was that, despite a high survival after irradiation, most tardigrades were unable to produce fertile eggs for doses >100 Gy [322]. As an example, the tardigrade Hypsibius dujardini treated with gamma radiation had an estimated LD50/48 h for survival of \u223c4200 Gy, and doses above 100 Gy dramatically impaired the production and hatching of laid eggs [331]."}
{"_id": "Radiology$$$2dcf7dda-e0e6-4a35-a2d9-c97d4ba0a838", "text": "As an alternative to other animal models, the use of rotifers and tardigrades was proposed for space research. Indeed, these animals may contribute to better understanding damage and consequences induced by exposure to radiation and/or microgravity. How these organisms may respond and adapt to these stresses pave the road to the discovery of new molecules or candidate genes. Ultimately research outputs may be used to improve health span and protect astronauts or individuals subjected to radiation during space flights or medical treatments."}
{"_id": "Radiology$$$414c1f0b-170c-43d7-a007-6b4c98ed0d7c", "text": "The use of rotifers and tardigrades as space research models was proposed because of the following aspects. (1) Complexity: they are Metazoans (multicellular animals), containing tissues and organs, having a complete gut and a complex muscular structure, yet being very simple animals. Rotifers and tardigrades are however made up of about 1000 cells, while a human is made up of several millions of cells. This simplification allows to disentangle complex problems through easier approaches. (2) Miniaturization: rotifers and tardigrades are small; experiments performed with numerous individuals require small vessels. (3) Distribution: rotifers and tardigrades are readily found in nature and are easily cultivated under controlled conditions. (4) Life span: rotifers and tardigrades have short life cycles that can be studied in a reasonable time period. (5) Reproductive mode: all bdelloid rotifers and some tardigrade species reproduce parthenogenetically. This reproduction system offers two key advantages: a rapid expansion of the population, and a high degree of reliability, as the genome is fully transmitted to the offspring. Therefore, the use of clonal lines reduces the biological variability noise in biological experiments. (6) Extremotolerance: both bdelloid rotifers and tardigrades were described to be able to deal with a high number of DNA DSBs and various stressors encountered by astronauts during space flight. Small extremotolerant animals can provide new perspectives in the adaptation of life to the space environment and ultimately lead to enhancing radio-resistance. For both clades, radiation resistance and radiation-sensitive species can be used in comparative experiments. (7) Storage: as most tardigrades and bdelloids survive desiccation and freezing, they can be stored easily before and after scientific experiments with limited impact on their biology and the scientific output. (8) Desiccation resistance: the desiccated state of tardigrades and bdelloid rotifers correlates with increased resistance to stresses, including deep space vacuum and extreme temperatures. These multiple properties and advantages for space experiments make bdelloid rotifers and tardigrades good candidates to test the limits of life during space exposure. An overview of space experiments involving tardigrades and rotifers is presented in the next two sub-sections."}
{"_id": "Radiology$$$6b94a9e9-c90d-48c9-b593-699faaccfd05", "text": "In September 2007, tardigrades were exposed to LEO within the Biopan-6 experimental platform provided by the European Space Agency (ESA) (\u201cTardigrades in Space,\u201d TARDIS. FOTON-M3 mission). During 10 days at LEO (258\u2013281 km above sea level) samples of desiccated adult eutardigrades of the species Richtersius coronifer, Milnesium tardigradum, Echiniscus testudo, and Ramazzottius oberhaeuseri were exposed to space vacuum, cosmic radiations, and two different UV-radiation spectral ranges [323]. It was demonstrated that tardigrades were able to survive space vacuum and cosmic radiation with a survival rate ranging between 70% and 80%. Any impact on the reproductive capacities of exposed animals was reported. However, samples exposed to full solar radiation experienced high mortality. A small fraction of survivors died a few days post-rehydration without the production of any viable offspring. By filtering UV and restricting the exposure of desiccated tardigrades only to UVA and UVB, a significant part of desiccated tardigrades was able to be reactivated and was able to reproduce. Since the fertility of descendant generations of M. tardigradum was not impacted, it was suggested that survivors were able to repair a priori the damages induced by the spaceflight and did not transfer them to future generations [332]."}
{"_id": "Radiology$$$33097fc0-c881-4766-9d78-fbb21d1dfcde", "text": "In parallel to the TARDIS experiment (Fig. 10.19), two other experiments were launched onboard of the FOTON-M3: the (1) RoTaRad mission (Rotifers, Tardigrades, and Radiation) and (2) Tarse project (Tardigrade Resistance to Space Effects). RoTaRad experiment confirmed that desiccated tardigrades stored under controlled atmosphere were able to survive while being exposed to a combination of cosmic radiations and microgravity. However, the survival rates were reduced during this experiment likely due to the applied desiccation protocol [333]. With the Tarse project focusing on the eutardigrade Macrobiotus richtersi species, hydrated and desiccated individuals were exposed to the space environment for 12 days. In both states, microgravity and radiation had no effect on the survival rate, reproductive capacity, and DNA integrity of exposed animals. Despite the absence of visible morphological changes, it was nevertheless reported that the activity of key antioxidant proteins (including catalase and superoxide dismutase) was decreased during spaceflight. The amount of Heat Shock Proteins 70 and 90, known to be involved in stress resistances of tardigrades, did not differ after this short-term exposure to spaceflight.\n\nTwo photographs depict Bio pan facility with open lid on the outside of Foton capsule and the chambers in which tardigrades were placed, some are with sun filters.\n\nFig. 10.19\nView of TARDIS experiment. (a) View of the exobiology Biopan platform containing TARDIS experiment. For 12 days in September 2007, approximately 3000 water bears were launched in space during the Foton-M3 mission. Reprinted with permission from ESA. (b) Details of the sample holder containing the tardigrades Richtersius coronifer. Tardigrades on the top level were exposed to the Sun and were optionally protected with filters. (Image kindly provided by K. Ingemar J\u00f6nsson and reprinted with his permission)"}
{"_id": "Radiology$$$a709f944-9fcd-4a62-b4d2-629d41a5114a", "text": "Two photographs depict Bio pan facility with open lid on the outside of Foton capsule and the chambers in which tardigrades were placed, some are with sun filters."}
{"_id": "Radiology$$$c88b969e-1940-4683-b3ce-14d51db6f9b1", "text": "A few years later, the TARDIKISS experiments (Tardigrades In Space) were launched with the last Space Shuttle mission (STS-134 2011) [334]. During this 16-days mission, the enzyme activity of key antioxidants was investigated in desiccated tardigrades from the two species Paramacrobiotus richtersi and Ramazzottius oberhaeuseri [334]. Supporting the idea that desiccated animals were weakly affected by microgravity and cosmic radiation, comparative data analysis between flight and ground samples showed no significant differences in the enzymatic activity of antioxidants."}
{"_id": "Radiology$$$6207755a-0a10-442f-af9d-8cc0faba8010", "text": "In June 2021, a fifth experiment was launched onboard of the ISS to investigate the short-term and multigenerational survival of tardigrades. The aim of the Cell Science-04 experiment (CS-04) was to evaluate the transcriptomic response of hydrated tardigrades cultured on the ISS using a dedicated cell culture system (Bioculture System, developed at NASA Ames Research Center). For this experiment, the tardigrade Hypsibius exemplaris was used as model species. Scientists are currently evaluating the ability of these animals to survive onboard of ISS for short and long periods of time (up to four generations). In parallel, the transcriptomic responses of these animals are being investigated to follow the evolution of the expression profiles of tardigrades in a microgravity environment. A progressive adaptation of tardigrades onboard of ISS may lead to a better understanding of the molecular responses involved in gravity sensing and will help expand research to secure astronaut\u2019s health for future space missions. Among others, tardigrades were described to express several antioxidant proteins to face desiccation and radiation stresses [322, 335]. In particular, tardigrades were described to express specific proteins binding to DNA and protecting their genome from ROS induced by desiccation and ionizing radiation [336, 337]."}
{"_id": "Radiology$$$0c9f0abe-4f36-427d-b2d0-9cb00a161e82", "text": "How microgravity and cosmic radiation may affect desiccated bdelloid rotifers was tested for the first time in 1997. For their first exposure to space, dry samples of Macrotrachela quadricornifera were transported onboard of the space shuttle STS-81 for a total of 10 days. The data revealed a similar survival rate and reproductive fitness for ground controls and flight samples [312]. Since desiccated rotifers appeared to be protected from the impact of microgravity and cosmic radiation, at least in this short-term exposure experiment, researchers started to investigate the consequences of space flight on hydrated bdelloids. In absence of gravity, it has been hypothesized that the distribution of cytoskeletal elements or yolk granules in the egg cytoplasm is impacted. This abnormal organization of the cytoskeleton could impact the rotifer reproduction. Therefore, researchers first investigate the capacity of bdelloid rotifers to complete their embryological development under microgravity was initially investigated. Pre-flight experiments were performed under hyper-gravity environment (up to 20 g) and under simulated microgravity (as low as 0.0001 g) using a 3D random positioning machine (3DRPM). Results showed that the rotifer development remained constant regardless of the treatment experienced, except for some minor modifications in early embryos experiencing 20 g with no subsequent impact on the development. This first investigation suggests that bdelloid rotifers continue embryological development despite changes in g-force. Unfortunately, no data from flight experiment development associated with embryological development of bdelloid rotifers exposed to space environment was released post-flight."}
{"_id": "Radiology$$$b526805f-3130-45af-9f0f-29b8122fa03a", "text": "Twenty years later, the bdelloid rotifer A. vaga was sent onboard of the ISS for two independent experiments. In December 2019, two autonomous hardware, each containing five culture bags loaded with 10,000 individuals, were transported onboard of ISS. Hydrated animals were exposed to launch conditions and exposed to 12 days of microgravity. At the same time, a ground reference experiment was implemented on Earth to compare the biological responses of rotifers to space conditions on ISS. The aim of this first experiment (RoB1, Fig. 10.20) was to compare the transcriptomic responses of hydrated A. vaga samples exposed to space environment with the ground control samples. Preliminary results confirmed the successful maintenance of hydrated bdelloid individuals on ISS, without additional food or oxygen supply and without astronaut intervention. All the replicates (ten) of the autonomous A.vaga cultures survived and reproduced on ISS with no visible impact on the morphology in space-exposed samples.\n\nThree photographs depict Rob 1 hardware, P L T bags filled with rotifer cultures, and an astronaut keeping the Rob 1 hardware in K U B I K incubator going to the I S S.\n\nFig. 10.20\nView of Rob1 hardware used to culture hydrated A. vaga individuals onboard of ISS (December 2019). Top left: Rob1 hardware after its assembly at the launch site at Kennedy Space Center. Rob1 hardware is a passive hardware containing five culture bags containing hydrated specimens of A. vaga. Hardware enables gas exchanges between rotifer cultures and the outside through a permeable membrane. Top right: View of the culture bags assembled inside Rob1 hardware. Culture bags, loaded with 10,000 A. vaga individuals each, are made of Teflon and ensure an optimal gas exchange between the culture medium and the outside. Bags are waterproof and avoid any leakage of the medium (composed of mineral water and sterile lettuce juice) or rotifers. Reprinted with permission of Marc Guillaume. Bottom left: View of ESA astronaut Luca Parmitano loading two Rob1 hardware on KUBIK. KUBIK is a small incubator, temperature-controlled, with removable inserts designed for self-contained microgravity experiments. (Reprinted with permission of NASA)"}
{"_id": "Radiology$$$b3f70954-a157-45e7-9c86-7cbb00d9e564", "text": "Three photographs depict Rob 1 hardware, P L T bags filled with rotifer cultures, and an astronaut keeping the Rob 1 hardware in K U B I K incubator going to the I S S."}
{"_id": "Radiology$$$68e764e3-adc7-455e-867c-0f8790d08504", "text": "While it is well documented that astronauts experience DNA damage when exposed to cosmic radiation, accumulating DNA mutations and/or genomic rearrangements [163], the combined effect of cosmic radiation and microgravity on the living organism is still debated. It is suspected that microgravity reduces the efficiency of DNA repair and increases cancer risk [207, 215, 338]. Several studies using simulated microgravity highlighted a decrease in DNA repair efficiency. However, no effects of spaceflight on the cellular capacity to repair artificially induced DNA was observed (see Moreno-Villanueva et al. [209] for review). In order to obtain more insights, bdelloid rotifers have been used as a model system to evaluate their DNA repair efficiency of induced DNA breaks in space environment as compared to Earth samples. By the end of 2020, desiccated and irradiated A. vaga individuals were sent onboard of ISS. Before launch, desiccated animals were irradiated with 500 Gy of X-ray or proton radiation. Onboard, bdelloids were rehydrated and cultivated for different time periods to (1) follow the putative DNA repair process occurring post-rehydration and (2) investigate whether these irradiated rotifers still produce offspring under microgravity. In addition, half of the samples were exposed to simulated gravity using a centrifuge on ISS. Finally, a ground experiment was conducted in parallel at the launch site at Kennedy Space Center for comparison. Data generated by this second space experiment (entitled RoB2, see Fig. 10.21) will enable: first, to compare the DNA repair kinetic of rehydrated bdelloids post irradiation in 1G, \u03bcG, and simulated 1G; second, to compare the radiation responses of rehydrated rotifers after exposure to low LET or high LET; and third, to compare the DNA repair efficiency in space and on Earth by isolating eggs or juveniles from the exposed samples and use whole genome sequencing to compare the genomic structure of these animals pre- and post-exposure. This space experiment with bdelloid rotifers will contribute to our understanding of DNA repair process activity in space, in the presence or absence of microgravity. Moreover, studying the molecular processes involved in the DDR process of A. vaga will be of huge interest for future space travel.\n\nTwo photographs depict a pair of gloved hands holding a Rob 2 hardware and a spaceman conducting an experiment with the samples of Adineta vaga in I S S.\n\nFig. 10.21\nView of one Rob2 hardware used onboard of the ISS (left) and Astronauts checking the correct rehydration of A. vaga individuals. Sixteen pieces of hardware were sent to ISS, each containing 40,000 dry rotifers. Once onboard, rotifers were automatically rehydrated and cultivated 11 days before their fixation and download to Earth. (Reprinted with permission of Boris Hespeels and NASA)"}
{"_id": "Radiology$$$41bacf2f-fb29-4401-b730-c4a11e438891", "text": "Two photographs depict a pair of gloved hands holding a Rob 2 hardware and a spaceman conducting an experiment with the samples of Adineta vaga in I S S."}
{"_id": "Radiology$$$4a1e5acd-2283-4ab5-9e51-148dfdfa683b", "text": "In general, the ongoing rotifer space experiments will contribute to a better understanding of the mechanisms involved in the protection and repair of damages induced by radiation. They pave the road to the discovery of new molecules or candidate genes that could ultimately be used to improve health span and protect astronauts or individuals subjected to radiation during space flights or medical treatments. This research is also of fundamental importance for the understanding of extreme biology and the questions raised on the origin of life and its ability to spread through outer space. A third experiment, supported by ESA, is under preparation to evaluate whether rotifers can survive full space exposure, outside ISS, as was previously reported for tardigrades."}
{"_id": "Radiology$$$aca72935-c365-4d81-bbba-88a4197620a4", "text": "Long space exploration missions, settlement on orbital stations, or future planetary settlement (e.g., on Mars) will require further development of Life Support Systems (LSS). The LSS are able to regenerate a great amount of essential resources for survival and represent an ideal solution since it is not technically and economically feasible in long space missions to transport a large amount of consumables from the Earth [339\u2013341]. Bioregenerative Life Support Systems (BLSS) are an artificial closed ecosystem characterized by the same structure as a terrestrial ecosystem: producers (plants), consumers (humans/animals), and decomposers (microorganisms)."}
{"_id": "Radiology$$$2b7b08d3-9277-43c7-83f7-cfb005b477f9", "text": "Among biological components within BLSS, higher plants would have the same role on Earth as producers. Through photosynthesis, plants would utilize carbon dioxide produced by space crew and provide oxygen and fresh food. Moreover, they would use nutrients derived from human wastes and guarantee water purification by transpiration. Furthermore, plant cultivation in space also would provide psychological support against isolation [342, 343]."}
{"_id": "Radiology$$$df6ad9f6-9614-43a4-904b-d243cd4e665f", "text": "Each organism in Space is subjected to several factors which are potential constraints for biological life. Among the environmental factors (e.g., altered gravity, interaction between microgravity and fluid-dynamics, modified conditions of pressure, temperature, confinement, etc.) limiting plant growth in space, ionizing radiation influences severely the development of organisms at molecular, morpho-structural, and physiological levels [163, 182, 344]. Indeed, ionizing radiation is considered one of the main constraints for the long permanence of humans in Space."}
{"_id": "Radiology$$$dfc9df4c-2def-499e-b260-b37227c179d5", "text": "All organisms in extraterrestrial environments are subject to higher levels of ionizing radiation than on Earth and, notwithstanding the large number of studies aimed at understanding the effect of ionizing radiation on animals, the knowledge on plant reaction is limited. Available information is limited to horticultural model crops which are candidate for fresh food production in BLSS. Moreover, most experiments are based on the irradiation of dry seeds and data from irradiation tests using other biological models (e.g., seedlings, adult plants, actively growing tissues) are scanty."}
{"_id": "Radiology$$$34ccbac0-c7cb-416c-9fbb-b2894d188970", "text": "In Fig. 10.22, a comparison of the responses of plants and mammals to ionizing radiation exposure is shown. Generally, plants are more resistant than mammals. Ionizing radiation is known to have differential effects on plant growth, development, and reproduction, ranging from detrimental outcomes at high doses, harmful consequences at intermediate levels, and stimulatory effects at very low doses. This phenomenon is called \u201chormesis.\u201d Particularly, low doses of ionizing radiation have been reported to stimulate seed germination and root growth [345, 346].\n\nAn illustration depicts radiation hormesis, radiosensitivity, D N A repair mechanisms, high versus low L E T ionizing radiation, features conferring radio resistance in irradiated plants and mammals.\n\nFig. 10.22\nA comparison among different responses of Plants (P) and Mammals (M) to ionizing radiation. (Reprinted with permission from Arena et al. [346])"}
{"_id": "Radiology$$$55d65750-31ca-487f-ba02-ad4402ddc261", "text": "An illustration depicts radiation hormesis, radiosensitivity, D N A repair mechanisms, high versus low L E T ionizing radiation, features conferring radio resistance in irradiated plants and mammals."}
{"_id": "Radiology$$$35598530-e1a6-49a1-9868-e252520b238d", "text": "However, ionizing radiation can also induce dwarf growth that is a desirable trait under conditions of limited volume availability in missions on orbital stations or during exploration traveling. The increased radioresistance of plants is still a debated issue since it can be associated with a genetic basis, but it can also reflect biochemical and biomolecular mechanisms of shelter from genotoxic damage."}
{"_id": "Radiology$$$9be67b4f-00ed-42bd-b793-c688dbf469cd", "text": "The severity of the effects of ionizing radiation on plants is dependent upon several factors including radiation-related parameters (e.g., dose, LET) and organism-related traits (e.g., species, cultivar, physiological status, and structural properties, as well as plant genome organization including the polyploidy) [345, 347]."}
{"_id": "Radiology$$$49964a25-f23b-4800-9ba1-37c5dc3af4a0", "text": "In adult plants, in the case of organs at complete development, resistance to stressors can be often ascribed to integrated mechanisms of adaptation operating at morpho-structural and eco-physiological levels since the limits of major metabolic and physiological processes are dictated by the plant\u2019s structure [348, 349]. Growth, reproduction, and, ultimately, survival of plants in Space depend on photosynthesis which is strongly responsive to ionizing radiation acting on the various components of the photosynthetic apparatus, such as pigment\u2013protein complexes responsible for light absorption, electron transport carriers, and enzymes of carbon reduction cycle [345]. Ionizing radiation leads to several detrimental effects in photosynthetic apparatus, such as loss of functionality of photosystem II (PSII) and generation of free radicals causing photosynthetic membranes\u2019 oxidation [350\u2013352]. Changes in the total antioxidant pool and in the distribution of phenolic compounds in leaf tissues were observed in plants exposed to very high doses of X-rays, namely 50 and 100 Gy [353]."}
{"_id": "Radiology$$$957a3d2e-b679-479e-8499-446808665564", "text": "However, chronic exposure to low doses of ionizing radiation seems to enhance the activity of some antioxidant enzymes, providing plants with a radio-resistance [354, 355]. Moreover, the degree of plasticity of leaf cytological and anatomical traits in response to environmental changes can be responsible for enhancing or constraining processes such as light interception and gas exchanges, definitely affecting photosynthesis. Similarly, the correct functioning of the whole water transport system throughout the plant is responsible for water supply up to the leaves, necessary for efficient photosynthesis. The ability of xylem to transport water efficiently depends on the morphological features of its conduits and on the ultra-structural properties of conduit cell walls, whose main components can be differently affected by ionizing radiation."}
{"_id": "Radiology$$$cd56ac82-008e-45dc-996d-1c6b90a0a636", "text": "Apart from a few findings mainly related to specific ultra-structural modifications occurring on irradiated seeds, the effect of cosmic radiation on organ/tissue organization, especially in relationship with eco-physiological traits, is still poorly explored. Moreover, most of the studies regard experiments with low-LET ionizing radiation [346, 355], and only a few data are available on the effects of chronic radiation exposure on plants in general, mainly deriving from nuclear accidents as Chernobyl in Ukraine (1986) and Fukushima in Japan (2011)."}
{"_id": "Radiology$$$19ddf3a1-d6fb-4957-9de2-37fef21dfece", "text": "Regarding the complexity of their cells, all living organisms can be classified into two groups-prokaryotes and eukaryotes. Compared to prokaryotes, eukaryotic cells are highly organized and contain a cell nucleus. Prokaryotes are bacteria and archaea, while protists, plants (see Sect. 10.5.8), animals (see Sect. 10.5.7), and fungi (see Sect. 10.5.9) are eukaryotes."}
{"_id": "Radiology$$$100225c8-69b5-475e-bb3a-37cb155f788d", "text": "In the following the effect of space radiation on in vitro models (conducted in a cell culture dish) and ex vivo models (experiments outside a living body) will be described."}
{"_id": "Radiology$$$f381ead2-984b-4b56-876a-bb02c0c93cbc", "text": "In vitro models used in science, are very important, as they provide insight into cells. With this, the function of primary cells and cell lines of various origin (vertebrates including human, insects, and mussels) can be studied."}
{"_id": "Radiology$$$1dd522c3-8011-4585-b571-f8d9535a8cc8", "text": "Ex vivo models or tissue explants allow studying complex functions and interactions of different cells within an organ. For these experiments, the living tissues are directly removed from a living organism or can be generated by means of pluripotent stem cells and cultivated under controlled conditions."}
{"_id": "Radiology$$$fc00aec3-6b80-40b6-b6cd-5fa4b094d290", "text": "In comparison to cells in monolayer cultures (2D), cells in 3D cultures react completely differently. The biggest disadvantages of 2D cultures are the unnatural contact with a plastic or glass surface, the flat morphology of the cells on the growth surface that restricts intercellular contacts and the lack of an extracellular matrix which surrounds cells in vivo. These conditions modify the metabolism and functioning of cells and often result in the loss of the specific differentiation of a cell. The structure, function, and composition of organs and tissues can thus be better studied in 3D cell culture systems. They enable cell\u2013cell and cell\u2013extracellular matrix interactions in a three-dimensional space. 3D cultures are a very helpful tool before performing whole-animal studies. They can further be used to study the understanding of how processes in tissues are affected by spaceflight conditions, including space radiation and microgravity, which otherwise cannot be investigated in animal or human subject studies."}
{"_id": "Radiology$$$5227cc26-ee69-4647-b6e1-b48fff085095", "text": "There are many different models of 3D cell cultures, including organoids, ex vivo tissue, or slice cultures, which are explained in the following. Furthermore, it is possible to create these models with 3D bioprinting, which have then a structure which closely resembles the organization of tissue or organs. In fact, the European Space Agency (ESA) recently summarized the capability science requirements for 3D bioprinting on the ISS to support medical treatment on long-term space missions."}
{"_id": "Radiology$$$79fe6f83-1ad1-46de-bf67-35a071ad3e90", "text": "In all given examples two or more cell types can be co-cultured, closely simulating the situation in organs or tissues, e.g., investigation of cellular differentiation processes in tissues, nerve-muscle function, tissue regeneration and repair, vascular tissue function, brain tissue homeostasis and aging, immune system processes or cardiac muscle function."}
{"_id": "Radiology$$$e55c7cce-3835-45b1-a364-733e5f86c445", "text": "Human organoids, derived from stem cells or progenitor cells, are tiny self-organized organ-specific 3D cultures, recreating the physiological and cytoarchitecture of human organs. With this, the model reflects the in vivo situation much better than single cell cultures. For research purposes, it is feasible to create organoids that resemble the brain, kidney, lung, intestine, stomach, and liver."}
{"_id": "Radiology$$$482c4a12-527e-4b04-b9cb-a813844ee5b2", "text": "Organoids will help to study the effect of space radiation on the overall response of organs, including cellular heterogeneity, cell-matrix interactions, cell-cell interactions, morphology, and functional changes [356, 357], which cannot be studied in in vitro systems. One major disadvantage compared to in vivo systems is the lack of microenvironment."}
{"_id": "Radiology$$$60f5bd5b-5ce2-4efe-914e-5701bd68093c", "text": "The effects of microgravity on human brain organoids were tested on the ISS during the Space Tango-human Brain investigation in 2019 (NASA). Of special interest was the effect on the brain cells including survival, migration, metabolism, and the formation of neuronal networks (Muotri, unpublished)."}
{"_id": "Radiology$$$d5682195-4511-44ed-a47d-03207bb7c811", "text": "Spheroids are also 3D cell cultures, but in comparison to organoids, they form simple clusters into sphere-like formation, but they cannot self-assemble or regenerate. Whereby the cellular functions inside spheroids are closely correlated to the size, uniformity is especially important for reproducible results. To guarantee this, several methods for culturing are available such as hanging drops, scaffolds, liquid overlay technique, and hydrogels [358]. Nowadays spheroids are highly used to study the microenvironments of tumors or their response to radiotherapy."}
{"_id": "Radiology$$$3156a513-1335-47e7-a02d-818ca7970bd7", "text": "Already in 2016, the SPHEROIDS project was launched on the ISS. Here, endothelial cells, which under simulated microgravity form small, rudimentary blood vessels, were exposed to real microgravity for 12 days on the ISS. The formation of spheroids under space conditions and under simulated microgravity on Earth were similar [359], underlining the important role of microgravity in spheroids formation."}
{"_id": "Radiology$$$29d52a82-15bd-48e0-8cb6-38ef17af131d", "text": "Differences between the three types of cultures are summarized in Fig. 10.23.\n\nA table depicts the cell types, derived from, morphology, represent, and examples of monolayer, spheroid, and organoid, with corresponding diagrams.\n\nFig. 10.23\nDifference between the different cultures"}
{"_id": "Radiology$$$c7b79912-7501-4d3b-9f65-869128bb5fb3", "text": "A table depicts the cell types, derived from, morphology, represent, and examples of monolayer, spheroid, and organoid, with corresponding diagrams."}
{"_id": "Radiology$$$5a244ec8-91f9-44fc-9ec2-d3b3e8446946", "text": "Organotypic slice cultures are tissue samples that are cut in thinly, about 300 \u03bcm, thick slice and are then cultivated on semipermeable insert. Most common are organotypic slice cultures that originate from different parts of the brain (e.g., hippocampus, cerebellum, or cortex) and can be kept in cultures for long term, while slices originating from liver tumors can only be kept in culture for a short time [360, 361]. Also, this 3D culture has the advantage that the composition and architecture of the extracellular matrix as well as the tissue are preserved. During analysis of the slices, it has to be considered that every slice, even from the same organ, has a partly different composition, cell counts, and viability, limiting the reproducibility of results produced by this method."}
{"_id": "Radiology$$$f5857127-a803-4fd4-a4cf-0b484ac13216", "text": "Organ cultures were developed from tissue and slice cultures. By using organ cultures, it is possible to study the functions of an organ in various conditions and states in an in vitro organ. Hereby, the entire organs or only a part of the organ are excised from the body and cultured. Also, with this method, the 3D structure of the tissue of choice is preserved."}
{"_id": "Radiology$$$ad5d7604-6389-4b08-a947-5b735b5beff9", "text": "For space exploration, the eye lens is of special interest, because it is amongst the most radiosensitive tissues in the human body. Ionizing radiation can cause a posterior sub-capsular cataract [287, 362, 363]. Whole lenses and lens epithelial cells in culture enable the study of early mechanisms of space radiation-induced cataractogenesis and of the relative biological efficiency of different space radiation components to induce early changes. With regard to the human lens in anatomy and size, the porcine eye is very similar. Thus, it is used to study the radiation response in the whole organ. Translation to the human eye lens can be enabled by using human-transformed epithelial cells or lens epithelial cells from donor patients. As the viability of eye lenses in cultures is limited to a few weeks, studies on radiation-induced full-blown cataract formation usually require animal experiments over their lifespan (Sect. 10.5)."}
{"_id": "Radiology$$$9502e405-385d-41a5-9f0f-a4c30d0b9f84", "text": "In addition to that, the microgravity environment on the ISS suits perfectly to 3D print tissue cultures and later maybe entire organs. Compared to conditions on Earth where scaffolds or matrices are needed to form organoids, in space cells can easily self-organize into their precise structure. On the one hand, the bioprinted tissue could be used in the future to treat injured astronauts [364] and on the other hand the technique can be transferred to Earth and then be applied to the field of regenerative medicine for organ transplantations [365]. In July 2019, the 3D BioFabrication Facility (BFF\u2014see Fig. 10.24) has arrived onboard of the ISS, with this it is now possible to study 3D bioprinting of different human tissues in space. Also, here real microgravity has the benefit that printed structures will not collapse, enabling also the printing of soft human tissue (NASA) (Box 10.10).\n\nA photograph of the three-dimensional bio fabrication facility, the first bioprinter capable of manufacturing human tissue in the microgravity of space.\n\nFig. 10.24\nNASA\u2019s 3D BioFabrication Facility BFF. (Image JSC2019E037579, Credits NASA)"}
{"_id": "Radiology$$$c7082e77-25cd-4f91-a113-beaf63ae8fad", "text": "A photograph of the three-dimensional bio fabrication facility, the first bioprinter capable of manufacturing human tissue in the microgravity of space."}
{"_id": "Radiology$$$ef5cb6b9-a601-4b07-a23b-501eb3daf445", "text": "Several cell cultures system can be studied under space conditions\n\nThe microgravity environment on the ISS suits perfectly to print 3D tissue cultures"}
{"_id": "Radiology$$$72993841-1345-4f52-aa4a-5bb2eb7c5dfb", "text": "The microgravity environment on the ISS suits perfectly to print 3D tissue cultures"}
{"_id": "Radiology$$$a6d609fb-7106-4063-b4f6-1083d5c60895", "text": "Understanding the effects of the space environment on microorganisms has witnessed recently considerable progress (whereas the main factors are microgravity, radiation, and vacuum). However, explicit knowledge of molecular mechanisms responsible for survival and adaptation in space is still missing. Space environment affects a variety of physiological features of microorganisms. The above features include metabolism, motility and proliferation rate, division of cells, and also virulence and biofilm production (Fig. 10.25) [366]. Molecular-level understanding of the above effects in space-exposed microorganisms is still lacking. It is believed that omics-based approach, together with classical phenotyping and physiological measurements, will be a useful toolbox for understanding mechanisms of microbial survivability in the harsh conditions of outer space. \u201cOmics\u201d stands for genomics, transcriptomics, proteomics, metabolomics, and more.\n\nAn illustration describes the stress response, membrane-associated readjustments, metabolic rearrangements, and genetic alterations for the survival of microbial entity in space environment.\n\nFig. 10.25\nMolecular response experienced by microorganisms in the outer space environment revealed with the help of global and integrative \u2013omics approaches of systems biology that have been recently used to study microorganisms exposed to real and simulated space conditions. (Reprinted with permission from Milojevic et al. [366])"}
{"_id": "Radiology$$$598a3dae-48e2-4fee-b5c1-f65ded7e4755", "text": "An illustration describes the stress response, membrane-associated readjustments, metabolic rearrangements, and genetic alterations for the survival of microbial entity in space environment."}
{"_id": "Radiology$$$af7310f6-055d-4c3a-be33-56d2505dd7cb", "text": "Systems biology is an interdisciplinary approach in biomedical research aiming at understanding the biological system at the organism, tissue, and cell level. Systems biology incorporates the results of \u2013omics techniques, genome-scale metabolic and regulatory biomathematical models to understand molecular interactions, evolution, functional and phenotypical diversity, and molecular adaptation. The omics-based approach integrates various pieces of biological information from genomes, mRNA, and proteins to metabolites [367]."}
{"_id": "Radiology$$$7df5f84b-fcd9-4416-8fb8-198c57f1c079", "text": "The \u2013omics-based approach has recently opened a window for a deep insight into molecular machinery implicated in the survivability of space-exposed microorganisms by revealing expression, metabolic functioning, and regulation of the genes and proteins encoded by the genomes of \u201cspace travelers.\u201d The diverse biological activities of microorganisms in space are affected by metabolic alterations caused in turn by genetic regulations (Fig. 10.26). It has been demonstrated by means of \u2013omics-based approaches that exposed microbes switch to \u201cenergy saving mode.\u201d Research identified some global regulatory molecules that drive molecular response of a few space-exposed microorganisms [366\u2013369]. Various kinds of stress responses (e.g., general, osmotic, and oxidative) experienced by microorganisms in conditions of real and simulated outer space have been deciphered via \u2013omics-assisted analyses [366]. Various genes with altered expression after microbs\u2019 exposure to real and simulated outer space environment (Fig. 10.25) have been identified [366].\n\nAn illustration lists the genes and proteins expressed in different microbes during general stress response, osmotic stress response, tellurium resistance, and oxidative stress response in space.\n\nFig. 10.26\nStress responses experienced by microorganisms in outer space real and simulated conditions, revealed with \u2013omics-assisted investigations. Proteins and genes of stress responses with altered abundance and expression after exposure of microorganisms to the outer space real and simulated environment [366]"}
{"_id": "Radiology$$$f7cbb387-0ac5-4010-90ec-2a220d0c8e60", "text": "An illustration lists the genes and proteins expressed in different microbes during general stress response, osmotic stress response, tellurium resistance, and oxidative stress response in space."}
{"_id": "Radiology$$$a64bd4db-1373-44b9-a3b0-52aa8ead9c1a", "text": "State-of-the-art \u2013omics technologies have been successfully used to understand molecular mechanisms responsible for alterations of microbial virulence in space conditions (Fig. 10.27) [366].\n\nAn illustration lists factors of pathogenicity, virulence, and biofilm formation in space by K. pneumonia, S. aureus, D. radiodurans, B. cereus, P. aeruginosa, S. cerevisiae, C. albicans, Salmonella.\n\nFig. 10.27\nMolecular alterations underlying microbial pathogenicity, virulence, and biofilm formation in the outer space environment, resolved with \u2013omics-assisted investigations [366]"}
{"_id": "Radiology$$$736d25f0-8b66-40b8-9a69-ca2b8dad8c6a", "text": "An illustration lists factors of pathogenicity, virulence, and biofilm formation in space by K. pneumonia, S. aureus, D. radiodurans, B. cereus, P. aeruginosa, S. cerevisiae, C. albicans, Salmonella."}
{"_id": "Radiology$$$634c11d0-8550-4b72-90c5-d75900a89875", "text": "Space exposure imposes stresses that affect microbial survival rates and may lead to certain discrepancies in \u2013omics-assisted analysis of returned/exposed microorganisms. The composition of the cultivation medium influences the microbial space response [369], e.g., by providing specific antioxidants presented in rich medium, which may protect microbial cells against ionizing radiation. The majority of space experiments have been performed on satellites, where microorganisms are cultivated in environment protected from all factor but microgravity [366]. Direct exposure to real space environment outside the ISS followed by investigation with \u2013omics techniques was performed on a few microbial species only [367, 370, 371]. Therefore, in order to broaden our knowledge of molecular mechanisms of microbial survivability in outer space, there is an urgent need for further experiments with direct exposure. Often, a multi-omics post-flight analysis has the problem of a limited number of microbiological samples exposed to the space environment. Therefore, the researchers should critically assess the design of outerspace experiments to provide a sufficient number of independent biological samples in order to enable statistically significant results in processing the \u2013omics data. It is also extremely important to avoid artifacts: due to very high sensitivity of the \u2013omics techniques of occasional occurrence of uncontrolled conditions, stress-related artifacts cannot be ruled out. In this context, it is highly desired to develop novel approaches for the efficient extraction of DNA, RNA, proteins, and metabolites simultaneously from the minimal amount of microbial cells [367, 372]. Furthermore, the absence of detailed reports regarding the environmental conditions during space exposure and corresponding ground control experiments is, unfortunately, a frequent reality that requires a critical reassessment of research planning. Providing a full record of controlled parameters (like temperature, humidity, and pressure profiles) during flight, simulated, and control experiments is highly desired to achieve a comprehensive and artifacts-free analysis of the effects of the space environment on the physiology and molecular machinery of microorganisms."}
{"_id": "Radiology$$$d934f8d0-e21b-42e2-8b4e-e1e9300ae929", "text": "It has been proposed that in future space experiments, detailed metabolomic analysis of exposed microorganisms should be performed in addition to the proteotranscriptomic profiling. This novel approach has provided already plenty of new findings on fine molecular networks regulating the space response [367]. Recent works (e.g., the NASA twins\u2019 study) used a multi-omics, systems biology analytical approach to analyze biomedical profiles of astronauts [120]. Results of performed targeted and untargeted metabolomics combined with proteomics effectively revealed the biomedical responses of a human body during a year-long spaceflight indicating mitochondrial stress as a consistent phenotype of spaceflight [120, 373]. Finally, the combination of molecular data with a genome-scale metabolic reconstruction of the respective species should be implemented, delivering the space-induced microbiome signatures [366]."}
{"_id": "Radiology$$$bcb7402a-41a1-41b2-8340-6fddf15b2589", "text": "Humans have all evolved in an environment containing a persistent low level of constant exposure to different endogenous and exogenous mutagenic agents, and consequently have developed many cellular mechanisms for either DNA protection or repair (see Chap. 2). However, when humans travel into space, these naturally evolved cellular mechanisms might not be enough as many major health threats from space radiation has been identified, e.g., central nervous system injury, cardiovascular diseases, immune dysfunction, cancer development, and premature aging. To reduce the risk of humans in space, there are some possible interventions which can limit the effects of space radiation. A dedicated review can be found elsewhere [374]."}
{"_id": "Radiology$$$33fd6e49-8776-4541-bd3c-406f7f584bc0", "text": "One way of reducing the health risk from space radiation exposure in humans is selecting more radioresistant humans during the selection campaigns of space agencies. The most used way is to perform in vitro adaptive response studies, in which cells collected from the candidates are used to measure their response to a fixed dose of ionizing radiation. While the results of these studies are not necessarily used during candidate selection, they hold great value in selecting the right people that will be more protected against space radiation. Another strategy would be to pharmacologically hamper the processes underlying the molecular (side) effects of space radiation exposure. Examples are the application of radioprotectors and geroprotectors, as well as supplementation with antioxidants or antioxidative capacity increasing compounds (see Chap. 11). While these pharmaceuticals hold great promise, many of them are still under investigation and not allowed to be used on humans."}
{"_id": "Radiology$$$beec7f97-084b-4580-ae78-8a7ee8bcd4c3", "text": "An alternative method to elevate humans\u2019 natural radiation protection capacity is inducing a hibernating or hypostasis state. It is well-known that natural hibernators become more radioresistant during their inactive state. The reason for this has not yet been fully elucidated. It is probably due to several factors related to slower cell metabolism and increased tissue hypoxia."}
{"_id": "Radiology$$$11c3447e-8f92-45e7-86d2-b4b1d6c5f82e", "text": "In recent years, a technique has been developed that allows hibernation to be reproduced even in those animals that would not usually be able to hibernate, such as rats. This technique is nowadays known as synthetic hibernation or synthetic torpor [375]. Although this research has a big potential to limit radiation-associated risks in space, it is quite far from practical use yet. Another futuristic method is the use of deuterium, the stable isotope of hydrogen. As carbon-deuterium bonds need more energy to break than normal carbon-hydrogen bonds, the necessary energy to break the hydrogen bonds between DNA bases would be higher, making deuterated DNA less sensitive than normal DNA to DNA damage following ionizing radiation exposure. However, a lot of issues have to be solved before deuterium could be applied in humans: lack of evolutionary adaption to catabolize organic compounds containing deuterium, consequent slower rate of vital metabolic reactions, and their potential toxic effects. Nevertheless, it has been shown that deuterated food or water intake helps to increase life or health spans from numerous model organisms."}
{"_id": "Radiology$$$b0936279-5c7b-4b3b-8ce1-1ae5f0bd28f9", "text": "Gene therapy stands for the use of genetic modifying techniques in order to achieve a therapeutic effect. In the context of radiation and radiation protection, this has been studied for several radioresistance mechanisms making these techniques interesting for deep space missions, where radiation protection concerns arise [374]"}
{"_id": "Radiology$$$1b5a2255-76db-45fb-ba00-2cddf0d4213d", "text": "One of the strategies for gene therapy in radioresistance is the overexpression of endogenous antioxidants, for example, magnesium superoxide dismutase (MnSOD) that acts as a scavenger for reactive oxygen species produced after the interaction of radiation with the cell [376]."}
{"_id": "Radiology$$$19a4828a-c800-4a5a-b014-2bf56dab177c", "text": "Another angle in which gene therapy can be useful for improving radioresistance is by enhancing the DNA damage repair such as the overexpression of certain repair proteins that are normally active in repairing the damage in the DNA strands after radiation exposure [377]."}
{"_id": "Radiology$$$d9c66ce2-d8df-4b5a-b980-db07b4c28365", "text": "A promising approach takes its inspiration from extremophiles and their impressive radioresistance capabilities, in concrete, the tardigrades, a microscopic animal that is capable of surviving in extreme conditions. A protein identified in these organisms, termed damaged suppressor (Dsup), has been made to be expressed in human cell lines, reducing the number of DNA strand breaks and preserving cellular proliferative abilities after high doses of radiation [337]."}
{"_id": "Radiology$$$b3096002-626a-47b7-987b-89a2d3518f07", "text": "Extreme conditions in a natural environment are only extreme from a human point of view. Extremophiles can only live under these conditions and depend on them. Often organisms living under these conditions are called \u201cextremophiles\u201d or \u201cpolyextremophiles\u201d since most of them are coping with different extremes in their natural environment [378]."}
{"_id": "Radiology$$$306eff0c-5b00-4d2b-bce5-a9761e03a1d6", "text": "Plenty of different (poly) extremophiles in natural and human-made extreme environments exist in natural and human-made harsh environments. Examples include anaerobes, (hyper-) thermophiles, psychrophiles, halophiles, acidophiles, xerophiles, and piezophiles. For all the named organismic groups, cellular adaptation mechanisms are known that protect the cells themselves or enable them to live under extreme conditions in their natural habitat. In addition to the intracellular protection mechanisms, general protection mechanisms like spore formation are well-known. For example, the spore of the Bacterium Bacillus subtilis is characterized by a thick layer of peptidoglycan, a low water content inside the cell, a DNA conformation changed from B to A, and the presence of \u03b1/\u03b2-type small acid-soluble spore proteins which accumulate within the spore. In general, spores are more tolerant to inactivating physical stresses, like radiation as vegetative cells [379, 380]. Spore formation is known to be an answer to changing conditions in the environment that is used by microorganisms and fungi; special forms like the anhydrobiotic state are also observed in other eukaryotic cells like tardigrades, nematodes, and rotifers [381]. Spore formation and the anhydrobiotic state, as well as intracellular adaptation mechanisms, are relevant for possible survival after exposure to ionizing (space) radiation [323, 382]. In addition to spore formation, biofilm growth by the production of extracellular polymeric substances (EPS) also leads to a higher ionizing radiation tolerance [383]."}
{"_id": "Radiology$$$43854c2e-5851-4004-8d1d-816736502aa9", "text": "Besides the named cellular adaptation mechanisms, there are also different intracellular adaptation mechanisms possible to cope with extreme environmental stresses. As described before, ionizing radiation exposure does not only lead to direct effects and intracellular damage, such as DNA strand breaks, it also leads to indirect effects, like ROS production. Hyperthermophilic Archaea, like Pyrococcus furiosus, are partly tolerant to the indirect effects of ionizing radiation, due to mechanisms protecting the DNA from the influence of ROS [384]. In these Archaea, DNA binding proteins play a major role as they bind and protect the DNA thereby limiting the accessibility of the DNA to ROS. In addition, increased expression of different enzymes like superoxide dismutase and the glutathione peroxidase can also reduce the level of intracellular ROS."}
{"_id": "Radiology$$$4342c3c6-c4c7-4142-8c89-0f47217adf72", "text": "For the Bacterium Deinococcus radiodurans as well as for the Archaeon Halobacterium salinarum special intracellular Mn/Fe ratios are described: they demonstrate an intracellular accumulation of high amounts of manganese along with low iron levels, which contribute to their high radiation tolerance [385, 386]. This special Mn/Fe ratio was not found in radiation-tolerant anaerobic microorganisms. It is proposed that the low levels of IR-generated ROS under anaerobic conditions combined with highly constitutively expressed detoxification systems in these anaerobes are key to their radiation resistance and circumvent the need for the accumulation of Mn-antioxidant complexes in the cell [387]."}
{"_id": "Radiology$$$577cc765-d1c7-4d8b-9bd5-64fd7ac0959d", "text": "Furthermore, polyploidy or the presence of several DNA copies within one single cell has been discussed to contribute to tolerance to desiccation and therefore also to ionizing radiation [388]."}
{"_id": "Radiology$$$b24a2b52-c2df-4885-af03-be16fb3fa2cf", "text": "Halophilic organisms have different strategies to cope with a high salt concentration in their natural habitat. One option is the intracellular accumulation of salt or other compatible solutes [389]. It is also known that compatible solutes can contribute to the tolerance to ionizing radiation in halophilic microorganisms [389]. Additionally, protective mechanisms such as membrane pigments, including carotenoids, melanin, scytonemin, and bacterioruberin were found to be important in ionizing radiation protection in different organisms through the scavenging of hydroxyl radicals [390, 391]."}
{"_id": "Radiology$$$b69f3376-6330-4820-b368-089e7e73b1b9", "text": "In general, there is no direct adaptation of microorganisms to space conditions or space radiation known as all organisms evolved on Earth. Nevertheless, there have been and still are space experiments ongoing where the adaptability of different organisms is investigated during exposure to space conditions. In this context, we speak about the side effects of other tolerances or resistances which enable the organisms to endure space stressors. In general, organisms which are tolerant to desiccation developed mechanisms to repair the DNA which is damaged during the desiccation process. The same repair mechanisms can also be used to repair DNA damage caused by other stressors, such as ionizing radiation. One prominent example is the desiccation and radiation tolerance of the microorganism Deinococcus radiodurans. This organism uses the same cellular adaptation and repair strategies after exposure to drought and ionizing radiation exposure. However, not all desiccation-tolerant organisms are tolerant to (ionizing) radiation exposure [392]. The same is true for other repair machineries, where no direct correlation between hyper-/thermophilic organisms or the ability to produce compatible solutes and radiation tolerance could be identified [393, 394]. In addition, some microorganisms (e.g., Ignicoccus hospitalis) demonstrate a high survival rate after ionizing radiation exposure but possess a repair mechanism which is not known up to now [395]."}
{"_id": "Radiology$$$00e30089-4180-4fef-965d-5d86aa7ffd00", "text": "As mentioned at the beginning of this chapter, protons account for nearly 87% of the total flux of the galactic cosmic radiation (GCR), helium ions\u2014for approximately 12%, and the remaining heavy ions, or high-Z elements (HZE),\u2014for less than 1%. However, the relative distribution of the effective dose is quite different. Multiplying the abundance by Z2 provides an estimate of the contribution to the dose. One should further consider the quality factor of the biological effectiveness of the corresponding radiation. As a result, HZE particles contribute approximately 89% of the total dose equivalent (mSv) in free space. Among the HZE particles in GCR, iron is the largest contributor (26%) to the effective dose [396]."}
{"_id": "Radiology$$$4b6cacc4-7016-454c-8f7d-fcbe5beeffe1", "text": "Low dose rate irradiation is usually provided in a laboratory either by X-ray machines or radioactive sources, and neither mimics GCR well. The X-rays are low-energy radiation and do not mimic the penetrating capability of GCR. Usual radioactive sources emit \u03b1-, \u03b2-, and \u03b3-radiation. While \u03b1-particles are helium nuclei abundant in GCR, the energy of typical \u03b1-particles is 4\u20139 MeV as compared with above 1000 MeV in GCR. As a result, \u03b1-particles cannot penetrate the thinnest screen (even the skin) and cannot be used for GCR simulation."}
{"_id": "Radiology$$$438e60ab-162a-40a4-bbff-87de3ddd0c6e", "text": "\u03b3-Radiation has a much stronger penetration capability, and \u03b3-emitters are used [397]. However, the biological effects of \u03b3-radiation and ions are different. As for the \u03b2-radiation, in the sense of GCR simulation it combines the drawbacks of \u03b1 and \u03b3: having low penetrating capability, its biological effects are similar to \u03b3 and far from high-energy ions."}
{"_id": "Radiology$$$816fe3bb-7aa5-40e8-b163-7477fe30c581", "text": "A partial solution has been found by using a unique artificial isotope Californium-252, which exhibits exceptionally high neutron emission. 252Cf is used, e.g., at the ESA test station and the new facility in Japan [398]."}
{"_id": "Radiology$$$4119b73d-227c-4e27-b27e-5505d8382456", "text": "Although low-energy charged particles (up to about 20 MeV) do not reproduce the characteristics found in the GCR spectrum, low-energy facilities are widely available and are useful to help in the screening and the design of experiments that will be further carried out on higher energy accelerators (see next subsection)."}
{"_id": "Radiology$$$5e07ab2d-9dff-406c-940f-e5d633f3cf6b", "text": "Several accelerator types can be used to produce such low-energy beams, but electrostatic tandem accelerators are probably the most widely used. A schematic representation of such accelerator is given in Fig. 10.28. The first part consists of an ion source, which can produce any negative ion (with one extra electron) from hydrogen to uranium. The produced negative ion beam is then extracted from the source and guided to the main tube. The acceleration is carried out in two stages hence the name \u201ctandem accelerator.\u201d First, the negative ions are attracted to the positive high-voltage \u201cterminal\u201d located in the center of the tube. Then, negative ions can be stripped of part of their electrons (usually 2\u20133) in the stripper channel, turning to positive ions. These positive ions are repelled by the positive terminal voltage to the end of the tube, which is at ground potential. High-energy ions are focused by (usually superconducting) magnets and deflected into one of the beamlines, according to the particle energy, mass, and charge.\n\nA diagram depicts particles from ion source passing through accelerator, energy selection magnet, aperture, beam switch and scanning with control, focusing unit, and sample. Detector gives the signal.\n\nFig. 10.28\nSchematic view of the SNAKE (Superconducting nanoprobe for (kern) particle physics experiments) setup, including linear particle accelerator (orange), focusing unit (superconducting magnetic lens) and detection system with the particle detector and ultrafast high-voltage switch"}
{"_id": "Radiology$$$f6a629f4-3c12-4049-8fdc-4cbd03e70a2f", "text": "A diagram depicts particles from ion source passing through accelerator, energy selection magnet, aperture, beam switch and scanning with control, focusing unit, and sample. Detector gives the signal."}
{"_id": "Radiology$$$fdfd0abc-728b-41ad-a038-6a8b5f22fe8c", "text": "Regarding the beam size, two configurations are used: microbeam and broad beam."}
{"_id": "Radiology$$$791a91b7-92cf-458e-9ec1-81b0b92d1f4f", "text": "The initial accelerated ion beam is always a microbeam with a diameter often below 5 \u03bcm. Microbeams are a useful tool in studying the bystander effect (described in detail in Chap. 2). Indeed, such a beam permits to irradiate selectively one or more cells inside a population. This offers the possibility to either target the cell nucleus, the conventional target in radiobiology, the cytoplasm, or organelles. It also provides the advantage of knowing precisely the dose delivered to the cells and the number of particle shoots being determined in advance. In the context of space radiation, where the flux of high-mass particles is very low and the occurrence of a single shoot-in through a cell is very high, the bystander effect is a topic of crucial importance. Indeed, it is observed through a variety of endpoints: reduction in cell survival, double strand break induction, micronuclei, mutations, and expression of apoptosis, inflammation, and cell cycle-related genes."}
{"_id": "Radiology$$$407b344c-a03d-44cc-b3a6-e153f1f80788", "text": "Broad beams can be produced either by using scattering foils, by scanning microbeam, or by defocusing them. Beam homogeneity is controlled by plastic scintillators or silicon-based detectors."}
{"_id": "Radiology$$$87cac328-b6de-4b78-9b27-482f41f2075e", "text": "The importance of accelerator-based studies was acknowledged by NASA decades ago. After preliminary research at the existing accelerators, it was decided to build a dedicated beamline. In 2003, the NASA Space Radiation Laboratory (NSRL) was commissioned at the Brookhaven National Laboratory (BNL). The NSRL layout is presented in Fig. 10.29. The facility is capable of supplying particles from protons (p) to gold (Au). Available beam energies range from 50 to 2500 MeV for protons and 50 to 1500 MeV per nucleon for ions between helium (He-2) and iron (Fe-56; Z\u00a0=\u00a026). Heavier ions with atomic numbers up to Z = 79 (Au) are limited to approximately 350\u2013500 MeV per nucleon (https://\u200bwww.\u200bbnl.\u200bgov/\u200bnsrl/\u200b).\n\nAn airborne photograph depicts the buildings of N S R L, target room, Linac, and E B I S enveloped by W fifth avenue and Michelson street.\n\nFig. 10.29\nAerial view and general layout of the NASA Space Radiation Laboratory (NSRL) facility in Upton, NY, USA. EBIS electron beam ion source. (Satellite view courtesy Google Earth)"}
{"_id": "Radiology$$$e8a034b0-9b28-4958-843e-3ef17b1d13ba", "text": "An airborne photograph depicts the buildings of N S R L, target room, Linac, and E B I S enveloped by W fifth avenue and Michelson street."}
{"_id": "Radiology$$$43ff316a-0833-48db-90b8-65f1140f8b7c", "text": "The choice of Fe-56 ions is justified by a sharp decline in abundance for ions heavier than iron [396] while the chosen energy is around the peak of the galactic cosmic radiation spectrum. Moreover, the linear energy transfer is about 140 keV/\u03bcm, around the peak of effectiveness for late radiation effects [399]. The three key areas developed together to ultimately provide the GCR simulator at NSRL are illustrated in Fig. 10.30. Several important results have been obtained at NSRL. We can mention, for example, the observation that, despite being high-LET particles, heavy ions are not more effective than \u03b3-radiation in the induction of leukemia in mice [400]. Another example is the discovery of specific types of brain damage caused by heavy ions [401], types that had not been known from X-ray studies.\n\nAn illustration lists the varied exploration missions, N S R L facility parameters, and animal and cell models in the simulation of G C R by NASA.\n\nFig. 10.30\nThree key areas developed to provide the GCR simulator at NSRL. (Source: Simonsen et al. [396], reproduced with permission)"}
{"_id": "Radiology$$$da799118-8b23-4f04-96bc-bfc9bb2a7af3", "text": "An illustration lists the varied exploration missions, N S R L facility parameters, and animal and cell models in the simulation of G C R by NASA."}
{"_id": "Radiology$$$d3a4ae87-29ce-4cb2-8f59-a2f25ec567fa", "text": "The basic idea of a high-energy accelerator is illustrated schematically in Fig. 10.31. Each accelerating section itself consists of a sequence of resonant cavities in which the RF (radio frequency) electromagnetic field is oscillating. Ions traverse RF cavities subsequently; the timing of the passage of each cavity is synchronized with the direction and phase of the electric field\u2014therefore, each ion is accelerated from cavity to cavity. In case of a linear accelerator (LINAC), the accelerating sections are positioned adjacently along a straight line. In case of a synchrotron (like EBIS in Fig. 10.31), the accelerating sections are positioned along a circumference, while the charged particle beam is bent between the sections by a magnetic field.\n\nThe diagram depicts an injector made of an ion gun and buncher and an accelerating section with radio frequency. The ion gun has a source and a grid gate. Charged particles\u2019 bunches enter the buncher at a radio frequency.\n\nFig. 10.31\nGeneral layout of a linear high-energy particle accelerator. RF radio frequency"}
{"_id": "Radiology$$$d8ce025a-8229-4226-a9a0-0b5a1cf0d47c", "text": "The diagram depicts an injector made of an ion gun and buncher and an accelerating section with radio frequency. The ion gun has a source and a grid gate. Charged particles\u2019 bunches enter the buncher at a radio frequency."}
{"_id": "Radiology$$$adb6b357-9a98-467f-a7ca-d167394695b5", "text": "The resonant frequency is usually either about 1 GHz (L-band of the RF spectrum) or about 3 GHz (S-band). The electromagnetic power for feeding the RF cavities is generated usually by a high-power klystron."}
{"_id": "Radiology$$$93587e7e-070a-42c3-bb4e-22645fe0bbc8", "text": "The accelerating cavities can be made either of normal-conducting metal (\u201cwarm\u201d cavities usually made of copper) or of superconductor (usually, niobium). In the last case, cryogenic cooling to liquid-helium temperature is needed. Accelerating gradients are usually in the range of 10\u201330 MeV/m, e.g., the 3-km long SLAC accelerator commissioned back in the 1960s, accelerating electrons to the energy of 50 GeV, has an average accelerating gradient of about 17 MeV/m (with 3-GHz copper cavities)."}
{"_id": "Radiology$$$257bce5d-5eef-44de-b3b9-d93d8a0fef3c", "text": "Output of RF-driven particle accelerator necessarily consists of single bunches. Such bunches are called micropulse, and their duration is just a fraction of the oscillating field period. For example, for the S-band with period of about 300 ps = (3 GHz)\u20131, the typical micropulse duration is below 20 ps. The train of micropulse is called \u201cmacropulse.\u201d While there is no theoretical limit for macropulse length, practically it is limited by the driving klystron pulse length: For S-band normal-conducting linacs the typical value is 5\u201320 \u03bcs, for L-band superconducting linacs\u2014much longer (1 ms and more)."}
{"_id": "Radiology$$$4f89db40-9853-4fbb-9538-0c394311d40d", "text": "Particle beams are collimated and bent \u201cmagnetic lenses\u201d\u2014magnetic fields created by electromagnets or permanent magnets. These magnetic devices, governing the charged particle beam propagation, are called electron-optic (or ion-optic) devices. Such devices have some similarities to classical light optics in terms of mathematics, but in general comprise a separate field of knowledge. The reader interested in learning the field of particle beam optics is referred to the classical textbook of Reiser [402]."}
{"_id": "Radiology$$$98e46ea2-1f2e-4c39-9682-f3b58178318b", "text": "Although ionizing radiations were identified as the main showstopper to exploration mission, there are additional stresses in the space environment. While most of the factors below are not relevant to astronauts, they are important in studying extremophiles."}
{"_id": "Radiology$$$c70565e0-7932-4989-b566-dbc2e615d266", "text": "1.\nLow pressure: The pressure varies from 10\u20131 Pa near Earth atmosphere to 10\u201314 Pa in deep space. Due to the degassing, pressure around the ISS is higher than in deep space ranging from 10\u22127\u00a0Pa in the Ram direction (e.g., front of the ISS relative to flight direction) to 10\u22124 Pa in the Wake direction (e.g., rear of the ISS relative to flight direction) [403].\n\u00a02.\nCold temperature: The low-pressure environment previously described drastically increases the molecular mean free path in space resulting in low heat transfer. Consequently, the temperature in deep space ranges from 3 to 4 K (\u2013270 to \u2013260\u00b0C) [404].\n\u00a03.\nSolar radiation: Highly energetic phenomena are occurring in the Sun leading to the emission of high-intensity electromagnetic radiations. By moving away from the Sun, the emitted solar radiations are spread out over a large surface area reducing the solar irradiance with increased Sun-object distance. ISS, located at one astronomical unit distance from the Sun, is exposed to an approximate 1400\u00a0W/m2 heat flux. The associated electromagnetic spectrum extends from X-rays to radio waves with a higher proportion in the visible (47%), infrared (45%), and ultraviolet (7%) ranges [405].\n\u00a04.\nDay and night cycles: As ISS orbits around the Earth and the latter around the Sun, the stress exposure has a cyclic temporal behavior with two main periods. The \u201cday and night\u201d cycle caused by the rotation around the Earth has a period of 91 min resulting in fluctuation in total irradiance and temperature of more than 1000 W/m2 and 5\u201310 \u00b0C. The second cycle (period of approximately 1 month) is due to the position change of ISS orbital plane relative to the Sun. In this case, greater variations of temperature (up to 60 \u00b0C) with a maximal temperature of about 50 \u00b0C were reported [406]."}
{"_id": "Radiology$$$6f87b200-b5b2-4368-8ad7-f6b6a988c4fd", "text": "Low pressure: The pressure varies from 10\u20131 Pa near Earth atmosphere to 10\u201314 Pa in deep space. Due to the degassing, pressure around the ISS is higher than in deep space ranging from 10\u22127\u00a0Pa in the Ram direction (e.g., front of the ISS relative to flight direction) to 10\u22124 Pa in the Wake direction (e.g., rear of the ISS relative to flight direction) [403]."}
{"_id": "Radiology$$$b58aca5f-1256-43e1-a86d-04944bbe770f", "text": "Cold temperature: The low-pressure environment previously described drastically increases the molecular mean free path in space resulting in low heat transfer. Consequently, the temperature in deep space ranges from 3 to 4 K (\u2013270 to \u2013260\u00b0C) [404]."}
{"_id": "Radiology$$$184ea765-347f-444b-bc50-bbc3b4084cb5", "text": "Solar radiation: Highly energetic phenomena are occurring in the Sun leading to the emission of high-intensity electromagnetic radiations. By moving away from the Sun, the emitted solar radiations are spread out over a large surface area reducing the solar irradiance with increased Sun-object distance. ISS, located at one astronomical unit distance from the Sun, is exposed to an approximate 1400\u00a0W/m2 heat flux. The associated electromagnetic spectrum extends from X-rays to radio waves with a higher proportion in the visible (47%), infrared (45%), and ultraviolet (7%) ranges [405]."}
{"_id": "Radiology$$$53a03bad-39de-4e77-b5a6-753c44f08c33", "text": "Day and night cycles: As ISS orbits around the Earth and the latter around the Sun, the stress exposure has a cyclic temporal behavior with two main periods. The \u201cday and night\u201d cycle caused by the rotation around the Earth has a period of 91 min resulting in fluctuation in total irradiance and temperature of more than 1000 W/m2 and 5\u201310 \u00b0C. The second cycle (period of approximately 1 month) is due to the position change of ISS orbital plane relative to the Sun. In this case, greater variations of temperature (up to 60 \u00b0C) with a maximal temperature of about 50 \u00b0C were reported [406]."}
{"_id": "Radiology$$$d0076acc-bd44-4bfd-a050-09d6d74924af", "text": "To study the biological impact of the space environment, modules outside the ISS are an ideal environment to expose biological samples to LEO, where the conditions strongly differ from the ones encountered on Earth. However, the poor availability of these facilities stimulated the creation of exposure chambers on Earth capable of reproducing this LEO environment. The Laboratory for Analysis by Nuclear Reactions (LARN, University of Namur, Belgium, https://\u200bwww.\u200bunamur.\u200bbe/\u200ben/\u200bsci/\u200bphysics/\u200bur-en/\u200blarn-en) has developed an exposure module to simulate the aforementioned conditions on the ground for extended periods of time (several months). To this end, biological samples are placed into a vacuum chamber and exposed to various constraints. A cooling system located underneath the sample tray and an electromagnetic source reproducing the solar spectrum are controlled by a monitoring system capable to simulate the slow and fast cycles described above. In addition, a variety of neutral density filters and cut-off waveband filters enables to create multiple irradiance conditions within the same experiment, in order to investigate what part of the UV-visible spectrum is the most deleterious."}
{"_id": "Radiology$$$d10fffa0-2550-4fe3-9b4b-f9afef3c6657", "text": "A similar facility also exists at DLR Cologne and has been recurrently used for pre-flight test programs and mission ground reference experiments for several astrobiological long-term space missions [405]."}
{"_id": "Radiology$$$94fda1fe-ec9d-418b-8b41-683c1de764f7", "text": "Q1.\nWhich types of radiation exist in space?\n\u00a0Q2.\nAre astronauts fully protected from radiation by spacecraft walls?\n\u00a0Q3.\nCan you describe the difference between the radiation environment on Earth (on ground) and the one at the surface of Mars?\n\u00a0Q4.\nWhat do we know now about specific health problems of astronauts?\n\u00a0Q5.\nWhat is the role of plants in Bioregenerative Life Support Systems (BLSS)?\n\u00a0Q6.\nWhat is the 3R Principle?\n\u00a0Q7.\nWhat kind of chronic effects on the CNS (central nervous system) were observed?\n\u00a0Q8.\nWhat is the difference between organoids and spheroids?\n\u00a0Q9.\nFrom which cells organoids can be cultured?\n\u00a0Q10.\nWhat is the main reason why bioprinting and other 3D cultures can be better cultured in Space?\n\u00a0Q11.\nWhat parameters should be considered if we would like to simulate conditions on Moon/Mars surface or in deep space (including stress unrelated to radiation)?\n\u00a0Q12.\nWhat is the interest to study the biological effects of low energy charged particles in the context of space radiation exposure?"}
{"_id": "Radiology$$$a28cbcdc-0c58-4594-8911-84971ab1daba", "text": "Can you describe the difference between the radiation environment on Earth (on ground) and the one at the surface of Mars?"}
{"_id": "Radiology$$$241f015f-cccb-4bc1-9c8e-742a1e51e195", "text": "What do we know now about specific health problems of astronauts?"}
{"_id": "Radiology$$$fa80aab6-f90d-48c2-99d4-12edf43ef2a1", "text": "What is the role of plants in Bioregenerative Life Support Systems (BLSS)?"}
{"_id": "Radiology$$$33a5c5bb-6595-4509-ab40-eac3ec0569c8", "text": "What kind of chronic effects on the CNS (central nervous system) were observed?"}
{"_id": "Radiology$$$c7a32bd2-69c5-45ef-ab09-7e3bbde6aa12", "text": "What is the main reason why bioprinting and other 3D cultures can be better cultured in Space?"}
{"_id": "Radiology$$$4fe1280c-b359-4260-ae0d-c4be5f8ba85a", "text": "What parameters should be considered if we would like to simulate conditions on Moon/Mars surface or in deep space (including stress unrelated to radiation)?"}
{"_id": "Radiology$$$96b8938b-a4ff-4ce0-bae1-e4aceb94ae89", "text": "What is the interest to study the biological effects of low energy charged particles in the context of space radiation exposure?"}
{"_id": "Radiology$$$0118d4da-192a-4fdc-892e-ceaecd6a3392", "text": "SQ1.\nGalactic Cosmic Rays, Solar Energetic Particles, Trapped radiation, and the solar wind\n\u00a0SQ2.\nNo, the high penetrating character of GCRs and the cascades of secondary particles generated by the passage of GRCs ions through the spacecraft walls create an intravehicular field which is of high concern for the health risk of astronauts\n\u00a0SQ3.\nOn Earth we are protected by both the atmosphere and the magnetic field: GCRs hitting the top of the atmosphere create particle showers but only a few of such secondaries (and very few of direct GCR ions) reach the ground. SEP are mostly shielded by the atmosphere and are of concern only for extreme events and mostly for high latitude/high-altitude flights for eventual biological risks, or on ground for infrastructures. On Mars, the very thin atmosphere offers very little shielding, and the exposure to GRCs, their secondary particles, and SEP is a concern.\n\u00a0SQ4.\nThough there are many concerns, the present evidence does not provide a conclusive answer. Astronauts as a cohort are not less healthy than US Air Force pilots, e.g., and much healthier than the general public (due to selection). The LNT-estimated cancer death risk for prolonged missions is considerable, but applicability of LNT for low dose rates is questionable.\n\u00a0SQ5.\nPlants in LSS remove carbon dioxide and provide oxygen, help water purification, can recycle wastes of the astronauts, and provide fresh food for the crew.\n\u00a0SQ6.\nReduction (first R) of animal numbers, Refining (second) the test methods to lower the harm to the animal to a minimum, and Replace (third) animal experiments with alternative methods, when possible\n\u00a0SQ7.\nReduction of dendrites, reduced neurogenesis and increased neuroinflammation, diminished hippocampal neuron excitability\n\u00a0SQ8.\nSpheroids are also a 3D cell cultures, but in comparison to organoids, they form simple clusters into sphere-like formation, but they cannot self-assemble or regenerate.\n\u00a0SQ9.\nPluripotent stem cells\n\u00a0SQ10.\nMicrogravity\n\u00a0SQ11.\nThe particular profile of radiation spectrum can vary according to the location of interest. The ISS environment benefits from some protection granted by the Earth magnetic field. This is not the case for deep space or Mars, where the full spectrum of galactic cosmic rays should be considered. Solar proton events should be included, can vary in magnitude and their extent also depends on the distance to the sun. Beside radiation, day and night cycle can impact temperature conditions, which lead to biological effects on some model organisms. Pressure value and the presence or not of atmosphere should also be considered.\n\u00a0SQ12.\nAlthough the vast majority of particles in the GCR spectrum have very high energy, low energy charged particles are still produced in shielding materials and arise from fragmentation of heavier energetic nuclei. These low-energy particles often traverse shielding and remain of concern."}
{"_id": "Radiology$$$5e15182a-ec7b-405e-b0e4-979eec3125e7", "text": "Galactic Cosmic Rays, Solar Energetic Particles, Trapped radiation, and the solar wind"}
{"_id": "Radiology$$$2a32b13d-9cd3-4ecb-be10-45c7dc20a2f7", "text": "No, the high penetrating character of GCRs and the cascades of secondary particles generated by the passage of GRCs ions through the spacecraft walls create an intravehicular field which is of high concern for the health risk of astronauts"}
{"_id": "Radiology$$$cd8548a5-a5f7-4a5b-8530-d2fa53f77ebb", "text": "On Earth we are protected by both the atmosphere and the magnetic field: GCRs hitting the top of the atmosphere create particle showers but only a few of such secondaries (and very few of direct GCR ions) reach the ground. SEP are mostly shielded by the atmosphere and are of concern only for extreme events and mostly for high latitude/high-altitude flights for eventual biological risks, or on ground for infrastructures. On Mars, the very thin atmosphere offers very little shielding, and the exposure to GRCs, their secondary particles, and SEP is a concern."}
{"_id": "Radiology$$$7491715b-fa68-4e14-ad07-9d1997e7918b", "text": "Though there are many concerns, the present evidence does not provide a conclusive answer. Astronauts as a cohort are not less healthy than US Air Force pilots, e.g., and much healthier than the general public (due to selection). The LNT-estimated cancer death risk for prolonged missions is considerable, but applicability of LNT for low dose rates is questionable."}
{"_id": "Radiology$$$1d92e47e-0bf0-4ce2-a307-04d87120071f", "text": "Plants in LSS remove carbon dioxide and provide oxygen, help water purification, can recycle wastes of the astronauts, and provide fresh food for the crew."}
{"_id": "Radiology$$$c4ecded3-5c60-4e94-be2f-371db05950e8", "text": "Reduction (first R) of animal numbers, Refining (second) the test methods to lower the harm to the animal to a minimum, and Replace (third) animal experiments with alternative methods, when possible"}
{"_id": "Radiology$$$a48fe0b6-bb77-4363-9fc9-81b086bf2a56", "text": "Reduction of dendrites, reduced neurogenesis and increased neuroinflammation, diminished hippocampal neuron excitability"}
{"_id": "Radiology$$$e07be078-7319-43dd-a3b3-ecc21411e28f", "text": "Spheroids are also a 3D cell cultures, but in comparison to organoids, they form simple clusters into sphere-like formation, but they cannot self-assemble or regenerate."}
{"_id": "Radiology$$$1d1a7b5a-18e3-4229-b896-e8db070e1cbd", "text": "The particular profile of radiation spectrum can vary according to the location of interest. The ISS environment benefits from some protection granted by the Earth magnetic field. This is not the case for deep space or Mars, where the full spectrum of galactic cosmic rays should be considered. Solar proton events should be included, can vary in magnitude and their extent also depends on the distance to the sun. Beside radiation, day and night cycle can impact temperature conditions, which lead to biological effects on some model organisms. Pressure value and the presence or not of atmosphere should also be considered."}
{"_id": "Radiology$$$29b75283-e9fc-4448-aff9-53f9fa498579", "text": "Although the vast majority of particles in the GCR spectrum have very high energy, low energy charged particles are still produced in shielding materials and arise from fragmentation of heavier energetic nuclei. These low-energy particles often traverse shielding and remain of concern."}
{"_id": "Radiology$$$1a9d19bb-7818-4929-bd93-f0c533d2c4e5", "text": "Radiation protection aims to reduce unnecessary radiation exposure with the intention to minimize the harmful effects of radiation on human health. With increasing use of radiation technologies and radioisotopes in medicine and industry, the risk of radiological and nuclear accidents escalates, affecting human health. Nuclear power plants and industrial accidents pose a serious threat to public health. Emergency preparedness in an event of nuclear terrorism and nuclear warfare requires the use of existing radiomodifiers and public health measures such as sheltering in place and the use of personal protective equipment (PPE). New approaches are urgently needed for protecting the persons working in a radiation field, first responders, and general population in the form of safe, effective, and easily accessible radioprotective agents."}
{"_id": "Radiology$$$1ff7026f-84d0-4cf8-8b1e-c3706afa95bf", "text": "Cellular exposure to IR induces genomic instability or mutations predisposing to carcinogenesis and/or cell death. Upon exposure, radiation induces DNA damage, lipid peroxidation, oxidation of thiol groups located in the plasma membrane and membranes of the cellular organelles, DNA strand breaks, and base alterations in cells, tissues, and organs. These changes may trigger a series of cellular responses, including activation of DNA damage repair pathways, signal transduction responses, gene transcription, and immune and proinflammatory responses. Triggering these pathways helps to recover damaged cells or eliminate the dysfunctional cells. However, they may also result in the development of tissue toxicities. The radiation research program of the National Cancer Institute (NCI) has proposed the following pharmacological classification of agents with IR response modification properties according to the timing of administration (Fig. 11.1):\n\nAn illustration of the biological properties of radioprotectors, radiomitigators, and radiosensitizers.\n\nFig. 11.1\nClassification of radiomodifiers with their biological properties"}
{"_id": "Radiology$$$85730628-2e4f-42af-a93a-2c3dd1d9fc80", "text": "An illustration of the biological properties of radioprotectors, radiomitigators, and radiosensitizers."}
{"_id": "Radiology$$$98fd8dfb-9928-4bf1-bedf-d250c6527fd5", "text": "A radioprotective agent/drug prevents harmful effects of radiation exposure while a radiosensitizing agent makes tumor cells more susceptible to radiation, in order to maximize the effect of radiotherapy while having less effect on normal tissues. Radiomitigators can attenuate IR damages even when they are delivered at the same time or after radiation exposition.\u00a0The use of radiation-effect modulators (radioprotectors, radiomitigators, and/or radiosensitizers) can mitigate side\u00a0effects and increase the efficacy of RT in cancer patients (Fig. 11.2).\n\nAn illustration of the use of radio modulators and their classification. Radio modulators increase the resistance of the body to irradiation by adaptively shifting the effectiveness of antioxidative protection. The three radio modulators are radioprotectors, radiomitigators, and radiosensitizers.\n\nFig. 11.2\nThe use of radioprotectors, radiomitigators, and radiosensitizers before, during, or after irradiation"}
{"_id": "Radiology$$$775eda17-d080-43f4-b7f9-341ba1a47503", "text": "An illustration of the use of radio modulators and their classification. Radio modulators increase the resistance of the body to irradiation by adaptively shifting the effectiveness of antioxidative protection. The three radio modulators are radioprotectors, radiomitigators, and radiosensitizers."}
{"_id": "Radiology$$$5e60058e-eef6-4875-b3ae-2ee74cfb1072", "text": "The extent of radiation damage to living cells and organisms depends on the type of radiation (alpha (\u03b1) particles, beta (\u03b2) particles, positrons, X-rays, gamma rays (\u03b3-rays), UV, etc.). Attempts to protect against the damaging effects of radiation were made as early as 1949. Efforts are actively being continued to search for radioprotectors suitable to be used in specific scenarios of radiation exposure. Possible applications of radioprotectors are outlined in Fig. 11.3.\n\nAn illustration of the applications of radioprotectors. The two major applications are protecting personnel and providing safeguards. The different ways for protecting personnel and providing safeguards are listed.\n\nFig. 11.3\nVarious applications of radioprotectors"}
{"_id": "Radiology$$$8f4d7247-5c9d-4468-980d-0c06b891c36e", "text": "An illustration of the applications of radioprotectors. The two major applications are protecting personnel and providing safeguards. The different ways for protecting personnel and providing safeguards are listed."}
{"_id": "Radiology$$$28e84084-2178-4835-ace0-76beb78c58f8", "text": "Over the last few decades, many natural and synthetic compounds have been investigated for their potential as radioprotectors. Natural or synthetic radioprotectors are able to (i) reduce direct or indirect radiation damage, (ii) repair direct and indirect damage once they have occurred, and (iii) facilitate the repair of damaged cells or recover depleted cell populations [1]."}
{"_id": "Radiology$$$e8a31a85-87eb-48d0-b9fc-a774a6c56e3b", "text": "It should be stressed that the majority of the compounds discussed below are currently not used in routine clinical practice and are still under preclinical or clinical evaluation."}
{"_id": "Radiology$$$62180409-a903-4a15-a20d-99a1228c3239", "text": "Early development of synthetic radioprotectors focused on thiol compounds (e.g., amifostine) and their derivatives, which have been used in cancer patients, to prevent complications of RT. In addition, they have been thought to be useful in accidental radiation exposure scenarios [2]. However, the practical applicability of the majority of these synthetic compounds remained limited owing to their limited administration routes, narrow administration window for efficacy, high toxicity at high doses or at recurrent usage, and cost factors as well. Besides thiol compounds, various compounds with different chemical structures are being investigated to develop an ideal radioprotector; there is still an urgent need to identify and develop novel, nontoxic, effective, and biocompatible compounds which can adequately protect normal tissues with no sparing of the tumor cells."}
{"_id": "Radiology$$$bb14ab20-6335-4490-b72f-d68f7ec0e1c9", "text": "An interest has been emerging in developing potential new candidate drugs from natural plants and phytochemicals. Plant products could bridge the gaps in the search for an ideal radioprotector due to its abundance, typically low toxicity, and relatively low cost."}
{"_id": "Radiology$$$07d24bd0-a73b-45fc-95ff-11691a2428d0", "text": "An ideal radioprotective agent should (a) be efficient in providing multifaceted protection, (b) prevent direct and indirect acute or chronic effects on normal tissue, (c) be easily and comfortably administered without toxicity, (d) cause no or minimal adverse effects on the test organism, (e) have a sufficiently long time window of effectiveness after administration and also have a sufficiently long shelf life, (f) have an acceptable stability profile (both of bulk active product and formulated compound), (g) be compatible with a wide range of other drugs, (h) not protect tumors from IR, and (i) be easily accessible and economical and should not require special handling and transportation temperatures (Box 11.1)."}
{"_id": "Radiology$$$a20e3cc8-de44-4fc3-8a06-6890b5d0e526", "text": "Radioprotectors (synthetic compounds, natural plant extracts, and phytochemical derivatives) are designed to lessen the effects of radiation-induced damage in healthy tissues.\n\nRadioprotective drugs are effective when administered prior to or during radiation exposure to reduce the radiation-induced injuries/toxicities.\n\nSafe, novel, nontoxic, and easily accessible radioprotective agents are needed to be developed for human health."}
{"_id": "Radiology$$$c5575299-2be9-4643-88c8-e1f45f1c3e6a", "text": "Radioprotectors (synthetic compounds, natural plant extracts, and phytochemical derivatives) are designed to lessen the effects of radiation-induced damage in healthy tissues."}
{"_id": "Radiology$$$ce48a160-c6eb-4819-b9eb-df6bf61b8bbe", "text": "Radioprotective drugs are effective when administered prior to or during radiation exposure to reduce the radiation-induced injuries/toxicities."}
{"_id": "Radiology$$$a51d6040-abaa-4d46-94f9-c8c2cd4795a2", "text": "Safe, novel, nontoxic, and easily accessible radioprotective agents are needed to be developed for human health."}
{"_id": "Radiology$$$a486dd2b-62e4-465c-9a56-3257f089a768", "text": "Radioprotectors are diverse and elicit their action by various mechanisms (Fig. 11.4) such as:\nScavenging free radicals (either by suppressing the formation or by detoxifying radiation-induced free radical species).\n\nInducing hypoxia in cells in order to avoid synthesis of reactive oxygen species (ROS).\n\nIncreasing levels of antioxidant defenses such as GSH (reduced\u00a0glutathione) and/or antioxidant enzymes (superoxide dismutase (SOD), glutathione peroxidase (GPx), thioreductase, catalase (CAT),\u00a0etc.).\n\nTriggering one or more cellular DNA damage repair pathways.\n\nImpeding cell division or inhibiting apoptotic cell death.\n\nModulating redox-sensitive genes.\n\nModulating growth factors and cytokine production.\n\nControlling inflammatory response.\n\nChelating or decorporating radionuclides.\n\nPromoting tissue regeneration (intestinal or hematopoietic and immunostimulant compounds), gene therapy, and/or stem cell therapy. In most cases, these molecules are administered after exposure to radiation, which is why they should be also considered radiomitigators.\n\n\nAn illustration of actions of radioprotectors. They are: scavenge free radicals, induce cellular radioprotectors and hypoxia in tissues, synchronize cells, modulate redox sensitive genes, growth factors, and cytokines, enhance D N A repair and stem cells, delay cell division, and inhibit apoptosis.\n\nFig. 11.4\nPotential mechanism of action of radioprotectors against cell damage due to IR"}
{"_id": "Radiology$$$5f941895-3a7f-4453-b747-1da8ece3086e", "text": "Scavenging free radicals (either by suppressing the formation or by detoxifying radiation-induced free radical species)."}
{"_id": "Radiology$$$eccef72a-7cd2-48aa-92f1-36a2b322d29a", "text": "Inducing hypoxia in cells in order to avoid synthesis of reactive oxygen species (ROS)."}
{"_id": "Radiology$$$22a9fa3b-8d7a-4186-bb23-4241a47c4d67", "text": "Increasing levels of antioxidant defenses such as GSH (reduced\u00a0glutathione) and/or antioxidant enzymes (superoxide dismutase (SOD), glutathione peroxidase (GPx), thioreductase, catalase (CAT),\u00a0etc.)."}
{"_id": "Radiology$$$7590b693-e307-4d33-8554-f76766dea1bc", "text": "Promoting tissue regeneration (intestinal or hematopoietic and immunostimulant compounds), gene therapy, and/or stem cell therapy. In most cases, these molecules are administered after exposure to radiation, which is why they should be also considered radiomitigators."}
{"_id": "Radiology$$$39c14c95-ae81-4127-9c1d-d7d8f572a90b", "text": "An illustration of actions of radioprotectors. They are: scavenge free radicals, induce cellular radioprotectors and hypoxia in tissues, synchronize cells, modulate redox sensitive genes, growth factors, and cytokines, enhance D N A repair and stem cells, delay cell division, and inhibit apoptosis."}
{"_id": "Radiology$$$f3e3577f-2315-4db2-885d-90ade72dc0e1", "text": "The most common mechanisms of radioprotection are the scavenging of free radicals, repair of DNA damages, inhibition of apoptosis\u00a0or inflammation, increase antioxidant defenses, and modulation of growth factors, cytokines, and redox genes. Thus, the management of radiation exposure may require a holistic multimechanistic approach to achieve optimal radiation protection during RT of cancer patients and in cases of nuclear accidents\u00a0or emergencies [3] (Box 11.2)."}
{"_id": "Radiology$$$0ec6cd00-b1bc-4bb5-80c3-07e386ff1b7e", "text": "Radioprotectors can be screened for their effective emerging strategies, such as modulation of growth factors, cytokines, redox genes, and tissue renewal.\n\nThe radioprotective agents are often antioxidants, which may suppress or scavenge the radiation-induced free radicals from the cell.\n\nThese compounds are cofactors or\u00a0can induce/stimulate antioxidants\u00a0enzymes (like SOD, GPx, and)\u00a0activity, which would likely lead to both prevent DNA damage and decrease in lipid peroxidation.\n\nThey may have the ability to enhance DNA repair, reduce the postradiation inflammatory response, or even delay cellular division allowing more time for cells to repair the DNA damage or undergo cell death."}
{"_id": "Radiology$$$d41cfef5-46ea-443e-a50f-469db751ed65", "text": "Radioprotectors can be screened for their effective emerging strategies, such as modulation of growth factors, cytokines, redox genes, and tissue renewal."}
{"_id": "Radiology$$$927404e7-05b3-453b-bad8-665585ef7b3c", "text": "The radioprotective agents are often antioxidants, which may suppress or scavenge the radiation-induced free radicals from the cell."}
{"_id": "Radiology$$$5dcc8904-a576-4ed8-bcc1-f6133702e8e8", "text": "These compounds are cofactors or\u00a0can induce/stimulate antioxidants\u00a0enzymes (like SOD, GPx, and)\u00a0activity, which would likely lead to both prevent DNA damage and decrease in lipid peroxidation."}
{"_id": "Radiology$$$9b48c00c-d6cc-4c32-ab8d-2c3695b345d6", "text": "They may have the ability to enhance DNA repair, reduce the postradiation inflammatory response, or even delay cellular division allowing more time for cells to repair the DNA damage or undergo cell death."}
{"_id": "Radiology$$$6e1a26ea-2bea-4965-bf81-23bdff949b72", "text": "Antioxidant Activity\n\nAn illustration of different targets of radioprotectors. The targets are free radical stress, oxidative stress, cellular response, cell cycle, D N A repair pathway, and cell death.\n\nFig. 11.5\nGeneral therapeutic approaches to develop novel radioprotective agents. IR, directly or indirectly, causes damage to macromolecules such as DNA, lipids, and proteins. As a result, oxidative stress is generated, which either triggers DNA damage repair or induces p53-mediated cell disorders, such as cell cycle arrest and cell apoptosis. When the damage exceeds the cell\u2019s ability to repair itself, the cell appears to follow the death program. The protective activities of potential radioprotectors should target such phases/mechanisms (described in blue dotted box) with the aim to shield the normal cells from harmful insults of irradiation. Inspired from/based on \u201cGeneral principles of developing novel radioprotective agents for nuclear emergency\u201d from Radiation Medicine and Protection (Volume 1, Issue 3, Pages 120\u2013126), by Du et al. 2020, Copyright Elsevier (2022)"}
{"_id": "Radiology$$$f77de5aa-1edc-4d42-bb17-4566acf5c7f7", "text": "An illustration of different targets of radioprotectors. The targets are free radical stress, oxidative stress, cellular response, cell cycle, D N A repair pathway, and cell death."}
{"_id": "Radiology$$$8ac4a5f7-7cb7-458b-a386-6c5ca8d13c40", "text": "Radioprotectors should prevent/suppress the formation of radiation-induced free radicals (most of them are produced during radiolysis with water), thereby inhibiting their reactions with biomolecules, reducing the incidence of DNA strand breaks, and preventing the occurrence of cellular malfunction (more detail in Chap. 2). Since free radicals are short-lived (approximately 10\u221210\u00a0s) and interact rapidly with biomolecules, it is necessary that radioprotectors are present in sufficient concentration in the cellular milieu, at the time of radiation exposure."}
{"_id": "Radiology$$$004af879-118c-4952-8d5f-750f67dd87a7", "text": "Molecules or compounds which increase the activity or expression of antioxidant enzymes are also considered radioprotectors. Many antioxidants have the potential to act as radioprotectors; however, not all antioxidants offer radioprotection, and this paradox may be explained by the relative activity of a compound when reacting with radiation-induced reactive species compared with those generated under H2O2 induced oxidative stress. Conventional antioxidants may not be able to scavenge this less reactive secondary species because either they do not accumulate in proximity to the secondary radicals or they may not have enough kinetic reactivity to scavenge them effectively. Thiols (e.g., amifostine), hydrophilic antioxidants (e.g., GSH), and newly developed cyclic nitroxides have adequate reactivity to effectively scavenge \u2022OH and secondary radicals as well."}
{"_id": "Radiology$$$cd4f44fe-4da6-4d2f-8e16-6e0829f8f25b", "text": "Molecules or events that play a role late in signaling and IR-induced apoptotic pathways may act as potential targets for post-irradiation interventions.\nATM/ATR is activated by DNA damage and DNA replication stress; however, they often work together to signal DNA damage and trigger apoptotic cell death by upregulating proapoptotic proteins such as apoptotic protease-activating factor-1 (Apaf-1), phorbol-12-myristate-13-acetate-induced protein 1 (Noxa), and Bcl2-associated X (Bax) after IR.\n\nPifithrin (PFT)-\u03bc (2-phenylethynesulfonamide) directly inhibits p53 binding to mitochondria as well as inactivates the antiapoptotic proteins Bcl-xL and Bcl-2 on the mitochondrial surface, thereby suppressing subsequent release of cytochrome c and apoptosis, whereas PFT-\u03bc reversibly inhibits transcriptionally mediated p53-dependent apoptosis.\n\nSignal transducer and activator of transcription 3 (STAT3) can be activated by various growth factors and protects against IR damage. The protection mediated by STAT3 is attributed to its genomic actions as a transcription factor (such as upregulating genes that are antioxidative, antiapoptotic, and proangiogenic, but suppressing anti-inflammatory and antifibrotic genes) and other nongenomic roles targeting mitochondrial function and autophagy.\n\nNuclear factor-erythroid 2-related factor 2 (Nrf2) is a well-characterized ubiquitous master transcription factor, whose activity is tightly controlled by cytoplasmic association along with its redox-sensitive transcriptional inhibitor Kelch-like ECH-associated protein 1 (Keap1). A well-known mechanism of activation of Nrf2 signaling protects cells against radiation-induced oxidative stress and also maintains cellular reduction-oxidation homeostasis. Upon oxidative stress, Nrf2 dissociates from Keap1 and translocates into the nucleus to activate a series of antioxidant response elements, such as GPx, SOD, CAT, and heme oxygenase-1 (HO-1), increasing total cellular antioxidant capacity (TAC), accompanied by suppressed expression of inflammatory-related genes, avoiding oxidative stress and excessive inflammatory response, which is particularly important in radioprotection.\n\nHeat-shock proteins (HSPs), molecular chaperones, are induced in cells during stress conditions. Importantly, HSPs are cytoprotective and can mediate cell and tissue repair after IR-induced deleterious effects. Higher cytosolic levels of HSPs have been shown to induce radioprotective effects by interfering with apoptotic pathways.\n\nPeroxisome proliferator-activated receptor-\u03b3 (PPAR-\u03b3), ligand-activated transcription factors, is a part of the nuclear hormone receptor family. It suppresses IR-induced survival signals and DNA damage responses and enhances IR-induced apoptosis signaling in human cells."}
{"_id": "Radiology$$$14d8f7fd-8cb7-40d7-b0bb-3764a8348ab4", "text": "ATM/ATR is activated by DNA damage and DNA replication stress; however, they often work together to signal DNA damage and trigger apoptotic cell death by upregulating proapoptotic proteins such as apoptotic protease-activating factor-1 (Apaf-1), phorbol-12-myristate-13-acetate-induced protein 1 (Noxa), and Bcl2-associated X (Bax) after IR."}
{"_id": "Radiology$$$3e962f7a-00a1-42fb-ad59-bf501450a97e", "text": "Pifithrin (PFT)-\u03bc (2-phenylethynesulfonamide) directly inhibits p53 binding to mitochondria as well as inactivates the antiapoptotic proteins Bcl-xL and Bcl-2 on the mitochondrial surface, thereby suppressing subsequent release of cytochrome c and apoptosis, whereas PFT-\u03bc reversibly inhibits transcriptionally mediated p53-dependent apoptosis."}
{"_id": "Radiology$$$a49f5286-d8d9-4c10-8101-49ea88de446c", "text": "Signal transducer and activator of transcription 3 (STAT3) can be activated by various growth factors and protects against IR damage. The protection mediated by STAT3 is attributed to its genomic actions as a transcription factor (such as upregulating genes that are antioxidative, antiapoptotic, and proangiogenic, but suppressing anti-inflammatory and antifibrotic genes) and other nongenomic roles targeting mitochondrial function and autophagy."}
{"_id": "Radiology$$$47dc511b-447e-429e-8c68-e6f062d6b3bb", "text": "Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a well-characterized ubiquitous master transcription factor, whose activity is tightly controlled by cytoplasmic association along with its redox-sensitive transcriptional inhibitor Kelch-like ECH-associated protein 1 (Keap1). A well-known mechanism of activation of Nrf2 signaling protects cells against radiation-induced oxidative stress and also maintains cellular reduction-oxidation homeostasis. Upon oxidative stress, Nrf2 dissociates from Keap1 and translocates into the nucleus to activate a series of antioxidant response elements, such as GPx, SOD, CAT, and heme oxygenase-1 (HO-1), increasing total cellular antioxidant capacity (TAC), accompanied by suppressed expression of inflammatory-related genes, avoiding oxidative stress and excessive inflammatory response, which is particularly important in radioprotection."}
{"_id": "Radiology$$$d18c6e1a-94ca-4903-9b3f-8217b9b8c0f8", "text": "Heat-shock proteins (HSPs), molecular chaperones, are induced in cells during stress conditions. Importantly, HSPs are cytoprotective and can mediate cell and tissue repair after IR-induced deleterious effects. Higher cytosolic levels of HSPs have been shown to induce radioprotective effects by interfering with apoptotic pathways."}
{"_id": "Radiology$$$f9606aea-697a-480a-affc-73e6eda9e672", "text": "Peroxisome proliferator-activated receptor-\u03b3 (PPAR-\u03b3), ligand-activated transcription factors, is a part of the nuclear hormone receptor family. It suppresses IR-induced survival signals and DNA damage responses and enhances IR-induced apoptosis signaling in human cells."}
{"_id": "Radiology$$$0733f960-ec1a-4cde-a726-058f2db6c7f4", "text": "In the search for an effective radioprotective agent, the Walter Reed Army Research Institute (USA) screened approximately 4500 compounds from the late 1950s. Cysteine was the first agent to confer radiation protection in mice after total body irradiation (TBI) in 1949. Later, various synthetic compounds with the aminothiol group were developed and proved to be highly effective\u00a0in preclinical models [4]. Among them, the most effective was WR-2721 or amifostine, a prodrug activated by alkaline phosphatase to an active sulfhydryl compound WR-1065, and at this moment, it is the only cytoprotective agent specifically approved by the FDA as a radioprotector (Fig. 11.6). The efficacy of amifostine is attributed to the free radical scavenging, along with DNA protection and repair, all of which are coupled with the initial induction of cellular hypoxia. At the cellular level, amifostine has significant effects on cell cycle progression and has antimutagenic and anticarcinogenic properties [5]. In fact, amifostine indirectly induces the expression of proteins involved in DNA repair and triggers antiapoptotic pathways [6] and expression of antioxidant enzymes. Some authors have also\u00a0proposed that it may enhance protective effects by increasing nuclear accumulation and inducing transcription factors related to p53 expression [7].\n\nAn illustration of the mechanism of Amifostine. It gives radioprotection to normal cells and no radioprotection to cancer cells. After hydrolysis, Amifostine becomes W R 1065 that binds to reactive nucleophiles, resulting in D N A protection in normal cells and D N A damage in cancer cells.\n\nFig. 11.6\nMechanisms of radioprotection by amifostine"}
{"_id": "Radiology$$$96500ba2-fe0e-4e91-b056-a33c5802f252", "text": "An illustration of the mechanism of Amifostine. It gives radioprotection to normal cells and no radioprotection to cancer cells. After hydrolysis, Amifostine becomes W R 1065 that binds to reactive nucleophiles, resulting in D N A protection in normal cells and D N A damage in cancer cells."}
{"_id": "Radiology$$$8ae70820-3c59-431b-bdb5-0a1b543fb96d", "text": "Moreover, WR-1065 accumulates more rapidly in normal tissues than in malignant cells, because the concentration of membrane-bound alkaline phosphatase tends to be higher on normal cells. Moreover, the lower vascular supply and the acidic environment of many tumors reduce the rate of dephosphorylation of WR-2721 and its uptake. It thus seems to be a really unique molecule that might potentiate radiotherapy (RT) efficacy in two opposite ways at the same time [8]. The US FDA has approved the use of amifostine in preventing/reducing xerostomia (dry mouth) in head and neck cancer patients undergoing RT [5]. It has also been assayed in clinical trials to reduce mucositis, dysphagia, dermatitis, and pneumonitis during radiotherapy of head and neck cancers [9]."}
{"_id": "Radiology$$$f2f2707c-490a-4b7a-9362-a42d5c1866e2", "text": "However, like other radioprotective aminothiols, the safety profile of amifostine has considerable limitations. Although the side effects such as nausea, vomiting, and hypotension are not life threatening, they can further aggravate the gastrointestinal syndrome. As it will be exposed latter,\u00a0amifostine has been assessed in combination with other FDA-approved drugs (growth factors, cytokines, vitamin E, metformin, etc) looking for additive or synergistic radioprotective effects to prevent Acute Radiation Syndrome (ARS). Nevertheless, in most of cases none of these novel\u00a0strategies completely counteracts amifostine\u2019s toxic side effects\u00a0at the doses needed to be efficacious as radioprotector [5]."}
{"_id": "Radiology$$$4388cbad-f8b6-4e66-bb1a-4d5e9721afd1", "text": "Dimethyl sulfoxide (DMSO)\u00a0has been shown to prevent the loss of proliferative lingual epithelial stem and progenitor cells upon irradiation by facilitating DNA DSB repair, thereby protecting against radiation-induced mucositis without tumor protection. Given its high efficacy and low toxicity, DMSO appears to be a potential treatment option to prevent radiation-induced oral mucositis [10]."}
{"_id": "Radiology$$$dd8c5c5d-b515-4fd3-b701-e8340a2e2b70", "text": "GSH (L-\u03b3-glutamyl-L-cysteinyl-glycine) plays a crucial role in the detoxification of reactive oxygen species, H2O2, lipid peroxyl radicals, peroxynitrites through enzymatic reactions, such as those catalyzed by GPxs, glutathione-S-transferases (GSTs), formaldehyde dehydrogenase, maleylacetoacetate isomerase, and glyoxalase I [11]. GSH not only protects DNA and other biomolecules against oxidative stress and radioinduced damages, it is also essential to activate DNA repairment mechanisms,\u00a0to activate proliferation and to avoid radio-induced cell death\u00a0[12].\u00a0In fact, the selective depletion of GSH in cancer cells has been shown to have potent radiosensitizing effects on tumor cells\u00a0[13]."}
{"_id": "Radiology$$$9b4b8cb7-53c1-42c9-a34c-ddddd943c816", "text": "N-acetylcysteine (NAC) has a powerful antioxidant capacity, preserves GSH cellular levels, and prevents oxidative stress-induced apoptosis. NAC treatment (300\u00a0mg/kg, subcutaneous), starting either 4\u00a0h prior to or 2\u00a0h after radiation exposure reduced early deaths in abdominally irradiated (X-rays, 20\u00a0Gy) C57BL/6 mice, attenuating gastrointestinal syndrome [14]. More recently, preclinical studies have evidenced that NAC can prevent/reduce cardiac, ovarian, renal, and testicular radiation-induced toxicity in rats. Nevertheless, NAC and GSH cannot be used as a radioprotector in cancer patients because they also enhance antioxidant defenses in cancer cells and may increase their metastatic potential [12]."}
{"_id": "Radiology$$$07b153d5-12e3-460f-ab59-368d458c4d9f", "text": "Treatment with erdosteine (a homocysteine derivative) before \u03b3-radiation exposure ameliorated nephrotoxicity and altered kidney function in rats. It is a potent scavenger of free radicals, increases GPx and CAT activity, and reduces oxidized glutathione levels displaying almost normal concentrations with respect to the irradiated group. Moreover, IL-1, IL-6, and TNF-\u03b1 circulating levels were also significantly improved thus erdosteine provide substantial protection against radiation-induced inflammatory damage as evidenced in the biochemical and histopathological samples [15]."}
{"_id": "Radiology$$$15c1391d-94ce-4178-9cdb-b558de136d93", "text": "Phosphorothioates and other aminothiols are usually administered shortly before irradiation. They have been hypothesized to act as radioprotectors by one or a combination of the following effects: scavenging radiation-induced free radicals before their reaction with biomolecules; inducing hypoxia; scavenging metals; repairing DNA damage through hydrogen donation to carbon-centered radicals; and stabilizing genome. Moreover, high doses of phosphorothioates administered to mice before radiation have demonstrated anticarcinogenic effects [4]. However, as it happens with other more powerful thiolic radioprotectors (such as amifotine), its use is limited due to undesirable side effects."}
{"_id": "Radiology$$$ed2e7ec5-592a-4b26-96a8-a5ef3ccbce6d", "text": "NRs, like\u00a0Tempol, JP4\u2013039, XJB-5-131, TK649.030, or JRS527.084, are stable free radicals containing a nitroxyl group (-NO.) with an unpaired electron. The action of nitroxides to metabolize ROS is ascribed primarily to cyclic one- or two-electron transfer among three oxidation states: the oxoammonium cation, the nitroxide, and the hydroxylamine. Nitroxides undergo a very rapid, one-electron reaction to the corresponding hydroxylamine, which has antioxidant activity. In addition to their ability to neutralize free radicals, NR can easily diffuse through the cell membranes (and have SOD-like activity) (Fig. 11.7), prevent Fenton and Haber-Weiss reactions by oxidation of transition metal ions to a higher oxidation state, confer catalase-like activity on heme proteins, and inhibit lipid peroxidation. NRs are able to mitigate TBI-induced hematopoietic syndrome, when are\u00a0administered before or as late as 72\u00a0h after radiation exposition [16].\n\nAn illustration of oxidative and reductive reversible chemical processes. Hydroxylamines form oxoammonium with the loss of two electrons. Hydroxylamines and oxoammonium form nitroxide radicals, an antioxidant, with the loss of one electron.\n\nFig. 11.7\nRadioprotective properties of cyclic nitroxides include scavenger free radical capacity and SOD-like activity. Adapted from \u201cNitroxides as Antioxidants and Anticancer Drugs,\u201d by Lewandowski M. and Gwozdzinski K. 2017, Licensed under CC BY 4.\u200b0"}
{"_id": "Radiology$$$149b214d-eb1f-47bc-93aa-aa3581297977", "text": "An illustration of oxidative and reductive reversible chemical processes. Hydroxylamines form oxoammonium with the loss of two electrons. Hydroxylamines and oxoammonium form nitroxide radicals, an antioxidant, with the loss of one electron."}
{"_id": "Radiology$$$8489ecf3-9c05-413a-a68d-94c5e5bdc486", "text": "Gramicidin S-derived nitroxide (JP4\u2013039) is an effective TBI mitigator when\u00a0is delivered intravenously up to 72\u00a0h after exposure. JP4\u2013039 treatment ameliorated head and neck radiation-induced mucositis and distant marrow suppression in mice [17]. In a comparative study with other four nitroxides, JP4-039\u00a0demonstrated the best median survival after radiation exposition [18]. The potential of this type of molecules as radioprotectors and/or mitigators has raised the interest of researchers, and nitroxidic structures has evidenced radioprotective activity. That is the case of nitronyl- nitroxide radical spin-labeled resveratrol [19]."}
{"_id": "Radiology$$$7d253e1f-b9c5-4529-b567-8212b0347bf2", "text": "Primary experiments performed in the 1960s reported that antibiotic treatment and a single transfusion of allogeneic platelets significantly reduced mortality among monkeys exposed to TBI X-irradiation. Oral administration of streptomycin, kanamycin, neomycin, or gentamicin with drinking water (4\u00a0mg/mL) for 2\u00a0weeks before supralethal TBI (28.4\u00a0Gy) prolonged mean survival in mice (8.2\u20138.9\u00a0days vs. 6.9 for controls) [20]. The efficacy of antibiotics and other antimicrobials (antifungal and antiviral agents) is best explained as a countermeasure for radiation-induced neutropenia and immunosuppression."}
{"_id": "Radiology$$$6863db54-ca1a-4012-8710-a16883d784a4", "text": "Tetracycline and ciprofloxacin protected human lymphoblastoid cells, reducing radiation-induced DNA double-strand breaks\u00a0(DSB) by 33% and 21%, respectively. Their radioprotective efficacy was attributed to the activation of the Tip60 histone acetyltransferase and altered chromatin structure [21]. Tetracycline hydrochloride is a free radical scavenger, protects DNA, and increases survival of C57BL/6 mice by 20% upon a lethal radiation dose of 9 Gy [22]."}
{"_id": "Radiology$$$154e011f-27fb-476c-afe2-4cfd850ed4d1", "text": "Mucositis is the most common side effect of RT for head and neck cancers. Preventive measures used in clinical medicine include good oral hygiene, dental and periodontal treatment, avoidance of tobacco products and alcohol, and frequent oral rinsing with a bland mouthwash such as povidone-iodine. Nonabsorbable antibiotic lozenges and/or antifungal topical agents (i.e., bicarbonates and amphotericin B) are also recommended [23]."}
{"_id": "Radiology$$$04fa8bca-5d8f-476e-865c-8b73313190e7", "text": "Minocycline prevented radiation-induced apoptosis and promoted radiation-induced autophagy in primary neurons in vitro. Minocycline also increases the counts of splenic macrophages, granulocytes, natural killer cells, and lymphocytes, and accelerates neutrophil recovery in C57BL/6 mice exposed to 1-3 Gy 60Co \u03b3-rays. The mechanisms involved in this radioprotective effect were the suppression of cytokines that could prevent hematopoiesis (e.g. macrophage inflammatory protein-1\u03b1, TNF-\u03b1 and INF-\u03b3) and the increased production of IL-1\u03b1 and \u03b2, granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF)\u00a0[24]."}
{"_id": "Radiology$$$33515591-b18b-4406-8eed-a3d7be4f0ebf", "text": "Furazolidone (FZD) is an antimicrobial agent effective on both Gram+ and Gram\u2212 bacteria by interfering with bacterial oxidoreductase activity. In vitro, FZD treatment reduced unstable chromosomal aberrations (CAs) (such as acentric and dicentric chromosomes (DC)), chromosome breaks, and radiosensitivity of intestinal epithelial cells. Ma et al. [25] showed that FZD treatment significantly improved the survival of lethal dose-irradiated mice, decreased the number of micronuclei (MN), increased the number of leukocytes and immune organ indices, and reversed the apoptosis and autophagy in the small intestine, thus restoring intestinal integrity. Their experiments showed that irradiation resulted in villous shortening and crypt dilation accompanied by epithelial atrophy or slough, and even marked edema and inflammatory cell infiltration, and how FZD significantly induced damage recovery. FZD is a clinically used antibiotic with few side effects and has been proposed as an efficacious medical countermeasure (MCM). However, detailed radiation protection activity and clinical applications need to be further studied, because radioprotective efficacy of antibiotics has not yet been tested in clinical trials."}
{"_id": "Radiology$$$4e2fb97d-91b0-47fb-b56f-2508563f2747", "text": "Considerable information from in vivo, ex vivo, and/or in vitro studies suggests that crude extracts, fractionated extracts, isolated phytoconstituents, and plant polysaccharides from various plants such as Alstonia scholaris, Centella asiatica, Hippophae rhamnoides, Ginkgo biloba, Ocimum sanctum, Panax ginseng, Podophyllum hexandrum, Amaranthus paniculatus, Emblica officinalis, Phyllanthus amarus, Piper longum, Tinospora cordifolia, Mentha arvensis, Mentha piperita, Syzygium cumini, Zingiber officinale, Ageratum conyzoides, Aegle marmelos, and Aphanamixis polystachya protect against radiation-induced lethality, lipid peroxidation, and DNA damage [26]. From these extracts, polyphenolic and nonpolyphenolic active principles and a range of secondary metabolites (e.g., carotenoids, alkaloids, sulfur compounds), already known for their anticancer properties, have also demonstrated radioprotective potential. Although many have been tested for brevity, this chapter focuses on those with the most promising results in vivo."}
{"_id": "Radiology$$$d90737fd-6fbd-456a-b64d-d40d749d6a35", "text": "Over the last decades, plant-derived polyphenols have been screened for their potential ability to confer radioprotection. The free radical scavenger potential and antioxidant activity of polyphenols depends, in part, on their ability to delocalize electron distribution, resulting in a more stable phenoxy group. Moreover, intercalation in DNA double helices induces stabilization and condensation of DNA structures making them less susceptible to free radicals\u2019 attack, reducing genotoxic damage induced by IR [27]. They are capable of trapping and neutralizing lipoperoxide radicals and can chelate metal ions (i.e., iron and copper), which play an important role in the initiation of oxidative stress reactions [28, 29]. Polyphenols\u00a0radioprotective efficacy is mainly attributed to its\u00a0(Fig. 11.8) antioxidant and antiinflammatory properties, to their capacity to detoxify free radicals, eliciting DNA repair pathways, stimulating the recovery of hematopoietic\u00a0and immune functions\u00a0[28, 29].\n\nAn illustration of the biological properties of polyphenols. They are neuroprotection, cardiovascular protection, anti-inflammatory, anti-diabetic, anti-microbial, anti-viral, anti-aging, anti-proliferative, anti-tumor, and cytoprotective against radiation with anti-oxidant properties.\n\nFig. 11.8\nRadioprotective and biological properties of polyphenols"}
{"_id": "Radiology$$$cf65b404-bc7c-4437-bf70-2730e7a76a6d", "text": "An illustration of the biological properties of polyphenols. They are neuroprotection, cardiovascular protection, anti-inflammatory, anti-diabetic, anti-microbial, anti-viral, anti-aging, anti-proliferative, anti-tumor, and cytoprotective against radiation with anti-oxidant properties."}
{"_id": "Radiology$$$2f71c252-e381-4c69-a610-cc7da058b4b3", "text": "In addition to the biochemical scavenger theory, there is also evidence of another potential mechanism by which polyphenols activate Nrf2, exhibiting cellular protection against excessive ROS production, oxidative stress, and inflammation as well. Since the chemical features of these natural organic compounds are analogous to phenolic substances, their antioxidant and antiradical/scavenging radical (such as H2O2, 2,2-diphenyl-1-picrylhydrazyl) properties may be correlated positively with the number of hydroxyl groups bonded to the aromatic ring. They can exert their protection against environmental stimuli with the aid of remarkable antioxidant power by balancing the organic oxidoreductase enzyme system, regulating antioxidant-responsive signaling pathways, and restoring mitochondrial function."}
{"_id": "Radiology$$$74c4fbb5-b4c8-46d8-9d2d-898a866d3774", "text": "Although topically administered polyphenols may provide strong antioxidant protection, various challenges still exist and are onerous as well: (1) improving the bioavailability of polyphenols more effectively in order to promote their effectiveness is challenging; (2) if the polyphenols are extracted as the medicine or as health supplements, attention should be paid to the activity loss and degradation of polyphenols during the extraction process; (3) the effects cannot be generalized for all kinds of polyphenols, because each polyphenol has its own unique features; and (4) polyphenols have limited water solubility, and so it is important for polyphenols to be involved in rapid metabolism and also prove its chemical stability and solubility under in vivo conditions. To overcome this limitation, Obrador et al. [30] suggested a few feasible options: structural modifications of natural molecules (e.g., in the form of salts) to increase their hydro-solubility for intravenous administration or oral formulations to increase their bioavailability (e.g., cocrystals, nanoparticles, nanozymes). The promising phytochemical, pharmacodynamic, and toxicological research into the properties of polyphenols may serve as potential candidates for radioprotection in the near future."}
{"_id": "Radiology$$$b00a86b1-a5ff-4d09-8b95-c5253fd6ef88", "text": "Apigenin exhibits anticancer properties associated with its prooxidant activity, inhibiting tumor growth and inducing cell cycle arrest and apoptosis. Apigenin pretreatment displayed efficacy for radioprotection in TBI\u00a0Swiss albino mice by reducing cytogenetic alterations and biochemical and hematological changes [31]. Further, when apigenin was administered intraperitoneally at a dose level equal to 15\u00a0mg/kg body, it was found to ameliorate radiation-induced gastrointestinal (GI) damages and restore intestinal crypt-villus architecture [32]. These attributes could be due to its ability to activate the endogenous antioxidants, suppress lipid peroxidation, and modulate inflammatory (NF-\u03baB) and apoptotic signaling mediator/marker (p53, p21, Bax, caspase-3, caspase-9) expression. The in vivo efficacy of apigenin was also evidenced when\u00a0it was intraperitoneally administered to mice 3\u00a0h after receiving \u03b3-rays [33]. A significant reductions in the level of 8-hydroxy-2-deoxyguanosine (8-OH-dG), suppressed expression of NF-\u03baB and NF-\u03baB-regulated proinflammatory cytokines were observed, thus showing the radioprotective potential of apigenin."}
{"_id": "Radiology$$$53b27d3a-f640-45d1-9c16-614199410435", "text": "Curcumin, a yellow pigment of turmeric, is naturally found in the rhizome of Curcuma longa and other Curcuma spp. It is an active immunomodulatory agent which has many scientifically proven health benefits, such as the potential to improve symptoms of anxiety, depression, arthritis, and heart health and prevent Alzheimer\u2019s, cancer, and oxidative and inflammatory conditions. Administration of curcumin in patients undergoing RT has demonstrated a dual action: radioprotection to normal cells through its ability to reduce oxidative stress, scavenge free radicals, inhibit transcription of genes related to oxidative stress, and suppress inflammatory response, as well as radiosensitization in tumor cells [34]. Curcumin, administered before or after a single 50 Gy radiation dose, showed protective effect on radiation-induced cutaneous damage in mice by significantly decreasing mRNA expression of early-responding cytokines (IL-1, IL-6, IL-18, TNF-\u03b1, and lymphotoxin-beta) and fibrogenic cytokines [35]. Oral administration of curcumin in mouse before irradiation resulted in a significant rise in activities of GPx and SOD enzymes while declining lipid peroxidation significantly, which indicates increased antioxidant status in mouse exposed to different doses of fractionated \u03b3-radiation\u00a0[36]. These protective qualities of curcumin may be due to free radical scavenging and upregulation of Nrf2 expression."}
{"_id": "Radiology$$$ad65e8b9-8d35-4379-8fa4-52559c15e568", "text": "Ellagic acid (EA), a strong natural antioxidant, has a major protecting role against different diseases associated with oxidative stress and inflammation. It also exerts antiangiogenesis effects via down regulation of vascular endothelial growth factor-2 (VEGF-2) signaling pathways in cancer. The amount and duration of EA used play a significant role in suppressing in vivo and in vitro oxidative stresses. In vitro studies [37] displayed high DPPH radical scavenging and lipid peroxidation inhibition activities of EA. It triggered the actions of antioxidant enzymes such as SOD, CAT, and GPx in V79\u20134 cells; reduced cell proliferation; and induced apoptosis in human osteogenic sarcoma cells as evidenced by chromosomal DNA degradation and apoptotic body appearance. When the human breast cancer cells (MCF-7) were treated with EA (10\u03bcM) and exposed with \u03b3-radiation, the rate of apoptotic cell death in sub-G1 phase of cell cycle was high due to decreased mitochondrial membrane potential, upregulated proapoptotic Bax, and downregulated Bcl2, suggesting EA\u2019s role in tumor toxicity to improve cancer radiotherapy [38]."}
{"_id": "Radiology$$$36d42d93-1ec3-482a-8023-771104dfd57f", "text": "Epicatechin (EC) is a common flavanol found in tea, cocoa, dark chocolates, and red wine. It has the ability to cross the blood-brain barrier and activate brain-derived neurotrophic factor pathways, suggesting its neuroprotective effects. In addition to general antioxidant activities, it aids with the modulation of metabolism of nitric oxide (NO)\u00a0and other\u00a0reactive nitrogen species\u00a0(RNS). To evaluate the radioprotective effects of EC, Swiss albino mice were administered with EC for three consecutive days before exposing them to 5 Gy 60Co \u03b3-irradiation [39]. EC pretreatment ameliorated \u03b3-radiation-mediated alterations in mice, protected the liver and testis from radiation-induced oxidative stress, prevented systemic and cellular stress, and developed inflammation. It may possibly be due to the influence on the endogenous antioxidant defenses system after TBI in mice [40]. Another study [41] intended to investigate the effectiveness of EC in scavenging mitochondrial ROS and mitigating mitochondrial damage as radiation countermeasure agents by using human and mouse cells. It was observed that preradiation and postradiation treatments with EC mitigated ROS-mediated mitochondrial damage and IR-induced oxidative stress responses in mice. Also, oral administration of EC significantly enhanced the recovery of mouse hematopoietic cells from radiation injury in vivo, suggesting EC as a potentially viable countermeasure agent which is immediately effective against accidental IR exposure."}
{"_id": "Radiology$$$f70cd594-e4b4-4677-b375-16a84a8d1a3b", "text": "Epigallocatechin-3-gallate (EGCG) is a natural polyphenolic antioxidant found in a number of plants, predominantly in green tea and black tea and also in small amounts in fruits and nuts. It gets a lot of attention for its potential positive impact on health. It aids weight loss, reduces inflammation, and helps prevent certain chronic conditions, including heart disease, diabetes, and cancers. Pretreatment with EGCG significantly enhanced the viability of human skin cells which were irradiated with X-rays and decreased radiation-induced apoptosis [42]. It was found that EGCG suppressed IR-induced damage to mitochondria via upregulation of SOD2 and induced expression of cytoprotective molecule HO-1 in a dose-dependent manner via transcriptional activation. The therapeutic effects and mechanism of EGCG on radiation-induced intestinal injury (RIII) have not yet been determined; however, Xie et al. recently [43] investigated it both in vitro and in vivo and revealed that treatment with EGCG not only prolonged the survival time of lethally irradiated mice, but also mitigated RIII. Besides, it significantly augmented proliferation and survival of intestinal stem cells and their progeny cells in irradiated mice. Their findings demonstrated that EGCG protected against RIII by reducing the level of IR-induced ROS and DNA damage, inhibiting apoptosis and ferroptosis through activating transcription factor Nrf2-mediated signaling pathway and its downstream targets comprising antioxidant proteins Slc7A11, HO-1, and GPx4, suggesting that EGCG could be a promising medical countermeasure for the alleviation of RIII."}
{"_id": "Radiology$$$c5a65699-ea54-4697-b507-976a3c69cf8e", "text": "Genistein (GEN), an isoflavonoid compound, is commonly found in soybeans and its products. Mechanistic insights reveal its potential beneficial effects on human diseases such as cancer, by inducing apoptosis and cell cycle arrest. GEN has antiangiogenic, antimetastatic, and anti-inflammatory effects. Besides, various studies of GEN have revealed its radioprotective properties by protecting against radiation-induced DNA damage, scavenging free radicals, and altering cell cycle effects. Davis et al. [44] revealed GEN-induced radioprotection against hematopoietic- acute radiation syndrome (H-ARS) by altering the cell cycle of hematopoietic stem and progenitor cells in a murine model. The extracted GEN displayed protection against IR-induced GI injury and bone marrow toxicity by upregulating the Rassf1a and Ercc1 genes to effectively attenuate DNA damage in a TBI mouse model [45]. Moreover, Song et al. [46] showed that low concentration of GEN (1.5\u03bcM) lessened radiation-induced injuries by way of inhibiting apoptosis, alleviating chromosomal and DNA damage, downregulating GRP78, and upregulating HERP, HUS1, and hHR23A. In contrast, high concentration of GEN (20\u03bcM) demonstrated radiosensitizing characteristics in cancer cells. The role of genistein as a radiosensitizer will be further discussed in Sect. 11.4."}
{"_id": "Radiology$$$67efdc55-61c8-41c3-90c3-8590035f1c51", "text": "Naringin, a predominant flavone glycoside, is present in citrus fruits. Manna et al. [47] demonstrated that pretreatment with naringin significantly prevented \u03b3-radiation (6Gy)-induced intracellular ROS-mediated oxidative DNA damage; inhibited radiation-induced G1/S-phase cell cycle arrest by modulating p53-dependent p21/WAF1, cyclin E, and cyclin dependent kinase 2 (CDK2) activation; and reversed the inflammation through downregulating nuclear factor kappa B (NF-kB) signaling pathways and balancing the expression of C-reactive protein, monocyte chemoattractant protein-1 (MCP-1), and iNOS2 at sites of inflammation in murine splenocytes. Besides, naringin pretreatment could effectively deter UVB-mediated DNA damage, alter apoptotic marker expression (Bax, BCl-2, caspase-9, and caspase-3), and potentially modulate NER gene (XPC, TFIIH, XPE, ERCC1, and GAPDH) expression, thereby augmenting DNA repair [48]."}
{"_id": "Radiology$$$f5925890-8577-4995-96dc-2f8319e478a5", "text": "Naringenin is present in peppermint and citrus fruits such as oranges, grapefruit, and tangerines. It is endowed with biological effects on human health, which includes a great ability to modulate signaling pathways; efficient impairing of plasma lipid and lipoprotein accumulation; and antiatherogenic and anti-inflammatory effects. To evaluate radioprotective effects of naringenin in vivo, Swiss albino mice were orally administered 50\u00a0mg/kg body weight of naringenin prior to radiation exposure [49], and it protected mice against radiation-induced DNA, chromosomal, and membrane damage. Naringenin pretreatment increased antioxidant status and survival chances, inhibited NF-kB pathway, and downregulated radiation-induced apoptotic proteins (p53, Bax, and Bcl-2) in normal cells resulting in radioprotection at the cellular, tissue, and organism levels."}
{"_id": "Radiology$$$3a3859d4-78c9-417c-91ab-c59e216c4a96", "text": "Resveratrol (RV), a natural polyphenol, is produced in several plants in response to stress, injury, and UV radiation. It is present in fruits such as grapes, strawberries, and red wine. It is known for its analgesic, antiviral, cardioprotective, neuroprotective, and antiaging actions. Different doses of RV were administered intraperitoneally to mice prior to total-body \u03b3-irradiation (2\u00a0Gy), and it was observed that RV significantly reduced lymphocyte damage in mice caused by \u03b3-radiation due to its ability to scavenge free radicals, restore the levels of intracellular antioxidants (GPx, SOD, CAT activity), and cause cell cycle arrest [50]. RV is also known to have a significant effect in stabilizing p53 and altering proapoptotic and antiapoptotic protein concentration [51]. Zhang et al. [52] treated with RV\u00a0IR-exposed\u00a0C57BL/6N mice.\u00a0RV reduced radioinduced-intestinal injury (upregulating Sirt1 and acetylating p53 expression),\u00a0improved intestinal morphology, decreased apoptosis of crypt cells, maintained cell regeneration, and ameliorated SOD2 expression, evidencing its radioprotective potential. The role of RV together with pterostilbene as a radiosensitizer will be further discussed in Sect. 11.4."}
{"_id": "Radiology$$$7b674a52-4f43-4a09-a479-e74b467286a1", "text": "Pterostilbene (PT), is another stilbenoid compound, structurally similar to RV, present in blueberries, grapes, and other similar fruits. It is an active phytonutrient with many biomedical applications in cancer treatment, insulin sensitivity, cardiovascular diseases, aging, and cognition. Moreover, it has a greater bioavailability, efficacy and lower toxicity than RV\u00a0[53]. Sirerol et al. [54] evidenced that pterostilbene reduced chronic UVB irradiation-induced skin damage and carcinogenesis in hairless mice through maintaining antioxidant defenses, including GSH, CAT, SOD, and GPx.\u00a0Recently, a combination of natural polyphenols (PT and silibinin) with a NAD+ precursor and a TLR2/6 ligand was shown to protect mice against lethal \u03b3-radiation, increasing long term survival up to 90% of the treated mice [55]."}
{"_id": "Radiology$$$7518b8d2-61ec-4741-8896-b05c72d674b8", "text": "Caffeic acid/caffeic acid phenethyl ester (CAPE) is found in coffee, tea, chocolate, and colas. It has numerous pharmacological and physiological effects, including cardiovascular, respiratory, renal, and smooth muscle effects, as well as effects on mood, memory, alertness, and physical and cognitive performance. It is essentially regarded as a radiosensitizer by virtue of its inhibition of DNA repair after irradiation. The radioprotective properties of CAPE have also been shown in the bone marrow chromosomes of mice exposed to TBI (1.5 Gy 60Co \u03b3-rays), regardless of its time of administration [56]. Caffeic acid, a known dietary antioxidant, could be used as a supplemental drug which has a dual effect: ameliorating hematopoietic stem cell (HSC) senescence-accompanied long-term BM injury in single (sublethal dose of 5\u00a0Gy) TBI and stimulating apoptotic cell death of colon cancer cells in mice [57]. Khayyo et al. [58] intraperitoneally administered CAPE prior to total-head \u03b3-irradiation and observed that the oxidant stress parameters (total oxidant status, oxidative stress index, and lipid hydroperoxide) were significantly reduced, whereas antioxidant parameters (activity of paraoxonase, arylesterase, total GSH levels) were increased in the rat brain tissue, signifying the protective role of CAPE as an important antioxidant against ROS accumulation induced by total-head irradiation. The role of CAPE as a radiosensitizer will be further discussed in Sect. 11.4.1.7."}
{"_id": "Radiology$$$19b441fd-a6a6-46d9-837f-4f290d2d79cd", "text": "Sesamol is found in sesame seeds and oil. It has many biological activities and health-promoting benefits such as inducing growth arrest and apoptosis in cancer and cardiovascular cells and enhancing vascular fibrinolytic capacity, antioxidant activity, chemoprevention, antimutagenic, and antihepatotoxic activities. Naturally occurring or synthetic substances of sesamol counteract the damaging effects of oxidation by inhibiting or retarding oxidation reactions. Also, it has the potential to scavenge free radicals and therefore reduces the radiation-induced cytogenetic damage in cells. Kumar et al. [59] investigated its radioprotective potential against radiation-induced genotoxicity in hematopoietic bone marrow of whole-body \ud835\udefe-irradiated (2Gy) mice. Preadministration of 20\u00a0mg/kg body weight sesamol reduced the frequency of radiation-induced MN, CAs, and comets (% damaged DNA streak in tail), suggesting its major role in direct scavenging of free radicals to protect bone marrow, spleen, and lymphocytes from radiation-induced cytogenetic damages and genotoxicity. Besides, intraperitoneal pretreatment of sesamol offered protection to hematopoietic and GI systems against \u03b3-radiation-induced injury in C57BL/6 male mice by inhibiting lipid peroxidation; translocating gut bacteria to spleen, liver, and kidney; enhancing regeneration of crypt cells in GI; reducing the expression of p53 and Bax apoptotic proteins in the bone marrow, spleen, and GI; and alleviating the total antioxidant capacity in spleen and GI tissue [60]. Recently, Majdaeen et al. [61] concluded that regular oral consumption of sesamol extract is more effective than consuming it once before irradiation."}
{"_id": "Radiology$$$c71966d4-58d8-4e3d-84ce-dd27de843e2a", "text": "3,3\u2032-Diindolylmethane (DIM), a small-molecule compound and a major bioactive metabolite, is formed by acid hydrolysis of indole-3-carbinol (one of the best characterized components in Cruciferae). It can inhibit invasion, angiogenesis, and proliferation and induce apoptosis in tumor cells by modulating signaling pathways involving AKT, NF-kB, and FOXO3 [62]. Chen et al. [63] investigated the radioprotective effects of DIM in normal tissues using a mouse model approach. It was indicated that treatment with DIM increased the expression of some stress-responsive genes without causing DNA damage, delayed radiation-induced cell cycle arrest, and apoptosis. Fan et al. [64] reported that administration of DIM in a multidose schedule protected rodents against lethal doses of TBI up to 13 Gy. Transcriptomic profiling showed that DIM\u2019s mechanism of radioprotection involved regulation of responses to DNA damage and oxidative stress by inducing ataxia-telangiectasia mutated (ATM)-driven DDR-like response, enhancing radiation-induced ATM signaling and NF-\u03baB activation, suggesting its potential role as a MCM in protecting or mitigating adverse effects of RT."}
{"_id": "Radiology$$$d3388cce-e545-4c77-b302-f2aaa5f0f558", "text": "With the understanding that free radicals perpetuate a significant amount of the damage caused by IR, vitamins with antioxidant potential (A, C, and E and its derivatives) have been assayed as radioprotectors (Fig. 11.9). Vitamin A and \u03b2-carotenes (lutein, lycopene, phytofluene, phytoene, and others) reduced mortality and morbidity in mice exposed to partial or TBI. Dietary vitamin A offered protection in mice subjected to localized radiation exposure focused on the intestine (13\u00a0Gy, TBI) and the esophagus (29\u00a0Gy) [30]. A single dose of vitamin A injected intraperitoneally 2\u00a0h before 2 Gy of \u03b3-radiation exposition, significantly reduced the number of MN in the bone marrow and the genetic damages, due to its capacity to trap free radicals [65]. Carotenoids such as crocin and crocetin (isolated from the dietary herb saffron) have antioxidant, anti-inflammatory, and antiapoptotic effects. In mice bearing pancreatic tumors, crocin significantly reduced tumor burden, radiation-induced toxicity, and hepatic damage and preserved liver morphology [66] while crocetin also reduced radiation injury in intestinal epithelial cells [67].\n\nAn illustration of the vitamins that provide radioprotection with their effects. The vitamins are beta carotene, or provitamin A, ascorbic acid, or vitamin C, retinol or vitamin A, vitamin E, alpha lipoic acid, and vitamin D.\n\nFig. 11.9\nRadioprotective effects of vitamins"}
{"_id": "Radiology$$$43748c68-88c7-418b-bf3c-e6590ced694f", "text": "An illustration of the vitamins that provide radioprotection with their effects. The vitamins are beta carotene, or provitamin A, ascorbic acid, or vitamin C, retinol or vitamin A, vitamin E, alpha lipoic acid, and vitamin D."}
{"_id": "Radiology$$$7cc70fdc-c1bc-47ec-ad12-d9a887cb3583", "text": "Lutein is a pigment classified as a carotenoid, found in plants such as green leafy vegetables (spinach, kale), fruits, corn, egg yolk, and animal fats. While this pigment plays an important role in eye health, lutein supplements also help to prevent colon and breast cancer, diabetes, and heart disease due to its powerful antioxidant potential. In vitro and in vivo lutein was found to scavenge free radicals and inhibit lipid peroxidation by increasing the activity of CAT, SOD, and glutathione reductase [68]. Lutein showed maximum survival in mice treated with 250\u00a0mg/kg body weight against a lethal dose of 10 Gy \u03b3-radiation. Pretreatment of lutein maintained near-normal levels of hematological parameters indicating resistance/recovery from the radiation-induced damages [69]. Furthermore, lycopene has the highest antioxidant activity among carotenoids, and it reduces proinflammatory cytokine expression such as IL-8, IL-6, and NF-\u03baB. Many preclinical studies evidence its radioprotective efficacy, in particular, if it is administered before or as soon as possible after radiation exposure [70]."}
{"_id": "Radiology$$$cece59b1-6550-4f06-95d3-798e12a4fb15", "text": "Vitamin C is the reduced form of ascorbic acid (AA) and a water-soluble vitamin. The intake of vitamin C decreases the risk of getting cataracts after radiation exposition. AA has low toxicity and cost and is easily available, making it an attractive radioprotective agent. Administration of AA before \u03b3-irradiation prevents chromosomal damage in bone marrow cells, mainly due to its scavenging activity of ROS, protecting lipid membranes and proteins from oxidative damage. It has also been reported that AA can prevent the adverse effects of TBI by increasing the antioxidant defense systems in the liver and kidney of irradiated animals [71]. Sato et al. [72] demonstrated the significant radioprotective effect of AA on the ARS in special GI syndrome, especially if it is administered before or not later than 24\u00a0h after radiation exposition."}
{"_id": "Radiology$$$2413be10-7602-4ca8-b21a-2c24eb966346", "text": "Vitamin E is an essential fat-soluble nutrient with antioxidant, neuroprotective, and anti-inflammatory properties. Vitamin E family includes eight vitamers, four saturated (\u03b1, \u03b2, \u03b3, and \u03b4) called tocopherols, and four unsaturated analogs (\u03b1, \u03b2, \u03b3, and \u03b4) referred to as tocotrienols, which are collectively called tocols, with \u03b1-tocopherol being the most abundant in human tissues. Tocols administered subcutaneously 1\u00a0h prior to or during 15 min postirradiation improved the 30-day survival in mice, and other tocopherol derivatives, such as \u03b1-tocopherol-succinate and \u03b1-tocopherol-mono-glucoside, have also shown radioprotective effects in vivo. Moreover, subcutaneous injection of \u03b3-tocotrienol (100\u2013200\u00a0mg/kg) 24\u00a0h prior to 60Co \u03b3-irradiation showed a significant protective effect in mice facing radiation doses as high as 11.5 Gy and increased mice survival rate [73]."}
{"_id": "Radiology$$$1568f06d-2d93-4534-9921-1542a309c52e", "text": "Preclinical studies have provided evidence that tocotrienols exert radioprotection at least in part via induction of G-CSF, reducing inflammatory response suppressing the expression of TNF\u03b1, inducible NO synthase (iNOS), and IL-6 and 8, as well as inhibiting NF-\u03baB signaling [74]. Endothelial cells activated through IR downregulate the expression of thrombomodulin (TM) and increase endothelial surface expression of adhesion molecules, which allow the attachment of immune cells, and thereby contribute to inflammation and activation of the coagulation cascade. The greater efficacy of tocotrienols is attributed to their higher antioxidant potential and its ability to inhibit HMG-CoA reductase activity (decreasing serum cholesterol levels) and increase TM expression in endothelial cells, which result in antipermeability, anti-inflammatory, and antithrombotic response in order to decrease radiation-induced vascular damages."}
{"_id": "Radiology$$$5fce5d97-75f1-4f70-b1bd-ee4b573ec240", "text": "Nevertheless, low bioavailability of tocotrienols is an important limiting factor for their use as radioprotectants, and thus a novel water-soluble liposomal formulation of \u03b3-tocotrienol (GT3) has been developed. GT3 has shown to increase the delivery of \u03b3-tocotrienol in the spleen and bone marrow and offered significant radioprotection in vivo [75]. Despite these promising results, the use of vitamin E derivatives as radioprotectants must be evaluated with caution for their potential toxic effects. More recently, several laboratories have assayed the potential synergistic effect of tocols with other radioprotectants, such as pentoxifylline (PTX) (an antioxidant and anti-inflammatory xanthine derivative, approved by the FDA) which increased survival of mice subjected to 12 Gy 60Co \u03b3-irradiation. Efficacy of PTX and \u03b1-tocopherol against radiation-induced fibrosis has been observed in animal models and clinical studies, even though the treatment started after radiation-induced fibrosis manifested clinically. Three clinical trials have evaluated if PTX enhances the radiation-protective properties of \u03b3-tocotrienol, but the results of these studies have not yet been published [74]. At least, two randomized controlled trials provided evidence that dietary supplementation of \u03b1-tocopherol and \u03b2-carotene during radiation therapy could reduce the severity of treatment adverse effects, but these trials\u00a0also evidenced that the use of high doses of antioxidants might compromise radiation treatment efficacy. Other combinations like \u03b1-tocopherol, acetate and AA showed radioprotective effects and enhanced apoptosis in irradiated cancer cells [76]."}
{"_id": "Radiology$$$89cdb542-2753-4f16-a3a5-8506c594e3a3", "text": "Cholecalciferol (D3) and ergocalciferol (D2) are the two forms of vitamin D provided by the food. Exposure to UV radiation of the skin also\u00a0induces the endogenous synthesis of D3, and for that reason, it is also called the \u201csunshine vitamin.\u201d D3 and D2 have to undergo a double hydroxylation (in the liver and in the kidney) to form the biologically active derivative, that is, calcitriol (1,25-(OH)2-vitamin D), an essential hormone in the regulation of phosphocalcic metabolism. In vitro and in vivo studies evidenced the radioprotective efficacy of calcitriol enhancing the expression of genes coding for antioxidant enzymes (such as SODs and GPxs) and metallothioneins which are ROS scavengers [77]. Jain and Micinski [78] showed a positive link between vitamin D and GSH concentrations, as well as reduction in levels of ROS and proinflammatory cytokines, which is undoubtedly beneficial in protecting against IR. Populations of radiologically contaminated areas close to the Chernobyl accident had lower vitamin D blood levels compared to those in the uncontaminated Ukrainian regions [79]. Therefore, oral supplementation with vitamin D during RT or in medical professionals chronically exposed to low IR doses should be taken into consideration also because radiation toxicity can reduce mineral bone density. Recent studies evidence that calcitriol also radiosensitizes cancer cells by activating the NADPH/ROS pathway, which can\u00a0makes it a promising adjuvant in RT [80]."}
{"_id": "Radiology$$$a7634015-a622-42a9-ab92-4e894a295bbd", "text": "Many antioxidant/defense enzymes, like SOD and metalloproteins, require trace elements as cofactors. The main oligoelements showing protective effects against radiation-induced DNA damage are zinc (Zn), manganese (Mn), and selenium (Se) [81] (Fig. 11.10). Se is an essential component of selenoenzymes such as GPx, thioredoxin reductase-1\u00a0(TR1), and ribonucleotide reductase\u00a0(RNR). Se compounds and their metabolites possess a wide range of biological functions including anticancer and cytoprotection effects and modulation of hormetic genes and antioxidant enzyme activities. Exposure to radiation has been associated with a decrease in Se blood levels, and thus administration of seleno-compounds has emerged as a radioprotective strategy to reduce radiation toxicity. Mechanisms underlying the radioprotection effects include Nrf2 transcription factor activation and the consequent upregulation of the antioxidant-adaptive response in bone marrow stem cells and hematopoietic precursors [82]. 3,3-Diselenopropionic acid (at an IP dose of 2\u00a0mg/kg for 5\u00a0days prior to \u03b3-TBI) showed radioprotection in mice by decreasing DNA damage and apoptosis [83]. Another recent formulations, poly-vinylpyrrolidone and selenocysteine-modified Bi2Se3 nanoparticles, improved the RT efficacy against tumors while exerting radioprotection in normal tissues [84]. Cancer patients, treated orally with Selenium Selenite, experienced a a lower incidence of diarrhoea compared to the placebo group [85]. Selenomethionine also reduces mucositis in patients with advanced head and neck cancer who are receiving cisplatin and radiation therapy (NCT01682031, www.\u200bclinicaltrials.\u200bgov).\n\nAn illustration of copper, zinc, manganese, selenium, or metal complexes causing different types D N A damage.\n\nFig. 11.10\nRadioprotection by oligoelements"}
{"_id": "Radiology$$$cf4541a0-cef1-4fa0-8cd0-ee593bda38b0", "text": "An illustration of copper, zinc, manganese, selenium, or metal complexes causing different types D N A damage."}
{"_id": "Radiology$$$f0f2595b-5b6d-4a5f-8e2c-c8a7fa9f6f29", "text": "Radiation-induced lung pneumonitis is a major\u00a0dose-limiting side effect of thoracic RT, and the therapeutic\u00a0options for its prevention are limited. 3,3\u2032-Diselenodipropionic acid (DSePA), a synthetic organoselenium compound, shows moderate GPx-like activity and is an excellent scavenger of ROS. DSePA reduced the radiation-mediated infiltration of polymorphonuclear neutrophils (PMN) and suppressed NF-kB/IL-17/G-CSF/neutrophil axis as well as elevation in levels of proinflammatory cytokines such as IL1-\u03b2, ICAM-1 (intercellular adhesion molecule-1), E-selectin, IL-17, and TGF-\u03b2 in the bronchoalveolar fluid of irradiated mice, thus ameliorating inflammatory responses. Administration of DSePA has shown a survival advantage against TBI and a significant protection to lung tissue against thoracic irradiation [86]. Wang et al. [87, 88] developed a highly efficient radioprotection strategy using a selenium-containing polymeric drug, with low toxicity and long-term bioavailability, The radioprotection activity of (VSe) and N-(2-hydroxyethyl) acrylamide shows more remarkable effects both in cell culture and mice models compared to the commercially available ebselen (organoselenium compound) and also exhibits a much longer retention time in blood (half-life \u223c10\u00a0h)."}
{"_id": "Radiology$$$96dcd3e9-3f7c-46c0-a4c5-aca61ca8ba64", "text": "Crescenti et al. [89] evaluated in vivo the tolerance induced by the combination of Se, Zn, and Mn (4 microg/mL each) plus Lachesis muta venom (O-LM) (4\u00a0ng/mL) to high doses of TBI (10\u00a0Gy, 137Cs source) IR in mice. Mice who received daily O-LM subcutaneous injections, starting 30\u00a0days before irradiation, showed a higher number of crypts, enhanced villous conservation, and lack of edema or vascular damage compared to the untreated and irradiated group. O-LM treatment also decreased vascular damage and grade of aplasia of mice bone marrow. O-LM treatment safety and efficacy were tested in a phase I clinical trial, and results indicated that it is an attractive candidate as a radioprotective agent for patients undergoing RT. Other clinical evidence indicates that Zn supplementation may act as an effective radioprotector in patients during RT. In a randomized clinical study, patients treated with Zn sulfate suffered a lower degree of mucositis compared to the placebo group [90]. Orally administered Zn-carnosine reduced oral mucositis and xerostomia in head and neck cancer patients [91]."}
{"_id": "Radiology$$$ab92d334-ae68-4218-8a9c-fce1b42d0f9d", "text": "SODs are a group of metalloenzymes that catalyze the dismutation of superoxide radicals (O2\u02d9-) to H2O2 and O2, thus are\u00a0first line of defense to prevent\u00a0IR damages.\u00a0In the event of a radio-nuclear attack or nuclear accident, the skin damage used to be severe. A synthetic SOD/CAT mimetic (EUK-207) administered 48\u00a0h after irradiation significatively mitigated radiation dermatitis, suppressed indicators of tissue oxidative stress, and enhanced wound healing [92]."}
{"_id": "Radiology$$$603d53e2-0365-4a4c-9f0e-dec84d40a307", "text": "Clinical applications of SODs mimetics are\u00a0limited by their structural instability deficient availability\u00a0and high cost. Compared with natural enzymes, nanozymes (nanomaterials with enzyme-like activity) are more stable, are economically affordable, and can be easily modified. Due to these characteristics, nanozymes are expected to become effective substitutes for natural enzymes for medical applications. Nanozymes with SOD-like activity have been developed and proved to have a mitigating effect on diseases involving oxidative stress [93]. As shown in Fig. 11.11, after administration, they are internalized by the cells and imitate SOD2 activity in order to inhibit ROS-induced cell damage.\n\nAn illustration of the actions of antioxidants when a nanozyme with S O D like activity attacks a cell. The antioxidants that respond against free radicals are superoxide dismutase, S O D, catalase, C A T, and glutathione peroxidase, G P x. These inhibit various R O S induced cell damage.\n\nFig. 11.11\nNanozymes with SOD-like activities"}
{"_id": "Radiology$$$a58600c4-5aa1-44bb-96c1-e33e89cd960a", "text": "An illustration of the actions of antioxidants when a nanozyme with S O D like activity attacks a cell. The antioxidants that respond against free radicals are superoxide dismutase, S O D, catalase, C A T, and glutathione peroxidase, G P x. These inhibit various R O S induced cell damage."}
{"_id": "Radiology$$$67357eea-e65b-4d7e-9ad1-644682e14871", "text": "Patients treated with RT for cancers of the head, neck, or lung suffer damage to the mucosa of the upper aerodigestive tract. Most of them develop ulcerative forms of mucositis, and severe forms lead to inability to eat solid foods, and in some cases, they cannot drink liquids. Results of clinical trials (now in phase III, e.g., NCT03689712) demonstrated the efficacy of the SOD mimetic, avasopasem manganese (GC4419) [94]."}
{"_id": "Radiology$$$fa4cc97c-534b-4ed8-82d6-231e6ff30c4f", "text": "Mn porphyrin-based SOD mimics (MnPs) are reactive with superoxide and with other reactive oxygen, nitrogen, and sulfur species (Fig. 11.12). MnPs have CAT and GPx-like activities and peroxynitrite-reducing activity [93]. MnPs administered before and continued after radiation exposure protect from \u03b3-ray, X-ray, and proton beam irradiation damages in different animal models, and a few studies indicate that beginning treatment with MnPs after radiation exposure is also effective. In normal tissues, MnPs treatment reduces oxidative stress, NF-\u03baB, and TGF-\u03b2 signaling pathways and activates Nrf2-dependent pathways. On the contrary, MnPs administration in combination with cancer therapy results in more oxidative stress in cancer cells, which leads to the reduction of NF-\u03baB and HIF-1\u03b1 and their downstream signaling pathways (Fig. 11.12). These changes are associated with increasing apoptosis and reducing overall cancer growth [95].\n\nAn illustration of the effect of M n porphyrin based S O D mimics, M n Ps, on normal cells and cancer cells Normal cells: Protection against radiation induced toxicity. Cancer cell: Enhancing cancer cell radiation therapy efficacy.\n\nFig. 11.12\nEffects of Mn porphyrin-based SOD mimics in normal and cancer cells"}
{"_id": "Radiology$$$2cbb7bb8-acc7-4229-9f09-1b6f9a07f10c", "text": "An illustration of the effect of M n porphyrin based S O D mimics, M n Ps, on normal cells and cancer cells Normal cells: Protection against radiation induced toxicity. Cancer cell: Enhancing cancer cell radiation therapy efficacy."}
{"_id": "Radiology$$$fa582815-f02b-4573-806e-212dd06be1c6", "text": "BMX-001 is a porphyrin mimetic of the human mitochondrial manganese SOD, with the capacity to cross the blood-brain barrier and protect the brain against IR while acting as a tumor radiosensitizer [96]. It has been assayed as a radioprotector in different clinical trials, e.g., NCT03386500 (patients with recently diagnosed anal cancer), NCT03608020 (cancer patients with multiple brain metastases), NCT02990468 (head and neck cancer), and NCT02655601 (high-grade glioma treated with radiation therapy and temozolomide) [30]."}
{"_id": "Radiology$$$0318f764-65b9-4a0f-9d97-f083a31d5515", "text": "All previous SOD mimetics suppress oxidative stress-mediated injuries, supporting the survival of the normal tissue, while promoting apoptotic processes in tumor tissues. The results from the clinical trials will provide us invaluable information on their real clinical utility as radioprotectors."}
{"_id": "Radiology$$$b7458f23-0ea8-4698-9800-aa7b34fd1331", "text": "Radiation dermatitis is a common side effect of irradiation that limits cancer RT courses. It has already been described how the induction of hypoxia limits the damage associated with radiation, and consequently the option of using vasoconstrictor substances as radioprotectors has been proposed. Topical application of adrenergic vasoconstrictors (epinephrine or norepinephrine) to rat skin before radiation exposition (17.2\u00a0Gy) confers 100% protection against radiation dermatitis [97], and similar results were obtained when phenylephrine was topically administered to prevent radiation mucositis."}
{"_id": "Radiology$$$0f34e421-ae65-4ed4-9a7b-0a4d02ae9d69", "text": "Indralin is an \u03b11-adrenoceptor agonist with vasoconstrictor effects similar to those of epinephrine. Indralin (120\u00a0mg/kg)-treated rhesus monkeys survived better (five of six) after being exposed to a lethal TBI 60Co \u0263-irradiation of 6.8\u00a0Gy, than nontreated ones (all died). Moreover, less pronounced manifestations of hemorrhagic syndrome, leukopenia, and anemia were also noted [98]. Norepinephrine and \u03b11-adrenoceptor agonists accelerate differentiation of hematopoietic stem cells by blocking their proliferation, thus avoiding, at least, earlier manifestation of radiation injury. A common feature of the radioprotective action of biogenic amines like indralin and aminothiols is the induction of hypoxia, although their mechanisms of action differ significatively. Norepinephrine and indralin exert their effect through the neurohormonal \u03b11-adrenoceptors, but sulfur-containing radioprotectors act directly on tissues. Nevertheless, the use of \u03b1-catecholaminergic agonists entails a high risk of increased blood pressure or pressure decompensation in hypertensive patients, which would compromise their widespread use in an accidental emergency radiation exposure."}
{"_id": "Radiology$$$dec2bf5a-e2ba-4ea9-b910-caa5c6033764", "text": "GI radiation vulnerability to a certain extent can be caused by release of potent pancreatic enzymes into the intestinal lumen after radiation exposure. Therefore, reducing intraluminal proteolytic activity may help attenuate intestinal radiation toxicity."}
{"_id": "Radiology$$$33441b79-8058-4aa3-9940-2b592adf07a7", "text": "Somatostatin and its analogs (octreotide and pasireotide) inhibit exocrine pancreatic secretions. Octreotide reduces both acute and delayed intestinal radiation injury and diarrhea [99], as it has also been evidenced in a randomized controlled trial in patients who were undergoing radiation therapy to the pelvis (NCT00033605, www.\u200bclinicaltrials.\u200bgov). Nevertheless, some common side effects such as allergy, nausea, rash, and light-headedness may limit the routine use of octreotide. Moreover, it could also induce hypoglycemia [99] and reduce secretion of GH and IGF1, which could be highly counterproductive for the recovery of damaged tissues."}
{"_id": "Radiology$$$8ecd1988-4980-4d61-a3a8-398a4ab94a81", "text": "SOM230 (pasireotide) is another somatostatin analog under preclinical evaluation as a radioprotector. SOM230 reduced intestinal mucosa injury and increased mouse survival after TBI by inhibiting exocrine pancreatic secretion. Moreover, SOM230 has a 40-fold improved affinity to somatostatin receptor 5 than other somatostatin analogs, and it proved to be beneficial when administered prior to radiation exposure, and also when the treatment started up to 48\u00a0h following the exposure [100]."}
{"_id": "Radiology$$$b0e50eb7-4643-434b-bd12-f53436062b18", "text": "Several hormones are known to exhibit radioprotective characteristics, and melatonin, N-acetyl-5-methoxytryptamine, is one of them. It is the main secretory product of the pineal gland. Its radioprotective properties are outlined in Figs. 11.13 and 11.14.\n\nAn illustration of the properties of melatonin. Melatonin enhances endogenous D N A repair activity, directly neutralized R O S and R N S and acts as free radical scavenger, ameliorates inflammatory response, and increases expression of antioxidant levels, reducing oxidative stress.\n\nFig. 11.13\nRadioprotective properties of melatonin\n\n\nAn illustration of the different radioprotective and radio mitigative effects of melatonin in the extracellular and intracellular regions and in the nucleus.\n\nFig. 11.14\nMelatonin can exert radioprotective and radiomitigative effects"}
{"_id": "Radiology$$$60550642-4e79-49d7-904a-0be4195c7971", "text": "An illustration of the properties of melatonin. Melatonin enhances endogenous D N A repair activity, directly neutralized R O S and R N S and acts as free radical scavenger, ameliorates inflammatory response, and increases expression of antioxidant levels, reducing oxidative stress."}
{"_id": "Radiology$$$fcf3667d-c092-4230-ba64-d5b2aa542dc1", "text": "An illustration of the different radioprotective and radio mitigative effects of melatonin in the extracellular and intracellular regions and in the nucleus."}
{"_id": "Radiology$$$f0783da6-8979-4243-88d2-351047d36a1f", "text": "Melatonin has the ability to neutralize both ROS and NO directly leading to the production of less/nontoxic agents or indirectly increasing the activity of antioxidant enzymes such as SODs, GPx, GR, and CAT at the same time suppressing prooxidant enzymes like xanthine oxidase (XO) [101]. In addition, melatonin induces DNA repair mechanisms, which reduce mutagenic damage and also induction of DNA DSBs, which are lethal events for the cell. Melatonin administration before irradiation with a lethal dose of 60Co \u03b3-rays reversed the upregulation of Bax and p53 proapoptotic genes and elevated Bcl-2, which led to 100% survival and preservation of hematopoietic and GI systems in mice [102]. Inflammation and fibrosis are two degenerative phenomena that are typical pathophysiological processes following RT. Melatonin via inhibition of NF-kB, COX-2, and iNOS enzymes has the ability to reduce the release of inflammatory cytokines and chemokines. Attenuation of these enzymes\u2019 activities is associated with reduced level of oxidative stress, infiltration of macrophages and lymphocytes, as well as suppression of fibrosis, which prevents radio-induced pneumonitis and lung fibrosis [103], and also heart [104] and brain [105] damage associated with radiation exposition."}
{"_id": "Radiology$$$d492b6f9-7e6f-4d18-b829-d7e57a584a82", "text": "The physiological concentrations of melatonin in the human blood are approximately much lower during the day than during the night. Therefore, it seems that radiation therapy with supplementary melatonin leads to more beneficial effects during the nighttime. Melatonin exhibits multiple neutralizing actions to reduce radio-induced damage. Together with its low toxicity and its ability to cross biological barriers, these are all significant properties to consider it for clinical RT applications as well as for mitigation of radiation injury in a possible radiation accident scenario; however, its short half-life in vivo (<1\u00a0h) and the need of high doses to achieve radioprotective effects could limit its use in practice."}
{"_id": "Radiology$$$f404e577-1e16-48a9-b9a6-f7f07bd5cd10", "text": "At this moment, just a few clinical trials have studied the therapeutic usefulness of melatonin as a radiosensitizer. Many preclinical studies evidence that it increases ROS production, inhibits telomerase activity and DNA repair mechanisms in cancer cells, reduces tumor angiogenesis and inflammatory response associated with high doses of radiation exposure, and enhances anticancer immunity. All these oncostatic properties make melatonin an interesting molecule to increase the efficacy of RT on cancer cells [106]."}
{"_id": "Radiology$$$cd2e5c55-3964-4615-aa17-d6a6ac1a29cb", "text": "Apart from being a common antidiabetic drug, MTF has demonstrated potential antioxidant, radioprotective, and anticarcinogenic properties [107]. It is a hydrogen-rich agent able to neutralize free radicals, increase GSH, and upregulate the activity of SOD and CAT enzymes [108], which all favors the antioxidant defense of normal cells. MTF has been reported to reduce the generation of ROS at the complex 1 and to prevent mitochondrial mediated apoptosis [109]. It also decreases production of the inflammatory cytokine IL-1\u03b2 in response to lipopolysaccharide (LPS) in macrophages [110] and inhibits NADPH oxidase, COX-2, and inducible NO synthase, thereby limiting macrophage recruitment and inflammatory responses. MTF stimulates the DNA repair pathways of nonhomologous end joining\u00a0(NHEJ) or homologous recombination\u00a0(HR), and nucleotide excision repair (NER)\u00a0pathways [111]."}
{"_id": "Radiology$$$97e50e2d-cee4-4130-aa6f-bae0df67023d", "text": "In contrast to other radioprotectors, MTF has shown modulatory effects through induction of several redox-related genes, such as the PRKAA2 gene (which encodes the AMPK), thereby suppressing redox reactions, protecting cells from accumulation of unrepaired DNA, and attenuating initiation of inflammation as well as fibrotic pathways [108] involved in lung fibrosis [104]. Cardiovascular disease is one of the most pivotal disorders after RT. The administration of MTF to \u03b3-irradiated (5\u00a0Gy) rats significantly ameliorated the changes in cardiac disease biomarkers (LDH and CK-MB) and in NF-\u03baB, IL-6, and TNF-\u03b1 levels compared to the control group. MTF also reduced E-selectin as well as ICAM and VCAM-1. These results demonstrate that concomitant administration of MTF during RT can act as an efficient heart protector from oxidative stress, inflammatory mediators, and endothelial dysfunction-induced damages [112\u2013114]. MTF does not have significant adverse effects at the normal clinical level, but it may cause severe lactic acidosis and increase the risk of hypoglycemia. In animal models, MTF has demonstrated synergistic effects with melatonin mitigating the radiation-associated damages, and both of them radiosensitize cancer cells increasing RT efficacy (this will be later exposed in Sect. 11.4)."}
{"_id": "Radiology$$$952eea0e-a7b0-4b75-93f6-64a273d948c0", "text": "Radiomitigators are those agents/compounds which can be administered during or shortly after radiation therapy or IR exposure to reduce the effects of radiation on normal tissues before the onset of symptoms. These compounds are capable of minimizing the toxicity even after radiation has been delivered, which differentiates them from radioprotectors (reducing direct damage caused by radiation in normal tissues). At this moment, all FDA-approved radiation countermeasures (filgrastim, a recombinant DNA form of the naturally occurring G-CSF; pegfilgrastim, a PEGylated form of the recombinant human G-CSF; sargramostim, a recombinant GM-CSF) are classified as radiomitigators [30]."}
{"_id": "Radiology$$$9531f291-3e86-4dd4-a9b7-d83e32e0fad0", "text": "In some cases, these agents have protective properties that are similar to the action of \u201cclassic\u201d radioprotectors, even if they are administered after radiation exposure. However, these agents are most effective not only at administration shortly after irradiation, but also during the irradiation. For radiologic terrorism and space research, much of the focus of radiomitigators has been in the field of developing chemopreventives\u00a0strategies in order to reduce carcinogenesis of TBI."}
{"_id": "Radiology$$$fe47da3a-c2bb-42a2-a3c5-ea28ffc004b6", "text": "An ideal radiomitigator should (a) offer the possibility of easy administration, (b) protect normal sensitive tissues which are associated with dose-limiting toxicity and significant reduction in quality of life, (c) be stable and easily available, and (d) have no relevant toxicity."}
{"_id": "Radiology$$$422b0c56-420d-4a39-bc50-8827c4f79cf6", "text": "Postradiation changes in normal tissue such as constant mitotic cell death and perpetually active cytokine cascades can sooner or later lead to vascular damage, tissue hypoxia, and excessive extracellular matrix deposition [115]. Radiation mitigators should aim to interrupt these cascades prior to the manifestation of toxicity or intervene to prevent the prolongation of molecular and cellular damage, and therefore reduce the expression of radiation-induced tissue toxicity or prevent the acute toxicity."}
{"_id": "Radiology$$$d7d3ab43-5510-404d-9842-b32ec27d38a1", "text": "Potential radiation mitigators are described in this chapter; their possible mechanism of action is represented in Fig. 11.15.\n\nAn illustration of the mechanism of action of radiomitigators. The mechanisms are mitigation D N A damage, accelerate D N A damage repair, gene expression, signal transduction, repopulation or proliferation, physiological effects, inflammation, differentiation, and activation of host cells.\n\nFig. 11.15\nRadiomitigators: mechanism of action"}
{"_id": "Radiology$$$01f949bc-5944-49fc-ab9e-e9e3f73eb57a", "text": "An illustration of the mechanism of action of radiomitigators. The mechanisms are mitigation D N A damage, accelerate D N A damage repair, gene expression, signal transduction, repopulation or proliferation, physiological effects, inflammation, differentiation, and activation of host cells."}
{"_id": "Radiology$$$434ee275-beb1-4cda-8976-18fd54c813a9", "text": "Radiomitigators can modulate the radiation-induced molecular, cellular, and tissue toxicity/injuries even\u00a0when they are\u00a0administered after radiation exposure. Gene and stem cell therapies as therapeutic radiation countermeasures are being developed and may be applied in the near future to minimize the side effects of radiation exposure through tissue regeneration."}
{"_id": "Radiology$$$b3929c2e-2a12-4f6b-802c-aa2d3c2577cb", "text": "Several\u00a0studies have suggested that cellular recovery and repair processes can be enhanced by radiomitigators. Double-strand breaks (DSBs) are the most common form of DNA damage associated with IR. After DSBs are generated, a cascade of enzymatic processes, such as, HR and NHEJ (mediated by BRCA 1 and BRCA 2 enzymes), activation of p53, and induction of cell cycle arrest triggered to allow DNA repair or to induce apoptosis. The pharmacological improvement of these mechanism can contribute to mitigate IR damages. However, this must be done with care, because failure of these processes can lead to carcinogenic transformation [116]. Future studies should focus on compounds that have the potential to enhance the process of DNA repair after radiation exposure. In that sense, higher cellular pools of DNA precursors can create a radioprotective cellular environment, and drugs and chemicals that stimulate the activity of precursor-synthesizing enzymes can function as radiomitigators [117]."}
{"_id": "Radiology$$$bdc3255d-e882-4b1a-93f7-0020b3881e4e", "text": "Anti-inflammatory Activity\n\nAn illustration of anti-inflammatory activity. I R activates the immune response, causing inflammation. Inflammation occurs in the presence of pro inflammatory cytokines and chemokines, such as I L 1, I L 6, T N F alpha, and T G F beta."}
{"_id": "Radiology$$$d90e41b3-d09d-4d0d-888c-dd788749be58", "text": "An illustration of anti-inflammatory activity. I R activates the immune response, causing inflammation. Inflammation occurs in the presence of pro inflammatory cytokines and chemokines, such as I L 1, I L 6, T N F alpha, and T G F beta."}
{"_id": "Radiology$$$bad5377a-e582-4663-a4e0-4f6c5f8f43be", "text": "IR is indirectly toxic by activating immune response, and patients undergoing radiation therapy may occasionally suffer from widespread inflammation. Various proinflammatory cytokines and chemokines are generated after radiation exposure, which particularly mediate inflammation, fibrosis, and other serious injuries in tissues and organs. Some natural products and their bioactive components can reduce the expression of these small cell signaling protein molecules and relieve the inflammation-associated side effects through their healing properties. Some phytochemicals, nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoid, and other molecules reduce inflammatory response, reducing long-term side effects like fibrosis.\n\nAn illustration of I R causing death. I R causes dose-depended cascade or hematopoietic syndrome, resulting in injury to lymphoid and hematopoietic system. The injury causes septicemia, anemia, and hemorrhages, leading to death."}
{"_id": "Radiology$$$c6cf3565-533f-449e-a3d6-4499a23563b8", "text": "An illustration of I R causing death. I R causes dose-depended cascade or hematopoietic syndrome, resulting in injury to lymphoid and hematopoietic system. The injury causes septicemia, anemia, and hemorrhages, leading to death."}
{"_id": "Radiology$$$7fd63219-3375-4975-8757-5e63086591ba", "text": "Hematopoietic stem cell injury is the primary cause of death after accidental or intentional exposure to a moderate or high dose of IR. Hence, compounds which can stimulate the regeneration of hematopoietic cells and immune system by mechanisms such as increasing spleen colony-forming units in synergy with interleukins may have good ability to protect cells and tissues against radiation exposure. A range of endogenous compounds like IL-1, TNF\u03b1, G-CSF, stem cell factor (SCF), erythropoietin (EPO), and GM-CSF stimulate stem cell progenitors and promote hematopoietic bone marrow repopulation and thus have been further investigated as potential radiomitigators. So, agents that upregulate endogenous radioprotective factors can also act as radioprotectors."}
{"_id": "Radiology$$$b687b89f-8af5-49a2-9449-04c09f4ec769", "text": "A variety of agents (such as vitamins, TLR ligands, and \u03b2-glucan) and many natural antioxidants are classified as immunomodulators as they regulate different cytokines (cell growth factors, colony-stimulating factors, etc.) in order to facilitate patient recovery\u00a0from IR-induced injuries. These regulators inhibit cell apoptosis, promote differentiation and development of gastrointestinal or hematopoietic stem cells, and have radiomitigator effects (Box 11.3)."}
{"_id": "Radiology$$$10d10ea1-31b3-46de-a284-40a81cd98d6a", "text": "Radiomitigators (cytokines, growth factors, hormones, synthetic analogs, immunological adjuvants, immune regulatory peptides, etc.) accelerate the postradiation restoration of radiosensitive tissues.\n\nAt times, these agents can exert protective effects in a similar way to the action of \u201cclassic\u201d radioprotectors; therefore, radiomitigators reduce oxidative stress and inflammatory damages, activate enzymes involved in repair mechanisms, and/or stimulate the replenishment of damaged tissues.\n\nCompared to radioprotectors, they have the advantage of being effective despite being administered after exposure to IR. They are usually administered during the early period of postradiation and prior to the development of acute radiation syndrome (ARS)."}
{"_id": "Radiology$$$bf55e260-b3c3-4343-9ae5-28b70da57c1d", "text": "Radiomitigators (cytokines, growth factors, hormones, synthetic analogs, immunological adjuvants, immune regulatory peptides, etc.) accelerate the postradiation restoration of radiosensitive tissues."}
{"_id": "Radiology$$$cbae31f1-fcca-44ca-91a6-2ffa89ef2c8a", "text": "At times, these agents can exert protective effects in a similar way to the action of \u201cclassic\u201d radioprotectors; therefore, radiomitigators reduce oxidative stress and inflammatory damages, activate enzymes involved in repair mechanisms, and/or stimulate the replenishment of damaged tissues."}
{"_id": "Radiology$$$4ecd610f-728a-4065-8605-e4ca0a24cc68", "text": "Compared to radioprotectors, they have the advantage of being effective despite being administered after exposure to IR. They are usually administered during the early period of postradiation and prior to the development of acute radiation syndrome (ARS)."}
{"_id": "Radiology$$$d325a6b8-40d9-4ee9-bc7d-cece469bf18d", "text": "Four radiomitigators have been approved by the US Food and Drug Administration (US FDA) for the management of hematopoietic acute radiation syndrome (H-ARS). They include human recombinant G-CSF (filgrastim/Neupogen\u00ae), long-acting PEGylated form of G-CSF (filgrastim/Neulasta\u00ae), GM-CSF (sargramostim/Leukine\u00ae), and romiplostim (Nplate\u00ae), a fusion protein containing a peptide region that binds to the thrombopoietin receptor (c-Mpl) and an Fc carrier domain that increases its circulating half-life. Romiplostim was approved for use in radiation injury by the FDA based on the Animal Rule (United States Food and Drug Administration, 2021, Highlights of prescribing information. Nplate\u00ae (romiplostim) for injection, for subcutaneous use). Except for romiplostim, they have all been used to treat radiation accident victims with beneficial results [118\u2013121]."}
{"_id": "Radiology$$$04a7b6b9-49ff-4564-803e-a9a8b4db29e5", "text": "G-CSF and PEGylated G-CSF promote the differentiation and proliferation of myeloid progenitor cells and their progeny. These effects promote neutrophil recovery after radiation-induced neutropenia. In addition, they enhance the function of neutrophils and improve survival. A World Health Organization Consultancy recommended that Neupogen and Neulasta should be administered subcutaneously, as soon as possible to individuals who have been exposed to radiation doses of >2 Gy [118]. Neulasta has the advantage that it is administered weekly, compared to daily administrations that is required for Neupogen treatment. GM-CSF increases the differentiation and proliferation of macrophage and granulocyte progenitor cells. When administered as late as 48\u00a0h after radiation exposure, GM-CSF reduced the recovery time for neutropenia and thrombocytopenia and decreased the rate of infection [5]. In addition, GM-CSF appears to exhibit an antifibrotic effect in the setting of radiation-induced lung injury (RILI) in experimental animals and humans [122, 123]."}
{"_id": "Radiology$$$b58893e1-adb7-4af8-ab81-0cf23ac18724", "text": "Keratinocyte growth factor (KGF), a factor that is produced by mesenchymal cells, protects and repairs epithelial tissues. Early studies suggested that KGF promotes the recovery of the oral mucosa after radiation-induced injury, improves gastrointestinal barrier function, and limits bacterial translocation and subsequent sepsis after irradiation. In clinical studies, Palifermin\u00ae, a human recombinant KGF product, reduced the incidence, duration, and severity of oral mucositis and esophagitis in patients treated with chemoradiotherapy and stimulated immune reconstitution following hematopoietic stem cell transplantation [124]."}
{"_id": "Radiology$$$e5bbd776-2097-44cd-9326-c08ca678c532", "text": "Many cell types release epidermal growth factor (EGF), which promotes the regeneration of hematopoietic stem cells in vivo. EGF was reported to have an additive effect on overall survival with G-CSF (survival of 20% for controls, 67% for EGF, 86% for EGF plus G-CSF) [125]. Fibroblast growth factor (FGF) is found in many tissues throughout the body, and its levels decrease after irradiation. FGF-P is a human recombinant derivative that is capable of activating FGF receptor-1, resulting in protection of the crypts located in the duodenum and improved survival in a GI-ARS mouse model. In addition, platelet counts were found to be higher in FGF-P-treated animals, resulting in decreased hemorrhages and cutaneous ulcerations postirradiation. It has been suggested that FGF-P has the potential to treat radiation-induced skin ulcerations and thermal burns and that it holds potential promise in the management of ischemic wounds and the promotion of tissue engineering and stem cell regeneration [125]."}
{"_id": "Radiology$$$52417e29-0e09-4711-8fb4-ef11d2208a98", "text": "Interleukin-12 (IL-12) has pleiotropic effects on the innate and adaptive immune cells, including stimulation of hematopoiesis. Treatment with HemaMax\u00ae (human recombinant IL-12) restored all cell types in bone marrow when administered at 24 and 48\u00a0h post-TBI in non-human primates (HNPs) and mice, respectively. Compared to Neupogen, Neulasta, and Leukine, the single administration of HemaMax\u00ae is another advantage in the event of a mass casualty incident [126]. A novel, PEGylated IL-11 (Neumega\u00ae) is approved to treat thrombocytopenia in cancer patients, but must be injected daily, making its use inconvenient as a radiomitigator. To circumvent this problem, another mono-PEGylated IL-11 analog (BBT-059) was designed and demonstrated higher bioavailability and potency in vivo. In mouse model exposed to high TBI doses, BBT-059 leads to bone marrow cell reconstitution, leading to an accelerated recovery of platelets, erythrocytes, and neutrophils and an increase of survival higher than that obtained with treatment with the PEGylated derivatives of G-CSF and GM-CSF [125]."}
{"_id": "Radiology$$$27ba605a-546f-45ca-8f1d-bebcefb91894", "text": "Erythropoietin is prescribed for the treatment of severe anemia arising from intense chemo- and/or radiation therapies. Erythropoietin and thrombopoietin (TPO) have been used for the victims of radiation exposure in the Tokaimura accident. Romiplostim (Nplate) is a synthetic TPO receptor agonist that preferentially increases platelet generation in bone marrow; contributes to mitigation of radiation-induced thrombocytopenia, anemia, and leukopenia; gives protection; and enhances regeneration of vascular endothelium. Romiplostim has recently received FDA approval to treat acutely irradiated and severely myelosuppressed adult and pediatric patients. More recently, ALXN4100TPO (a TPO receptor agonist) has been shown to stimulate megakaryopoiesis, reduce bone marrow atrophy and radiation-induced mortality in acutely irradiated mice, with the advantage of being less immunogenic than Nplate."}
{"_id": "Radiology$$$069f63fc-cef3-4efe-8dff-3b3a4e220892", "text": "Combinations of hematopoietic growth factors and cytokines (G-CSF, GM-CSF, EPO, SCF, and IL-3) have already been used in the treatment of radiological accident victims, but the relative efficacy of this combined treatment is difficult to evaluate due to differing radiation sources, exposure doses, and other circumstances [127]."}
{"_id": "Radiology$$$3f4bf022-83a1-4deb-aeed-a3a0598e249a", "text": "As explained in detail in Chap. 2, irradiation directly causes ROS overproduction, apoptosis, and/or necrosis, which activate the inflammatory response. In the short term, proinflammatory cytokines, such as IL-1, IL-6, IL-8, IL-33, TNF-\u03b1, and TGF-\u03b2, help to activate the immune response and bone marrow cellular recovery, but if it is excessive or is maintained for a long time, it can contribute to bystander/nontargeted effect (damages in tissues that have not been directly exposed), in special autoimmune diseases, fibrosis, and/or cancer initiation and progression. Therefore, the use of cytokines or growth factors capable of increasing the inflammatory response should be carefully evaluated. Moreover, the use of substances that inhibit its release or antagonize its proinflammatory effects has been shown to have mitigating effects on the damage caused by IR."}
{"_id": "Radiology$$$1422bbde-78cf-49e5-aad3-ac3742b9b407", "text": "Fibrogenic cytokines like TGF-\u03b2, vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF) are involved in radiation-induced fibrosis. TGF-\u03b2 is able to stimulate ROS and NO production by the immune system, involved in the initiation and progression of chronic oxidative damage after exposure to a high dose of radiation. It is therefore not surprising that combined inhibition of TGF-\u03b2 and PDGF signaling attenuates radiation-induced pulmonary fibrosis associated with decreased pneumonitis and leading to prolonged survival. Inhibition of TGF-\u03b2 also reduced radiation-induced endothelial vascular damages [113, 114]. Moreover, different phase I/II clinical trials have shown more successful RT response with the combined use of TGF-\u03b2 inhibitor in metastatic breast cancer patients (LY2157299, NCT02538471). This is of special interest, because the reduction in plasma levels of TGF-\u03b2 is associated with greater efficacy of RT on different types of cancer and some studies have proposed that attenuation of cytokines by genistein or quercetin ameliorates late effects of IR such as pneumonitis and fibrosis [128]."}
{"_id": "Radiology$$$a9bf42f2-8053-4108-840e-ca0472152866", "text": "The necrosis of central nervous system (CNS) tissue is one of brain irradiation\u2019s main risk factors. The same is true for radiation-induced increase of capillary permeability resulting from cytokine release, causing extracellular edema. A recombinant human monoclonal antibody (bevacizumab), which prevents the VEGF from binding to its receptors, reduced brain necrosis in a patient subjected to cranial irradiation and further experiments evidenced its efficacy for the management of edema associated with radiation necrosis [129]."}
{"_id": "Radiology$$$d87ec93c-f399-49b8-a1e0-eb5fe412122f", "text": "Toll-like receptors (TLRs) play critical roles in basal resistance to IR in animals and multiple radiosensitive tissues. Several TLR ligands had been proved to exert protective roles against IR both in vitro and in vivo, downstream effectors including NF-\u03baB (controller of inflammation, and immune response), interferon regulatory factors, and stress-activated protein kinase (Jnk), which in turn results in inhibition of apoptosis, promotion of cell proliferation, regulation of cell cycle, and secretion of cytokines. In cultured cells, TLR2, TLR5, or TLR9 agonists inhibit radiation-induced apoptosis and increase cell survival. CBLB502 (a TLR5 agonist) was reported to alleviate bone marrow and intestinal injuries in mice and rhesus monkeys. Activation of TLR4 by its agonist LPS can protect bone marrow damage and lower mice mortality after irradiation. Moreover, some kinds of TLR agonists, such as TLR2/6 coagonist CBLB613, were reported to be more effective in radiomitigation than single-TLR agonists. In conclusion, TLRs and their ligands provide novel strategies for radiation protection in nuclear accidents [28, 29,\u00a055]."}
{"_id": "Radiology$$$c636d96b-b2c9-4a62-a34f-decc14af405f", "text": "IR is known to be especially damaging on highly proliferative tissues. Cellular sensitivities in approximate descending order from most to least sensitive are lymphocytes, germ cells, proliferating bone marrow and intestinal epithelial cells, and epithelial stem cells. Hematopoietic syndrome (HS) is the dominant manifestation after whole-body doses of about 1\u20136 Gy and consists of a generalized pancytopenia, due to bone marrow stem cell depletion, although, excepting lymphocytes, mature blood cells in circulation are largely unaffected. Patients remain asymptomatic during a latent period as the impediment to hematopoiesis progresses. Risk of infection and sepsis is increased as a result of neutropenia (most prominent at 2\u20134\u00a0weeks) and decreased antibody production. Petechiae and bleeding result from thrombocytopenia, which develops within 3\u20134\u00a0weeks and can persist for months. Anemia develops more slowly because circulating erythrocytes have a longer life span. Clinical management of the HS with risk of sepsis, hemorrhage, and/or acute anemia is related to the standard clinical protocols. Therapy would certainly encompass, but not limited to, the use of antibiotics, blood, and platelet transfusion, although the latter is limited by the recipient\u2019s own immune response. Moreover, aseptic protocols must be rigidly employed. Allogeneic hematopoietic stem cell transplantation can restore bone marrow and immune functions. In the past, stem cells were harvested directly from donor bone marrow in the operating room, but at present, peripheral blood is most used as a source of stem cells for both autologous and allogeneic grafts [130]. Bone marrow stromal cell transplantation has also been shown to renew the irradiated intestinal stem and alleviate radiation-induced GIS [131]. To date, about 50 patients with acute radiation sickness have been treated with allogeneic hematopoietic stem cell transplants, but the median survival time has not yet exceeded 1\u00a0month. Despite these results, the efficacy of bone marrow transplantation in patients undergoing RT treatments highlights the need to have mechanisms in place to implement this procedure for patients exposed during a nuclear emergency [132]."}
{"_id": "Radiology$$$188584fc-6996-46db-833b-c007aac10899", "text": "Mesenchymal stem cells (MSCs) are nonhematopoietic adult stem cells with self-renewal and multilineage differentiation potential, low immunogenicity, and capacity to restore cell loss in damaged microenvironments. Moreover, MSCs secrete different interleukins, which help in the repair and recovery of cells. Although MSCs were traditionally isolated from bone marrow, cells with MSC-like characteristics are much easier to isolate from a variety of neonatal and adult tissues, including amniotic fluid, umbilical cord, peripheral blood, fat tissue, etc. Treatment with MSCs has shown efficacy in protecting the liver against radiation-induced injury; healing irradiated skin in mice; mitigating radiation-induced GIS, HS, brain injury, and neurological complications of RT; and increasing survival in irradiated mice [102]. Moreover, MSCs have successfully been assayed against radiation-induced pulmonary fibrosis (NCT02277145) and xerostomia (NCT03876197) (www.\u200bclinicaltrials.\u200bgov) [30]. Nevertheless, despite the extensive use of MSCs in preclinical and ongoing clinical trials, there is a lack of long-term safety in humans. During recent years, it has been demonstrated in animal models that MSC-derived extracellular (EVs). EVs can exert the same therapeutic effect of MSC; therefore, EVs can be used as an alternative MSC-based therapy [133]. To cite some examples, EVs inhibit DNA damage and cell death and preserve intestinal function [134] and bone marrow activity providing long-term survival in mice exposed to TBI [135]."}
{"_id": "Radiology$$$e9e5233f-5d62-4063-84a9-a768e236511f", "text": "Radiation initiates many enzymes such as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) to produce ROS or NO, involved in the activation of inflammatory response. Most NSAIDs, such as aspirin, ibuprofen, indomethacin, diclofenac, and flurbiprofen, are able to inhibit COX-1 and COX-2 enzymes. The protective action COX inhibitors (COXi) is ascertained to the inhibition of the prostaglandin synthesis and directly or indirectly linked with the ability of NSAIDs to arrest cells in the G0 or G1 phase where cells are less sensitive to radiation damage and/or stimulation of the hematopoietic recovery [136]. Both pre- and post-irradiation treatments with sodium diclofenac reduced radiation-induced formation of DC and MN formation in human peripheral blood lymphocytes [137]. Flurbiprofen also showed radioprotection in clinical studies, e.g., delaying the onset of mucositis and reducing its severity after RT in 12 head and neck cancer patients, although the overall severity or duration of mucositis was not improved [138]. A recent meta-analysis of randomized controlled trials indicates that aspirin reduces the overall risk of recurrence and mortality of colorectal cancer and/or colorectal adenomas, which increases the interest in its possible use as a radiomitigator [24, 25]. However, nonselective COXi are known to cause undesirable side effects including GI ulcers and bleeding when taken for continued periods of time."}
{"_id": "Radiology$$$84a4d567-e92f-4307-bd77-e5e5301bf2ac", "text": "Increase of COX-2 gene expression is associated with decreased survival in patients receiving RT [139]. COX-2 selective inhibitors (COXi, as celecoxib, meloxicam, indomethacin) lack the GI toxicity of classical NSAIDs, and therefore, the use of COX-2i like meloxicam has been extensively assayed. Meloxicam administered either before or repeatedly after irradiation exposure has enhanced the recovery of hematopoietic progenitor cells committed to granulocyte-macrophage and erythroid development in sublethally irradiated mice [140], but the increase in survival was only observed when meloxicam was applied before lethal TBI. Sequential administration of PGE2 and meloxicam was shown to increase hematopoiesis and survival in irradiated mice [141], and meloxicam combined with ibuprofen treatment reduced bone loss after radiation exposure [142]. Radiation pneumonitis is a severe and dose-limiting side effect in lung cancer treatment. In this regard, celecoxib was tested in rats after single-dose X-ray irradiation of the right hemithorax and mediastinal region with 20 Gy revealing a dose-dependent protective effect on lipid peroxidation (MDA levels) and histopathological parameters. Celecoxib treatment induced a decrease in severe skin reactions after a high single dose of 50 Gy [136]. Moreover, celecoxib was also found to alleviate radiation-induced brain injury by maintaining the integrity of the BBB (blood-brain barrier) and reducing the inflammation in the rat brain tissues by inhibition of apoptosis in vascular endothelial cells [143]. RIVAD018 is another selective COX-2i which adds to its anti-inflammatory effects the ability to exert antioxidant activity, preventing oxidation of low-density lipoproteins, showing protection on both cellular and vascular models [144]."}
{"_id": "Radiology$$$7d000413-45b6-47bd-a952-b2b11e41ee05", "text": "Several studies have also described that overexpression of COX-2 in cancer cells results in increased tumor angiogenesis, growth, and metastasis; thus, several COX-2 inhibitors have been described as radiosensitizers [136]. Celecoxib restricts neoangiogenesis, leading to a reduction in the survival of hepatocarcinoma and lung and skin cancer cells. In glioblastoma cells, the combined effect of radiation and celecoxib increased tumor cell necrosis, showing a significant reduction in tumor microvascular density compared to irradiation alone [139]."}
{"_id": "Radiology$$$46c2b54e-af90-44cb-8b8c-2aa88be7ac3d", "text": "Radiation exposure of skin with high doses (>20\u00a0Gy) results in erythema, blistering, and necrosis in sequence. The necrosis generally occurs 10\u201330\u00a0days after exposure, although it may appear earlier in the most severe cases. The earliest administration of systemic and topical anti-inflammatory agents reduces the need for surgical excision of the affected tissue. Current therapy might make use of transplanted autologous keratinocytes combined with allogeneic stem cells. Advances in the knowledge of the radiomitigating properties of these compounds may prove to be very useful, particularly for the relatively low cost and toxicity, and specially for their analgesic effects [139]."}
{"_id": "Radiology$$$8c41f627-173b-4667-a5f5-5aff3130b28e", "text": "Steroidal anti-inflammatory drugs such as dexamethasone can be administered after radiation exposure to attenuate fever and inflammatory or pain symptoms or to treat acute pathologies such as pneumonitis. Some authors reported that dexamethasone administration prior or immediately after radiation exposure reduced the risk of cardiac and other tissue fibrosis. Moreover, dexamethasone is often used to manage the inflammatory response in the brain during RT treatment of glioblastoma and other intracranial tumors. The effects of dexamethasone on patient survival however remain controversial because several clinical studies suggest that dexamethasone could potentially restrict effective RT [145]."}
{"_id": "Radiology$$$0cebcbd2-163d-4176-a484-0f637068aa96", "text": "Pathologically, acute intestinal epithelium damage is described as dilatation or destruction of crypt cells, decrease in villous height and number, ulceration, severe mucosal and submucosal inflammation, and sepsis associated with a pathogen bacterial translocation. Because of the rapid turnover of intestinal mucosa, the acute-phase symptoms (nausea, vomiting, diarrhea, abdominal pain, and acute mucositis) persist for hours to several months, while other intestinal complications such as obliterative vasculitis, mucosal ulceration, bowel wall thickening or progressive interstitial fibrosis, bowel obstruction, and fistulae formation, with or without fecal incontinence, are late events, often associated with chronic radiation exposition [146]. The reported incidence of severe late chronic radiation enteritis varies between 5 and 15% of patients treated with pelvic RT."}
{"_id": "Radiology$$$dff59177-cc07-48e3-8cba-106362d936b1", "text": "Probiotics, prebiotics, and FMT target intestinal microbiota by inhibiting colonization of pathogenic bacteria and restoring microbiome normobiosis. They increase production of mucin in the intestinal epithelial cells and expression of tight junction protein and occludin, thereby enhancing mucus layer function and improving survival of intestinal crypts\u00a0(Fig. 11.16).\u00a0\n\nAn illustration of the effect of probiotics, prebiotics, and fecal microbiota transplantation. The effects include inhibition, restoration, enhancement, reduction, increase, decrease, release, and recruitment.\n\nFig. 11.16\nEffect of probiotics, prebiotics, and FMT on the function of the intestinal epithelium and gut microbiome"}
{"_id": "Radiology$$$3fdaff19-8c8c-4fa4-a1cf-98685d7948a6", "text": "An illustration of the effect of probiotics, prebiotics, and fecal microbiota transplantation. The effects include inhibition, restoration, enhancement, reduction, increase, decrease, release, and recruitment."}
{"_id": "Radiology$$$39fc999a-29de-4fc0-aabe-8d3212d811a3", "text": "A diverse and healthy commensal intestinal microbiota plays an essential role in GI homeostasis. It has been found that postirradiation enteropathy is associated with low mucosal microbiota diversity, in particular, a decrease of Lactobacillus and Bifidobacterium spp. and an increase in the relative abundance of opportunistic pathogens. Gut microbiota dysbiosis aggravates radiation enteritis, reduces the absorbing surface of intestinal epithelial cells, weakens intestinal epithelial barrier function, promotes intestinal inflammation, and contributes to the development of mucositis, leading to a persistent diarrhea and bacteremia [147]. Correction of the microbiome by application of probiotics, prebiotics, FMT, and/or antibiotics helps to prevent and treat radiation-induced enteritis [148]."}
{"_id": "Radiology$$$bc3b65c4-8c77-4230-aacb-584c68e6042e", "text": "Probiotics are live microorganisms, added to aliments, that have a beneficial role in reducing pathogenic bacteria multiplying without competitors, promoting intestinal immune barrier function, and preventing translocation of harmful bacteria. Preparations containing Bifidobacterium, Lactobacillus, and Streptococcus ameliorated radiation-induced gut toxicity, reducing the incidence of diarrhea, and delaying the necessity for rescue treatment with loperamide [147]. Randomized controlled trial evidenced that live Lactobacillus acidophilus plus Bifidobacterium bifidum treatment reduced the incidence of radiation-induced diarrhea and the need for antidiarrheal medication and had a significant benefit on stool consistency [149]. The anti-inflammatory effect of probiotics has been shown in other pathologies such as ulcerative colitis and Crohn\u2019s disease. The administration of Lactobacillus spp. decreased levels of different colonic inflammatory cytokines such as IL-6, TNF-\u03b1, or NF-\u03baB p65 and recruitment of leukocytes to the colonic mucosa. In mice model, administration of Lactobacillus rhamnosus increased the crypts survival in radiation-induced enteritis by approximately twofold and reduced epithelial cell apoptosis, which depends on intact TLR2 and COX-2 inhibition in mesenchymal stem cells of crypt [150]. Genetically engineered species of Lactobacillus plantarum and Lactococcus lactis release SOD inducing anti-inflammatory effects and attenuation of enteritis symptoms [151]. Increased production of short-chain fatty acids is one of the most important probiotic protective effects implicated in GI and hematopoietic tissue protection and increased survival of irradiated mice [152]. Several clinical trials seem to indicate that probiotics reduce the incidence of radiotherapy-induced mucositis [148], even though results are difficult to evaluate, as they vary in the type of cancer patients recruited, radiotherapy modalities used, and type of bacteria used as probiotic [146]. In this regard, choosing the right probiotic can be crucial, and a recently published systematic review concludes that a combination of Bifidobacterium longum, Lactobacillus acidophilus, Bifidobacterium breve, Bifidobacterium infantis, and Saccharomyces boulardii could be a good combination of probiotics to reduce incident rates of mucositis or ameliorate its symptoms in chemo- or radiotherapy-treated patients [153]."}
{"_id": "Radiology$$$b22b43d1-7dc5-489c-8abd-38e5269be057", "text": "Prebiotics offer a source of enrichment to the microbiome, and dietary interventions have demonstrated to reduce the severity of inflammatory intestinal pathologies and thus can potentially serve as a radiomitigative strategy. In fact, a clinical trial (NCT01549782) evidenced that increased consumption of certain prebiotics (fiber and plant sugars) was associated with a reduction in days of diarrhea and improved quality of life for irradiated patients [154]."}
{"_id": "Radiology$$$1c00393b-cb13-4513-a3b6-2e88fde83968", "text": "FMT increased the survival rate, elevated peripheral white blood cell counts, and alleviated GI toxicities and intestinal epithelial integrity in irradiated mice [155]. Radiation-induced intestinal edema was strikingly alleviated after 8\u00a0weeks of FMT of gut microbes from healthy donors, enhancing beneficial bacteria such as Alistipes, Phascolarctobacterium, Streptococcus, and Bacteroides recovery, whereas the abundance of Faecalibacterium decreased. FMT can reduce the intestinal leakage and enhance the intestinal functions and epithelial integrity in patients with chronic radiation enteritis [156]."}
{"_id": "Radiology$$$c5da2b1c-3e9c-40a2-8e60-261ff6739551", "text": "Researchers have long known that administering antibiotics to irradiated animals can enhance survival by avoiding opportunistic infections. As previously have been exposed, antibiotics such as fluoroquinolones and ciprofloxacin also have the advantage of reducing radiation damage to hematopoietic progenitor cells. Antibiotic cocktail and metronidazole pretreatment are beneficial to the reconstruction of gut microbes in irradiated mice. Abx pretreatment regulates macrophage polarization in the ileum and downregulates the expression of TGF-\u03b21, thereby preventing intestinal fibrosis and ultimately improving the survival of mice with radiation-induced intestinal injury [157]."}
{"_id": "Radiology$$$78861cc3-66c7-4e5b-af5b-06e91a596256", "text": "Radiation nephropathy has emerged as a significant complication in RT and is a potential sequela of radiological terrorism and radiation accidents. The use of a high-salt diet in the immediate post-irradiation period significantly decreases renal injury but is deleterious for the treatment of established disease. FDA-approved drugs that modify the renin-angiotensin system are habitually used for the treatment of hypertension and cardiac and/or renal insufficiency. ACEIs constrain angiotensin-converting enzyme (ACEs) and reduce the formation of angiotensin II (AII). Angiotensin receptor blockers (ARBs) impede the function of the angiotensin AT1 or AT2 receptors and decrease the actions of AII."}
{"_id": "Radiology$$$1c70336c-3a56-4341-a4b5-581b22549ed7", "text": "The efficacy of ACEIs and ARBs has also been long studied for their effects in radiation protection, modulation, or mitigation (Fig. 11.17). Clinical trials have evidenced the potential of ACE inhibitors to reduce radiation-induced pneumonitis and fibrosis (enalapril, NCT01754909, www.\u200bclinicaltrials.\u200bgov).\n\nAn illustration of the release of different receptors and their roles. Angiotensinogen with renin releases angiotensin 1, which releases angiotensin 2, and angiotensin 1 to 7. Angiotensin 2 releases types 1 and 2 receptors and angiotensin 1 to 7, which in turn releases M A S receptor.\n\nFig. 11.17\nRole of ACEIs, ARBs, and renin inhibitors in the renin\u2013angiotensin system"}
{"_id": "Radiology$$$ca3b87e0-036f-4bea-b8d1-e5323ed7a57d", "text": "An illustration of the release of different receptors and their roles. Angiotensinogen with renin releases angiotensin 1, which releases angiotensin 2, and angiotensin 1 to 7. Angiotensin 2 releases types 1 and 2 receptors and angiotensin 1 to 7, which in turn releases M A S receptor."}
{"_id": "Radiology$$$2848a7eb-0dd7-4531-a279-91172fd22931", "text": "Results of a recent meta-analysis review evidenced that the use of ACEIs, but not ARBs, effectively reduced the incidence of radiation pneumonitis in most lung cancer patients. That has important clinical implications because lung cancer patients receiving thoracic radiation could take an appropriate dose of ACEIs to prevent radiation-induced pneumonitis, during or after the period of RT, which would greatly improve the quality of life and therapeutic effect. By contrast, even the most expensive ARBs were ineffective [158]."}
{"_id": "Radiology$$$39f55bd7-8197-4497-9227-792c39180c21", "text": "Five different ACEIs (captopril, lisinopril, enalapril, ramipril, and fosinopril), at clinically relevant doses, have been examined for efficacy as mitigators of radiation-induced nephropathy. Overall, survival in rats is higher after an 11\u201312 Gy TBI when treated with any of the ACEIs captopril, enalapril, or fosinopril starting 1\u00a0week postirradiation [159]. All, except fosinopril, effectively abrogated radiation nephropathy, with captopril being the most effective [160]."}
{"_id": "Radiology$$$26b04f7b-4032-4985-a19f-16601956e841", "text": "Captopril treatment increased survival from thoracic irradiation to 75% compared with 0% survival in vehicle-treated animals, and suppression of inflammation and senescence markers, combined with an increase of anti-inflammatory factors, was part of the mechanism involved in its therapeutic effects [161]. Captopril reduced radiation-induced cytokines EPO, G-CSF, and SAA (Non-invasive serum amyloid A) in the plasma, mitigated brain microhemorrhage at 21\u00a0days postirradiation, and increased EPO levels postirradiation if started prior to radiation exposure. These data suggest that captopril may be an ideal countermeasure to mitigate H-ARS following accidental radiation exposure [162]. A trial of captopril in patients receiving TBI demonstrated not only safety, but also efficacy against renal and pulmonary injury [163]. Moreover, prophylactic administration of captopril reduced radiation-induced hypertension and renal failure and mitigated pulmonary endothelial dysfunction and radiation-induced pneumonitis and fibrosis. The isoflavone genistein appears to work synergistically with captopril, improving the 30-day survival in mice receiving both drugs from 0 to 95% after 8.25 Gy TBI. The combination therapy reduced anemia and increased the number of circulating hematopoietic cells [164]."}
{"_id": "Radiology$$$ff2a2b0b-bf3d-45a4-908d-a15743317ccd", "text": "In murine models, administration of AT1 receptor antagonist before, during, and after fractionated whole-brain irradiation prevented or reduced cognitive impairment. It is also hypothesized that ARBs may attenuate radiation-induced brain injury by increasing the generation of anti-inflammatory peptide, angiotensin (1\u20137). ACEI or AT1 antagonist treatment in hypertensive patients increases blood levels of angiotensin (1\u20137); prevents oxidative stress, inflammatory cytokine release, and fibrotic events; and also has anticarcinogenic effects, thus having radiomitigating potential as it has been evidenced recently [165]."}
{"_id": "Radiology$$$36967a7d-9fea-4d9a-a549-d7ab09a8c3da", "text": "While other types of antihypertensive drugs are ineffective, ACEIs and AII receptor antagonist type I are effective in the mitigation of radiation damages. Moreover, some of them also exhibit antitumor effects; thus, there is a strong case for the clinical use of these agents in the treatment of radiation-induced late effects."}
{"_id": "Radiology$$$453ed73f-a5b1-4999-a837-fe2e21fba592", "text": "The incidence of cardiovascular disease was observed in the atomic bomb survivors, and cardiovascular disease is a known side effect of radiation therapy [166]. Statins (simvastatin, lovastatin, pravastatin, and others) are inhibitors of the 3-hydroxy-3-methylglutaryl coenzyme A reductase, which is a rate-limiting enzyme for the synthesis of cholesterol and serves to upregulate low-density lipoprotein (LDL) synthesis. Therefore, statins are clinically used to reduce LDL levels in the blood and, consequently, to treat atherosclerosis and hypercholesterolemia. Statins also strongly induce thrombomodulin (TM) expression, which in turn forms a complex with thrombin. Thrombin-TM complexes activate protein C, which has anti-inflammatory, anticoagulant, and antioxidant properties. All these beneficial effects may help to attenuating radiation injuries [167]."}
{"_id": "Radiology$$$940e3b6d-f6f9-4406-a842-e28ba987e5b2", "text": "Radiation exposure (5 Gy X-rays) increased cholesterol levels, and those were reduced by simvastatin treatment [168]. Simvastatin treatment (20\u00a0mg/kg/d over 2\u00a0weeks) mitigates, to a limited extent, radiation-induced enteric injury (4\u20138\u00a0Gy), as evidenced by improved structural integrity of the mucosa, reduced neutrophil infiltration, decreased thickening of the intestinal wall, and reduced accumulation of collagen I in jejunum and bone marrow in male C57BL/6J mice [169]. Simvastatin also prevented radiation-induced marrow adipogenesis and provided radioprotection to the niche cells [170], and attenuated radiation-induced salivary gland dysfunction in mice [171]. Pathak et al. [167] demonstrated that a single subcutaneous dose of \u03b3-tocotrienol (GT3) rescues mice from lethal radiation doses, and combined treatment (GT3\u00a0+\u00a0simvastatin) provides substantial protection against radiation-induced lethality, hematopoietic injury, and bone marrow damage compared to the single treatment."}
{"_id": "Radiology$$$813cf470-0e56-4b33-80bc-84f67098892d", "text": "A combination of statin and ACEI agents has shown efficacy in reducing GI toxicity in patients receiving pelvic RT [172]. Lovastatin treatment of irradiated mice (15 Gy whole-lung irradiation), starting immediately after irradiation or 8\u00a0weeks post-irradiation (three times a week), demonstrated a reduction in lung tissue lymphocytes and macrophages, decreased collagen content, prevented lung fibrosis, and improved rates of survival [173]."}
{"_id": "Radiology$$$f24ce93a-2e29-4948-aaf5-a9c278f879bb", "text": "Pravastatin (30\u00a0mg/kg body weight given 4\u00a0h before irradiation) protected the normal intestine and lung tissues from radiation. The radiomitigating effect of pravastatin was associated with a reduction in the level of radiation-induced DNA DSB. The pravastatin-treated group showed a significantly lower apoptotic index of the lung and intestinal epithelial cells and reduced the intestinal expression of ataxia-telangiectasia mutated and \u03b3-H2A histone family member X (H2AX) after irradiation [174]. Statins are generally well tolerated, and their effect was pronounced for delayed radiation injury and for that reason shows potential as radiomitigators."}
{"_id": "Radiology$$$4181b105-b371-4f76-a969-9bce50cfdc9f", "text": "Long et al. [175] demonstrated that chimeric protein dTMP-GH, a tandem dimer formed by thrombopoietin mimetic peptide and GH treatment, increased survival in mice exposed to 60Co \u03b3-ray photons (6\u00a0Gy). Meanwhile, dTMP-GH treatment accelerated the recovery of bone marrow hematopoiesis, promoted skin wound closure, and mitigated ileum injury. Zinc sulfate and GH administration prevented radiation-induced dermatitis in rats [176], and increased GH/IGF1 levels also reduced radio-induced intestinal epithelial cell apoptosis preserving, in the short term, the efficacy of RT on tumors [177]. GH significantly restored follicular development and preserved fertility in female rats exposed to a single TBI of 3.2 Gy [178]. However, in oncology, GH and IGF1 reduce the effectiveness of RT and may frequently cause metastasis and cancer recurrence. Therefore, even if GH/IGF-derived radiomitigative effects are confirmed, further studies of these hormonal treatments would be necessary before translating the results to human clinical trials."}
{"_id": "Radiology$$$a8a289f9-9f4a-47ae-a0c1-806cc0f68248", "text": "Hydrogen\u00a0can mitigate IR damages through various mechanisms [122, 123]: (a) directly neutralizes hydroxyl radicals and peroxynitrite [179]; (b) indirectly reduces oxidative stress, by upregulating the expression of different endogenous antioxidant enzymes, i.e., SOD, CAT, and GPx; and (c) shows antiapoptotic and anti-inflammatory properties [180]. H2 reduces 8-hydroxy-2\u2032-deoxyguanosine and malondialdehyde levels and increases SOD activity and GSH levels.These findings suggest that the radioprotective effect of H2 is largely due to the inhibition of oxidative stress.\u00a0In that sense, H2 has demonstrated in vitro radioprotective effects in cells especially sensitive to IR, such as intestinal epithelial cells, hematopoietic precursors, and spermatogonia [180] these protective effect of H2 are not significant when it is administered after radiation [181]."}
{"_id": "Radiology$$$fed08b41-4be2-4afe-a46d-554d1cf91e1e", "text": "Shin et al. [182] observed that application of H (H2O) to human skin prevented UV-induced erythema and DNA damage,\u00a0administered even after exposure to RI. Although a lot of in vitro and in vivo research has been done to investigate the potential use\u00a0of H2 as a radiomitigator, there are scarce clinical data. Kang et al. [183] performed a placebo-controlled, randomized study to evaluate the validity of ingesting hydrogen-rich water in 49 patients with malignant liver tumors, while they were receiving RT at the same time. Patients drinking H2-rich water had considerably higher quality of life (QOL) scores, notably less appetite loss, and much fewer tasting disorders than patients drinking placebo water, and most importantly, no differences were found in tumor response to RT comparing both groups of patients [183]. In cancer patients, H2 has also shown protective effects against brain, lung, and myocardial injury associated with RT, furthermore preventing side effects like anorexia, taste disorders, or bone marrow damage without compromising the antitumor effects of the treatment [180]."}
{"_id": "Radiology$$$e42b1870-a6d4-41c4-be4f-b3221406c207", "text": "The use of H2 is feasible in the clinical practice because it is stable at normal temperatures; it can be easily administered through various routes such as inhalation, drinking, injection, etc. (Fig. 11.18); it can even cross the blood-brain barrier; has a very favorable tolerability profile; and it shows great efficacy as a potential radioprotective agent [122, 123]. Although the human body does not have the enzymes necessary to produce H2, the colonic microbiota can produce about 12 L of H2 per day under physiological conditions. Many results support the idea that upregulation of H2 gas produced by intestinal bacteria could be used as a valid treatment strategy for various diseases. Since there are several methods to supply external H2, it can be easily administered with little or no adverse effects.\n\nAn illustration of different ways of delivering molecular hydrogen, H 2, to different body parts. Eyes through Eye drops. Bone marrow and cardiovascular system through Injection. Intestine through Drinking. Skin through Bathing. Lungs through Inhalation.\n\nFig. 11.18\nDelivery of hydrogen and its protective and therapeutic opportunities in various systems. Adapted from \u201cMolecular hydrogen: A potential radioprotective agent,\u201d by Hu et al. [122, 123], Licensed under CC BY 4.\u200b0"}
{"_id": "Radiology$$$15bff2d2-db4f-408a-9b41-2675ef0c3373", "text": "An illustration of different ways of delivering molecular hydrogen, H 2, to different body parts. Eyes through Eye drops. Bone marrow and cardiovascular system through Injection. Intestine through Drinking. Skin through Bathing. Lungs through Inhalation."}
{"_id": "Radiology$$$a932b28b-6808-432c-a568-6fb5c35a7683", "text": "1-Methyl nicotinamide (MNA), a derivative of vitamin B3, significantly prolonged survival of mice irradiated at LD30/30 (6.5\u00a0Gy), LD50/30 (7.0\u00a0Gy), or LD80/30 (7.5\u00a0Gy) of \u03b3-rays when the MNA administration started as late as 7\u00a0days post-irradiation. Another vitamin B3 derivative, 1-methyl-3-acetylpyridine, was slightly less efficient when it was administered after 7.5 Gy \u03b3-ray exposition. These prosurvival effects might be related to the anti-inflammatory and/or antithrombotic properties of the vitamin B3 derivatives and do not seem to be mediated by stimulation of hematopoiesis. These results show that MNA may represent a prototype of a radiomitigator because it reduces the severity and/or progression of radiation-induced injuries when applied several hours or days after exposure to high doses of IR [184]."}
{"_id": "Radiology$$$379b61cb-c02c-4735-8a0a-4ef2f9e3843a", "text": "After various radiological and nuclear incidents, radioactive materials (radionuclides) may be released in the atmosphere where they could be either inhaled as gas, ingested as particulates, or absorbed through intact skin or subcutaneous tissue [185]."}
{"_id": "Radiology$$$d83f140e-61a0-4376-9472-b9e8a58a193d", "text": "The medical consequences of internal contamination are determined primarily by radiation dose and radiation quality. Deleterious effects include dose-dependent deterministic (i.e., predictable) effects; stochastic (i.e., random) effects such as cancer in tissues where radionuclides are retained for prolonged times, and at a sufficiently high quantity of contamination; multiorgan failure; and death. The radiation quality or specific radionuclide(s) has (have) a characteristic emitted energy (alpha, beta, or gamma/X-ray), solubility, radioactive half-life, and biological half-life, which is determined by the time required for a compartment, defined by a body organ or tissue or part of an organ or tissue (see Fig. 11.19) to eliminate half of its radionuclide content. The particle size and chemical composition of the radioactive material impact the site of deposition within the body and route of elimination. Finally, comorbidities such as renal insufficiency, hepatic failure, and pulmonary disorders may impair pathways needed for radionuclide elimination from the body, thereby prolonging exposure [186].\n\nAn illustration of arrows pointing from the transfer compartment to the respiratory tract, liver, gastrointestinal tract, kidney, subcutaneous tissue, lymph nodes, and other organs.\n\nFig. 11.19\nBiological compartments for radionuclide intake and distribution. Reproduced from Dainiak N and Albanese J, Assessment and clinical management of internal contamination, JRP, 2022, in press, and modified from ICRP, 2015, Occupational Intakes of Radionuclides: Part 1. ICRP Publication 130. Ann. ICRP 44(2)"}
{"_id": "Radiology$$$a4ab9262-d06b-42eb-b4c4-7a91276cc35e", "text": "An illustration of arrows pointing from the transfer compartment to the respiratory tract, liver, gastrointestinal tract, kidney, subcutaneous tissue, lymph nodes, and other organs."}
{"_id": "Radiology$$$ec109e76-8fc7-4340-af55-933453694fef", "text": "The\u00a0internal contamination with radionuclides involves four\u00a0metabolic phases:1.\nIntake (incorporation)\n\u00a02.\nUptake (absorption into the circulatory system)\n\u00a03.\nRetention (deposition)\n\u00a04.\nExcretion (decorporation)"}
{"_id": "Radiology$$$7f82bcb4-719f-4ee9-8dc7-6b7ea4d7a6d0", "text": "The excretion of these radionuclides by natural processes can be accelerated using decorporation therapies. This consists of enhancing the action of biological processes through chemical or biological agents, thereby facilitating radionuclide elimination. In the event that radionuclides have been incorporated internally, the objective of the therapy is to reduce the internal dose and thus the risk of biological effects on health. This can be achieved by preventing the incorporation, reducing the absorption and internal deposit of radionuclides, and also promoting their excretion. The decorporation process may have adverse side effects. Therefore, these therapies must be based on risk criteria and applied as soon as possible."}
{"_id": "Radiology$$$c9375e99-8bd6-4ad5-81a8-9778e26c6acf", "text": "The general procedures are intended to reduce or inhibit the absorption of radionuclides from the GI system, the respiratory tract, or the skin and wounds (Fig. 11.19). Some examples of general procedures are the use of emetics, gastric lavage, laxatives, gastric alkalinization, and irrigation if there are wounds, especially in an emergency scenario. The use of specific drugs to impede the deposition of radionuclides (decorporation agents) in organs or tissues could avoid accumulation and retention of radionuclides and, obviously, is more effective if treatment is started immediately after internal contamination. Decorporation agents can reduce radionuclide absorption, entry, and deposit in organs and tissues and/or accelerate its excretion, finally minimizing the absorbed dose."}
{"_id": "Radiology$$$08d4530d-750f-4f81-b991-beb348615c0e", "text": "Blocking agents work by reducing the absorption of the radionuclide in the body, since they saturate tissues, organs, and metabolic processes using a stable isotope (identical to the nonradioactive element). Among these agents, the best known is potassium iodide (KI), used to prevent the deposit in the thyroid gland of radioactive iodine delivered to the atmosphere as a result of uncontrolled nuclear accident, which can lead to an increased risk of developing thyroid cancers, particularly in infants and young children [187]. KI prevents binding of radioiodine by three mechanisms: a) it will dilute the radioiodine circulating inside the body and available for thyroid uptake; b) it will saturate the active transport mechanism of iodine mediated by the sodium iodine symporter (NIS); and c) it will inhibit the organification of iodine, also called Wolff-Chaikoff phenomenon, a mechanism that could lead to a decrease in the synthesis of thyroid hormones and a possible hypothyroidism; but this effect is usually of short duration. This measure only protects the thyroid from radioactive iodine, not other parts of the body."}
{"_id": "Radiology$$$71f13903-6f74-4cea-b93c-3cd7d1318714", "text": "Pharmacologic thyroid blockade by oral KI (50\u2013100 mg in adults) can substantially reduce radioiodine\u00a0thyroid uptake and was one of the first and urgent protective actions recommended\u00a0by the World Health Organization (WHO) (1960\u20131970s)."}
{"_id": "Radiology$$$1e95f2bd-5b68-4dd3-8285-9d83d0698af0", "text": "The recommendations adopted for iodine prophylaxis, in particular those regarding the administration timing, the iodine quantity to be given, and the possible side effects occurring as a result of this measure, are included in the Guide [188]. Although stable iodine is usually considered as the standard for thyroid protection against radioiodine [189], perchlorate can be considered as an alternative, provided that it is administered at equi-effective dosages (1000 mg perchlorate is as effective as 100 mg stable iodine in the aftermath of an acute radioiodine exposure). Perchlorate also protects the thyroid by competition with radioiodine at the NI-symporter site. Considering its simpler protective mechanism and potential advantages in particularly vulnerable subpopulations and its acceptable adverse effects, it seems promising for future studies to focus more closely on perchlorate as an alternative to stable iodine for thyroid protection against radioiodine [187]."}
{"_id": "Radiology$$$cd8c454e-fb84-447e-b6c5-4338d2b6195d", "text": "Absorption is defined as a movement of material that reaches the blood regardless of the mechanism. This generally applies to the entrance in the bloodstream of soluble substances and material dissociated from particles (NCRP 161)."}
{"_id": "Radiology$$$a0ae3092-7e93-4b0e-a71d-f7f5c5834e95", "text": "Prussian blue, a nonabsorbable resin (approved by the FDA), acts as a laxative agent that promotes the fecal elimination of ingested radiocesium and thallium. The most effective form of this compound is its colloidal soluble form. This compound was used in the Goi\u00e2nia accident extensively and successfully for the decorporation of 137Cs. Different silica-based materials have also been tested to capture various radionuclides of plutonium, americium, uranium, and thorium [190]."}
{"_id": "Radiology$$$cfea8787-9cda-4b9a-b142-a5674626285f", "text": "Natural products have also been used to reduce the absorption of radionuclides. An example is that orally administered Chlorella algae inhibited the absorption of strontium (90Sr) into the blood and enhanced its fecal elimination [191]."}
{"_id": "Radiology$$$2ad467bc-8476-482d-aab3-86b66bfa11b7", "text": "Increasing the intake of liquids, such as water, milk, and tea, or intravenous administration of isotonic saline solution, is a rapid method to increase the excretion of soluble radionuclides. This would be the case of tritium, where ingestion of sufficient liquids reduces the time of permanence in the body [192]."}
{"_id": "Radiology$$$15430d6b-b8ac-4197-b0d9-8f2bc1c12e37", "text": "Displacement shares the same principle as dilution and blocking therapies. However, in this specific case, an element is used that has a different atomic number. Thereby, that element will compete for internal scavenging sites, displacing the radioisotope from a receptor/target. Calcium gluconate, for example, competes with radiostrontium in bone deposition, or stable iodine, which displaces technetium-99m [193]."}
{"_id": "Radiology$$$ac132f59-e081-4f47-8235-1b94677073a2", "text": "This method consists of increasing the natural renewal process of the release of radionuclides from organs and tissues, thus reducing deposition and improving the elimination rate by diuresis. As an example, ammonium chloride, which if administered orally, lowers the pH of the blood and increases the elimination of radiostrontium once internalized. Or the use of sodium bicarbonate increases the pH of the blood and favors the removal of uranium [194]."}
{"_id": "Radiology$$$27ad2c70-b8e4-433e-81af-bd06cb726d21", "text": "Chelating agents are classified as organic or inorganic agents capable of binding to metal ions and forming complex ring structures, known as \u201cchelates.\u201d These agents possess atoms of union or \u201cligands\u201d that generally form covalent bonds and facilitate the excretion by the kidneys or other organs [186]."}
{"_id": "Radiology$$$58d8bda5-267e-4635-811d-bc497987ac50", "text": "Some examples of this method are the one used to facilitate the elimination of plutonium complexes by the kidneys and the GI. DTPA (diethylenetriaminepentaacetic acid with calcium or zinc) is the chelator with the widest range of potential use [186]. Other chelators commonly used are dimercaptosuccinic acid, dimercaprol, and deferoxamine. Different silica-based materials (such as isomers of diphosphonic acid, hydroxypyridinone, acetamide phosphonic acid, DTPA, and glycinyl-urea) have also been tested to capture various radionuclides of plutonium, americium, uranium, and thorium [190]. Importantly, factors that can potentially affect the stability of any chelating agent must always be taken into account, i.e., (but not limited to) acidity and alkalinity, chemical properties of the agent, its selectivity, and concentration of competing metals."}
{"_id": "Radiology$$$2db08a0d-9543-4309-ab0b-1cbeab53ae43", "text": "Internal contamination with actinides, whether by inhalation, ingestion, or injuries, represents a serious risk to the health. Some guidelines to assist physicians or other professionals in treating workers or members of the public who may suffer internal contamination with compounds such as plutonium tributyl phosphate, plutonium nitrate, americium oxide, or nitrate can be found in [195]."}
{"_id": "Radiology$$$51483939-2475-4e0b-8c2d-74984e873363", "text": "The use of these types of agents is most effective when administered immediately after exposure to radiation because the radionuclides are still circulating in the body and may not yet have deposited in target organs or cells (liver and bone are examples of preferred targets)."}
{"_id": "Radiology$$$b18547ba-3748-409d-a52a-b1c137573a43", "text": "This method is used for the elimination of a fixed radionuclide contaminant in the body. The surgery must be evaluated carefully, taking into account risks and benefits, and must be carried out with the support and collaboration of radiation protection staff [196]."}
{"_id": "Radiology$$$ee10ce7b-de9c-4639-ab3e-09d5db061087", "text": "Occasionally, debridement and excision of the wound may be necessary in order to remove the fixed contamination. It is important that a well-established evaluation is carried out by specialized personnel to support the medical decision, considering the benefits and risks of the surgical procedure. When surgical exploration is necessary, as well as the removal of tissue/foreign material, it should be performed with the help of a radiation protection professional, a radiophysicist who uses a specific probe for wounds. Once the surgical material has been removed, it should be saved for subsequent radioanalysis. There are no contraindications regarding the use of local anesthetics or systemic anesthetic agents."}
{"_id": "Radiology$$$3ce3c7e8-100b-4eb3-be32-de21c0f98db0", "text": "Lung lavage is an invasive medical procedure that involves the same risks as general anesthesia and is only indicated for a limited number of cases. The parameters that are taken into account are the patient\u2019s age, clinical status, existence of comorbidities, radiotoxicity of the contaminant, and dose."}
{"_id": "Radiology$$$da212022-91a4-4fff-9737-0071ebc819c8", "text": "This technique will only be used after a meticulous medical and dosimetric evaluation, and in case inhaled and insoluble radioactive particles (plutonium for example) are deposited in the lungs. Other isotopes and focal accumulation are depicted in Fig. 11.20. A flexible bronchoscopy should be performed to enhance bronchoalveolar lavage [197]. This type of bronchoscopy should be performed only if the lung load is high and incorporates a large amount of insoluble inhaled particles, such as alpha particles (\u03b1).\n\nAn illustration of isotopes in different parts of the body. Lungs: A m, P u, P o. Lymph nodes: P o. Kidney: C o, P o, U. Ovaries and testicles: P u. Thyroid gland: I. Liver: A m, C f, C o, P u, P o. Spleen: I r, P o. Bone marrow: A m, P u, P, P o. Bone: A m, C f, C u, P, P u, R a, S e, T h, U, Y.\n\nFig. 11.20\nIsotopes and focal accumulation in the body"}
{"_id": "Radiology$$$074f05ba-1ecb-40b4-8bdb-519de2ec70c9", "text": "An illustration of isotopes in different parts of the body. Lungs: A m, P u, P o. Lymph nodes: P o. Kidney: C o, P o, U. Ovaries and testicles: P u. Thyroid gland: I. Liver: A m, C f, C o, P u, P o. Spleen: I r, P o. Bone marrow: A m, P u, P, P o. Bone: A m, C f, C u, P, P u, R a, S e, T h, U, Y."}
{"_id": "Radiology$$$8a72104d-0e58-478a-811c-1efae023d43c", "text": "The objective of this procedure is to avoid deterministic effects for pulmonary doses above 6\u00a0Gy-equivalents (Gy-Eq) and is stochastic when the committed doses are lower in the lung. All this within a period of 30\u00a0days and individualized for each case."}
{"_id": "Radiology$$$b96ba319-4e2d-4228-b632-cc81343d439e", "text": "The Clinical Decision Guide (CDG) and the IAEA EPR 2018 Guide provide bases that can be used by healthcare providers to treat cases where radionuclides have been deposited internally as explained above. Both guides are useful for medical management of individuals contaminated with radionuclides as a consequence of a nuclear or radiological emergency, or due to an industrial scintigraphy accident, or in patients undergoing treatments with radionuclides."}
{"_id": "Radiology$$$b5c44a23-e38c-477d-a94c-f36941a6ecf9", "text": "Radiotherapy (RT) is a treatment that uses high doses of radiation to kill cancer cells and shrink tumors. Radiosensitizers are chemicals or pharmaceutical agents that increase the cytotoxic effect of IR on cancer cells by accelerating DNA damage and producing free radicals, suppressing the antioxidant mechanism of defenses, or inhibiting the repair of biomolecules, among others. In most cases, radiosensitizers have less effect on normal cells; however, some can also be administered after radiation exposure to treat or reduce the late side effects to healthy tissue. The effectiveness of potential radiosensitizers is measured in terms of the enhancement ratio (ER) (Box 11.4):"}
{"_id": "Radiology$$$9e05886d-c1cb-426c-9811-878ff7866477", "text": "Radiosensitizers specifically target tumor cells and make them more\u00a0susceptible to IR during RT.\n\nThese therapeutic compounds apparently enhance the radiation-induced damage to cancer cells at the molecular level and may also further limit the harmful effects of radiation on normal tissue.\n\nRadiosensitizing agents promote fixation of free radicals by their electron affinity, rendering the molecules incapable of repair.\n\nTheir mechanism of action is comparable to the oxygen effect, as biochemical reactions of the damaged molecules preclude the repair of cellular damage."}
{"_id": "Radiology$$$4cd1b876-82b2-4e49-b9c4-929d98c22f60", "text": "Radiosensitizers specifically target tumor cells and make them more\u00a0susceptible to IR during RT."}
{"_id": "Radiology$$$1f7860de-8ec2-41f0-acdd-e6c61cac6d09", "text": "These therapeutic compounds apparently enhance the radiation-induced damage to cancer cells at the molecular level and may also further limit the harmful effects of radiation on normal tissue."}
{"_id": "Radiology$$$dbb0105c-2659-473e-ab59-9e18e0fb50cb", "text": "Radiosensitizing agents promote fixation of free radicals by their electron affinity, rendering the molecules incapable of repair."}
{"_id": "Radiology$$$eaba12a2-9594-4783-a69d-49fff2672cae", "text": "Their mechanism of action is comparable to the oxygen effect, as biochemical reactions of the damaged molecules preclude the repair of cellular damage."}
{"_id": "Radiology$$$a1a50431-5b6e-4775-a115-90b1aa226b8d", "text": "For use as an adjunct in RT, an ideal radiosensitizer should not be harmful to healthy tissues and not interfere with other therapies, as well as should be highly efficient on tumor and hypoxic cells. It should also be economically affordable."}
{"_id": "Radiology$$$0e501c30-a825-4201-ba21-f2f4f21fa278", "text": "A radiosensitizer should be nontoxic and should produce an advantage in enlarging the therapeutic window, increasing tumor control probability, and limiting the normal tissue toxicity. This effective gain could result from a selective uptake or absorption rate or half-life of the radiosensitizing molecule in a tumor with respect to normal tissue."}
{"_id": "Radiology$$$cd15bc06-9122-492e-8c96-d2974a83965d", "text": "Radiosensitizers have been developed to modulate the response that occurs during or after the radiation exposure. At a molecular level, these molecules stimulate the fixing of free radicals generated by radiation. Similarly to the oxygen effect, the biochemical mechanism prevents the repair of damaged molecules. The electron affinity of the radiosensitizers captures independently existing free radicals, rendering the molecules incapable of repair [198]. Although each radiosensitizer has different rationales and limitations, they interact with specific biological targets, i.e., the signaling pathway/cascade (Table 11.1) at diverse levels (Fig. 11.21) from molecules to cells to tissues to organs to a whole organism. The core mechanisms for radiosensitization include:\nInhibiting repair of radiation-induced DNA damage, thereby increasing the degree of radiation-induced apoptosis and DNA damage\n\nImproving cytotoxicity by disrupting the cell cycle and organelle function\n\nActivating and regulating the expression of radiation-sensitive genes or silencing genes related to radioresistance\nTable 11.1\nPotential biological targets at different levels for developing radiosensitizers\n\nLevels\n\nTarget (molecules/proteins/enzymes involved in signaling pathways/cascades)\n\nReactive oxygen species\n\nTargeting mechanisms to generate free radicals\n\nDNA damage response\n\nTargeting key DDR proteins\n\u2003\u2022 DNA-PKcs\n\u2003\u2022 ATM/ATR\n\u2003\u2022 PARP family\n\u2003\u2022 MRN (MRE11-RAD50-NBS1) complex\n\u2003\u2022 MDC1, Wee1, LIG4, CDK1, BRCA1, CHK1, and HIF-1\n\nFunctional organization of genome (chromatin organization)\n\nTargeting inhibitors of chromatin changes\n\u2003\u2022 DNA methyltransferase\n\u2003\u2022 Histone acetyltransferase, deacetylase, methyltransferase, demethylase\n\nCellular response to signals\n\nTargeting cell cycle proteins\n\u2003\u2022 Blockage of cell cycle checkpoints (G2/M transition)\n\u2003\u2022 Inhibitors of cell survival proteins\n\u2003\u2022 Oncogenes (p53, ras)\n\u2003\u2022 Evading growth suppressors\n\u2003\u2022 Biomechanical effects of microbubbles\n\nTumor microenvironment\n\nTargeting\n\u2003\u2022 Prolyl-4-hydroxylases (PDH)\n\u2003\u2022 Oxygen-independent mechanism, including PI3K/AKT and MAPK, or through loss of tumor suppressor protein von Hippel-Lindau (VHL)\n\u2003\u2022 VEGF\n\u2003\u2022 ECM remodeling within tumors\n\nTissue-level effects\n\nTargeting\n\u2003\u2022 Inhibitors of angiogenesis (antiangiogenic and/or vascular targeting agents)\n\u2003\u2022 Inhibitors of growth factor signaling\n\u2003\u2022 Anti-VEGF/VEGFR antibodies, antisense suppression of VEGF, VEGFR tyrosine kinase inhibitors, viral-directed targeting of VEGFR signaling\n\u2003\u2022 Blockage of growth factor secretion from dying cells\n\nAbbreviations: DDR DNA damage response, DNA-PKcs DNA-dependent protein kinase, ATM/ATR ataxia\u2013telangiectasia mutated and ATM and Rad3 related, PARP poly[ADP-ribose] polymerase, MDC1 mediator of DNA damage checkpoint protein 1, LIG4 ligase IV, CDK1 cyclin-dependent kinase 1, BRCA1 breast cancer gene 1, CHK1 checkpoint kinase 1, HIF-1 hypoxia-inducible factor-1, ECM extracellular matrix\n\n\nAn illustration of the effect of nutraceutical compounds and ionizing radiation on a cell. Nutraceutical compounds: Inflammation, migration, autophagy, and angiogenesis. Ionizing radiation: D N A double strand breaks, D N A fragmentation, apoptosis, and R O S production.\n\nFig. 11.21\nDevelopment of potential radiosensitizers at different levels. Potential radiosensitizers can be developed focusing on the molecular, cellular, or organismic levels, which may be useful in modulating the radiation effects on cancer cells as well as on normal cells"}
{"_id": "Radiology$$$5c8fa382-0b44-41bb-aafe-343544b07160", "text": "Inhibiting repair of radiation-induced DNA damage, thereby increasing the degree of radiation-induced apoptosis and DNA damage"}
{"_id": "Radiology$$$3cea9d25-c106-4b57-9e69-c106e740a089", "text": "Activating and regulating the expression of radiation-sensitive genes or silencing genes related to radioresistance"}
{"_id": "Radiology$$$35a40061-2270-43ce-8df4-cb32b29d8e21", "text": "An illustration of the effect of nutraceutical compounds and ionizing radiation on a cell. Nutraceutical compounds: Inflammation, migration, autophagy, and angiogenesis. Ionizing radiation: D N A double strand breaks, D N A fragmentation, apoptosis, and R O S production."}
{"_id": "Radiology$$$5106741e-5b6c-4385-8903-86fff4f59696", "text": "Based on the DNA damage and repair mechanisms, radiosensitizers are divided into five groups [199, 200]: (1) reduction of thiols or other intracellular radioprotective molecules; (2) radiolysis of the radiosensitizer, which results in the production of cytotoxic chemicals; (3) inhibitors of repair of biomolecules; (4) thymine analogs incorporated into DNA chain; and (5) oxygen mimetics with electrophilic properties."}
{"_id": "Radiology$$$1f9fdf22-4fe0-48bc-addf-2f76d4ac7607", "text": "With the continuous technological innovation, radiosensitizers can be classified into three categories: (1) molecular structures of small molecules (Table 11.2); (2) macromolecules with their mechanism of radiosensitivity (Table 11.3); and (3) nanomaterials (Table 11.4) with low cytotoxicity, good biocompatibility, usability, and functionality (Box 11.5).Table 11.2\nSmall molecules as radiosensitizers\n\nHyperbaric oxygen\n\u2003A potent radiosensitizer, which promotes toxic and relatively stable free radical formation, useful to effectively enhance the radiosensitivity of the tumors which contain numerous hypoxic cancer cells.\n\nNItroxides\n\u2003The most representative are nitro-containing compounds (such as nitrobenzene, nitroimidazoles, and its derivatives) and nitric oxides (NOs). These are \u201ctrue radiosensitizers,\u201d having higher electron affinity and better diffusion properties than molecular oxygen. It can theoretically substitute for oxygen in \u201crepairing/fixing\u201d radiation-induced DNA damage.\n\nCarbogen\n\u2003A mixture of 95% oxygen and 5% carbon dioxide, which improves tumor oxygenation contrasting with hypoxia.\n\nHypoxia-specific cytotoxins\n\u2003Bioreductive agents, such as aromatic N-oxides, transition metal complexes, quinones (mitomycin C, porfiromycin, and E09), aliphatic N-oxides, and nitro compounds, that selectively radiosensitize the hypoxic cells by virtue of their preferential cytotoxicity.\n\nChemical radiosensitizers\n\u2003Chemicals targeting a variety of cell signaling pathways, suppressing radioprotective substances, pseudo-substrates, and targeted delivery systems for radiosensitization. Examples are BKM120 (an oral pan-class I PI3K inhibitor), targets of PI3K-Akt pathway, NVP-BEZ235 (a mTOR inhibitor), AMG 232 (an MDM2-p53 interaction), GSH inhibitors, and radiosensitizing nucleosides (5-fluorouracil (FUra), bromodeoxyuridine (BrdUrd), iododeoxyuridine (IdUrd), hydroxyurea, gemcitabine (dFdCyd), fludarabine).\n\nNatural radiosensitizers\n\u2003Natural molecules are safer than synthetic compounds and have anti-inflammatory and antioxidant properties: curcumin, genistein, resveratrol, zerumbone, ursolic acid, etc.\nTable 11.3\nMacromolecules as radiosensitizers\n\nProteins and peptides\n\u2003Antibody conjugates and cell-penetrating peptides selectively deliver a cytotoxic payload to a tumor and spare most healthy cells. Examples are HER3-ADC (targeting HER3), SYM004, and nimotuzumab (targeting EGFR) and cetuximab (inhibitor of EGFR).\n\nmiRNAs\n\u2003Endogenous noncoding microRNAs (miRNAs) can be used as RT sensitization targets. These can be regulatory miRNAs of DNA damage response (DDR) and HR repair factors.\n\nsiRNAs\n\u2003Exogenous short interfering RNAs or silencing RNAs (siRNAs), which are noncoding RNA molecules, that can selectively target key mRNAs belonging to pathways involved in the response to radiation, such as DDR, cell cycle regulation, and survival/apoptosis balance.\n\nOligonucleotides\n\u2003Small DNA or RNA sequences are able to disturb key mRNA translation. Studies have concerned oligonucleotides targeting the telomerase RNA subunit or telomerase reverse transcriptase (hTERT) or cyclic AMP response element (CRE) decoy oligonucleotide.\nTable 11.4\nNanomaterials as radiosensitizers\n\nNoble metal nanomaterials\n\u2003Nanoparticles, such as gold (Au, Z\u00a0=\u00a079), silver (Ag, Z\u00a0=\u00a047), and platinum (Pt, Z\u00a0=\u00a078), can effectively interact with radiation, emitting secondary electrons which amplify the radiation effects.\n\nHeavy metal nanomaterials\n\u2003Physical dose enhancement methods are comparable for gadolinium (Gd, Z\u00a0=\u00a064), hafnium (Hf, Z\u00a0=\u00a072), tantalum (Ta, Z\u00a0=\u00a073), tungsten (W, Z\u00a0=\u00a074), and bismuth (Bi, Z\u00a0=\u00a083) or their stable forms such as oxides, sulfides, and selenides. Examples are gadolinium-based nanoparticles (AGuIX), hafnium oxide (HfO2) nanoparticle (NBTXR3), tantalum pentoxide (Ta2O5) and tantalum oxide (TaOx), bismuth oxide (BiO) nanoparticles, and tungsten oxide nanopowder or nanoparticles (WO3).\n\nFerrite nanomaterials\n\u2003They can catalyze the reaction of H2O2, generating highly toxic hydroxyl free radicals in the tumor microenvironment with the aim of boosting the radiation therapeutic efficacy. Explored examples are superparamagnetic magnesium ferrite spinel (MgFe2O4) nanoparticles (SPMNPs) and zinc ferrite (ZnFe2O4) nanoparticles\n\nSemiconductor nanomaterials\n\u2003Semiconductor nanosensitizer materials, such as silicon (Si), germanium (Ge), gallium arsenide (GaAs), and semiconductor quantum dots, have unique properties making them great candidates as photosensitizers and radiosensitizers for tumor treatment ([201]; [202]). Explored examples are WO2.9-WSe2-PEG semiconductor heterojunction nanoparticles (WSP NPs), titanium peroxide (PAA-TiOx) nanomaterial, copper bismuth sulfide (Cu3BiS3,CBS) nanoparticles, and TiO2 nanotubes.\n\nNonmetallic nanomaterials\n\u2003Similarly to the metallic nanoparticles\u2019 mechanism of action, nonmetallic nanomaterials can increase oxidative damage. Explored examples are ultrasmall uncapped and amino-silanized oxidized silicon nanoparticles; nanocrystals of underivatized fullerene, C60, (nano-C60); nanodiamonds and carbon nanotubes; and selenium (Se) nanoparticles.\n\nNanostructured substances and drug delivery systems\n\u2003Chemicals, oxygen carriers, siRNAs, and other radiosensitizing agents are transported via relatively new nano-based delivery systems. Explored examples are the poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles containing paclitaxel (a cell cycle-specific radiosensitizer) and etanidazole (a hypoxic radiosensitizer)."}
{"_id": "Radiology$$$51c3eb2e-6dec-411b-83da-d35cc8e7b34b", "text": "Small molecules are classified based on radiation-induced free radicals, pseudo-substrates, and other mechanisms.\n\nMacromolecules such as miRNAs, proteins, peptides, and oligonucleotides have been explored to develop radiosensitizers as they are capable of regulating radiosensitivity.\n\nPromising nanotechnology methods used as radiosensitizers include well-developed nanomaterials with low toxicity, good biocompatibility, and functionalization ease.\n\nOther technologies, such as molecular cloning technology, analysis of molecular structure, and bioinformatics, can speed up the development of new effective radiosensitizing drugs."}
{"_id": "Radiology$$$28b82259-2983-422d-aa58-b7de57e6e63d", "text": "Small molecules are classified based on radiation-induced free radicals, pseudo-substrates, and other mechanisms."}
{"_id": "Radiology$$$ba8e502c-d39d-4c4d-919d-bee76aba2a81", "text": "Macromolecules such as miRNAs, proteins, peptides, and oligonucleotides have been explored to develop radiosensitizers as they are capable of regulating radiosensitivity."}
{"_id": "Radiology$$$b3e49ef2-dcfc-4f1d-a549-6343368652e6", "text": "Promising nanotechnology methods used as radiosensitizers include well-developed nanomaterials with low toxicity, good biocompatibility, and functionalization ease."}
{"_id": "Radiology$$$2a99b221-e158-441b-b061-741be215db7e", "text": "Other technologies, such as molecular cloning technology, analysis of molecular structure, and bioinformatics, can speed up the development of new effective radiosensitizing drugs."}
{"_id": "Radiology$$$602bcc1a-5945-4027-baab-2dbec96ae594", "text": "Several nutraceutical chemicals have attracted significant interest in recent decades due to their possible involvement in the prevention and treatment of various illnesses, as well as their favorable effects in boosting human and animal health. In particular, literature data often report their positive effect in combination with chemotherapy in cancer care. Even while intriguing results have been published on this issue at multiple cellular levels, less is known about their role as radiosensitizers. Presence of these compounds during radiation augments their effect by several mechanisms including the lethal reactions of free radicals."}
{"_id": "Radiology$$$94054b17-b9ea-450f-918a-3b40ff8f4628", "text": "Among compounds of various origins that showed radiosensitizer potential, numerous studies have revealed the important role of molecules of natural origin, when administered in combination to IR."}
{"_id": "Radiology$$$bd6e99dc-038b-407f-b2e5-24fe8a20dd77", "text": "The use of nutraceuticals as sensitizers, in addition to being generally well tolerated, is also easily recovered and less expensive in comparison to synthesized drugs. Their administration reduces the collateral effects frequently associated with medication delivery, and in certain situations, they can help attenuate IR adverse effects through biological processes like those shown in Fig. 11.22. Indeed, in most cases, they show anti-inflammatory and antioxidant properties, which are precious arms to counter the RI side effects on healthy tissues.\n\nAn illustration of potential radiosensitizers for different levels. The levels are reactive oxygen species, D N A damage response, functional organization of genome or chromatin organization, cellular response to signals, tumor microenvironment, and tissue level effects.\n\nFig. 11.22\nRadiation therapy and nutraceutical substances may influence signaling pathways involved in migration, inflammatory response, autophagy, and formation of reactive oxygen species (ROS). Adapted from \u201cNutraceutical Compounds as Sensitizers for Cancer Treatment in Radiation Therapy,\u201d by [203], Licensed under CC BY 4.\u200b0"}
{"_id": "Radiology$$$0a95c99f-f9e6-4687-bdc7-29656d0e59ec", "text": "An illustration of potential radiosensitizers for different levels. The levels are reactive oxygen species, D N A damage response, functional organization of genome or chromatin organization, cellular response to signals, tumor microenvironment, and tissue level effects."}
{"_id": "Radiology$$$c5d3de16-761c-4517-a583-e1740ec57c23", "text": "However, in most cases, they showed direct anticancer activity, as demonstrated by numerous scientific papers. The most studied natural compounds are exposed in Table 11.5 [203].Table 11.5\nNatural compounds related to cancer radiation treatments\n\nNatural compounds\n\nTumor target\n\nType of treatment\n\nCurcumin\n\nColorectal cancer, glioblastoma, head and neck squamous cancer, prostate cancer\n\nX-rays\n\nResveratrol\n\nBreast cancer, glioblastoma, head and neck squamous cancer, melanoma, nasopharyngeal carcinoma, non-small cell lung cancer, prostate cancer\n\n\u03b3-rays, X-rays\n\nWithaferin A\n\nBreast cancer, cervical cancer, Ehrlich ascites carcinoma, fibrosarcoma, histiocytic human lymphoma, liver cancer, melanoma, renal carcinoma\n\n\u03b3-rays, X-rays\n\nCelastrol\n\nLung cancer, prostate cancer\n\n\u03b3-rays, X-rays\n\nUrsolic acid\n\nColon carcinoma, gastric adenocarcinoma, non-small cell lung cancer, melanoma, prostate cancer\n\n\u03b3-rays, X-rays\n\nZerumbone\n\nColorectal cancer, glioblastoma, lung adenocarcinoma, non-small cell lung cancer, prostate cancer\n\n\u03b3-rays, X-rays\n\nCaffeic acid phenethyl ester\n\nAdenocarcinoma, breast cancer, lung cancer, medulloblastoma\n\n\u03b3-rays, X-rays\n\nEmodin\n\nCervical cancer, hepatocellular carcinoma, nasopharyngeal carcinoma, sarcoma\n\n\u03b3-rays, X-rays\n\nFlavopiridol\n\nCervix cancer, esophageal adenocarcinoma, esophageal squamous carcinoma, glioma, lung carcinoma, ovarian carcinoma, prostate cancer, zebrafish model\n\n\u03b3-rays, X-rays\n\nBerberine\n\nBreast cancer, esophageal carcinoma, nasopharyngeal carcinoma, osteosarcoma, prostate cancer\n\n\u03b3-rays, X-rays\n\nGenistein\n\nBreast cancer, cervical cancer, non-small cell lung cancer\n\n\u03b3-rays, X-rays\n\nSelenium\n\nMelanoma, glioma, breast cancer\n\n\u03b3-rays, X-rays"}
{"_id": "Radiology$$$c5b99774-76db-4581-a5ad-48163b2a27c8", "text": "Curcumin, the main component in the Indian culinary spice turmeric (Curcuma longa), has been shown to have anticancer potential in several studies. The biological mechanism can be ascribed to cell signaling pathway effects, resulting in the inhibition of cell proliferation and induction of apoptosis."}
{"_id": "Radiology$$$da7f4556-c5ad-4be4-b331-b018213edb5c", "text": "Regarding its radiosensitizing properties evaluated by an in vitro approach, the inhibition of survival and proliferation has been observed on the MCF-7 breast cancer cell line. In addition, the effect of vehicolated curcumin, using solid nanoparticles, combined with X-ray radiation was tested by Minafra and coworkers [204] on the human nontumorigenic breast epithelial MCF10A cell line and the breast adenocarcinoma MCF7 and MDA-MB-231 cell lines. The vehicolated curcumin has been shown to be more effective than the free curcumin on MCF7 and MCF10A, whereas the free molecule resulted to be slightly more effective on MDA-MB-231. The dose-modifying factors (DMFs) were calculated to quantify the radiosensitizing effect, which resulted in 1.78 for MCF7 using vehicolated curcumin and 1.38 with free curcumin on MDA-MB-231 cells. Transcriptomic and metabolomics approach supported this study, revealing the double-positive effect of curcumin as an autophagy enhancer for tumor cells and antioxidant agents [204]."}
{"_id": "Radiology$$$a4ea1d3e-369c-4118-92a2-396644204839", "text": "Antiapoptotic signals and block in G2/M cell cycle phase mediated by Bcl-2 were demonstrated in human immortalized prostate adenocarcinoma cells (PC-3) after 5 Gy irradiation combined with 2\u03bcM curcumin. Instead, an increased radiosensitivity was observed in HCT116 and HT29 human colorectal cancer cell lines treated with 25\u03bcM of curcumin and a single dose of X-ray radiation (10\u00a0Gy). Curcumin was also able to decrease COX-2 expression by the inhibition of EGFR phosphorylation both in vitro on the human head and neck squamous cell carcinoma (HNSCC) cell line and in two in vivo models of head and neck tumor."}
{"_id": "Radiology$$$5d5fec83-69a7-4464-b228-787ae83d5c32", "text": "On the human glioblastoma U87MG cell line, the viability was reduced in a dose-dependent manner by 3 Gy of X-ray combined with curcumin at a concentration range of 5\u201310\u03bcM, sustained by the arrest of cell cycle in phase G2/M (which is the most sensitive step to radiation) and the inhibition of two master regulators of tumor progression, the MAP kinases ERK and JNK [203]."}
{"_id": "Radiology$$$5a637aa6-a5a4-4c43-9860-78b99bb67ac1", "text": "However, curcumin is an unstable, nonbioavailable compound due to its poor absorption in the GI system. Hence, its therapeutic application is delimited by its pharmacokinetics. Despite promising preclinical studies, no double-blinded placebo-controlled clinical trial, using curcumin as a radiosensitizer, has been successful. The interaction of curcumin with RT on different cancer types has been reviewed by Verma [205]; however, there is still a lack of solid clinical evidence of radiosensitization. For instance, in vitro and in vivo studies together with clinical bioavailability data do not give evidence for a radiosensitizing effect of curcumin in the treatment of high-grade brain tumors (glioblastoma multiforme). On the other hand, there is limited data on curcumin\u2019s radioprotective function, despite the fact that some clinical trials suggest that curcumin is beneficial for the management of radiation toxicities [205]."}
{"_id": "Radiology$$$c6fabe62-b01e-4d18-9014-830dd084d3de", "text": "The antineoplastic ability of RV encouraged its application also as a radiosensitizer to overcome radioresistance of many cancers."}
{"_id": "Radiology$$$c6c98bf8-eb0f-45ec-bd0a-45a91b08ff89", "text": "A dose-dependent reduction in the surviving fraction of a non-small cell lung cancer (NSCLC) cell line after irradiation with 0\u20138 Gy of \u03b3-rays in combination with 20\u03bcM of RV was observed along with accelerated senescence and cell death following enhanced DNA DSB induced by ROS [203]."}
{"_id": "Radiology$$$118e3043-836e-4a3f-92dd-8828d52e743b", "text": "However, an increased expression of LC3-II for autophagy response after X-ray and RV treatment (75\u03bcM) was demonstrated in SU-2 glioblastoma multiforme cell lines [206]. Also, in GBM, RV showed inhibition of the hypoxia-inducible factor HIF-1\u03b1, which is responsible for a well-known mechanism of radioresistance. Moreover, the interaction of RV with other agents as iododeoxyuridine (IUdR) was also tested and demonstrated the ability to decrease the formation of cancer colonies [203]."}
{"_id": "Radiology$$$1220e12a-ceae-4d81-b0ae-b77b52c62610", "text": "In the HNSCC cancer model, suppression of cell proliferation was obtained on a cell line, treated with 100\u03bcM of RV combined with 10 Gy of X-ray, also observing the inhibition of STAT3 phosphorylation, a well-known transcription factor driving inflammation and cancer progression. Even the peanut stem extract (PSE), which contains a high amount of RV, has been tested in combination with X-rays, which showed similar radiosensitization effects on radioresistant human prostate cancer cell lines. In this regard, the tumor growth of a prostate cancer xenograft mouse model was reduced with RV and/or PSE (total dose 12\u00a0Gy, 5 or 250\u00a0mg/kg, respectively) [203]. RV was also used as a pretreatment (25\u2013150\u03bcM) to treat the human NPC CNE-1 cell line with X-ray irradiation (0\u20136\u00a0Gy), revealing the inhibition of the AKT phosphorylated form, a known proproliferative marker. These effects were also confirmed in NPC xenograft models, combining the RV treatment with 4 Gy for 3\u00a0days, resulting in a tumor volume reduction."}
{"_id": "Radiology$$$df58dd66-27a5-41f7-ba82-cc5cb38ad634", "text": "Nevertheless, a key problem is the short RV half-life and low bioavailability under in vivo conditions. In vivo, pterostilbene was proven to be beneficial in the treatment of melanoma and pancreatic cancer. This study demonstrated that PT can be helpful against melanoma by inhibiting the generation of adrenocorticotropic hormone in the brain of a mouse, which impairs the Nrf2-dependent antioxidant defenses of melanoma and pancreatic tumors. This produces tumor growth restraining and tumor sensitization to oxidative stress. In addition, PT has been shown to increase cancer cell death by the induction of lysosomal membrane permeabilization [53]."}
{"_id": "Radiology$$$f0d5692d-55ef-43c2-a122-c7f0dc825fb7", "text": "Withaferin A (WA) was the first withanolide to be isolated and extracted from the plant Withania somnifera. WA-induced radiosensitization has been observed in human histiocytic lymphoma, renal carcinoma, and liver, breast, and several other types of cancer. Overall, these studies highlight the effect of combined treatment, mediated by the increase of apoptosis and production of ROS."}
{"_id": "Radiology$$$e07195fa-5182-4212-a1fe-4216192aa0d4", "text": "WA has been shown to suppress cancer cell growth by targeting the intermediate filament protein vimentin, a structural protein of the cell cytoskeleton. In light of its anticancer capability, WA was also tested in order to investigate its effect in inducing the radiosensitization of cancer cells."}
{"_id": "Radiology$$$5663c617-3867-4b00-8f16-cf36c8851292", "text": "WA\u2019s effects were initially investigated in vitro and in combination with \u03b3-irradiation on a lung fibroblast cell line, and WA was found to be well tolerated by cells and to mediate a synergistic impact with \u03b3-rays in terms of cell death. Based on these encouraging results, WA was further tested in vivo to assess its effect as a radiosensitizing agent in several cancer models such as the spontaneous murine mammary adenocarcinoma (Ehrlich ascites carcinoma\u2014EAC), a mouse model of fibrosarcoma, and a mouse model of melanoma. Overall, each of the studies demonstrated that the WA and \u03b3-ray combined treatment inhibits tumor growth, increasing tumor-free survival and median survival time of animals [203]."}
{"_id": "Radiology$$$9489a5b0-2da3-4424-87e0-e74587036bbf", "text": "Celastrol, also known as tripterine, is a triterpenoid derived from the root of the \u201cthunder god wine\u201d plant often found in China and utilized in traditional Chinese medicine for its anti-inflammatory qualities in a variety of conditions, including autoimmune diseases. Moreover, anticancer properties have been revealed, due to its proteasome inhibitory activity and antimetastatic ability."}
{"_id": "Radiology$$$d319f4cc-7516-4814-99a9-7cac993a18ce", "text": "A study has evaluated its radiosensitizer effect on PC-3 cells, both in vitro and in vivo. The in vitro pretreatment with celastrol before irradiation with X-rays resulted in a significant dose-dependent enhancement of IR-induced clonogenic cell killing. This effect was explained by (1) a longer gH2AX activation for a longer time in combined treated cells with respect to the only irradiated ones, thus revealing a DNA repair impairment action by celastrol, and (2) a major expression of apoptosis markers (cleaved PARP and caspase-3)."}
{"_id": "Radiology$$$da1f3114-4a72-4452-8ff2-5090c1fd755b", "text": "Thus, the same group tested the celastrol radiosensitizer effect on a PC-3 xenograft model. 1\u00a0mg/kg of celastrol (5\u00a0days/week for 3\u00a0weeks) was given to the mice 1\u00a0h before irradiation with a single dose of 2 Gy (5\u00a0days/week for 2\u00a0weeks). The histological analysis showed a significantly increased apoptosis and angiogenesis reduction in the combined treated tumors [203]."}
{"_id": "Radiology$$$a2a35e3f-689b-40e1-9c48-8c94992cf3e6", "text": "Similar effects have been found on the NCI-H460 human lung cancer cell line, combining celastrol with 0\u20134 Gy of X-rays. Indeed, the EGFR, ErbB2, and survivin irradiation markers were found to be reduced, whereas the celastrol-dependent inhibition of HSP90 was observed. Furthermore, celastrol induces a more pronounced ROS generation after irradiation, thanks to its quinone methide moiety [203]."}
{"_id": "Radiology$$$e6d2db49-1189-4b49-abc0-ea1e526c845c", "text": "Finally, the effect of celastrol as a radiosensitizer was evaluated on lung cancer with different approaches. Indeed, one research group has identified it as one of the most promising sensitizer candidates among 30 drugs, by an in silico study. Thus, they tested its effect in vitro on A549 and H460 cells, subjected to pretreatment with celastrol and 2\u201310 Gy of dose range. The encouraging results from this in vitro study were the premises for a preclinical study on a A549 xenograft mouse model. The combined treatment using 2\u00a0mg/kg/5 each day and 10 Gy of IR for 12\u00a0days produced larger intratumoral necrotic areas [203]."}
{"_id": "Radiology$$$f0ca8f96-d968-4337-aa87-105de976fb64", "text": "Ursolic acid (UA) belongs to the family of the pentacyclic triterpenoids. It is generally obtainable from the peel of many fruits, e.g., apples, blueberries, and prunes, and also in many herbs, such as rosemary and thyme. Recently, the following therapeutic properties of UA have been described: anticancer, anti-inflammatory, and antimicrobial, and also its radiosensitization activity in models in in vitro and in vivo studies. For example, in human prostate and colon cancer cells, and in mouse melanoma cells, the UA is able to radiosensitize cells with a significant reduction in cell viability associated with an increase of typical signs of apoptosis cascade, such as cell volume reduction, nuclei fragmentation or condensation, caspase-3 activation (one of the key enzymes involved in the apoptotic pathway), increased levels of cleaved PARP (enzyme involved in DNA repair processes), DNA fragmentation, and also increased ROS generation. In melanoma mouse models, the treatment with UA and IR is able to inhibit tumor growth owing to a downregulation of Bcl-2 and survivin, two known key protein regulators of cell survival [203]."}
{"_id": "Radiology$$$5e47a6a1-757b-4890-af7f-594c62fbadd5", "text": "Moreover, UA can also exert a differential effect after exposure of normal or cancer cells to UV, acting as a photosensitizer for the latter and as a photoprotector for normal ones. This action was observed in human melanoma cells and in human retinal pigment epithelium control cells, where induced oxidative stress by ROS production, cell cycle arrest, and cell death induction were evaluated following UA and UV treatments. Furthermore, the UA has a significant radiosensitizing effect in human gastric adenocarcinoma cells, as evidenced by (i) a decrease in the cell survival fraction and otherwise an increase in the number of apoptotic cells (positive to the propidium iodide and annexin V apoptotic markers); (ii) the arrest of the cell cycle (in the G1 and G2/M phases); and (iii) the increase in ROS amount and a decrease of Ki-67-positive proliferating cells [207]."}
{"_id": "Radiology$$$59f41fbb-0b7a-4336-a10d-1d40b2de8639", "text": "Zerumbone (ZER) is a cyclic ketone and a sesquiterpene compound, a cytotoxic component obtained by steam distillation of the Zingiber zerumbet Smith. ZER is used in food and herbal medicine, and it also has anti-inflammatory, antiproliferative, and antitumor properties, as observed in many tumor types (including breast, pancreas, colon, lung, and skin). In addition, the radiosensitizing effects of ZER on tumors, by means of its regulatory activities on DNA DSB repair, cell cycle, and apoptotic pathways, have been highlighted too [203]."}
{"_id": "Radiology$$$582932c6-20a4-4ba1-b782-8d9e7c9be6a5", "text": "ZER was able to significantly increase radiation-induced cell death in human lung adenocarcinoma cells by inhibiting heat-shock proteins (HSP), increasing caspase 3 and PARP cleavage, and inhibiting HSP27 binding to apoptotic molecules such as PKC\u03b4 and cytochrome C [203]."}
{"_id": "Radiology$$$7386389e-793d-4cf3-9d3b-53f1822ccebd", "text": "In addition, the radiosensitizing effect was also observed in human glioblastoma cells. The same authors showed an IR-induced decrease of cell survival on human prostate cancer cells, associated with a reduced expression of proteins involved in the DNA damage repair pathway, such as \u03b3H2AX and ATM [203]."}
{"_id": "Radiology$$$9f45c32f-fa4d-403b-a979-f88541a426cb", "text": "Moreover, in human colon-rectal cancer cells, ZER pretreatment is able to induce apoptosis and enhance radiation-induced G2/M arrest and reduction of activation of the DSB DNA repair machinery."}
{"_id": "Radiology$$$4064c7fd-0239-4312-a1d0-fc76fd69a0b5", "text": "CAPE is an active component of honeybee propolis, a phenolic compound, and a structural derivative of flavonoids. It was described for its antiviral, bactericidal, anti-inflammatory, and antioxidant properties. CAPE compound is also able to change the redox state by perturbing the activation of GSH and to induce apoptosis. Furthermore, it has been shown to be more toxic to cancer cells than normal cells, as well as to amplify the action of RT in a variety of cancers."}
{"_id": "Radiology$$$cf5236ae-b006-44f2-a476-de5d628b9641", "text": "CAPE has been shown to improve radiation-induced cell cycle arrest and death in human medulloblastoma DAOY cells. In particular, the combined treatment with CAPE and 2 Gy of IR caused an ROS enhancement production, a significant inhibition of NF-kB activity, apoptosis activation, and downregulation of cyclin B1 protein expression. In line with these data, a strong reduction of cell survival, in a concentration-dependent manner, was described in the same cell line pretreated with CAPE (0.1\u201310\u00a0M) for 24\u00a0h before exposure to \u03b3-ray irradiation at various doses (0\u20138\u00a0Gy), associated with cell cycle progression inhibition, by arresting cells in the S phase [203]."}
{"_id": "Radiology$$$67f1efcc-2953-44b0-9ab8-9c28070683ba", "text": "The CAPE pretreatment radiosensitizing effect was also shown in mouse CT26 adenocarcinoma cells, using both in vitro and in vivo approaches showing decreased cell survival rate and reduced NF-kB activation. CAPE-induced decrease of survival rate was also described in breast and lung cancer cell lines. In particular, in MDA-MB-231 and T47D breast cancer cell lines, CAPE and X-ray combined treatments decreased cell growth and delayed the DNA repair process for up to 60 min after exposure [203]."}
{"_id": "Radiology$$$ae54c91d-9f00-4a05-9793-21db67ef8d1c", "text": "Traditional Chinese medicine uses emodin (6-methyl-1,3,8-trihydroxyanthraquinone), a natural phenolic derived from the roots and rhizomes of numerous plants (e.g., Polygonum cuspidatum and Cascara buckthorn)."}
{"_id": "Radiology$$$ef319302-1c84-4a06-9220-46ad3b7501b4", "text": "Emodin is chemically similar to the mitochondrial ubiquinone named DMNQ (2,3-dimethoxy-1,4-naphthoquinone), an endogenous ROS inductor, as it is able to transfer electrons. It is also known to have antibacterial, antiviral, anti-inflammatory, and anticancer effects. The emodin\u2019s antitumor effect has been observed in several types of cancer (leukemia, breast, colon, and lung cancer), also in combination with RT schedules, although its mechanism of action still remains unclear."}
{"_id": "Radiology$$$4523b6a3-b0bb-462f-8da8-912828d75b02", "text": "Under hypoxic conditions, emodin treatment enhanced the radiosensitivity of CNE-1 NPC human nasopharyngeal carcinoma cell line. In particular, treatment with 3.9 and 7.8\u00a0g/mL emodin 24\u00a0h before 2 Gy IR induced an increase in the apoptosis ratio and cell cycle arrest in the G2/M phase. Moreover, an increase of ROS production in tandem with a downregulation of HIF-1 levels (both mRNA and protein) was also described. These data were also confirmed by using CNE-1 xenograft models where a tumor growth delay was observed after emodin and IR combined treatments [203]."}
{"_id": "Radiology$$$beb2a9b0-f286-4893-805f-f41ac0f89006", "text": "The radiosensitizing effect of emodin has also been observed in the HeLa cervical cancer cell line, where pretreatment with different concentrations of aloe emodin (AE) before X-ray irradiation (0\u201310\u00a0Gy) leads to decrease in the mean lethal dose (D0) in a concentration-dependent manner, as well as an enhancement in the percentage of cells in the G2/M phase and a sub-G1 peak at 24, 48, and 72\u00a0h, using 50 M and 4 Gy IR. In addition, an increased expression of cyclin B, \u03b3-H2AX, and alkaline phosphatase (ALP) activity was also described. Similar data regarding a decrease of cell growth and viability were observed also in human HepG2 hepatocellular carcinoma cell line treated with 10 Gy of \u03b3-irradiation and AE, under hypoxic conditions. This combined treatment leads to higher increase in both G2/M and apoptotic populations [203]."}
{"_id": "Radiology$$$beb6992d-9ac8-4891-9443-a72c4449da74", "text": "Flavopiridol is a flavone originating from the Dysoxylum binectariferum plant commonly used in Indian medicine. This molecule is able to arrest cell cycle by acting on cyclin-dependent kinases (CDKs) during the G1/S or G2/M phases, which is confirmed in several cancer cell types (chronic lymphocytic leukemia, squamous cancer, breast cancer cells). In addition, flavopiridol is able to induce the transcriptional suppression of genes involved in the proliferation pathways, to stimulate apoptosis, to inhibit angiogenesis, and to increase the chemotherapeutic effects [203]."}
{"_id": "Radiology$$$9a4dd363-2cc6-43d8-b182-250ad3da94a1", "text": "The power of flavopiridol to affect cell radiosensitivity, in tandem with docetaxel, was described in H460 human lung carcinoma, by using both in vitro and in vivo approaches. Multiple treatments with docetaxel (10\u00a0M), \u03b3-irradiation (0\u20135\u00a0Gy), and flavopiridol (120\u00a0M) are able to augment radiation effects by inducing cell cycle arrest in the G1 and G2/M phases. On the other hand, in esophageal squamous carcinoma cell lines, cell cycle arrest after irradiation was described with the decrease of cyclin D1 and retinoblastoma protein (Rb) levels. Additionally, in the SEG-1 esophageal cancer cell line, treatment with flavopiridol 24\u00a0h before \u03b3-radiation (2\u20136\u00a0Gy) increased radiosensitivity compared to the control, due to inhibition of several CDKs, cell cycle redistribution in G1 and G2 phases, and induction of apoptosis [203]."}
{"_id": "Radiology$$$8f968fd6-a58d-4614-bec9-978215b465d6", "text": "The experimental evidences show that cells containing mutated p53 or overexpressed Bcl-2 are more radioresistant than wild type. However, flavopiridol increased the cytotoxic effects of radiation in cells with altered status of p53 and Bcl-2, confirming the hypothesis according to which these two pathways are targeted by radiosensitizer mechanism exerted by flavopiridol [203]. Moreover, the radiosensitizing effects of flavopiridol were evaluated in vivo on glioma xenograft models using GL261 cells. The interaction of \u03b3-radiation (5\u00a0Gy), fractionated for 10\u00a0days, with flavopiridol (5\u00a0mg/kg) resulted in a decrease in cell proliferation, which was mainly mediated by the flavopiridol\u2019s antiangiogenic activity, which also inhibited the HIF-1 pathway [203]."}
{"_id": "Radiology$$$37a61bd4-dcc2-4d64-b8b2-444da354e62a", "text": "On the other hand, as described in OCA-I ovarian carcinoma cells, the radiosensitizing action of flavopiridol could be sustained also by the downregulation of Ku70 and Ku80 proteins, known to be involved in DNA repair mechanisms after radiation exposure, by the redistribution of the cell cycle with a greater accumulation of cells in the two more radiosensitive G1 and G2 phases [203]."}
{"_id": "Radiology$$$22a58b56-16d7-4972-bc3a-aebd0934612b", "text": "Berberine is an alkaloid which can be extracted from the roots of many plants like the barberry, the tree turmeric, and the California poppy. Berberine is used to treat health problems like hypercholesterolemia and type 2 diabetes mellitus."}
{"_id": "Radiology$$$1ae1aa62-c303-49bc-ad8b-36975f5f5ae7", "text": "Berberine works by inhibiting cell cycle progression, thereby exerting, in vitro, an antitumor activity in a large array of tumors, and its radiosensitizing properties were investigated on lung, esophageal, and breast cancer cells. Since berberine interferes with the expression and activity of RAD51, involved in DNA damage repair response, its radiosensitizing mechanism is based on hindering DNA damage recovery after X-ray irradiation. In vitro and in vivo experimental data has revealed the ability of berberine to inhibit HIF-1\u03b1 and suppress VEGF. For example, in an in vitro nasopharyngeal carcinoma study, berberine when combined with \u03b3-rays demonstrated a reduction of cancer cell proliferation, viability, and Sp1 decreased expression, a protein involved in tumor motility and invasion [203]."}
{"_id": "Radiology$$$6dc34e24-c997-4823-95f2-58aedaa20db0", "text": "As expected, genistein also acts as a radiosensitizing agent, if combined with \u03b3-irradiation, as shown in vitro in cervical cancer cells, where the growth inhibition was associated with survivin downregulation, a prosurvival protein. Again, in cervical neoplasms, genistein enhanced RT effects in multiple ways: by inhibiting G2/M phase of cell cycle; by reducing the expression of two prosurvival proteins, Mcl-1 and AKT; and by triggering cell apoptosis via cytochrome c release, cleavage of caspase-3 and -8, inhibition of Bcl-2, and enhancement of Bax expression. Similar results were also shown on breast and non-small cell lung cancers, where the radiosensitizing ability was associated with the inhibition of Bcl-x, ROS production enhancement, and antioxidant molecule downregulation [203]."}
{"_id": "Radiology$$$4cb51d46-d8ec-4601-af4d-df9c9b1d8aaa", "text": "BP-C2, a lignin-derived polymer containing benzene polycarboxylic acids complexed with ammonium molybdate, is an antioxidant that promotes the release of prorepair cytokines (IL-4 and IL-10) and suppresses the release of proinflammatory cytokines (TNF-\u03b1 and IL-6). Orally administered BP-C2 was found to have radioprotective and mitigative activity in H-ARS and GI-ARS [208]. Topical BP-C2 was found to have radiomitigative activity in a cutaneous radiation injury model (CRI-ARS) [209]."}
{"_id": "Radiology$$$5171cc8c-ba84-4964-b868-02c75f469a81", "text": "Several studies have revealed the prooxidant and cytotoxic properties of sodium selenite, with respect to other selenium compounds, recognized for their antioxidant activity. In particular, the effect on natural killer (NK) cell activation is known, as well as the inhibition of the disulfide exchange on cell surface, a remodeling process, which drives cancer to uncontrolled cell division [203]."}
{"_id": "Radiology$$$cb6be91f-b12c-4f00-b730-82b7426987b1", "text": "Schueller et al. [210] tested a 14-day pretreatment of C6 rat glioma cell line with selenite in the range concentration of 2\u20133.6\u00a0mM, before applying 0\u201320 Gy of \u03b3-rays. The results showed a significant difference between the 0\u00a0mM and 3\u00a0mM survival curves applying 5 Gy (p\u00a0=\u00a00.02) and 10 Gy (p\u00a0=\u00a00.009). Also, the vehiculated sodium selenite nanoparticles (nano-Se) were tested as radiosensitizers, using the 0\u20133\u00a0mg/mL range concentrations pretreatment, before treating with 0\u20138 Gy of X-rays. In this case, the authors showed the effect on MCF7 breast cancer cells, observing that combined treatment generated a higher mortality rate of the IR or nano-Se single treatments, inducing block at the G2/M phase of cell cycle, autophagy activation, and ROS generation. Moreover, A375 melanoma cells were subjected to 4-h pretreatment with a selenium nanosystem, using 0\u201315\u00a0mM coated hemocompatible erythrocyte membrane combined with bevacizumab (RBCs@Se/Av) and 2\u20138 Gy of X-rays. This study showed a strong cell survival reduction, an increase in the sub-G1 cell proportion, apoptotic pathway activation, and ROS generation. In addition, as expected by the bevacizumab treatment, decreased VEGF and VEGF2 levels were observed as tumor angiogenesis reduction [203]."}
{"_id": "Radiology$$$8c982b5e-4faa-4182-9dde-a0bc79975785", "text": "Corticosteroids are a group of hormones, produced by the cortex of the adrenal glands, having the characteristic steroid nucleus and derived from subsequent degradations of the cholesterol side chain. They include numerous molecules with different actions, including sex hormones. However, they are divided into glucocorticoids, such as cortisol which controls the metabolism, and mineralocorticoids, such as aldosterone which controls the concentration of electrolyte and water in the blood."}
{"_id": "Radiology$$$665c9464-300d-493e-9ae0-b1e2db932500", "text": "Among these molecules, many are used for their potent anti-inflammatory and immunosuppressive properties, such as corticosterone (C21H30O4) and cortisone (C21H28O5, 17-hydroxy-11-dehydrocorticosterone)."}
{"_id": "Radiology$$$c5ddffe4-4689-4e17-b249-aebf9c6cc6b4", "text": "In the context of clinical RT, corticosteroids are currently used as mitigators of side effects caused by irradiation [211]. However, some researchers have highlighted the radiosensitizing effects of these molecules, used in the pretreatment phase."}
{"_id": "Radiology$$$3517e024-bcd6-4991-86f0-182bf94a3e0e", "text": "Glucocorticoids (GCs), acting on stress pathways, are well known in the treatment of different types of tumors. They have a strong inhibitory action on the proinflammatory cytokine production, although their action mechanisms need deeper investigation, if used in combination with IR."}
{"_id": "Radiology$$$c80cd514-afc5-412e-9370-8a5f71b0d86d", "text": "An in vitro study has investigated the role of dexamethasone (Dex), a synthetic glucocorticoid, in DNA damage response (DDR) pathway, on three astrocytoma cell lines (CT2A, APP.PS1 L.1, and APP.PS1 L.3). The results showed increased basal levels of \u03b3-H2AX foci, keeping them higher 4\u00a0h after irradiation (IR) of the cells, while no effect was shown on the 53BP1 foci formation, compared to untreated cells. The high-level expression of \u03b3-H2AX was reversed by ascorbic acid administration, a strong inhibitor of reactive oxygen species, showing that DEXA induces DNA damage by oxidative stress [203]."}
{"_id": "Radiology$$$23384c64-5deb-4a58-944c-92d4c0b08c0b", "text": "In addition, in a preclinical study on rat model, the effect of 1 mg Dex was studied alone or in combination with radioprotective molecules turpentine oil (TO), \u03b12-macroglobulin (\u03b12-M), or amifostine, before the administration of 6.7 Gy (LD50/30) of RI, evaluating survival and blood inflammatory markers. The results showed that Dex alone was lethal for 45% and 55% of control and irradiated rats, respectively. On the other hand, from the combination of pretreatments, it emerged that 1 mg Dex reduced the radioprotective efficacy of TO and Ami to 30% and 40%, respectively, even if, given together, TO and Ami provided 70% protection to rats receiving Dex. Instead, TO and \u03b12-M enhanced the rate of survival from 50% to 90% and 100%, respectively [203]."}
{"_id": "Radiology$$$517fb793-f845-4f13-b21a-07b63a808d97", "text": "A crucial question for cancer treatment is how to increase the therapeutic window, enhancing radiation damage in tumors, while preserving the surrounding healthy tissues. One promising strategy is the accumulation of nanoparticles composed of high-Z materials (e.g., gold, palladium, platinum, gadolinium) in the tumor cells."}
{"_id": "Radiology$$$003c7516-a4bd-4085-9068-74c2afca37b6", "text": "High-atomic-number (Z) compounds have long been used as image contrast agents due to their high X-ray attenuation properties compared to soft tissues. The higher energy absorption of elements such as iodine and barium can enhance the contrast of the organs and tissues in which they are injected. The concentration of the compounds and the radiation doses used for diagnostic applications are usually so low that radiation effects and risks can be neglected. However, the same differential energy absorption principle can be exploited for therapeutic use. Recent developments in nano-manufacturing have provided reasonable and affordable methods to produce high-Z structures with dimensions smaller than 100\u00a0nm, which can be loaded in tumor volumes and in tumor cells. Their small size allows the nanostructures to escape the leaky vasculature system of tumor regions, providing a natural method for passive tumor accumulation. The majority of work has been concentrated on gold thanks to its biocompatibility and easy functionalization. The former means that considerable concentrations of gold nanostructures can be administered without toxicity effects, while the latter allows for the development of bespoke products able to accumulate in specific tissues/cells (active accumulation). Gold\u2019s high atomic number (Z\u00a0=\u00a079) provides excellent radiation absorption contrast as indicated in Fig. 11.23. Other materials such as gadolinium (Z\u00a0=\u00a064) and more recently superparamagnetic iron oxide nanoparticles (SPION, ZFe\u00a0=\u00a026) have also been suggested and explored.\n\nA line graph of the change in mu over rho and ratio of gold over water versus energy in mega electron volts plots 3 fluctuating trends.\n\nFig. 11.23\nMass energy absorption coefficient (left-hand-side Y-axis) for gold (purple) and soft tissue (blue) as a function of X-ray energy. Right-hand-side Y-axis indicates the ratio (black)"}
{"_id": "Radiology$$$1242c116-f3ae-4721-ab49-11ff8e777e51", "text": "A line graph of the change in mu over rho and ratio of gold over water versus energy in mega electron volts plots 3 fluctuating trends."}
{"_id": "Radiology$$$8e3bb21e-ac39-4a58-95f4-65d19d7dbaf7", "text": "Early work by Hainfeld [212] demonstrated the potential of high-Z nanostructures to enhance the effect of radiation and improve tumor control in mice treated with kilovoltage X-rays minutes after injection of gold nanoparticles (GNP). In vitro work using a wide range of cell lines and radiation qualities confirmed that the presence of GNP can enhance the effect of radiation by 10\u2013100% [213]."}
{"_id": "Radiology$$$21cbe0ed-9e90-47b6-bcf9-96330e73c616", "text": "Interestingly, the radiation sensitization observed in in vitro and in vivo work is often significantly greater than that predicted from simple macroscopic dose models. Furthermore, the size, shape, and surface coating of the nanoparticle as well as the radiation quality and cell line have been shown to affect the radiation response observed. The discrepancy between dosimetric and experimental results regarding the radiosensitization effect emphasizes that complex physical, chemical, and biological interactions are involved in high-Z nanoparticle-mediated radiosensitization, which still need to be fully elucidated in order to extrapolate the nanoparticle radiosensitization concept to patient cancer RT. Physical, chemical, and biological mechanisms of nanoparticle radiosensitization are shown in Fig. 11.24.\n\nAn illustration of the effect of nanoparticles and radio exposure on cancer cells. The effects are physical dose enhancement, chemical effects, and biological changes, eventually leading to cell death, such as apoptosis, necrosis, mitotic cell death, autophagy, and senescence.\n\nFig. 11.24\nPhysical, chemical, and biological mechanisms of nanoparticle. Nanoparticles radiosensitization. Reproduced with permission of Dove Medical Press Ltd., from Application of Radiosensitizers in Cancer Radiotherapy, International Journal of NanoMedicine, 16: 1083\u20131102, by Gong L et al. 2021"}
{"_id": "Radiology$$$59772fe0-21fc-4e56-a4e5-4ba4043d5f34", "text": "An illustration of the effect of nanoparticles and radio exposure on cancer cells. The effects are physical dose enhancement, chemical effects, and biological changes, eventually leading to cell death, such as apoptosis, necrosis, mitotic cell death, autophagy, and senescence."}
{"_id": "Radiology$$$dabe6d15-2f03-4a03-97a0-816a57250049", "text": "The physical processes driving the enhancement in radiation effectiveness in the presence of nanoparticles strongly depend on the radiation quality used. For medium-energy X-rays (<300\u00a0kVp), the radiation-nanoparticle interaction is dominated by the photoelectric effect, especially for photons with energies around the L- and K-shell excitation edges. This causes the emission of inner shell electrons from the high-Z material, resulting in a cascade of low-energy Auger electrons (10\u201320 electrons per interaction). The majority of these low-energy electrons are reabsorbed by the nanoparticle. Only a few Auger electrons escape the nanoparticle, releasing their energy in a few 10\u00a0s of nm around the nanoparticle [214]. As a result, the presence of high-Z nanoparticles increases the dose absorbed by the volume in which the nanoparticles are loaded, and it changes the spatial distribution of the ionizations concentrating the energy deposition around the nanoparticles."}
{"_id": "Radiology$$$5ef854c2-abb0-4318-8589-bcef2df7ca35", "text": "At higher photon energies (such as MV which is routinely used for cancer treatment), the dominant process in the interaction between radiation and nanoparticles is Compton scattering. At these energies, the Compton cross sections for high-Z materials are similar to that of soft tissues, and therefore no differences should be expected from the presence of high-Z nanoparticles. However, MV photon beams usually contain a considerable fraction of lower keV photons and electrons, which can also increase due to scattering processes (e.g., at 10 cm depth, the fraction of <150\u00a0keV photons from a flattening filter-free beam is between 13% and 20%). MV photon beams can therefore produce a considerable amount of Auger electrons from interaction with high-Z nanoparticles and alter both the macroscopic and the microscopic dose absorbed."}
{"_id": "Radiology$$$859f0ee0-016d-4b5b-868f-f98719e685eb", "text": "With protons and charged particles, the probability of interaction between the primary beam particle and the nanoparticles is considerably smaller than that for photon beams due to the lower number of primary tracks required to deliver a given dose. The dominant interaction process is the production of secondary electrons from the nanoparticle via small-angle scattering, which is proportional to the density and therefore higher for high-Z nanoparticles than for soft tissues. In contrast to the photon interactions, these secondary electrons are produced from the outer atomic orbital of the nanoparticle and contribute only a few percentages of the additional absorbed dose."}
{"_id": "Radiology$$$604aa45d-059e-4d77-98eb-c4a4dfe94141", "text": "In all cases, the presence of high-Z nanoparticles causes an increase in the overall macroscopic dose absorbed and high localized energy deposition spikes. The former was initially thought to be the main cause of the observed radiobiological enhancement. However, calculations clearly show that the additional absorbed macroscopic dose by itself is not enough to explain the increased effectiveness observed in experimental studies. The localized energy deposition spikes, caused by the presence of nanoparticles, are similar to those produced by the traversal of charged particles, and their impact on the biological effects can therefore be estimated using radiobiological models based on microscopic dose distributions. The local effect model (LEM) is widely used for charged particles and has been employed to demonstrate that higher radiosensitization enhancement ratios can be expected when local energy distribution is taken into account. Radiosensitization prediction by the LEM-based model strongly depends on the location of the nanoparticles and the radiation quality, with the closer the nanoparticles are to the critical structures of the cell (e.g., DNA), the larger the effect."}
{"_id": "Radiology$$$7fd0886a-1fec-406f-942a-8e81d0c49a8c", "text": "A key property of nanoparticles is the increased interaction with the surrounding environment (due to the high surface-to-volume ratio). The intracellular nanoparticle concentration is an important determinant for radiation sensitization. Numerous studies have investigated the importance of the nanoparticle size on cellular uptake, and an optimum diameter appears to range between 10 nm and 50\u00a0nm, showing a strong correlation between radiosensitization and nanoparticle concentration [215]. However, the precise value also depends on the coating and on the cell line. High-Z nanostructures are generally coated with a layer of polyethylene glycol (PEG) to provide a hydrophilic nature, preventing the nanostructures from aggregating and increasing their cellular internalization by macrophage recognition. Moreover, nanoparticles are often also conjugated with other biomolecules to achieve specific cellular and subcellular targeting. By using such an approach, it is possible to manufacture nanoparticles that dock to specific cell surface proteins or distinct subcellular compartments such as mitochondria using specific peptide sequences. The presence of the chemical coating and the high-Z element itself also change the chemical environment of the cell."}
{"_id": "Radiology$$$2999ee03-e985-4920-a1be-fc7be8a827ef", "text": "Reactive oxygen species (ROS) play an important role in mediating DNA damage produced by radiation. In fact, 50\u201370% of the DNA lesions in standard RT upon X-ray irradiation are attributed to the hydroxyl radical (OH). By altering the chemical environment of the cell, the nanoparticles can in principle affect both the yield and the spectrum of ROS produced, which in turn has consequences for the DNA damage. Competing mechanisms may be at play depending on the composition of the nanoparticles and their coating. For instance, certain chemical compounds, such as PEG, can act as ROS scavengers and actually detoxify radicals formed by the interaction of radiation with water molecules. Studies aiming at quantifying the G-value (i.e., the number of molecules of a specific radical produced per 100\u00a0eV of energy absorbed) have indicated three possible mechanisms through which nanoparticles can affect the ROS production by radiation and therefore affect the radiation effectiveness (Fig. 11.25). Increased radicals can be produced as a result of direct interaction between radiation and nanoparticles through the production of electrons and low-energy photons emitted by the nanoparticles. As the energy spectrum of the secondary radiation emitted by the nanoparticle is different from the primary radiation beam, a different spectrum of radicals is to be expected and the yield is generally higher due to their lower energy and cascade of secondary electrons. The presence of the nanoparticles, however, can also affect the yield of radicals produced by the direct interaction of radiation with the water molecules. This may occur through scavenging action from the nanoparticle-coating elements or by chemical interaction between the nanoparticles and the radiolysis products.\n\nThree illustrations, a through c, of different mechanisms. a. Primary water radiolysis. b. Secondary water radiolysis. c. Radical scavenging from nanoparticles.\n\nFig. 11.25\nSchematic representation of the possible pathways through which nanoparticles can affect the yield of radicals following radiation exposure: (a) primary water radiolysis, (b) secondary water radiolysis, and (c) radical scavenging from nanoparticles"}
{"_id": "Radiology$$$f814889e-3bb2-47fc-9e08-1a9e5416f38e", "text": "Three illustrations, a through c, of different mechanisms. a. Primary water radiolysis. b. Secondary water radiolysis. c. Radical scavenging from nanoparticles."}
{"_id": "Radiology$$$6a9e794f-8a32-4a67-b0c3-7eee904b7470", "text": "When nanoparticles reach the cell surface, they are usually internalized via endocytosis and end up in intracellular vesicles, also called endosomes. This endosomal pathway is often a barrier hindering biological or therapeutic effects of nanoparticles. Nevertheless, nanoparticles are able to escape the endosomal transport system, accessing the cytoplasm and organelles by destabilizing the endosomal membrane, inducing osmotic swelling and membrane rupture, or passively crossing the plasma membrane or the endosomal membrane [216]. Once internalized, the nanoparticles can affect different cellular and molecular processes. For instance, apart from creating additional DNA damage, nanoparticles directly or indirectly affect the functioning of DNA repair proteins by preventing their synthesis, posttranslational modification, or recruitment to the site of damage. For instance, due to the large specific surface area, nanoparticles are very efficient in capturing a large amount of proteins, including DNA repair proteins, eventually leading to their deprivation and hence reducing the DNA repair efficiency [217]. On the other hand, the release of metal ions could imbalance the metal homeostasis in the cells, which is critical for protein folding and could replace the metallic cofactor in active sites of enzymes that are involved in the antioxidant defense system, altering their structure and inhibiting their activity."}
{"_id": "Radiology$$$1b867fe9-5863-4bea-8fcf-1962d3b8d7ce", "text": "Besides affecting the DNA damage repair machinery and causing antioxidant enzyme inhibition, multiple in vitro studies showed that nanoparticles can cause cell cycle disruption. The radiosensitivity of cells can vary depending on their cell cycle phase, with cells in the late G2 and mitosis (G2/M) phases being the most radiosensitive, presumably because the condensed chromatin in mitotic cells is more susceptible to radiation-induced double-strand breaks, which are commonly repaired by the error-prone NHEJ mechanism. On the other hand, cells in the late S phase are the most radioresistant, due to the diffused chromatin regions and the fact that during the S phase, DNA damage is usually repaired by the accurate HR mechanism. Multiple research groups reported an elevated proportion of cells in the G2/M phase and a decreased cell number in the G0/G1 phase after gold nanoparticle exposure [218]. As a result, the radiosensitizing effects of gold nanoparticles can also be attributed to stalling of the cell cycle in the radiosensitive G2/M phase."}
{"_id": "Radiology$$$5cb60c68-22f5-47e3-9c3c-f6aed9c39522", "text": "Finally, mitochondria, located in the cytoplasm and having their own DNA, are another potential target for nanoparticle-mediated radiosensitization as the same processes as described above for nuclear DNA may affect mitochondrial (mt) DNA. However, nanoparticles are hardly ever detected in mitochondria and are often accumulated in endosomes and lysosomes. In general, although hypothetical, nanoparticles accumulated and irradiated within lysosomes or other organelles may decrease cell survival by directly harming these organelles and their functions [219]. Even milder damage to organelles could potentially lead to altered signaling and eventually increased cell death."}
{"_id": "Radiology$$$12648cdf-2d0c-4ddf-93d9-0dcd327465ae", "text": "Cytoplasmic organelles might thus represent a parallel or even dominant target to nuclear DNA. It is obvious from the previous paragraphs that nanoparticle-mediated radiosensitization is not fully understood. The research is complicated by extreme complexity and variability of the systems studied, including different materials, sizes, shapes, and modifications of nanoparticles; different cell types; different types of radiation and irradiation conditions, etc. Under certain experimental conditions, a plethora of biological processes may be induced so that it might not be excluded that different types and sizes of nanoparticles do interact according to specific mechanisms and their combinations (Box 11.6)."}
{"_id": "Radiology$$$f5065b78-8f76-40fc-80d6-46b1defbf502", "text": "The physical mechanisms of nanoparticle radiosensitization are related to both the higher attenuation cross section of high-Z materials compared to soft tissues and an increased clustering of ionizations from the secondary electrons emitted by the nanoparticle.\n\nThe chemical mechanisms are related to production and/or scavenging of reactive radical species mainly from the chemical compounds surrounding the nanoparticle.\n\nThe biological mechanisms are related to the interaction of the nanoparticles with the cellular and molecular processes, including antioxidant enzyme activities, the DNA repair pathways, the cell cycle and organelle functioning (e.g., mitochondria, lysosomes, ER, Golgi apparatus)."}
{"_id": "Radiology$$$e62dc800-be73-446d-9a33-7481ee72b4c3", "text": "The physical mechanisms of nanoparticle radiosensitization are related to both the higher attenuation cross section of high-Z materials compared to soft tissues and an increased clustering of ionizations from the secondary electrons emitted by the nanoparticle."}
{"_id": "Radiology$$$e306a7c0-7208-4ef3-a022-4e10bf9920d9", "text": "The chemical mechanisms are related to production and/or scavenging of reactive radical species mainly from the chemical compounds surrounding the nanoparticle."}
{"_id": "Radiology$$$e6d182ca-8454-4b62-8919-c07f4f7f2799", "text": "The biological mechanisms are related to the interaction of the nanoparticles with the cellular and molecular processes, including antioxidant enzyme activities, the DNA repair pathways, the cell cycle and organelle functioning (e.g., mitochondria, lysosomes, ER, Golgi apparatus)."}
{"_id": "Radiology$$$6cdf6675-a6f4-49a8-abe7-b3e581398998", "text": "Autophagy is a basic catabolic mechanism that involves cell degradation of unnecessary or dysfunctional cell components, such as damaged endoplasmic reticulum (ER) and other cytoplasmic constituents through lysosome action."}
{"_id": "Radiology$$$bd84949f-0558-49cb-8954-40b313736de3", "text": "The autophagy is mediated by protein complexes, such as class III PI3K, autophagy-related gene (Atg) proteins, and others containing microtubule-associated protein 1 light-chain subunit 3 (LC3), recruited to the membrane favoring membrane expansion and phagophore elongation. Particularly, autophagy can be activated by multiple signaling pathways, mainly through energy signals via AMPK. AMPK activation can phosphorylate ULK1, inhibit mTOR signaling, and activate Beclin-1 and Vps34 molecules resulting in the upregulation of autophagy intensity. Thus, the AMPK-mTOR-ULK1 pathway plays an important role in autophagy. Recently, the autophagy-related protein BECN1 has been shown to regulate radiation-induced G2/M arrest. In the context of a disease, autophagy has been described as an adaptive response to survival, a strategy to maintain metabolic homeostasis. In cancer cells, autophagy is a double-edged sword. In early stages, it could limit tumorigenesis. However, it could also provide a prosurvival function for adaptation and detoxification in a stressful environment, such as starvation, hypoxia, and chemotherapy/radiotherapy."}
{"_id": "Radiology$$$23763556-2995-484e-a237-07b809275997", "text": "Some studies show that the autophagy preventing is radiosensitive, while the autophagy promoting is radioprotective, suggesting that IR-induced autophagy may represent an adaptive response to maintain tumor growth and survival. In order to improve IR tumor responses, several sensitization agents to radiation-induced autophagy are currently being studied. The molecular machinery involved in IR-induced autophagy is still not clear. Recent studies show that p53 and PARP-1, a DNA repair enzyme triggered by DNA damage, exert essential roles in starting the autophagy process regulating the PI3K/PKB/AKT/mTOR signaling pathway that represents an autophagy key regulator. Reports by investigators have recently shown that autophagy activity increased after IR and chemotherapy. It is an escape mechanism for cell survival in response to cytotoxic agents, including IR and temozolomide (TMZ) in glioblastoma (GBM) treatment [220]. In radioresistant breast cancer (BC) cells, a strong postirradiation autophagy induction has been observed as a protective and prosurvival mechanism of radioresistance after exposure to IR. Studies have also shown that induced autophagy in some radioresistant cancers, such as GBM, causes IR sensitization and increased cell death."}
{"_id": "Radiology$$$85468bdb-8afa-47da-aa3a-f1432a1d38a1", "text": "In normal conditions, microautophagy and chaperone-mediated autophagy permit the breakdown of abnormal proteins, cellular debris, or damaged organelles, maintaining cellular homeostasis and/or as tools to recycle biological constituents (e.g., amino acid, fatty acid, and energy in the form of ATP). After stress stimuli, such as nutrient starvation, protein aggregation, organelle damage, and oxidative or genotoxic stress, including by IR, the autophagy hyperactivation promotes cell death, via nonapoptotic and caspase-independent mechanisms, and this case is also called macroautophagy [221]."}
{"_id": "Radiology$$$9f1a62c5-45db-44bf-a23e-c028848a4a99", "text": "As described above, AMPK promotes the activation of autophagy. Among factors activated by AMPK, an interesting and not well-described role in the autophagy process, it was supposed to be for glucose transporter GLUT-1, often upregulated in cancer cells. In this sense, the cross talk among GLUT1, curcumin, and AMPK pathway in LC remains vague. Interestingly, it was recently described that the treatment with GLUT1 siRNA alone or in combination with curcumin resulted in profound improvement of the radiosensitivity of LC cells after irradiation. In particular, curcumin and GLUT1 siRNA combined treatment not only promoted apoptosis of LC cells, but also induced autophagy-associated cell death through activation of AMPK/mTOR/ULK1 signaling-mediated autophagy with or without irradiation treatment [222]."}
{"_id": "Radiology$$$90fc3f60-2de5-45c0-a670-98f11a3c7b71", "text": "Taking all these observations, we can speculate that the role of autophagy in cancer cells depends upon certain factors, such as cell type, specific characteristics of tumor cells, microenvironment of the tumor, and type of treatment applied. In addition, a variety of radiation-resistant molecules, such as PI3K/AKT, EGFR, NF-\u03baB, and p53, may play an important role in the regulation of autophagy, thus indicating that the mechanisms that regulate autophagy are very complex. Thus, many questions and contradictory findings have yet to be clarified."}
{"_id": "Radiology$$$f3265bf3-5e60-49b2-8621-7a9be5b0cacd", "text": "In cancer patients, MTF may affect tumor growth and treatment response in two different ways: directly by inhibiting mitochondrial metabolism and activating downstream cell signaling pathways in cancer cells or indirectly by keeping low the levels of glucose, insulin, and other factors which can activate cancer cell proliferation [223]. MTF has also shown anticancer effects in nondiabetic patient populations (described in Sect. 11.1.9)."}
{"_id": "Radiology$$$e77b261e-1804-431d-a42d-194ff8f5e76d", "text": "With regard to the relationship between MTF and IR, MTF is able to increase intrinsic radiosensitivity, as tested in vitro in many cell lines of different tumors, including lung, head and neck, breast, liver, prostate, and pancreas cancers and murine fibrosarcoma, with specific cell line-dependent radiosensitizing effect [203, 223]."}
{"_id": "Radiology$$$8ca952e3-ab8e-4f55-84e0-8ffa2b4cf42c", "text": "Several clinical data on the effect of MTF on patient outcome, focused particularly on patient populations undergoing RT, have shown that these patients have better outcomes if they are treated with MTF. These and other data show the significant role of MTF in enhancing the RT efficacy and suggest an interaction between MTF and IR [223]."}
{"_id": "Radiology$$$b50ccc1e-125b-4ac3-bf26-31f5e7ba683e", "text": "In vitro and in vivo studies, concerning the MTF radiosensitizing effect, have showed an enhanced DNA damage after MTF treatment combined with RT, as tested by phosphorylation of histone \u03b3H2AX, a well-known marker for DNA damage [203]."}
{"_id": "Radiology$$$8650f5cf-187e-42f9-a4ba-eb57829aabf3", "text": "In particular, MTF may increase initial DNA damage or inhibit repair processes, being able to reduce the expression of DNA repair protein Ku70 and hamper radiation-induced activation of EGFR and DNA-dependent protein kinase catalytic subunit (DNA-PKcs). Considering that the primary targets of MTF are the mitochondrial complex I and mGPD (glycerol-3-phosphate dehydrogenase), it may induce an increase of ROS generation and oxidative damage to lipids, protein, and DNA that could strengthen the effects of IR. Indeed, several data have demonstrated that MTF can increase ROS in cancer cells when delivered alone or in combination with IR. In general, as regards the main known MTF mechanisms of action when combined with RT, in vitro and in vivo data show a significant role of MTF in affecting at least four different parameters at radiobiological level, including intrinsic cell radiosensitivity (SF2, i.e., the fraction of cells surviving after a single IR dose of 2\u00a0Gy), cancer stem cell fraction, tumor proliferation rates, and tumor hypoxia [223]."}
{"_id": "Radiology$$$2e5b5290-56e2-424c-8807-84880ee56b85", "text": "Poly-(adenosine diphosphate-ribose)-polymerase (PARP) are cellular enzymes that play crucial roles in various cell processes like replication, transcription, cellular repair, and also death [224]. PARP detects single-strand breaks and triggers the activation of cellular machinery involved in the repair of the single-strand break. Studies have shown that PARP inhibitors (PARPi) exhibit enhanced radiosensitivity when combined with IR. Radiation works by damaging the DNA, which can activate the single-strand break (SSB) repair pathway like base excision repair (BER) or double-strand break (DSB) pathways like the\u00a0HR and the NHEJ pathway (more details in Chap. 3). SSB, if unrepaired, gets converted to double-stranded breaks, which consequently hinder normal cellular processes. PARPi imparts radiosensitivity through the SSB and base excision pathway, which substantially increases the risk to collapsed replication fork, thereby producing a stable DSB [225]. Due to the crucial role of PARP in the DNA repair pathway, PARPi have proved as effective radiosensitizers, especially in tumors harboring DNA repair deficiencies like the BRCA mutation. The replication-reliant operations of PARPi facilitate the establishment of differential outcomes in tumor and healthy tissues. Other mechanisms that are known to induce the radiosensitization effects include inhibition of chromatin remodeling, G2/M arrest, vasodilatory effect induced by PARPi, etc. Characteristically, factors that affect radiosensitivity are the capability of tumors to repair the damage, redistribution of the cell cycle, process of reoxygenation, vascular endothelial damage process, tumor immunity, and repopulation of the tumor tissue. A radiosensitizer should have the potential not only to influence these processes but also prevent the increase in the toxicity. Since PARPi possess most of these qualities necessary for being a potential radiosensitizer (Fig. 11.26), it has gained interest in the medical community [226].\n\nAn illustration of modes of action and advantages. Mode of action: Inhibition of D N A repair and chromatin remodeling, G 2 M arrest, decrease in hypoxia, and vasodilatory effect. Advantages: Replication, protection of normal tissue, impairing synthetic lethality, and low toxicity molecules.\n\nFig. 11.26\nThe advantages and various modes of action by which PARPi enhance the radiosensitivity of tumor cells. Adapted from \u201cPoly-(ADP-ribose)-polymerase inhibitors as radiosensitizers: a systematic review of preclinical and clinical human studies,\u201d by [224], Licensed under CC BY 3.\u200b0"}
{"_id": "Radiology$$$63f87866-27d4-49a6-8baf-1ca9f4eae25d", "text": "An illustration of modes of action and advantages. Mode of action: Inhibition of D N A repair and chromatin remodeling, G 2 M arrest, decrease in hypoxia, and vasodilatory effect. Advantages: Replication, protection of normal tissue, impairing synthetic lethality, and low toxicity molecules."}
{"_id": "Radiology$$$e5dc316b-9247-4862-8ea0-3b4dec0a225e", "text": "Nitroxides are a class of stable free radical compounds that exhibit antioxidant mechanisms, thereby safeguarding the cells from several lethal agents like superoxide and hydrogen peroxide (also described in Sect. 11.1.2). However, the rationale to use nitroxides in cancer RT comes from the role of free radicals in tumor development and capacity of inhibitors of radical reactions to suppress tumorigenesis. The underlying mode of action of nitroxyls exhibiting the radiosensitization effect can be attributed to cell signaling, enhanced blood flow to the tumor, consequences on the cellular respiration, and generation of reactive oxygen and nitrogen species that can operate as metabolite radiosensitizers. The effects of nitroxides with radiation were found conflicting, leading to uncertainty about their radiosensitizing nature."}
{"_id": "Radiology$$$15dc90b0-afd2-4f91-87e6-91e45e265165", "text": "Tempol (TPL) is a piperidine nitroxide that possesses an unpaired electron and goes through swift reversible transfer among the three forms: nitroxide, hydroxylamine, and oxoammonium cation. Based on its concentration in the cell, it can act as an oxidative or reductive agent. In cancer cells, TPL favorably inhibits growth by increasing the generation of cellular ROS [227]. When used with RT and chemotherapy, TPL exhibits a differential effect of protecting the normal healthy cells from RT and cisplatin-mediated damage, whereas in cancer cells, tempol is reduced to its hydroxylamine form that is unable to protect the cells from radiation and cisplatin-mediated damage. This differential or selective acting on cancer cells while sparing the normal cells is particularly of significance in cancer radio- as well as chemotherapy [228]. It was observed that the anticancer effects of cisplatin increased due to the prooxidant activity of TPL via the increased ROS-mediated cell apoptosis [227]. In several cancer cell lines, TPL was able to free radical-dependent apoptosis. On 24-h exposure to TPL, human promyelocytic leukemic cell line (HL-60) showed reduced levels of mitochondrial and intracellular glutathione, failure in the oxidative phosphorylation process, and diminished mitochondrial membrane potential. TPL also particularly targeted the respiratory chain complex I and showed some insignificant effects on the complexes II and IV. This can be attributed to the role of mitochondria in apoptosis and it being a free radical resource and target. In HL-60, TPL works by targeting the mitochondria, which subsequently leads to mitochondria associated with oxidative stress and apoptosis. This in turn can sensitize the tumor cells to the proapoptotic effects of cytotoxic agents [229]. When human breast cancer cells (MDA-MB 231) were treated with tempo, another nitroxide, it exhibited considerable levels of tyrosine phosphorylation of numerous unknown proteins when evaluated with the equimolar concentration, i.e., 10 mm TPL. The compounds tempo and TPL lead to the phosphorylation of tyrosine and trigger the Raf-1 protein kinase (30\u00a0min, two- to threefold) [230]. Nevertheless, TPL leads to augmented extracellular signal-regulated kinase 1 activity. Tempo also activated the stress-associated protein kinase (2\u00a0h, threefold) and induced apoptosis (2\u00a0h, >50%). The ceramide levels significantly increase (54% over control) at 30 min and (71% over control) at 1\u00a0h after treatment, prior to activation of stress-activated protein kinase and cell death via apoptosis [230]. TPL protects normal cells and tissues from oxidative damage and remarkably hampers the proliferation of cancer cells. These clearly imply that the nitroxide TPL shows the potential to be a good prooxidant and can be a potent radiosensitizing agent for cancer treatment."}
{"_id": "Radiology$$$df41094d-c9c2-42db-82f8-62e40fd35e79", "text": "Q1.\nHow do radioprotectors work?\n\u00a0Q2.\nWhat is the purpose of radioprotectors in RT?\n\u00a0Q3.\nWhat is TRUE: All the antioxidants are radioprotectors or all the potential radioprotectors are often antioxidants?\n\u00a0Q4.\nWhat are radiomitigators?\n\u00a0Q5.\nCan immunomodulators be classified as radiomitigators?\n\u00a0Q6.\nWhat is the purpose of a radiosensitizing agent in cancer RT?\n\u00a0Q7.\nDescribe the curcumin action mechanism when administered with irradiation.\n\u00a0Q8.\nGenerate a graph similar to Fig. 11.1 for gadolinium nanoparticles and estimate the mass attenuation coefficient ratio at 100\u00a0keV."}
{"_id": "Radiology$$$22679267-0b6c-491e-9449-8be200aa6c61", "text": "What is TRUE: All the antioxidants are radioprotectors or all the potential radioprotectors are often antioxidants?"}
{"_id": "Radiology$$$0dce6e0f-5bb3-4713-9ebe-c0160849fe7a", "text": "What is the purpose of a radiosensitizing agent in cancer RT?"}
{"_id": "Radiology$$$a5fcbda8-ec2c-4e5f-a1b3-d18c715019b5", "text": "Generate a graph similar to Fig. 11.1 for gadolinium nanoparticles and estimate the mass attenuation coefficient ratio at 100\u00a0keV."}
{"_id": "Radiology$$$bcefdafc-c505-4af9-9009-1a7e422c7d7a", "text": "SQ1.\nThe detailed mechanisms are described in Sect. 11.1.1. The possible mechanisms are listed in Box 11.2 as well.\n\u00a0SQ2.\nRadioprotectors, which should be safe and nontoxic for human health, are used to protect the normal cells or nontumor cells from the harmful insults of ionizing irradiation and to increase survival rate in patients when administered before the exposure to radiation or at the time of RT for their effectiveness.\n\u00a0SQ3.\nThe potential radioprotectors are often antioxidants, but not all the antioxidants are radioprotectors.\n\u00a0SQ4.\nRadiomitigators are used to minimize the toxicity or damage caused by ionizing irradiation in noncancerous cells even after radiation has been delivered and thus able to improve the effectiveness of radiation therapy.\n\u00a0SQ5.\nYes. Radioprotective agents with potency to stimulate the proliferation and modify the function of hematopoietic and immunopoietic stem cells, often referred to as immunomodulators, can be considered as radiomitigators. The mode of action (MOA) of radiomitigators is depicted in the figure (figure number will be written).\n\u00a0SQ6.\nRadiosensitizer is a chemical or pharmaceutical agent which enhances the killing effect on tumor cells by making them more susceptible/sensitive to radiation therapy and at the same time having less effect on normal tissues/cells.\n\u00a0SQ7.\nCurcumin has been shown to have a double-face mechanism. Indeed, on the one hand, it is an antioxidant and anti-inflammatory molecule, useful in limiting the IR-induced ROS generation and IR side effects. On the other, it acts as an anticancer molecule, interacting with cellular processes, such as cell cycle, proliferation, apoptosis, and autophagy.\n\u00a0SQ8.\nGd/water mass attenuation coefficient ratio @ 100\u00a0keV\u00a0=\u00a072.6.\n\nA line graph of the decrease in mass attenuation coefficients of G d and water with an increase in photon energy."}
{"_id": "Radiology$$$f402adf9-8f08-41ee-b4e4-69cf6e7f775c", "text": "The detailed mechanisms are described in Sect. 11.1.1. The possible mechanisms are listed in Box 11.2 as well."}
{"_id": "Radiology$$$8062fbf3-54f0-4286-a803-ad2c976d1585", "text": "Radioprotectors, which should be safe and nontoxic for human health, are used to protect the normal cells or nontumor cells from the harmful insults of ionizing irradiation and to increase survival rate in patients when administered before the exposure to radiation or at the time of RT for their effectiveness."}
{"_id": "Radiology$$$3df77ef2-b055-4320-abe6-53bf00520652", "text": "The potential radioprotectors are often antioxidants, but not all the antioxidants are radioprotectors."}
{"_id": "Radiology$$$8518c4e2-f1bf-49c3-8b03-78c00aafac79", "text": "Radiomitigators are used to minimize the toxicity or damage caused by ionizing irradiation in noncancerous cells even after radiation has been delivered and thus able to improve the effectiveness of radiation therapy."}
{"_id": "Radiology$$$db697f2b-c999-486a-837b-6c9cc7d439fe", "text": "Yes. Radioprotective agents with potency to stimulate the proliferation and modify the function of hematopoietic and immunopoietic stem cells, often referred to as immunomodulators, can be considered as radiomitigators. The mode of action (MOA) of radiomitigators is depicted in the figure (figure number will be written)."}
{"_id": "Radiology$$$389f65ba-3a87-4d5c-ae6c-548ee37f418a", "text": "Radiosensitizer is a chemical or pharmaceutical agent which enhances the killing effect on tumor cells by making them more susceptible/sensitive to radiation therapy and at the same time having less effect on normal tissues/cells."}
{"_id": "Radiology$$$e15401a7-f2bd-4077-b948-e61a65884556", "text": "Curcumin has been shown to have a double-face mechanism. Indeed, on the one hand, it is an antioxidant and anti-inflammatory molecule, useful in limiting the IR-induced ROS generation and IR side effects. On the other, it acts as an anticancer molecule, interacting with cellular processes, such as cell cycle, proliferation, apoptosis, and autophagy."}
{"_id": "Radiology$$$b3eeaaa2-ecbd-4d5f-997b-ca897b55ece4", "text": "Gd/water mass attenuation coefficient ratio @ 100\u00a0keV\u00a0=\u00a072.6.\n\nA line graph of the decrease in mass attenuation coefficients of G d and water with an increase in photon energy."}
{"_id": "Radiology$$$88c2cd8c-bf1a-4954-bdeb-9969db3faf94", "text": "A line graph of the decrease in mass attenuation coefficients of G d and water with an increase in photon energy."}
{"_id": "Radiology$$$1a41e45c-2308-49b6-a157-e8ba5064950b", "text": "Ionizing radiation and radioactive substances can be natural or human-made. Humans have always been exposed to natural ionizing radiation (background radiation), because of the exposure of the Earth\u2019s surface to cosmic rays and the radioactivity contained in rocks that form the continental crust. The use of radiation and radioactive substances in medicine, research, industry, agriculture, and teaching, as well as the generation of nuclear power, have brought important benefits to society. Acceptance by society of the risks associated with radiation depends on the perceived relationship between these risks and the benefits to be gained from the use of radioactive sources. Logically, risks must be limited, and adequate protection provided. This does not mean that individuals or the environment must be protected from any and all effects of ionizing radiation, but rather to ensure that the amount of radiation absorbed does not have negative consequences that outweigh the benefits. The need to balance risks and benefits makes radiation a matter of science and values, meaning that in addition to technical assessments, ethical and legal issues also apply in the judgement of the acceptability of radiation risks."}
{"_id": "Radiology$$$e7713ff4-ab1f-4f7d-8650-204304160bd2", "text": "After the initial and isolated observations of the first health effects of ionizing radiation (i.e., skin burns and cancers) by the pioneers at the turn of the nineteenth and twentieth centuries, two decades passed before a clear need for radiation protection\u00a0was identified. One of the first signs was the leukemia epidemic that developed among radiologists after World War I, reflecting the use of X-ray radioscopy by military surgeons, without any kind of protection, to localize shrapnel in wounded soldiers. This epidemic lasted until the 1950s and affected approximately 500 radiologists [1]."}
{"_id": "Radiology$$$1c7e5fa6-9c47-4fe7-b65b-f2ed28a91d2f", "text": "To face the situation, the International Society of Radiology created the International Committee on Radiation Units (ICRU) in 1925 to develop the first concepts regarding dose quantification which were obviously needed. This was followed by the creation in 1928 of the International X-ray and Radium Protection Committee which was restructured in 1950 to take account of new uses of radiation outside the medical area and then renamed the International Commission on Radiological Protection (ICRP). Both ICRU and ICRP are still major actors of radiological protection."}
{"_id": "Radiology$$$8f5b80aa-435f-4c21-be07-387f2612960e", "text": "Although the radiological protection (RP) system was established by ICRP, it is worth noticing the critical contribution of the United Nations Scientific Committee on the Effects of Atomic Radiations (UNSCEAR) created in 1955. The ICRP RP system is developed on the basis of the scientific knowledge gathered and synthetised by UNSCEAR."}
{"_id": "Radiology$$$83a1d1d4-bbff-4bad-bcd6-d6c36ae5559f", "text": "The ICRP publishes a wide range of recommendations dealing with various aspects of radiological protection, but the current RP system with the three principles of justification, optimization, and dose limitation was first established with recommendation 26 [2]. It has been updated since then by recommendations ICRP 60 [3] and ICRP 103 [4]."}
{"_id": "Radiology$$$d82f907c-fa99-42ba-94e1-a35e9bc65daf", "text": "ICRP has designed dosimetric factors to properly quantify the exposures to IR and then to establish links between dose and effects. The absorbed dose D is the energy deposited in the tissue: the unit of 1\u00a0J/kg is the Gray (Gy) in memory of James Gray. To take into account that different types of radiation do not produce the same biological effects for the same absorbed dose, a radiation weighting factor WR is used to convert the absorbed dose into the so-called equivalent dose HR\u00a0=\u00a0WR\u22c5D. This unit is the Sievert (Sv) in memory of Rolf Sievert. But the biological response also depends on the tissue and a tissue weighting factor WT is used to convert the equivalent dose for each organ to the so-called effective dose E by adding the contributions of all organs E\u00a0=\u00a0\u03a3R,TWTHR,T. The effective dose unit is still the Sv and when a dose is given in Sv it is mandatory to indicate if it relates to an equivalent dose or to an effective dose. Thus, only the absorbed dose is a physical parameter. Equivalent and effective doses are calculated parameters reflecting the likelihood of detriments in humans."}
{"_id": "Radiology$$$cb5d15fc-156d-4c0c-b93d-9ee2b3778186", "text": "The effects of IR have been classified for years into two categories named deterministic and stochastic effects. Deterministic effects, e.g., skin burns, are due to high doses of ionizing radiation and the responsibility of radiation in their occurrence is clear. Deterministic effects always occur after a dose threshold is exceeded even though some individual variation exists, and the severity of the effect increases with dose. Stochastic effects, such as cancers, may occur after exposure to ionizing radiation but it is only possible to statistically express the occurrence. In other words, it is impossible to say who will develop cancer and when it will appear. One can only say that a percentage of cancers will appear in a population of persons exposed to a given dose, and the probability of developing cancer will increase with dose. Partly because of relatively high background rates of cancers in human populations, the establishment of a causal relationship between exposure to ionizing radiation exposure and the occurrence of cancer can be quite difficult (see Chap.\u00a04)."}
{"_id": "Radiology$$$2bdb99b6-b124-43d1-9cdf-cb449443e6ea", "text": "More recently the separation between deterministic and stochastic effects does not appear to be so clear since some effects may combine both approaches, such as radio-induced cataracts. Therefore, ICRP now uses the classification tissue effect instead of deterministic effects."}
{"_id": "Radiology$$$276abf47-0355-451d-b133-43715527f35a", "text": "Risk evaluation has resulted from epidemiologic studies that have established solid correlations (but not causality) between the frequency of cancers and the dose of IR in the dose range above 100\u00a0mGy. But ICRP recommendations are not so clear since the same numerical value is given sometimes in Sv. The calculated risk of cancer is roughly 5% per Sv of effective dose, while the risk to the developing fetus is 50% per Sv. The risk of hereditary disease has been estimated as 0.5% per Sv based on animal models, although it has not been documented so far in humans."}
{"_id": "Radiology$$$e75490f2-e0ec-4e03-b7aa-9d85d79e8d8e", "text": "Epidemiologic studies have paved the way for effective management of radiation protection with the three ICRP principles of radiological protection, i.e., justification of all exposures, optimization of the justified exposures (ALARA principle), and limitation of doses for the workers and the population. Dose limitation does not apply for patients because doses need to be adapted for both diagnosis and treatment. The overarching goal was to suppress the deterministic effects and to substantially minimize the probability of the occurrence of stochastic effects."}
{"_id": "Radiology$$$b07fd602-d1a9-45f2-99e0-202fc0a892b9", "text": "On the basis of scientific evidence, ICRP has progressively recommended the mandatory decrease in the exposure to the level of low doses. The actual exposure of workers to ionizing radiation has clearly decreased over the years and is now in the order of or below 1\u00a0mSv/year of effective dose in most countries, although the legal limit is still 20\u00a0mSv/year for the effective dose. The dose limit of 1\u00a0mSv effective dose for the public is below the variations of natural background. At present, the dose limits of the system of radiological protection are quite low and are therefore not foreseen to be changed in the near future. However, doses from medical exposures are still steadily rising."}
{"_id": "Radiology$$$fcb648a5-e5d2-4467-93c3-9ec2a33c6dca", "text": "The ethical foundations of the system of radiological protection were reviewed by ICRP in its publication 138 [5]. This underlined that radiological protection is not only a matter of science but has been developed on ethical values either intentionally or indirectly. Four core ethical values (beneficence/non-maleficence, prudence, justice, and dignity) underpin the present system and relate to the three principles of radiological protection. This publication also addresses key procedural values (accountability, transparency, and inclusiveness) required for the practical implementation of the system (see the following section for more details)."}
{"_id": "Radiology$$$2ccb410b-abe5-4323-aac3-12d10746719f", "text": "Although the system of radiological protection developed and updated by ICRP for more than eight decades has proved robust and operational, there remain a number of ethical, legal, and social challenges\nRisk evaluation is a major concern since this drives the allocation of resources for radiation protection. The majority of doses in humans are in the low-dose range with a very low risk of cancer. The effective dose should not be used for risk evaluation for a specific individual [4]. Regarding medical exposures, there is a need to develop individual risk evaluation based on doses to the organs exposed [6].\n\nThe human individual response to ionizing radiation should be included in the system in order to optimize radiological protection. This will be part of personalized and predictive medicine, for example, in persons with a high familial risk of cancer or in patients who are likely to be repeatedly exposed to ionizing radiation for medical reasons (especially children, women, prior to radiotherapy or to repeated screening).\n\nThere should be an increased focus on communication with the public and media. There is a need to understand the psychological aspects of risk perception, especially when these show diversion from the real exposures and risks."}
{"_id": "Radiology$$$00f9bbfe-65bd-4169-9e07-6b8206ae5205", "text": "Risk evaluation is a major concern since this drives the allocation of resources for radiation protection. The majority of doses in humans are in the low-dose range with a very low risk of cancer. The effective dose should not be used for risk evaluation for a specific individual [4]. Regarding medical exposures, there is a need to develop individual risk evaluation based on doses to the organs exposed [6]."}
{"_id": "Radiology$$$e20ce766-a859-456b-8318-53013c7e66d6", "text": "The human individual response to ionizing radiation should be included in the system in order to optimize radiological protection. This will be part of personalized and predictive medicine, for example, in persons with a high familial risk of cancer or in patients who are likely to be repeatedly exposed to ionizing radiation for medical reasons (especially children, women, prior to radiotherapy or to repeated screening)."}
{"_id": "Radiology$$$13353b10-0884-4c6e-8cf5-0cd2fc259cb0", "text": "There should be an increased focus on communication with the public and media. There is a need to understand the psychological aspects of risk perception, especially when these show diversion from the real exposures and risks."}
{"_id": "Radiology$$$57cc0f71-c8e4-4d1e-aa45-6d3331aa1cb6", "text": "Discussion about the meaning and appropriateness of the acronym LNT has been central in the debate on radiation protection against low-level exposure situations. As an acronym, LNT is non-translatable; a fact that does not facilitate communication. LNT is aimed to denote an imprecise expression: \u201clinear-non-threshold,\u201d a short reference to the relationship between the probability of suffering a radiation health effect and the incurred radiation dose, following low doses, low dose rate, radiation exposures."}
{"_id": "Radiology$$$042f4dcf-f027-4b5d-b4c8-3dfe96274204", "text": "It is to be noted that this imprecise acronym has been widely used with different connotations by relevant professional communities, a conundrum that can be simplistically summarized as follows:\nFor radiation biologists, LNT usually refers to a biological hypothesis postulating that at low radiation doses a given increment in dose will produce a directly proportionate increment in the probability of incurring malignancies or heritable effects attributable to radiation.\n\nFor radiation epidemiologists, LNT is an epidemiological conjecture by which the incidence of effects per unit dose measured at radiation exposure situations involving relatively high doses delivered at relatively high dose rates, where an epidemic of increases in malignancies have been recorded, is presumed to occur also at radiation exposure situations involving low doses and low dose rates in spite that epidemiological evidence is not achievable in such situations.\n\nFor radiation-protectionists, LNT represents a practical operational model for managing radiation protection and controlling that protection against additional doses regardless of the level of accumulated dose, and, therefore, preventing discrimination\u2014particularly age-related labor discrimination in cases of occupational radiation protection."}
{"_id": "Radiology$$$d6d48351-3828-4018-aff5-09ff0ec950dc", "text": "For radiation biologists, LNT usually refers to a biological hypothesis postulating that at low radiation doses a given increment in dose will produce a directly proportionate increment in the probability of incurring malignancies or heritable effects attributable to radiation."}
{"_id": "Radiology$$$50ffb878-d484-44a1-b216-51eb597a69c3", "text": "For radiation epidemiologists, LNT is an epidemiological conjecture by which the incidence of effects per unit dose measured at radiation exposure situations involving relatively high doses delivered at relatively high dose rates, where an epidemic of increases in malignancies have been recorded, is presumed to occur also at radiation exposure situations involving low doses and low dose rates in spite that epidemiological evidence is not achievable in such situations."}
{"_id": "Radiology$$$7a1957c4-b6f4-4b18-9069-6a3b22739a09", "text": "For radiation-protectionists, LNT represents a practical operational model for managing radiation protection and controlling that protection against additional doses regardless of the level of accumulated dose, and, therefore, preventing discrimination\u2014particularly age-related labor discrimination in cases of occupational radiation protection."}
{"_id": "Radiology$$$0d07e200-e59d-44ac-be05-82210b4b9691", "text": "The wide and imprecise use of the acronym LNT without clarification of its precise meaning has been a cause of serious confusion on the health effects attributable following low dose, low dose rate, and radiation exposure situations."}
{"_id": "Radiology$$$59ab53a9-4439-4db9-a202-90052eccc20e", "text": "It could be succintly said that LNT is intended to mean a practical model rather than a sophisticated scientific theory and that it is based on the globally accepted principles of ethical prudence and on labor rights for non-discrimination\u2014long established by international undertakings."}
{"_id": "Radiology$$$893f10f4-a214-493f-a601-de7be44ee379", "text": "What are we speaking about when we speak about ethical, legal, social, and psychological aspects in relation to the radiological risk? Dealing with radioactivity in society is a complex challenge in any respect, but one can distinguish four fundamental \u201ccontexts of concern\u201d that require different visions on complexity, and what it would mean to responsibly deal with it. When considering ethical, legal, social, and psychological aspects of radiation exposure, it is important to always do this with the context of application or \u201cthe context of concern,\u201d in mind."}
{"_id": "Radiology$$$37970e64-521d-4af8-a224-14d99ffcd396", "text": "The first context is the context of \u201cnaturally enhanced\u201d natural radiation. The second context concerns industrial practices that involve technically enhanced natural radiation. The third context is the context of peaceful applications of nuclear technology. These include applications of nuclear physics processes, such as the fission or fusion of nuclei for energy production or the use of decay radiation in medical treatment and diagnosis or for industrial purposes. The fourth context is the use of nuclear technology or material as a weapon, either as a means for political deterrence, in organized military operation or in terrorist actions."}
{"_id": "Radiology$$$fb844cd4-c639-46ce-8816-b92bff4a91d2", "text": "The reason to distinguish these different contexts is motivated by a specific understanding of the ethics of radiological risk governance and its relation to the social and political aspects of governance, and this as well in theory as in practice. To put it simply, if we consider average natural background radiation as an element of our natural habitat, then any significantly enhanced level of radioactivity in the vicinity of living species represents a risk\u2014in the sense of a potential harm\u2014to the health of those living species. In these cases, pragmatic reasoning thus requires us to consider the possibility of protection, mitigation, or avoidance, but essentially to first evaluate why the additional radioactivity occurs in the first place, and whether we can possibly justify it. But whether that justification exercise can be done meaningfully or not depends on how we perceive the context of the occurrence of radiation."}
{"_id": "Radiology$$$58ae6161-5a9a-4189-8e13-ddb2f43aa7f7", "text": "From what the first context is concerned, whether we want it or not, natural radiation is there and any naturally enhanced occurrence (e.g., in the case of high concentrations of Radon) has a potential impact on health. Thinking in terms of justification of the presence of that radiation is meaningless, which leaves us with evaluating the justification of exposure, and thus of the possibility of protection, mitigation, or avoidance of its impact."}
{"_id": "Radiology$$$9c78a2c1-0412-4058-9713-d8d1456336bc", "text": "In the second context of technically enhanced natural radiation (for example, in the oil refinery industry or in aviation), radiation exposure manifests as a \u201cside effect.\u201d Practices as such may be contested (as is the case with the oil or phosphate industry), but very rarely the issue of radiation exposure will become a decisive factor in the evaluation of the justification of these practices. Similar to the case of naturally enhanced natural radiation, the radiation justification exercise thus restricts itself to the evaluation of exposure, and thus to the evaluation of the possibility of protection, mitigation, or avoidance of its impact."}
{"_id": "Radiology$$$3fd5318d-4183-440f-8f87-0cd9df2285d0", "text": "In the third context, evaluation of the justification of the use of nuclear technology obviously takes the reason for that proposed use (the projected \u201cbenefits\u201d) as a first criterion, with the aim to \u201cbalance\u201d it with the projected risks. Despite the fact that opinions on these projected benefits and risks differ among people, in this context, an evaluation of the justification of the use of a risk-inherent technology, or thus of the presence or \u201ccreation\u201d of radiation, remains meaningful, and this is because the application context is \u201cneutral\u201d; while opinions may differ on how to produce energy or perform a medical treatment, nobody is \u201cagainst energy\u201d or \u201cagainst medical care\u201d as such. The neutral context thus makes a meaningful joint evaluation of the justification of the nuclear technology application possible, and it will not affect possible outcomes (rejection or acceptance of the technology) as such."}
{"_id": "Radiology$$$2c2320d2-fb01-45fd-963b-8d5b76033301", "text": "Finally, in the fourth context, a meaningful joint evaluation of the justification of (the risk of) the nuclear technology application is not possible, and this is for the reason that the context of application itself is not neutral. A pacifist perspective does not support a principal justification of nuclear deterrence and armed conflict strategies, while, in a perspective that sees politics always as a politics of power and conflict, these strategies may be perceived as justified."}
{"_id": "Radiology$$$51d5f1d3-22a1-47de-9691-d22a5d91623d", "text": "Any evaluation of the acceptability of a radiological risk is characterized by a \u201cdouble\u201d complexity. Firstly, it needs to take into account the uncertainties with regard to whether and how the risk will manifest. Science has an authoritative voice in this evaluation, but it needs to recognize that there will always be uncertainties that cannot be cleared out (stochasticity of biological effects at low radiation dose, possible delayed harm of medical diagnosis or therapy, the possibility of a nuclear accident, the fate of a radioactive waste disposal site in the far future, \u2026). In addition, we have to accept that important factors remain to a large degree beyond control: human behavior, nature, time, and potential misuse of technology\u2026 Secondly, an evaluation of the acceptability of a radiological risk also needs to consider diverse value judgments with regard to the acceptability of the risk. In philosophical terms, one can say that the evaluation is troubled by moral pluralism: even if we would all agree on the scientific knowledge base for the assessment of the risk, then opinions on its acceptability could still differ. The reason is that evaluations of acceptability do not only rely on \u201cknowledge\u201d but are also influenced by references to things people value as important, such as freedom, security, the value of nature, the rights of the next generations, and their safety and that of their loved ones. In that case, science may thus inform the technical and societal aspects of options, it cannot instruct or clarify the choice to make."}
{"_id": "Radiology$$$78d0d844-5482-4cb1-9c40-1771e4391bfd", "text": "Taking this complexity into account, one may understand that risk cannot be justified through a one-directional \u201cconvincing explanation\u201d by scientific experts or political decision-makers. Ethics supports the idea that the evaluation of a possible justification of a radiological risk needs to be done in deliberation among all concerned, including those potentially affected by the risk. In that deliberation, visions from science, policy, civil society, and citizens have an equal place, bearing in mind that (quoting the philosopher Philip Kitcher) \u201cThere are no ethical experts. The only authority is the authority of conversation\u201d [7]. Obviously, the outcome of that conversation can either be to reject or to accept the radiological risk. In other words, from an ethical perspective, the argument is that the justice of justification, ensured by the possibility of self-determination of the potentially affected, should be the central concern of risk governance. In practice, that means formal methods for decision-making and formal procedures within the organization should care for the possibility of participation of those potentially affected by the radiological risk."}
{"_id": "Radiology$$$8ef8934d-5581-4e1c-87af-a9594cf96b0f", "text": "Seen from a different perspective, ethics in relation to radiological protection is also about considering and recognizing the limits of the radiological protection system when it comes to providing a rationale for justification of radiation risk. In other words, we cannot question the ethical dimensions of the radiological protection system without also questioning the ethical dimensions of the \u201cbigger\u201d systems in which the radiological protection system operates and on which it depends. Given that the radiological protection system, in its concern for providing guidance for decision-making, relies on science but also and essentially wants to take into account human and societal values, the bigger systems that need to be questioned in terms of their ethics, are those of knowledge production (research and policy advice) and decision-making. For risks that manifest in medical diagnostic or therapeutic practices, that \u201csystem\u201d is the possibility of deliberative dialog between the patient, the doctor, the nurse, the radiation control and protection service of the hospital, other hospital agencies, as well as regulatory and professional bodies. For risks that manifest in an occupational context, the system of decision-making is the radiation control and protection service, the management system of the organization, other relevant agencies, trade unions, and professional bodies. For risks that manifest on a societal level, that system of decision-making is the system of democracy, including input from citizens, civil society, trade unions, professional bodies, advocacy groups, and of scientific and ethical advisory committees."}
{"_id": "Radiology$$$6e133463-b04e-44bc-818a-6c5d9866967f", "text": "The evolving ethics of the developing international system of protection against ionizing radiation could be viewed as the branch of some kind of embryonic radiological protection philosophy, which from the beginning of the profession was dealing with main protection principles and their values. It challenged questions about the morality of the protection principles\u2014that is, concepts such as good and bad, right and wrong, virtue and vice in radiological protection. It tried to tackle issues such as the meaning and reference of moral propositions on radiological protection; the practical means of determining a moral protective action, how moral protective outcomes can be achieved in specific situations, how a moral capacity for recommending a protection paradigm develops and what its nature should be and what moral values on radiological protection people in general and stakeholders in particular should actually abide by."}
{"_id": "Radiology$$$9bd16bcd-1cef-465e-8593-38e7b9d3be4a", "text": "Ethics was the primordial earliest concept for judging human actions such as those involved in radiological protection and provides its fundamental basis. Radioprotectionists had been (and continue to be) very keen on exploring and reassessing the rules and standards governing their professional conduct. They have had an unusual curiosity to self-inspect whether they hold the right behavior and what is the set of principles for self-ensuring that such behavior is right. This interest in self-appraisal of conduct correlates with the notion of ethics."}
{"_id": "Radiology$$$9cf49f89-b2ed-4ab8-85b9-695a27075f77", "text": "The ethical basis of radiological protection was early recognized by the profession\u2019s forefathers [1]. The primordial radiation protection principle related to individuals (in fact these individuals were at the beginning just radiologists; it would take a number of years to incorporate individual members of the public, and some more to incorporate individual patients undergoing radiodiagnostic or radiotherapy), as follows:\nThe principle of individual dose restrictions, which was aimed at ensuring that the total dose incurred by any individual should be restricted to protect the individual exposed. Although not explicitly, it was implicitly based on an ethics of duty, the so-called deontological ethics, which is usually expressed with the aphorism \u201cOne should do unto others as they would have done unto them.\u201d"}
{"_id": "Radiology$$$701ccd42-9ff1-438c-88de-d34f60c6eb7a", "text": "The principle of individual dose restrictions, which was aimed at ensuring that the total dose incurred by any individual should be restricted to protect the individual exposed. Although not explicitly, it was implicitly based on an ethics of duty, the so-called deontological ethics, which is usually expressed with the aphorism \u201cOne should do unto others as they would have done unto them.\u201d"}
{"_id": "Radiology$$$eb25395d-c74c-46ee-ba2b-96591fc539bb", "text": "Over time it became clear that the protection of individual was a necessary but not necessarily a sufficient condition, and the system of collective ethical requirements evolved. Two basic principles would fill this gap, as follows:\nThe principle of justification, which was aimed at ensuring that any decision that alters the radiation exposure situation should do more good than harm\u2014meaning that by introducing new radiation sources or by intervening for reducing existing doses, sufficient individual or societal benefit should be achieved to offset the detriment such actions may cause. This principle was based on the ethics of consequence or teleological ethics, which is usually expressed with the aphorism \u201cThe ends justify the means.\u201d\n\nThe principle of optimization, which aimed at ensuring that the level of protection would be the best under the prevailing circumstances, maximizing the margin of benefit over harm, and thus the number of people exposed and of their individual doses be kept as low as reasonably achievable, taking into account economic and societal factors. This was based on the ethics of efficacy or utilitarian ethics, which is usually expressed with the aphorism \u201cProvide the greatest good for the greatest number of people.\u201d"}
{"_id": "Radiology$$$c19441d5-0465-480b-a97e-122f5db3361f", "text": "The principle of justification, which was aimed at ensuring that any decision that alters the radiation exposure situation should do more good than harm\u2014meaning that by introducing new radiation sources or by intervening for reducing existing doses, sufficient individual or societal benefit should be achieved to offset the detriment such actions may cause. This principle was based on the ethics of consequence or teleological ethics, which is usually expressed with the aphorism \u201cThe ends justify the means.\u201d"}
{"_id": "Radiology$$$88a021c2-fa04-4696-8553-d51e249b35f4", "text": "The principle of optimization, which aimed at ensuring that the level of protection would be the best under the prevailing circumstances, maximizing the margin of benefit over harm, and thus the number of people exposed and of their individual doses be kept as low as reasonably achievable, taking into account economic and societal factors. This was based on the ethics of efficacy or utilitarian ethics, which is usually expressed with the aphorism \u201cProvide the greatest good for the greatest number of people.\u201d"}
{"_id": "Radiology$$$9b76738c-96ef-4278-8d64-6014395ac101", "text": "These two principles and their ethics are the basis of the radiation protection paradigm recommended by the ICRP."}
{"_id": "Radiology$$$c7c90bfa-abdf-4f85-873a-f3c0e795f57d", "text": "In addition, there was an intrinsic value of these principles, or de facto principle in its own right, which unfortunately was not specifically declared as such by ICRP, but which is implicitly referred to in many statements and underlines most of the ICRP recommendations and it was recognized in subsequent international standards. It could be formulated as follows:\nThe principle of intergenerational prudence, also termed principle of protection of present and future generations in international standards, is aimed at ensuring that protection extends to all humanity and its environment, regardless of where and when people live, and which implies that all humans, present and future, and their environment shall be afforded with a level of protection that is not weaker than the level provided to those populations causing the protection needs. It can be construed that this important principle is mainly based on the ethics of virtue or ethics of ar\u00eate, which is usually expressed with the aphorism \u201cNo return should be expected from good actions, as goodness is an ideal that transcends human nature.\u201d."}
{"_id": "Radiology$$$72705c29-aeee-4fb3-a39e-2cb3da7c407f", "text": "The principle of intergenerational prudence, also termed principle of protection of present and future generations in international standards, is aimed at ensuring that protection extends to all humanity and its environment, regardless of where and when people live, and which implies that all humans, present and future, and their environment shall be afforded with a level of protection that is not weaker than the level provided to those populations causing the protection needs. It can be construed that this important principle is mainly based on the ethics of virtue or ethics of ar\u00eate, which is usually expressed with the aphorism \u201cNo return should be expected from good actions, as goodness is an ideal that transcends human nature.\u201d."}
{"_id": "Radiology$$$b6057700-5d4d-4a90-b661-8b10072e77a0", "text": "Teleological and utilitarian ethics belong to a family of \u201csocial-oriented\u201d ethics; deontological and ar\u00eate ethics belong to a family of \u201cindividual-oriented\u201d ethics. In relation to radiation protection, teleological and utilitarian ethics aim at protecting society as a whole, while deontological and virtue ethics are more focused on individual protection and individual rights. Teleological, utilitarian, and deontological ethics have evolved in a mainly anthropocentric framework. Conversely, ar\u00eate ethics is able to deal with more general ethical issues such as intergenerational and environmental protection."}
{"_id": "Radiology$$$bf487b4e-a0f6-42c7-80eb-646173c31c42", "text": "The start of the twenty-first century saw a growing criticism of the anthropocentric focus of the system of radiological protection, exemplified by the statement that \u201c\u2026 the standard of environmental control needed to protect man to the degree though desirable will ensure that other species are not put at risk\u201d [3]. Critics noted that there were cases where human doses could be low and doses to wildlife high (e.g., waste disposal), that the approach was not in line with management of other environmental stressors, and that there was a need to demonstrate explicitly that non-human species were being protected [8\u201310]. The IAEA published a report on \u201cEthical Considerations in protection of the environment from the effects of ionising radiation,\u201d exploring ethical principles that might underlie a system of protection and stressing the need to be compatible with international legal instruments such as those related to sustainability and protection of biodiversity [11]. The requirement to address the impacts of ionizing radiation on the environment is now included in international radiation protection recommendations and standards [4, 12, 13]."}
{"_id": "Radiology$$$dd43e959-056e-404d-99da-952b97cc1d6f", "text": "Previous writers have compared the ICRP principles with ethical theories, highlighting the similarities between the principle of justification with teleological or contractarian ethics, the principle of optimization with utilitarian approaches, and the principle of dose limitation with deontological ethics [14, 15]. In its recent work on the ethical foundations of radiological protection, ICRP has focused on commonly recognized ethical values, rather than overarching ethical theories such as utilitarianism or deontology [5]. This is in line with approaches to ethical assessment applied in biomedical and public health ethics [16], as well as work on cross-cultural ethics [17], underlining that it is easier to find agreement on fundamental values than on ethical doctrines. ICRP highlights four core values underpinning the system of radiological protection: beneficence/non-maleficence, justice, dignity, and prudence [5]."}
{"_id": "Radiology$$$40f1818d-8854-48cb-a6ef-5fec2dd7de6b", "text": "Examples of how these values can be applied in the analysis of ethical challenges are given in the following sections. But briefly, beneficence and non-maleficence refer to the principles of promoting well-being and avoiding the causation of harm. In radiological protection, this is clearly related to the reduction of radiation exposures, and the avoidance of resultant harms, but can also include a range of different costs and benefits, including economic and societal aspects. There will always be questions about how to measure consequences and who or what should count in such an evaluation (e.g., animals and future generations). Dignity is concerned with respect for autonomy and the self-determination and choice of affected populations and includes issues related to privacy, human rights, as well as individual and community empowerment. The ethical principles of fairness and justice stress the importance of addressing the way in which risks, costs, and benefits are distributed (distributive justice), as well as the way in which decisions are carried out (procedural justice). Prudence is the ability to make discerning and informed choices without the full knowledge of the scope and consequences of our actions. While precaution and prudence are rarely alluded to in general medical ethics and bioethics, the precautionary principle is well recognized in environmental ethics. The ICRP also introduces the procedural values of transparency and accountability, in the practical application of radiological protection, especially in the need to engage stakeholders in decision-making processes [5]. While there has been a general consensus on the fundamental values proposed by ICRP, there have been proposals that the system should include additional values such as empathy and honesty [18]."}
{"_id": "Radiology$$$638b82d0-9cce-4f34-b42b-ea6be408ed85", "text": "The public\u2019s aversion to radiation\u2014and especially that associated with nuclear power rather than natural or medical exposures\u2014is often cited as an example of irrationality or misunderstanding, and is best combated by improved education. But to understand risk perception, we need to recognize that risk is in part quantifiable but also a social construct that is interpreted differently by people in various situations, environments, and cultures. It is true that people misunderstand probabilities; however, numerous studies of the psychological and psychometric factors that influence risk perception show that the situation is more complex than this alone. Public or lay perceptions of risk vary widely between people and can differ from the calculated, technical approach to the assessment of risks. Whereas an expert will often tend to rank risks as being synonymous with the size or probability of harm, risk tolerance or aversion is dependent on many additional characteristics [19, 20]. Many of the characteristics have strong psychological as well as societal and ethical relevance (such as control, voluntariness, and distribution of risks and benefits)."}
{"_id": "Radiology$$$91f4965e-5be5-4698-b6cc-8f7757426223", "text": "People tend to be less tolerant of risks that are imposed without their choice or personal control. The phenomenon applies to a range of different risks and actions, such as driving a car compared with flying. Personal control is closely related to the fundamental ethical value of autonomy (i.e., respect for the free will of individuals), dignity, integrity, and individual rights. It is also linked to the requirement for free informed consent within medical ethics and can explain why people are less concerned over medical radiation exposures (which are largely voluntary and for an obvious personal benefit). People often feel a lack of personal control over radiation exposure [19], particularly those associated with accidents. They are dependent on information from authorities or media and have to deal with both the risks from the exposure as well as the consequences of measures to reduce exposure such as relocation or agricultural bans."}
{"_id": "Radiology$$$c4ba53e6-406d-4fb9-a8bd-a589d8f714b5", "text": "In risk management, measures that increase personal control and understanding, such as the provision of dosimeters or counting equipment, and participation in decision-making are considered positive and can help populations in coping. Provision of counting equipment and independent monitoring are methods that have been successfully applied in both Chernobyl- and Fukushima-affected communities [21\u201323]. When combined with access to experts to help interpret results, such actions can help empower populations. Ethically, procedures that involve the populations themselves can help promote the principle of informed personal control over radiation risks."}
{"_id": "Radiology$$$1c21d76b-ecdf-4e47-852a-c2cda58b54dd", "text": "The Chernobyl and the Fukushima accidents both resulted in a wide range of social and economic consequences. Many evacuees lost their jobs, social network, and connection to places of a particular community or historical value like graveyards or places where they played as children [24]. Resettlement and long-term evacuation in Fukushima have changed the social structure of the villages and city districts [25]. After Chernobyl, the emigration of young people impeded the whole social and economic development of the region, including a shortage of teachers and doctors [26]. Similar demographic changes have been seen after Fukushima, with young families more likely to evacuate and less likely to return [25]. These lead in turn to a variety of social and health effects such as alcoholism, obesity, and depression in affected populations."}
{"_id": "Radiology$$$b20e17bf-36c9-42cd-a7cc-5c19b3102563", "text": "The economic costs of accidents are complex and wide-reaching. Loss of consumer trust in food from a contaminated area can have economic consequences that go beyond the loss of food production. Stress, ill-health, and even suicide can accompany job loss and bankruptcy. Loss of consumer trust can have profound consequences both for a range of industries (particularly food or tourist industries) and for the local identities of people and groups. This has been well-documented in Fukushima with price drops for produce from the entire region, including areas not affected by the accident, as well as impacts on tourism [25]. Negative economic side effects can arise from rural breakdown and stigma of contaminated communities. Discrimination and stigmatization of the Hiroshima and Nagasaki Hibakusha and their children have an important historical dimension in Japan [27] and is a particular concern for Fukushima evacuees. Hibakusha is a Japanese term referring to the survivors of the Hiroshima and Nagasaki atomic bombs, which translates literally as \u201cbomb-affected people.\u201d TEPCO workers also cited discrimination as one of the main causes of psychological stress [28]. In addition to experienced prejudice, concerns of the populations affected by Fukushima Daiichi accident include worries about whether their children would be able to find partners or marry in the future and reports of discrimination against Fukushima children after moving to new schools."}
{"_id": "Radiology$$$3876c7d0-fa44-4a56-bd0d-b170e685dd75", "text": "The aftermath of an accident can also be economically beneficial to parts of the community, for example, through the generation of local employment opportunities. This may lead to some sections of the population making a profit from remediation (such as selling or hiring equipment), which can lead to further social inequity and division."}
{"_id": "Radiology$$$f90c25aa-861e-477e-8015-b1e76745aaf7", "text": "Distribution of the costs, risks, and benefits of radiation exposure relate to the fundamental ethical values of equity, justice, and fairness. After an accident, doses received by individuals can vary widely, and the risks of those exposures differ between adults and children. The consequences of remediation can impact different members of the affected communities. Some may lose their livelihood, while others can continue more or less as before the accident. For example, after Fukushima the situation was particularly harsh for the elderly evacuees, particularly those living in temporary housing who experienced greater isolation from family and communities [25]."}
{"_id": "Radiology$$$b67be287-42e4-4b0a-8b7f-22dea14994ff", "text": "The potential for increased health risks from radiation in children means that the risk perceptions go beyond consideration for personal risks, as is seen by anxiety over thyroid cancer in Fukushima populations [35, 36]. The fear that your child could be affected in the future can overshadow any personal concern [24]. Such concerns create challenges for health surveillance, particularly thyroid screening of children. While parents may, understandably, request screening, the procedure can lead to unnecessary surgery (e.g., 4000 thyroid surgeries in Chernobyl children may explain most of 15 deaths attributed to exposure), and without a carefully thought communication plan may raise anxiety (Shamisen 2020). Some measures to reduce exposures could result in an equitable distribution of cost and dose reduction, such as investment by taxpayers to reduce activity concentrations in public areas; while others are less equitable, for example, when a reduction of dose to the majority is only possible at the expense of a higher dose, cost, or welfare burden, on a minority (e.g., banning all farm production in a small community)."}
{"_id": "Radiology$$$dede31d5-0ccf-4502-8182-f6c624a4ee22", "text": "To conclude, public reaction to disasters is the result of complex and intrinsic features of risk perception, many of which have strong ethical and societal relevance. A holistic approach to disaster management should integrate economic, ecological, and health measures. Risk management strategies should be designed to accommodate varied needs. For nuclear accidents, it is not sufficient to simply focus on the dose reduction aspects of radiation protection as societal aspects will play a major role in how individuals cope with, and communities recover from the disaster. Engaging with the affected population with regard to increasing their understanding and personal control and involving them in decision-making processes respects people\u2019s fundamental right to shape their own future. In addition to increasing trust and compliance, such approaches can lead to significant improvements in the effectiveness and acceptability of disaster management in communities."}
{"_id": "Radiology$$$c4ef142e-8624-4f3a-a589-00011401db97", "text": "Testing for radiosensitivity has the potential to improve patient treatment and diagnosis or protect workers. Assays might be applied prior to radiotherapy, to avoid adverse reactions in radiosensitive individuals, or to avoid enhanced cancer risk in connection with radiodiagnoses such as CT scans or mammography [31]. While not yet applied in medicine or worker protection, assays are currently under development, and their potential application raises a number of ethical and legal challenges. These go beyond the simple question of whether the assay will \u201cdo more good than harm\u201d to include, for example, questions about how the costs and benefits might be distributed in society, concerns about privacy and data protection, and considerations of the potential for discrimination."}
{"_id": "Radiology$$$27c9d542-570e-485d-8872-801688aeb652", "text": "Radiosensitivity and radiosusceptibility assays have a clear potential to provide physical health benefits by improving cancer treatment, avoiding negative side effects, and enhancing worker protection. There are also economic aspects, such as balancing the cost of the assays against the opportunity to save money through tailored treatment. Psychosocial consequences could include reassurance but might also cause worry about sensitivity to other stressors. Information on the magnitude of the effect, its relation to other potential risk factors, and indeed any dose\u2013response relationship, as well rates of false positives and false negatives would be needed to be able to balance the physical harms and benefits. But this would also have knock-on effects on economic, psychological as well as legal assessments. Could doctors be sued for the negative effects of not carrying out a test?"}
{"_id": "Radiology$$$c77c23f2-20d1-41f5-8b89-14997b143379", "text": "Information on individual radiosensitivity and radiosusceptibility could clearly enhance patient or worker empowerment and personal control, but this would depend strongly on the context in which this information was used. The issues are similar to other challenges with personal health information, such as conforming to data protection laws and the increasing commercialization of genetic testing [32]. For example, the degree to which data from patients undergoing an assay as part of radiotherapy would be stored, anonymized, and made available for further research would need to be addressed. A debate on the implications of these issues would need to include engagement with the various stakeholders but could also play an important role in risk communication, by putting the risks of ionizing radiation in context with other environmental and genetic risk factors."}
{"_id": "Radiology$$$4d515a69-1b59-42f2-bf02-7b0c2a6f7508", "text": "Increased understanding of the differences in radiosensitivity within populations is relevant to an assessment of justice. Other questions would include whether the assays would provide equal access to health care and support or have any impact on health insurance (would sensitive populations have to pay higher premiums?) or compensation claims (will it change the balance of probabilities that cancers were caused by radiation exposure?). Even in countries with national health insurance, there is the question of whether people should be obliged to disclose the results of genetic testing before taking out private health or life insurance schemes. If sensitivity or susceptibility was linked to a genetic trait, there would be additional issues associated with implications for children or other family members. While identification of increased radiosusceptibility in workers could be used for protective purposes, it might also lead to discrimination, or raise questions about \u201cresponsibility\u201d for any diseases or negative side effects (lifestyle, predisposition, occupational exposure, etc.). These issues could be linked to broader debates on the implications for radiological protection of populations with different risk factors such as whether children or women should be treated differently on the basis of increased radiation cancer risks."}
{"_id": "Radiology$$$789f1efc-d7e2-475c-ae13-966ef5efdeb8", "text": "To conclude, many of the ethical challenges associated with the field of radiosensitivity and radiosusceptibility have parallels with existing challenges in medical, occupational, and public health. They also raise important questions about the implications for radiological protection. For example, will population-level differences in radiation susceptibility impact the assessment of health risk? Will they lead to a change in dose constraints? These questions can only be addressed with the participation of a wide variety of stakeholders. Assessing the implications for well-being requires knowledge from experts in radiation biology, medicine, occupational health, health economics, social scientists, etc., as well as transparency about uncertainties and assumptions. Respecting both the principles of dignity and fairness in the procedure requires the participation of affected persons (workers, patients, the public, etc.) in decision-making."}
{"_id": "Radiology$$$b971bcea-2fd2-4900-8c4e-909ffbcd5af3", "text": "Looking at the societal impacts of science and technology, nuclear technology probably represents the most extreme case of how science and technology can serve both cure and destruction. While medical applications of nuclear technology save individual lives every day, nuclear weapons have enormous destructive potential. Nuclear energy is a low-carbon source of electricity, but a nuclear accident can have dramatic impacts on the environment and on the physical and psychological health of a whole population for a long time. In addition, disposal of radioactive waste unavoidably requires taking responsible action toward future generations thereby taking into account time dimensions longer than ever faced before in human history."}
{"_id": "Radiology$$$6d3f9373-7161-4790-af74-4249c7535571", "text": "The case of nuclear energy technology is also an example of how technology assessment can be troubled by the fact that \u201cbenefits and burdens\u201d of a technology are essentially incomparable. Referring to the general considerations related to the radiological risk and the need to include values in its assessment above, we can say that, taking into account the specific character of the nuclear energy risk, also the societal justification of nuclear energy is troubled by moral pluralism. That is, even if we would all agree on the scientific knowledge base for the assessment of the risk, then opinions on its acceptability could still differ. The matter becomes even more complex if we take into account the fact that science can only deliver evidence to a certain extent. Nuclear science and engineering are mature, but we have to acknowledge that the existence of knowledge-related uncertainties puts fundamental limits to understanding and forecasting technological, biological, and social phenomena in the interest of risk assessment and governance. Last but not least, we have to accept that important factors remain to a large degree beyond control. These are human behavior, nature, time, and potential misuse of technology."}
{"_id": "Radiology$$$fbea8df1-8d88-4067-903f-5c33191b7b11", "text": "The resulting room for interpretation complicates the evaluation of risk-inherent technologies in general and of nuclear technology in particular and puts a specific responsibility on science and technology assessment as a policy-supportive research practice. And this is the point where ethics come in. In simple terms, that responsibility comes down to acknowledging and taking into account uncertainty and pluralism as described above, and the consequences thereof for research and policy. That \u201cresponsible attitude\u201d does not only apply to scientists but to everyone concerned with applications of science and technology in general and with the issue of nuclear technology in particular. The idea is that this responsible attitude can only be enabled and stimulated in \u201cinteraction methods\u201d for policy and scientific research that are able to generate societal trust by their \u201cmethod.\u201d Today we know that this in principle translates as doing politics differently by involving the potentially affected and other stakeholders in deliberative decision-making, and as doing science differently, namely as transdisciplinary science advancing from a holistic perspective and enriched with insights and ideas from the social sciences and the humanities, from lay knowledge and the arts and from civil society and citizens (see, among other [33\u201335]). For science in particular, confronted with the need to deal with incomplete and speculative knowledge and value pluralism in providing policy advice on issues of social well-being, its challenge is no longer the production of credible proofs but the construction of credible hypotheses [33]. From an ethical perspective, in the general interest of rendering hypotheses with credibility (and the potential to generate societal trust), one could say science has no choice but to \u201copen up its method\u201d for transdisciplinarity and public involvement, in addition to the \u201ctraditional\u201d quality criteria of objectivity and independence and the need to recognize uncertainty, value pluralism, contingency, and potential misuse. Obviously, the aim of this ethically inspired \u201creflexivity\u201d is not to undermine the credibility of science but to stimulate dialog and (self) critical thinking, and to make science more resilient against pressure from politics and the market to deliver evidence it cannot (yet) deliver."}
{"_id": "Radiology$$$e9747257-0275-40a4-99da-b58ddedf5b35", "text": "The complex dimensions of radiological risk, particularly after large-scale accidents raise particular challenges for cost-benefit analysis of post-accident response. Emotional descriptions of such emergencies seem more common than quantitative cost-effectiveness considerations. Noteworthy, a few weeks before the first atomic bomb test in July 1945, an official report warned that \u201ccivilization would have the means to commit suicide at will\u201d [36]. Kahn [37] considered a full-scale 10,000,000 kiloton nuclear exchange between the Soviet Union and the USA, and deliberated in detail why the above statement is far from being based on evidence."}
{"_id": "Radiology$$$3687b5bf-257c-45b1-b9f1-ea134d878249", "text": "Quantitative considerations show that the direct health consequences\u2014radiation sickness, carcinogenesis, etc.\u2014of any past (or future practically probable) radiological accident are much less far-reaching than those which are usually perceived. In each scenario, direct health effects are only a small part of the damage caused by fear and anxiety. For example, the two major humanitarian disasters after the Chernobyl and Fukushima nuclear accidents turned out to be such disasters not because of their radiogenic effects, either actual or averted. The main health consequences could be attributed to countermeasures by the authorities, and socio-psychosomatic problems among the public. The relocation of hundreds of thousands of people created very real suffering, morbidity, and mortality [38]. Rational decision-making should have quantitatively compared the human cost of evacuation and long-term relocation with the human cost of radiation exposure. Such comparison was performed only decades later. For example, Yanovskiy et al. [39] estimated that in Fukushima the evacuation was not justified at all, and in Chernobyl the evacuated zone could have been repopulated after 1 month."}
{"_id": "Radiology$$$5c310cc8-994a-4ac2-a569-960e2beebbd6", "text": "The human cost of evacuations should be considered as follows. First, there is always a direct loss of life due to the temporary loss of medical care, psychosomatic disorders, and even suicides; After Fukushima, e.g., 1% of the evacuees died during the first 2 years due to evacuation-related causes (on top of the natural mortality). Second, evacuees\u2019 quality of life deteriorates by about 20% [39]. Last but not least, evacuation is expensive. While associating human life with monetary value is psychologically difficult and may seem ethically challenging, it is actually an ethical necessity since extraneous expenditure leads to a statistical shortening of life. A cost-effectiveness analysis is routinely performed when formulating health policies [40]. Safety expenditures should be treated in a similar way since both healthcare and safety deal with life extension [41]."}
{"_id": "Radiology$$$d68b84bd-97be-4501-9b43-e544100abd84", "text": "In this context, it is worth mentioning that life expectancy varies considerably not only for different countries but also for different locations of each country: the main reasons are probably socioeconomic and environmental. This disparity in life expectancy across countries is typically of several years; in the extreme case of Calton in the UK it was 25\u00a0years below the country average [42]. It is needless to mention that evacuation of less-successful locations is nowhere considered as a viable option."}
{"_id": "Radiology$$$a3efbda8-5a90-49e9-a813-0b2da02c0337", "text": "The purpose of nuclear law is to establish a legal framework for the safe management of all sources and types of radiation and endeavors involving exposure to ionizing radiation [43]. Nuclear law should thus ensure the adequate protection of individuals, society, and the environment, both present and future, against radiological hazards. Specifically, nuclear law should cover the exposure of the general public\u2014i.e., any individual in the population\u2014of workers\u2014i.e., any person who works, whether full-time, part-time, or temporarily, for an employer and who has recognized rights and duties in relation to occupational radiation protection\u2014as well as exposures related to medical uses of radiation, situations in which a patient is voluntarily exposed for therapeutic purposes (radiodiagnostic or radiotherapy) and who may incur high doses of radiation, possibly with unwanted side effects as a result. Radiation protection rules and regulations should always include special provisions relating to the way in which the application of fundamental principles of justification of actions involving radiation exposure, optimization, or protection, and limitation of individual radiation risk is applied."}
{"_id": "Radiology$$$3e5d36ed-2778-43f8-bc25-b723fc192d5a", "text": "The general principles of nuclear law broadly apply to all nuclear-related activities and facilities where ionizing radiation is used or produced."}
{"_id": "Radiology$$$60661730-9e2b-427e-98e6-726fb4e75765", "text": "Section 12.4 will first define nuclear law. Important principles will then be covered followed by a summary and explanation of relevant legislative frameworks. Certain specific potential exposure situations and how the law treats them will also be expanded upon such as employer and medical liability, as well as the legal framework for airline personnel and astronauts."}
{"_id": "Radiology$$$1ac1183c-8c32-41fe-a131-4bdb19dd998c", "text": "Legal attribution and imputation of radiation harm to radiation exposure situations, a topic that has distinct epistemological elements, will be discussed in Sect. 12.5 after the more formal legal aspects."}
{"_id": "Radiology$$$1c943a77-5f8e-42f0-bd43-c9a48f4905aa", "text": "The scope of nuclear law can be succinctly defined as any issue or matter relating to the use of, production of, or exposure to ionizing radiation in specific situations."}
{"_id": "Radiology$$$63c1897b-f071-4115-ae7b-c53bdc74cd1c", "text": "In more detail, nuclear law can be defined as \u201cThe body of special legal norms created to regulate the conduct of legal or natural persons engaged in activities related to fissionable materials, ionizing radiation, and exposure to natural sources of radiation\u201d while its primary objective is \u201cTo provide a legal framework for conducting activities related to nuclear energy and ionizing radiation in a manner which adequately protects individuals, property, and the environment\u201d [44]."}
{"_id": "Radiology$$$c89da487-2aec-4590-8c84-3996bc343918", "text": "This definition has four key elements. Firstly, nuclear law is a body of special legal standards and norms. These are recognized as a part of general national legislation. Since it is a sovereign right of countries to choose how they enact laws, national legislations may differ when it relates to nuclear issues."}
{"_id": "Radiology$$$2a568adf-2f7c-4d46-9630-86b4beba4dd1", "text": "Secondly, nuclear law serves a regulatory purpose. The use of and exposure to radiation needs to be regulated given that whilst there is a potential benefit to social and economic development, there also a potentially detrimental effects."}
{"_id": "Radiology$$$dad47d13-7e51-4f4d-bb04-ca12c7d90a21", "text": "Thirdly, nuclear law relates to the conduct of legal and natural persons. These persons could be commercial, academic, scientific, governmental, or natural. A legal person is a body corporate (or corporate organization) such as a company while a natural person is an individual human being [45]."}
{"_id": "Radiology$$$17ce4762-ed7a-4d54-a16e-136288332df5", "text": "Fourthly, nuclear law primarily relates to radioactivity, ionizing radiation, and the products of nuclear fission, with the clarification that in this context, it means those that have potentially unwanted biological effects. We could add to the definition that the effects of fusion reactions\u2014still largely in a developmental phase at the time of the redaction of this work\u2014should also be included under the umbrella of nuclear law. The property of protection of the population from the adverse effects of radioactivity and radiation is considered to be the defining aspect justifying the need for a special legal regime."}
{"_id": "Radiology$$$f8f4d00f-4e05-4ef6-aab2-d41435590c8e", "text": "A number of basic concepts, often expressed as fundamental principles, distinguish nuclear law from other aspects of law. These principles and various theories are crucial to understand because they help understand why the law exists in the form it does."}
{"_id": "Radiology$$$b9855925-8553-493e-b18b-617af6f43bb6", "text": "The safety principle is arguably the central concept in nuclear law [43]. Within the safety principle, there are a number of other principles. These include the prevention principle that postulates that, given the special nature of the risks associated with the use of nuclear energy, the primary objective of nuclear law is to promote the exercise of caution and foresight to prevent damage and minimize adverse effects. Another principle is the protection principle which postulates that when the risks associated with an activity are found to outweigh the benefits, priority must be given to protecting public health, safety, security, and the environment. The precautionary principle also prioritizes protection and the prevention of foreseeable harm as fundamental requirements."}
{"_id": "Radiology$$$8da38bcb-b8a0-43c4-baad-e76e6a2cdab0", "text": "Fundamental safety principles codified in legislation may be applied to a wide variety of activities and facilities that pose very different types and levels of risk. Activities posing significant radiation hazards will obviously require stringent technical safety measures and, in parallel, strict legal arrangements. Activities posing little or no radiation hazard will need only elementary technical safety measures, with limited legal arrangements."}
{"_id": "Radiology$$$5ae194ff-823c-479b-ab2e-53b485f381d8", "text": "The security principle [43] is an underlying principle of the special legal measures that are required to protect and account for the types and quantities of nuclear material that may pose security risks. These measures should protect against both accidental and intentional diversion from the legitimate uses of these materials and technologies. Lost or abandoned radiation sources can cause physical injury to persons unaware of the associated hazards. The acquisition of radiation sources by terrorist or criminal groups could lead to the production of radiation dispersion devices to be used to commit malevolent acts. The diversion of certain types of nuclear material could contribute to the spread of nuclear weapons to both subnational and national entities. It is for these reasons that legal measures regarding physical protection, emergency preparedness, response, and transport, import and export of radioactive material have been adopted."}
{"_id": "Radiology$$$9aa10244-49cf-454b-b557-246bc9749011", "text": "While safety is of the utmost importance, it is important to carry out a balancing of both the risks and the benefits of exposure. There are situations in which the benefits clearly outweigh the risks, and it is important to not dismiss outright any and all exposure based solely on hazard."}
{"_id": "Radiology$$$c912face-6dd9-4a02-8a76-06ad035fdda1", "text": "The aforementioned principles are not the only ones used in a nuclear law context. For example, the IAEA Basic International Safety Standards (BSS, infra, Sect. 12.4.4.1) represent a broad international consensus on the appropriate handling of radioactive sources to ensure that nuclear-related activities can be conducted in a safe, secure, and environmentally acceptable way. The BSS consists of three sets of publications: the Safety Fundamentals, the Safety Requirements, and the Safety Guides. The Fundamentals establish the fundamental safety objectives and principles of protection and safety, the Requirements set out the requisite conditions that must be met to protect the population and the environment and the Safety Guides provide practical recommendations and guidance on how to comply with the requirements."}
{"_id": "Radiology$$$95a26ec1-2aab-4c37-b5ef-8b30708c5a7e", "text": "The Fundamental Safety Principles are the basis of international and intergovernmental standards of radiation and nuclear safety. They have been established under the aegis of the IAEA and are jointly sponsored by the European Atomic Energy Community (Euratom), the Food and Agriculture Organization of the United Nations (FAO), the International Atomic Energy Agency (IAEA), the International Labour Organization (ILO), the International Maritime Organization (IMO), the OECD Nuclear Energy Agency (OECD/NEA), the Pan American Health Organization (PAHO), the United Nations Environment Programme (UNEP), and the World Health Organization (WHO)."}
{"_id": "Radiology$$$4d661678-8361-4f87-bd01-fcd7a9fc2466", "text": "The fundamental safety principles are more detailed elements of the safety principle previously discussed:\nThe first principle is the responsibility for safety: The prime responsibility for safety must rest with the person or organization responsible for facilities and activities that give rise to radiation risks.\n\nThe second safety principle relates to the role of the government: An effective legal and governmental framework for safety, including an independent regulatory body, must be established and sustained.\n\nThe third safety principle relates to the leadership and management for safety: Effective leadership and management for safety must be established and sustained in organizations concerned with, and facilities and activities that give rise to, radiation risks.\n\nThe fourth safety principle calls for the justification of facilities and activities: Facilities and activities that give rise to radiation risks must yield an overall benefit.\n\nThe fifth safety principle refers to the optimization of protection and safety: Protection must be optimized to provide the highest level of safety that can reasonably be achieved.\n\nThe sixth principle requests the limitation of risks to individuals: Measures for controlling radiation risks must ensure that no individual bears an unacceptable risk of harm.\n\nThe seventh principle calls for the protection of present and future generations: People and the environment, present and future, must be protected against radiation risks.\n\nThe eighth principle refers to the prevention of accidents: All practical efforts must be made to prevent and mitigate nuclear or radiation accidents.\n\nThe ninth principle relates to emergency preparedness and response: Arrangements must be made for emergency preparedness and response for nuclear or radiation incidents.\n\nThe tenth and final principle refers to protective actions to reduce existing or unregulated radiation risks: Protective actions to reduce existing or unregulated radiation risks must be justified and optimized."}
{"_id": "Radiology$$$fcf41227-759e-45c5-a0ca-f2ab457e1f17", "text": "The first principle is the responsibility for safety: The prime responsibility for safety must rest with the person or organization responsible for facilities and activities that give rise to radiation risks."}
{"_id": "Radiology$$$c8e00059-9e86-4b4e-a5be-8be465d14c4d", "text": "The second safety principle relates to the role of the government: An effective legal and governmental framework for safety, including an independent regulatory body, must be established and sustained."}
{"_id": "Radiology$$$50e66682-d3dd-48c2-8f8b-696a850ce467", "text": "The third safety principle relates to the leadership and management for safety: Effective leadership and management for safety must be established and sustained in organizations concerned with, and facilities and activities that give rise to, radiation risks."}
{"_id": "Radiology$$$bf57ca71-052e-4de4-91b8-7ce9dcb9fe16", "text": "The fourth safety principle calls for the justification of facilities and activities: Facilities and activities that give rise to radiation risks must yield an overall benefit."}
{"_id": "Radiology$$$384dcbe7-bc0f-4235-9599-1f6361ac9780", "text": "The fifth safety principle refers to the optimization of protection and safety: Protection must be optimized to provide the highest level of safety that can reasonably be achieved."}
{"_id": "Radiology$$$830743da-fe5c-4f9f-aacb-67008a9a8a49", "text": "The sixth principle requests the limitation of risks to individuals: Measures for controlling radiation risks must ensure that no individual bears an unacceptable risk of harm."}
{"_id": "Radiology$$$ff011757-4c59-4c5b-816a-4aec5f2868e0", "text": "The seventh principle calls for the protection of present and future generations: People and the environment, present and future, must be protected against radiation risks."}
{"_id": "Radiology$$$bdc76f1f-5199-4c16-9432-43d4c1e60ff4", "text": "The eighth principle refers to the prevention of accidents: All practical efforts must be made to prevent and mitigate nuclear or radiation accidents."}
{"_id": "Radiology$$$da8c282d-aac0-43fe-a9e2-d237a76cae16", "text": "The ninth principle relates to emergency preparedness and response: Arrangements must be made for emergency preparedness and response for nuclear or radiation incidents."}
{"_id": "Radiology$$$d94911e0-f8d4-4f00-bfa9-05cdaf9a1cb4", "text": "The tenth and final principle refers to protective actions to reduce existing or unregulated radiation risks: Protective actions to reduce existing or unregulated radiation risks must be justified and optimized."}
{"_id": "Radiology$$$245d0dd6-22af-4e17-b70e-8a6fd26b0070", "text": "The central underlying principle of nuclear law is safety. If a situation arises in which a law\u2019s interpretation is unclear, it is useful to ask which interpretation would lead to the safest outcome. This should of course take into account the beneficial impacts relating to the exposure, but it is a good starting point if confusion arises."}
{"_id": "Radiology$$$dbcf05ec-b077-4327-9553-87a57683704e", "text": "An international regime based on broad international consensus has produced over time a set of recommendations and standards that govern radiation protection. These are not set in stone but have evolved and will still evolve over time as new fundamental scientific insights develop. The United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) compiles, assesses, and disseminates scientific information on the causal link between incurred doses of radiation and possible adverse health effects outcomes. Its findings are periodically reported to the UN General Assembly (UNGA) and are made available to the public on its website. Since 1950, the International Commission on Radiological Protection (ICRP), a private nongovernmental charity, has been developing internationally agreed-upon recommendations in all areas of radiation protection. The Annals of the ICRP are mostly freely available to the general public."}
{"_id": "Radiology$$$fea31019-519b-4dd5-982a-4efaf09901e1", "text": "International radiation protection standards are established under the aegis of the International Atomic Energy Agency (IAEA) with the cosponsoring of other relevant international organizations. Since 1962, the IAEA takes into account UNSCEAR publications as well as ICRP recommendations in order to establish and issue Basic Safety Standards (BSS), which provide fundamental principles, requirements, and recommendations to ensure nuclear safety. The IAEA considers these standards as a global reference for protecting people and the environment and a main contribution to a harmonized high level of safety worldwide. Scientific and technical publications are issued annually and include international safety standards, technical guides, conference proceedings, and scientific reports. They cover the breadth of the IAEA\u2019s work, focusing among other topics on nuclear power generation, the use of sealed radioactive sources in medicine, radiation therapy, agriculture, nuclear safety and security, and nuclear law."}
{"_id": "Radiology$$$51f114ab-b011-4ae0-b7b4-b85e761f8166", "text": "The publications by UNSCEAR, the ICRP, and the IAEA are comprised of general principles, mandatory requirements, and binding rules, recommendations, and guidelines. In addition, a growing structure of international treaty obligations and accepted rules of best practices have been developed. Important to note are that these recommendations and standards, while broadly recognized on an international level, are not adopted by all countries in a uniform way. Almost all ICRP recommendations and most IAEA standards are considered to be \u201csoft law\u201d meaning that countries and institutions are encouraged to implement them in regulations and national legislation, without an actual legal obligation to do so."}
{"_id": "Radiology$$$5cf6cf2d-9e5e-48dc-acd9-862b926ccafd", "text": "It is important to note that the national variations in the implementation of nuclear law do not vary from country to country simply due to varying levels of scientific understanding, but is also influenced by political motives and public perception. For example, states that are generally wary of the use of nuclear energy may have a notably different legal framework than states that generally favor the use of nuclear energy, despite these states having essentially the same access to the same scientific information."}
{"_id": "Radiology$$$998533f5-4df9-492e-b60b-f7add08729f7", "text": "There are few hard laws at the international level. Nation states generally retain a large measure of self-determination in regulating nuclear activities within their borders. There is however a substantial international consensus in many areas of radiation protection and consequently in the basic concepts of nuclear law, expressed on the one hand in binding treaties and on the other in rules of soft law, i.e., quasi-legal instruments such as recommendations or guidelines that are strictly speaking not legally binding but are nevertheless widely adopted and may become legally binding in the future."}
{"_id": "Radiology$$$3bd794de-df1f-4811-ba0c-57c212e27f93", "text": "Adherence to international instruments (e.g., conventions and treaties) has both an external and an internal aspect. As a matter of international law, states that take the necessary steps under their national laws to approve (or ratify) such instruments are then bound by the obligations arising out of that instrument in their relations with other States Parties. When this is the case, states need to establish legal arrangements for implementing those obligations internally. Most States require that the provisions of international instruments be adopted as separate national laws. This approach is, for example, reflected in Article 4 of the Convention on Nuclear Safety [46], which states that: \u201cEach Contracting Party shall take, within the framework of its national law, the legislative, regulatory and administrative measures and other steps necessary to implement its obligations under this Convention.\u201d"}
{"_id": "Radiology$$$5641795d-16ce-461b-bf98-c54ecfd2a5fe", "text": "When analyzing nuclear law on a national level, there are basic concepts shared by different states and thus large overlaps in national public law even though national laws remain territorial, meaning only applicable to the state or its nationals. It would be impossible to even summarize, let alone provide a comprehensive overview and compare various nuclear laws in different countries."}
{"_id": "Radiology$$$3f7ad683-d541-4eef-a25b-c1373cbe58ce", "text": "The EU is a notable exception to the fragmented incorporation of international binding regulations into national legislation.\u00a0This is because\u00a0EU regulations provide a legislative framework that is directly applicable within the EU. The most recent regulatory framework is the consolidated version of the 2013 Directive laying down the basic safety standards for protection against the dangers of ionizing radiation. The Directive establishes uniform basic safety standards for the protection of the health of individuals subject to occupational, medical, and public exposures. It applies to any planned, existing, or emergency exposure situation that involves a health risk from exposure to ionizing radiation. The Directive does not apply to natural levels of background radiation, aboveground exposure to radionuclides present in the undisturbed Earth\u2019s crust, exposure of members of the public, or exposure of workers other than air or space crew to cosmic radiation in flight or in space. Exposure to naturally occurring radioactive material (NORM), e.g., in the context of industry or mining activity is regulated if it leads to exposure of workers or members of the public which cannot be disregarded from a radiation protection point of view."}
{"_id": "Radiology$$$e254ce35-f65b-4189-8c47-1df278bcf21c", "text": "Whether national or regional, it is important to recognize that nuclear law must take its place within the national legal hierarchy. The legal framework in which most states operate consists of several levels. The constitutional level establishes the basic institutional and legal structure governing all relationships within the state. Immediately below the constitutional level is the statutory level, at which specific laws are enacted by the legislative branch of government in order to establish other necessary bodies and to adopt measures relating to the broad range of activities affecting national interests. The third level comprises regulations, detailed and often highly technical rules issued by regulatory bodies to the nuclear industry."}
{"_id": "Radiology$$$45d269af-fe97-4767-ba57-35f83b03d15c", "text": "A fundamental element of any national nuclear framework is the creation or maintenance of regulatory bodies with the legal powers and technical competence necessary to ensure that operators of nuclear facilities and users of nuclear material and ionizing radiation operate and use them safely and securely. For example, article 7 of the Convention on Nuclear Safety (CNS) [46] and article 19 of the Joint Convention [47] require the establishment and maintenance of a legislative and regulatory framework to govern the safety of, respectively, nuclear installations and radioactive waste management, identifying a number of functions to be performed by a regulatory body within such a framework."}
{"_id": "Radiology$$$5c4116be-bc81-4d1b-a872-6d450580c9af", "text": "The central consideration is that a regulatory body should possess the attributes necessary to correctly, self-sufficiently, and independently apply the national laws and regulations designed to protect public health, safety, and the environment. Its tasks can be roughly grouped into four categories: preliminary assessment (establishing requirements and determining whether regulatory control is needed); authorization (licensing and registration, including the prohibition of operations without a license); inspection of nuclear installations and assessment through periodical reviews and enforcing compliance through issuing administrative orders or prohibitions, fines or other penalties. A fifth category, not mentioned in the two aforementioned conventions but considered essential by most regulatory bodies, is the provision of information, including consultation, on regulated activities with the public, the media, the legislature, and other relevant stakeholders. Finally, a regulatory body should be permitted to coordinate its activities with the activities of international and other national bodies involved in nuclear safety."}
{"_id": "Radiology$$$3ac6e13e-9fb3-4f69-9e36-4fd7722fed85", "text": "An example of successful regulation within these parameters can be found in the UK\u2014although the UK is no longer a member of the EU since January 1, 2021\u2014they remain compliant with both article 7 of the CNS and article 19 of the Joint Convention."}
{"_id": "Radiology$$$fc7e13e3-87f7-43ec-8ab0-f696b6b1215b", "text": "A crucial area of nuclear law is nuclear liability. This area is especially important in the context of unplanned emergency exposure to radiation. The occurrence of nuclear and radiological accidents cannot be completely excluded even in situations in which the highest standard of safety has been achieved. All states that engage in nuclear-related activities have generally concluded that general tort law is not an appropriate instrument for providing a liability regime adequate to the specifics of nuclear risks. Tort law is the branch of the law that deals with civil suits alleging negligence, intentional harm, and strict liability, with the exception of disputes involving contracts and is considered to be a form of restorative justice since it seeks to remedy losses or injury from the wrongful acts of others by providing awarding monetary damages to provide full compensation for proved harms. Since civil law is generally designed to cope with large-scale catastrophes, special measures are required, and states have enacted specific nuclear liability legislation."}
{"_id": "Radiology$$$c341a327-d161-4ed3-bb8a-ed3298c7044a", "text": "The Paris Convention [48], the Vienna Convention [49], the Brussels Supplementary Convention [50], the Joint Protocol [51], the Convention on Supplementary Compensation [52], and the Revised Vienna Convention [53] (hereafter \u201cthe Conventions\u201d) establish comprehensive regimes for civil liability for nuclear damage. Application of the international nuclear liability regime created by the conventions and the corresponding national legislation will be triggered if an installation or activity causes a nuclear incident."}
{"_id": "Radiology$$$e92b2f47-02e2-47e8-a47a-ce02eb22d83a", "text": "A nuclear installation must have a person in charge: the operator. In the nuclear liability conventions, the operator is the person\u2014whether this is an individual or any other private or any public entity having a legal personality\u2014designated or recognized as the operator of a nuclear installation by the installation state. The operator, most often the license holder but possibly the owner of the installation, will always be the person responsible (and thus liable) for safety."}
{"_id": "Radiology$$$4c28eb29-28c1-490d-98f6-0e21ddeae22d", "text": "The term \u201cnuclear incident\u201d means any occurrence, or any series of occurrences having the same origin, that causes nuclear damage or, but only with respect to preventive measures, creates a grave and imminent threat of causing such damage. Since the occurrence has to cause or threaten nuclear damage, the definition of what constitutes \u201cnuclear damage\u201d is paramount. In general tort law, the concept of compensable damage is well established. If states seek to obtain the benefits of the Conventions, they must accept the definitions."}
{"_id": "Radiology$$$51204f0e-e550-46cd-a33e-2422136e3405", "text": "\u201cNuclear liability\u201d is understood to be the legal regime based upon the following principles:\n\u201cExclusive liability of the operator of the nuclear installation concerned;\n\n\u201cAbsolute\u201d or \u201cstrict\u201d liability, so that the injured party is not required to prove fault or negligence on the part of the operator;\n\nMinimum amount of liability;\n\nObligation for the operator to cover liability through insurance or other financial security;\n\nLimitation of liability in time;\n\nEqual treatment of victims, irrespective of nationality, domicile, or residence, provided that damage is suffered within the geographical scope of the convention;\n\nExclusive jurisdictional competence of the courts of the contracting party in whose territory the incident occurs or, in case of an incident outside the territories of contracting parties (in the course of transport of nuclear material), of the contracting party in whose territory the liable operator\u2019s installation is situated);\n\nRecognition and enforcement of final judgments rendered by the competent court in all Contracting Parties.\u201d (IAEA Joint Convention on the Safety of Spent Fuel Management and on the Safety of Radioactive Waste Management [47]).\nAccording to Article 1 of the Paris Convention (Third Party Liability), a \u201cnuclear incident\u201d is considered to be \u201cany occurrence or series of occurrences having the same origin which causes nuclear damage.\u201d"}
{"_id": "Radiology$$$8f26500f-6470-4039-869f-7fa880de29cd", "text": "\u201cAbsolute\u201d or \u201cstrict\u201d liability, so that the injured party is not required to prove fault or negligence on the part of the operator;"}
{"_id": "Radiology$$$87b855d5-39a5-4805-8388-0b5be00918ab", "text": "Obligation for the operator to cover liability through insurance or other financial security;"}
{"_id": "Radiology$$$aeedc3b1-5e5d-4cc0-a33d-81a30930f8b7", "text": "Equal treatment of victims, irrespective of nationality, domicile, or residence, provided that damage is suffered within the geographical scope of the convention;"}
{"_id": "Radiology$$$97fce321-3d13-4b6a-9bb5-d19012b7669d", "text": "Exclusive jurisdictional competence of the courts of the contracting party in whose territory the incident occurs or, in case of an incident outside the territories of contracting parties (in the course of transport of nuclear material), of the contracting party in whose territory the liable operator\u2019s installation is situated);"}
{"_id": "Radiology$$$5c749244-50b0-46e6-8207-44be85719da1", "text": "Recognition and enforcement of final judgments rendered by the competent court in all Contracting Parties.\u201d (IAEA Joint Convention on the Safety of Spent Fuel Management and on the Safety of Radioactive Waste Management [47])."}
{"_id": "Radiology$$$f7420570-252e-4c03-9225-ab00fba6568d", "text": "Furthermore, there must be a causal link between a certain nuclear installation, a certain nuclear incident, and the damage suffered. The burden of proof of the causal link is on the person claiming compensation. The Conventions do not contain any provisions regarding causality. This issue is left to the law of the competent court (i.e., to national law), so states may apply the principles of causality applied in their national law. In most states not all causes of damage are legally relevant; for example, remote causes may not be considered. In many states, the law requires \u201cadequate causality,\u201d which means that a cause is only legally relevant if that cause is likely to have directly caused the damage for which compensation is claimed."}
{"_id": "Radiology$$$3801ddea-d531-4c14-b909-6abbc0368fcb", "text": "The operator of a nuclear installation is held liable, regardless of fault. This concept is sometimes referred to as the channeling of liability. This kind of liability is called strict liability, or sometimes absolute liability or objective liability. It follows that the claimant does not need to prove negligence or any other type of fault on the part of the operator and the simple existence of causation of damage is the basis of the operator\u2019s liability. Furthermore, the operator of a nuclear installation is exclusively liable for nuclear damage. No other person may be held liable, and the operator cannot be held liable under other legal provisions (e.g., tort law). Liability is legally channeled solely onto the operator of the nuclear installation. This concept is a feature of nuclear liability law unmatched in other fields of law. With the exceptions of Austria and the USA, all states party to the Conventions that have enacted nuclear liability laws have accepted the concept of legal channeling. Exonerations from this strict liability are limited; the operator being held liable even if the nuclear incident is caused by force majeure (i.e., \u201can act of God\u201d)."}
{"_id": "Radiology$$$c9c4d945-ef6d-4b0e-8769-0b3604bf58af", "text": "It is also important to note that the financial compensation which results from the liability may be limited in amount because legislators feel that unlimited financial liability would discourage people from engaging in nuclear-related activities. It is important to note that not all states have chosen to limit liability. In the Conventions, claims for compensation for nuclear damage must be submitted within 30\u00a0years in the event of personal injury and within 10\u00a0years in the event of other damage."}
{"_id": "Radiology$$$5ea6e70d-ff92-45c2-ac36-851262db63a8", "text": "The nuclear liability conventions require that the operators maintain insurance or provide other financial security covering liability for nuclear damage in such amount, of such type, and in such terms as the installation state specifies. Insurance against nuclear risks is quite different in that there are not many nuclear clients in the insurance industry and while the risk is low in frequency, it is potentially very high in severity, resulting in very high amounts to be covered. On an international level international nuclear pools of insurance exist, where insurance companies net their capacity in order to bring together the financial capacities of the entire pool, which is then used to insure domestic civil nuclear risks and to provide inter-pool reinsurance (reciprocation). This pooling principle trickles down to the national level, where the domestic insurance industry is also organized into nuclear insurance pools."}
{"_id": "Radiology$$$d3e0c8e8-bc2b-4e40-a205-657765e17d4b", "text": "With regard to the compensation rights of those affected by nuclear energy accidents, the Protocols to amend the Paris Convention on Third Party Liability in the Field of Nuclear Energy and the Brussels Convention Supplementary to the Paris Convention have entered into force on 1 January 2022. The revised conventions combined ensure that those suffering damage resulting from an accident in the nuclear energy sector will be able to seek more compensation\u2014the operator liability will be of at least EUR 700 million under the Paris Convention and the public funds provided under the Brussels Supplementary Convention will complement up to EUR 1.5 billion, a sharp increase from the previous 5 million Special Drawing Rights (SDR) (approximately EUR 6 million as of 13 December 2021) and SDR 125 million (approximately EUR 155 million as of 13 December 2021), respectively. The revised Paris Convention also provides now for a minimum of EUR 70 million and EUR 80 million in case of accidents at low-risk installations and during the transport of nuclear substances, respectively. A total of 16 countries will be parties to the amended Paris Convention, covering 105 operating reactors and 7 under construction, out of a total of 442 operating reactors worldwide and 51 under construction. Of those countries, 13 are also parties to the amended Brussels Supplementary Convention (NEA COM 2021)."}
{"_id": "Radiology$$$53aaa125-0720-40fc-90d2-6c9de7a3a11a", "text": "Finally, with regard to jurisdiction, national procedural law(s) across countries may indicate several courts to have jurisdiction when dealing with claims arising out of a nuclear incident with transboundary or international effects\u2014meaning several courts could be allowed to claim competence to seize proceedings. The more complicated the different causes and effects, the more parties internationally involved and the larger the effects of the contamination, the greater the selection of potentially competent courts. For this reason, the Conventions provide, firstly, that only courts of the state in which the nuclear incident occurs, have jurisdiction and, secondly, that each member state party to the Conventions shall ensure that only one of its courts has jurisdiction in relation to any one nuclear incident. The concentration of procedures within a single court not only creates legal certainty but also excludes the possibility that victims of nuclear incidents will go \u201cforum shopping\u201d and seek to submit claims in states where their claims are likely to receive more favorable treatment."}
{"_id": "Radiology$$$566204f5-3cad-4a9d-8817-62d2013582af", "text": "If an activity or facility could cause public exposure in neighboring states through the release of radioactive substances to the environment, the regulatory body in the state of the licensee should take steps to ensure that the activity or facility will not cause greater public exposure in neighboring states than in the state of the licensee [55]. The concept of neighboring states does not require that these states share a border."}
{"_id": "Radiology$$$b2a0cf65-c570-4965-a40f-59eda5d3d98b", "text": "The Convention on Early Notification of a Nuclear Accident (the Early Notification Convention) [56] and the Convention on Assistance in the Case of a Nuclear Accident or Radiological Emergency (the Assistance Convention) [57] cover situations in which an accident involving activities or facilities in one state have resulted or may result in a transboundary release that could be of radiological safety significance for other states. In this context, legally binding obligations as adapted in national legislations may arise for radiobiologists, requiring them to notify, directly or through the IAEA, those states which are or may be affected by a nuclear accident. The nature of the nuclear incident, the time of its occurrence and its exact location should be promptly provided to those States affected in order to minimize the radiological consequences in those states."}
{"_id": "Radiology$$$0041ec07-aee2-49f8-a4ba-0874db458474", "text": "The nuclear liability conventions cover neither radiation damage caused by radioisotopes used for scientific, medical, commercial, and other purposes nor radiation damage caused by X-rays. This is because the use of radioisotopes and X-ray equipment does not present risks comparable to those for which the conventions were designed. The regime created by the conventions is intended for extraordinary nuclear risks only."}
{"_id": "Radiology$$$af7de87f-0617-464e-8d89-d14b92cbb41b", "text": "Even though experience has shown that radioisotopes and medical irradiation equipment can also cause serious damage if not handled properly, most states deal with liability for radiation damage caused by radioisotopes and X-rays under general tort law. States are free to enact, at the national level, special liability laws for damage caused by these types of exposure, providing for modified strict liability where the principle of liability without fault is maintained but the person liable may be exonerated if they can prove that they could not prevent the occurrence of the damage even though they complied with all radiation protection requirements and if they prove that any equipment used was not defective."}
{"_id": "Radiology$$$b4d0d171-a417-40a9-a737-12fa591bd2c1", "text": "In a medical context, harm caused could potentially amount to a breach of the duty of care that is owed to a patient from a medical professional or radiologist. If the person liable owes a duty of care to the patient, it must be proven that this duty was breached, resulting directly in the harm suffered by the patient. Where the breach is caused by gross carelessness, the liable party may be criminally negligent."}
{"_id": "Radiology$$$3c0ebe56-3517-4a45-8e82-7b9c89cf435a", "text": "One of the key principles of the radiation protection system recommended by ICRP is the principle of optimization of protection. The aim is to select the best protection option under the prevailing circumstances in order to keep the likelihood of exposure, the number of people exposed, and the magnitude of the individual doses incurred, all \u201cas low as reasonably achievable\u201d often abbreviated to the acronym \u201cALARA,\u201d taking into account economic and societal factors alongside health factors."}
{"_id": "Radiology$$$368589a3-b864-48da-887a-127151b3be35", "text": "It is important to stress that \u201cALARA\u201d does not simply mean \u201cas low as reasonably achievable\u201d in the sense that it should always be the \u201cvery lowest\u201d level of radiation exposure that can technically be achieved. \u201cALARA\u201d should rather be the \u201cbest\u201d protection option, nuanced and well-reasoned, where the highest level of safety that can be achieved from a health perspective, always needs to be balanced by social, environmental, and economic considerations."}
{"_id": "Radiology$$$abbd8d25-19ff-4bb3-993f-7273ea357f82", "text": "Standards are established and safety measures prescribed in order to ensure that facilities and activities with radiation risks achieve the highest level of safety throughout the lifetime of the facility or duration of the activity, without unduly limiting its utilization or usefulness. In order to determine whether radiation risks are at a level as low as reasonably achievable, any and all risks, whether arising from normal operations, abnormal conditions, or accidents, must be assessed using a graded approach that is periodically reassessed throughout the progression of the activity or lifetime of the facility."}
{"_id": "Radiology$$$3194808c-b966-458f-991c-8906237ece70", "text": "The optimization of protection requires careful judgment on the basis of scientific fact that is generally highly influenced by subjective appraisal tailored to individual situations, which makes it a difficult principle difficult to implement uniformly and consequently legally. The relative significance of various goals, events, and factors have to be judged, including the number of people (both workers and the general public) who may be exposed to radiation, the likelihood of exposure, the magnitude and the radiation doses likely to be received as a result of foreseeable and unforeseeable events, as well as the economic, social, and environmental factors involved with the installation or activity."}
{"_id": "Radiology$$$46ba2545-28ec-4477-8a6b-c4a1e2eb3d3c", "text": "The ICRP recommends, develops, and maintains the International System of Radiological Protection, based on an evaluation of the large body of scientific studies available to equate risk to received dose levels."}
{"_id": "Radiology$$$8108d52b-aac1-4a38-b799-7172cd72fc9f", "text": "The system\u2019s health objectives are relatively straightforward \u201cto manage and control exposures to ionizing radiation so that deterministic effects are prevented, and the risks of stochastic effects are reduced to the extent reasonably achievable\u201d (ICRP Publication 103)."}
{"_id": "Radiology$$$8a1ab5a3-461d-4cba-a6ce-45d02f32f59f", "text": "To this end, the ICRP has established a system of radiological protection with three main principles: justification, optimization of protection, and individual dose limitation that apply to planned, emergency, and existing exposure situations. Planned exposure situations are situations involving the deliberate introduction and operation of sources of radiation, either anticipated (normal exposures) or not anticipated to occur (potential exposures). Emergency exposure situations are situations that may occur during the operation of a planned situation, or from a malicious act, or from any other unexpected situation requiring urgent action. Existing exposure situations are exposure situations that already exist when a decision relating to control has to be taken, including prolonged exposure situations after emergencies. The ICRP considers exposure to cosmic radiation to be an existing exposure situation."}
{"_id": "Radiology$$$884ad463-6cd7-4c9d-98d0-0a32723b088c", "text": "The first two principles, justification and optimization of protection are source-related and apply in all exposure situations. The principle of justification states that any decision that alters the radiation exposure situation should be more beneficial than detrimental. The principle of optimization of protection states that the likelihood of incurring exposures, the number of people exposed, and the magnitude of their individual doses should all be kept As Low As Reasonably Achievable (ALARA), also taking into account economic and societal factors. The third principle concerning individual dose limitation is individual-related and applies in planned exposure situations: the total dose to any individual from regulated sources in planned exposure situations other than medical exposure of patients should not exceed certain appropriate limits."}
{"_id": "Radiology$$$1c094219-723f-4a1b-9336-3746c816c693", "text": "The ICRP further distinguishes between three categories of exposures: occupational exposures, public exposures, and medical exposures of patients. Occupational exposure is defined as all radiation exposure of workers incurred due to their work. ICRP limits the use of \u201coccupational exposures\u201d to radiation incurred at work in situations that can reasonably be regarded as being the responsibility of the operating management. The employer has the main responsibility for the protection of workers. Public exposure encompasses all exposures of the public other than occupational exposures and medical exposures of patients. The component of public exposure due to natural sources is by far the largest, but this provides no justification for reducing the attention paid to smaller, but more readily controllable, exposures to man-made sources. Exposures of the embryo and fetus of pregnant workers are considered to be public exposures and regulated as such."}
{"_id": "Radiology$$$dd8791f9-c939-4866-9189-b1137a8d139a", "text": "While dose is a measure of the total amount of radiation received, the dose limit is a value of the effective or equivalent dose to individuals that may not be exceeded in activities under regulatory control. The regulatory body sets the dose limits for various activities. These dose limits are sometimes found in the nuclear laws, but more often in the accompanying and more detailed regulations, where regulatory bodies principally rely on IAEA publications."}
{"_id": "Radiology$$$ed9c44f9-afc3-4d33-8f32-2bedf84978fe", "text": "Restricting an individual\u2019s radiation dose is another key factor of the international radiation protection system. Restrictions include dose limits, dose constraints, and reference levels of dose. Each of these restrictions has different legal implications."}
{"_id": "Radiology$$$e809d779-d0d7-466e-b408-f5a8d8500895", "text": "The dose limit is the value of dose to individuals from planned exposure situations that shall not be exceeded. A dose constraint is a prospective and source-related restriction on the individual dose from a source, which provides a basic level of protection for the most highly exposed individuals from a source, and serves as an upper bound on the dose in optimization of protection for that source."}
{"_id": "Radiology$$$ab4f0d8f-12cf-4c93-bab7-4c84cafd7e97", "text": "For occupational exposures, the dose constraint is a value of individual dose used to limit the range of options, both short- and long-term, considered in the process of optimization. For public exposure, the dose constraint is an upper limit on the annual doses from the planned operation of any controlled source that members of the public should not exceed. In emergency or existing controllable exposure situations, a reference level is established to represent the level of dose or risk, above which it is judged to be inappropriate to plan to allow exposures to occur, and below which optimization of protection should be implemented. The chosen value for a reference level will depend upon the prevailing circumstances of the exposure under consideration."}
{"_id": "Radiology$$$c3b2cb49-4960-44cb-8a87-97f002404958", "text": "Dose limits are not uniform, neither in concept nor in the quantities that they are expressed. The three dose quantities used for establishing dose limits are the absorbed dose, the equivalent dose, and the effective dose. The absorbed dose is a measurable, physical quantity expressing the amount of energy deposited by radiation in a mass. The equivalent dose is a weighted absorbed dose designed for specific radiation protection purposes and is calculated for individual organs while the effective dose, which is also designed for specific radiation protection purposes, is calculated for the whole body. Dose limits may vary depending on factors such as pregnancy. It is worth noting again that dose limits do not apply to emergency, existing, or medical exposures. Dose limits only apply to occupational, public, and planned exposure. The current dose limits set out by the ICRP in Publication 103 are as set out in Table 12.1 below.Table 12.1\nRecommended dose limits in planned exposure situations\n\nType of limit\n\nOccupational\n\nPublic\n\nEffective dose\n\n20\u00a0mSv/year, averaged over defined periods of 5\u00a0years\n\u00a0\nAnnual equivalent dose in:\n\u00a0\u00a0\nLens of the eye\n\n150\u00a0mSv\n\n15\u00a0mSv\n\nSkin\n\n500\u00a0mSv\n\n50\u00a0mSv\n\nHands and feet\n\n500\u00a0mSv\n\n\u2013"}
{"_id": "Radiology$$$9ddaab6d-1798-4ca1-bbde-548ead5f558e", "text": "Dose limits set by the ICRP are not hard law but most countries have implemented these limits into their national legislation making the exceeding of dose limits illegal. The industry may also choose to set dose limits for their workers even lower than those required by law to both ensure the safety of their employees and reduce the likelihood of lawsuits."}
{"_id": "Radiology$$$d88958c5-bb4c-44b7-b073-0e2b0b1676e9", "text": "Radiation workers are obviously more at risk to be exposed to radiation than the average individual and dose limits for occupational exposure are different from dose limits for public exposure, specifying an upper limit and a relevant time span."}
{"_id": "Radiology$$$583d545e-fbf3-4a60-a2b6-fdf719a9ed86", "text": "In case of a nuclear emergency, workers will likely be exposed to significantly higher doses, often much higher than the annual recommended dose limit. A very careful assessment will have to be made weighing the rescuer\u2019s own risk versus a clear benefit to others."}
{"_id": "Radiology$$$510eef70-bbc3-482f-98b6-49c0c3cdeda6", "text": "The ALARA principle encourages practitioners and other individuals who have an influence on radiation dosage to limit dosage as much as practically possible, even when accounting for the benefits the exposure situation might bring. This also means that if the exposure does not present a direct and sufficient benefit, it should be avoided. In order to optimize protection for radiation workers, the duration of the exposure should always be minimized while the distance between the source of the radiation and the individual should be maximized. A third essential factor is shielding."}
{"_id": "Radiology$$$8c635158-263b-4d50-8133-e68f8a5f8f38", "text": "The legally binding obligations related to occupational radiation protection are established in the Radiation Protection Convention No. 115 adopted by The General Conference of the International Labour Organization [58]. This Convention, which has been ratified by most countries, applies to all activities involving exposure of workers to ionizing radiations in the course of their work and who, in applying its provisions the state party\u2019s competent authority, have to consult with representatives of employers and workers."}
{"_id": "Radiology$$$8c46ddd5-7bfb-40be-a704-aecba8af3a93", "text": "Sources of ionizing radiation are essential to modern healthcare as they span a range of purposes, such as the sterilization of disposable medical supplies, central to combating disease [59]. To give a more recent example, China has optimized the use of radiation to cut down sterilization times from 7\u00a0days to just 1 in order to combat the COVID-19 pandemic [60]. Radiology is also a vital diagnostic tool; CT and X-rays have been crucial\u00a0to healthcare in terms of diagnostic precision, which in turn improve treatment response."}
{"_id": "Radiology$$$514a615c-d926-4f64-9dda-4f88b5707f56", "text": "However, as ionizing radiation can be detrimental to living organisms, humans included, it is essential that sources of ionizing radiation be covered by measures to protect individuals. Medical treatment involving planned exposure to ionizing radiation can only take place if the patient has agreed after being carefully informed about the risks."}
{"_id": "Radiology$$$31fe152b-2c72-4166-b03f-7089164f9d96", "text": "Radiation exposures of patients occur in diagnostic, interventional, and therapeutic procedures. There are several features of radiological practices in medicine that require an approach that differs from radiological protection in other planned exposure situations. The exposure is intentional and for the direct benefit of the patient. Particularly in radiotherapy, the biological effects of high-dose radiation, e.g., cell killing, are used for the benefit of the patient to treat cancer and other diseases. The medical uses of radiation therefore require separate guidelines."}
{"_id": "Radiology$$$5699a470-f4b9-4c94-957b-07b12ced0843", "text": "A relatively recent topic of discussion is that of adventitious exposure, i.e., unintended exposure happening as a result of primary, intended exposure. A patient undergoing therapeutic exposure to ionizing radiation\u2014exposure that is considered to be beneficial, contributing to a positive medical outcome\u2014probably will suffer to some extent, effects that are neither intended nor desired because these are an unavoidable by-product of radiotherapy procedures. Adventitious exposure can occur in any part of the body and cause secondary cancers as a malignant result of radiotherapy, the effects remaining latent, manifesting only after the treatments. It is important to distinguish that cancer forming due to adventitious exposure is not a metastasis of the original malignancy, but rather a primary malignancy in itself. The incidence of such cancers is being investigated worldwide, also by UNSCEAR, and may contribute to litigation initiated by patients or their next of kin against radiobiologists or other radiation specialists in the medical field. A deep understanding of this complex mechanism is still evolving, but the medical professional would do well to document\u2014either by measurement or estimation\u2014the scenario of adventitious exposure situations through dosimetric quantities or suitable proxies. It may even prove to be necessary to dutifully inform and obtain explicit patient agreement on the subject."}
{"_id": "Radiology$$$8d23bce1-e2fc-4424-bd4c-a5f48699baa0", "text": "Most countries have regulations to guide the medical professional involved with treatment that includes medical exposure of a patient to ionizing radiation in order to protect both the professional and the patient. In the EU, Council Directive 2013/59/Euratom Chapter VII [61] centers the relevant articles 55 and 56 once again around the principles of justification and optimization. In the assessment and justification of the use of radiology with any specific patient, the practitioner should consider all relevant aspects of their medical history and decide, with feedback and consent from the patient, the radiation therapy most suited to that individual patient."}
{"_id": "Radiology$$$c6adc9b4-2f22-4af3-b168-eac322483a60", "text": "Cosmic rays at ground level are not considered to warrant regulatory control. Mankind has been exposed to\u2014and has evolved with\u2014radiation from the universe reaching Earth since the beginning of time. However, at high altitudes, where cosmic rays are less attenuated by the atmosphere or, even higher, by the Earth\u2019s magnetic field, they undoubtedly pose a risk to people and equipment because of the very high energies involved. As a consequence, astronauts and aircraft personnel need to be well informed about these exposure risks during the course of their careers and possible consequences and outcomes as a result."}
{"_id": "Radiology$$$31ea03ec-374f-4297-9cb1-7954a16564b3", "text": "Disregarding the Space Treaties that arguably do not really deal with exposure to ionizing radiation, the protective framework for astronauts in this context is not regulated by international law, but rather designed and governed by the space agencies by which they are employed, on the basis of an ever-evolving scientific insight and assessment. All major space agencies have very stringent safety precautions in place, specifying dose, dose rate, and career limits for their astronauts in order to make sure there is no statistical risk of radiation exposure-induced death (REID) and other adverse effects. Even though astronauts are generally extremely healthy and are unlikely to suffer health effects at a level worse than that of the general population, the advent of deep space travel, notably the Moon and Mars missions planned in the near future, will likely expose them to high fluxes of solar energetic particles and heavy ions, in possibly problematic amounts. Radiation mitigation strategies, shielding and careful mission planning, and astronaut selection will prove to be crucial to attempt these types of interplanetary exploratory missions. Being continuously monitored and genetically screened for suitability may however create some legal issues as well. Not only are privacy issues imaginable with the extreme scrutiny astronauts are subjected to, but unequal treatment and an imbalance in career opportunities due to individual genetic predisposition to adverse health effects from ionizing radiation may at some point also become an object of contention, as is discussed more in depth in Sect. 12.3.8 on emerging occupational challenges from new methods to determine individual radiosensitivity (supra)."}
{"_id": "Radiology$$$bcbc4ca6-e190-4241-a262-8dc59a3a580d", "text": "Guidance and protection for other jobs at slightly lower altitudes are much more regulated. Airline pilots and personnel\u2014and even frequent flyers\u2014repeatedly expose themselves to ionizing radiation, primarily from charged particles and therefore require employment protection. Compared to astronauts, aircraft personnel make up a substantially larger group of radiation workers, inspiring governments to implement special mandatory protection measures. For example, Directive 96/29/Euratom 1996 requires appropriate radiological protection of aircrew. Article 42 of the Directive obliges member states to regulate the sector, specifically regarding the exposure to cosmic radiation at flight altitudes. As a result, each member state is obliged to force airline companies to take account of exposure to cosmic radiation of aircrew who are liable to be subject to exposure to more than 1\u00a0mSv/year. EU airline companies need to record a continual assessment of the exposure of the crew concerned and use this information when organizing working schedules with a view to reducing the doses of highly exposed aircrew. Aircraft personnel needs to be informed of the health risks their work involves and female aircrew in particular, when pregnant, will have the terms of her employment adapted to ensure that the equivalent dose to the child to be born is ALARA and that it will be unlikely that this dose will exceed 1\u00a0mSv during at least the remainder of the pregnancy. As soon as a nursing woman informs her employer of her condition, she cannot be employed in work involving a significant risk of bodily radioactive contamination. This is of course not to say that female airline crew are the only radiation workers protected through nuclear law; different rules for pregnancy, varying from country to country, are applicable for workers in other nuclear industries."}
{"_id": "Radiology$$$c0ea5f83-5129-4ed4-880f-7fc458a01d87", "text": "Legal action based on radiation harm, i.e., legal proceedings or a lawsuit, generally requires two elements to succeed; attribution and imputation. First, a causal link must be established; a certain health effect needs to be attributed to a certain radiation exposure using objective factual evidence. Second, there needs to be imputation, meaning someone\u2019s responsibility for the radiation harm needs to be determined. In a legal context, imputation means placing the responsibility for the physical injury (actual or potential ill effects) that is attributable to the radiation exposure, on another (natural or legal) person. While \u201cattribution,\u201d meaning establishing the factual link between a nuclear incident and a health effect and \u201cimputation,\u201d meaning ascribing responsibility for the radiation harm are closely related in that they both attempt to establish a causal link, they have often been used as synonyms, causing confusion. Examples range from the use by the International Labour Organization (ILO), International Atomic Energy Agency (IAEA) to the World Health Organization (WHO)."}
{"_id": "Radiology$$$78e0dfec-1425-4816-abcc-f5215dcb72ea", "text": "When attribution between the incident and the effect is established, imputation is crucial to allow for subsequent legal actions such as charging, indicting, and prosecuting\u2014if a criminal element is involved\u2014or simply initiating a civil suit if another form of negligence can be demonstrated. The end goal for the plaintiff is to obtain reparation for damages incurred."}
{"_id": "Radiology$$$62357e37-192f-4b78-8584-71312c778a76", "text": "Attribution and imputation both generate controversy and two basic challenges dominate the issue. The first challenge is the attribution of specific health effects to a specific radiation exposure situation, which requires qualified experts to demonstrate that a factual occurrence can be causally linked\u2014meaning without a doubt\u2014to radiation harm. The second challenge is of a more formal nature; how to proceed with relevant legal actions consistent with the legal practice in the applicable jurisdiction or legal system. In high-exposure incidents with obvious harmful effects, this is relatively straightforward. On the other hand, a challenge arises in situations involving low to very low radiation doses. This issue is amply discussed in the literature [62\u201364] but no clear solution, let alone a consensus between experts, has been found yet."}
{"_id": "Radiology$$$3bd71c5f-1b38-4741-b65c-a7ff566ebefc", "text": "The attribution of health effects to radiation means no more than factually linking the health effects of radiation exposure to objective and indisputable evidence of any given radiation exposure situation. When establishing attribution, there can generally be no reasonable doubt between the cause and the health effect. When moving away from a high-dose, high-probability scenario, in cases where low or lower doses are concerned, the lines become blurred and direct attribution can be problematic. As a consequence, in low-dose scenarios the causal link often needs to be inferred, meaning a reasonable conclusion needs to be reached on the basis of evidence and experience. In contrast to attribution, inference entails the process of drawing conclusions from subjective conjectures involving indirect conclusions based on scientific observations and reasoning on radiation risks, while allowing an element of uncertainty. The discussion involving the attribution of health effects to radiation and the inference of radiation risks is closely followed on an international level by the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) (UNSCEAR [65] Report to the General Assembly with Scientific Annexes). UNSCEAR, which has been compiling and discussing decades of case material, scientific research, and expert opinions on the subject, periodically reports its findings to the United Nations General Assembly [66]. The United Nations Environment Program (UNEP) has summarized the progressing UNSCEAR insights and has made an abridged version available to the general public, in an illustrated volume [67] containing the illustrations that are used in this chapter. The UNSCEAR findings are simplistically condensed in a dose\u2013response relationship, a graphical representation of the probability that people would suffer health effects and the radiation doses they have incurred, shown in Fig. 12.1.\n\nA chart illustrates the relationship between radiation doses and health effects for the probability of the effect versus dose of natural background, occupational, Chernobyl child thyroid dose, Chernobyl firemen. The increasing values of biologically plausible, statistically observable in populations, and clinically observable in individuals.\n\nFig. 12.1\nAdapted from UNSCEAR 2012, Annex A Schematic of the relationship between dose, additional to that from typical exposure to natural background radiation, and probability of occurrence of health effects, Fig. AV-I p68"}
{"_id": "Radiology$$$afe23e09-32fb-4072-af7d-00fcc5601ad0", "text": "A chart illustrates the relationship between radiation doses and health effects for the probability of the effect versus dose of natural background, occupational, Chernobyl child thyroid dose, Chernobyl firemen. The increasing values of biologically plausible, statistically observable in populations, and clinically observable in individuals."}
{"_id": "Radiology$$$fdb4fcc3-2424-432f-8f4a-acdfbb2d727f", "text": "UNSCEAR has highlighted the importance of distinguishing between two types of effects (see yellow ellipses in Fig.\u00a012.1). Purely observational health effects in exposed individuals and populations will lead to attribution if the health effect to radiation exposure situation is observed and then attested. On the other hand, plausible health effects for which occurrence is likely conceivable but not directly verifiable, only allow one to infer health effects from known risks, but without clear attribution."}
{"_id": "Radiology$$$f263c412-bad1-4ffe-9ff3-2f5783883391", "text": "In the figure, the doses on the x-axis are expressed from very low to high. A \u201chigh dose\u201d indicates an effective dose around 1 Sv and up, many orders of magnitude higher than the annual levels of natural background radiation. A \u201cmoderate dose\u201d is situated between 100\u00a0mSv and 1 Sv, while a \u201clow dose\u201d is in the tens of mSv, and a \u201cvery low dose\u201d is around 1\u00a0mSv."}
{"_id": "Radiology$$$f436c379-a183-44aa-852d-4fa4b043d621", "text": "Note too that the probabilities on the y-axis are expressed in percentages between 0% and 100%, where 100% corresponds to the certainty that the effect will occur and 0% corresponds to the certainty that the effect will not occur. In between these values, probabilities need to be calculated, which can be done in two ways. Frequentist probabilities are most often used in the high-dose range and take into account the verifiable existence of radiation health effects, defined as the limit of the relative frequency of incidence of the effect in a series of certifiable epidemiological studies. Frequentist probabilities are based on fact. In low-dose ranges, clear-cut evidence and unambiguous studies are scarce and a frequentist probability is out of the question. The solution then would be to include subjective\u2014or \u201cBayesian\u201d\u2014probabilities, that are expressed as an expectation that radiation health effects could occur, but these are not so much based on and quantified by scientific reasoning as on an expert\u2019s judgment that may arguably not be substantiated by the frequency or propensity that the effects actually occur. In other words, reasoned conjecture."}
{"_id": "Radiology$$$448ecd7c-0f44-4305-957a-d1c9060f2675", "text": "The attribution of radiation harm is an essential component of any legal action. A professionally qualified expert witness should provide clear evidence on the occurrence of radiation effects, caused by a radiation incident, by formally declaring that a causal effect exists. It is obviously not necessary for an expert to have witnessed first-hand the incident at the origin of a radiation-related lawsuit, but he or she does need to be a specialist in radiation effects and able to offer, without reasonable doubt, an expert opinion after considering the chronology of events and factual occurrence of the causes and the effects."}
{"_id": "Radiology$$$7dda56cf-73a9-423a-aa8a-87a24ef30044", "text": "Crucially, the type of expert a plaintiff would rely upon to bring evidence to the case is related to the dose and dose rate, or more precisely the dose\u2013response relationship connected to the incident. This of course is related to the factual observability and thus the scientific attestability of the effects\u2014ranging from attributing to inferring. In a high-dose scenario, the effects are most likely clinically observable, easily attributable and therefore diagnosable in exposed individuals by a qualified expert radiopathologist. In the region of moderate doses, the effects are not directly attributable in individuals because similar effects can occur due to other causes, but they are statistically consistent with the background incidence of the effect that has been studied in certain population cohorts. This incidence can be mathematically quantified as a probability and attested by a radioepidemiologist. Both radiopathologists and radioepidemiologists rely on frequentist probabilities with a high degree of certainty. In the low to very low-dose range, most effects are neither observable nor attributable and thus their occurrence is not attestable with any reasonable certainty. However, a case can be made that the effects of a low-dose incident may be biologically plausible and therefore risk and potential radiation harm could be inferred through the personal judgment of radioprotectionists by assigning probabilities. The probabilities offered in these low-dose cases by radioprotectionists are arguably less objective than the frequentist probabilities demonstrated by radiopathologists and radioepidemiologists since they are skewed towards expert opinion based on experience rather than indisputable scientific fact. This is visible in Fig. 12.2.\n\nA chart illustrates the probability of effect versus dose of natural background, occupational doses, Chernobyl child thyroid doses, and Chernobyl firemen of radio-protection, radio-epidemiology, and radio-pathology.\n\nFig. 12.2\nAdapted from UNSCEAR 2012, Annex A Schematic of the relationship between dose, additional to that from typical exposure to natural background radiation, and probability of occurrence of health effects, Fig. AV-I p68"}
{"_id": "Radiology$$$8674ec9a-ff76-4435-ad3c-6846b52bc061", "text": "A chart illustrates the probability of effect versus dose of natural background, occupational doses, Chernobyl child thyroid doses, and Chernobyl firemen of radio-protection, radio-epidemiology, and radio-pathology."}
{"_id": "Radiology$$$16568d47-8081-466f-954c-be51d1f12053", "text": "Radiopathologists, radioepidemiologists, and radioprotectionists can all be qualified expert witnesses in the context of legal action, the first attesting the factual occurrence of health effects that can be diagnosed in individuals, the second attesting the factual occurrence of radiation health effects that can be estimated in population cohorts using statistics on the incidence and distribution of diseases associated with radiation exposure, and the third by inferring radiation risks from theory rather than fact. Radiobiologists are a fourth group of scientists that could be situated somewhere between radiopathologists and radioepidemiologists. A radiobiologist has expertise in the branch of biology concerned with the effects of ionizing radiation on organisms, organs, tissues, and cells which can be useful\u2014without directly attesting the factual occurrence of biological changes in an individual\u2014to demonstrate probable effects on tissue after radiation exposure by extrapolating data collected during the study and analysis of specialized bioassay specimens, hematological and cytogenetic samples."}
{"_id": "Radiology$$$c17570d0-799a-4ee6-8f3c-2e1077703689", "text": "The ability to attribute health effects to specific exposure situations and to attest their occurrence by means of a qualified expert witness has a direct influence on the chances of successful litigation if the radiation harm can be clearly attributed to an incident, imputed to the persons responsible and subsequently compensation awarded to the victims by a court of law. Physical injuries and harmful effects inflicted by those who have caused the exposure, if proven, allow radiation workers or the general public to bring a lawsuit against employers, licensees of nuclear installations, or even the regulatory authorities in the event of a lack of oversight or effective control."}
{"_id": "Radiology$$$143e862c-0307-4436-bca6-6404485f8517", "text": "The legal playing field however is not quite level. Legislation and regulatory frameworks that deal with the attribution of radiation health effects are inhomogeneous, sometimes incoherent, and inconsistent among countries and even within countries. A major fault line exists between legal systems based on jurisprudential legislation and those who rely on detailed codified legislation. A comparison of case law exceeds the scope of this chapter, but\u2014at the risk of being overly coarse\u2014we could state that jurisprudential legal systems that employ a case-by-case approach are generally more flexible and provide a higher degree of legal certainty for the plaintiff. Jurisdictions that rely on codified legislation are not bound by legal precedent, placing a high degree of autonomy on the court in applying the rule of law, which can lead to less predictable results."}
{"_id": "Radiology$$$49dba30e-d875-43ec-b27c-fa50d2885ec4", "text": "Figure 12.3 attempts to broadly define what would be feasible when litigating the following situations.\n\nA chart illustrates the relationship between radiation doses and the health effects of probability of effect versus dose for uncertain claims, ambiguous facts, subjective judgment, class action lawsuits, and classic lawsuits.\n\nFig. 12.3\nAdapted from UNSCEAR 2012, Annex A Schematic of the relationship between dose, additional to that from typical exposure to natural background radiation, and probability of occurrence of health effects, Fig. AV-I p68"}
{"_id": "Radiology$$$a0bbd2c2-ac46-469d-9c24-c785c62dbe4f", "text": "A chart illustrates the relationship between radiation doses and the health effects of probability of effect versus dose for uncertain claims, ambiguous facts, subjective judgment, class action lawsuits, and classic lawsuits."}
{"_id": "Radiology$$$c1d947b8-6e93-4ad2-a85b-42b2a98a3cab", "text": "In the high-dose region, individual health effects are clinically attributable and attestable, and imputation of harm incurred by the affected individual is therefore straightforward. Attribution is clear; imputation is often directly linking the individual suffering radiation harm to the responsible person and a classic lawsuit, where civil legal action by one person or entity against another person or entity has a high chance of success."}
{"_id": "Radiology$$$10712439-afdc-4b5a-9cea-eaceac13c754", "text": "In the moderate dose region, increased incidences of harmful effects in population groups are epidemiologically attributable and attestable and imputation to the responsible person is therefore feasible. When dealing with the harmful effects of moderate doses, a collective or group imputation is more logical, e.g., via a class action lawsuit where the plaintiffs are more likely than not a group of people presenting a collective claim."}
{"_id": "Radiology$$$70abff09-9970-45e3-8593-c59d50cfdadd", "text": "In the low-dose region, radiation harm is neither attributable nor attestable on an individual or collective level, but some radiation risk might be inferred. From a legal perspective, claims based on a low dose or low dose rate exposure are uncertain. Since radiation harm might not yet have presented itself or, if present, might be quite removed in time from the alleged exposure situation, a court might struggle with establishing, beyond a reasonable doubt, a causal link between the exposure situation and any health effects allegedly suffered by the plaintiff. The problem presented here is one of objectivity. The cause cannot be attested, the harmful result is only inferred considering theoretical risk and perhaps statistical probability, and any judgment based on these ambiguous facts would have a high degree of subjectivity."}
{"_id": "Radiology$$$76110b09-5918-4a85-818a-29219f155f53", "text": "The scientific consensus on health effects attributable to radiation exposure\u2014consensus that in itself is not entirely uniform and still progressing\u2014should serve as a basis for the development of legal instruments in order to have a more uniform treatment of legal actions. In particular, the issue of legal imputation when considering low dose rates should be carefully considered. This issue has not yet crystallized in any type of universal approach, in large part given the fundamental differences between case-based and codified legal systems. The scientific community is eager to provide legal experts with guidance based on the progressing insight into the attribution of radiation effects following radiation exposure situations."}
{"_id": "Radiology$$$45557a14-b5b3-4a77-ad5b-fe3cd5c159b1", "text": "Given the cultural, regulatory, and legislative differences among countries, two fundamental objectives stand out. First, it seems imperative to foster a common legal understanding of cause and effect when dealing with radiation harm and radiation exposure situations. From a scientific perspective, this seems feasible, and if adopted by the legal community, this would greatly enhance legal certainty. Second\u2014and perhaps even more optimistically\u2014the establishment of a universal scientific and legal consensus to direct the application of the law in any situation would reduce uncertainty even further and might even benefit the development and harmonization of different national legislations. In reality however \u201cthe law\u201d is not a uniform concept and nations, courts and judges, prosecutors and lawyers will always want to look at the facts of any individual case, assess the differences and exceptions to the rules if there are any and, in general, assert their independent reasoning. Today, the road ahead for the legal community dealing with nuclear law seems long and far from determined."}
{"_id": "Radiology$$$478a4362-c2b4-4c33-bb3e-3011e61344b8", "text": "Human behavior is primarily driven by perception and not by facts [68]. In practice, this pattern is clearly demonstrated also in people\u2019s behavior related to ionizing radiation. For instance, exposure to the medical application of ionizing radiation is highly acceptable for most people, while food irradiation used to increase the safety of food may be unacceptable for many people, although in the first case the patient may receive a relatively high radiation dose and in the second case the consumer will not receive any radiation due to the sterilization [69, 70]."}
{"_id": "Radiology$$$b2bed174-0dc7-4aa8-afcd-f6527b7e55ac", "text": "Likewise, 10\u00a0mSv received as a worker\u2019s exposure or 10\u00a0mSv received during an accidental release of radioactivity to the environment may cause different behavior. This section examines the social and psychological aspects of radiation exposure. First, we will explain the phenomena of radiation risk perception and second we will identify and discuss determinants of health and radiation protection behavior. Finally, we will conclude this chapter with radiation risk communication advice for experts in radiobiology in order to be able to communicate effectively and help people to make informed decisions related to radiation risks."}
{"_id": "Radiology$$$b1380436-d304-40c3-8bdb-eeb271e7928f", "text": "Risk perception mainly denotes the ways individuals think and feel about the risks they face [71\u201373]. Radiation risk perception has been extensively studied, for example, in the context of nuclear power [74\u201376], nuclear testing [77], radioactive waste [78], radon [79], food sterilization by irradiation [80], and nuclear accidents [81]. It is interesting that people perceive radiation risks differently, depending on the origins of this radioactivity, and the contexts in which it is encountered."}
{"_id": "Radiology$$$3252660d-73b8-4a5d-aa68-294f3ac03c90", "text": "In order to demonstrate diversity in radiation risk perception, we present the results of a public opinion survey conducted in a high radon-prone area in Belgium [82]. Figure 12.4 illustrates how residents of radon-prone areas think and feel about environmental and radiation risks. It shows that residents living in radon-prone areas in Belgium perceive the risk from environmental pollution as the highest potential risk to their health within the next 20\u00a0years, followed by the risk of a climate crisis. Among risks related to radon and naturally occurring radioactive material, the risk of indoor air pollution due to radon is perceived as the highest potential risk to their health within the next 20\u00a0years, followed by the use of recycled material with low levels of radioactivity for buildings. The lowest risk for health within the next 20\u00a0years is perceived to come from natural radiation from the soil or from space. Interestingly, in this 2021 survey, the risk of medical applications of ionizing radiation is perceived as one of the lowest radiation risks by residents of radon-prone areas in Belgium, although medical exposure presents the most significant dose in Belgium.\n\nA horizontally stacked bar graph of risk perception for environmental pollution, climate crisis, natural radiation, the use of recycled material with low levels of radioactivity for buildings, the use of ionizing radiation for medical tests or treatments, indoor air pollution due to radon of no, very low, low, moderate, high, very high risk, and don't know or no answer.\n\nFig. 12.4\nPerception of environmental and radiation risks by residents of high radon-prone area in Belgium, 2021 [82]"}
{"_id": "Radiology$$$9a994cba-c100-4d39-a317-155a70a0bc52", "text": "A horizontally stacked bar graph of risk perception for environmental pollution, climate crisis, natural radiation, the use of recycled material with low levels of radioactivity for buildings, the use of ionizing radiation for medical tests or treatments, indoor air pollution due to radon of no, very low, low, moderate, high, very high risk, and don't know or no answer."}
{"_id": "Radiology$$$ecfbd94f-2c58-4a13-a5e5-1050fceadf78", "text": "Research also shows that experts and the general public often disagree about the potential danger posed to their health by nuclear waste, an accident in a nuclear installation, natural radioactivity, medical X-rays, or the Daiichi nuclear accident in Fukushima [83]. In the study of Perko [84], the public had significantly higher risk perceptions of all radiation risks when compared to experts, with the only exception being medical exposure. However, expert opinion and lay perception need to be perceived as complementing rather than competing with each other [85]. Remarkably, empirical results show that experts\u00a0too do not think and feel the same about radiation risk. When a distinction was made between experts that received a dose of more than 0.5\u00a0mSv due to their professional exposure, and those who did not, those who were exposed to more than 0.5\u00a0mSv perceived the risk of radiation waste and an accident in a nuclear installation significantly lower than their colleagues did. Similarly to this, they also did not agree about risks from nuclear accidents in Japan. On the other hand, the employees receiving a dose higher than 0.5\u00a0mSv had significantly higher risk perceptions of natural radioactivity and medical use of ionizing radiation than their colleagues. These results can be explained by the characteristics of risk, suggesting that familiarity with risk, knowledge, personal control, and voluntariness decrease risk perception."}
{"_id": "Radiology$$$31b16836-a12a-4459-b4f7-3fcb5be41bd9", "text": "Characteristics of risk and their impact on (un)acceptability have been studied and identified by scholars using a psychometric method [68, 86, 87]. Studies of risk perception examine the opinions people express when they are asked, in various ways, to characterize and evaluate hazardous activities and technologies [85, 88]. The method is based on a number of explanatory scales corresponding to various risk characteristics, which are an explanation of contextual traits that people use when they make decisions related to risks. Some of these scales involve traits focusing on whether the risk has an influence on children, whether it is involuntary or not, whether people are familiar with the risk or it is new to them, whether the risk has a catastrophic potential, whether it can cause delayed or immediate consequences, whether the risk is already known to science or not. Table 12.2 demonstrates the characteristics of risks, their influence on risk (un)acceptance, how they can be explained in a scale from maximum to minimum, as well as providing descriptive examples of radiation risk acceptance as hypothetical scenarios.Table 12.2\nExamples of acceptable radiation risks in relation to risk perception\n\nDescriptive example of an acceptable radiation risk\u2014a hypothetical scenario\n\nSelected characteristics of risk\n\nInfluence on risk (un)acceptability\n\nExplanatory scale\n\nA catastrophic potential of a nuclear accident made the risk more threatening since low-probability high-consequence radiation risks are usually perceived as more threatening than more probable risks with low or medium consequences.\n\nCatastrophic potential\n\nDecreases risk acceptability\n\nCatastrophic\u2014chronic\n\nMedical personnel is wearing assigned personal radiation dosimeters during a procedure using ionizing radiation, which gives a feeling of control and increases the acceptability of radiation exposure.\n\nPersonal control\n\nIncreases risk acceptability\n\nControllable\u2014not controllable\n\nA phosphate factory is recognized as a trustworthy organization since they communicate openly about the risks of naturally occurring radioactive material as a side product.\n\nInstitutional control\n\nDepends upon confidence in institutional performance\n\nTrust, confidence in the institution\n\nPopulation density around nuclear installation is low thus controlled releases of radioactivity from a nuclear installation in an environment is acceptable.\n\nNumber of exposed\n\nDecreases risk acceptability\n\nLocal\u2014global\n\nWorkers get employed at a nuclear installation on a voluntarist basis thus they accept workers\u2019 exposure to ionizing radiation.\n\nVoluntariness\n\nIncreases risk acceptability\n\nVoluntary\u2014involuntary\n\nA patient receives a low dose of ionizing radiation during X-ray which makes it acceptable.\n\nMortality\n\nDecreases risk acceptability\n\nFatal\u2014not fatal\n\nVisitors learned about radiation and technology used by researchers during an open-door day at a nuclear research institute. New insights and knowledge influenced their acceptability of potential radiation risks.\n\nKnowledge\n\nIncreases risk acceptability\n\nNew technology\u2014established technology\n\nLiving in a home with high radon concentration for many years (more generations) made residents accept radon risk and not performing radon test or necessary remediation of a house\n\nFamiliarity\n\nIncreases risk acceptability\n\nFamiliar\u2014not familiar\n\nA traffic accident with transport of radionuclides for a hospital in a citizen\u2019s region is not as dreadful as a nuclear accident in another continent is.\n\nDread/fear\n\nDecreases risk acceptability\n\nFear\u2014no fear\n\nHigh natural background of radiation is for many people acceptable because it is natural due to the geological characteristics of a region.\n\nArtificiality of risk source\n\nAmplifies attention to risk\nOften decreases risk acceptability\n\nHuman\u2014natural\n\nDuring an environmental remediation process, residents had a feeling of fairness since they could co-decide on how, where, and to which level should be environment remediated. Thus, they accepted radioactive residues in a dedicated part of their administrative community.\n\nFairness\n\nIncreases quest for social and political responses\n\nFair\u2014unfair\n\nReceiving compensation for radioactive waste disposal made the project acceptable.\n\nBenefit\n\nIncrease risk acceptability\n\nBenefit to self-vs. unclear or inequitable\n\nIntake of stable iodine as an effective countermeasure for reducing the risk of thyroid cancer in an eventual release of radioactive iodine following a nuclear accident, especially for children, made the pre-distribution of the iodine tablets to residents and un uptake of a tablet if necessary, an acceptable option.\n\nEffect on children\n\nDecrease risk acceptability\n\nChildren specifically at risk"}
{"_id": "Radiology$$$f65dc719-2eea-4194-b111-dd60549a612f", "text": "Research shows that only one person in five is prepared to take health-related actions at any given time [89, 90]. Radiation protection behavior is not an exception to this finding. Authorities and other radiation protection actors are often challenged with what has been termed a \u201cvalue-action gap.\u201d This gap refers to a situation where the values or attitudes of an individual or a group of people do not correlate with their actions; a positive attitude towards good health does not lead to an action to improve/protect health [91]."}
{"_id": "Radiology$$$c6240ad8-2ffa-4d32-80da-a413f095f581", "text": "For instance, testing for radon and remediating your home if radon concentrations are too high are scientifically and technically straightforward actions. However, empirical studies indicate that testing and remediation are generally low among those exposed to high indoor radon, although these persons have relatively high-risk perceptions [92], the cost of radon mitigation measures for most homes is similar to that of common home repairs, and this cost is often an eligible expense covered by national health care programs [93\u201395]."}
{"_id": "Radiology$$$d9687b7f-5f63-4cd9-bbf5-bd3b4b7ab739", "text": "A similar value-action gap is repeatedly reported in studies related to the behavior of people before, during, and after nuclear or radiation emergencies. For example, the study of Turcanu et al. [54] conducted in Belgium, Norway, and Spain, provides empirical evidence that people in the analyzed countries have difficulties complying with some protective actions in case of a nuclear accident. Leaving children at school, avoiding the use of phones during an emergency, not rejecting food produced in affected areas even when it satisfies legal norms or taking iodine tablets when not needed, were identified as the most critical protective actions with which a large number of people would not comply [96]."}
{"_id": "Radiology$$$08dfbbc7-912b-47e6-89c5-0c5ba540c1e6", "text": "This raises the question what determinants of health and radiation protection behavior can be discerned. Different determinants have been studied in the context of health behavior models. The most known and tested models in the radiation protection field are the Protection-Motivation Model [97], the Health Belief Model [98], the Theory of Planned Behavior [99], the Transtheoretical Model of Health Behavior Change (TTM) [90], and the Precautionary Adoption Process Model [100]."}
{"_id": "Radiology$$$3969c30f-f4de-4513-9f42-37fed6d47cda", "text": "Those health protection models suggest that knowledge about the risk is only one of the health behavior determinants, other determinants, explained in Table 12.3 below, being attitudes, perceived behavioral control, subjective norm, descriptive norms, moral norms, self-efficacy, risk perception, protective efficiency of an action, threat, and trust among others. Table 12.3 presents potential health protection determinants, descriptive explanations, and a reference to selected studies that have been tested in the radiation protection field.Table 12.3\nDeterminants of health and radiation protection behavior tested in radiation risk studies\n\nPotential determinants of health and radiation behavior\n\nDescriptive explanation\n\nSelected studies from radiation protection field\n\nAnticipatory emotion\u2014worry\n\nThe anticipatory emotion\u2014worry is an emotion where a person experiences increased levels of anxiety by thinking about an event or situation in the future.\n\nMcGlone et al. [101], Witte et al. [102]\n\nAnticipatory emotion\u2014severity\n\nAnticipatory emotion\u2014severity refers to people\u2019s beliefs about how serious are the negative consequences of a hazard. In the radon exposure situations, the threat involves cancer, which is severe.\n\nMazur and Hall [103], Dragojevic et al. [104]\n\nConditional/perceived susceptibility\n\nPerceived susceptibility is the subjective belief that a person may acquire a disease or enter a dire state due to a particular behavior.\n\nD\u2019Antoni et al. [105], Weinstein et al. [106], Niemeyer and Keller [107]\n\nCoping of efficacy appraisal: response efficacy\n\nCoping appraisal is needed to adopt or maintain a health protection behavior and is essential for overcoming fears and mental blocks. Coping appraisal consists of three dements: response efficacy/response costs/self-efficacy. Only if the individual is convinced that a behavior leads to the desired outcome will she or he be more likely to intend to perform the behavior.\n\nWeinstein et al. [108, 109], Witte et al. [110], Dragojevic et al. [104]\n\nCoping or efficacy appraisal\u2014self efficacy\n\nSelf-efficacy refers to the belief in one\u2019s own competence to perform a behavior even in the face of barriers or in other words, the individual in carrying out the recommended coping response.\n\nHahn et al. [111], Larsson [112], Rhodes et al. [113]\n\nPerceived costs\n\nThe \u201cPerceived costs\u201d captures the person\u2019s perceptions of the disadvantages of, or barriers to, undertaking the behavior.\n\nHampson et al. [114], Sheeran [115]\n\nAnticipated emotions/regret\n\nAnticipated emotions are a component of the immediate consequences of the decision; they are emotions that are expected to occur when outcomes are experienced. The most extensively researched anticipated emotions regret, guilt, and shame.\n\nHampson et al. [114], Sheeran [115]\n\nPerceived informed choice\n\nInformed choice means that people under radon risk make decisions that are consistent with their goals and values\n\nWeinstein and Man [116, 117]\n\nSubjective norms\n\nSubjective norms refer to the belief that an important person or group of people will approve and support and particular behavior, for instance protection against radon\n\nClifford et al. [118], Park et al. [119]\n\nDescriptive norms\n\nDescriptive norms refer to what most people in a group think, feel, or do. Descriptive norms are a reflection on \u201cWhat is typical or normal \u2026 what most people do\u201d, including \u201cevidence as to what will likely be effective and adaptive action.\n\u00a0\nMoral norms\n\nMoral norms are internalised, unconditional and emotional internalised and enforced through self-generated emotions such as guilt.\n\nTurcanu et al. [120]\n\nKnowledge/awareness\n\nIncreasing radiation (specific) knowledge and awareness is often set as a primary objective of risk communication efforts.\n\nPerko et al. [84, 121]\n\nTrust\n\nTrust concept includes different dimensions for instance fairness, unbiasedness, perceived competence, objectivity, consistency, commitment, caring, and predictability, social trust, general trust and transparency.\n\nPerko and Martell [122], Perko et al. [123]"}
{"_id": "Radiology$$$850bcd60-7ff3-408c-b09d-c8a319a35ea8", "text": "In particular, the Theory of Planned Behavior [124] proved that the higher the intent, the higher the probability an individual will engage in the action they intend. This theory has been for instance applied in research on attitudes and behavior related to new nuclear research installations [120]. In this study, authors found that attitudes towards participation and moral norms are the strongest determinants for the studied behavior\u2014in this case, participation intention. Other determinants were time constraints, attitude towards nuclear energy, subjective and descriptive norms, and level of specific radiation-related knowledge. The Extended Parallel Process Model (EPPM) focuses on two constructs which mediate an individual\u2019s level of fear and proposes an individual will engage in behavior change when they have a combination of (a) fear the health threat will happen to them (susceptibility) and (b) perception they are able to address/deal with the risk [108]. The Transtheoretical Model of Health Behavior Change which has been applied among others also to behavior related to radon exposure [125], postulates that individuals move through six stages of change: pre-contemplation, contemplation, preparation, action, maintenance, and termination. The model has two major components: change and decisional balance, where neither knowledge nor risk perception is not identified as the main health protection change determinants [126]. Similarly, the message design theories, such as the Extended Parallel Processing Model (EPPM) which has been used as the theoretical framework for formative and summative analysis of radon communication campaigns, indicate the importance of threat and efficacy [110]."}
{"_id": "Radiology$$$1c821fb6-6794-4050-920b-16d8c9763b73", "text": "Responsible risk communication requires a legitimate procedure, an ethically justified risk message, and concern for and valuation of the effects of the message and procedure. This way, it is stressed, that risk communication should not only be effective but also ethical, which requires taking moral values into consideration. During radiation risk communication moral values are at stake, which means that decisions have to be made in a democratic way, after serious debate about values and not merely about numbers [127]."}
{"_id": "Radiology$$$8854ca0b-a2c8-4ed4-88b2-33f81a1b0db7", "text": "Risk communication was in previous century seen as a form of a technical communication and education whereby the public should be informed about risk estimates. Later on, risk communication was seen as a marketing practice with the aim to persuade people to adopt a certain message. In nowadays societies\u00a0(sic), risk communication is seen as a socio-centric communication based on public participation with which the gaps between stakeholders can be bridged. The procedure should be legitimate (requires legitimate procedure for discussing the moral values and emotions associated with risks), it should be ethically justified (ethical deliberation about the values and emotions involved in different messages) and the effects should be adequately addressed. [128, p. 8\u20139]."}
{"_id": "Radiology$$$0081b7a4-1cb2-4f4b-9e4f-43130c6b0ef3", "text": "Radiation risk communication has several aims: (a) to warn people in case of radiation danger, (b) to the enlightenment of people to be able to understand risks and become \u201crisk-literate,\u201d (c) to prevent panic and outrage, (d) to empower stakeholders to make informed decisions related to radiation risks, (e) to establish two-way communication and joint problem solving including conflict resolution, and (f) to build trust between different stakeholders."}
{"_id": "Radiology$$$0f1a12b7-3d7d-4d14-9bc9-6978e3d91a5f", "text": "Bauder and colleagues (2021) guide communication practitioners towards radiation risk communication which is strategic (e.g., based on formats and methods that have been proven to reach its preconceived objectives), evidence-based (e.g., based on the qualitative and quantitative empirical data, surveys, experiments), and theory-based (e.g., drawing from empirically supported theories of health behavior, behavior, and information processing) [129]."}
{"_id": "Radiology$$$271800b4-0f41-42d7-acbc-b5f882257a33", "text": "For instance, information processing theories applied in radiation risk communication [130] show that efficient communication about radiation risks requires thorough insight into the factors that influence people\u2019s attentiveness, recall of risk-related information, level of agreement with the communicated message, and behavior change or more generally speaking: how people process risk-related information and turned it in a behavior."}
{"_id": "Radiology$$$b90c7c02-df82-4d32-8d90-c1519242c890", "text": "The information processing models are seen as applicable for each individual, regardless of the societal or cultural bias [131\u2013139] however countries may differ in beliefs, cultural values, past social and risk experiences, the saliency of particular aspects of a policy issue, the socioeconomic profile and trust in regulatory agencies. In general, people process information using two different modes: (1) heuristic and (2) systematic mode [140]. Heuristic processing is characterized by low effort and reliance on existing knowledge and simple cues for instance trust. Systematic processing on the other hand is characterized by greater effort and the desire to evaluate information formally [141]."}
{"_id": "Radiology$$$9bd1050b-3b3f-4cb6-8326-736ec7c8428c", "text": "Radiobiologists may be challenged by public communication due to the following reasons [122]:\u00a0there is no single audience for scientific information; the complexity of scientific methods and information, and the ways in which science progresses; the ways in which people process such information; in the radiobiology, the societal implications of science are controversial, for instance, Linear Dose Response Model; there is substantial disagreement about the findings within the scientific community, for instance, related to low doses; the complex, dynamic, and competitive communication media environment, with evolving social media and pace of information flow; and because the results of research can be insufficient, ambiguous or uncertain, and scientific conclusions can change over time as new findings emerge."}
{"_id": "Radiology$$$f8c98343-9a43-4164-8969-aec6db0ba0dc", "text": "Science Media Centre (2012) developed practical guidance to be used by scientists during their public and mass media communication. For a complete and original guide, look at https://\u200bwww.\u200bsciencemediacent\u200bre.\u200borg/\u200bwp-content/\u200buploads/\u200b2012/\u200b09/\u200b10-best-practice-guidelines-for-science-and-health-reporting.\u200bpdf."}
{"_id": "Radiology$$$fa8a5b36-a3f8-4dc7-a3b9-819ffa62225c", "text": "Some of the central points are summarized here:\nHeadlines should not mislead the reader about a story\u2019s contents and quotation marks should not be used to dress up overstatement.\n\nDuring your communication related to health risks, include the absolute risk whenever it is available in the press release or the research paper (e.g., if \u201clow dose exposure increases the cancer risk\u201d state the outright risk of that cancer, with and without particular exposure).\n\nEspecially on a story with public health implications, try to present a new finding in the context of other evidence (e.g., does it reinforce or conflict with previous studies?). If it attracts serious scientific concerns, they should not be ignored.\n\nWhen reporting a link between two things, it is recommended to indicate whether or not there is evidence that one causes the other.\n\nSpecify the size and nature of the study (e.g., who/what were the subjects, how long did it last, what was tested or was it an observation?). Provided there is enough space and time, it could be of interest to mention also the major limitations.\n\nState where the research has been published or presented or reported (e.g., conference, journal article, survey, etc.). Ideally, the article should include a web link or enough information for readers to look it up.\n\nGive a sense of the stage of the research (e.g., new dosimeter, clean-up stage, cells in a laboratory, or trials in humans), and a realistic time frame for any new technology.\n\nIf there is enough space, quote both the researchers themselves and external sources with appropriate expertise. Be wary of scientists and press releases over-claiming for studies.\n\nDistinguish between findings and interpretation or extrapolation; do not suggest health advice if none has been offered."}
{"_id": "Radiology$$$2d16d56f-58b2-4d57-8ee3-c29cfe288385", "text": "Headlines should not mislead the reader about a story\u2019s contents and quotation marks should not be used to dress up overstatement."}
{"_id": "Radiology$$$21a370c8-8396-411d-8cd3-e217b1abf1b5", "text": "During your communication related to health risks, include the absolute risk whenever it is available in the press release or the research paper (e.g., if \u201clow dose exposure increases the cancer risk\u201d state the outright risk of that cancer, with and without particular exposure)."}
{"_id": "Radiology$$$53acfb0f-4001-48ce-a258-1a85e3053839", "text": "Especially on a story with public health implications, try to present a new finding in the context of other evidence (e.g., does it reinforce or conflict with previous studies?). If it attracts serious scientific concerns, they should not be ignored."}
{"_id": "Radiology$$$2fe75ea3-3233-44f9-9eb1-7520c67a6dfc", "text": "When reporting a link between two things, it is recommended to indicate whether or not there is evidence that one causes the other."}
{"_id": "Radiology$$$83153aa7-ee15-46d0-9993-f84abb9ebd98", "text": "Specify the size and nature of the study (e.g., who/what were the subjects, how long did it last, what was tested or was it an observation?). Provided there is enough space and time, it could be of interest to mention also the major limitations."}
{"_id": "Radiology$$$44fb3651-372b-4e80-bd88-7efb9f121a20", "text": "State where the research has been published or presented or reported (e.g., conference, journal article, survey, etc.). Ideally, the article should include a web link or enough information for readers to look it up."}
{"_id": "Radiology$$$ad8993f7-d798-4c24-9199-bae895dd67c7", "text": "Give a sense of the stage of the research (e.g., new dosimeter, clean-up stage, cells in a laboratory, or trials in humans), and a realistic time frame for any new technology."}
{"_id": "Radiology$$$fe679bb2-78e5-4600-85eb-4a6615f665a4", "text": "If there is enough space, quote both the researchers themselves and external sources with appropriate expertise. Be wary of scientists and press releases over-claiming for studies."}
{"_id": "Radiology$$$6a50c924-da98-4abe-a56f-f0b98eba496c", "text": "Distinguish between findings and interpretation or extrapolation; do not suggest health advice if none has been offered."}
{"_id": "Radiology$$$b1c7af6d-20fd-4d34-a7f9-bb36d00e9e4a", "text": "1.\nThe most difficult thing in finding trust in decision-making on nuclear today might be in the way we deal with moral pluralism. What is moral pluralism? Simply the idea that if we all know the same thing, opinions on what to do can still be different, and this is because our opinions do not only rely on knowledge but also on ethical values. As an example choosing for retrievability or non-retrievability of underground stored nuclear waste is making a choice dealing with moral pluralism: science can describe the options, but not help us to make a choice. Some would say we should dispose and seal the waste so that future generations do not need to bother about it anymore, while others would argue that we should give them the possibility to intervene or do something better with the waste. Imagine yourself being a moderator in this discussion: what are the values and interests at stake here, and how would you moderate this discussion towards a consensus, also taking into account that an important stakeholder (the future generations) cannot participate in the discussion?\n\u00a02.\nStudies have shown that the public is more averse to relatively low radiation exposures from nuclear power than to higher doses from medical exposures. Is this irrational?\n\u00a03.\nWhat other ethically relevant factors impact perceptions of radiation risks?"}
{"_id": "Radiology$$$b065527d-1aa9-4861-ae2b-4579b592c7f2", "text": "The most difficult thing in finding trust in decision-making on nuclear today might be in the way we deal with moral pluralism. What is moral pluralism? Simply the idea that if we all know the same thing, opinions on what to do can still be different, and this is because our opinions do not only rely on knowledge but also on ethical values. As an example choosing for retrievability or non-retrievability of underground stored nuclear waste is making a choice dealing with moral pluralism: science can describe the options, but not help us to make a choice. Some would say we should dispose and seal the waste so that future generations do not need to bother about it anymore, while others would argue that we should give them the possibility to intervene or do something better with the waste. Imagine yourself being a moderator in this discussion: what are the values and interests at stake here, and how would you moderate this discussion towards a consensus, also taking into account that an important stakeholder (the future generations) cannot participate in the discussion?"}
{"_id": "Radiology$$$206cd328-8c7f-4ce9-9854-59741b524689", "text": "Studies have shown that the public is more averse to relatively low radiation exposures from nuclear power than to higher doses from medical exposures. Is this irrational?"}
{"_id": "Radiology$$$d0502eb0-cc98-4659-a687-2b83252fba23", "text": "1.\nWhich is the main underlying principle of nuclear law and how does this translate to the concept of optimization of protection? Can you give an example of two planned exposure situations?\n\u00a02.\nDo you think the exposure to cosmic rays is a planned exposure situation or an existing exposure? Could it be both in the context of air travel? Is radiological protection different in either situation?\n\u00a03.\nWhat attributes should a regulatory body have and what are some of its main tasks?\n\u00a04.\nNuclear liability is different from general tortious liability. Give an example and explain the reason."}
{"_id": "Radiology$$$a28c2d51-7c6d-4cd3-9fd7-b9f901ff6b34", "text": "Which is the main underlying principle of nuclear law and how does this translate to the concept of optimization of protection? Can you give an example of two planned exposure situations?"}
{"_id": "Radiology$$$3fea0574-06de-4c36-89c8-e1f8686792f9", "text": "Do you think the exposure to cosmic rays is a planned exposure situation or an existing exposure? Could it be both in the context of air travel? Is radiological protection different in either situation?"}
{"_id": "Radiology$$$77d35739-b811-4e77-85ce-3892406693e2", "text": "What attributes should a regulatory body have and what are some of its main tasks?"}
{"_id": "Radiology$$$fb5f02c2-2d6c-42f8-8559-2ed4df95b8d0", "text": "Nuclear liability is different from general tortious liability. Give an example and explain the reason."}
{"_id": "Radiology$$$53d34711-0f78-4d4a-8ddb-27d04c9af054", "text": "1.\nTaking into consideration the legal structure of your country, please elaborate on the potential legal developments of the following situations:(a)\nA worker is damaged (burned) by an over-exposure to radiation and decides the damage is to be attributed to the exposure and imputed on his/her employer;\n\u00a0(b)\nA large group of conscripts is subjected to a collective medical screening using old X-ray equipment when joining the army. About a decade later, those still meeting in social encounters discover that a large number among them are suffering from unusual cancers for their young age and decide to impute the army;\n\u00a0(c)\nA family is living near a nuclear power plant that appears to function as designed. There have been no reports of any anomalous events, incidents, or anomalous measured values. One of their children incurs thyroid cancer. The parents have contacted a lawyer."}
{"_id": "Radiology$$$a52a0c5b-1e6f-4124-bcd1-80c768a3e7ec", "text": "Taking into consideration the legal structure of your country, please elaborate on the potential legal developments of the following situations:(a)\nA worker is damaged (burned) by an over-exposure to radiation and decides the damage is to be attributed to the exposure and imputed on his/her employer;\n\u00a0(b)\nA large group of conscripts is subjected to a collective medical screening using old X-ray equipment when joining the army. About a decade later, those still meeting in social encounters discover that a large number among them are suffering from unusual cancers for their young age and decide to impute the army;\n\u00a0(c)\nA family is living near a nuclear power plant that appears to function as designed. There have been no reports of any anomalous events, incidents, or anomalous measured values. One of their children incurs thyroid cancer. The parents have contacted a lawyer."}
{"_id": "Radiology$$$d84aab68-6ea4-4a2f-9c73-a81ea40957f8", "text": "A worker is damaged (burned) by an over-exposure to radiation and decides the damage is to be attributed to the exposure and imputed on his/her employer;"}
{"_id": "Radiology$$$6ae86084-7f06-467b-8169-1df9c6412358", "text": "A large group of conscripts is subjected to a collective medical screening using old X-ray equipment when joining the army. About a decade later, those still meeting in social encounters discover that a large number among them are suffering from unusual cancers for their young age and decide to impute the army;"}
{"_id": "Radiology$$$099b79e5-cbfb-4ec7-9162-470a10dd74d3", "text": "A family is living near a nuclear power plant that appears to function as designed. There have been no reports of any anomalous events, incidents, or anomalous measured values. One of their children incurs thyroid cancer. The parents have contacted a lawyer."}
{"_id": "WikiPedia_Radiology$$$corpus_1", "text": "Nuclear medicine  ( nuclear radiology ,  nucleology ), [ 1 ] [ 2 ]  is a  medical specialty  involving the application of  radioactive  substances in the  diagnosis  and treatment of  disease . Nuclear imaging is, in a sense,  radiology  done inside out , because it records  radiation   emitted  from within the body rather than  radiation  that is  transmitted  through the body from external sources like  X-ray generators . In addition, nuclear medicine scans differ from radiology, as the emphasis is not on imaging anatomy, but on the function. For such reason, it is called a  physiological imaging modality .  Single photon emission computed tomography  (SPECT) and  positron emission tomography  (PET) scans are the two most common imaging modalities in nuclear medicine. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2", "text": "In nuclear medicine imaging,  radiopharmaceuticals  are taken internally, for example, through inhalation, intravenously, or orally. Then, external detectors ( gamma cameras ) capture and form images from the radiation emitted by the radiopharmaceuticals. This process is unlike a diagnostic X-ray, where external radiation is passed through the body to form an image. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3", "text": "There are several techniques of diagnostic nuclear medicine."}
{"_id": "WikiPedia_Radiology$$$corpus_4", "text": "Nuclear medicine tests differ from most other imaging modalities in that nuclear medicine scans primarily show the physiological function of the system being investigated as opposed to traditional anatomical imaging such as CT or MRI. Nuclear medicine imaging studies are generally more organ-, tissue- or disease-specific (e.g.: lungs scan, heart scan, bone scan, brain scan, tumor, infection, Parkinson etc.) than those in conventional radiology imaging, which focus on a particular section of the body (e.g.: chest X-ray, abdomen/pelvis CT scan, head CT scan, etc.). In addition, there are nuclear medicine studies that allow imaging of the whole body based on certain cellular receptors or functions. Examples are whole body  PET scans  or  PET/CT  scans,  gallium scans ,  indium white blood cell scans ,  MIBG  and  octreotide scans ."}
{"_id": "WikiPedia_Radiology$$$corpus_5", "text": "While the ability of nuclear metabolism to image disease processes from differences in metabolism is unsurpassed, it is not unique. Certain techniques such as  fMRI  image tissues (particularly cerebral tissues) by blood flow and thus show metabolism. Also, contrast-enhancement techniques in both CT and MRI show regions of tissue that are handling pharmaceuticals differently, due to an inflammatory process."}
{"_id": "WikiPedia_Radiology$$$corpus_6", "text": "Diagnostic tests in nuclear medicine exploit the way that the body handles substances differently when there is disease or pathology present. The radionuclide introduced into the body is often chemically bound to a complex that acts characteristically within the body; this is commonly known as a  tracer . In the presence of disease, a tracer will often be distributed around the body and/or processed differently. For example, the ligand methylene-diphosphonate ( MDP ) can be preferentially taken up by bone. By chemically attaching  technetium-99m  to MDP, radioactivity can be transported and attached to bone via the hydroxyapatite for imaging. Any increased physiological function, such as due to a fracture in the bone, will usually mean increased concentration of the tracer. This often results in the appearance of a \"hot spot\", which is a focal increase in radio accumulation or a general increase in radio accumulation throughout the physiological system. Some disease processes result in the exclusion of a tracer, resulting in the appearance of a \"cold spot\". Many tracer complexes have been developed to image or treat many different organs, glands, and physiological processes."}
{"_id": "WikiPedia_Radiology$$$corpus_7", "text": "In some centers, the nuclear medicine scans can be superimposed, using software or hybrid cameras, on images from modalities such as CT or MRI to highlight the part of the body in which the radiopharmaceutical is concentrated. This practice is often referred to as image fusion or co-registration, for example SPECT/CT and PET/CT. The fusion imaging technique in nuclear medicine provides information about the anatomy and function, which would otherwise be unavailable or would require a more invasive procedure or surgery."}
{"_id": "WikiPedia_Radiology$$$corpus_8", "text": "Although the risks of low-level radiation exposures are not well understood, a cautious approach has been universally adopted that all human radiation exposures should be kept  As Low As Reasonably Practicable , \"ALARP\". (Originally, this was known as \"As Low As Reasonably Achievable\" (ALARA), but this has changed in modern draftings of the legislation to add more emphasis on the \"Reasonably\" and less on the \"Achievable\".)"}
{"_id": "WikiPedia_Radiology$$$corpus_9", "text": "Working with the ALARP principle, before a patient is exposed for a nuclear medicine examination, the benefit of the examination must be identified. This needs to take into account the particular circumstances of the patient in question, where appropriate. For instance, if a patient is unlikely to be able to tolerate a sufficient amount of the procedure to achieve a diagnosis, then it would be inappropriate to proceed with injecting the patient with the radioactive tracer."}
{"_id": "WikiPedia_Radiology$$$corpus_10", "text": "When the benefit does justify the procedure, then the radiation exposure (the amount of radiation given to the patient) should also be kept \"ALARP\". This means that the images produced in nuclear medicine should never be better than required for confident diagnosis. Giving larger radiation exposures can reduce the noise in an image and make it more photographically appealing, but if the clinical question can be answered without this level of detail, then this is inappropriate."}
{"_id": "WikiPedia_Radiology$$$corpus_11", "text": "As a result, the  radiation dose  from nuclear medicine imaging varies greatly depending on the type of study. The effective radiation dose can be lower than or comparable to or can far exceed the general day-to-day environmental annual  background radiation  dose. Likewise, it can also be less than, in the range of, or higher than the radiation dose from an abdomen/pelvis CT scan."}
{"_id": "WikiPedia_Radiology$$$corpus_12", "text": "Some nuclear medicine procedures require special patient preparation before the study to obtain the most accurate result. Pre-imaging preparations may include dietary preparation or the withholding of certain medications. Patients are encouraged to consult with the nuclear medicine department prior to a scan."}
{"_id": "WikiPedia_Radiology$$$corpus_13", "text": "The result of the nuclear medicine imaging process is a dataset comprising one or more images. In multi-image datasets the array of images may represent a time sequence (i.e. cine or movie) often called a \"dynamic\" dataset, a cardiac gated time sequence, or a spatial sequence where the gamma-camera is moved relative to the patient.  SPECT  (single photon emission computed tomography) is the process by which images acquired from a rotating gamma-camera are reconstructed to produce an image of a \"slice\" through the patient at a particular position. A collection of parallel slices form a slice-stack, a  three-dimensional  representation of the distribution of radionuclide in the patient."}
{"_id": "WikiPedia_Radiology$$$corpus_14", "text": "The nuclear medicine computer may require millions of lines of source code to provide quantitative analysis packages for each of the specific imaging techniques available in nuclear medicine. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_15", "text": "Time sequences can be further analysed using  kinetic  models such as  multi-compartment models  or a  Patlak plot ."}
{"_id": "WikiPedia_Radiology$$$corpus_16", "text": "Radionuclide therapy can be used to treat conditions such as  hyperthyroidism ,  thyroid cancer , skin cancer and blood disorders."}
{"_id": "WikiPedia_Radiology$$$corpus_17", "text": "In nuclear medicine therapy, the radiation treatment dose is administered internally (e.g. intravenous or oral routes) or externally direct above the area to treat in form of a compound (e.g. in case of skin cancer)."}
{"_id": "WikiPedia_Radiology$$$corpus_18", "text": "The radiopharmaceuticals used in nuclear medicine therapy emit ionizing radiation that travels only a short distance, thereby minimizing unwanted side effects and damage to noninvolved organs or nearby structures. Most nuclear medicine therapies can be performed as outpatient procedures since there are few side effects from the treatment and the radiation exposure to the general public can be kept within a safe limit."}
{"_id": "WikiPedia_Radiology$$$corpus_19", "text": "In some centers the nuclear medicine department may also use implanted capsules of isotopes ( brachytherapy ) to treat cancer."}
{"_id": "WikiPedia_Radiology$$$corpus_20", "text": "The history of nuclear medicine contains contributions from scientists across different disciplines in physics, chemistry, engineering, and medicine. The multidisciplinary nature of nuclear medicine makes it difficult for medical historians to determine the birthdate of nuclear medicine. This can probably be best placed between the discovery of artificial radioactivity in 1934 and the production of radionuclides by  Oak Ridge National Laboratory  for medicine-related use, in 1946. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_21", "text": "The origins of this medical idea date back as far as the mid-1920s in  Freiburg , Germany, when  George de Hevesy  made experiments with radionuclides administered to rats, thus displaying metabolic pathways of these substances and establishing the  tracer  principle. Possibly, the genesis of this medical field took place in 1936, when  John Lawrence , known as \"the father of nuclear medicine\", took a leave of absence from his faculty position at  Yale Medical School , to visit his brother  Ernest Lawrence  at his new radiation laboratory (now known as the  Lawrence Berkeley National Laboratory ) in  Berkeley ,  California . Later on, John Lawrence made the first application in patients of an artificial radionuclide when he used  phosphorus-32  to treat  leukemia . [ 7 ] [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_22", "text": "Many historians consider the discovery of artificially produced radionuclides by  Fr\u00e9d\u00e9ric Joliot-Curie  and  Ir\u00e8ne Joliot-Curie  in 1934 as the most significant milestone in nuclear medicine. [ 6 ]  In February 1934, they reported the first artificial production of radioactive material in the journal  Nature , after discovering radioactivity in aluminum foil that was irradiated with a polonium preparation. Their work built upon earlier discoveries by  Wilhelm Konrad Roentgen  for X-ray,  Henri Becquerel  for radioactive uranium salts, and  Marie Curie  (mother of Ir\u00e8ne Curie) for radioactive thorium, polonium and coining the term \"radioactivity.\"  Taro Takemi  studied the application of  nuclear physics  to medicine in the 1930s. The history of nuclear medicine will not be complete without mentioning these early pioneers."}
{"_id": "WikiPedia_Radiology$$$corpus_23", "text": "Nuclear medicine gained public recognition as a potential specialty when on May 11, 1946, an article in the Journal of the American Medical Association (JAMA) by Massachusetts General Hospital's Dr.  Saul Hertz  and Massachusetts Institute of Technology's Dr. Arthur Roberts, described the successful use of treating Graves' Disease with radioactive iodine (RAI) was published. [ 9 ]  Additionally,  Sam Seidlin . [ 10 ]  brought further development in the field describing a successful treatment of a patient with thyroid cancer metastases using radioiodine ( I-131 ). These articles are considered by many historians as the most important articles ever published in nuclear medicine. [ 11 ]  Although the earliest use of I-131 was devoted to therapy of thyroid cancer, its use was later expanded to include imaging of the thyroid gland, quantification of the thyroid function, and therapy for hyperthyroidism. Among the many radionuclides that were discovered for medical-use, none were as important as the discovery and development of  Technetium-99m . It was first discovered in 1937 by C. Perrier and E. Segre as an artificial element to fill space number 43 in the Periodic Table. The development of a  generator  system to produce Technetium-99m in the 1960s became a practical method for medical use. Today, Technetium-99m is the most utilized element in nuclear medicine and is employed in a wide variety of nuclear medicine imaging studies."}
{"_id": "WikiPedia_Radiology$$$corpus_24", "text": "Widespread clinical use of nuclear medicine began in the early 1950s, as knowledge expanded about radionuclides, detection of radioactivity, and using certain radionuclides to trace biochemical processes. Pioneering works by  Benedict Cassen  in developing the first  rectilinear scanner  and  Hal O. Anger 's scintillation camera ( Anger camera ) broadened the young discipline of nuclear medicine into a full-fledged medical imaging specialty."}
{"_id": "WikiPedia_Radiology$$$corpus_25", "text": "By the early 1960s, in southern  Scandinavia ,  Niels A. Lassen ,  David H. Ingvar , and  Erik Skinh\u00f8j  developed techniques that provided the first blood flow maps of the brain, which initially involved  xenon-133  inhalation; [ 12 ]  an intra-arterial equivalent was developed soon after, enabling measurement of the local distribution of cerebral activity for patients with  neuropsychiatric  disorders such as schizophrenia. [ 13 ]  Later versions would have 254  scintillators  so a two-dimensional image could be produced on a color monitor. It allowed them to construct images reflecting brain activation from speaking, reading, visual or auditory perception and voluntary movement. [ 14 ]  The technique was also used to investigate, e.g., imagined sequential movements, mental calculation and mental spatial navigation. [ 15 ] [ 16 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_26", "text": "By the 1970s most organs of the body could be visualized using nuclear medicine procedures. In 1971,  American Medical Association  officially recognized nuclear medicine as a medical specialty. [ 17 ]  In 1972, the  American Board of Nuclear Medicine  was established, and in 1974, the  American Osteopathic Board of Nuclear Medicine  was established, cementing nuclear medicine as a stand-alone medical specialty."}
{"_id": "WikiPedia_Radiology$$$corpus_27", "text": "In the 1980s, radiopharmaceuticals were designed for use in diagnosis of heart disease. The development of single photon emission computed tomography (SPECT), around the same time, led to three-dimensional reconstruction of the heart and establishment of the field of nuclear cardiology."}
{"_id": "WikiPedia_Radiology$$$corpus_28", "text": "More recent developments in nuclear medicine include the invention of the first positron emission tomography scanner ( PET ). The concept of emission and transmission tomography, later developed into single photon emission computed tomography (SPECT), was introduced by  David E. Kuhl  and Roy Edwards in the late 1950s. [ citation needed ]  Their work led to the design and construction of several tomographic instruments at the University of Pennsylvania. Tomographic imaging techniques were further developed at the  Washington University School of Medicine . These innovations led to fusion imaging with SPECT and CT by Bruce Hasegawa from  University of California, San Francisco  (UCSF), and the first PET/CT prototype by D. W. Townsend from  University of Pittsburgh  in 1998. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_29", "text": "PET and PET/CT imaging experienced slower growth in its early years owing to the cost of the modality and the requirement for an on-site or nearby cyclotron. However, an administrative decision to approve medical reimbursement of limited PET and PET/CT applications in oncology has led to phenomenal growth and widespread acceptance over the last few years, which also was facilitated by establishing 18F-labelled tracers for standard procedures, allowing work at non-cyclotron-equipped sites. PET/CT imaging is now an integral part of oncology for diagnosis, staging and treatment monitoring. A fully integrated MRI/PET scanner is on the market from early 2011. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_30", "text": "99m Tc is normally supplied to hospitals through a  radionuclide generator  containing the parent radionuclide  molybdenum-99 .  99 Mo is  typically obtained  as a fission product of  235 U  in nuclear reactors, however global supply shortages have led to the exploration of  other methods of production . About a third of the world's supply, and most of Europe's supply, of medical isotopes is produced at the  Petten nuclear reactor  in the  Netherlands . Another third of the world's supply, and most of North America's supply, was produced at the  Chalk River Laboratories  in  Chalk River ,  Ontario , Canada until its permanent shutdown in 2018. [ 18 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_31", "text": "The most commonly used radioisotope in PET,  18 F , is not produced in a nuclear reactor, but rather in a circular accelerator called a  cyclotron . The cyclotron is used to accelerate  protons  to bombard the stable heavy isotope of oxygen  18 O . The  18 O constitutes about 0.20% of ordinary  oxygen  (mostly  oxygen-16 ), from which it is extracted. The  18 F is then typically used to make  FDG ."}
{"_id": "WikiPedia_Radiology$$$corpus_32", "text": "Z = atomic number, the number of protons T 1/2  = half-life decay = mode of decay \n photons = principal photon energies in kilo-electron volts,  keV , (abundance/decay) \n \u03b2 = beta maximum energy in kilo-electron volts,  keV , (abundance/decay) \n \u03b2 +  =  \u03b2 +  decay ; \u03b2 \u2212  =  \u03b2 \u2212  decay ; IT =  isomeric transition ; ec =  electron capture \n * X-rays from progeny,  mercury , Hg"}
{"_id": "WikiPedia_Radiology$$$corpus_33", "text": "A typical nuclear medicine study involves administration of a  radionuclide  into the body by intravenous injection in liquid or aggregate form, ingestion while combined with food, inhalation as a gas or aerosol, or rarely, injection of a radionuclide that has undergone  micro-encapsulation . Some studies require the labeling of a patient's own blood cells with a radionuclide ( leukocyte scintigraphy  and  red blood cell  scintigraphy). Most diagnostic radionuclides emit  gamma rays  either directly from their decay or indirectly through  electron\u2013positron annihilation , while the cell-damaging properties of  beta particles  are used in therapeutic applications. Refined radionuclides for use in nuclear medicine are derived from  fission  or fusion processes in  nuclear reactors , which produce radionuclides with longer half-lives, or  cyclotrons , which produce radionuclides with shorter half-lives, or take advantage of natural decay processes in dedicated generators, i.e. molybdenum/technetium or strontium/rubidium."}
{"_id": "WikiPedia_Radiology$$$corpus_34", "text": "The most commonly used intravenous radionuclides are technetium-99m, iodine-123, iodine-131, thallium-201, gallium-67, fluorine-18  fluorodeoxyglucose , and indium-111 labeled  leukocytes . [ citation needed ]  The most commonly used gaseous/aerosol radionuclides are xenon-133, krypton-81m, ( aerosolised ) technetium-99m. [ 23 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_35", "text": "A patient undergoing a nuclear medicine procedure will receive a  radiation dose . Under present international guidelines it is assumed that any radiation dose, however small, presents a risk. The radiation dose delivered to a patient in a nuclear medicine investigation, though unproven, is generally accepted to present a very small risk of inducing cancer. In this respect it is similar to the risk from X-ray investigations except that the dose is delivered internally rather than from an external source such as an X-ray machine, and dosage amounts are typically significantly higher than those of X-rays."}
{"_id": "WikiPedia_Radiology$$$corpus_36", "text": "The radiation dose from a nuclear medicine investigation is expressed as an  effective dose  with units of  sieverts  (usually given in millisieverts, mSv). The effective dose resulting from an investigation is influenced by the amount of radioactivity administered in mega becquerels  (MBq), the  physical properties  of the  radiopharmaceutical  used, its distribution in the body and its rate of clearance from the body."}
{"_id": "WikiPedia_Radiology$$$corpus_37", "text": "Effective doses can range from 6 \u03bcSv (0.006 mSv) for a 3 MBq  chromium -51 EDTA measurement of  glomerular filtration rate  to 11.2 mSv (11,200 \u03bcSv) for an 80 MBq  thallium -201  myocardial imaging  procedure. The common bone scan with 600 MBq of technetium-99m  MDP  has an effective dose of approximately 2.9 mSv (2,900 \u03bcSv). [ 24 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_38", "text": "Formerly, units of measurement were:"}
{"_id": "WikiPedia_Radiology$$$corpus_39", "text": "The rad and rem are essentially equivalent for almost all nuclear medicine procedures, and only  alpha radiation  will produce a higher Rem or Sv value, due to its much higher  Relative Biological Effectiveness  (RBE). Alpha emitters are nowadays rarely used in nuclear medicine, but were used extensively before the advent of nuclear reactor and accelerator produced radionuclides. The concepts involved in radiation exposure to humans are covered by the field of  Health Physics ; the development and practice of safe and effective nuclear medicinal techniques is a key focus of  Medical Physics ."}
{"_id": "WikiPedia_Radiology$$$corpus_40", "text": "Different countries around the world maintain regulatory frameworks that are responsible for the management and use of radionuclides in different medical settings. For example, in the US, the  Nuclear Regulatory Commission  (NRC) and the  Food and Drug Administration  (FDA) have guidelines in place for hospitals to follow. [ 26 ]  With the NRC, if radioactive materials aren't involved, like X-rays for example, they are not regulated by the agency and instead are regulated by the individual states. [ 27 ]  International organizations, such as the  International Atomic Energy Agency  (IAEA), have regularly published different articles and guidelines for best practices in nuclear medicine as well as reporting on emerging technologies in nuclear medicine. [ 28 ] [ 29 ]  Other factors that are considered in nuclear medicine include a patient's medical history as well as post-treatment management. Groups like  International Commission on Radiological Protection  have published information on how to manage the release of patients from a hospital with unsealed radionuclides. [ 30 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_41", "text": "Angelika Bischof-Delaloye  is a former  emeritus   professor  at the  University of Lausanne  in  Lausanne , Switzerland. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_42", "text": "From 1998 to 2009, Bischof-Delaloye was a full professor at the  Nuclear Medicine  Department at the University Lausanne, and the Department Head of Nuclear Medicine at  Lausanne University Hospital . [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_43", "text": "She served on the  European Board of Nuclear Medicine  in 2006. [ 4 ]  In 2011, she wrote the editorial article for  European Journal of Nuclear Medicine and Molecular Imaging  (EJNMMI) to introduce the  open-access journal  called European Journal of Nuclear Medicine and Molecular Imaging Research (EJNMMI Res) [ 5 ]  in the area of basic, translational and clinical research in nuclear medicine. She currently serves as the  editor-in-chief  of the EJNMMI Res journal. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_44", "text": "She obtained her  MD degree  from the  University of Innsbruck , Austria in 1968. She published her first  scientific paper  in 1971 titled \"Segmental, Sequential and Quantitative Pulmonary Investigations Using the Scintillation Camera\" in the  Journal of Nuclear Biology and Medicine . [ 7 ]  During her career, she published over 254 scientific manuscripts with more than 4713 citations, [ 8 ]  written many book chapters, [ 9 ] [ 10 ] [ 11 ] [ 12 ]  and organised symposiums. [ 13 ]  She is also mentioned in the book  History of Nuclear Medicine in Europe , which was published in 2003. [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_45", "text": "A  cardiac stress test  is a cardiological examination that evaluates the cardiovascular system's response to external stress within a controlled clinical setting. This stress response can be induced through physical exercise (usually a treadmill) or intravenous pharmacological stimulation of heart rate. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_46", "text": "As the heart works progressively harder (stressed) it is monitored using an  electrocardiogram  (ECG) monitor. This measures the heart's electrical rhythms and broader  electrophysiology . Pulse rate, blood pressure and symptoms such as chest discomfort or fatigue are simultaneously monitored by attending clinical staff. Clinical staff will question the patient throughout the procedure asking questions that relate to pain and perceived discomfort. Abnormalities in blood pressure, heart rate, ECG or worsening physical symptoms could be indicative of  coronary artery disease . [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_47", "text": "Stress testing does not accurately diagnose all cases of coronary artery disease, and can often indicate that it exists in people who do not have the condition. The test can also detect heart abnormalities such as  arrhythmias , and conditions affecting  electrical conduction within the heart such as various types of fascicular blocks. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_48", "text": "A \"normal\" stress test does not offer any substantial reassurance that a future unstable coronary plaque will not rupture and block an artery, inducing a  heart attack . As with all medical diagnostic procedures, data is only from a moment in time. A primary reason stress testing is not perceived as a robust method of CAD detection \u2014 is that stress testing generally only detects arteries that are severely narrowed (~70% or more). [ 4 ] [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_49", "text": "A stress test may be accompanied by  echocardiography . [ 7 ]  The echocardiography is performed both before and after the exercise so that structural differences can be compared."}
{"_id": "WikiPedia_Radiology$$$corpus_50", "text": "A resting echocardiogram is obtained prior to stress. The ultrasound images obtained are similar to the ones obtained during a full surface echocardiogram, commonly referred to as  transthoracic echocardiogram . The patient is subjected to stress in the form of exercise or chemically (often  dobutamine ). After the target heart rate is achieved, 'stress' echocardiogram images are obtained. The two echocardiogram images are then compared to assess for any abnormalities in wall motion of the heart. This is used to detect obstructive coronary artery disease. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_51", "text": "While also measuring breathing gases (e.g.,  oxygen saturation , maximal oxygen consumption), the test is often referred to as a cardiopulmonary exercise test. Common indications for a cardiopulmonary exercise test include evaluation of shortness of breath, workup before  heart transplantation , and prognosis and risk assessment of heart failure patients."}
{"_id": "WikiPedia_Radiology$$$corpus_52", "text": "The test is also common in sport science for measuring athletes' maximal oxygen consumption,  V\u0307O 2  max . [ 9 ]  In 2016, the  American Heart Association  published an official scientific statement advocating that  cardiorespiratory fitness , quantifiable as  V\u0307O 2  max  and measured during a cardiopulmonary exercise test, be categorized as a clinical vital sign and should be routinely assessed as part of clinical practice. [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_53", "text": "The CPX test can be done on a  treadmill  or  cycle ergometer . In untrained subjects, V\u0307O 2  max is 10% to 20% lower when using a cycle ergometer compared with a treadmill. [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_54", "text": "A nuclear stress test uses a  gamma camera  to image radioisotopes injected into the bloodstream. The best known example  is  myocardial perfusion imaging . Typically, a  radiotracer  ( Tc-99 sestamibi ,  Myoview  or  thallous chloride 201 ) may be injected during the test. After a suitable waiting period to ensure proper distribution of the radiotracer, scans are acquired with a gamma camera to capture images of the blood flow. Scans acquired before and after exercise are examined to assess the state of the coronary arteries of the patient. By showing the relative amounts of radioisotope within the heart muscle, the nuclear stress tests more accurately identify regional areas of reduced blood flow. [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_55", "text": "Stress and potential cardiac damage from exercise during the test is a problem in patients with ECG abnormalities at rest or in patients with severe motor disability. Pharmacological stimulation from vasodilators such as dipyridamole or adenosine, or positive chronotropic agents such as dobutamine can be used. Testing personnel can include a cardiac radiologist, a nuclear medicine physician, a nuclear medicine technologist, a cardiology technologist, a cardiologist, and/or a nurse. The typical dose of radiation received during this procedure can range from 9.4 to 40.7  millisieverts . [ 13 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_56", "text": "The American Heart Association recommends ECG treadmill testing as the first choice for patients with medium risk of coronary heart disease according to risk factors of smoking, family history of coronary artery stenosis, hypertension, diabetes and high cholesterol. In 2013, in its \"Exercise Standards for Testing and Training\", the AHA indicated that  high frequency QRS  analysis during ECG treadmill test have useful test performance for detection of coronary heart disease. [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_57", "text": "The common approach for stress testing recommended by the American College of Cardiology [ 17 ] [ 18 ]  and the American Heart Association [ 19 ]  involves several methods to assess cardiac health. These methods provide information for diagnosing and managing heart-related conditions. Two primary stress tests utilized are a treadmill test using  ECG / electrophysiology  metrics and nuclear testing, each have unique sensitivity and specificity values."}
{"_id": "WikiPedia_Radiology$$$corpus_58", "text": "The treadmill test, employing the modified  Bruce protocol , [ 20 ]  demonstrates a sensitivity range of around 73-90% and a specificity range of around 50-74%. Sensitivity refers to the percentage of individuals with the condition correctly identified by the test, while specificity denotes the percentage of individuals without the condition correctly identified as not having it. [ 21 ]  The nuclear stress test exhibits a sensitivity of 81% and a specificity ranging from 85 to 95%. [ 22 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_59", "text": "To arrive at the patient's post test likelihood of disease, the interpretation of the stress test result necessitates the integration of the patient's pretest likelihood with the test's sensitivity and specificity. This method, initially introduced by Diamond and Forrester in the 1970s, provides an estimate of the patient's post-test likelihood of disease. [ 23 ] [ 24 ]  Stress tests have limitations in assessing the significance and nature of cardiac problems, they should be seen in context - as an initial assessment that can lead to a number of other diagnostic approaches in the broader management of cardiac diseases. [ 25 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_60", "text": "According to data from the US  Centers for Disease Control and Prevention  (CDC) common first systems of coronary artery disease is a heart attack. According to the American Heart Association, a significant percentage of individuals, approximately 65% of men and 47% of women, present with a heart attack or sudden cardiac arrest as their first symptom of cardiovascular disease. Consequently, stress tests performed shortly before these events may not be highly relevant for predicting infarction in the majority of individuals tested. [ 26 ] [ 27 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_61", "text": "Stress cardiac imaging is not recommended for asymptomatic, low-risk patients as part of their routine care. [ 28 ]  Some estimates show that such screening accounts for 45% of cardiac stress imaging, and evidence does not show that this results in better outcomes for patients. [ 28 ]  Unless high-risk markers are present, such as diabetes in patients aged over 40,  peripheral arterial disease , or a risk of  coronary heart disease  greater than 2 percent yearly, most health societies do not recommend the test as a routine procedure. [ 28 ] [ 29 ] [ 30 ] [ 31 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_62", "text": "Absolute contraindications to cardiac stress test include:"}
{"_id": "WikiPedia_Radiology$$$corpus_63", "text": "Indications for termination:\nA cardiac stress test should be terminated before completion under the following circumstances: [ 33 ] [ 34 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_64", "text": "Absolute indications for termination include:"}
{"_id": "WikiPedia_Radiology$$$corpus_65", "text": "Relative indications for termination include:"}
{"_id": "WikiPedia_Radiology$$$corpus_66", "text": "Side effects from cardiac stress testing may include [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_67", "text": "Pharmacologic stress testing relies on  coronary steal . Vasodilators are used to dilate coronary vessels, which causes increased blood velocity and flow rate in normal vessels and less of a response in stenotic vessels. This difference in response leads to a steal of flow and perfusion defects appear in cardiac nuclear scans or as ST-segment changes. [ 36 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_68", "text": "The choice of pharmacologic stress agents used in the test depends on factors such as potential drug interactions with other treatments and concomitant diseases."}
{"_id": "WikiPedia_Radiology$$$corpus_69", "text": "Pharmacologic agents such as adenosine, regadenoson (Lexiscan), or dipyridamole is generally used when a patient cannot achieve adequate work level with treadmill exercise, or has poorly controlled  hypertension  or left  bundle branch block . However, an exercise stress test may provide more information about exercise tolerance than a pharmacologic stress test. [ 37 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_70", "text": "Commonly used agents include:"}
{"_id": "WikiPedia_Radiology$$$corpus_71", "text": "Regadenoson or dobutamine is often used in patients with severe  reactive airway disease  ( asthma  or  COPD ) as adenosine and dipyridamole can cause acute exacerbation of these conditions. If the patient's asthma is treated with an inhaler then it should be used as a pre-treatment prior to the injection of the pharmacologic stress agent. In addition, if the patient is actively wheezing then the physician should determine the benefits versus the risk to the patient of performing a stress test especially outside of a hospital setting.  Caffeine  is usually held 24 hours prior to an adenosine stress test, as it is a competitive antagonist of the A2A adenosine receptor and can attenuate the vasodilatory effects adenosine. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_72", "text": "Aminophylline  may be used to attenuate severe and/or persistent adverse reactions to adenosine and regadenoson. [ 39 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_73", "text": "Cardiac stress testing, used since the 1960s, has a history rooted in the diagnostic and prognostic assessment of patients with suspected  coronary artery disease . It has evolved to evaluate inducible  myocardial ischemia  as an indicator of adverse outcomes. The factors influencing mortality risk have changed over time due to decreasing angina symptoms, increasing prevalence of conditions like  diabetes  and  obesity , and the rise in pharmacologic testing for patients unable to exercise during stress tests. [ 40 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_74", "text": "A  cyclotron  is a type of  particle accelerator  invented by  Ernest Lawrence  in 1929\u20131930 at the  University of California, Berkeley , [ 1 ] [ 2 ]  and patented in 1932. [ 3 ] [ 4 ]  A cyclotron accelerates  charged particles  outwards from the center of a flat cylindrical vacuum chamber along a spiral path. [ 5 ] [ 6 ]  The particles are held to a spiral trajectory by a static  magnetic field  and accelerated by a rapidly varying  electric field . Lawrence was awarded the 1939  Nobel Prize in Physics  for this invention. [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_75", "text": "The cyclotron was the first \"cyclical\" accelerator. [ 8 ]  The primary accelerators before the development of the cyclotron were  electrostatic accelerators , such as the  Cockcroft\u2013Walton generator  and the  Van de Graaff generator .  In these accelerators, particles would cross an accelerating  electric field  only once.  Thus, the energy gained by the particles was limited by the maximum  electrical potential  that could be achieved across the accelerating region. This potential was in turn limited by  electrostatic breakdown  to a few million volts. In a cyclotron, by contrast, the particles encounter the accelerating region many times by following a spiral path, so the output energy can be many times the energy gained in a single accelerating step. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_76", "text": "Cyclotrons were the most powerful particle accelerator technology until the 1950s, when they were surpassed by the  synchrotron . [ 9 ]  Nonetheless, they are still widely used to produce particle beams for  nuclear medicine  and basic research. As of 2020, close to 1,500 cyclotrons were in use worldwide for the production of  radionuclides  for nuclear medicine. [ 10 ]  In addition, cyclotrons can be used for  particle therapy , where particle beams are directly applied to patients. [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_77", "text": "In 1927, while a student at Kiel, German physicist  Max Steenbeck  was the first to formulate the concept of the cyclotron, but he was discouraged from pursuing the idea further. [ 11 ]  In late 1928 and early 1929, Hungarian physicist  Leo Szil\u00e1rd  filed patent applications in Germany for the  linear accelerator , cyclotron, and  betatron . [ 12 ]  In these applications, Szil\u00e1rd became the first person to discuss the resonance condition (what is now called the cyclotron frequency) for a circular accelerating apparatus. However, neither Steenbeck's ideas nor Szilard's patent applications were ever published and therefore did not contribute to the development of the cyclotron. [ 13 ]  Several months later, in the early summer of 1929, Ernest Lawrence independently conceived the cyclotron concept after reading a paper by  Rolf Wider\u00f8e  describing a drift tube accelerator. [ 14 ] [ 15 ] [ 16 ]  He published a paper in  Science  in 1930 (the first published description of the cyclotron concept), after a student of his built a crude model in April of that year. [ 17 ]  He patented the device in 1932. [ 18 ] [ 19 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_78", "text": "To construct the first such device, Lawrence used large electromagnets recycled from obsolete  arc converters  provided by the  Federal Telegraph Company . [ 20 ]  He was assisted by a graduate student,  M. Stanley Livingston . Their first working cyclotron became operational on January 2, 1931.  This machine had a diameter of 4.5 inches (11\u00a0cm), and accelerated protons to an energy up to 80\u00a0 keV . [ 21 ] [ 22 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_79", "text": "At the Radiation Laboratory on the campus of the  University of California, Berkeley  (now the  Lawrence Berkeley National Laboratory ), Lawrence and his collaborators went on to construct a series of cyclotrons which were the most powerful accelerators in the world at the time; a 27\u00a0in (69\u00a0cm) 4.8\u00a0MeV machine (1932), a 37\u00a0in (94\u00a0cm) 8\u00a0MeV machine (1937), and a 60\u00a0in (152\u00a0cm) 16\u00a0MeV machine (1939). Lawrence received the 1939  Nobel Prize in Physics  for the invention and development of the cyclotron and for results obtained with it. [ 23 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_80", "text": "The first European cyclotron was constructed in 1934 in the  Soviet Union  by  Mikhail Alekseevich Eremeev , at the  Leningrad Physico-Technical Institute . It was a small design based a prototype by Lawrence, with a 28 cm diameter capable of achieving 530 keV proton energies. Research quickly refocused around the construction of a larger MeV-level cyclotron, in the physics department of the  V.G. Khlopin Radium Institute  in  Leningrad , headed by  Vitaly Khlopin \u00a0[ ru ] . This instrument was first proposed in 1932 by  George Gamow  and  Lev Mysovskii \u00a0[ ru ]  and was installed and became operative in March 1937 at 100 cm (39 in) diameter and 3.2 MeV proton energies. [ 24 ] [ 25 ] [ 26 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_81", "text": "The first Asian cyclotron was constructed at the  Riken  laboratory in Tokyo, by a team including  Yoshio Nishina , Sukeo Watanabe, Tameichi Yasaki, and Ryokichi Sagane. Yasaki and Sagane had been sent to  Berkeley Radiation Laboratory  to work with Lawrence. The device had a 26 in diameter and the first beam was produced on April 2, 1937, at 2.9 MeV deuteron energies. [ 27 ] [ 28 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_82", "text": "Cyclotrons played a key role in the  Manhattan Project . The published 1940 discovery of  neptunium  and the withheld 1941 discovery of  plutonium  both used bombardment in the  Berkeley Radiation Laboratory 's 60 in cyclotron. [ 29 ] [ 30 ]  Furthermore Lawrence invented the  calutron  (California University cyclotron), which was industrially developed at the  Y-12 National Security Complex  from 1942. This provided the bulk of the  uranium enrichment  process, taking  low-enriched uranium  (<5% uranium-235) from the  S-50  and  K-25  plants and electromagnetically separating isotopes up to 84.5%  highly enriched uranium . This was the first production of HEU in history, and was shipped to Los Alamos and used in the  Little Boy  bomb  dropped on Hiroshima , and its precursor  Water Boiler  and  Dragon  test reactors. [ 31 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_83", "text": "In France,  Fr\u00e9d\u00e9ric Joliot-Curie  constructed a large 7 MeV cyclotron at the  Coll\u00e8ge de France  in Paris, achieving the first beam in March 1939. With the  Nazi occupation of Paris  in June 1940 and an incoming contingent of German scientists, Joliot ceased research into uranium fission, and obtained an understanding with his German former colleague  Wolfgang Gentner  that no research of military use would be carried out. In 1943 Gentner was recalled for weakness, and a new German contingent attempted to operate the cyclotron. However, it is likely that Joliot, a member of  French Communist Party  and in fact president of the  National Front  resistance movement, sabotaged the cyclotron to prevent its use to the  Nazi German nuclear program . [ 32 ] [ 33 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_84", "text": "One cyclotron was built within  Nazi Germany , in  Heidelberg , under the supervision of  Walther Bothe  and  Wolfgang Gentner , with support from the  Heereswaffenamt . At the end of 1938, Gentner was sent to  Berkeley Radiation Laboratory  and worked most closely with  Emilio Segr\u00e8  and  Donald Cooksey , returning before the start of the war.  Construction was slowed by the war and completed in January 1944, but difficulties in testing made it unusable until the war's end. [ 34 ] [ 35 ] [ 36 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_85", "text": "By the late 1930s it had become clear that there was a practical limit on the beam energy that could be achieved with the traditional cyclotron design, due to the effects of  special relativity . [ 37 ]   As particles reach relativistic speeds, their effective mass increases, which causes the resonant frequency for a given magnetic field to change.  To address this issue and reach higher beam energies using cyclotrons, two primary approaches were taken,  synchrocyclotrons  (which hold the magnetic field constant, but decrease the accelerating frequency) and isochronous cyclotrons (which hold the accelerating frequency constant, but alter the magnetic field). [ 38 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_86", "text": "Lawrence's team built one of the first synchrocyclotrons in 1946. This 184\u00a0in (4.7\u00a0m) machine eventually achieved a maximum beam energy of 350\u00a0MeV for protons. However, synchrocyclotrons suffer from low beam intensities (<\u00a01\u00a0\u03bcA), and must be operated in a \"pulsed\" mode, further decreasing the available total beam. As such, they were quickly overtaken in popularity by isochronous cyclotrons. [ 39 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_87", "text": "The first isochronous cyclotron (other than classified prototypes) was built by F. Heyn and K.T. Khoe in Delft, the Netherlands, in 1956. [ 40 ]  Early isochronous cyclotrons were limited to energies of ~50\u00a0MeV per nucleon, but as manufacturing and design techniques gradually improved, the construction of \"spiral-sector\" cyclotrons allowed the acceleration and control of more powerful beams. Later developments included the use of more compact and power-efficient  superconducting magnets  and the separation of the magnets into discrete sectors, as opposed to a single large magnet. [ 39 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_88", "text": "In a particle accelerator, charged particles are accelerated by applying an electric field across a gap.  The force on a particle crossing this gap is given by the  Lorentz force law :"}
{"_id": "WikiPedia_Radiology$$$corpus_89", "text": "F \n \n = \n q \n [ \n \n E \n \n + \n ( \n \n v \n \n \u00d7 \n \n B \n \n ) \n ] \n \n \n {\\displaystyle \\mathbf {F} =q[\\mathbf {E} +(\\mathbf {v} \\times \\mathbf {B} )]}"}
{"_id": "WikiPedia_Radiology$$$corpus_90", "text": "where  q  is the  charge  on the particle,  E  is the  electric field ,  v  is the particle  velocity , and  B  is the  magnetic flux density .  It is not possible to accelerate particles using only a static magnetic field, as the magnetic force always acts perpendicularly to the direction of motion, and therefore can only change the direction of the particle, not the speed. [ 41 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_91", "text": "In practice, the magnitude of an unchanging electric field which can be applied across a gap is limited by the need to avoid  electrostatic breakdown . [ 42 ] :\u200a21\u200a  As such, modern particle accelerators use alternating ( radio frequency ) electric fields for acceleration. Since an alternating field across a gap only provides an acceleration in the forward direction for a portion of its cycle, particles in RF accelerators travel in bunches, rather than a continuous stream. In a  linear particle accelerator , in order for a bunch to \"see\" a forward voltage every time it crosses a gap, the gaps must be placed further and further apart, in order to compensate for the increasing  speed  of the particle. [ 43 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_92", "text": "A cyclotron, by contrast, uses a magnetic field to bend the particle trajectories into a spiral, thus allowing the same gap to be used many times to accelerate a single bunch.  As the bunch spirals outward, the increasing distance between transits of the gap is exactly balanced by the increase in speed, so a bunch will reach the gap at the same point in the RF cycle every time. [ 43 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_93", "text": "The frequency at which a particle will orbit in a perpendicular magnetic field is known as the  cyclotron frequency , and depends, in the non-relativistic case, solely on the charge and mass of the particle, and the strength of the magnetic field:"}
{"_id": "WikiPedia_Radiology$$$corpus_94", "text": "f \n = \n \n \n \n q \n B \n \n \n 2 \n \u03c0 \n m \n \n \n \n \n \n {\\displaystyle f={\\frac {qB}{2\\pi m}}}"}
{"_id": "WikiPedia_Radiology$$$corpus_95", "text": "where  f  is the (linear) frequency,  q  is the charge of the particle,  B  is the magnitude of the magnetic field that is perpendicular to the plane in which the particle is travelling, and  m  is the particle mass. The property that the frequency is independent of particle velocity is what allows a single, fixed gap to be used to accelerate a particle travelling in a spiral. [ 43 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_96", "text": "Each time a particle crosses the accelerating gap in a cyclotron, it is given an accelerating force by the electric field across the gap, and the total particle energy gain can be calculated by multiplying the increase per crossing by the number of times the particle crosses the gap. [ 44 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_97", "text": "However, given the typically high number of revolutions, it is usually simpler to estimate the energy by combining the equation for  frequency  in  circular motion :"}
{"_id": "WikiPedia_Radiology$$$corpus_98", "text": "f \n = \n \n \n v \n \n 2 \n \u03c0 \n r \n \n \n \n \n \n {\\displaystyle f={\\frac {v}{2\\pi r}}}"}
{"_id": "WikiPedia_Radiology$$$corpus_99", "text": "with the cyclotron frequency equation to yield:"}
{"_id": "WikiPedia_Radiology$$$corpus_100", "text": "v \n = \n \n \n \n q \n B \n r \n \n m \n \n \n \n \n {\\displaystyle v={\\frac {qBr}{m}}}"}
{"_id": "WikiPedia_Radiology$$$corpus_101", "text": "The kinetic energy for particles with speed  v  is therefore given by:"}
{"_id": "WikiPedia_Radiology$$$corpus_102", "text": "E \n = \n \n \n 1 \n 2 \n \n \n m \n \n v \n \n 2 \n \n \n = \n \n \n \n \n q \n \n 2 \n \n \n \n B \n \n 2 \n \n \n \n r \n \n 2 \n \n \n \n \n 2 \n m \n \n \n \n \n \n {\\displaystyle E={\\frac {1}{2}}mv^{2}={\\frac {q^{2}B^{2}r^{2}}{2m}}}"}
{"_id": "WikiPedia_Radiology$$$corpus_103", "text": "where  r  is the radius at which the energy is to be determined. The limit on the beam energy which can be produced by a given cyclotron thus depends on the maximum radius which can be reached by the magnetic field and the accelerating structures, and on the maximum strength of the magnetic field which can be achieved. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_104", "text": "In the nonrelativistic approximation, the maximum kinetic energy per atomic mass for a given cyclotron is given by:"}
{"_id": "WikiPedia_Radiology$$$corpus_105", "text": "T \n A \n \n \n = \n \n \n \n ( \n e \n B \n \n r \n \n max \n \n \n \n ) \n \n 2 \n \n \n \n \n 2 \n \n m \n \n a \n \n \n \n \n \n \n \n ( \n \n \n Q \n A \n \n \n ) \n \n \n 2 \n \n \n = \n K \n \n \n ( \n \n \n Q \n A \n \n \n ) \n \n \n 2 \n \n \n \n \n {\\displaystyle {\\frac {T}{A}}={\\frac {(eBr_{\\max })^{2}}{2m_{a}}}\\left({\\frac {Q}{A}}\\right)^{2}=K\\left({\\frac {Q}{A}}\\right)^{2}}"}
{"_id": "WikiPedia_Radiology$$$corpus_106", "text": "where  \n \n \n \n e \n \n \n {\\displaystyle e} \n \n  is the elementary charge,  \n \n \n \n B \n \n \n {\\displaystyle B} \n \n  is the strength of the magnet,  \n \n \n \n \n r \n \n max \n \n \n \n \n {\\displaystyle r_{\\max }} \n \n  is the maximum radius of the beam,  \n \n \n \n \n m \n \n a \n \n \n \n \n {\\displaystyle m_{a}} \n \n  is an  atomic mass unit ,  \n \n \n \n Q \n \n \n {\\displaystyle Q} \n \n  is the charge of the beam particles, and  \n \n \n \n A \n \n \n {\\displaystyle A} \n \n  is the atomic mass of the beam particles.  The value of  K"}
{"_id": "WikiPedia_Radiology$$$corpus_107", "text": "K \n = \n \n \n \n ( \n e \n B \n \n r \n \n max \n \n \n \n ) \n \n 2 \n \n \n \n \n 2 \n \n m \n \n a \n \n \n \n \n \n \n \n {\\displaystyle K={\\frac {(eBr_{\\max })^{2}}{2m_{a}}}}"}
{"_id": "WikiPedia_Radiology$$$corpus_108", "text": "is known as the \"K-factor\", and is used to characterize the maximum kinetic beam energy of protons (quoted in MeV).  It represents the theoretical maximum energy of protons (with  Q  and  A  equal to 1) accelerated in a given machine. [ 45 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_109", "text": "While the trajectory followed by a particle in the cyclotron is conventionally referred to as a \"spiral\", it is more accurately described as a series of arcs of constant radius. The particle speed, and therefore orbital radius, only increases at the accelerating gaps. Away from those regions, the particle will orbit (to a first approximation) at a fixed radius. [ 46 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_110", "text": "Assuming a uniform energy gain per orbit (which is only valid in the non-relativistic case), the average orbit may be approximated by a simple spiral. If the energy gain per turn is given by  \u0394 E , the particle energy after  n  turns will be:\n \n \n \n \n E \n ( \n n \n ) \n = \n n \n \u0394 \n E \n \n \n {\\displaystyle E(n)=n\\Delta E} \n \n \nCombining this with the non-relativistic equation for the kinetic energy of a particle in a cyclotron gives:\n \n \n \n \n r \n ( \n n \n ) \n = \n \n \n \n \n 2 \n m \n \u0394 \n E \n \n \n \n q \n B \n \n \n \n \n \n n \n \n \n \n \n {\\displaystyle r(n)={{\\sqrt {2m\\Delta E}} \\over qB}{\\sqrt {n}}} \n \n \nThis is the equation of a  Fermat spiral ."}
{"_id": "WikiPedia_Radiology$$$corpus_111", "text": "As a particle bunch travels around a cyclotron, two effects tend to make its particles spread out.  The first is simply the particles injected from the ion source having some initial spread of positions and velocities. This spread tends to get amplified over time, making the particles move away from the bunch center.  The second is the mutual repulsion of the beam particles due to their electrostatic charges. [ 47 ]  Keeping the particles focused for acceleration requires confining the particles to the plane of acceleration (in-plane or \"vertical\" [ a ]  focusing), preventing them from moving inward or outward from their correct orbit (\"horizontal\" [ a ]  focusing), and keeping them synchronized with the accelerating RF field cycle (longitudinal focusing). [ 46 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_112", "text": "The in-plane or \"vertical\" [ a ]  focusing is typically achieved by varying the magnetic field around the orbit, i.e. with  azimuth . A cyclotron using this focusing method is thus called an azimuthally-varying field (AVF) cyclotron. [ 48 ]  The variation in field strength is provided by shaping the steel poles of the magnet into sectors [ 46 ]  which can have a shape reminiscent of a spiral and also have a larger area towards the outer edge of the cyclotron to improve the vertical focus of the particle beam. [ 49 ]  This solution for focusing the particle beam was proposed by  L. H. Thomas  in 1938 [ 48 ]  and almost all modern cyclotrons use azimuthally-varying fields. [ 50 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_113", "text": "The \"horizontal\" [ a ]  focusing happens as a natural result of cyclotron motion.  Since for identical particles travelling perpendicularly to a constant magnetic field the trajectory curvature radius is only a function of their speed, all particles with the same speed will travel in circular orbits of the same radius, and a particle with a slightly incorrect trajectory will simply travel in a circle with a slightly offset center.  Relative to a particle with a centered orbit, such a particle will appear to undergo a horizontal oscillation relative to the centered particle. This oscillation is stable for particles with a small deviation from the reference energy. [ 46 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_114", "text": "The instantaneous level of synchronization between a particle and the RF field is expressed by phase difference between the RF field and the particle. In the first harmonic mode (i.e. particles make one revolution per RF cycle) it is the difference between the instantaneous phase of the RF field and the instantaneous azimuth of the particle. Fastest acceleration is achieved when the phase difference equals 90\u00b0 ( modulo 360\u00b0). [ 46 ] :\u200ach.2.1.3\u200a  Poor synchronization, i.e. phase difference far from this value, leads to the particle being accelerated slowly or even decelerated (outside of the 0\u2013180\u00b0 range)."}
{"_id": "WikiPedia_Radiology$$$corpus_115", "text": "As the time taken by a particle to complete an orbit depends only on particle's type, magnetic field (which may vary with the radius), and  Lorentz factor  (see  \u00a7\u00a0Relativistic considerations ), cyclotrons have no longitudinal focusing mechanism which would keep the particles synchronized to the RF field. The phase difference, that the particle had at the moment of its injection into the cyclotron, is preserved throughout the acceleration process, but errors from imperfect match between the RF field frequency and the cyclotron frequency at a given radius accumulate on top of it. [ 46 ] :\u200ach.2.1.3\u200a  Failure of the particle to be injected with phase difference within about \u00b120\u00b0 from the optimum may make its acceleration too slow and its stay in the cyclotron too long. As a consequence, half-way through the process the phase difference escapes the 0\u2013180\u00b0 range, the acceleration turns into deceleration, and the particle fails to reach the target energy. Grouping of the particles into correctly synchronized bunches before their injection into the cyclotron thus greatly increases the injection efficiency. [ 46 ] :\u200ach.7"}
{"_id": "WikiPedia_Radiology$$$corpus_116", "text": "In the non-relativistic approximation, the cyclotron frequency does not depend upon the particle's speed or the radius of the particle's orbit. As the beam spirals outward, the rotation frequency stays constant, and the beam continues to accelerate as it travels a greater distance in the same time period. In contrast to this approximation, as particles approach the  speed of light , the cyclotron frequency decreases due to the change in  relativistic mass . This change is proportional to the particle's  Lorentz factor . [ 41 ] :\u200a6\u20139"}
{"_id": "WikiPedia_Radiology$$$corpus_117", "text": "The relativistic mass can be written as:"}
{"_id": "WikiPedia_Radiology$$$corpus_118", "text": "m \n = \n \n \n \n m \n \n 0 \n \n \n \n 1 \n \u2212 \n \n \n ( \n \n \n v \n c \n \n \n ) \n \n \n 2 \n \n \n \n \n \n = \n \n \n \n m \n \n 0 \n \n \n \n 1 \n \u2212 \n \n \u03b2 \n \n 2 \n \n \n \n \n \n = \n \u03b3 \n \n \n m \n \n 0 \n \n \n \n , \n \n \n {\\displaystyle m={\\frac {m_{0}}{\\sqrt {1-\\left({\\frac {v}{c}}\\right)^{2}}}}={\\frac {m_{0}}{\\sqrt {1-\\beta ^{2}}}}=\\gamma {m_{0}},}"}
{"_id": "WikiPedia_Radiology$$$corpus_119", "text": "where:"}
{"_id": "WikiPedia_Radiology$$$corpus_120", "text": "Substituting this into the equations for cyclotron frequency and angular frequency gives:"}
{"_id": "WikiPedia_Radiology$$$corpus_121", "text": "f \n \n \n \n = \n \n \n \n q \n B \n \n \n 2 \n \u03c0 \n \u03b3 \n \n m \n \n 0 \n \n \n \n \n \n \n \n \n \n \u03c9 \n \n \n \n = \n \n \n \n q \n B \n \n \n \u03b3 \n \n m \n \n 0 \n \n \n \n \n \n \n \n \n \n \n \n {\\displaystyle {\\begin{aligned}f&={\\frac {qB}{2\\pi \\gamma m_{0}}}\\\\[6pt]\\omega &={\\frac {qB}{\\gamma m_{0}}}\\end{aligned}}}"}
{"_id": "WikiPedia_Radiology$$$corpus_122", "text": "The  gyroradius  for a particle moving in a static magnetic field is then given by: [ 41 ] :\u200a6\u20139\u200a \n \n \n \n \n r \n = \n \n \n \n \u03b3 \n \u03b2 \n \n m \n \n 0 \n \n \n c \n \n \n q \n B \n \n \n \n = \n \n \n \n \u03b3 \n \n m \n \n 0 \n \n \n v \n \n \n q \n B \n \n \n \n = \n \n \n \n m \n \n 0 \n \n \n \n q \n B \n \n \n \n v \n \n \u2212 \n 2 \n \n \n \u2212 \n \n c \n \n \u2212 \n 2 \n \n \n \n \n \n \n \n \n \n {\\displaystyle r={\\frac {\\gamma \\beta m_{0}c}{qB}}={\\frac {\\gamma m_{0}v}{qB}}={\\frac {m_{0}}{qB{\\sqrt {v^{-2}-c^{-2}}}}}}"}
{"_id": "WikiPedia_Radiology$$$corpus_123", "text": "Expressing the speed in this equation in terms of frequency and radius\n \n \n \n \n v \n = \n 2 \n \u03c0 \n f \n r \n \n \n {\\displaystyle v=2\\pi fr} \n \n \nyields the connection between the magnetic field strength, frequency, and radius:\n \n \n \n \n \n \n ( \n \n \n 1 \n \n 2 \n \u03c0 \n f \n \n \n \n ) \n \n \n 2 \n \n \n = \n \n \n ( \n \n \n \n m \n \n 0 \n \n \n \n q \n B \n \n \n \n ) \n \n \n 2 \n \n \n + \n \n \n ( \n \n \n r \n c \n \n \n ) \n \n \n 2 \n \n \n \n \n {\\displaystyle \\left({\\frac {1}{2\\pi f}}\\right)^{2}=\\left({\\frac {m_{0}}{qB}}\\right)^{2}+\\left({\\frac {r}{c}}\\right)^{2}}"}
{"_id": "WikiPedia_Radiology$$$corpus_124", "text": "Since  \n \n \n \n \u03b3 \n \n \n {\\displaystyle \\gamma } \n \n  increases as the particle reaches relativistic velocities, acceleration of relativistic particles requires modification of the cyclotron to ensure the particle crosses the gap at the same point in each RF cycle. If the frequency of the accelerating electric field is varied while the magnetic field is held constant, this leads to the  synchrocyclotron . [ 43 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_125", "text": "In this type of cyclotron, the accelerating frequency is varied as a function of particle orbit radius such that:"}
{"_id": "WikiPedia_Radiology$$$corpus_126", "text": "f \n ( \n r \n ) \n = \n \n \n 1 \n \n 2 \n \u03c0 \n \n \n \n \n ( \n \n \n \n m \n \n 0 \n \n \n \n q \n B \n \n \n \n ) \n \n \n 2 \n \n \n + \n \n \n ( \n \n \n r \n c \n \n \n ) \n \n \n 2 \n \n \n \n \n \n \n \n \n \n {\\displaystyle f(r)={\\frac {1}{2\\pi {\\sqrt {\\left({\\frac {m_{0}}{qB}}\\right)^{2}+\\left({\\frac {r}{c}}\\right)^{2}}}}}}"}
{"_id": "WikiPedia_Radiology$$$corpus_127", "text": "The decrease in accelerating frequency is tuned to match the increase in gamma for a constant magnetic field. [ 43 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_128", "text": "If instead the magnetic field is varied with radius while the frequency of the accelerating field is held constant, this leads to the  isochronous cyclotron . [ 43 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_129", "text": "B \n ( \n r \n ) \n = \n \n \n \n m \n \n 0 \n \n \n \n q \n \n \n \n \n ( \n \n \n 1 \n \n 2 \n \u03c0 \n f \n \n \n \n ) \n \n \n 2 \n \n \n \u2212 \n \n \n ( \n \n \n r \n c \n \n \n ) \n \n \n 2 \n \n \n \n \n \n \n \n \n \n {\\displaystyle B(r)={\\frac {m_{0}}{q{\\sqrt {\\left({\\frac {1}{2\\pi f}}\\right)^{2}-\\left({\\frac {r}{c}}\\right)^{2}}}}}}"}
{"_id": "WikiPedia_Radiology$$$corpus_130", "text": "Keeping the frequency constant allows isochronous cyclotrons to operate in a continuous mode, which makes them capable of producing much greater beam current than synchrocyclotrons. On the other hand, as precise matching of the orbital frequency to the accelerating field frequency is the responsibility of the magnetic field variation with radius, the variation must be precisely tuned."}
{"_id": "WikiPedia_Radiology$$$corpus_131", "text": "An approach which combines static magnetic fields (as in the synchrocyclotron) and alternating gradient focusing (as in a  synchrotron ) is the fixed-field alternating gradient accelerator (FFA).  In an isochronous cyclotron, the magnetic field is shaped by using precisely machined steel magnet poles.  This variation provides a focusing effect as the particles cross the edges of the poles.  In an FFA, separate magnets with alternating directions are used to focus the beam using the principle of  strong focusing .  The field of the focusing and bending magnets in an FFA is not varied over time, so the beam chamber must still be wide enough to accommodate a changing beam radius within the field of the focusing magnets as the beam accelerates. [ 52 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_132", "text": "There are a number of basic types of cyclotron: [ 53 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_133", "text": "The particles for cyclotron beams are produced in  ion sources  of various types."}
{"_id": "WikiPedia_Radiology$$$corpus_134", "text": "To make use of the cyclotron beam, it must be directed to a target. [ 57 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_135", "text": "For several decades, cyclotrons were the best source of high-energy beams for  nuclear physics  experiments.  With the advent of strong focusing synchrotrons, cyclotrons were supplanted as the accelerators capable of producing the highest energies. [ 43 ] [ 9 ]  However, due to their compactness, and therefore lower expense compared to high energy synchrotrons, cyclotrons are still used to create beams for research where the primary consideration is not achieving the maximum possible energy. [ 54 ]  Cyclotron based nuclear physics experiments are used to measure basic properties of isotopes (particularly short lived radioactive isotopes) including half life, mass, interaction cross sections, and decay schemes. [ 59 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_136", "text": "Cyclotron beams can be used to bombard other atoms to produce short-lived isotopes with a variety of medical uses, including  medical imaging  and  radiotherapy . [ 60 ]   Positron  and  gamma  emitting isotopes, such as  fluorine-18 ,  carbon-11 , and  technetium-99m [ 61 ]  are used for  PET  and  SPECT  imaging. While cyclotron produced radioisotopes are widely used for diagnostic purposes, therapeutic uses are still largely in development.  Proposed isotopes include  astatine -211,  palladium -103,  rhenium -186, and  bromine -77, among others. [ 62 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_137", "text": "The first suggestion that energetic protons could be an effective treatment method was made by  Robert R. Wilson  in a paper published in 1946 [ 63 ]  while he was involved in the design of the  Harvard Cyclotron Laboratory . [ 64 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_138", "text": "Beams from cyclotrons can be used in  particle therapy  to treat  cancer . Ion beams from cyclotrons can be used, as in  proton therapy , to penetrate the body and kill tumors by  radiation damage , while minimizing damage to healthy tissue along their path."}
{"_id": "WikiPedia_Radiology$$$corpus_139", "text": "As of 2020, there were approximately 80 facilities worldwide for radiotherapy using beams of protons and heavy ions, consisting of a mixture of cyclotrons and synchrotrons. Cyclotrons are primarily used for proton beams, while synchrotrons are used to produce heavier ions. [ 65 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_140", "text": "The most obvious advantage of a cyclotron over a  linear accelerator  is that because the same accelerating gap is used many times, it is both more space efficient and more cost efficient; particles can be brought to higher energies in less space, and with less equipment. The compactness of the cyclotron reduces other costs as well, such as foundations, radiation shielding, and the enclosing building. Cyclotrons have a single electrical driver, which saves both equipment and power costs. Furthermore, cyclotrons are able to produce a continuous beam of particles at the target, so the average power passed from a particle beam into a target is relatively high compared to the pulsed beam of a synchrotron. [ 66 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_141", "text": "However, as discussed above, a constant frequency acceleration method is only possible when the accelerated particles are approximately obeying  Newton's laws of motion . If the particles become fast enough that  relativistic  effects become important, the beam becomes out of phase with the oscillating electric field, and cannot receive any additional acceleration. The classical cyclotron (constant field and frequency) is therefore only capable of accelerating particles up to a few percent of the speed of light. Synchro-, isochronous, and other types of cyclotrons can overcome this limitation, with the tradeoff of increased complexity and cost. [ 66 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_142", "text": "An additional limitation of cyclotrons is due to  space charge  effects \u2013 the mutual repulsion of the particles in the beam.  As the amount of particles (beam current) in a cyclotron beam is increased, the effects of  electrostatic repulsion  grow stronger until they disrupt the orbits of neighboring particles.  This puts a functional limit on the beam intensity, or the  number  of particles which can be accelerated at one time, as distinct from their energy. [ 67 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_143", "text": "A  superconducting cyclotron  uses  superconducting magnets  to achieve high magnetic field in a small diameter and with lower power requirements. These cyclotrons require a  cryostat  to house the magnet and cool it to -269\u00b0C or 4.2 K. Some of these cyclotrons are being built for medical therapy. [ 39 ] :\u200a6"}
{"_id": "WikiPedia_Radiology$$$corpus_144", "text": "The spiraling of electrons in a cylindrical vacuum chamber within a transverse magnetic field is also employed in the  magnetron , a device for producing high frequency radio waves ( microwaves ). In the magnetron, electrons are bent into a circular path by a magnetic field, and their motion is used to excite  resonant cavities , producing electromagnetic radiation. [ 82 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_145", "text": "A  betatron  uses the  change  in the magnetic field to accelerate electrons in a circular path. While static magnetic fields cannot provide acceleration, as the force always acts perpendicularly to the direction of particle motion, changing fields can be used to induce an  electromotive force  in the same manner as in a  transformer .  The betatron was developed in 1940, [ 83 ]  although the idea had been proposed substantially earlier. [ 84 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_146", "text": "A  synchrotron  is another type of particle accelerator that uses magnets to bend particles into a circular trajectory.  Unlike in a cyclotron, the particle path in a synchrotron has a fixed radius.  Particles in a synchrotron pass accelerating stations at increasing frequency as they get faster.  To compensate for this frequency increase, both the frequency of the applied accelerating electric field and the magnetic field must be increased in tandem, leading to the \"synchro\" portion of the name. [ 85 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_147", "text": "The  United States Department of War  famously asked for dailies of the  Superman  comic strip to be pulled in April 1945 for having Superman bombarded with the radiation from a cyclotron. [ 86 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_148", "text": "In the 1984 film  Ghostbusters ,  a miniature cyclotron forms part of the  proton pack  used for catching ghosts. [ 87 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_149", "text": "Diagnostically acceptable irreversible compression  ( DAIC ) is the amount of  lossy compression  which can be used on a  medical image  to produce a result that does not prevent the reader from using the image to make a  medical diagnosis ."}
{"_id": "WikiPedia_Radiology$$$corpus_150", "text": "The term was first introduced at a workshop on irreversible compression convened by the  European Society of Radiology  (ESR) in  Palma de Mallorca  October 13, 2010, the results of which were reported in a subsequent position paper. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_151", "text": "The \"amount of compression\" in irreversible compression used to be determined by the  compression ratio , where the acceptable minimum is determined by the algorithm (typically  JPEG  or  J2K ) and the data type (body part and imaging method). Such a definition is easy to follow, and has been used by medical bodies in 2010 around the world. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_152", "text": "However, its downside is obvious: the compression ratio tells nothing about the real quality of the image, as different compressors can produce vastly different qualities under the same file size. [ 1 ]  For example, the JPEG format of 1992 can perform as well as many modern formats given newer techniques exploited in  mozjpeg  and  ISO libjpeg , yet they would be lumped together with the legacy encoders in such a scheme. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_153", "text": "The image compression community has long used objective  quality metrics  like  SSIM  to measure the effects of compression. In the absence of good data regarding SSIM, the ESR review of 2010 concluded that it is still difficult to establish a criterion for whether a particular  irreversible compression  scheme applied with particular parameters to a particular individual image, or category of images, avoids the introduction of some quantifiable risk of a diagnostic error for any particular diagnostic task. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_154", "text": "A 2017 study showed that a SSIM variant called 4-G-r* (4-component,  gradient , structural component of SSIM) best reflects changes in images that affect the decision of radiologists out of 16 SSIM variants. [ 3 ]  A 2020 study shows that  visual information fidelity  (VIF),  feature similarity index  (FSIM), and  noise quality metric  (NQM) best reflect radiologist preferences out of ten metrics. It also mentions that the original version of SSIM works as poorly as a basic root-mean-square distance (RMSD) for this purpose, a result echoed by the 2017 study. The 4-G-r* modification is not tested in the study. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_155", "text": "This article related to  medical imaging  is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Radiology$$$corpus_156", "text": "Dose area product  (DAP) is a quantity used in assessing the radiation risk from diagnostic  X-ray   radiography  examinations and interventional procedures, like  angiography . It is defined as the  absorbed dose  multiplied by the area irradiated, expressed in  gray - centimetres squared  (Gy\u00b7cm 2 [ 1 ]  \u2013 sometimes the  prefixed  units dGy\u00b7cm 2 , mGy\u00b7cm 2  or cGy\u00b7cm 2  are also used). [ 2 ]  Gray (Gy) is the  SI unit  of absorbed dose of  ionizing radiation , while milligray (mGy) is its subunit equivalent to  milliSievert  (mSv) for gamma (\u03b3) and X-rays. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_157", "text": "Manufacturers of DAP meters usually calibrate them in terms of absorbed dose to air. DAP reflects not only the dose within the radiation field but also the area of  tissue  irradiated. Therefore, it may be a better indicator of the overall risk of inducing cancer than the dose within the field. It also has the advantage of being easily measured, with the permanent installation of a DAP meter on the X-ray set.\nDue to the divergence of a beam emitted from a \"point source\", the area irradiated (A) increases with the square of distance from the source (A \u221d d 2 ), while radiation intensity (I) decreases according to the inverse square of distance (I \u221d 1/d 2 ). Consequently, the product of intensity and area, and therefore DAP, is independent of distance from the source."}
{"_id": "WikiPedia_Radiology$$$corpus_158", "text": "DICOM  \"X-Ray Acquisition Dose Module\" metadata within each medical imaging study often includes various DAP and dose length product (DLP) parameters. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_159", "text": "An ionization chamber is placed beyond the X-ray  collimators  and must intercept the entire X-ray field for an accurate reading. Different parameters of the X-ray set, such as peak voltage (kVp),  X-ray tube  current (mA), exposure time, or the area of the field, can also be changed. \n \nFor example, a  5 cm \u00d7 5 cm  X-ray field with an entrance dose of 1\u00a0mGy will yield a 25\u00a0mGy\u00b7cm 2  DAP value. When the field is increased to  10 cm \u00d7 10 cm  with the same entrance dose, the DAP increases to 100\u00a0mGy\u00b7cm 2 , which is four times the previous value."}
{"_id": "WikiPedia_Radiology$$$corpus_160", "text": "Kerma  area product  (KAP) [ 1 ]  is a related quantity, which for all practical radiation protection purposes is equal to dose area product. However, strictly speaking  \n \n \n \n \n D \n A \n P \n \n = \n \n K \n A \n P \n \n \u00d7 \n ( \n 1 \n \u2212 \n g \n ) \n \n \n {\\displaystyle \\mathrm {DAP} =\\mathrm {KAP} \\times (1-g)} \n \n , where  g  is the fraction of energy of liberated charged particles that is lost in radiative processes in the material [ 5 ]  and the dose is expressed in absorbed dose to air. The value of  g  for diagnostic X-rays is only a fraction of a percent."}
{"_id": "WikiPedia_Radiology$$$corpus_161", "text": "Adult  coronary angiography  and  PCI procedures  expose patients to an average DAP in the range of 20 to 106\u00a0Gy\u00b7cm 2  and 44 to 143\u00a0Gy\u00b7cm 2  respectively. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_162", "text": "Onia"}
{"_id": "WikiPedia_Radiology$$$corpus_163", "text": "Electron\u2013positron annihilation  occurs when an  electron  ( e \u2212 ) and a  positron  ( e + , the electron's  antiparticle ) collide. At low energies, the result of the collision is the  annihilation  of the electron and positron, and the creation of energetic  photons :"}
{"_id": "WikiPedia_Radiology$$$corpus_164", "text": "At high energies, other particles, such as  B mesons  or the  W and Z bosons , can be created. All processes must satisfy a number of  conservation laws , including:"}
{"_id": "WikiPedia_Radiology$$$corpus_165", "text": "As with any two charged objects, electrons and positrons may also interact with each other without annihilating, in general by  elastic scattering ."}
{"_id": "WikiPedia_Radiology$$$corpus_166", "text": "There are only a very limited set of possibilities for the final state. The most probable is the creation of two or more gamma photons. Conservation of energy and linear momentum forbid the creation of only one photon. (An exception to this rule can occur for tightly bound atomic electrons. [ 1 ] ) In the most common case, two gamma photons are created, each with  energy  equal to the  rest energy  of the electron or positron ( 0.511\u00a0 MeV ). [ 2 ]  A convenient  frame of reference  is that in which the system has  no net linear momentum  before the annihilation; thus, after collision, the gamma photons are emitted in opposite directions. It is also common for three to be created, since in some angular momentum states, this is necessary to conserve  charge parity . [ 3 ]  It is also possible to create any larger number of photons, but the probability becomes lower with each additional gamma photon because these more complex processes have lower  probability amplitudes ."}
{"_id": "WikiPedia_Radiology$$$corpus_167", "text": "Since  neutrinos  also have a smaller mass than electrons, it is also possible \u2013 but exceedingly unlikely \u2013 for the annihilation to produce one or more neutrino\u2013 antineutrino  pairs. The probability for such process is on the order of 10000 times less likely than the annihilation into photons. The same would be true for any other particles, which are as light, as long as they share at least one  fundamental interaction  with electrons and no conservation laws forbid it. However, no other such particles are known."}
{"_id": "WikiPedia_Radiology$$$corpus_168", "text": "If either the electron or positron, or both, have appreciable  kinetic energies , other heavier particles can also be produced (such as  D mesons  or  B mesons ), since there is enough kinetic energy in the relative velocities to provide the  rest energies  of those particles. Alternatively, it is possible to produce photons and other light particles, but they will emerge with higher kinetic energies."}
{"_id": "WikiPedia_Radiology$$$corpus_169", "text": "At energies near and beyond the mass of the carriers of the  weak force , the  W and Z bosons , the strength of the weak force becomes comparable to the  electromagnetic  force. [ 3 ]  As a result, it becomes much easier to produce particles such as neutrinos that interact only weakly with other matter."}
{"_id": "WikiPedia_Radiology$$$corpus_170", "text": "The heaviest particle pairs yet produced by electron\u2013positron annihilation in  particle accelerators  are  W + \u2013 W \u2212  pairs (mass 80.385 GeV/c 2  \u00d7 2). The heaviest single-charged particle is the  Z boson  (mass 91.188 GeV/c 2 ). The driving motivation for constructing the  International Linear Collider  is to produce the  Higgs bosons  (mass 125.09 GeV/c 2 ) in this way. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_171", "text": "The electron\u2013positron annihilation process is the physical phenomenon relied on as the basis of  positron emission tomography  (PET) and  positron annihilation spectroscopy  (PAS). It is also used as a method of measuring the  Fermi surface  and  band structure  in  metals  by a technique called  Angular Correlation of Electron Positron Annihilation Radiation .\nIt is also used for nuclear transition.\nPositron annihilation spectroscopy is also used for the study of  crystallographic defects  in metals and semiconductors;\nit is considered the only direct probe for vacancy-type defects. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_172", "text": "The reverse reaction, electron\u2013positron creation, is a form of  pair production  governed by  two-photon physics ."}
{"_id": "WikiPedia_Radiology$$$corpus_173", "text": "A  gamma camera  ( \u03b3-camera ), also called a  scintillation camera  or  Anger camera , is a device used to image gamma radiation emitting radioisotopes, a technique known as  scintigraphy . The applications of scintigraphy include early  drug development  and  nuclear medical imaging  to view and analyse images of the human body or the distribution of medically injected, inhaled, or ingested  radionuclides  emitting  gamma rays ."}
{"_id": "WikiPedia_Radiology$$$corpus_174", "text": "Scintigraphy  (\"scint\") is the use of gamma cameras to capture emitted radiation from internal radioisotopes to create two-dimensional [ 1 ]  images."}
{"_id": "WikiPedia_Radiology$$$corpus_175", "text": "SPECT  (single photon emission computed tomography) imaging, as used in nuclear  cardiac stress testing , is performed using gamma cameras. Usually one, two or three detectors or heads, are slowly rotated around the patient."}
{"_id": "WikiPedia_Radiology$$$corpus_176", "text": "A gamma camera consists of one or more flat crystal planes (or detectors) optically coupled to an array of  photomultiplier tubes  in an assembly known as a \"head\", mounted on a gantry. The gantry is connected to a computer system that both controls the operation of the camera and acquires and stores images. [ 2 ] :\u200a82\u200a  The construction of a gamma camera is sometimes known as a compartmental radiation construction."}
{"_id": "WikiPedia_Radiology$$$corpus_177", "text": "The system accumulates events, or counts, of  gamma   photons  that are absorbed by the crystal in the camera. Usually a large flat crystal of  sodium iodide  with thallium doping NaI(Tl) in a light-sealed housing is used. The highly efficient capture method of this combination for detecting gamma rays was discovered in 1944 by  Sir Samuel Curran [ 3 ] [ 4 ]  whilst he was working on the  Manhattan Project  at the  University of California at Berkeley . Nobel prize-winning physicist  Robert Hofstadter  also worked on the technique in 1948. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_178", "text": "The crystal  scintillates  in response to incident gamma radiation. When a gamma photon leaves the patient (who has been injected with a  radioactive pharmaceutical ), it knocks an electron loose from an iodine atom in the crystal, and a faint flash of light is produced when the dislocated electron again finds a minimal energy state. The initial phenomenon of the excited electron is similar to the  photoelectric effect  and (particularly with gamma rays) the  Compton effect . After the flash of light is produced, it is detected.  Photomultiplier  tubes (PMTs) behind the crystal detect the fluorescent flashes (events) and a computer sums the counts. The computer reconstructs and displays a two dimensional image of the relative spatial count density on a monitor. This reconstructed image reflects the distribution and relative concentration of radioactive tracer elements present in the organs and tissues imaged. [ 6 ] :\u200a162"}
{"_id": "WikiPedia_Radiology$$$corpus_179", "text": "Hal Anger  developed the first gamma camera in 1957. [ 7 ] [ 8 ]  His original design, frequently called the Anger camera, is still widely used today. The Anger camera uses sets of  vacuum tube   photomultipliers  (PMT). Generally each tube has an exposed face of about  7.6 cm  in diameter and the tubes are arranged in hexagon configurations, behind the absorbing crystal. The electronic circuit connecting the photodetectors is wired so as to reflect the relative coincidence of light fluorescence as sensed by the members of the hexagon detector array. All the PMTs simultaneously detect the (presumed) same flash of light to varying degrees, depending on their position from the actual individual event. Thus the spatial location of each single flash of fluorescence is reflected as a pattern of voltages within the interconnecting circuit array."}
{"_id": "WikiPedia_Radiology$$$corpus_180", "text": "The location of the interaction between the gamma ray and the crystal can be determined by processing the voltage signals from the photomultipliers; in simple terms, the location can be found by weighting the position of each photomultiplier tube by the strength of its signal, and then calculating a mean position from the weighted positions. [ 2 ] :\u200a112\u200a  The total sum of the voltages from each photomultiplier, measured by a  pulse height analyzer  is proportional to the energy of the gamma ray interaction, thus allowing discrimination between different isotopes or between scattered and direct photons. [ 6 ] :\u200a166"}
{"_id": "WikiPedia_Radiology$$$corpus_181", "text": "In order to obtain spatial information about the gamma-ray emissions from an imaging subject (e.g. a person's heart muscle cells which have absorbed an intravenous injected radioactive, usually thallium-201 or  technetium-99m , medicinal imaging agent) a method of correlating the detected photons with their point of origin is required."}
{"_id": "WikiPedia_Radiology$$$corpus_182", "text": "The conventional method is to place a  collimator  over the detection crystal/PMT array.  The collimator consists of a thick sheet of  lead , typically 25 to 55 millimetres (1 to 2.2\u00a0in) thick, with thousands of adjacent holes through it. There are three types of collimators: low energy, medium energy, and high energy collimators. As the collimators transitioned from low energy to high energy, the hole sizes, thickness, and septations between the holes also increased.  [ 9 ]  Given a fixed septal thickness, the collimator resolution decreases with increased efficiency and also increasing distance of the source from the collimator. [ 10 ]  Pulse-height analyser determines the  Full width at half maximum  that selects certain photons to contribute to the final image, thus determining the collimator resolution. [ 11 ] [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_183", "text": "The individual holes limit photons which can be detected by the crystal to a cone shape; the point of the cone is at the midline center of any given hole and extends from the collimator surface outward.  However, the collimator is also one of the sources of blurring within the image; lead does not totally attenuate incident gamma photons, there can be some  crosstalk  between holes."}
{"_id": "WikiPedia_Radiology$$$corpus_184", "text": "Unlike a lens, as used in visible light cameras, the collimator attenuates most (>99%) of incident photons and thus greatly limits the sensitivity of the camera system. Large amounts of radiation must be present so as to provide enough exposure for the camera system to detect sufficient scintillation dots to form a picture. [ 2 ] :\u200a128"}
{"_id": "WikiPedia_Radiology$$$corpus_185", "text": "Other methods of image localization ( pinhole , rotating slat collimator with  CZT ) have been proposed and tested; [ 12 ]  however, none have entered widespread routine clinical use."}
{"_id": "WikiPedia_Radiology$$$corpus_186", "text": "The best current camera system designs can differentiate two separate point sources of gamma photons located at 6 to 12\u00a0mm depending on distance from the collimator, the type of collimator and radio-nucleide. Spatial resolution decreases rapidly at increasing distances from the camera face. This limits the spatial accuracy of the computer image: it is a fuzzy image made up of many dots of detected but not precisely located scintillation. This is a major limitation for heart muscle imaging systems; the thickest normal heart muscle in the left ventricle is about 1.2\u00a0cm and most of the left ventricle muscle is about 0.8\u00a0cm, always moving and much of it beyond 5\u00a0cm from the collimator face. To help compensate, better imaging systems limit scintillation counting to a portion of the heart contraction cycle, called gating, however this further limits system sensitivity."}
{"_id": "WikiPedia_Radiology$$$corpus_187", "text": "A  gamma probe  is a handheld device containing a  scintillation counter  for  intraoperative  use following  injection  of a  radionuclide  to locate  sentinel lymph nodes  by their radioactivity. [ 1 ]  It is used primarily for sentinel lymph node mapping and  parathyroid  surgery. Gamma probes are also used for RSL (radioactive seed localization) to locate small and non- palpable  breast  lesions . [ 2 ] [ 3 ] :\u200a243"}
{"_id": "WikiPedia_Radiology$$$corpus_188", "text": "The sentinel node market experienced high growth in the early and mid-1990s, starting with melanoma sentinel node surgical search and breast cancer sentinel node staging; both are currently considered standards of care. [ 4 ]  The use of a radioactive tracer, rather than a coloured dye, was proposed in 1984. [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_189", "text": "To locate the draining lymph nodes or sentinel lymph nodes from a breast cancer tumour, a  Technetium-99m  based  radiopharmaceutical  is common. This may be a nanocolloid or  sestamibi . [ 7 ]  Although imaging with a  gamma camera  may also take place, the idea of a small gamma probe is that it can be used to identify lymph nodes (or other sites) with uptake at a much higher resolution during an operation. The probe may be collimated to restrict the field of detection further. [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_190", "text": "Internal dosimetry  is the science and art of internal  ionising radiation  dose assessment due to  radionuclides  incorporated inside the human body. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_191", "text": "Radionuclides deposited within a body will irradiate tissues and organs and give rise to  committed dose  until they are excreted from the body or the radionuclide is completely decayed."}
{"_id": "WikiPedia_Radiology$$$corpus_192", "text": "The internal doses for workers or members of the public exposed to the intake of radioactive particulates can be estimated using  bioassay  data such as lung and body counter measurements, urine or faecal radioisotope concentration, etc. The  International Commission on Radiological Protection  (ICRP) biokinetic models are applied to establish a relationship between the individual intake and the bioassay measurements, and then to infer the internal dose."}
{"_id": "WikiPedia_Radiology$$$corpus_193", "text": "The internal radiation dose due to injection, ingestion or inhalation radioactive substances is known as  committed dose ."}
{"_id": "WikiPedia_Radiology$$$corpus_194", "text": "The ICRP defines Committed effective dose, E( t ) as the sum of the products of the committed organ or tissue equivalent doses and the appropriate tissue weighting factors  W T , where  t  is the integration time in years following the intake. The commitment period is taken to be 50 years for adults, and to age 70 years for children. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_195", "text": "The ICRP further states \"For internal exposure, committed effective doses are generally determined from an assessment of the intakes of radionuclides from bioassay measurements or other quantities (e.g., activity retained in the body or in daily excreta). The radiation dose is determined from the intake using recommended dose coefficients\". [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_196", "text": "There are a few routes of intake (of radionuclide) namely,"}
{"_id": "WikiPedia_Radiology$$$corpus_197", "text": "In a radioactive area, radionuclide particulate may be suspended in the air and can enter the body by inhalation. These particulates may be deposited in different parts of the respiratory tract depending upon their  aerodynamic diameter . [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_198", "text": "In-vivo monitoring  \nInternal dose monitoring of the radionuclides which emit radiation which can penetrate out of the body. For example, X-rays, gamma rays of sufficient energy. It can be measured by devices such as a whole body counter."}
{"_id": "WikiPedia_Radiology$$$corpus_199", "text": "A  whole body counter [ 5 ]  has a low background arrangement with counting systems"}
{"_id": "WikiPedia_Radiology$$$corpus_200", "text": "HPGe detectors are replacing detectors for measuring the low energy and high energy photons with appropriate electronic systems. \nCalibration of these systems is carried out with different type of physical and mathematical phantoms. Physical phantoms include  BOMAB , LLNL, JAERI, thyroid and the knee phantoms. Some of the renowned mathematical phantoms are MIRD, CRISTY and nowadays voxel phantoms also known as  Computational human phantoms ."}
{"_id": "WikiPedia_Radiology$$$corpus_201", "text": "In-vitro monitoring \n Monitoring of the radionuclides present in the body using the bio-assay sample taken out of the body; this includes samples of urine, sweat, feces, etc."}
{"_id": "WikiPedia_Radiology$$$corpus_202", "text": "The ICRP models are used to simulate the distribution of the isotopes inside the human being. All current ICRP models, compiled in the OIR (ICRP134/137) data viewer, [ 6 ]  can be represented by compartmental systems with constant coefficients. The conceptual model used by ICRP can be summarized as it follows."}
{"_id": "WikiPedia_Radiology$$$corpus_203", "text": "The human body can be divided into three systems:"}
{"_id": "WikiPedia_Radiology$$$corpus_204", "text": "a)  The human respiratory tract model (HRTM).   This model is applied for modeling the intake of radioactive aerosols by inhalation. The detailed description is given in ICRP 130 (2016) updating the ICRP 66 (1994). If a person inhales instantaneously a quantity I, it is deposited directly in some compartments of the HRTM. The fraction deposited in each compartment is called Initial Deposition Fraction or IDF. It is a function of Activity Median Aerodynamic Diameter (AMAD), which includes size, shape, density, anatomical and physiological parameters as well as various conditions of exposure. The IDF values may be calculated either following the procedure described in ICRP 130/66  or obtaining it from their Annex. The general model of the HRTM is common to any element except the absorption rates {fr, ss, sr} which are related to the chemical form of the element. ICRP gives default values of absorption rates according to types F, M or S, but specific value for some compounds are available in ICRP 134 and ICRP 137."}
{"_id": "WikiPedia_Radiology$$$corpus_205", "text": "b)  The Human Alimentary Tract Model (HATM).  This is applied for modeling the intake of particles in the GI tract following the model provided ICRP 105 (ICRP 2005). Particles can be introduced in the GI Tract directly by ingestion, or from the RT. Deposition is in the stomach (ST). Part or all the flow is transferred, through SI, to the blood (B). The rate transfer from SI to B, is given by fA. The value of fA is associated to the element and their chemical form."}
{"_id": "WikiPedia_Radiology$$$corpus_206", "text": "c)  Systemic compartments.   They are specific compartments to be applied for an element. Current models are described in ICRP 134 and ICRP 137. A few computer codes have been developed to estimate intake and calculate internal dose using biassay data. [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_207", "text": "Biokinetic modeling is widely used in internal dosimetry and to evaluate  bioassay  data. Computer programs can be used for bioassay evaluations. [ 8 ]  The bioassay measurement values can be used to estimate unknown intake. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_208", "text": "A  Jaszczak phantom  ( Polish pronunciation:   [\u02c8ja\u0282.t\u0361\u0282ak]   \u24d8 ) aka  Data Spectrum ECT phantom [ 1 ]  is an  imaging phantom  used for validating scanner geometry, 3D contrast, uniformity, resolution, attenuation and scatter correction or alignment tasks in  nuclear medicine . It is commonly used in academic centers and hospitals to characterize a  SPECT  or some gamma camera systems for  quality control  purposes. It is used for accreditation by clinical and academic facilities for the  American College of Radiology . [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_209", "text": "The phantom was developed by Ronald J. Jaszczak [ 4 ]  of  Duke University , [ 5 ]  and was filed for a patent in 1982. [ 6 ]  It is a cylinder containing fillable inserts that is often used with a radionuclide such as  Technetium-99m [ 7 ]  or  Fluorine-18 . [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_210", "text": "Although the phantom can be used for acceptance testing, the  National Electrical Manufacturers Association  recommends a 30 million count acquisition and section reconstruction of the phantom be performed quarterly. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_211", "text": "In 1981 Ronald J. Jaszczak founded Data Spectrum Corporation which manufactures the Jaszczak phantom and several other nuclear imaging tools, [ 10 ]  such as the Hoffman Brain phantom."}
{"_id": "WikiPedia_Radiology$$$corpus_212", "text": "Jaszczak phantoms consist of a main cylinder or tank made of acrylic plastic with several inserts. The circular phantom comes in two varieties: flanged and flangeless. The latter is recommended by the  American College of Radiology  for accreditation of  nuclear medicine  departments. [ 11 ]  All Jaszczak phantoms have six solid spheres and six sets of 'cold' rods. In flanged models, the sizes of the spheres vary. The number of rods in each set depends on the size of the rod in that set as different models of the phantom have rods of different sizes. In flangeless models, the diameters of the spheres are 9.5, 12.7, 15.9, 19.1, 25.4 and 31.8\u00a0mm, while the rod diameters are 4.8, 6.4, 7.9, 9.5, 11.1 and 12.7\u00a0mm. Both solid spheres and rod inserts mimic cold lesions in a hot background. Spheres are used to measure the image contrast while the rods are used to investigate the image resolution in SPECT systems. [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_213", "text": "The  linear no-threshold model  ( LNT ) is a  dose-response  model used in  radiation protection  to estimate  stochastic health effects  such as  radiation-induced cancer , genetic  mutations  and  teratogenic  effects on the human body due to exposure to  ionizing radiation . The model assumes a linear relationship between dose and health effects, even for very low doses where biological effects are more difficult to observe. The LNT model implies that all exposure to ionizing radiation is harmful, regardless of how low the dose is, and that the effect is cumulative over lifetime."}
{"_id": "WikiPedia_Radiology$$$corpus_214", "text": "The LNT model is commonly used by regulatory bodies as a basis for formulating  public health  policies that set regulatory dose limits to protect against the effects of radiation. The validity of the LNT model, however, is disputed, and other models exist: the  threshold model , which assumes that very small exposures are harmless, the  radiation hormesis  model, which says that radiation at very small doses can be beneficial, and the supra-linear model. It has been argued that the LNT model may have created an irrational fear of radiation. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_215", "text": "Scientific organizations and government regulatory bodies generally support use of the LNT model, particularly for optimization. However, some caution against estimating health effects from doses below a certain level (see  \u00a7\u00a0Controversy )."}
{"_id": "WikiPedia_Radiology$$$corpus_216", "text": "Stochastic health effects are those that occur by chance, and whose probability is proportional to the  dose , but whose severity is independent of the dose. [ 3 ]  The LNT model assumes there is no lower threshold at which stochastic effects start, and assumes a linear relationship between dose and the stochastic health risk. In other words, LNT assumes that radiation has the potential to cause harm at  any  dose level, however small, and the sum of several very small exposures is just as likely to cause a stochastic health effect as a single larger exposure of equal dose value. [ 1 ]  In contrast,  deterministic health effects  are radiation-induced effects such as  acute radiation syndrome , which are caused by tissue damage. Deterministic effects reliably occur above a threshold dose and their severity increases with dose. [ 4 ]  Because of the inherent differences, LNT is not a model for deterministic effects, which are instead characterized by other types of dose-response relationships."}
{"_id": "WikiPedia_Radiology$$$corpus_217", "text": "LNT is a common model to calculate the probability of  radiation-induced cancer  both at high doses where  epidemiology  studies support its application, but controversially, also at low doses, which is a dose region that has a lower predictive  statistical confidence . [ 1 ]  Nonetheless, regulatory bodies, such as the  Nuclear Regulatory Commission  (NRC), commonly use LNT as a basis for regulatory dose limits to protect against stochastic health effects, as found in many  public health  policies. Whether the LNT model describes the reality for small-dose exposures is disputed, and challenges to the LNT model used by NRC for setting radiation protection regulations were submitted. [ 2 ]  NRC rejected the petitions in 2021 because \"they fail to present an adequate basis supporting the request to discontinue use of the LNT model\". [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_218", "text": "Other dose models include: the  threshold model , which assumes that very small exposures are harmless, and the  radiation hormesis  model, which claims that radiation at very small doses can be beneficial. Because the current data is inconclusive, scientists disagree on which model should be used, though most national and international cancer research organizations explicitly endorse LNT for regulating exposures to low dose radiation. The model is sometimes used to quantify the cancerous effect of  collective doses  of low-level radioactive contaminations, which is controversial. Such practice has been criticized by the  International Commission on Radiological Protection  since 2007. [ 6 ] [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_219", "text": "The association of exposure to radiation with cancer had been observed as early as 1902, six years after the discovery of  X-rays  by  Wilhelm R\u00f6ntgen  and  radioactivity  by  Henri Becquerel . [ 8 ]  In 1927,  Hermann Muller  demonstrated that radiation may cause genetic mutation. [ 9 ]  He also suggested mutation as a cause of cancer. [ 10 ]   Gilbert N. Lewis  and Alex Olson, based on Muller's discovery of the effect of radiation on mutation, proposed a mechanism for biological  evolution  in 1928, suggesting that genomic mutation was induced by cosmic and terrestrial radiation and first introduced the idea that such mutation may occur proportionally to the dose of radiation. [ 11 ]  Various laboratories, including Muller's, then demonstrated the apparent linear dose response of mutation frequency. [ 12 ]  Muller, who received a  Nobel Prize  for his work on the  mutagenic  effect of radiation in 1946, asserted in his Nobel lecture,  The Production of Mutation , that mutation frequency is \"directly and simply proportional to the dose of irradiation applied\" and that there is \"no threshold dose\". [ 13 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_220", "text": "The early studies were based on higher levels of radiation that made it hard to establish the safety of low level of radiation. Indeed, many early scientists believed that there may be a tolerance level, and that low doses of radiation may not be harmful. [ 8 ]  A later study in 1955 on mice exposed to low dose of radiation suggests that they may outlive control animals. [ 14 ]  The interest in the effects of radiation intensified after the dropping of atomic bombs on  Hiroshima  and  Nagasaki , and studies were conducted on the survivors. Although compelling evidence on the effect of low dosage of radiation was hard to come by, by the late 1940s, the idea of LNT became more popular due to its mathematical simplicity. In 1954, the  National Council on Radiation Protection and Measurements  (NCRP) introduced the concept of  maximum permissible dose . In 1958, the  United Nations Scientific Committee on the Effects of Atomic Radiation  (UNSCEAR) assessed the LNT model and a threshold model, but noted the difficulty in acquiring \"reliable information about the correlation between small doses and their effects either in individuals or in large populations\". The  United States Congress Joint Committee on Atomic Energy  (JCAE) similarly could not establish if there is a threshold or \"safe\" level for exposure; nevertheless, it introduced the concept of \" As Low As Reasonably Achievable \" (ALARA). ALARA would become a fundamental principle in radiation protection policy that implicitly accepts the validity of LNT. In 1959, the United States Federal Radiation Council (FRC) supported the concept of the LNT extrapolation down to the low dose region in its first report. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_221", "text": "By the 1970s, the LNT model had become accepted as the standard in radiation protection practice by a number of bodies. [ 8 ]  In 1972, the first report of National Academy of Sciences (NAS)  Biological Effects of Ionizing Radiation  (BEIR), an expert panel who reviewed available peer reviewed literature, supported the LNT model on pragmatic grounds, noting that while \"dose-effect relationship for x rays and gamma rays may not be a linear function\", the \"use of linear extrapolation ... may be justified on pragmatic grounds as a basis for risk estimation.\" In its seventh report of 2006, NAS BEIR VII writes, \"the committee concludes that the preponderance of information indicates that there will be some risk, even at low doses\". [ 15 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_222", "text": "The Health Physics Society (in the United States) has published a documentary series on the origins of the LNT model. [ 16 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_223", "text": "Radiation precautions have led to  sunlight  being listed as a carcinogen at all sun exposure rates, due to the  ultraviolet  component of sunlight, with no safe level of sunlight exposure being suggested, following the precautionary LNT model. According to a 2007 study submitted by the University of Ottawa to the Department of Health and Human Services in Washington, D.C., there is not enough information to determine a safe level of sun exposure. [ 17 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_224", "text": "The linear no-threshold model is used to extrapolate the expected number of extra deaths caused by exposure to  environmental radiation , and it therefore has a great impact on  public policy . The model is used to translate any  radiation release , into a number of lives lost, while any reduction in  radiation exposure , for example as a consequence of  radon  detection, is translated into a number of lives saved. When the doses are very low the model predicts new cancers only in a very small fraction of the population, but for a large population, the number of lives is extrapolated into hundreds or thousands."}
{"_id": "WikiPedia_Radiology$$$corpus_225", "text": "A linear model has long been used in  health physics  to set maximum acceptable radiation exposures."}
{"_id": "WikiPedia_Radiology$$$corpus_226", "text": "The LNT model has been contested by a number of scientists. [ 1 ]  It has been claimed that the early proponent of the model  Hermann Joseph Muller  intentionally ignored an early study that did not support the LNT model when he gave his 1946 Nobel Prize address advocating the model. [ 18 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_227", "text": "In  very high dose radiation therapy , it was known at the time that radiation can cause a physiological increase in the rate of pregnancy anomalies; however, human exposure data and animal testing suggests that the \"malformation of organs appears to be a  deterministic effect  with a  threshold dose \", below which no rate increase is observed. [ 19 ]  A review in 1999 on the link between the Chernobyl accident and  teratology  (birth defects) concludes that \"there is no substantive proof regarding radiation\u2010induced teratogenic effects from the Chernobyl accident\". [ 19 ]  It is argued that the human body has defense mechanisms, such as  DNA repair  and  programmed cell death , that would protect it against carcinogenesis due to low-dose exposures of carcinogens. [ 20 ]  However, these repair mechanisms are known to be error prone.  [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_228", "text": "A 2011 research of the cellular repair mechanisms support the evidence against the linear no-threshold model. [ 21 ]  According to its authors, this study published in the Proceedings of the National Academy of Sciences of the United States of America \"casts considerable doubt on the general assumption that risk to ionizing radiation is proportional to dose\"."}
{"_id": "WikiPedia_Radiology$$$corpus_229", "text": "A 2011 review of studies addressing childhood leukaemia following exposure to ionizing radiation, including both diagnostic exposure and natural background exposure from  radon , concluded that existing risk factors, excess  relative risk  per sievert (ERR/Sv), is \"broadly applicable\" to low dose or low dose-rate exposure, \"although the uncertainties associated with this estimate are considerable\". The study also notes that \"epidemiological studies have been unable, in general, to detect the influence of natural background radiation upon the risk of childhood leukaemia\" [ 22 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_230", "text": "Many expert scientific panels have been convened on the risks of ionizing radiation. Most explicitly support the LNT model and none have concluded that evidence exists for a threshold, with the exception of the French Academy of Sciences in a 2005 report. [ 23 ] [ 24 ]  Considering the uncertainty of health effects at low doses, several organizations caution against estimating health effects below certain doses, generally below natural background, as noted below:"}
{"_id": "WikiPedia_Radiology$$$corpus_231", "text": "Based upon the current state of science, the NRC concludes that the actual level of risk associated with low doses of radiation remains uncertain and some studies, such as the INWORKS study, show there is at least some risk from low doses of radiation. Moreover, the current state of science does not provide compelling evidence of a threshold, as highlighted by the fact that no national or international authoritative scientific advisory bodies have concluded that such evidence exists. Therefore, based upon the stated positions of the aforementioned advisory bodies; the comments and recommendations of NCI, NIOSH, and the EPA; the October 28, 2015, recommendation of the ACMUI; and its own professional and technical judgment, the NRC has determined that the LNT model continues to provide a sound regulatory basis for minimizing the risk of unnecessary radiation exposure to both members of the public and occupational workers. Consequently, the NRC will retain the dose limits for occupational workers and members of the public in 10 CFR part 20 radiation protection regulations."}
{"_id": "WikiPedia_Radiology$$$corpus_232", "text": "The assumption that any stimulatory hormetic effects from low doses of ionizing radiation will have a significant health benefit to humans that exceeds potential detrimental effects from the radiation exposure is unwarranted at this time."}
{"_id": "WikiPedia_Radiology$$$corpus_233", "text": "The scientific research base shows that there is no threshold of exposure below which low levels of ionizing radiation can be demonstrated to be harmless or beneficial."}
{"_id": "WikiPedia_Radiology$$$corpus_234", "text": "Underlying the risk models is a large body of epidemiological and radiobiological data. In general, results from both lines of research are consistent with a linear, no-threshold dose (LNT) response model in which the risk of inducing a cancer in an irradiated tissue by low doses of radiation is proportional to the dose to that tissue"}
{"_id": "WikiPedia_Radiology$$$corpus_235", "text": "The Committee concluded that there remains good justification for the use of a non-threshold model for risk inference given the robust knowledge on the role of mutation and chromosomal aberrations in carcinogenesis. That said, there are ways that radiation could act that might lead to a re-evaluation of the use of a linear dose-response model to infer radiation cancer risks."}
{"_id": "WikiPedia_Radiology$$$corpus_236", "text": "A number of organisations caution against using the Linear no-threshold model to estimate risk from radiation exposure below a certain level:"}
{"_id": "WikiPedia_Radiology$$$corpus_237", "text": "In conclusion, this report raises doubts on the validity of using LNT for evaluating the carcinogenic risk of low doses (< 100 mSv) and even more for very low doses (< 10 mSv). The LNT concept can be a useful pragmatic tool for assessing rules in radioprotection for doses above 10 mSv; however since it is not based on biological concepts of our current knowledge, it should not be used without precaution for assessing by extrapolation the risks associated with low and even more so, with very low doses (< 10 mSv), especially for benefit-risk assessments imposed on radiologists by the European directive 97-43."}
{"_id": "WikiPedia_Radiology$$$corpus_238", "text": "The Health Physics Society advises against estimating health risks to people from exposures to ionizing radiation that are near or less than natural background levels because statistical uncertainties at these low levels are great."}
{"_id": "WikiPedia_Radiology$$$corpus_239", "text": "The Scientific Committee does not recommend multiplying very low doses by large numbers of individuals to estimate numbers of radiation-induced health effects within a population exposed to incremental doses at levels equivalent to or lower than natural background levels."}
{"_id": "WikiPedia_Radiology$$$corpus_240", "text": "It has been argued that the LNT model had caused an  irrational fear of radiation , whose observable effects are much more significant than non-observable effects postulated by LNT. [ 1 ]  In the wake of the 1986  Chernobyl accident  in  Ukraine , Europe-wide anxieties were fomented in pregnant mothers over the perception enforced by the LNT model that their children would be born with a higher rate of mutations. [ 37 ]  As far afield as the country of  Switzerland , hundreds of excess  induced abortions  were performed on the healthy unborn, out of this no-threshold fear. [ 38 ]  Following the accident however, studies of data sets approaching a million births in the  EUROCAT  database, divided into \"exposed\" and control groups were assessed in 1999. As no Chernobyl impacts were detected, the researchers conclude \"in retrospect the widespread fear in the population about the possible effects of exposure on the unborn was not justified\". [ 39 ]  Despite studies from Germany and Turkey, the only robust evidence of negative pregnancy outcomes that transpired after the accident were these elective abortion indirect effects, in Greece, Denmark, Italy etc., due to the anxieties created. [ 40 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_241", "text": "The consequences of low-level radiation are often more  psychological  than radiological. Because damage from very-low-level radiation cannot be detected, people exposed to it are left in anguished uncertainty about what will happen to them. Many believe they have been fundamentally contaminated for life and may refuse to have children for fear of  birth defects . They may be shunned by others in their community who fear a sort of mysterious contagion. [ 41 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_242", "text": "Forced evacuation from a radiation or nuclear accident may lead to social isolation, anxiety, depression, psychosomatic medical problems, reckless behavior, or suicide. Such was the outcome of the 1986  Chernobyl nuclear disaster  in Ukraine. A comprehensive 2005 study concluded that \"the mental health impact of Chernobyl is the largest public health problem unleashed by the accident to date\". [ 41 ]   Frank N. von Hippel , a U.S. scientist, commented on the 2011  Fukushima nuclear disaster , saying that \"fear of ionizing radiation could have long-term psychological effects on a large portion of the population in the contaminated areas\". [ 42 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_243", "text": "Such great psychological danger does not accompany other materials that put people at risk of cancer and other deadly illness. Visceral fear is not widely aroused by, for example, the daily emissions from coal burning, although as a National Academy of Sciences study found, this causes 10,000 premature deaths a year in the US. It is \"only nuclear radiation that bears a huge psychological burden \u2013 for it carries a unique historical legacy\". [ 41 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_244", "text": "Redirect to:"}
{"_id": "WikiPedia_Radiology$$$corpus_245", "text": "Medical imaging  is the technique and process of  imaging  the interior of a body for clinical analysis and medical intervention, as well as visual representation of the function of some organs or tissues ( physiology ). Medical imaging seeks to reveal internal structures hidden by the skin and bones, as well as to diagnose and treat  disease . Medical imaging also establishes a database of normal  anatomy  and  physiology  to make it possible to identify abnormalities. Although imaging of removed  organs  and  tissues  can be performed for medical reasons, such procedures are usually considered part of  pathology  instead of medical imaging. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_246", "text": "Measurement and recording techniques that are not primarily designed to produce  images , such as  electroencephalography  (EEG),  magnetoencephalography  (MEG),  electrocardiography  (ECG), and others, represent other technologies that produce data susceptible to representation as a parameter graph versus time or  maps  that contain data about the measurement locations. In a limited comparison, these technologies can be considered forms of medical imaging in another discipline of  medical instrumentation ."}
{"_id": "WikiPedia_Radiology$$$corpus_247", "text": "As of 2010, 5\u00a0billion medical imaging studies had been conducted worldwide. [ 1 ]  Radiation exposure from medical imaging in 2006 made up about 50% of total ionizing radiation exposure in the United States. [ 2 ]  Medical imaging equipment is manufactured using technology from the  semiconductor industry , including  CMOS   integrated circuit  chips,  power semiconductor devices ,  sensors  such as  image sensors  (particularly  CMOS sensors ) and  biosensors , and processors such as  microcontrollers ,  microprocessors ,  digital signal processors ,  media processors  and  system-on-chip  devices. As of 2015 [update] , annual shipments of medical imaging chips amount to 46 \u00a0 million units and  $1.1 billion . [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_248", "text": "The term \" noninvasive \" is used to denote a procedure where no instrument is introduced into a patient's body, which is the case for most imaging techniques used."}
{"_id": "WikiPedia_Radiology$$$corpus_249", "text": "In the clinical context, \"invisible light\" medical imaging is generally equated to  radiology  or \"clinical imaging\". \"Visible light\" medical imaging involves digital video or still pictures that can be seen without special equipment. Dermatology and wound care are two modalities that use visible light imagery. Interpretation of medical images is generally undertaken by a physician specialising in radiology known as a  radiologist ; however, this may be undertaken by any healthcare professional who is trained and certified in radiological clinical evaluation. Increasingly interpretation is being undertaken by non-physicians, for example  radiographers  frequently train in interpretation as part of expanded practice. Diagnostic  radiography  designates the technical aspects of medical imaging and in particular the acquisition of medical images. The radiographer (also known as a radiologic technologist) is usually responsible for acquiring medical images of diagnostic quality; although other professionals may train in this area, notably some radiological interventions performed by radiologists are done so without a radiographer. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_250", "text": "As a field of scientific investigation, medical imaging constitutes a sub-discipline of  biomedical engineering ,  medical physics  or  medicine  depending on the context: Research and development in the area of instrumentation, image acquisition (e.g., radiography), modeling and quantification are usually the preserve of biomedical engineering, medical physics, and  computer science ; Research into the application and interpretation of medical images is usually the preserve of radiology and the medical sub-discipline relevant to medical condition or area of medical science ( neuroscience ,  cardiology ,  psychiatry ,  psychology , etc.) under investigation. Many of the techniques developed for medical imaging also have  scientific  and  industrial  applications. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_251", "text": "Two forms of radiographic images are in use in medical imaging. Projection radiography and fluoroscopy, with the latter being useful for catheter guidance. These 2D techniques are still in wide use despite the advance of 3D tomography due to the low cost, high resolution, and depending on the application, lower radiation dosages with 2D technique. This imaging modality uses a wide beam of  X-rays  for image acquisition and is the first imaging technique available in modern medicine."}
{"_id": "WikiPedia_Radiology$$$corpus_252", "text": "A magnetic resonance imaging instrument ( MRI scanner ), or \"nuclear magnetic resonance ( NMR ) imaging\" scanner as it was originally known, uses powerful magnets to polarize and excite  hydrogen  nuclei (i.e., single  protons ) of water molecules in human tissue, producing a detectable signal which is spatially encoded, resulting in images of the body. [ 5 ]  The MRI machine emits a radio frequency (RF) pulse at the resonant frequency of the hydrogen atoms on water molecules. Radio frequency antennas (\"RF coils\") send the pulse to the area of the body to be examined. The RF pulse is absorbed by protons, causing their direction with respect to the primary magnetic field to change. When the RF pulse is turned off, the protons \"relax\" back to alignment with the primary magnet and emit radio-waves in the process. This radio-frequency emission from the hydrogen-atoms on water is what is detected and reconstructed into an image. The resonant frequency of a spinning magnetic dipole (of which protons are one example) is called the  Larmor frequency  and is determined by the strength of the main magnetic field and the chemical environment of the nuclei of interest. MRI uses three  electromagnetic fields : a very strong (typically 1.5 to 3  teslas ) static magnetic field to polarize the hydrogen nuclei, called the primary field; gradient fields that can be modified to vary in space and time (on the order of 1\u00a0kHz) for spatial encoding, often simply called gradients; and a spatially homogeneous  radio-frequency  (RF) field for manipulation of the hydrogen nuclei to produce measurable signals, collected through an  RF antenna . [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_253", "text": "Like  CT , MRI traditionally creates a two-dimensional image of a thin \"slice\" of the body and is therefore considered a  tomographic  imaging technique. Modern MRI instruments are capable of producing images in the form of 3D blocks, which may be considered a generalization of the single-slice, tomographic, concept. Unlike CT, MRI does not involve the use of  ionizing radiation  and is therefore not associated with the same health hazards. For example, because MRI has only been in use since the early 1980s, there are no known long-term effects of exposure to strong static fields (this is the subject of some debate; see 'Safety' in  MRI ) and therefore there is no limit to the number of scans to which an individual can be subjected, in contrast with  X-ray  and  CT . However, there are well-identified health risks associated with tissue heating from exposure to the RF field and the presence of implanted devices in the body, such as pacemakers. These risks are strictly controlled as part of the design of the instrument and the scanning protocols used. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_254", "text": "Because CT and MRI are sensitive to different tissue properties, the appearances of the images obtained with the two techniques differ markedly. In CT, X-rays must be blocked by some form of dense tissue to create an image, so the image quality when looking at soft tissues will be poor. In MRI, while any nucleus with a net nuclear spin can be used, the proton of the hydrogen atom remains the most widely used, especially in the clinical setting, because it is so ubiquitous and returns a large signal. This nucleus, present in water molecules, allows the excellent soft-tissue contrast achievable with MRI. [ 6 ] [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_255", "text": "A number of different pulse sequences can be used for specific MRI diagnostic imaging (multiparametric MRI or mpMRI). It is possible to differentiate tissue characteristics by combining two or more of the following imaging sequences, depending on the information being sought: T1-weighted (T1-MRI), T2-weighted (T2-MRI), diffusion weighted imaging (DWI-MRI), dynamic contrast enhancement (DCE-MRI), and spectroscopy (MRI-S). For example, imaging of prostate tumors is better accomplished using T2-MRI and DWI-MRI than T2-weighted imaging alone. [ 7 ]  The number of applications of mpMRI for detecting disease in various organs continues to expand, including  liver  studies,  breast tumors ,  pancreatic tumors , and assessing the effects of  vascular  disruption agents on cancer tumors. [ 8 ] [ 9 ] [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_256", "text": "Nuclear medicine encompasses both diagnostic imaging and treatment of disease, and may also be referred to as molecular medicine or molecular imaging and therapeutics. [ 11 ]  Nuclear medicine uses certain properties of isotopes and the energetic particles emitted from radioactive material to diagnose or treat various pathology. Different from the typical concept of anatomic radiology, nuclear medicine enables assessment of physiology. This function-based approach to medical evaluation has useful applications in most subspecialties, notably oncology, neurology, and cardiology.  Gamma cameras  and  PET scanners  are used in e.g. scintigraphy, SPECT and PET to detect regions of biologic activity that may be associated with a disease. Relatively short-lived  isotope , such as  99m Tc  is administered to the patient. Isotopes are often preferentially absorbed by biologically active tissue in the body, and can be used to identify tumors or  fracture  points in bone. Images are acquired after collimated photons are detected by a crystal that gives off a light signal, which is in turn amplified and converted into count data."}
{"_id": "WikiPedia_Radiology$$$corpus_257", "text": "Fiduciary markers are used in a wide range of medical imaging applications. Images of the same subject produced with two different imaging systems may be correlated (called image registration) by placing a fiduciary marker in the area imaged by both systems. In this case, a marker which is visible in the images produced by both imaging modalities must be used. By this method, functional information from  SPECT  or  positron emission tomography  can be related to anatomical information provided by  magnetic resonance imaging  (MRI). [ 14 ]  Similarly, fiducial points established during MRI can be correlated with brain images generated by  magnetoencephalography  to localize the source of brain activity."}
{"_id": "WikiPedia_Radiology$$$corpus_258", "text": "Medical ultrasound  uses high frequency  broadband  sound waves in the  megahertz  range that are reflected by tissue to varying degrees to produce (up to 3D) images. This is commonly associated with  imaging the fetus  in pregnant women. Uses of ultrasound are much broader, however. Other important uses include imaging the abdominal organs, heart, breast, muscles, tendons, arteries and veins. While it may provide less anatomical detail than techniques such as CT or MRI, it has several advantages which make it ideal in numerous situations, in particular that it studies the function of moving structures in real-time, emits no  ionizing radiation , and contains  speckle  that can be used in  elastography . Ultrasound is also used as a popular research tool for capturing raw data, that can be made available through an  ultrasound research interface , for the purpose of tissue characterization and implementation of new image processing techniques. The concepts of ultrasound differ from other medical imaging modalities in the fact that it is operated by the transmission and receipt of sound waves. The high frequency sound waves are sent into the tissue and depending on the composition of the different tissues; the signal will be attenuated and returned at separate intervals. A path of reflected sound waves in a multilayered structure can be defined by an input acoustic impedance (ultrasound sound wave) and the Reflection and transmission coefficients of the relative structures. [ 13 ]  It is very safe to use and does not appear to cause any adverse effects. It is also relatively inexpensive and quick to perform. Ultrasound scanners can be taken to critically ill patients in intensive care units, avoiding the danger caused while moving the patient to the radiology department. The real-time moving image obtained can be used to guide drainage and biopsy procedures. Doppler capabilities on modern scanners allow the blood flow in arteries and veins to be assessed."}
{"_id": "WikiPedia_Radiology$$$corpus_259", "text": "Elastography is a relatively new imaging modality that maps the elastic properties of soft tissue. This modality emerged in the last two decades. Elastography is useful in medical diagnoses, as elasticity can discern healthy from unhealthy tissue for specific organs/growths. For example, cancerous tumours will often be harder than the surrounding tissue, and diseased livers are stiffer than healthy ones. [ 15 ] [ 16 ] [ 17 ] [ 18 ]  There are several elastographic techniques based on the use of ultrasound, magnetic resonance imaging and tactile imaging. The wide clinical use of ultrasound elastography is a result of the implementation of technology in clinical ultrasound machines. Main branches of ultrasound elastography include Quasistatic Elastography/Strain Imaging, Shear Wave Elasticity Imaging (SWEI), Acoustic Radiation Force Impulse imaging (ARFI), Supersonic Shear Imaging (SSI), and Transient Elastography. [ 16 ]  In the last decade, a steady increase of activities in the field of elastography is observed demonstrating successful application of the technology in various areas of medical diagnostics and treatment monitoring."}
{"_id": "WikiPedia_Radiology$$$corpus_260", "text": "Photoacoustic imaging  is a recently developed hybrid biomedical imaging modality based on the photoacoustic effect. It combines the advantages of optical absorption contrast with an ultrasonic spatial resolution for deep imaging in (optical) diffusive or quasi-diffusive regime. Recent studies have shown that photoacoustic imaging can be used in vivo for tumor angiogenesis monitoring, blood oxygenation mapping, functional brain imaging, and skin melanoma detection, etc."}
{"_id": "WikiPedia_Radiology$$$corpus_261", "text": "Tomography  is the imaging by sections or sectioning. The main such methods in medical imaging are:"}
{"_id": "WikiPedia_Radiology$$$corpus_262", "text": "When ultrasound is used to image the heart it is referred to as an  echocardiogram . Echocardiography allows detailed structures of the heart, including chamber size, heart function, the valves of the heart, as well as the pericardium (the sac around the heart) to be seen. Echocardiography uses 2D, 3D, and  Doppler  imaging to create pictures of the heart and visualize the blood flowing through each of the four heart valves. Echocardiography is widely used in an array of patients ranging from those experiencing symptoms, such as shortness of breath or chest pain, to those undergoing cancer treatments. Transthoracic ultrasound has been proven to be safe for patients of all ages, from infants to the elderly, without risk of harmful side effects or radiation, differentiating it from other imaging modalities. Echocardiography is one of the most commonly used imaging modalities in the world due to its portability and use in a variety of applications. In emergency situations, echocardiography is quick, easily accessible, and able to be performed at the bedside, making it the modality of choice for many physicians."}
{"_id": "WikiPedia_Radiology$$$corpus_263", "text": "FNIR Is a relatively new non-invasive imaging technique.  NIRS  (near infrared spectroscopy) is used for the purpose of  functional neuroimaging  and has been widely accepted as a  brain imaging  technique. [ 19 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_264", "text": "Using  superparamagnetic iron oxide nanoparticles , magnetic particle imaging ( MPI ) is a developing diagnostic imaging technique used for tracking  superparamagnetic   iron oxide   nanoparticles . The primary advantage is the high  sensitivity and specificity , along with the lack of signal decrease with tissue depth. MPI has been used in medical research to image  cardiovascular  performance,  neuroperfusion , and cell tracking."}
{"_id": "WikiPedia_Radiology$$$corpus_265", "text": "Medical imaging may be  indicated  in  pregnancy  because of  pregnancy complications , a  pre-existing disease  or an acquired disease in pregnancy, or routine  prenatal care .  Magnetic resonance imaging  (MRI) without  MRI contrast agents  as well as  obstetric ultrasonography  are not associated with any risk for the mother or the fetus, and are the imaging techniques of choice for pregnant women. [ 20 ]   Projectional radiography ,  CT scan  and  nuclear medicine  imaging result some degree of  ionizing radiation  exposure, but have with a few exceptions much lower  absorbed doses  than what are associated with fetal harm. [ 20 ]  At higher dosages, effects can include  miscarriage ,  birth defects  and  intellectual disability . [ 20 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_266", "text": "The amount of data obtained in a single MR or CT scan is very extensive. Some of the data that radiologists discard could save patients time and money, while reducing their exposure to radiation and risk of complications from invasive procedures. [ 21 ]  Another approach for making the procedures more efficient is based on utilizing additional constraints, e.g., in some medical imaging modalities one can improve the efficiency of the data acquisition by taking into account the fact the reconstructed density is positive. [ 22 ] [ 23 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_267", "text": "Volume rendering  techniques have been developed to enable CT, MRI and ultrasound scanning software to produce 3D images for the physician. [ 24 ]  Traditionally CT and MRI scans produced 2D static output on film. To produce 3D images, many scans are made and then  combined by computers  to produce a 3D model, which can then be manipulated by the physician.  3D ultrasounds  are produced using a somewhat similar technique.\nIn diagnosing disease of the viscera of the abdomen, ultrasound is particularly sensitive on imaging of biliary tract, urinary tract and female reproductive organs (ovary, fallopian tubes). As for example, diagnosis of gallstone by dilatation of common bile duct and stone in the common bile duct.\nWith the ability to visualize important structures in great detail, 3D visualization methods are a valuable resource for the diagnosis and surgical treatment of many pathologies. It was a key resource for the famous, but ultimately unsuccessful attempt by Singaporean surgeons to separate Iranian twins  Ladan and Laleh Bijani  in 2003. The 3D equipment was used previously for similar operations with great success."}
{"_id": "WikiPedia_Radiology$$$corpus_268", "text": "Other proposed or developed techniques include:"}
{"_id": "WikiPedia_Radiology$$$corpus_269", "text": "Some of these techniques [ example needed ]  are still at a research stage and not yet used in clinical routines."}
{"_id": "WikiPedia_Radiology$$$corpus_270", "text": "Neuroimaging  has also been used in experimental circumstances to allow people (especially disabled persons) to control outside devices, acting as a  brain computer interface ."}
{"_id": "WikiPedia_Radiology$$$corpus_271", "text": "Many medical imaging software applications are used for non-diagnostic imaging, specifically because they do not have an FDA approval [ 25 ]  and not allowed to use in  clinical research  for patient diagnosis. [ 26 ]  Note that many  clinical research  studies are not designed for patient diagnosis anyway. [ 27 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_272", "text": "Used primarily in  ultrasound  imaging, capturing the image produced by a medical imaging device is required for archiving and  telemedicine  applications. In most scenarios, a  frame grabber  is used in order to capture the video signal from the medical device and relay it to a computer for further processing and operations. [ 28 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_273", "text": "The  Digital Imaging and Communication in Medicine (DICOM)  Standard is used globally to store, exchange, and transmit medical images. The DICOM Standard incorporates protocols for imaging techniques such as radiography, computed tomography (CT), magnetic resonance imaging (MRI), ultrasound, and radiation therapy. [ 29 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_274", "text": "Medical imaging techniques produce very large amounts of data, especially from CT, MRI and PET modalities. As a result, storage and communications of electronic image data are prohibitive without the use of compression. [ 30 ] [ 31 ]   JPEG 2000  image compression is used by the  DICOM  standard for storage and transmission of medical images. The cost and feasibility of accessing large image data sets over low or various bandwidths are further addressed by use of another DICOM standard, called  JPIP , to enable efficient streaming of the  JPEG 2000  compressed image data."}
{"_id": "WikiPedia_Radiology$$$corpus_275", "text": "There has been growing trend to migrate from on-premise  PACS  to a  cloud-based  PACS. A recent article by Applied Radiology said, \"As the digital-imaging realm is embraced across the healthcare enterprise, the swift transition from terabytes to petabytes of data has put radiology on the brink of  information overload . Cloud computing offers the imaging department of the future the tools to manage data much more intelligently.\" [ 32 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_276", "text": "Medical imaging has become a major tool in clinical trials since it enables rapid diagnosis with visualization and quantitative assessment."}
{"_id": "WikiPedia_Radiology$$$corpus_277", "text": "A typical  clinical trial  goes through multiple phases and can take up to eight years.  Clinical endpoints  or outcomes are used to determine whether the therapy is safe and effective. Once a patient reaches the endpoint, he or she is generally excluded from further experimental interaction. Trials that rely solely on  clinical endpoints  are very costly as they have long durations and tend to need large numbers of patients."}
{"_id": "WikiPedia_Radiology$$$corpus_278", "text": "In contrast to clinical endpoints,  surrogate endpoints  have been shown to cut down the time required to confirm whether a drug has clinical benefits. Imaging  biomarkers  (a characteristic that is objectively measured by an imaging technique, which is used as an indicator of pharmacological response to a therapy) and surrogate endpoints have shown to facilitate the use of small group sizes, obtaining quick results with good statistical power. [ 33 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_279", "text": "Imaging is able to reveal subtle change that is indicative of the progression of therapy that may be missed out by more subjective, traditional approaches. Statistical bias is reduced as the findings are evaluated without any direct patient contact."}
{"_id": "WikiPedia_Radiology$$$corpus_280", "text": "Imaging techniques such as  positron emission tomography  (PET) and  magnetic resonance imaging  (MRI) are routinely used in oncology and neuroscience areas. [ 34 ] [ 35 ] [ 36 ] [ 37 ]  For example, measurement of  tumour  shrinkage is a commonly used surrogate endpoint in solid tumour response evaluation. This allows for faster and more objective assessment of the effects of anticancer drugs. In  Alzheimer's disease ,  MRI  scans of the entire brain can accurately assess the rate of hippocampal atrophy, [ 38 ] [ 39 ]  while PET scans can measure the brain's metabolic activity by measuring regional glucose metabolism, [ 33 ]  and beta-amyloid plaques using tracers such as  Pittsburgh compound B  (PiB). Historically less use has been made of quantitative medical imaging in other areas of  drug development  although interest is growing. [ 40 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_281", "text": "An imaging-based trial will usually be made up of three components:"}
{"_id": "WikiPedia_Radiology$$$corpus_282", "text": "Medical imaging can lead to patient and healthcare provider harm through exposure to  ionizing radiation ,  iodinated contrast ,  magnetic fields , and other hazards. [ 41 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_283", "text": "Lead  is the main material used for  radiographic shielding  against scattered X-rays."}
{"_id": "WikiPedia_Radiology$$$corpus_284", "text": "In  magnetic resonance imaging , there is  MRI RF shielding  as well as  magnetic shielding  to prevent external disturbance of image quality. [ 42 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_285", "text": "Medical imaging are generally covered by laws of  medical privacy . For example, in the United States the  Health Insurance Portability and Accountability Act  (HIPAA) sets restrictions for health care providers on utilizing  protected health information , which is any individually identifiable information relating to the past, present, or future physical or mental health of any individual. [ 43 ]  While there has not been any definitive legal decision in the matter, at least one study has indicated that medical imaging may contain biometric information that can uniquely identify a person, and so may qualify as PHI. [ 44 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_286", "text": "The UK General Medical Council's ethical guidelines indicate that the Council does not require consent prior to making recordings of X-ray images. [ 45 ]  However, the same guidance indicates that the images and recordings need to be anonimized, and acknowledges that in deciding whether a recording is anonymised, one should bear in mind that apparently insignificant details may still be capable of identifying a patient. As such, one should be particularly careful about the anonymity of a recordings of an X-ray image before using or publishing them without consent in journals and other learning materials, whether they are printed or in an electronic format. [ 46 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_287", "text": "Organizations in the medical imaging industry include manufacturers of imaging equipment, freestanding radiology facilities, and hospitals."}
{"_id": "WikiPedia_Radiology$$$corpus_288", "text": "The global market for manufactured devices was estimated at $5 billion in 2018. [ 47 ] [ 48 ]  Notable manufacturers as of 2012 included  Fujifilm , GE HealthCare ,  Siemens Healthineers ,  Philips ,  Shimadzu ,  Toshiba ,  Carestream Health ,  Hitachi ,  Hologic , and  Esaote . [ 49 ]  In 2016, the manufacturing industry was characterized as oligopolistic and mature; new entrants included in  Samsung  and  Neusoft Medical . [ 50 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_289", "text": "In the United States, as estimate as of 2015 places the US market for imaging scans at about $100b, with 60% occurring in hospitals and 40% occurring in freestanding clinics, such as the  RadNet  chain. [ 51 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_290", "text": "As per chapter 300 of the  Compendium of U.S. Copyright Office Practices , \"the Office will not register works produced by a machine or mere mechanical process that operates randomly or automatically without any creative input or intervention from a human author\" including \"Medical imaging produced by X-rays, ultrasounds, magnetic resonance imaging, or other diagnostic equipment.\" [ 52 ]  This position differs from the broad copyright protections afforded to photographs. While the Copyright Compendium is an agency statutory interpretation and not legally binding, courts are likely to give deference to it if they find it reasonable. [ 53 ]  Yet, there is no U.S. federal case law directly addressing the issue of the copyrightability of X-ray images."}
{"_id": "WikiPedia_Radiology$$$corpus_291", "text": "An extensive definition of the term  derivative work  is given by the United States Copyright Act in  17\u00a0U.S.C. \u00a0 \u00a7\u00a0101 :"}
{"_id": "WikiPedia_Radiology$$$corpus_292", "text": "A \"derivative work\" is a work based upon one or more preexisting works, such as a translation... [ note 1 ]  art reproduction, abridgment, condensation, or any other form in which a work may be recast, transformed, or adapted. A work consisting of editorial revisions, annotations, elaborations, or other modifications which, as a whole, represent an original work of authorship, is a \"derivative work\"."}
{"_id": "WikiPedia_Radiology$$$corpus_293", "text": "17\u00a0U.S.C. \u00a0 \u00a7\u00a0103(b)  provides:"}
{"_id": "WikiPedia_Radiology$$$corpus_294", "text": "The copyright in a compilation or derivative work extends only to the material contributed by the author of such work, as distinguished from the preexisting material employed in the work, and does not imply any exclusive right in the preexisting material. The copyright in such work is independent of, and does not affect or enlarge the scope, duration, ownership, or subsistence of, any copyright protection in the preexisting material."}
{"_id": "WikiPedia_Radiology$$$corpus_295", "text": "In Germany,  X-ray images  as well as  MRI ,  medical ultrasound ,  PET  and  scintigraphy  images are protected by (copyright-like)  related rights or neighbouring rights . [ 54 ]  This protection does not require creativity (as would be necessary for  regular  copyright protection) and lasts only for 50 years after image creation, if not published within 50 years, or for 50 years after the first legitimate publication. [ 55 ]  The letter of the law grants this right to the \"Lichtbildner\", [ 56 ]  i.e. the person who created the image. The literature seems to uniformly consider the medical doctor, dentist or veterinary physician as the rights holder, which may result from the circumstance that in Germany many X-rays are performed in ambulatory settings."}
{"_id": "WikiPedia_Radiology$$$corpus_296", "text": "Medical images created in the United Kingdom will normally be protected by copyright due to \"the high level of skill, labour and judgement required to produce a good quality X-ray, particularly to show contrast between bones and various soft tissues\". [ 57 ]  The Society of Radiographers believe this copyright is owned by employer (unless the radiographer is self-employed\u2014though even then their contract might require them to transfer ownership to the hospital). This copyright owner can grant certain permissions to whoever they wish, without giving up their ownership of the copyright. So the hospital and its employees will be given permission to use such radiographic images for the various purposes that they require for medical care. Physicians employed at the hospital will, in their contracts, be given the right to publish patient information in journal papers or books they write (providing they are made anonymous). Patients may also be granted permission to \"do what they like with\" their own images."}
{"_id": "WikiPedia_Radiology$$$corpus_297", "text": "The  Cyber Law in Sweden  states: \"Pictures can be protected as photographic works or as photographic pictures. The former requires a higher level of originality; the latter  protects all types of photographs, also the ones taken  by amateurs, or  within medicine  or science. The protection requires some sort of photographic technique being used, which includes digital cameras as well as holograms created by laser technique. The difference between the two types of work is the term of protection, which amounts to seventy years after the death of the author of a photographic work as opposed to fifty years, from the year in which the photographic picture was taken.\" [ 58 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_298", "text": "Medical imaging may possibly be included in the scope of \"photography\", similarly to a U.S. statement that \"MRI images, CT scans, and the like are analogous to photography.\" [ 59 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_299", "text": "Nuclear Medicine and Biology  is a  peer-reviewed   medical journal  published by  Elsevier  that covers research on all aspects of  nuclear medicine , including  radiopharmacology ,  radiopharmacy  and clinical studies of targeted  radiotracers . It is the official journal of the  Society of Radiopharmaceutical Sciences . According to the  Journal Citation Reports , the journal has a 2011  impact factor  of 3.023. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_300", "text": "The journal is abstracted and indexed in:"}
{"_id": "WikiPedia_Radiology$$$corpus_301", "text": "This  nuclear magnetic resonance \u2013related article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Radiology$$$corpus_302", "text": "This article about a  medical journal  is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Radiology$$$corpus_303", "text": "See tips for writing articles about academic journals . Further suggestions might be found on the article's  talk page ."}
{"_id": "WikiPedia_Radiology$$$corpus_304", "text": "This  nuclear medicine  article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Radiology$$$corpus_305", "text": "Nuclear Medicine Communications  ( abbreviated  Nucl. Med. Commun.)  is an official journal of the  British Nuclear Medicine Society  based in  Nottingham ,  United Kingdom . [ 1 ] [ 2 ]  The journal publishes studies based on  radionuclide   imaging  for basic, preclinical, and clinical research. Areas of interest include  radiochemistry ,  radiopharmacy ,  radiobiology ,  radiopharmacology ,  medical physics ,  computing  and  engineering , and technical and  nursing  professions involved in delivering nuclear medicine services."}
{"_id": "WikiPedia_Radiology$$$corpus_306", "text": "Nucl. Med. Commun.  has an  impact factor  of 1.465 and currently ranks 96 among the 129 journals publishing  radiology ,  nuclear medicine , and  medical imaging  scientific studies  [ citation needed ] . It has an International Standard Serial Number ( ISSN ) 0143-3636, and an online ISSN 1473-5628. The journal publishes 12 issues each year. [ 3 ]  The journal allows scientific manuscripts to be published at no charge to the authors, however, the manuscript are not open-access. Authors can pay a fee for the accepted articles to be published as open-access material."}
{"_id": "WikiPedia_Radiology$$$corpus_307", "text": "The  Nucl. Med. Commun.  journal published its first journal in March 1980. [ 4 ]  The website is operated from Riverwoods, IL,  United States . [ 5 ]  The current  editor-in-chief  is Professor  Jamshed Bmanji  based at the  University College Hospital , London. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_308", "text": "The history of pursuing  nuclear medicine  goes back to 1956, when the  Pakistan Atomic Energy Commission  (PAEC) was established under the executive order of the  Prime Minister of Pakistan ,  Huseyn Shaheed Suhrawardy . The PAEC, the scientific body that  is responsible for establishing the nuclear power plants in the country, has sat up a Nuclear Medicines laboratory. The PAEC also sat up the nuclear medicines lab and facilities throughout the country to fight against Cancer. Pakistan Atomic Energy Commission had provided the facilities of diagnosis and treatment of cancer and allied diseases to the patients from all over the country employing Nuclear Techniques at its Medical Centers. PAEC also sponsored the research program in the field of radiochemistry and biochemistry. PAEC also sat up the research institutes all over the country, some of them are below:"}
{"_id": "WikiPedia_Radiology$$$corpus_309", "text": "Nuclear medicine physicians , also called  nuclear   radiologists  or simply nucleologists, [ 1 ] [ 2 ]  are  medical  specialists that use tracers, usually  radiopharmaceuticals , for diagnosis and therapy.   Nuclear medicine  procedures are the major clinical applications of  molecular imaging  and molecular therapy. [ 3 ] [ 4 ] [ 5 ]  In the United States, nuclear medicine physicians are certified by the  American Board of Nuclear Medicine  and the  American Osteopathic Board of Nuclear Medicine ."}
{"_id": "WikiPedia_Radiology$$$corpus_310", "text": "In 1896,  Henri Becquerel  discovered  radioactivity . [ 6 ]   It was only a little over a quarter of a century (1925) until the first radioactive tracer study in animals was performed by  George de Hevesy , and the next year (1926) the first diagnostic tracer study in  humans  was performed by Herman Blumgart and Otto Yens. [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_311", "text": "Some of the earliest applications of radioisotopes were therapy of hematologic malignancies and therapy of both benign and malignant thyroid disease.  In the 1950s  radioimmunoassay  was developed by  Solomon Berson  and  Rosalyn Yalow .  Dr. Yalow was co-winner of the 1977 Nobel Prize in Physiology or Medicine (Dr. Berson had already died so was not eligible).  Radioimmunoassay was used extensively in clinical medicine but more recently has been largely replaced by non-radioactive methods."}
{"_id": "WikiPedia_Radiology$$$corpus_312", "text": "In 1950, human imaging of both  gamma  and  positron  emitting  radioisotopes  was performed.  Benedict Cassen 's work with a directional probe lead to the development of the first imaging with a  rectilinear scanner . [ 8 ]   Gordon Brownell developed the first  positron scanner . [ 9 ]   In the same decade (1954) the  Society of Nuclear Medicine  (SNM) was organized in Spokane, Washington (US), [ 10 ]  and (1958)  Hal Anger  developed the  gamma scintillation camera , [ 11 ]  which could image a whole region at the same time."}
{"_id": "WikiPedia_Radiology$$$corpus_313", "text": "Initial introduction of radioisotopes into medicine required individuals to acquire of a considerable background information which was foreign to their medical training.  Often a particular application drove the introduction of radioisotopes into a health care facility.  As other applications developed the physician or group that had developed knowledge of and experience with radioisotopes usually provided the new service.  Consequently, the radioisotope service found homes in several established specialties \u2013 commonly in radiology due to an interest in imaging, in pathology ( clinical pathology ) due to an interest in radioimmunoassay, and in endocrinology due to the early application of  131 I to thyroid disease. [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_314", "text": "Nuclear medicine became widespread and there was a need to develop a new specialty.  In the United States, the  American Board of Nuclear Medicine  was formed in 1972. [ 13 ]   At that time, the specialty include all of the uses of radioisotopes in medicine \u2013 radioimmunoassay, diagnostic imaging, and therapy.  As use of and experience with radioisotopes became more widespread in medicine, radioimmunoassay generally transferred from nuclear medicine to clinical pathology.  Today, nuclear medicine is based on the use of the  tracer principle  applied to diagnostic imaging and therapy."}
{"_id": "WikiPedia_Radiology$$$corpus_315", "text": "In the United States, the  Accreditation Council for Graduate Medical Education  (ACGME) and the  American Osteopathic Association Bureau of Osteopathic Specialists  (AOABOS) accredit nuclear medicine residency programs, and the  American Board of Nuclear Medicine  (ABNM) and the  American Osteopathic Board of Nuclear Medicine  (AOBNM) certify nuclear medicine physicians. After completing  medical school , a post-graduate  clinical year  is followed by three years of nuclear medicine  residency .  A common alternate path for physicians who have completed a radiology residency is a one-year residency in nuclear medicine, leading to sub-specialty certification by the American Board of Radiology.  A less common path for physicians who have completed another residency is a two-year residency in nuclear medicine. [ 15 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_316", "text": "Nuclear medicine procedures are performed by  Nuclear Medicine Radiographers , [ 16 ]  who require extensive training both in underlying principles (physics, instrumentation) but also in the clinical applications.   Nursing  support, especially in the hospital setting, is valuable, but may be shared with other services.  Nuclear medicine is a technology embedded specialty depending upon a large number of non-physician professional, including  medical physicists ,  health physicists ,  radiobiologists ,  radiochemists , and  radiopharmacists ."}
{"_id": "WikiPedia_Radiology$$$corpus_317", "text": "Residency trained nuclear medicine physicians have the most extensive training and highest level of certification, including all aspects of diagnosis and radionuclide therapy.  However, current U.S. regulations do not prohibit other physicians from interpreting nuclear medicine studies and perform radionuclide therapy.   Radiologists  who are not sub-specialty trained in the specialty, nonetheless often limit their practice to practicing nuclear medicine.  Some  cardiologists , especially non-invasive cardiologists, will interpret diagnostic cardiology studies including nuclear medicine studies.   Radiation oncologists  perform all forms of radiation therapy, sometimes including radionuclide therapy.  Some  endocrinologists  treat hyperthyroidism and thyroid cancer with  131 I.  The mix of physicians rendering nuclear medicine services varies both between different countries and within a single country."}
{"_id": "WikiPedia_Radiology$$$corpus_318", "text": "Nuclear pharmacy , also known as  radiopharmacy , involves preparation of  radioactive  materials for patient administration that will be used to diagnose and treat specific diseases in  nuclear medicine . It generally involves the practice of combining a  radionuclide tracer  with a pharmaceutical component that determines the biological localization in the patient. [ 1 ] [ 2 ]   Radiopharmaceuticals  are generally not designed to have a therapeutic effect themselves, but there is a risk to staff from  radiation exposure  and to patients from possible contamination in production. [ 3 ]  Due to these intersecting risks, nuclear pharmacy is a heavily regulated field. [ 4 ] [ 5 ]  The majority of diagnostic nuclear medicine investigations are performed using  technetium-99m . [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_319", "text": "The concept of nuclear pharmacy was first described in 1960 by Captain William H. Briner while at the  National Institutes of Health  (NIH) in  Bethesda, Maryland . Along with Mr. Briner, John E. Christian, who was a professor in the School of Pharmacy at  Purdue University , had written articles and contributed in other ways to set the stage of nuclear pharmacy. William Briner started the NIH Radiopharmacy in 1958. [ 7 ] [ 8 ]  John Christian and William Briner were both active on key national committees responsible for the development, regulation and utilization of radiopharmaceuticals. A  technetium-99m generator  was commercially available, followed by the availability of a number of Tc-99m based radiopharmaceuticals."}
{"_id": "WikiPedia_Radiology$$$corpus_320", "text": "In the  United States  nuclear pharmacy was the first  pharmacy  specialty established in 1978 by the  Board of Pharmacy Specialties . [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_321", "text": "Various models of production exist internationally. Institutional nuclear pharmacy is typically operated through large  medical centers  or  hospitals  while commercial centralized nuclear pharmacies provide their services to subscriber hospitals. They prepare and dispense radiopharmaceuticals as unit  doses  that are then delivered to the subscriber hospital by nuclear pharmacy personnel."}
{"_id": "WikiPedia_Radiology$$$corpus_322", "text": "A few basic steps are typically involved in technetium based preparations. First the active technetium is obtained from a  radionuclide generator  on site, which is then added to a non-radioactive kit containing the pharmaceutical component. Further steps may be required depending on the materials in question to ensure full  binding  of the two components. These procedures are usually carried out in a  clean room  or isolator to provide radiation shielding and sterile conditions. [ 10 ] [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_323", "text": "For  Positron Emission Tomography  (PET),  Fludeoxyglucose ( 18 F)  is the most common radiopharmaceutical, with the radioactive component usually obtained from a cyclotron. [ 11 ]  The short half life of  Fluorine-18  and many other PET  isotopes  necessitates rapid production. PET radiopharmaceuticals are now often produced by automated computer controlled systems to reduce complexity and radiation doses to staff. [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_324", "text": "Radiopharmacy is a heavily regulated field, as it combines several practices and fields which may come under the purview of multiple  regulators  and legislation. These include occupational exposure of staff to  ionising radiation , preparation of medicines, patient exposure to ionising radiation, transport of radioactive materials, and environmental exposure to ionising radiation. [ 13 ]  Different regulations may cover the various stages involved in radiopharmacies, ranging from production of \"cold\" (non-radioactive) kits, to the marketing and distribution of final products. [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_325", "text": "Staff working in nuclear pharmacies require extensive training on aspects of  good manufacturing practice ,  radiation safety  concerns and  aseptic dispensing . In the  United States  an authorised nuclear pharmacist must be a fully qualified pharmacist with evidence of additional training and qualification in nuclear pharmacy practice. [ 15 ]  Several  European Union   directives  cover radiopharmaceuticals as a special group of medicines, reflecting the wide range of types of producers and staff groups that may be involved. [ 16 ]  In the UK qualified pharmacists may be involved along with clinical scientists or technologists, with relevant training. [ 17 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_326", "text": "The  oxygen enhancement ratio  (OER) or  oxygen enhancement effect  in  radiobiology  refers to the enhancement of therapeutic or detrimental effect of  ionizing radiation  due to the presence of  oxygen . This so-called  oxygen effect [ 1 ]  is most notable when cells are exposed to an ionizing radiation  dose ."}
{"_id": "WikiPedia_Radiology$$$corpus_327", "text": "The OER is traditionally defined as the ratio of radiation doses during lack of oxygen compared to no lack of oxygen for the same biological effect. This may give varying numerical values depending on the chosen biological effect.  Additionally, OER may be presented in terms of hyperoxic environments and/or with altered oxygen baseline, complicating the significance of this value."}
{"_id": "WikiPedia_Radiology$$$corpus_328", "text": "The maximum OER depends mainly on the ionizing density or LET of the radiation. Radiation with higher  LET  and higher relative biological effectiveness (RBE) have a lower OER in mammalian cell tissues. [ 2 ]  The value of the maximum OER varies from about 1\u20134. The maximum OER ranges from about 2\u20134 for low-LET radiations such as X-rays, beta particles and gamma rays, whereas the OER is unity for high-LET radiations such as low energy alpha particles."}
{"_id": "WikiPedia_Radiology$$$corpus_329", "text": "The effect is used in  medical physics  to increase the effect of  radiation therapy  in  oncology  treatments. Additional oxygen abundance creates additional  free radicals  and increases the damage to the target tissue."}
{"_id": "WikiPedia_Radiology$$$corpus_330", "text": "In solid tumors the inner parts become less oxygenated than normal tissue and up to three times higher dose is needed to achieve the same  tumor control probability  as in tissue with normal oxygenation."}
{"_id": "WikiPedia_Radiology$$$corpus_331", "text": "The best known explanation of the  oxygen effect  is the oxygen fixation hypothesis which postulates that oxygen permanently fixes radical-induced DNA damage so it becomes permanent. [ 3 ]  Recently, it has been posited that the oxygen effect involves radiation exposures of cells causing their mitochondria to produce greater amounts of reactive oxygen species. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_332", "text": "Eric J. Hall and Amato J. Giaccia: Radiobiology for the radiologist, Lippincott Williams & Wilkins, 6th Ed., 2006"}
{"_id": "WikiPedia_Radiology$$$corpus_333", "text": "This  oncology  article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Radiology$$$corpus_334", "text": "Pentetic acid  or  diethylenetriaminepentaacetic acid  ( DTPA ) is an  aminopolycarboxylic acid  consisting of a  diethylenetriamine  backbone with five carboxymethyl groups. The molecule can be viewed as an expanded version of  EDTA  and is used similarly.  It is a white solid with limited solubility in water."}
{"_id": "WikiPedia_Radiology$$$corpus_335", "text": "The  conjugate base  of DTPA has a high affinity for metal  cations . Thus, the penta-anion DTPA 5\u2212  is potentially an  octadentate ligand  assuming that each nitrogen centre and each \u2013COO \u2212  group counts as a centre for coordination. The  formation constants  for its complexes are about 100 greater than those for EDTA. [ 3 ]   As a  chelating agent , DTPA wraps around a metal ion by forming up to eight bonds. Its complexes can also have an extra water molecule that coordinates the metal ion. [ 4 ]  Transition metals, however, usually form less than eight  coordination bonds . So, after forming a complex with a metal, DTPA still has the ability to bind to other reagents, as is shown by its derivative  pendetide . For example, in its complex with copper(II), DTPA binds in a hexadentate manner utilizing the three amine centres and three of the five carboxylates. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_336", "text": "Like the more common  EDTA , DTPA is predominantly used as  chelating  agent for complexing and   sequestering  metal ions."}
{"_id": "WikiPedia_Radiology$$$corpus_337", "text": "DTPA has been considered for treatment of radioactive materials such as  plutonium ,  americium , and other  actinides . [ 4 ]  In theory, these complexes are more apt to be eliminated in  urine . It is normally administered as the  calcium  or  zinc  salt (Ca or Zn-DTPA), since these ions are readily displaced by more highly charged cations and mainly to avoid to depleting them in the organism. DTPA forms complexes with  thorium (IV),  uranium (IV),  neptunium (IV), and  cerium (III/IV). [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_338", "text": "In August, 2004 the  US Food and Drug Administration  (USFDA) determined zinc-DTPA and calcium-DTPA to be safe and effective for treatment of those who have breathed in or otherwise been contaminated internally by plutonium, americium, or curium.  The recommended treatment is for an initial dose of calcium-DTPA, as this salt of DTPA has been shown to be more effective in the first 24 hours after internal contamination by plutonium, americium, or curium.  After that time has elapsed both calcium-DTPA and zinc-DTPA are similarly effective in reducing internal contamination with  plutonium ,  americium  or  curium , and zinc-DTPA is less likely to deplete the body's normal levels of zinc and other metals essential to health. Each drug can be administered by  nebulizer  for those who have breathed in contamination, and by  intravenous injection  for those contaminated by other routes. [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_339", "text": "DTPA is also used as  MRI   contrasting agent . DTPA improves the resolution of magnetic resonance imaging (MRI) by forming a soluble complex with a  gadolinium  (Gd 3+ ) ion, which alters the  magnetic resonance  behavior of the  protons  of the nearby  water molecules  and increases the images contrast. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_340", "text": "DTPA under the form of iron(II) chelate (Fe-DTPA, 10 \u2013 11 wt.\u00a0%) is also used as  aquarium plants   fertilizer . The more soluble form of iron, Fe(II), is a  micronutrient  needed by  aquatic plants . By binding to Fe 2+  ions DTPA prevents their  precipitation  as Fe(OH) 3 , or Fe 2 O 3  \u00b7 n H 2 O poorly soluble oxy-hydroxides after their  oxidation  by dissolved  oxygen . It increases the  solubility  of Fe 2+  and Fe 3+  ions in water, and therefore the  bioavailability  of iron for aquatic plants. It contributes so to maintain iron under a dissolved form (probably a mix of Fe(II) and Fe(III) DTPA complexes) in the  water column . It is unclear to what extent does DTPA really contribute to protect dissolved Fe 2+  against air oxidation and if the Fe(III)-DTPA complex cannot also be directly assimilated by aquatic plants simply because of its enhanced solubility. Under natural conditions,  i.e. , in the absence of complexing DTPA, Fe 2+  is more easily assimilated by most organisms, because of its 100-fold higher solubility than that of Fe 3+ ."}
{"_id": "WikiPedia_Radiology$$$corpus_341", "text": "In  pulp and paper mills  DTPA is also used to remove dissolved ferrous and ferric ions (and other redox-active metal ions, such as  Mn  or  Cu ) that otherwise would accelerate the  catalytic  decomposition of  hydrogen peroxide  (H 2 O 2  reduction by Fe 2+  ions according to the  Fenton reaction  mechanism). [ 9 ]  This helps preserving the  oxidation  capacity of the hydrogen peroxide stock which is used as  oxidizing agent  to  bleach pulp  in the chlorine-free process of paper making. [ 10 ]  Several thousands tons of DTPA are produced annually for this purpose in order to limit the non-negligible losses of H 2 O 2  by this mechanism. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_342", "text": "DTPA chelating properties are also useful in deactivating  calcium  and  magnesium  ions in  hair products . DTPA is used in over 150 cosmetic products. [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_343", "text": "DTPA is more effective than  EDTA  to deactivate redox-active metal ions such as Fe(II)/(III), Mn(II)/(IV) and Cu(I)/(II) perpetuating  oxidative damages  induced in  cells  by  superoxide  and  hydrogen peroxide . [ 12 ] [ 9 ]  DTPA is also used in  bioassays  involving redox-active metal ions."}
{"_id": "WikiPedia_Radiology$$$corpus_344", "text": "An unexpected negative environmental impact of chelating agents, as DTPA, is their toxicity for the  activated sludges  in the treatment of  Kraft pulping  effluents. [ 13 ]  Most of the DTPA worldwide production (several thousands of tons) [ 3 ]  is intended to avoid  hydrogen peroxide  decomposition by redox-active  iron  and  manganese  ions in the chlorine-free Kraft pulping processes (total chlorine free (TCF) and environmental chlorine free (ECF) processes). DTPA decreases the  biological oxygen demand  (BOD) of activated sludges and therefore their microbial activity."}
{"_id": "WikiPedia_Radiology$$$corpus_345", "text": "Compounds that are structurally related to DTPA are used in medicine, taking advantage of the high affinity of the triaminopentacarboxylate scaffold for metal ions."}
{"_id": "WikiPedia_Radiology$$$corpus_346", "text": "Positron emission tomography\u2013magnetic resonance imaging  ( PET\u2013MRI ) is a hybrid  imaging technology  that incorporates  magnetic resonance imaging  (MRI)  soft tissue  morphological imaging and  positron emission tomography  (PET)  functional imaging . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_347", "text": "The combination of PET and MRI was mentioned in a 1991 Phd thesis by R. Raylman. [ 2 ]  Simultaneous PET/MR detection was first demonstrated in 1997, however it took another 13 years, and new detector technologies, for clinical systems to become commercially available. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_348", "text": "Presently, the main clinical fields of PET-MRI are  oncology , [ 4 ] [ 5 ] [ 6 ]   cardiology , [ 7 ]   neurology , [ 8 ] [ 9 ] [ 10 ]  and  neuroscience . [ 11 ]  Research studies are actively conducted at the moment to understand benefits of the new PET-MRI diagnostic method. The technology combines the exquisite structural and functional characterization of tissue provided by MRI with the extreme sensitivity of PET imaging of metabolism and tracking of uniquely labeled cell types or cell receptors."}
{"_id": "WikiPedia_Radiology$$$corpus_349", "text": "Several companies offer clinical and pre-clinical combined PET-MR system; clinical systems are available from  United Imaging ,  Philips ,  Siemens , and  GE . There are varying approaches to the combination of the two technologies. Some designs are essentially separate machines, in the same room, with a bed that can transfer a patient from one scanner to another. [ 12 ] [ 13 ]  Fully integrated systems are the most technically challenging to achieve, but provide greatest benefits in terms of the ability to make simultaneous, exactly aligned, acquisitions. [ 14 ] [ 15 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_350", "text": "The first two clinical  whole body  PET-MRI systems were installed by Philips at Mount Sinai Medical Centre in the United States and at Geneva University Hospital in  Switzerland , in 2010. The system featured a PET and MRI scanner separated by a revolving bed. [ 16 ] [ 17 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_351", "text": "Siemens was the first company to offer simultaneous PET/MR acquisitions, with the first systems installed in 2010 based on  avalanche photodiode  detectors. [ 18 ] [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_352", "text": "Currently Siemens and GE are the only companies to offer a fully integrated whole body and simultaneous acquisition PET-MRI system. The Siemens system (Biograph mMR) received a  CE mark [ 19 ]  and  FDA  approval [ 20 ]  for customer purchase in 2011."}
{"_id": "WikiPedia_Radiology$$$corpus_353", "text": "The GE system (SIGNA PET/MR) received its 510K & CE mark in 2014. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_354", "text": "Currently, the combination of positron emission tomography (PET) and magnetic resonance imaging (MRI) as a hybrid imaging modality is receiving great attention not only in its emerging clinical applications but also in the preclinical field. Several designs based on several different types of PET detector technology have been developed in recent years, some of which have been used for first preclinical studies. [ 21 ] [ 22 ] [ 23 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_355", "text": "Several companies offer MR-compatible preclinical PET scanner inserts for use in the bore of an existing MRI, enabling simultaneous PET/MR image acquisition. [ 24 ] [ 25 ] [ 26 ] [ 27 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_356", "text": "The combination of PET with X-ray  computed tomography  (CT) is the more established PET imaging technology. With both PET-CT and PET-MR the intended advantage is to combine  functional imaging  provided by PET, with structural ( anatomical ) information from CT or MRI. Although images from different modalities collected at different scanning sessions can be overlaid by  image registration , a simultaneous acquisition offers better alignment of images and direct correlation. Combining imaging modalities in one single scanning session also has the advantage of reducing the number of appointments and therefore improving patient comfort. [ 28 ] [ 29 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_357", "text": "The same clinical decisions that would influence the choice between stand-alone CT or MR imaging would also determine areas where PET-CT or PET-MR would be preferred. [ 14 ]  For example, one advantage of MRI compared to CT is its superior soft tissue contrast, while CT has the advantage of being much faster than MRI."}
{"_id": "WikiPedia_Radiology$$$corpus_358", "text": "One clear advantage of PET-MR compared to PET-CT is the lower total  ionising radiation dose  obtained. For body PET-CT applications, the CT part of the examination constitutes approximately 60-80% of the radiation dose, with the remaining radiation dose originating from the PET  radiopharmaceutical . [ 30 ]  In contrast, no ionising radiation dose is obtained from MRI. PET-MR is therefore appealing in children, in particularly for serial follow-up examinations as used in oncology or chronic inflammatory conditions. [ 31 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_359", "text": "PET-MRI systems don't offer a direct way to obtain  attenuation  maps, unlike stand-alone PET or PET-CT systems. [ 32 ] [ 33 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_360", "text": "Stand alone PET systems' attenuation correction (AC) is based on a transmission scan (mu - map) acquired using a  68 Ge ( Germanium-68 ) rotating rod source, which directly measures photon attenuation at 511 keV. [ 32 ] [ 34 ]  PET-CT systems use a low-dose CT scan for AC. Since X-rays have a range of energies lower than 511 keV, AC values are closely approximated from  Hounsfield units . [ 35 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_361", "text": "There is no correlation between MR image intensity and electron intensity, therefore conversion of MR images into an attenuation map is difficult. [ 36 ] [ 32 ] [ 34 ]  This is an active area of research and a range of approaches have been developed. One method uses a Dixon  MRI sequence , and  segments  the resultant image into fat and water, with pre-set attenuation factors. Disadvantages of this method include a lack of bone attenuation, and loss of the true continuous range of attenuation factors. Comparisons with PET-CT attenuation maps for oncology purposes however have shown that this is a usable technique. [ 34 ]  The Dixon method can be combined with ultrashort echo time (UTE) sequences to better identify bone and increase the possible classes of tissue for segmentation. More sequences increase MRI acquisition time, and therefore the risk of motion artefacts. [ 37 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_362", "text": "In areas of the body with predictable structures (e.g. the head), segmentation (where tissue is categorised using the MRI image data), or \"atlas\" methods can be used. In atlas methods a standard MR image, with associated CT attenuation data, can be warped to fit the actual patient anatomy. Disadvantages of this method include difficulty with unusual anatomy, a need for a suitable library of images, and the need to account for MR coil attenuation. [ 34 ]  Synthetic, or Substitute CT (sCT) methods to generate CT like data from MRI are also of interest for  radiotherapy planning , and have been primarily investigated for sites in the head. While some of these use an atlas technique, many take a  voxel  approach where actual voxel intensities (contrast data) are used in combination with machine learning (trained on MR/CT data) to assign electron density values. [ 34 ] [ 38 ] [ 39 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_363", "text": "In many of the above methods,  MRI artifacts  (e.g. from physiological motion) can affect attenuation correction accuracy. [ 34 ] [ 40 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_364", "text": "PET radiotracer   is a type of  radioligand  that is used for the  diagnostic purposes  via  positron emission tomography  imaging technique. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_365", "text": "PET is a  functional imaging  technique that produces a three-dimensional image of functional processes in the body. The system detects pairs of  gamma rays  emitted indirectly by a  positron -emitting  radionuclide  ( tracer ), which is introduced into the body on a biologically active molecule. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_366", "text": "In  in vivo  systems it is often used to quantify the binding of a test molecule to the binding site of radioligand. The higher the affinity of the molecule the more radioligand is displaced from the binding site and the increasing radioactive decay can be measured by  scintillography . This assay is commonly used to calculate  binding constant  of molecules to receptors. Due to the probable injuries of PET-radiotracers, they could not be administered in the normal doses of the medications. Therefore, the binding affinity (P KD ) of the PET-tracers must be high. In addition, since via the PET imaging technique is desired to investigate a function accurately, the selectivity of bindings to the specific targets is very important. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_367", "text": "PET response criteria in solid tumors  ( PERCIST ) is a set of rules that define when tumors in cancer patients improve (\"respond\"), stay the same (\"stabilize\"), or worsen (\"progress\") during treatment, using  positron emission tomography  (PET). The criteria were published in May 2009 in the  Journal of Nuclear Medicine  (JNM). [ 1 ]  A  pooled analysis  from 2016 concluded that its application may give rather different results from  RECIST , and might be a more suitable tool for understanding tumor response to treatment. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_368", "text": "Complete metabolic response (CMR)"}
{"_id": "WikiPedia_Radiology$$$corpus_369", "text": "Partial metabolic response (PMR)"}
{"_id": "WikiPedia_Radiology$$$corpus_370", "text": "Stable metabolic disease (SMD)"}
{"_id": "WikiPedia_Radiology$$$corpus_371", "text": "Progressive metabolic disease (PMD)"}
{"_id": "WikiPedia_Radiology$$$corpus_372", "text": "Pretargeting  (imaging) is a tool for  nuclear medicine  and  radiotherapy .  Imaging  studies require a high contrast of target to background. This can be provided by using a  biomarker  which has a high affinity and specificity for its target (e.g. an  antibody )."}
{"_id": "WikiPedia_Radiology$$$corpus_373", "text": "Owing to their high affinity and specificity, antibodies have been considered as suitable vehicles for imaging and therapeutics, since the beginning of the 20th Century. [ 1 ] [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_374", "text": "The first radiolabelled antibodies were used in the early 1950s and got used for cancer therapy, [ 4 ] [ 5 ]  but it took roughly two more decades before it was demonstrated that they target human tumour associated antigens in cancer patients. [ 6 ]  Due to the  hybridoma technology  in 1975, monoclonal ( murine ) antibodies could easily be produced in practical amounts, [ 7 ]  consequently the number of studies increased drastically. However, these types of antibodies turned out to be quite troublesome, due to the triggering of the human anti-murine  antibody response . [ 8 ]  Consequently  chimeric ,  humanised  and  human monoclonal antibodies  have been created, produced and get used nowadays. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_375", "text": "Owing to the high  molecular weight  of antibodies and the  Fc domain  of the antibody, [ 10 ]  a slow  clearance  from the  blood  and non-target tissue occurs, which results in low tumour-to-blood and tumour-to-muscle ratios. [ 11 ] [ 12 ]  Because of this, antibodies which are going to be used for imaging purposes need to be labelled with  radionuclides  that have a long  half-life , [ 13 ]  which increases the  radiation dose  to the patient. This consequently encouraged the development of lower  molecular weight  antibodies and resulted in the development of minibodies, diabodies,  single chain variable fragments  (scFv) and single domain fragments (Fv). [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_376", "text": "To bypass the problem associated with the prolonged circulation time of radiolabelled antibodies, in the mid-1980s a strategy called pretargeted  radioimmunotherapy  was developed. [ 15 ] [ 16 ]  In short, this approach contained two important steps: 1. administration of a  macromolecular  targeting vector (usually antibody-based), and 2. a small radiolabelled molecule, which interacts with the targeting vector. Most importantly the small radiolabelled molecule gets injected after a predetermined lag period after which the macromolecule has had enough time to bind to its target and the residual unbound macromolecule to be cleared out of the system. [ 14 ]  To ensure sufficient interaction between the two components, suitable modifications with complementary species are required (like  bioorthogonal  modifications). [ 17 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_377", "text": "Pretargeting strategies can lead to an improved imaging contrast, as it combines the high target specificity and affinity of an antibody with the fast pharmacokinetic properties of a small molecule. The concept of pretargeting, although existing for several decades already, was limited to a few distinct classes. Developing chemical reactions that proceed quickly within living systems, without interacting with the large variety of existing functional groups, used to be an inherent difficulty. However, there have been several advancements in this area over the past few years. [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_378", "text": "The beginning of the pretargeting concept was based on  bispecific antibodies  which were able to bind a specific target  antigen  and a radiolabelled  hapten . [ 18 ] [ 19 ] [ 20 ] [ 21 ] [ 22 ] [ 23 ]  Possible was this approach because of the development of monoclonal Antibodies which could be connected to  radiometal  chelates. [ 15 ]  Also connecting two haptens via a two amino acid linker resulted in an enhancement effect of the affinity, which improved the uptake and retention of the radiolabelled compound without affecting the rapid clearance. [ 24 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_379", "text": "Limiting factor of this approach were the slow  binding constant  which was rarely higher than 10 \u221210  M, amongst other reasons. [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_380", "text": "After the discovery of the fast interaction between  Biotin  and  (Strept)Avidin , which show a high  binding affinity , this approach has been used in many different ways (e.g. for  protein purification  purposes like the  Step-tag ). [ 25 ] [ 26 ] [ 27 ] [ 28 ] [ 29 ] [ 30 ] [ 31 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_381", "text": "The  radioactive iodine uptake test  is a type of scan used in the diagnosis of  thyroid  problems, particularly  hyperthyroidism . It is entirely different from  radioactive iodine therapy  (RAI therapy), which uses much higher doses to destroy cancerous cells. The RAIU test is also used as a follow-up to RAI therapy to verify that no thyroid cells survived, which could still be cancerous. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_382", "text": "The patient swallows  a radioisotope  of  iodine  in the form of capsule or fluid, and the absorption (uptake) of this  radiotracer  by the thyroid is studied after 4\u20136 hours and after 24 hours with the aid of a  scintillation counter . The dose is typically 0.15\u20130.37  MBq  (4\u201310  \u03bcCi ) of  131 I iodide , or 3.7\u20137.4 MBq (100\u2013200 \u03bcCi) of  123 I iodide . [ 2 ]  The RAIU test is a reliable measurement when using a dedicated probe with a reproducibility of 1 percent and a 95%-least-significant-change of 3 percent. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_383", "text": "The normal uptake is between 15 and 25 percent, but this may be forced down if, in the meantime, the patient has eaten foods high in  iodine , such as dairy products and seafood. [ 4 ]  Low uptake suggests  thyroiditis , high uptake suggests  Graves' disease , [ 5 ]  and unevenness in uptake suggests the presence of a  nodule . [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_384", "text": "123 I has a shorter  half-life  than  131 I (a half day vs. 8.1 days), so use of  123 I exposes the body to less radiation, at the expense of less time to evaluate delayed scan images. [ 6 ]  Furthermore,  123 I emits  gamma radiation , while  131 I emits gamma and  beta radiation . [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_385", "text": "The test is inappropriate for patients who are pregnant or breastfeeding. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_386", "text": "A  radioactive nanoparticle  is a  nanoparticle  that contains  radioactive materials .  Radioactive nanoparticles have applications in  medical diagnostics ,  medical imaging ,  toxicokinetics , and  environmental health , and are being investigated for applications in  nuclear   nanomedicine .  Radioactive nanoparticles present special challenges in  operational health physics  and  internal dosimetry  that are not present for other substances, although existing  radiation protection  measures and  hazard controls for nanoparticles  generally apply."}
{"_id": "WikiPedia_Radiology$$$corpus_387", "text": "Engineered radioactive nanoparticles are used in  medical imaging  techniques such as  positron emission tomography  and  single-photon emission computed tomography , [ 2 ]  and an aerosol of carbon nanoparticles containing  technetium-99m  are used in a commercially available procedure for  ventilation/perfusion   scintigraphy  of the  lungs. [ 3 ] :\u200a122\u2013125\u200a   Engineered radioactive nanoparticles are also used as a  radiolabel  to detect the presence of the nanoparticles themselves in  environmental health  and  toxicokinetics  studies. [ 3 ] :\u200a119\u2013122"}
{"_id": "WikiPedia_Radiology$$$corpus_388", "text": "Engineered radioactive nanoparticles are being investigated for  therapeutic  use combining  nuclear medicine  with  nanomedicine , especially for cancer. [ 3 ] :\u200a125\u2013130\u200a   Neutron capture therapy  is one such potential application. [ 2 ] [ 4 ]   In addition, nanoparticles can help to sequester the toxic daughter nuclides of  alpha emitters  when used in radiotherapy. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_389", "text": "Nuclear imaging is non-invasive and has high sensitivity, and nanoparticles are useful as a platform for combining multiple copies of targeting vectors and effectors in order to selectively deliver radioisotopes to a specific region of interest. [ 5 ]   Other benefits of nanoparticles for diagnostic and therapeutic use include increased blood and tumor retention time, as well as the possibility of using their unique physical and chemical properties in treatment. [ citation needed ]   However, the nanoparticles must be engineered to avoid being recognized by the  mononuclear phagocyte system  and transported to the  liver  or  spleen , often through manipulating their surface functionalization. [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_390", "text": "Targeting techniques include functionalizing radioactive nanoparticles with  antibodies  to target them to a specific tissue, and using  magnetic nanoparticles  that are attracted to a magnet placed over the tumor site. [ 4 ]   Technetium-99m,  indium-111 , and  iodine-131  are common radioisotopes used for these purposes, [ 3 ] :\u200a119\u2013130\u200a [ 4 ]  with many others used as well. [ 6 ] [ 7 ]   Radioactive nanoparticles can be produced by either synthesizing the nanoparticles directly from the radioactive materials, or by irradiating non-radioactive particles with  neutrons  or  accelerated ions , sometimes  in situ . [ 3 ] :\u200a119\u200a [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_391", "text": "As with all nanoparticles, radioactive nanoparticles can also be naturally occurring or incidentally produced as a byproduct of industrial processes.  The main source of naturally occurring nanomaterials containing radionuclides is the decay of  radon  gas, whose immediate decay products are non-gaseous elements that precipitate into nanoscale particles along with atmospheric dust and vapors.  Minor natural sources include  primordial radionuclides  present in the nanoscale portion of  volcanic ash , and primordial and  cosmogenic nuclides  taken up by plants which are later burned.  Radioactive nanoparticles may be incidentally produced by procedures in the  nuclear industry  such as  nuclear reprocessing  and the cutting of contaminated objects. [ 3 ] :\u200a16\u201320"}
{"_id": "WikiPedia_Radiology$$$corpus_392", "text": "Radioactive nanoparticles combine the  hazards of radioactive materials  with the  hazards of nanomaterials. [ 3 ] :\u200a2\u20136\u200a   Inhalation exposure  is the most common route of exposure to airborne particles in the workplace.  Animal studies on some classes of nanoparticles indicate pulmonary effects including  inflammation ,  granulomas , and  pulmonary fibrosis , which were of similar or greater potency when compared with other known  fibrogenic  materials such as  silica ,  asbestos , and ultrafine  carbon black .  Some studies in cells or animals have shown  genotoxic  or  carcinogenic  effects, or systemic  cardiovascular  effects from pulmonary exposure. [ 9 ] [ 10 ]   The hazards of ionizing radiation depend on whether the exposure is  acute  or  chronic , and includes effects like  radiation-induced cancer  and  teratogenesis . [ 11 ] [ 12 ]   In some cases, the inherent physicochemical toxicity of the nanoparticle itself may lead to lower  exposure limits  than those associated with the radioactivity alone, which is not the case with most radioactive materials. [ 3 ] :\u200a2\u20136"}
{"_id": "WikiPedia_Radiology$$$corpus_393", "text": "Radioactive nanoparticles present special challenges in  operational health physics  and  internal dosimetry  that are not present for other substances, as the nanoparticles'  toxicokinetics  depend on their physical and chemical properties including  size ,  shape , and  surface chemistry .  For example, inhaled nanoparticles will deposit in different locations in the lungs, and will be metabolized and transported through the body differently, than vapors or larger particles. [ 3 ] :\u200a2\u20136\u200a   There may also be hazards from associated processes such as strong magnetic fields and  cryogens  used in imaging equipment, and handling of lab animals in experimental studies. [ 13 ]   Effective risk assessment and communication is important, as both nanotechnology and radiation have unique considerations with public perception. [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_394", "text": "In general, most elements of a standard  radiation protection  program are applicable to radioactive nanomaterials, and many  hazard controls for nanomaterials  will be effective with the radioactive versions.  The  hierarchy of hazard controls  encompasses a succession of five categories of control methods to reduce the risk of illness or injury.  The two most effective are  elimination  and  substitution , for example reducing dust exposure by eliminating a  sonication  process or substituting a nanomaterial  slurry  or  suspension  in a liquid solvent instead of a dry powder.  Substitutions should consider both the radioactivity and physicochemical hazards of all the options, and also take into account that radioactive nanomaterials are easier to detect than non-radioactive substances. [ 3 ] :\u200a2\u20136,\u200a35\u201341"}
{"_id": "WikiPedia_Radiology$$$corpus_395", "text": "Engineering controls  should be the primary form of protection, including local exhaust systems such as  fume hoods ,  gloveboxes ,  biosafety cabinets , and  vented balance enclosures ;  radiation shielding ; and  access control  systems. [ 3 ] :\u200a41\u201348\u200a   The need for  negative room pressure  to prevent contamination of outside areas can conflict with the customary use of  positive pressure  when pharmaceuticals are being handled, although this can be overcome through use of a cascade pressure system, or by handling nanomaterials in enclosures. [ 13 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_396", "text": "Administrative controls  include procedures to limit radiation doses, and  contamination control  procedures including encouraging good work practices and monitoring for contamination.   Personal protective equipment  is the least effective and should be used in conjunction with other hazard controls.  In general, personal protective equipment intended for radioactive materials should be effective with radioactive nanomaterials, including impervious  laboratory coats ,  goggles ,  safety gloves , and in some cases  respirators , although the greater potential penetration through clothing and mobility in air of nanoparticles should be taken into account. [ 3 ] :\u200a48\u201363"}
{"_id": "WikiPedia_Radiology$$$corpus_397", "text": "Radioimmunodetection  is an  imaging technique  using radiolabeled  antibodies . [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_398", "text": "This  immunology  article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Radiology$$$corpus_399", "text": "A  radionuclide generator  is a device which provides a local supply of a short-lived  radioactive  substance from the decay of a longer-lived parent  radionuclide . They are commonly used in  nuclear medicine  to supply a  radiopharmacy . [ 1 ]  The generator provides a way to separate the desired product from the parent, typically in a process that can be repeated several times over the life of the parent. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_400", "text": "Use of a generator avoids the challenge of distributing short-lived radionuclides from the original production site (typically a  nuclear reactor ) to individual users; the loss of  activity  due to decay in transit can result in too little being supplied or the need for much larger initial quantities to be sent out (incurring additional production and transport costs). [ 4 ]  An alternative to generators for on-site production of radionuclides is a  cyclotron , though it is uncommon that the same radionuclide can be provided by both methods. It is feasible to have cyclotrons at larger centres, but they are much more expensive and complex than generators. In some cases a cyclotron is used to produce the parent radionuclide for a generator. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_401", "text": "Long-lived radionuclides which are administered to a patient with a view to utilising useful properties of a daughter product have been termed  in-vivo  generators, though they are not routinely used clinically. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_402", "text": "Radionuclide therapy  ( RNT , also known as  unsealed source radiotherapy  or  molecular radiotherapy ) uses  radioactive  substances called  radiopharmaceuticals  to treat medical conditions, particularly  cancer . These are introduced into the body by various means ( injection  or  ingestion  are the two most commonplace) and localise to specific locations,  organs  or tissues depending on their properties and administration routes. This includes anything from a simple compound such as  sodium iodide  that locates to the  thyroid  via trapping the iodide ion, to complex biopharmaceuticals such as recombinant antibodies which are attached to radionuclides and seek out specific  antigens  on cell surfaces. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_403", "text": "This is a type of targeted therapy which uses the physical, chemical and biological properties of the radiopharmaceutical to target areas of the body for radiation treatment. [ 3 ]  The related diagnostic modality of  nuclear medicine  employs the same principles but uses different types or quantities of radiopharmaceuticals in order to  image  or analyse functional systems within the patient."}
{"_id": "WikiPedia_Radiology$$$corpus_404", "text": "RNT contrasts with sealed-source therapy ( brachytherapy ) where the radionuclide remains in a capsule or metal wire during treatment and needs to be physically placed precisely at the treatment position. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_405", "text": "When the radionuclides are  ligands  (such as with  Lutathera  and  Pluvicto ), the technique is also known as  radioligand therapy .\n [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_406", "text": "Iodine-131  ( 131 I) is the most common RNT worldwide and uses the simple compound  sodium iodide  with a radioactive isotope of  iodine . The patient (human or animal) may ingest an oral solid or liquid amount or receive an intravenous injection of a solution of the compound. The iodide ion is selectively taken up by the  thyroid  gland. Both benign conditions like  thyrotoxicosis  and certain malignant conditions like  papillary thyroid cancer  can be treated with the radiation emitted by  radioiodine . [ 6 ]  Iodine-131 produces  beta  and  gamma  radiation. The beta radiation released damages both normal thyroid tissue and any thyroid cancer that behaves like normal thyroid in taking up iodine, so providing the therapeutic effect, whilst most of the gamma radiation escapes the patient's body. [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_407", "text": "Most of the iodine not taken up by thyroid tissue is  excreted  through the  kidneys  into the  urine . After radioiodine treatment the urine will be radioactive or 'hot', and the patients themselves will also emit  gamma radiation . Depending on the amount of radioactivity administered, it can take several days for the radioactivity to reduce to the point where the patient does not pose a  radiation hazard  to bystanders. Patients are often treated as  inpatients  and there are international guidelines, as well as legislation in many countries, which govern the point at which they may return home. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_408", "text": "Radium-223  chloride,  strontium-89  chloride and  samarium-153   EDTMP  are used to treat  secondary cancer  in the bones. [ 9 ] [ 10 ]   Radium  and  strontium  mimic calcium in the body. [ 11 ]   Samarium  is bound to tetraphosphate  EDTMP , phosphates are taken up by  osteoblastic  (bone forming) repairs that occur adjacent to some metastatic lesions. [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_409", "text": "Beta  emitting  phosphorus-32  ( 32 P), as sodium phosphate, is used to treat  overactive   bone marrow , in which it is otherwise naturally metabolised. [ 13 ] [ 14 ] [ 15 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_410", "text": "An  yttrium-90  ( 90 Y)  colloidal  suspension is used for  radiosynovectomy  in the  knee  joint. [ 16 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_411", "text": "90 Y in the form of a  resin  or glass spheres can be used to treat primary and metastatic liver cancers. [ 17 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_412", "text": "131 I-mIBG ( metaiodobenzylguanidine ) is used for the treatment of  phaeochromocytoma  and  neuroblastoma . [ 18 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_413", "text": "177 Lu is bound with a  DOTA   chelator  to target  neuroendocrine tumours . [ 19 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_414", "text": "At the  Institute for Transuranium Elements  (ITU) work is being done on alpha-immunotherapy, this is an experimental method where antibodies bearing  alpha  isotopes are used.  Bismuth-213  is one of the isotopes which has been used. This is made by the alpha decay of  actinium-225 . The generation of one short-lived isotope from longer lived isotope is a useful method of providing a portable supply of a short-lived isotope. This is similar to the generation of  technetium-99m  by a  technetium generator . The actinium-225 is made by the irradiation of  radium-226  with a  cyclotron . [ 20 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_415", "text": "Targeted alpha-particle therapy  (or  TAT ) is an in-development method of targeted  radionuclide  therapy of various  cancers . It employs  radioactive  substances which undergo  alpha decay  to treat diseased tissue at close proximity. [ 1 ]  It has the potential to provide highly targeted treatment, especially to  microscopic   tumour   cells . Targets include  leukemias ,  lymphomas ,  gliomas ,  melanoma , and  peritoneal carcinomatosis . [ 2 ]  As in diagnostic  nuclear medicine , appropriate radionuclides can be  chemically bound  to a targeting  biomolecule  which carries the combined  radiopharmaceutical  to a specific treatment point. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_416", "text": "It has been said that \"\u03b1-emitters are indispensable with regard to optimisation of strategies for tumour therapy\". [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_417", "text": "The primary advantage of  alpha particle  (\u03b1) emitters over other types of radioactive sources is their very high  linear energy transfer  (LET) and  relative biological effectiveness  (RBE). [ 5 ]   Beta particle  (\u03b2) emitters such as  yttrium-90  can travel considerable distances beyond the immediate tissue before depositing their energy, while alpha particles deposit their energy in 70\u2013100\u2009\u03bcm long tracks. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_418", "text": "Alpha particles are more likely than other types of radiation to cause  double-strand breaks  to DNA molecules, which is one of several effective causes of  cell death . [ 7 ] [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_419", "text": "Some \u03b1 emitting isotopes such as  225 Ac  and  213 Bi  are only available in limited quantities from  229 Th  decay, although  cyclotron  production is feasible. [ 9 ] [ 10 ] [ 11 ]  Among alpha-emitting radiometals according to availability, chelation chemistry, and half-life,  212 Pb  is also a promising candidate for targeted alpha-therapy. [ 12 ] [ 13 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_420", "text": "The ARRONAX cyclotron can produce  211 At  by irradiation of  209 Bi . [ 14 ] [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_421", "text": "Though many \u03b1-emitters exist, useful isotopes would have a sufficient energy to cause damage to cancer cells, and a  half-life  that is long enough to provide a therapeutic  dose  without remaining long enough to damage healthy tissue."}
{"_id": "WikiPedia_Radiology$$$corpus_422", "text": "Several radionuclides have been studied for use in  immunotherapy . Though \u03b2-emitters are more popular, in part due to their availability, trials have taken place involving  225 Ac,  211 At,  212 Pb and  213 Bi. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_423", "text": "Treatment of peritoneal carcinomas has promising early results limited by availability of \u03b1-emitters compared to \u03b2-emitters. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_424", "text": "223 Ra  was the first \u03b1-emitter approved by the  FDA  in the United States for treatment of  bone metastases  from  prostate cancer , and is a recommended treatment in the UK by  NICE . [ 3 ] [ 15 ]  In a  phase III trial  comparing  223 Ra  to a  placebo , survival was significantly improved. [ 16 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_425", "text": "Early trials of  225 Ac and  213 Bi have shown evidence of anti-tumour activity in  Leukaemia  patients. [ 17 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_426", "text": "Phase I trials on  melanomas  have shown  213 Bi is effective in causing tumour  regression . [ 18 ] [ 19 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_427", "text": "The short  path length  of alpha particles in tissue, which makes them well suited to treatment of the above types of disease, is a negative when it comes to treatment of larger bodies of  solid tumour  by intravenous injection. [ 20 ] [ 21 ]  Potential methods to solve this problem of delivery exist, such as direct intratumoral injection [ 22 ]  and  anti-angiogenic drugs . [ 23 ] [ 3 ]  Limited treatment experience of low grade malignant  gliomas  has shown possible efficacy. [ 24 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_428", "text": "The  Therac-25  is a computer-controlled  radiation therapy  machine produced by  Atomic Energy of Canada Limited  (AECL) in 1982 after the Therac-6 and Therac-20 units (the earlier units had been produced in partnership with  Compagnie g\u00e9n\u00e9rale de radiologie (CGR)  of France). [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_429", "text": "The Therac-25 was involved in at least six accidents between 1985 and 1987, in which some patients were given massive  overdoses of radiation . [ 2 ] :\u200a 425 \u200a  Because of  concurrent programming errors  (also known as race conditions), it sometimes gave its patients radiation doses that were hundreds of times greater than normal, resulting in death or serious injury. [ 3 ]  These accidents highlighted the dangers of software  control  of safety-critical systems."}
{"_id": "WikiPedia_Radiology$$$corpus_430", "text": "The Therac-25 has become a standard case study in  health informatics ,  software engineering , and  computer ethics . It highlights the dangers of engineer overconfidence [ 2 ] :\u200a 428 \u200a  after the engineers dismissed end-user reports, leading to severe consequences."}
{"_id": "WikiPedia_Radiology$$$corpus_431", "text": "The French company CGR manufactured the  Neptune  and  Sagittaire  linear accelerators."}
{"_id": "WikiPedia_Radiology$$$corpus_432", "text": "In the early 1970s, CGR and the Canadian public company  Atomic Energy of Canada Limited  (AECL) collaborated on the construction of linear accelerators controlled by a DEC  PDP-11  minicomputer: the Therac-6, which produced X-rays of up to 6 MeV, and the Therac-20, which could produce X-rays or electrons of up to 20 MeV. The computer increased ease of use because the accelerator could operate without it. CGR developed the software for the Therac-6 and reused some subroutines for the Therac-20. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_433", "text": "In 1981, the two companies ended their collaboration agreement. AECL developed a new double pass concept for electron acceleration in a more confined space, changing its energy source from  klystron  to  magnetron . In certain techniques, the electrons produced are used directly, while in others they are made to collide against a tungsten anode to produce X-ray beams. This dual accelerator concept was applied to the Therac-20 and Therac-25, with the latter being much more compact, versatile, and easy to use. It was also more economical for a hospital to have a dual machine that could apply treatments of electrons and X-rays, instead of two machines."}
{"_id": "WikiPedia_Radiology$$$corpus_434", "text": "The Therac-25 was designed as a machine controlled by a computer, with some safety mechanisms switched from hardware to software as a result. AECL decided not to duplicate some safety mechanisms, and reused modules and code routines from the Therac-20 for the Therac-25."}
{"_id": "WikiPedia_Radiology$$$corpus_435", "text": "The first prototype of the Therac-25 was built in 1976 and was put on the market in late 1982."}
{"_id": "WikiPedia_Radiology$$$corpus_436", "text": "The software for the Therac-25 was developed by one person over several years using PDP-11 assembly language. It was an evolution of the Therac-6 software. In 1986, the programmer left AECL. In a subsequent lawsuit, lawyers were unable to identify the programmer or learn about his qualification and experience."}
{"_id": "WikiPedia_Radiology$$$corpus_437", "text": "Five machines were installed in the United States and six in Canada. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_438", "text": "After the accidents, in 1988 AECL dissolved the  AECL Medical  section and the company  Theratronics International Ltd  took over the maintenance of the installed Therac-25 machines. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_439", "text": "The machine had three modes of operation, with a turntable moving some apparatus into position for each of those modes: either a light, some  scan magnets , or a tungsten target and  flattener . [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_440", "text": "The patient is placed on a fixed stretcher. Above them is a turntable to which the components that modify the electron beam are fixed. The turntable has a position for the X-ray mode (photons), another position for the electron mode and a third position for making adjustments using visible light. In this position an electron beam is not expected, and a light that is reflected in a stainless steel mirror simulates the beam. In this position there is no ion chamber acting as a radiation dosimeter because the radiation beam is not expected to function."}
{"_id": "WikiPedia_Radiology$$$corpus_441", "text": "The turntable has some  microswitches  that indicate the position to the computer. When the plate is in one of the three allowed fixed positions a plunger locks it by  interlocking . In this type of machine, electromechanical locks were traditionally used to ensure that the turntable was in the correct position before starting treatment. In the Therac-25, these were replaced by software checks. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_442", "text": "The six documented accidents occurred when the high-current electron beam generated in X-ray mode was delivered directly to patients. Two software faults were to blame. [ 6 ]  One was when the operator incorrectly selected X-ray mode before quickly changing to electron mode, which allowed the electron beam to be set for X-ray mode without the X-ray target being in place. A second fault allowed the electron beam to activate during field-light mode, during which no beam scanner was active or target was in place."}
{"_id": "WikiPedia_Radiology$$$corpus_443", "text": "Previous models had hardware interlocks to prevent such faults, but the Therac-25 had removed them, depending instead on software checks for safety."}
{"_id": "WikiPedia_Radiology$$$corpus_444", "text": "The high-current electron beam struck the patients with approximately 100 times the intended dose of radiation, and over a narrower area, delivering a potentially lethal dose of  beta radiation . The feeling was described by patient Ray Cox as \"an intense electric shock\", causing him to scream and run out of the treatment room. [ 7 ]  Several days later,  radiation burns  appeared, and the patients showed the symptoms of  radiation poisoning ; in three cases, the injured patients later died as a result of the overdose. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_445", "text": "A Therac-25 had been in operation for six months in  Marietta, Georgia  at the Kennestone Regional Oncology Center when, on June 3, 1985, applied radiation therapy treatment following a  lumpectomy  was being performed on 61-year-old woman Katie Yarbrough. She was set to receive a 10-MeV dose of electron therapy to her  clavicle . When therapy began, she stated she experienced a \"tremendous force of heat...this red-hot sensation.\" The technician entered the room, to whom Katie stated, \"you burned me.\" The technician assured her this was not possible. She returned home where, in the following days, she experienced reddening of the treatment area. Shortly after, her shoulder became locked in place and she experienced spasms. Within two weeks, the aforementioned redness spread from her chest to her back, indicating that the source of the burn had passed through her, which is the case with radiation burns. The staff at the treatment center did not believe it was possible for the Therac-25 to cause such an injury, and it was treated as a symptom of her  cancer . Later, the hospital physicist consulted the AECL about the incident. He calculated that the applied dose was between 15,000 and 20,000 rad (radiation absorbed dose) when she should have been dosed with 200 rad. A dose of 1000 rad can be fatal. In October 1985, Katie sued the hospital and the manufacturer of the machine. In November 1985, the AECL was notified of the lawsuit. It was not until March 1986, after another incident involving the Therac-25, that the AECL informed the FDA that it had received a complaint from the patient."}
{"_id": "WikiPedia_Radiology$$$corpus_446", "text": "Due to the radiation overdose, her breast had to be surgically removed, an arm and shoulder were immobilized, and she was in constant pain. The treatment printout function was not activated at the time of treatment and there was no record of the applied radiation data. An out-of-court settlement was reached to resolve the lawsuit. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_447", "text": "The Therac-25 had been in operation in the clinic for six months when, on July 26, 1985, a 40-year-old patient was receiving her 24th treatment for  cervical cancer . The operator activated the treatment, but after five seconds the machine stopped with the error message \"H-tilt\", the treatment pause indication and the dosimeter indicating that no radiation had been applied. The operator pressed the  P  key (Proceed\u00a0: continue). The machine stopped again. The operator repeated the process five times until the machine stopped the treatment. A technician was called and found no problem. The machine was used to treat six other patients on the same day."}
{"_id": "WikiPedia_Radiology$$$corpus_448", "text": "The patient complained of burning and swelling in the area and was hospitalized on July 30. She was suspected of a radiation overdose and the machine was taken out of service. On November 3, 1985, the patient died of cancer, although the autopsy mentioned that if she had not died then, she would have had to undergo a hip replacement due to damage from the radiation overdose. A technician estimated that she received between 13,000 and 17,000 rad."}
{"_id": "WikiPedia_Radiology$$$corpus_449", "text": "The incident was reported to the FDA and the Canadian Radiation Protection Bureau."}
{"_id": "WikiPedia_Radiology$$$corpus_450", "text": "The AECL suspected that there might be an error with three microswitches that reported the position of the turntable. The AECL was unable to replicate a failure of the microswitches and microswitch testing was inconclusive. They then changed the method to be tolerant of one failure and modified the software to check if the turntable was moving or in the treatment position."}
{"_id": "WikiPedia_Radiology$$$corpus_451", "text": "Afterward, the AECL claimed that the modifications represented a five-order-of-magnitude increase in safety. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_452", "text": "In December 1985 a woman developed an  erythema  with a parallel band pattern after receiving treatment from a Therac-25 unit. Hospital staff sent a letter on January 31, 1986, to the AECL about the incident. The AECL responded in two pages detailing the reasons why radiation overdose was impossible on the Therac-25, stating both machine failure and operator error were not possible."}
{"_id": "WikiPedia_Radiology$$$corpus_453", "text": "Six months later, the patient developed chronic ulcers under the skin due to tissue necrosis. She had surgery and skin grafts were placed. The patient continued to live with minor  sequelae . [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_454", "text": "Over two years, this hospital treated more than 500 patients with the Therac-25 with no incident. On March 21, 1986, a patient presented for his ninth treatment session for a tumor on his back. The treatment was set to be 22-MeV of electrons with a dose of 180 rad in an area of 10x17 cm, with an accumulated radiation in 6 weeks of 6000 rad."}
{"_id": "WikiPedia_Radiology$$$corpus_455", "text": "The experienced operator entered the session data and realized that she had written an \u201cx\u201d for \u2018x-ray\u2019 instead of an \u201ce\u201d for \u2018electron beam\u2019 as the type of treatment. With the cursor she went up and changed the \u201cx\u201d to an \u201ce\u201d and since the rest of the parameters were correct she pressed  \u21b5 Enter  until she got down to the command box. All parameters were marked \"Verified\" and the message \"Rays ready\" was displayed. She hit the  B  key (\"Beam on\"). The machine stopped and displayed the message \"Malfunction 54\" (error 54). It also showed 'Treatment pause'. The manual said that the \"Malfunction 54\" message was a \"dose input 2\" error. A technician later testified that \"dose input 2\" meant that the radiation delivered was either too high or too low."}
{"_id": "WikiPedia_Radiology$$$corpus_456", "text": "The radiation monitor (dosimeter) marked 6 units supplied when it had demanded 202 units. The operator pressed  P  ( Proceed\u00a0: continue). The machine stopped again with the message \"Malfunction 54\" (error 54) and the dosimeter indicated that it had delivered fewer units than required. The surveillance camera in the radiation room was offline and the intercom had been broken that day."}
{"_id": "WikiPedia_Radiology$$$corpus_457", "text": "With the first dose the patient felt an electric shock and heard a crackle from the machine. Since it was his ninth session, he realized that it was not normal. He started to get up from the table to ask for help. At that moment the operator pressed  P  to continue the treatment. The patient felt a shock of electricity through his arm, as if his hand was torn off. He reached the door and began to bang on it until the operator opened it. A physician was immediately called to the scene, where they observed intense  erythema  in the area, suspecting that it had been a simple electric shock. He sent the patient home. The hospital physicist checked the machine and, because it was calibrated to the correct specification, it continued to treat patients throughout the day. The technicians were unaware that the patient had received a massive dose of radiation between 16,500 and 25,000 rads in less than a second over an area of one cm 2 . The crackling of the machine had been produced by saturation of the ionization chambers, which had the consequence that they indicated that the applied radiation dose had been very low."}
{"_id": "WikiPedia_Radiology$$$corpus_458", "text": "Over the following weeks the patient experienced paralysis of the left arm, nausea, vomiting, and ended up being hospitalized for radiation-induced  myelitis  of the spinal cord. His legs, mid-diaphragm and vocal cords ended up paralyzed. He also had recurrent herpes simplex skin infections. He died five months after the overdose."}
{"_id": "WikiPedia_Radiology$$$corpus_459", "text": "From the day after the accident, AECL technicians checked the machine and were unable to replicate error 54. They checked the grounding of the machine to rule out electric shock as the cause. The machine was back in operation on April 7, 1986. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_460", "text": "On April 11, 1986, a patient was to receive electron treatment for skin cancer on the face. The prescription was 10 MeV for an area of 7x10 cm. The operator was the same as the one in the March incident, three weeks earlier. After filling in all the treatment data she realized that she had to change the mode from X to E. She did so and pressed  \u21b5 Enter  to go down to the command box. As \"Beam ready\" was displayed, she pressed  P  (Proceed\u00a0: continue). The machine produced a loud noise, which was heard through the intercom. Error 54 was displayed. The operator entered the room and the patient described a burning sensation on his face. The patient died on May 1, 1986, just shy of 3 weeks later. The autopsy showed severe radiation damage to the right temporal lobe and brain stem."}
{"_id": "WikiPedia_Radiology$$$corpus_461", "text": "The hospital physicist stopped the machine treatments and notified the AECL. After strenuous work, the physicist and operator were able to reproduce the error 54 message. They determined that speed in editing the data entry was a key factor in producing error 54. After much practice, he was able to reproduce the error 54 at will. The AECL stated they could not reproduce the error and they only got it after following the instructions of the physicist so that the data entry was very rapid. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_462", "text": "On January 17, 1987, a patient was to receive a treatment with two film-verification exposures of 4 and 3 rads, plus a 79-rad photon treatment for a total exposure of 86 rads. Film was placed under the patient and 4 rads were administered through a 22\u00a0cm \u00d7 18\u00a0cm opening. The machine was stopped, the aperture was opened to 35\u00a0cm \u00d7 35\u00a0cm and a dose of 3 rad was administered. The machine stopped. The operator entered the room to remove the film plates and adjust the patient's position. He used the hand control inside the room to adjust the turntable. He left the room, forgetting the film plates. In the control room, after seeing the \"Beam ready\" message, he pressed the  B  key to fire the beams. After 5 seconds the machine stopped and displayed a message that quickly disappeared. Since the machine was paused, the operator pressed  P  (Proceed\u00a0: continue). The machine stopped, showing \"Flatness\" as the reason. The operator heard the patient on the intercom, but could not understand him, and entered the room. The patient had felt a severe burning sensation in his chest. The screen showed that he had only been given 7 rad. A few hours later, the patient showed burns on the skin in the area. Four days later the reddening of the area had a banded pattern similar to that produced in the incident the previous year, and for which they had not found the cause. The AECL began an investigation, but was unable to reproduce the event."}
{"_id": "WikiPedia_Radiology$$$corpus_463", "text": "The hospital physicist conducted tests with film plates to see if he could recreate the incident, which involved two X-ray parameters with the turntable in field-light position. The film appeared to match the film that was left by mistake under the patient during the accident. It was found the patient was exposed to between 8,000 and 10,000 rad instead of the prescribed 86 rad. The patient died in April 1987 from complications due to radiation overdose. The relatives filed a lawsuit that ended with an out-of-court settlement. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_464", "text": "A commission attributed the primary cause to generally poor software design and development practices, rather than singling out specific coding errors. In particular, the software was designed so that it was realistically impossible to test it in a rigorous,  automated  way. :\u200aSafeware,\u200a[48]\u200a [ additional citation(s) needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_465", "text": "Researchers who investigated the accidents found several contributing causes. These included the following institutional causes:"}
{"_id": "WikiPedia_Radiology$$$corpus_466", "text": "The researchers also found several  engineering  issues:"}
{"_id": "WikiPedia_Radiology$$$corpus_467", "text": "Leveson  notes that a lesson to be drawn from the incident is to not assume that reused software is safe: [ 9 ]  \"A naive assumption is often made that reusing software or using commercial off-the-shelf software will increase safety because the software will have been exercised extensively. Reusing software modules does not guarantee safety in the new system to which they are transferred\u00a0...\" [ 6 ]   In response to incidents like those associated with Therac-25, the  IEC 62304  standard was created, which introduces development life cycle standards for medical device software and specific guidance on using  software of unknown pedigree . [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_468", "text": "VistA Imaging  is an FDA-listed Image Management system used in the  Department of Veterans Affairs healthcare facilities nationwide . It is one of the most widely used image management systems in routine healthcare use, and is used to manage many different varieties of images associated with a patient's medical record. The system was started as a research project by  Ruth Dayhoff  in 1986 and was formally launched in 1991. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_469", "text": "The VistA Imaging System uses hardware components to provide short- and long-term storage. It takes advantage of network servers for storage. It uses a  DICOM  gateway system to communicate with commercial  Picture Archiving and Communication Systems  (PACS) and modalities such as CT, MR, and Computed Radiography (x-ray) devices for image capture. It utilizes a background processor for moving the images to the proper storage device and for managing storage space."}
{"_id": "WikiPedia_Radiology$$$corpus_470", "text": "The system not only manages radiologic images, but also is able to capture and manage  EKGs ,  pathology  images,  gastroenterology (endoscopic)  images,  laparoscopic  images, scanned paperwork, or essentially any type of health care image."}
{"_id": "WikiPedia_Radiology$$$corpus_471", "text": "VistA Imaging is currently integrated into the  VistA EMR  (electronic medical record) system used nationwide in Department of Veterans Affairs hospitals. This integration is able to provide increased efficiency of retrieval of images. [ 2 ]  It has also been used as a separate software package and can be used with  EHRs  other than VistA."}
{"_id": "WikiPedia_Radiology$$$corpus_472", "text": "VistA Imaging now connects to a nationwide backbone that allows clinicians to access the 350 million images stored in the VA system via Remote Image View software. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_473", "text": "The VA has developed interfaces for more than 250 medical devices in VistA Imaging, the images from which can be accessed through the desktop VistA Imaging Viewer. The Department of Defense will use the VistA Imaging Viewer to enhance its own EHR. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_474", "text": "As part of the US national mandate to co-ordinate care between Department of Defense and the VA, VistA Imaging is forming a cornerstone of the effort to exchange medical imagery between the two systems. \u201cWhen soldiers come back from Iraq and Afghanistan and eventually enter the VA system, images will be able to move from DOD to VA seamlessly.\" Eventually, DOD and VA should be able to share all image file types from all sites. Additional enhancements to VistA Imaging include development of a central archive for all VA images (whether acquired through VistA or a commercial system) and new indexing and search capabilities. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_475", "text": "The software for VistA Imaging has been made available through the  Freedom of Information Act  so that it is in the public domain. Due to its designation as a medical device, however, it can not be designated as free open source software and therefore can not be altered or implemented without FDA approval."}
{"_id": "WikiPedia_Radiology$$$corpus_476", "text": "Although it can be used in healthcare facilities that are outside the  Department of Veterans Affairs , this is possible only if the proprietary modules that have been integrated into it are also licensed and implementation is registered with the FDA. This has effectively limited its use to government institutions who have licensed the proprietary modules."}
{"_id": "WikiPedia_Radiology$$$corpus_477", "text": "The source code can be downloaded from  the OSEHRA VistA-M.git tree ."}
{"_id": "WikiPedia_Radiology$$$corpus_478", "text": "VistA Imaging uses proprietary modules not in the public domain. This makes its public domain use limited."}
{"_id": "WikiPedia_Radiology$$$corpus_479", "text": "The VistA Imaging system was robust enough to be restored after  Hurricane Katrina  damaged the data facility at the New Orleans VA. [ 5 ]  This type of backup proved superior to a paper record system."}
{"_id": "WikiPedia_Radiology$$$corpus_480", "text": "A  well counter  is a device used for measuring  radioactivity  in small samples. It usually employs a  sodium iodide   crystal detector . \nIt was invented in 1951 by  Hal Anger , who is also well known for inventing the  scintillation camera . [ 1 ]  Anger filed U.S. patent #2,779,876 on March 3, 1953 for his \"Radio-Activity Distribution Detector\"; the patent was issued on January 29, 1957. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_481", "text": "The well counter is so called because the samples are inserted into a well within the crystal in order to maximize sensitivity by collecting as many of the emitted  gamma rays  as possible."}
{"_id": "WikiPedia_Radiology$$$corpus_482", "text": "Modern well counters can automatically record activity in different samples sequentially. Samples in test tubes are inserted into the well, one sample at a time, and  counted  for a predetermined time. Results are presented as a  graphic , and corrected for the  decay  of the sample. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_483", "text": "Aarthi Scans and Labs  is an Indian  radiology  and pathology diagnostic provider, headquartered in  Chennai . The business has 40 diagnostic centres in India, and is accredited with the  NABL  and  NABH . [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_484", "text": "In 1985, V. Govindarajan and his wife made the decision to establish a  polyclinic  in the  Tamil Nadu  town of  Kovilpatti . However, they felt a lack of medical tools and technology for MRI scans and diagnostics, and thus decided to found Aarthi Scans and Labs in 2000. The business began as a single state operator and is now widespread throughout India. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_485", "text": "During the  COVID-19 pandemic , Aarthi Scans and Labs gathered 75,500 Swabs from homes. [ 4 ]  Additionally, it contributed   \u20b92,500,000  to a COVID-19 Relief Fund alongside other donors [ 5 ]  and offered scans and blood tests to COVID patients during pandemic. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_486", "text": "In 2021, Aarthi Scans and Labs signed a contract with Mindray Ultrasound India [ 7 ]  and partnered with health tech firm Qure.ai. [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_487", "text": "In May 2022, the company partnered with Indian radiology company Synapsica to provide Spine MRI. [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_488", "text": "Alliance Medical  is a radiology services company founded in 1989 by  Robert Waley-Cohen  operating across Europe."}
{"_id": "WikiPedia_Radiology$$$corpus_489", "text": "In 2010  Lloyds Bank ,  Commerzbank  and  M&G Investments  acquired 85% of the company in a debt-for-equity swap. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_490", "text": "A consortium, called the Collaborative Network, between the company and  Christie Hospital NHS Foundation Trust  won a ten-year NHS contract to provide PET-CT scanning services across 30 locations in England in January 2015. [ 2 ]  The contract provides for investment of \u00a387 million over 10 years to install new scanners and improve the current infrastructure. Twenty-four existing sites will remain where they are, and six new sites will be added at Maidstone Hospital;  William Harvey Hospital ;  Cumberland Infirmary ;  Lincoln County Hospital ;  Southmead Hospital ;  Royal United Hospital ; and  Royal Cornwall Hospital . [ 3 ]  The contract was awarded despite an NHS consortium bid being \u00a37m cheaper. [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_491", "text": "In 2013 the company acquired IBA Molecular UK and Erigal, two of the three companies in England that produce the radioactive drug  Fludeoxyglucose (18F) , which is injected into patients as part of the imaging process.   Siemens Healthcare  is the only other UK producer. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_492", "text": "It was bought by  LIFE Healthcare Group  for about 10.4 billion rand (\u00a3584 million, \u20ac680 million, $727 million) in November 2016. [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_493", "text": "It took over the running of the Taunton Diagnostic Centre, the first  community diagnostic centre  run by the independent sector in partnership with the NHS,  in November 2022 after  Rutherford Health  went into liquidation. It provides  Magnetic Resonance Imaging ,  Computed Tomography ,  Ultrasound  and  X-Ray  facilities.  [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_494", "text": "This article about a  medical ,  pharmaceutical  or  biotechnological  corporation or company is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Radiology$$$corpus_495", "text": "This article about a company of the UK is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Radiology$$$corpus_496", "text": "The  American Association for Women in Radiology  (or  AAWR ) is a  professional association  founded in 1981 as a resource for \"professional socialization\" for women in a male-dominated field of  radiology . [ 1 ] [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_497", "text": "AAWR\u2019s role model is  Marie Curie . [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_498", "text": "The main goals of the association were to provide a forum for issues unique to women in radiology,  radiation oncology  and related professions, to sponsor programs that promote opportunities for women, and to facilitate networking among women radiologists. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_499", "text": "Established in 1934, the  American Board of Radiology  ( ABR ) is an independent, not-for-profit  professional association  with headquarters in Tucson, Arizona. [ 1 ]  It oversees the certification and ongoing professional development of physician specialists in  diagnostic radiology ,  interventional radiology , and  radiation oncology , as well as  medical physicists  in  diagnostic ,  nuclear , and  therapy   medical physics . [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_500", "text": "The ABR certifies its diplomates through a comprehensive process involving educational requirements, professional peer evaluation, and examination."}
{"_id": "WikiPedia_Radiology$$$corpus_501", "text": "This article about a United States health organization is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Radiology$$$corpus_502", "text": "The  American College of Radiology  ( ACR ), founded in 1923, is a professional medical society representing nearly 40,000 diagnostic  radiologists , radiation  oncologists , interventional radiologists, nuclear medicine  physicians  and medical  physicists ."}
{"_id": "WikiPedia_Radiology$$$corpus_503", "text": "The ACR has 54 chapters in the United States, Canada and the Council of Affiliated Regional Radiation Oncology Societies (CARROS). [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_504", "text": "The ACR has accredited more than 39,000 medical imaging facilities [ 2 ]  in 10 imaging modalities since 1987, including:"}
{"_id": "WikiPedia_Radiology$$$corpus_505", "text": "The ACR provides patient information through the website Radiologyinfo.org, [ 7 ]  co-produced by the  Radiological Society of North America , to help patients understand how various radiology procedures and radiation therapy are performed."}
{"_id": "WikiPedia_Radiology$$$corpus_506", "text": "ACR's Imaging 3.0 initiative is a roadmap to transition the practice of radiology from volume-based to value-based care. Four main focus areas of Imaging 3.0 include; [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_507", "text": "The  American Osteopathic Board of Radiology  ( AOBR ) is an organization that provides  board certification  to qualified  Doctors of Osteopathic Medicine  (D.O.) who specialize in the use of  imaging  in the diagnosis and treatment of disease ( radiologists ). The board is one 18  medical specialty  certifying boards of the  American Osteopathic Association Bureau of Osteopathic Specialists  approved by the  American Osteopathic Association  (AOA), [ 4 ] [ 5 ]  and was established in 1939. [ 1 ]  The American Osteopathic Board of Radiology and the  American Board of Radiology  are the two certifying boards for radiologists in the United States. [ 6 ] [ 7 ]  As of December 2011, 732  osteopathic  radiologists held active certification with the AOBR. [ 8 ]  Radiologists board certified by the AOBR are eligible for membership in the  American College of Radiology . [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_508", "text": "Initial certification is available to osteopathic radiologists who have successfully completed an AOA-approved  residency  in diagnostic radiology or radiation oncology, two years of practice, and successful completion of oral and written exams. [ 10 ] [ 11 ] [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_509", "text": "Diplomates certified in  diagnostic radiology  or in  radiation oncology  prior to 2002 are eligible for voluntary recertification. Since 2002, the American Osteopathic Board of Radiology requires osteopathic radiologists to renew their certification every ten years to avoid expiration of their board certified status. [ 13 ]  Additionally, osteopathic radiologists who have completed the requirements set forth by the AOBR and completed an AOA-approved radiology residency may be eligible to pursue certification by the  American Board of Radiology . [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_510", "text": "Osteopathic radiologists may also receive Certification of Added Qualifications (CAQ) in the following areas: [ 15 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_511", "text": "The  American Osteopathic College of Radiology (AOCR) , founded in 1941, is a  non-profit   professional   medical association  in the  United States  representing  Doctors of Osteopathic Medicine  (D.O.) that specialize in  radiology . The AOCR is accredited by the  American Osteopathic Association  (AOA) and the  Accreditation Council for Continuing Medical Education  to oversee  continuing medical education  activities for  osteopathic  radiologists. [ 3 ] [ 4 ]  The AOCR is one of two professional organizations representing American radiologists, the other organization is the  American College of Radiology . The college publishes  The Journal of the American Osteopathic College of Radiology  ( JAOCR ). [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_512", "text": "Certified fellows of the American Osteopathic College of Radiology are eligible to become senior members of the American Society of Neuroradiology in addition to their certified peers from the  American Board of Radiology  and the  Royal College of Physicians and Surgeons of Canada . [ 6 ]  Additionally, osteopathic radiologists that have completed an  ACGME  radiology residency or completed an AOA/AOCR-approved residency in  diagnostic radiology  and subsequent  board certification  by the  American Osteopathic Board of Radiology , may also apply for board certification through the  American Board of Radiology . [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_513", "text": "John \u201cDrew\u201d Ridge, MD, PhD, Secretary \nQuynh-Thu Le, MD, Treasurer"}
{"_id": "WikiPedia_Radiology$$$corpus_514", "text": "The  American Radium Society  is a medical association devoted to the study and treatment of cancer. It was founded in 1916. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_515", "text": "The Society's original mission was to further \"the scientific study of radium in relation to its physical properties and therapeutic applications\" distinguishing it from the  American Roentgen Ray Society  (ARRS). The society's mission was expanded in 1950 to include \"the treatment of  neoplastic  and allied diseases and the study and application of  ionizing radiation .\" [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_516", "text": "In 1933, The ARS founded the annual Janeway Lecture in honor of  Henry Harrington Janeway , a pioneer in radium therapy. The first Janeway Lecture, \"Early Experience in Radium Therapy\", was given by the pathologist  James Ewing . The lecture is delivered at the society's annual general meeting with the lecturer chosen for their \"outstanding scientific contributions\". The 2014 Janeway Lecturer was Murray F. Brennan of the  Memorial Sloan Kettering Cancer Center . Since 1937 each Janeway Lecturer is presented with the Janeway Medal. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_517", "text": "The society's first president was the Canadian physician W. H. B. Aikins, known as the founder of  radiotherapy  in Canada. [ 4 ]  Other past presidents have included: [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_518", "text": "The  American Roentgen Ray Society  ( ARRS ) is the first and oldest  radiology  society in the United States. It was founded in 1900, in the early days of  X-ray  and radiation study."}
{"_id": "WikiPedia_Radiology$$$corpus_519", "text": "Headquartered in  Leesburg, Virginia , the society publishes a monthly peer-reviewed journal:   American Journal of Roentgenology  (previously  American Journal of Radiology ), providing a forum for advances in radiology and related fields.  It provides  scholarships , and presents awards. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_520", "text": "Its educational programs include seminars and a program of  continuing education  for  radiologic technologists . [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_521", "text": "Its 9th meeting, in 1908, was held in New York City.  There, it announced that there was \"no excuse whatever\" for anyone being injured during medical X-rays, which \"could be taken in a fraction of a second\". [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_522", "text": "The  Center for Radiological Research  (CRR) is a research institute in New York City. It was founded in 1916 at  Memorial Hospital  by  Gioacchino Failla  before moving to  Columbia University  in 1942. [ 1 ]  It has been described as the oldest and largest research center of its kind in the world. [ 2 ]  Achievements by the CRR under Failla include constructing the first radon generator in the US and building the first  human phantom  in the US. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_523", "text": "The  Centre for Radiation, Chemical and Environmental Hazards  (CRCE) is a British government environmental research site, run by  Public Health England  (PHE) in  Chilton, Oxfordshire  that monitors levels of toxic chemicals and background radiation in the British environment; it is largely a continuation of the former  National Radiological Protection Board  (NRPB)."}
{"_id": "WikiPedia_Radiology$$$corpus_524", "text": "The Radiation Protection Division of the  Health Protection Agency  was formed on 1 April 2005, due to the  Health Protection Agency Act 2004 , directly superseding the NRPB. This became the CRCE due to the  Health and Social Care Act 2012 , when Public Health England was formed. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_525", "text": "It is part of PHE's Radiation Protection Adviser Services. PHE was the UK's first Radiation Protection Adviser Body, under the  Ionising Radiations Regulations  (IRR) 17 (which came from the  International Commission on Radiological Protection ). [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_526", "text": "It monitors  background radiation  in the UK. Workers exposed to radiation include workers in  dental radiography [ 1 ]  and  nuclear power stations ; exposure to radiation for workers in the UK must be  ALARP . It offers 3-day training courses around twice a month, at a national level, for workers exposed to radiation."}
{"_id": "WikiPedia_Radiology$$$corpus_527", "text": "It produces reports on environmental background radiation in England. [ 2 ]  It works with the ICRP, the  United Nations Scientific Committee on the Effects of Atomic Radiation  (UNSCEAR), and the  International Atomic Energy Agency  (IAEA). Inside the UK, it works with the  Scottish Environment Protection Agency  (SEPA) and the  Environment Agency  (EA)."}
{"_id": "WikiPedia_Radiology$$$corpus_528", "text": "This article about an organisation in the  United Kingdom  is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Radiology$$$corpus_529", "text": "The  College of Radiology, Academy of Medicine Malaysia  is a  non-profit organization  of clinical radiologists, clinical oncologists, and medical physicists in  Malaysia ."}
{"_id": "WikiPedia_Radiology$$$corpus_530", "text": "It was established as the Malaysian Radiological Society (MRS) following the inaugural general meeting held on November 27, 1976, at the then General Hospital,  Kuala Lumpur . [ 1 ]  On August 23, 2001, the MRS became a chapter in the  Academy of Medicine of Malaysia  and from then on is known by its current name. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_531", "text": "It has adopted  Biomedical Imaging and Intervention Journal  as its official publication. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_532", "text": "This article about a medical organization or association is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Radiology$$$corpus_533", "text": "The  European Congress of Radiology  (Europ\u00e4ischer R\u00f6ntgenkongress)  is an annual meeting in Europe for  radiologists  from around the world.  Founded in 1967, the Congress is run by Verein Europ\u00e4ischer R\u00f6ntgenkongress (ECR)."}
{"_id": "WikiPedia_Radiology$$$corpus_534", "text": "When the congress was founded in 1967, it was held every four years in a different location.  However, this format did not allow for the creation of a consistent group of experienced  radiologists  responsible for the preparation of the congress. Furthermore, the radiological community in  Europe  wanted to create a common platform for European radiologists."}
{"_id": "WikiPedia_Radiology$$$corpus_535", "text": "In 1985, a committee chaired by Josef Lissner from  Munich  ( Germany ) was established to re-organise the Congress. The committee recommended holding the congress every two years in the same location,  Vienna  ( Austria ) . The society 'Verein Europ\u00e4ischer R\u00f6ntgenkongress' (ECR) was founded, and a congress-organising institution was established at the Medical Academy of Vienna. The first 'new' Congress opened on Saturday, September 15, 1991 under the presidency of Lissner. It attracted more than 9,000 participants."}
{"_id": "WikiPedia_Radiology$$$corpus_536", "text": "In 1999, the ECR changed the congress to an annual event."}
{"_id": "WikiPedia_Radiology$$$corpus_537", "text": "The Congress is the largest radiological meeting in Europe with more than 28,000 participants from around 100 countries and 4,000  scientific papers  and  exhibits . To answer growing demand, the ECR has developed EPOS, an online electronic  presentation system  and ECR Online, providing coverage of the majority of sessions via  live video streaming ."}
{"_id": "WikiPedia_Radiology$$$corpus_538", "text": "The  European Society of Radiology  ( ESR ) is an international medical society based in  Vienna ,  Austria  dedicated to the promotion and coordination of scientific, philanthropic, intellectual and professional activities of  radiology  in Europe. In addition to various other activities, the ESR serves as an umbrella organisation for European  radiologists , organises the annual  European Congress of Radiology  (ECR) and coordinates the publication of  European Radiology , a monthly peer-reviewed  medical journal . [ 1 ] [ 2 ]  Additionally, the ESR pilots the harmonisation of teaching programmes throughout Europe with various activities and initiatives."}
{"_id": "WikiPedia_Radiology$$$corpus_539", "text": "Founded in 2005, the European Society of Radiology (ESR) was created through the merger of two established radiological societies; the European Association of Radiology (EAR), a federation of national radiological societies founded in 1962, and the European Congress of Radiology (ECR), the organising body of the eponymous congress which was first held in 1967. [ 4 ] :\u200a30"}
{"_id": "WikiPedia_Radiology$$$corpus_540", "text": "The EAR was established on 15 December 1962 through the efforts of  Boris Rajewsky  of the  Max Planck Institute  in Frankfurt and Charles Marie Gros of the  University of Strasbourg  who would become the association's first president and first secretary-general respectively. [ 5 ]  The EAR was tasked with coordinating a European congress and establishing a European counterpart to the  Radiological Society of North America  (RSNA), which had existed since 1915. [ 4 ] :\u200a4,\u200a23\u200a  By the time it was formally registered, the association comprised radiological member societies from nine countries \u2013  Belgium ,  France ,  Italy ,  Luxembourg ,  The Netherlands ,  Portugal ,  Spain ,  Switzerland , and  West Germany . The  European Congress of Radiology  was to be held every four years in a different European city, starting in 1967 which  Barcelona  with took place in conjunction with the Radiological Federation of Latin Culture (F\u00e9deration Radiologique de Culture Latine). [ 4 ] :\u200a23"}
{"_id": "WikiPedia_Radiology$$$corpus_541", "text": "After successor congresses were held in  Amsterdam  (1971),  Edinburgh  (1975),  Hamburg  (1979),  Bordeaux  (1983) and  Lisbon  (1987), the EAR in 1985 founded a committee, chaired by  Josef Lissner  of the  University of Munich , specifically tasked with organising future congresses. An ever-changing location and the lack of a consistent group of experienced radiologists responsible for the congresses were deemed obstacles to the most effective congress possible. [ 4 ] :\u200a25\u200a [ 5 ]  As a result, the committee ultimately decided that the frequency of the congress should be increased to every two years and a permanent host location be selected. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_542", "text": "As the late 1980s, early 1990s was marked by the fall of the iron curtain and a call for greater European cooperation, a suitable host location was sought that could embody these ideals. Situated near the then border between eastern and western Europe,  Vienna  was chosen to host all future congresses beginning in 1991. [ 4 ] :\u200a24\u200a  By the late 1980s, the Verein Europaeischer Roentgenkongress, or European Congress of Radiology (ECR), had been founded and a congress-organising institution was established at the  Medical University of Vienna , both in support of the biennial meeting. [ 4 ] :\u200a24\u200a  With ECR'91, EAR remained a federation of national societies who sent delegates to the general assembly at the end of every congress. [ 5 ]  Due to the growing success of the ECR, it was decided that the congress would be held annually from 1999 on. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_543", "text": "By the beginning of the 2000s it had become clear to EAR leadership that a unified organisation combining all aspect of radiology including the ECR would better serve European radiology interests moving into the future. As the EAR had a federal structure with a restricted financial base, a new association would be necessary in order to create a unified \"House of European Radiology\" that could effectively combine the numerous and diverse responsibilities from the EAR and various congress planning organisations. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_544", "text": "After more than three years of meetings and discussions, the General Assembly of EAR held in the  Austria Center Vienna  on 7 March 2005 unanimously approved of the statutes of the ESR, paving the way for the creation of the society as it functions today. Nicholas Gourtsoyiannis of the  University of Crete , a guiding force behind the creation of the ESR and president of ECR 2003, served as its first president from December 2005 to March 2007. [ 4 ] :\u200a29\u201330"}
{"_id": "WikiPedia_Radiology$$$corpus_545", "text": "The House of European Radiology is the current headquarters of the European Society of Radiology (ESR) and has been since 2018 after the completion of its renovation. [ 7 ]   :\u200a14\u200a  The building is located in the historic central district of Vienna, across from the steps leading to  Maria am Gestade  church on Am Gestade square. Through renovations, the building has retained the style of its facade dating from 1823 with a newly constructed interior which houses a majority of ESR functions. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_546", "text": "Upon the founding of the European Society of Radiology (ESR) in 2005, the board of directors, executive council and all executive bodies were integrated from the bodies of the two founding societies (EAR & ECR) to form the executive council through a process of voting. [ 4 ] :\u200a30"}
{"_id": "WikiPedia_Radiology$$$corpus_547", "text": "The current structure of the ESR consists of a board of directors, committee chairs, the director of the European School of Radiology (ESOR) and the ESR executive director. These form the executive council which dictates and manages the various activities of the ESR. The composition of the board changes at the annual General Assembly which takes place on the last day of the European Congress of Radiology (ECR). The committee chairs and newest member of board of directors are elected by the voting members of the ESR. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_548", "text": "The board of directors consists of the Past-President, Chairperson of the Board of Directors, President, 1st Vice-President and 2nd Vice-President. The 2nd Vice-President (the newest member of the board) is elected every year for a five year period of office, holding the position of 2nd Vice-President in the first year, 1st Vice-President in the second year, President in the third year, Chairperson of the Board of Directors in the fourth year and finally the Past-President in the fifth year of office. Re-election is not possible.\nThe current chair of the ESR Board of Directors is Carlo Catalano from Rome, Italy. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_549", "text": "The European Society of Radiology (ESR) offers full membership to all European radiologists as well as professionals of allied sciences such as nuclear medicine physicians, radiographers, medical physicists, etc. Corresponding membership is offered to international radiologists and professionals of allied sciences. Membership is on a yearly basis and the ESR offers its members various benefits. [ citation needed ]  These include:"}
{"_id": "WikiPedia_Radiology$$$corpus_550", "text": "Membership is also extended to various European and international societies of radiology as institutional and associate institutional members. [ 11 ] [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_551", "text": "The core of the European Society of Radiology's (ESR) activities is the organisation of its annual meeting, the European Congress of Radiology (ECR). With more than 30,000 participants from around 120 countries, over 2,800 scientific presentations and 1,700 speakers, the ECR has developed into the largest radiological meeting in Europe since it was first held in its 'new' format in September 1991. It is held annually at the end of February or early March. Congress attendees include radiology professionals, professionals of allied sciences, industry representatives, and press reporters for both the medical and consumer press. [ 13 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_552", "text": "The ECR hosts an accompanying industrial exhibition over a space of 30,000\u00a0m 2 , which provides a chance for congress-goers to explore state-of-the-art medical imaging technology and related services. [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_553", "text": "ECR is a hybrid meeting. Participants can choose to attend onsite or online, with all sessions being streamed live via ESR Connect."}
{"_id": "WikiPedia_Radiology$$$corpus_554", "text": "The  International Day of Radiology  is an annual event held with the aim of building greater awareness of the value that radiology contributes to safe patient care and improving understanding of the role radiologists and radiological technologists play in healthcare. It was launched in 2012 and is a joint initiative of the European Society of Radiology (ESR), the  Radiological Society of North America  (RSNA) and the  American College of Radiology  (ACR). November 8, the day that  Wilhelm Conrad R\u00f6ntgen  discovered the existence of x-rays in 1895, was chosen as a day of action and awareness. [ 15 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_555", "text": "The  European Institute for Biomedical Imaging Research  (EIBIR), established in 2006 on the initiative of the European Society of Radiology (ESR), aims to improve cooperation between research institutes, academic departments and industry that form the European biomedical imaging community with the goal of improving the diagnosis, treatment and prevention of diseases. It actively supports research networking activities and common initiatives and interoperability in the field of biomedical imaging research. [ 16 ] [ 17 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_556", "text": "The European Society of Radiology (ESR) undertakes various international and EU-level initiatives designed to support member interests internationally and in government. One of these initiatives is the ESR's collaborative work on cancer. Various cancer initiatives have been undertaken including collaboration with the European Joint Action on Cancer Control (CanCon JA). The ESR is part of the European Commission Initiative on Breast Cancer (ECIBC) whose aim is to develop new European Breast Guidelines, evidence-based recommendations for breast cancer screening and diagnosis and develop a voluntary European Breast QA scheme for breast cancer services. [ 7 ] :\u200a43"}
{"_id": "WikiPedia_Radiology$$$corpus_557", "text": "Since 2012, the ESR has been a member of the EC's eHealth Stakeholder Group (eHSG), with the aim of recognising teleradiology as a medical act in its own right. Additionally, on 6 June 2018, the ESR organised an event at the European Parliament that brought together MEPs, EC officials, and health stakeholders to discuss the importance of effectively implementing health policies and legislation in clinical practice. [ 7 ] :\u200a44"}
{"_id": "WikiPedia_Radiology$$$corpus_558", "text": "As a member of the EMA Healthcare Professionals Working Party (HCPWP), the ESR can be actively involved in activities of the EMA while also facilitating direct dialogue, having addressed topics such as  gadolinium-based contrast agents  and the implications of Brexit on radiology in Europe. The ESR also contributes to the Digital Imaging Adoption Model (DIAM) with the goal of supporting organisations in the planning and implementation of imaging IT in radiology departments. [ 7 ] :\u200a46"}
{"_id": "WikiPedia_Radiology$$$corpus_559", "text": "European Radiology , established in 1991, [ 4 ] :\u200a27\u200a  is a monthly peer-reviewed medical journal that features articles on a wide range of radiological topics. The flagship journal of the European Society of Radiology (ESR) seeks to update scientific knowledge in clinical radiology by publishing research articles of general interest as well as state-of-the-art reviews, and short communications written by leading radiologists. It is available to all members of the ESR and thus reaches a regular audience of over 100,000 readers, making it one of the most widely disseminated journals in the field of radiology. [ 18 ]  In 2021, the journal had an  impact factor  (IF) of 7.034. [ 7 ] :\u200a18"}
{"_id": "WikiPedia_Radiology$$$corpus_560", "text": "The Editorial Board currently consists of 169 board members and over 3,000 active reviewers, racking up more than 2,000,000 downloads. [ 7 ] :\u200a61\u200a \nEuropean Radiology's Editor-in-Chief is Yves Menu, chairman of the department of radiology at Saint Antoine Hospital, Pierre & Marie Curie University in Paris, France. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_561", "text": "European Radiology Experimental , the youngest of the ESR journal family, is an open access scientific medical journal that focuses on modern multidisciplinary research involving radiology in the experimental setting and basic science. The journal publishes articles on a wide range of topics including new modalities/techniques (e.g.,  magnetic resonance  sequences or spectral  computed tomography  applications, molecular, hybrid, and  optical imaging ), 3D-modelling, printing and advanced  teleradiology  (e.g., virtual physician-patient interaction)."}
{"_id": "WikiPedia_Radiology$$$corpus_562", "text": "The current Editor-in-Chief is Francesco Sardanelli of the  University of Milan . [ 19 ] [ 7 ] :\u200a58\u200a  The Editorial Board currently consists of 72 members and the journal saw almost 300,000 downloads in 2022."}
{"_id": "WikiPedia_Radiology$$$corpus_563", "text": "Insights into Imaging  is an open access journal with a focus on critical reviews, guidelines and policy statements, and is dedicated to education and strategies in radiology. The current Editor-in-Chief is Luis Mart\u00ed-Bonmat\u00ed of the  University of Valencia . [ 20 ] [ 21 ] \nThe journal, which consists of 82 Editorial Board members and had over 3,600,000 downloads in 2022, [ 7 ] :\u200a62\u200a  currently holds an impact factor of 5.036 and ranks 29 of 136 in the journal category \"Radiology, Nuclear Medicine and Medical Imaging\"."}
{"_id": "WikiPedia_Radiology$$$corpus_564", "text": "The European School of Radiology (ESOR) is an institution fulfilling the mission of the European Society of Radiology (ESR) in the field of education. One of its main goals is to harmonise radiological education in Europe. It offers various programmes including fellowships, visiting professorships and courses. Additionally, ESOR also provides an e-learning platform and continuing medical education (CME) credits for its courses. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_565", "text": "The European Board of Radiology (EBR) is an organisation whose purpose is to investigate, develop and implement certification and accreditation activities and programmes in radiology. [ 22 ]  Some of its activities include:"}
{"_id": "WikiPedia_Radiology$$$corpus_566", "text": "Eurorad is an online radiological case database that has been freely available since 2009. Radiologists are able to submit cases which are then reviewed before being published on the site. The database's origins can be found in the late 1990s when the Europeans Association of Radiology (EAR) realized a comprehensive approach to case studies that could parallel their peer-reviewed journals would be necessary. Today the portal is an open resource to radiologists and researchers. [ 24 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_567", "text": "Education on Demand is the ESR's premium e-learning platform. The platform offers hundreds of video, presentation and literature-based courses for radiologists. With Education on Demand Premium users can access a higher number of courses and can also obtain Continuing Medical Education (CME) credits."}
{"_id": "WikiPedia_Radiology$$$corpus_568", "text": "ESR Connect is the ESR's on-demand video platform. On ESR Connect, users can participate in live courses and watch recorded sessions and lectures from previous ECRs. The platform offers on-demand access to more than 2,400 hours of on-demand educational video content with both free and subscription-based content."}
{"_id": "WikiPedia_Radiology$$$corpus_569", "text": "EuroSafe Imaging is the ESR's initiative to promote appropriateness in medical imaging. Officially launched at the European Congress of Radiology in March 2014, the initiative is meant to address radiation protection in patients. Newsletters, sessions in conferences and training material are generated for the goal of informing physicians on best practice. [ 25 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_570", "text": "[ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_571", "text": "Everlight Radiology  is a 24-hour provider of teleradiology services based in London and Australia. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_572", "text": "Everlight Radiology's chief executive is Alexander van der Laan. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_573", "text": "It was acquired by Teleradiology International, controlled by  Intermediate Capital Group , in 2016. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_574", "text": "The  South Australian Government  employed it to report on images at  Lyell McEwin Hospital  in 2016. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_575", "text": "It ran Radiology Reporting Online  which secured part of a \u00a33.8 million contract from  NHS Scotland  in 2017/8. [ 5 ]   It won a contract for reporting at  Mid Essex Hospital Services NHS Trust ,  Basildon and Thurrock University Hospitals NHS Foundation Trust  and  Southend University Hospital NHS Foundation Trust  in April 2018. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_576", "text": "In 2021, it was reported as supporting 250 client sites across Australia, the UK, New Zealand, and the Republic of Ireland with a global network of about 500 radiologists and more than 300 support staff. It has regional bases in London, Leicester, Doncaster, Penzance and Belfast. [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_577", "text": "In 2021, London-based private equity firm Livingbridge acquired Everlight. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_578", "text": "Everbright was awarded the Diagnostic Provider of the Year award at the 2024 HealthInvestor Awards. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_579", "text": "The  Gordon Center for Medical Imaging  is an American multidisciplinary research center at  Massachusetts General Hospital  (MGH) and  Harvard Medical School  that develops biomedical imaging technologies."}
{"_id": "WikiPedia_Radiology$$$corpus_580", "text": "The center's central activities include: research, training and education in  medical imaging , and translation of basic research into clinical applications. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_581", "text": "The MGH Gordon Center also operates the PET Core, an MGH research service facility that synthesizes  radiotracers  and provides positron emission tomography ( PET ) imaging services for investigators. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_582", "text": "Created in 2015 with an endowment from the  Bernard  and Sophia Gordon Foundation, [ 3 ]  the Gordon Center is a direct continuation of MGH's Division of  Radiological Sciences  where the first positron-imaging device was invented. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_583", "text": "Dr. Georges El Fakhri is the founding director of the Gordon Center. The center is located in two campuses in Boston and  Charlestown Navy Yard , Massachusetts. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_584", "text": "This article about an organization in the United States is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Radiology$$$corpus_585", "text": "The  Indiana University Health Proton Therapy Center , formerly known as the  Midwest Proton Radiotherapy Institute  (MPRI), [ 1 ]  was the first proton facility in the  Midwest . The center was located on the  Indiana University  campus in  Bloomington ,  Indiana ,  United States . The IU Health Proton Therapy Center was the only proton therapy center in the U.S. to use a uniform-scanning beam for dose delivery, [ 2 ]  which decreases undesirable  neutron  dose to patients. [ 3 ]  The Center opened in 2004, and ceased operations in 2014."}
{"_id": "WikiPedia_Radiology$$$corpus_586", "text": "The center was affiliated with the Melvin and Bren Simon Cancer Center and  Indiana University Health  and was the only U.S. proton therapy center associated with a university-based proton therapy technology research group, IU Cyclotron Operations. The center's pediatric program was affiliated with  Riley Hospital for Children ."}
{"_id": "WikiPedia_Radiology$$$corpus_587", "text": "Proton therapy is not experimental and has been used in the United States since 1946. [ 2 ]  In 2014 there were only 12 centers in the U.S. that provided proton therapy. The scarcity of proton centers was due to the cost of the  cyclotron  that produces a proton beam. [ 4 ]  IU Health Proton Therapy Center was able to repurpose the cyclotron located at the Indiana University Cyclotron Facility (IUCF), adapting the purpose from a research facility into a proton therapy center."}
{"_id": "WikiPedia_Radiology$$$corpus_588", "text": "The  Indiana University Cyclotron Facility  (IUCF). [ 5 ]  was a  cyclotron  located on the  Indiana University  campus in  Bloomington ,  Indiana ,  United States . It accelerated  protons  to an energy of 200  MeV , as well as light ions:  deuterium ,  3 He   4 He ,  6 Li  and  7 Li . [ 6 ]  The beam could be  polarized  and was delivered to experimental halls. The facility was operated between 1976 and 2010.\nin 1985 the IUCF was upgraded to operate a  cooled  beam (Cooler storage ring) able to accelerate protons to 500 MeV. [ 7 ] \nIn 2004, the IUCF was repurposed for medical use and became the Indiana University Health Proton Therapy Center [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_589", "text": "The proton therapy center and the cyclotron closed operations on December 5, 2014. [ 9 ]  The decision was made due to a lack of revenue and debt incurred by the center, as well as advances in proton therapy around the country that \"now make the equipment and methods at the proton therapy center out of date.\" [ 10 ]  The proton center was able to produce spot scanning beams in 2008 and gate to both lung and heart."}
{"_id": "WikiPedia_Radiology$$$corpus_590", "text": "Radiation oncologists have been using  proton therapy  to treat cancer since the 1950s. Long recognized for their targeting capability, proton beams achieve greater precision than traditional X-rays, while exposing healthy tissue to less radiation. This allows physicians to deliver high doses of radiation even when tumors are close to sensitive organs and tissue. A proton therapy beam's powerful energy is focused directly on a patient's tumor. Once released, the energy stops \u2013 there is no exit dose and no additional radiation unlike X-ray beams and gamma knife rays. [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_591", "text": "The  International Commission on Radiation Units and Measurements  ( ICRU ) is a standardization body set up in 1925 by the International Congress of Radiology, originally as the  X-Ray Unit Committee  until 1950. Its objective \"is to develop concepts, definitions and recommendations for the use of  quantities  and their  units  for  ionizing radiation  and its interaction with matter, in particular with respect to the biological effects induced by radiation\". [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_592", "text": "The ICRU is a sister organisation to the  International Commission on Radiological Protection  (ICRP). In general terms the ICRU defines the units, and the ICRP recommends how they are used for  radiation protection ."}
{"_id": "WikiPedia_Radiology$$$corpus_593", "text": "During the first two decades of its existence, its formal meetings were held during the International Congress of Radiology, but from 1950 onwards, when its mandate was extended, it has met annually.\nUntil 1953, the president of the ICRU was a national of the country that was hosting the ICR, but in that year it was decided to elect a permanent commission - the first permanent chairman being  Lauriston S. Taylor  who had been a member of the commission since 1928 and secretary since 1934.  Taylor served until 1969 and on his retirement was accorded the position of honorary chairman which we held until his death in 2004, aged 102. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_594", "text": "In the late 1950s the ICRU was invited by the CGPM to join other scientific bodies to work with the  International Committee for Weights and Measures  (CIPM) in the development of a system of units that could be used consistently over many disciplines.  This body, initially known as the \"Commission for the System of Units\" (renamed in 1964 as the \"Consultative Committee for Units\") was responsible overseeing the development of the  International System of Units  (SI). [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_595", "text": "In the late 1950s the ICRU started publishing reports on an irregular basis - on average two to three a year.  In 2001 the publication cycle was regularised and reports are now published bi-annually under the banner \"Journal of the ICRU\". [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_596", "text": "The commission has a maximum of fifteen members who serve for four years and who, since 1950, have been nominated by the  incumbent commissioners. Members are selected for their scientific ability and is widely regarded as the foremost\npanel of experts in radiation medicine and in the other fields of ICRU endeavor. The commission is funded by the sale of reports, by grants from the  European Commission , the  US National Cancer Institute  and the  International Atomic Energy Agency  and indirectly by organisations and companies who provide meeting venues.  Commissioners, many of whom have full-time university or research centre appointments, have their expenses reimbursed, but otherwise they receive no remuneration from the ICRU. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_597", "text": "The commission has been responsible for defining and introducing many of the following units of measure.  The number of different units for various quantities is indicative of changes of thinking in world metrology, especially the movement from  cgs  to  SI  units. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_598", "text": "The following table shows radiation quantities in SI and non-SI units."}
{"_id": "WikiPedia_Radiology$$$corpus_599", "text": "Although the United States Nuclear Regulatory Commission permits the use of the units  curie , rad, and  rem  alongside SI units, [ 7 ]  the  European Union   European units of measurement directives  required that their use for \"public health ... purposes\" be phased out by 31 December 1985. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_600", "text": "The Commission's secretariat is in Stockholm and its legal status is that of British  charity  (Not-for-profit organisation)."}
{"_id": "WikiPedia_Radiology$$$corpus_601", "text": "The  International Commission for Radiological Education  ( ICRE ) was the third of the three commissions established in 1928 at the second  International Congress of Radiology . It operates under the auspices of the International Congress of Radiology and is funded by the  International Society for Radiology . The commission's mandate is to coordinate the activities of radiologists in the field of education and to investigate educational standards and facilities in all countries in respect of radiological subjects. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_602", "text": "Its early records appear to have been lost during the  Second World War . [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_603", "text": "The  International Congress of Radiology  ( ICR ) is a meeting of radiologists for the exchange of ideas and the harmonisation of international standards and practice, first held in 1925 in London and held at regular intervals since then.  Since 1994 it has become a biennial event.  Until 1953 each congress was organised by radiological society of the host country, but in that year, a formal organisation, the  International Society for Radiology  was set up to provide continuity between the congresses."}
{"_id": "WikiPedia_Radiology$$$corpus_604", "text": "At the second congress, held in 1928 in Stockholm, three international commissions were set up - the  International Commission on Radiological Protection  (ICRP), the  International Commission on Radiation Units and Measurements  (ICRU) and the  International Commission on Radiological Education  (ICRE).  The former two have become fully functional organisations in their own right while the latter has remained a sub-committee of the ICR. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_605", "text": "Within years of  R\u00f6ntgen  discovering  X-Rays  in 1895, they were being used for imaging fractured bones.  Various societies sprung up in different countries where ideas were exchanged between like-minded people and national standards for the measurement of X-Ray intensity developed. These societies also tried to address the problems associated with the dangers of X-Rays, particularly  cancer ."}
{"_id": "WikiPedia_Radiology$$$corpus_606", "text": "By the end of the  First World War  a number of proposals on how to measure the intensity of X-Rays had been made, but there was little agreement between the various parties concerned. [ 1 ]  In 1925 the British Institute of Radiology, under the leadership of  Charles Thurstan Holland [ 2 ] [ 3 ]  invited delegates from a number of countries to attend the First International Congress on Radiation in London.  This congress set up a framework for future meetings - future congresses would meet every three years in a different country, would be organised by the host country. The host country would nominate the chairman of the congress. It was also established that three commissions should be set up which would meet at the congresses:"}
{"_id": "WikiPedia_Radiology$$$corpus_607", "text": "Until the outbreak of the Second World War, congresses were held every three years.  The 1940 congress was due to meet in Berlin in 1940, but was suspended due to the war. Apart from some copies of records kept by the 1973 Congress secretary-general, Benjamin Orndoff, the records of the congress, which had been handed to the German organisers in preparation for the next congress in Germany, were lost during the  Second World War . [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_608", "text": "The second congress was held in Stockholm under the chairmanship of  Manne Siegbahn  where the three commissions proposed in London met for the first time. Subsequent meetings were held in Paris (1931), Zurich (1934) and Chicago (1937)."}
{"_id": "WikiPedia_Radiology$$$corpus_609", "text": "After the war, the British Institute of Radiology organised the sixth Congress which was held in London, exactly 25 years after the first congress and in the same hall as the first congress. A total of 3364 people from 54 countries including 1,742 radiologists registered for the congress. [ 5 ]  The incumbent chairman of the ICR,  Arthur C. Christie , who had been nominated thirteen years before was unable to attend the London conference, so Orndoff, the secretary-general of that congress deputised handing the presidency to  Ralston Paterson . The congress also saw a resumption of the work of the three international commissions."}
{"_id": "WikiPedia_Radiology$$$corpus_610", "text": "At the seventh congress, held in Copenhagen in 1953, the organisational details of the conference were overhauled and an executive committee under the chairmanship of  Lauriston S. Taylor   was set up to oversee the organisation of future congresses and to provide continuity between congresses."}
{"_id": "WikiPedia_Radiology$$$corpus_611", "text": "Before the Second World War, the location of the congresses was dictated largely by the places of residence of the delegates who had to travel by rail or sea - a delegate from the western seaboard of the United States would have to commit a month to attend a week-long ICR congress in Europe.  The advent of air travel removed this restriction and subsequent congresses have since been held in many parts of the world. The following congresses have been held to date (or are scheduled): [ 4 ] [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_612", "text": "The International Society of Radiology was set up in 1953 to oversee the organisation of the International Congresses of Radiology and to provide continuity between congresses."}
{"_id": "WikiPedia_Radiology$$$corpus_613", "text": "The 1950 congress provided an occasion for workers in the radiology industry to meet for the first time in over a decade and to discuss the direction future congresses should take. At the 1953 congress, under the guidance of  Flemming Norgaard  in Copenhagen  the International Society of Radiology was set up to oversee the organisation of the International Congresses of Radiology rather than the ad hoc arrangement whereby the organisation of the next congress was left entirely in the hands of the host country. A permanent committee would also provide continuity between congresses. Norgard became the first secretary-general of the Society, while the radiologist from the sponsoring society who had been president of a congress was, by that token, president of the ISR until the next meeting. [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_614", "text": "The  Italian Society of Medical and Interventional Radiology  ( Italian :  Societ\u00e0 Italiana di Radiologia Medica e Interventistica ) is a medical association of Italian  radiologists , consisting of about 11,000 members (in 2019). [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_615", "text": "This article about an organisation based in Italy is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Radiology$$$corpus_616", "text": "The  National Council on Radiation Protection and Measurements  ( NCRP ), formerly the  National Committee on Radiation Protection and Measurements , and before that the  Advisory Committee on X-Ray and Radium Protection  ( ACXRP ), is a  U.S.  organization.  It has a  congressional charter  under  Title 36 of the United States Code , but this does not imply any sort of oversight by Congress; NCRP is not a government entity."}
{"_id": "WikiPedia_Radiology$$$corpus_617", "text": "The Advisory Committee on X-Ray and Radium Protection was established in 1929. [ 1 ]  Initially, the organization was an informal collective of scientists seeking to proffer accurate information and appropriate recommendations for radiation protection. In 1946, the organization changed its name to the National Committee on Radiation Protection and Measurements. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_618", "text": "In 1964, the  U.S. Congress  reorganized and chartered the organization as the National Council on Radiation Protection and Measurements. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_619", "text": "Nycomed Amersham Intercontinental Continuing Education in Radiology Institute  or  NICER Institute  was an educational institute for training in  radiology  headquartered in  Oslo ,  Norway . It was founded by Professor  Holger Pettersson , president of the  European Association of Radiology  and  Dr.  Harald Ostensen . It offered 50 courses in 22 countries over the world and published various educational materials, including collaboration in publishing of the comprehensive 8-volume  Encyclopaedia of Medical Imaging . The institute was closed in December 2001, partially due to financial reasons. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_620", "text": "This article relating to education in Europe is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Radiology$$$corpus_621", "text": "The  Norwich Radiology Academy , opened in November 2005, is part of the  Norfolk and Norwich University Hospital NHS Trust  and is one of only three training centres in  England  specially created for training consultant  radiologists . [ 1 ]  The Norwich Radiology Academy is located in the Cotman Centre on the Norwich Research Park  [ 2 ]  and was formally opened in February 2006 by the President of the  Royal College of Radiologists , Professor Janet Husband."}
{"_id": "WikiPedia_Radiology$$$corpus_622", "text": "The  Department of Health  and  Royal College of Radiologists  jointly developed the  Radiology-Integrated Training Initiative . The initiative provides additional radiology training by splitting training time between a teaching hospital and the radiology academy."}
{"_id": "WikiPedia_Radiology$$$corpus_623", "text": "52\u00b037\u203229\u2033N   1\u00b013\u203223\u2033E \ufeff / \ufeff 52.6247\u00b0N 1.2230\u00b0E \ufeff /  52.6247; 1.2230"}
{"_id": "WikiPedia_Radiology$$$corpus_624", "text": "The  Radiation and Nuclear Safety Authority  ( Finnish :  S\u00e4teilyturvakeskus ,  Swedish :  Str\u00e5ls\u00e4kerhetscentralen ), often abbreviated as  STUK , is a  government agency  tasked with  nuclear safety  and  radiation monitoring  in  Finland . [ 1 ]   The agency is a division of the Ministry of Social Affairs and Health; when founded in 1958 STUK was first charged with inspection of radiation equipment used in hospitals. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_625", "text": "The agency is also a scientific research and education organization, researching the nature, effects and damaging effects of radiation. The agency currently employs about 320 people, and is led by Petteri Tiippana. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_626", "text": "The agency works in collaboration with  EU  and other nearby countries, as part of the  European Nuclear Safety Regulators Group  (ENSREG), and with the  UN  organization  International Atomic Energy Agency  (IAEA) along with the  International Commission on Radiological Protection  (ICRP)."}
{"_id": "WikiPedia_Radiology$$$corpus_627", "text": "The director general of Nuclear Safety Authority was Jukka Laaksonen during 1997\u20132012, Tero Varjoranta in 2013, [ 4 ] [ 5 ]  and is now  Petteri Tiippana . [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_628", "text": "Tero Varjoranta was named as the deputy director general United Nations nuclear inspectorate the IAEA in 2013. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_629", "text": "The director general of Nuclear Safety Authority,  Jukka Laaksonen , became  Rosatom  Overseas Vice President immediately after retiring. This was criticised but according to media reporting there was no legislation to prevent it. In February 2013 he gave statements for the  Fennovoima  potential nuclear plant in  Pyh\u00e4joki . [ 7 ]  Fennovoima nuclear plant project is disputed.  Heidi Hautala  demanded in February 2013 new application for the Parliament since  E.ON  cancelled its participation with 34% ownership. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_630", "text": "\"The  Radiation Therapy Oncology Group (RTOG)  was initially organized in 1968 under the direction of Simon Kramer as a national cooperative group for the purpose of conducting  radiation therapy  research and  clinical investigations  in order to treat cancers, including  endometrial  and  cervical  cancer. [ 1 ]  Funding from the  National Cancer Institute  (NCI) began in 1971."}
{"_id": "WikiPedia_Radiology$$$corpus_631", "text": "Its first study was in 1968, an  adjuvant   methotrexate  study for  head and neck cancer . The methotrexate study employed combinations of radiation, methotrexate and surgery in the treatment of advanced head and neck cancer. 700 patients were used to this study clinical investigations in the area of head and neck cancer. [ 2 ]  In 2009, it was reported RTOG accrued a total of about 60,000 patients for studies. [ 2 ]  An academically controversial study RTOG published demonstrated good results for treating low-grade  glioma , although as of 2015 [update]  this treatment was generally incompatible with  chemotherapy  options for treatment such as  temozolomide . [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_632", "text": "RTOG headquarters are located at the offices of the American College of Radiology in  Philadelphia, Pennsylvania . [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_633", "text": "The  Radiological Society of North America  ( RSNA ) is a  non-profit organization  and an international society of radiologists, medical physicists and other medical imaging professionals representing 31 radiologic subspecialties from 145 countries around the world. [ 1 ]  Based in  Oak Brook , Illinois, it was established in 1915."}
{"_id": "WikiPedia_Radiology$$$corpus_634", "text": "The Society hosts an annual conference in Chicago and develops educational resources such as courses, workshops and webinars. RSNA also publishes six peer-reviewed radiology journals, offers quality improvement tools, [ 2 ]  sponsors research to advance quantitative imaging biomarkers, [ 3 ]  and conducts outreach to enhance radiology education and patient care in low-income and middle-income countries. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_635", "text": "RSNA hosts the world's largest annual [ 5 ]  medical imaging conference, [ 6 ]  a five-day event starting the last Sunday of November at the  McCormick Place  convention center in  Chicago ."}
{"_id": "WikiPedia_Radiology$$$corpus_636", "text": "RSNA publishes six peer-reviewed journals: [ 7 ]   Radiology , [ 8 ]  offering radiology research and reviews;  RadioGraphics , [ 9 ]  dedicated to continuing education in radiology;  Radiology: Artificial Intelligence , [ 10 ]  highlights the emerging applications of machine learning and  artificial intelligence  in the field of imaging across multiple disciplines;  Radiology: Cardiothoracic Imaging , [ 11 ]  emphasizes research advances and technical developments in medical imaging that drive cardiothoracic medicine;  Radiology: Imaging Cancer [ 12 ] ,  covers the best clinical and translational cancer imaging studies across organ systems and modalities, including leading-edge technological developments;  Radiology Advances [ 13 ] ,  an open access journal focusing on the publication of a broad spectrum of high-quality international radiology and medical imaging research."}
{"_id": "WikiPedia_Radiology$$$corpus_637", "text": "RSNA Case Collection [ 14 ]  is an online resource of clinical cases intended to be used as an educational tool. Developed by and created for radiologists, RSNA Case Collection includes image-focused case reports from across radiology subspecialties and consists of images, relevant patient information, final and differential diagnoses, case discussions and references. All cases undergo careful peer review before they are assigned a DOI - allowing them to be fully citable."}
{"_id": "WikiPedia_Radiology$$$corpus_638", "text": "RSNA Case Collection is supported by an active presence on X (formerly Twitter)."}
{"_id": "WikiPedia_Radiology$$$corpus_639", "text": "The RSNA Imaging AI Certificate program [ 15 ]  is a radiology-specific imaging AI certificate program that combines a case-based curriculum and on-demand learning with practical application."}
{"_id": "WikiPedia_Radiology$$$corpus_640", "text": "The program is for radiologists, radiology residents, physicists, data scientists and clinical researchers who want to learn how to safely evaluate, implement, use and monitor performance of AI-based tools for medical imaging."}
{"_id": "WikiPedia_Radiology$$$corpus_641", "text": "There are three courses currently available within the program: the Foundational Certificate course, the Advanced Certificate course and the Emergency Certificate course."}
{"_id": "WikiPedia_Radiology$$$corpus_642", "text": "Available in English and Spanish, RadiologyInfo.org [ 16 ]  is the public information website developed and funded by RSNA and the  American College of Radiology . It was established to inform and educate the general public about what  radiology  is and what  radiologists  do. Approximately half a million people visit RadiologyInfo.org each month [ citation needed ] ."}
{"_id": "WikiPedia_Radiology$$$corpus_643", "text": "The RSNA R&E Foundation supports radiology research through grant funding, training opportunities and industry initiatives that advance innovation in radiology. The Foundation has awarded $84 million in grants since 1984. [ 17 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_644", "text": "Curtis P. Langlotz, MD, PhD, is the 2023-2024 president of RSNA's Board of Directors. [ 18 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_645", "text": "Radiologists without Borders  is a 401(c)(3)  non-profit organization  that delivers humanitarian aid to developing countries, in the form of radiological services and equipment. [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 5 ] [ 6 ] [ 7 ] [ 8 ] [ 9 ]  Radiologists without Borders was founded in 2008, by New York-based radiologist Tariq Gill. [ 10 ]  The organization is composed entirely of volunteers, and its mission statement is \"to bring life saving diagnostic imaging solutions to medically underserved populations worldwide.\" [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_646", "text": "Radiologists without Borders began work in Haiti after the  2010 earthquake . They have provided an ultrasound to the City Hospital and provided training of medical personnel. [ 4 ]  The group worked with  Muhimbili University of Health and Allied Sciences (MUHAS)  and Muhimbili Hospital in 2010 and 2011 to research needs of the school and university. Radiologists without Borders arranged for training of medical personnel which took place at  Lourdes Hospital  in Binghamton, New York, has donated 2 mammography machines, and textbooks and computers for the school. [ 3 ] [ 4 ] [ 5 ] [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_647", "text": "This article related to a non-profit organization is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Radiology$$$corpus_648", "text": "The  Radiology-Integrated Training Initiative  ( R-ITI ) is a public-sector UK programme to provide an increased number of high-quality  radiologists  by 2008."}
{"_id": "WikiPedia_Radiology$$$corpus_649", "text": "R-ITI is a collaboration between the  Royal College of Radiologists , the UK  Department of Health  and the  NHS . It is tasked with providing three new  radiology  academies, a national archive of peer-validated cases (Validated Case Archive), and over 1,000  e-learning  sessions for self-paced learning & knowledge acquisition."}
{"_id": "WikiPedia_Radiology$$$corpus_650", "text": "The UK is currently not producing enough UK trained radiologists to meet clinical need. Calculations show that traditional training will not produce the necessary increase in numbers. Training schemes are becoming saturated and  consultant  training time is pressurised by heavy service workloads."}
{"_id": "WikiPedia_Radiology$$$corpus_651", "text": "The Radiology Integrated Training Initiative (R-ITI) has been created to respond to this need and develop a new approach to training radiologists, increasing capacity to meet demand without putting additional strain on current resources."}
{"_id": "WikiPedia_Radiology$$$corpus_652", "text": "Three academies have been established, one in  Leeds , one in  Norwich  at the  Norfolk and Norwich University Hospital  and one in  Plymouth . A fourth academy has been announced in South Wales, to begin intake in August 2017. Each academy offers trainees access to:"}
{"_id": "WikiPedia_Radiology$$$corpus_653", "text": "The Integrated Training Initiative (ITI) creates a stimulating learning environment by combining different teaching methods. These methods include:"}
{"_id": "WikiPedia_Radiology$$$corpus_654", "text": "The Royal Australian and New Zealand College of Radiologists  ( RANZCR ) is the leading professional organisation for the promotion of the science and practice of the medical specialties of clinical radiology (diagnostic and interventional  radiology ) and  radiation oncology  in Australia and  New Zealand . The college has members throughout the world. RANZCR provides the educational curricula for medical graduates training to enter the specialties."}
{"_id": "WikiPedia_Radiology$$$corpus_655", "text": "RANZCR is independent of universities and is scrutinised and externally accredited against industry standards by the  Australian Medical Council  (AMC). [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_656", "text": "The official journal of the college is the  Journal of Medical Imaging and Radiation Oncology ."}
{"_id": "WikiPedia_Radiology$$$corpus_657", "text": "Very soon after the discovery of X-rays in 1895, and radium in 1896, members of the fledgling specialties of radiology and radiation therapy had begun practising across Australia and New Zealand. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_658", "text": "In 1935, the Australian and New Zealand Association of Radiology was formed, with the purposes of setting minimum standards of training and conduct, stimulating interest in research, and otherwise enhancing the prestige and professionalism of the specialties. The Association was the third professional medical body to be formed in Australia. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_659", "text": "In 1949 the Association became the College of Radiologists (Australia and New Zealand). Further name changes followed in 1952 (College of Radiologists of Australasia), 1972 (Royal Australasian College of Radiologists) and 1997 (The Royal Australian and New Zealand College of Radiologists)."}
{"_id": "WikiPedia_Radiology$$$corpus_660", "text": "The RANZCR head office was for many years located in rooms on Macquarie Street, Sydney. Larger premises were purchased in Lower Fort Street, the Rocks, Sydney, in 1977 where the college head office remained until its move to 51 Druitt Street, Sydney, in 1997. The college's New Zealand offices are located in Wellington. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_661", "text": "RANZCR remains the peak body in Australia and New Zealand for practitioners of clinical radiology and radiation oncology, and continues to pursue the purposes of excellence in training, research and medical professionalism. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_662", "text": "Following earlier enquiries to the Portcullis Pursuivant of Arms, the RANZCR Council submitted the relevant documentation (numbers of Fellows, Members, Associates and Life Members, relevant Memoranda and Article) and \u00a3365 fee to the College of Arms in 1963. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_663", "text": "The following symbols are incorporated in the RANZCR crest: [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_664", "text": "The Coat of Arms was granted by  Queen Elizabeth II  on 2 September 1964. [ 4 ] [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_665", "text": "Members were asked to suggest a motto.  Latin :  Lumen Afferimus Morbis  (We Cast Light on Disease), suggested by Dr Colin Macdonald, was selected but not without protest regarding the accuracy of the Latin. Advice from the College of Arms and also Prof. A. J. Dunston, Professor of Latin at the  University of Sydney , was that the suggested motto was in order and suitable. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_666", "text": "Permission to use the \u2018Royal\u2019 prefix, first applied for in 1967 but rejected by the then Prime Minister, RG Menzies, was granted in September 1971 by W McMahon. On 28 July 1972, the Australasian College of Radiologists became \u2018The Royal Australasian College of Radiologists\u2019. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_667", "text": "RANZCR is led by clinicians who are democratically elected by the membership. The ultimate oversight and responsibility is vested in the RANZCR board of directors."}
{"_id": "WikiPedia_Radiology$$$corpus_668", "text": "The following individuals have served as president of The Royal Australian and New Zealand College of Radiologists, or any precedent name of the college: [ 4 ] [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_669", "text": "RANZCR has two faculties: the Faculty of Clinical Radiology (established 2013) and the Faculty of Radiation Oncology (established 1994). [ 4 ] [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_670", "text": "As of 31 December 2016, RANZCR had 3515 active members, including 2467 clinical radiologists, 421 radiation oncologists, and 627 trainees. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_671", "text": "There are six categories of membership, each with their own particular rights, entitlements and responsibilities as prescribed in the RANZCR's Articles of Association: [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_672", "text": "RANZCR is responsible for the training of clinical radiologists and  radiation oncologists  in Australia and New Zealand. Training, under the auspices of RANZCR, can also be undertaken in Singapore. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_673", "text": "Following a 1998 Australian Medical Council (AMC) undertaking to review all specialist medical training programs in Australia, RANZCR volunteered to be one of two medical colleges to undertake a review of their training programs. This 2004 review identified that a more structured approach to the training program assessment, including a formal curriculum, was required. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_674", "text": "Curricula were developed for each of the radiation oncology and clinical radiology training programs, launched in 2008 and 2009 respectively. These curricula follow key educational principles: [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_675", "text": "Following successful completion of training, graduates are awarded Fellowship of The Royal Australian and New Zealand College of Radiologists (FRANZCR)."}
{"_id": "WikiPedia_Radiology$$$corpus_676", "text": "Specialist medical registration with the Medical Board of Australia \u201cis available to medical practitioners who have been assessed by an AMC accredited specialist college as being eligible for fellowship.\u201d [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_677", "text": "Clinical radiology Fellows and trainees are able to undertake further sub-specialty study in nuclear medicine through the combined  Royal Australasian College of Physicians  (RACP)/RANZCR nuclear medicine training program. [ 13 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_678", "text": "The  Singapore Gamma Knife Centre  is a medical facility specialising in  gamma knife radiosurgery ."}
{"_id": "WikiPedia_Radiology$$$corpus_679", "text": "Construction of the  Singapore  Gamma Knife Centre was funded by the Health Corporation of Singapore (HCS) and the Singapore Technologies Precision Engineering (STPE). The project was the first of its kind in  Southeast Asia , and the budget totalled to around ten million dollars. The centre's official opening ceremony was held on 5 March 1996, [ 1 ] [ 2 ]  although surgeries at the centre only began on 27 November 1996. [ 3 ] [ a ]  As it did not involve incision of the brain, the public welcomed the introduction of gamma knife radiosurgery to  Singapore . [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_680", "text": "The facility is based in the  Balestier Road -based  ParkwayHealth  Day Surgery & Medical Centre. [ 3 ]  An independent medical centre, any member of the public, local or foreigner, is entitled to make use of it. [ 5 ]  The centre promotes itself as \"Asia's leading gamma knife centre\" and \"the only gamma knife facility in Singapore\". [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_681", "text": "1\u00b019\u203220\u2033N   103\u00b050\u203238\u2033E \ufeff / \ufeff 1.3221\u00b0N 103.8440\u00b0E \ufeff /  1.3221; 103.8440"}
{"_id": "WikiPedia_Radiology$$$corpus_682", "text": "The  Society for Pediatric Radiology  is a  professional association  of  pediatric radiologists . The Society publishes the journal  Pediatric Radiology  and holds a yearly meeting. It was founded in 1958 at an informal meeting in Washington, DC, United States. Instrumental in its founding were  John Caffey ,  Edward Neuhauser , and Frederic Silverman. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_683", "text": "This  pediatrics  article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Radiology$$$corpus_684", "text": "The  Society of Interventional Radiology  ( SIR ) is an American national organization of physicians, scientists and allied health professionals dedicated to improving public health through the use of minimally invasive, image-guided therapeutic interventions for  disease management . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_685", "text": "It was founded in 1973 as the  Society of Cardiovascular Radiology  by an active group in the field who wanted to further develop interventional aspects of radiology. It changed its name to the  Society of CardioVascular and Interventional Radiology  in 1983. In April 2002, the name was changed to  Society of Interventional Radiology  in order to emphasise the expanding role of  interventional radiology  that is no longer limited to the  cardiovascular system . The society comprises about 8,000 members (March 2023): including practicing physicians, trainees, scientists and clinical associates, such as physician assistants, nurse practitioners, radiologic technologists and paramedical professionals. [ 1 ]   Katharine L. Krol  served as the Society's first female president.  [ citation needed ]  The  Journal of Vascular and Interventional Radiology  (JVIR) is the Society's official journal."}
{"_id": "WikiPedia_Radiology$$$corpus_686", "text": "The Society of Interventional Radiology Political Action Committee (SIRPAC) is a nonpartisan political organization that supports political candidates and elected officials who are dedicated to advancing the interests of interventional radiologists and the patients they serve. SIRPAC is funded through donations from SIR members, and uses these funds to support political candidates who have demonstrated a commitment to policies that promote patient access to interventional radiology services and advance the specialty."}
{"_id": "WikiPedia_Radiology$$$corpus_687", "text": "During the 2022 election cycle, SIRPAC donated $135,682 to candidates (65.65% to Democrats, 34.35% to Republicans) and raised more than $180,000 from members. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_688", "text": "This article about a  medical association  is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Radiology$$$corpus_689", "text": "The  Society of Radiographers  ( SoR ) is a professional body and trade union that represents more than 90 percent of the  diagnostic  and  therapeutic radiographers  in the  United Kingdom . [ 8 ]  The  College of Radiographers  ( CoR ) is a charitable subsidiary of the Society, they are collectively known as the  Society and College of Radiographers  ( SCoR )."}
{"_id": "WikiPedia_Radiology$$$corpus_690", "text": "It was founded in 1920 in an effort to provide standardised training and registration for Radiographers within the British Isles. [ 9 ]  Until 1996, the SoR was also the professional body and trades union for radiographers in  Ireland  whereupon the  Irish Institute of Radiography and Radiation Therapy  was established. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_691", "text": "In the second decade of the 20th century the number of x-ray workers grew dramatically not least due to the impact of World War I and in post-war Britain the formation of an association of such workers was inevitable. This was hastened by the desire of medical practitioners (radiologists) to secure the 'ownership' of x-ray work and leading radiologists at the time approached the Institute of Electrical Engineers for support. As a result the Society of Radiographers was established in 1920 with its first council composed of six radiologists and six electrical engineers, to which were added six selected radiographers from the London area."}
{"_id": "WikiPedia_Radiology$$$corpus_692", "text": "In 1921, a syllabus was developed and examinations were introduced to facilitate competency checks before membership was granted to new members. The first batch to qualify for membership included  Kathleen Clark  who would establish rigour in the profession. [ 10 ]  Membership began to grow with 67 members in 1921 and 164 in 1923. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_693", "text": "The medical members with external assistance attempted to prevent radiographers from reporting on their images. This was to be a crucial step along the road to medical ownership of x-ray work and to establish consultant posts in radiology. It was in 1925  that there was agreement that non-medical members would not report and if they did they would be liable to dismissal from the society. There was opposition to this from some radiographer council members especially Mr Blake but also from the Electrical Engineers representatives. In fact they resigned en-masse including  A A Campbell Swinton  is said to be the first person in the UK to produce a radiograph. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_694", "text": "After this there followed a long period of medical dominance. It was not until the 1970s that Dr Swinburne, a radiologist, from Leeds said it was time for official recognition that radiographers assist in film interpretations. It was another 20 years before the first reporting courses for radiographers were established.  By 1997 it was official policy of the College of Radiographers that  \"reporting by radiographers is not an option. For the future, it is a requirement.\" [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_695", "text": "The society formed a South African branch in 1930 and established a pattern of branch formation with a local committee management which was propagated in the UK  during the 1930s. As a result, the Scottish Radiographic Society which was formed in 1927 became a branch of the society in 1936, the South West Branch in 1937, the North West in 1942, the Midland and the North East in 1943. The first Annual Conference of the Society of Radiographers was in 1947 held at Bath, England. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_696", "text": "In June 2015, the  National Institute for Health and Care Excellence (NICE)  granted accreditation to the processes used by the SCoR in order to generate current clinical guidance for Radiography practice, meaning that the SCoR is NICE accredited. [ 11 ] [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_697", "text": "The objectives for which The Society of Radiographers is established are as follows: [ 13 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_698", "text": "The college's objectives are directed towards education, research and other activities in support of the science and practice of radiography."}
{"_id": "WikiPedia_Radiology$$$corpus_699", "text": "The society and college is led by a council which is made-up of representatives from a number of  English regions  (Eastern region, London region, Midlands region, North West region, Northern region, South East region, South West region, Yorkshire & North Trent region) and from  Northern Ireland ,  Scotland  and  Wales . [ 14 ]  The Council determines the Society's policy and strategic direction in consultation with members and others that have a vested interest. It meets once a month, with the exception of August and December."}
{"_id": "WikiPedia_Radiology$$$corpus_700", "text": "The society is a  company limited by guarantee  and the members of council are  company directors  registered at  Companies House . The college, a registered  charity , has its own Board of directors comprising an equal number of members drawn from council and external directors representing the legal, financial and medical fields. They have responsibilities as representatives of the membership and also as directors of the company. Neither council members nor College Board members are paid for their duties but they can claim travelling and other  expenses ."}
{"_id": "WikiPedia_Radiology$$$corpus_701", "text": "The president is elected by the members of council and is inaugurated at the July council meeting each year. [ 13 ]  There is also a President-elect and a Vice-president, who also serve for one year."}
{"_id": "WikiPedia_Radiology$$$corpus_702", "text": "MSc BSc (Hons) PgCUTL FHEA"}
{"_id": "WikiPedia_Radiology$$$corpus_703", "text": "BSc (Hons) PgD"}
{"_id": "WikiPedia_Radiology$$$corpus_704", "text": "DCR(T)"}
{"_id": "WikiPedia_Radiology$$$corpus_705", "text": "The patron of the Society and College of Radiographers is  The Rt Hon Llinos \"Llin\" Golding, Baroness Golding of Newcastle-under-Lyme  who is a  Labour Party  politician and former  MP  who sits in the  House of Lords  and who previously practiced as a radiographer. [ 22 ] [ 23 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_706", "text": "Historically, the college was an awarding body for  academic awards  but no longer fulfils this function. The degree-equivalent [ 24 ]  radiography qualification awarded by the CoR was the Diploma of the College of Radiographers (DCR) and this was awarded following a three-year training course and successful completion of a national examination, either in Radiodiagnosis (the DCR(R)) or in Therapy Radiography (the DCR(T)). Following study equivalent to Masters level, students with a DCR could proceed by examination to the Higher Diploma of the College of Radiographers (HDCR). Holders of the HDCR undergoing specialist training in management were awarded the Management Diploma of the College of Radiographers (MDCR) and those undergoing specialist training in the teaching of radiography were awarded the Teaching Diploma of the College of Radiographers (TDCR). The first  Bachelor of Science  (BSc) in Radiography was validated in 1989 and with the widespread introduction of BSc courses in radiography during 1993, the DCR was phased out. The HRCR, TDCR and MDCR have been replaced by postgraduate level courses."}
{"_id": "WikiPedia_Radiology$$$corpus_707", "text": "The college maintains an Accreditation and Approval Board which aims to protect patients of radiographers by raising the standards of education and practice. It does so by monitoring and assessing programmes of both pre-registration degree courses and ongoing professional education ranging from ad-hoc events to professional postgraduate training. The college runs courses and conferences. Various guidances and guidelines are published by the CoR often in conjunction with the  Institute of Physics and Engineering in Medicine  (IPEM), the  Royal College of Radiologists  (RCR), the  British Institute of Radiology  (BIR) and the  Royal College of Nursing  (RCN)."}
{"_id": "WikiPedia_Radiology$$$corpus_708", "text": "Research grants are awarded by the college. An academic library is maintained. Further activities to promote the public interest includes the provision of advice to the public and to government and government agencies and activities to promote public awareness of radiography, radiology and oncology. Information on the activities of the CoR is published on the website of the UK's Charity Commission. [ 25 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_709", "text": "The society has a membership base throughout the United Kingdom. As such, the Trade Union is associated with the  Trade Union Congress (TUC) [ 5 ]  in the United Kingdom and with the  Scottish Trade Union Congress (STUC) . [ 6 ]  The organisation was previously associated with the  Irish Congress of Trade Unions(ICTU)  but it left in 2013 citing financial constraints as the reason. [ 26 ]  In 2003, before leaving and whilst still in affliction with the ICTU, the society opposed a motion to restrict affiliation of small unions with the ICTU stating that the motion was \"about bureaucracy.\" [ 27 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_710", "text": "The Society of Radiographers Benevolent Fund is a registered charity (No. 326398) and it assists SoR members, former members and their families in times of hardship or distress and in particular the old, the sick and the incapacitated among members and former members. Information on the activities of the Benevolent Fund is published on the website of the UK's Charity Commission. [ 28 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_711", "text": "The SCoR issues a number of publications: [ 29 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_712", "text": "The SCoR maintains a number of awards and grants."}
{"_id": "WikiPedia_Radiology$$$corpus_713", "text": "The Fellowship of the College of Radiographers (FCR) is an honorary title, bestowed upon individuals who have made significant contribution to the radiographic profession. It was first awarded, in its present format, in 1978 following the establishment of The College of Radiographers as the charitable subsidiary of The Society of Radiographers. Additionally, the individual receives complimentary life membership of The Society of Radiographers. [ 34 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_714", "text": "The Gold Medal is the highest award the Society may award and is only granted to individuals who have \"who have made exceptional contributions to radiography, developed the profession and advanced the Society and College of Radiographers.\" Fewer than 20 gold medals have ever been awarded. [ 35 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_715", "text": "The Silver Medal was first struck in 1985 and is awarded by The Society of Radiographers to recognise and acknowledge individuals for outstanding dedication and contribution to the profession of Radiography. Nominees must be members of the Society of Radiographers (or retired from active service and membership), or non-members who are outstanding contributors to the profession. Their work may span any aspect of the imaging and therapy modalities and/or the wider spheres of commerce, industry and management; as such overseas nominees are also eligible. Notable recipients include Stewart Whiteley [ 35 ]  who was the author for the revised editions of  Clark's positioning in Radiography , a fundamental diagnostic radiography textbook. [ 36 ] [ 37 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_716", "text": "Alan Nichols was a chief technical adviser to the Department of Radiology at  Oxford Hospitals  and since 1996, an award in his name has been given for the best paper proffered by a radiographer at the Radiology Congress. A representative of the Mr Nichols's family is invited to present the award. The Alan Nichols Memorial Award is currently \u00a3100. [ 38 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_717", "text": "This award, commemorating Beth Whittaker, has been awarded to the best poster presentation at the Annual Radiology Conference. The Beth Whittaker Award is currently \u00a350. [ 38 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_718", "text": "The Bryan Macey Scholarship, named for a former Chief Executive, is open to all Society Health and Safety and Industrial Relations representatives for trade union-related academic study. [ 39 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_719", "text": "The Forder Memorial Award, which commemorates the memory of Mr A O Forder, founder member of the SoR in 1920 and a member of the first council of the society. From 1995, it was agreed that it would be presented to the best paper proffered by a student at the Annual Students Conference. The winning student is awarded the prize of \u00a350. [ 38 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_720", "text": "In April 2009, the organisation launched the Arthur Kay Radiotherapy Award to support an annual award to an appropriately qualified and experienced therapeutic radiographer who wishes to travel to learn new and innovative techniques in therapeutic radiography. The fund will enable successful applicants to spend time studying innovations in technology and practice at a leading world class cancer institution(s). Applications for funding to the value of \u00a35000 will be considered although, for exceptional applications, more may be available to an absolute maximum of \u00a310,000. [ 40 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_721", "text": "The College of Radiographers Overseas Placement Fund was established in 1998. It is managed by the College of Radiographers Board of Trustees and a number of radiography placements in developing countries have been supported by the fund. A number of individual radiographers have taken an interest in this area and this has often resulted in periods of working overseas. [ 41 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_722", "text": "The Svedberg Laboratory [ 1 ]  (TSL) is a university facility, based in  Uppsala ,  Sweden . The activities at TSL are based around the  particle accelerator   Gustaf Werner cyclotron ."}
{"_id": "WikiPedia_Radiology$$$corpus_723", "text": "The main activity is  proton therapy  for the treatment of cancer, based on an agreement between the Oncology clinic at  Uppsala University Hospital  and  Uppsala University . Beamtime not used for proton therapy is devoted to commercial neutron and proton irradiation projects, mainly for Radiation testing. There is also some time for basic (academic) research and in this case the experiments should be associated to  Uppsala University  or to EC projects."}
{"_id": "WikiPedia_Radiology$$$corpus_724", "text": "TSL is supported by the European Community and belong to the EC projects ERINDA, [ 2 ]  SkyFlash [ 3 ]  and CHANDA. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_725", "text": "Theodor Svedberg  (1884\u20131971), professor in physical chemistry at  Uppsala University  from 1912 to 1949, was awarded the  Nobel Prize  in chemistry in 1926 [ 5 ]  for his research on dispersed systems (colloidal solutions). He invented the  Ultracentrifuge , which was used in the discovery that proteins consist of macromolecules."}
{"_id": "WikiPedia_Radiology$$$corpus_726", "text": "Towards the end of the 1930s The Svedberg and his colleagues built their first accelerator, a  Neutron generator . In 1945, a donation from the Gustaf Werner Corporation gave the opportunity to build a much larger accelerator, a synchrocyclotron. The Gustaf Werner Institute with the synchrocyclotron as the main research instrument was founded in 1949 and continued to act as a base for research in high-energy physics and radiation biology until 1986 when The Svedberg Laboratory was established."}
{"_id": "WikiPedia_Radiology$$$corpus_727", "text": "Intensive discussions concerning the type and size of accelerators Swedish research in nuclear and high-energy physics should have at its disposal took place in the early 1980s, One result of this process was that a decision was taken to bring the magnets of the so-called ICE-ring (Initial Cooling Experiment) from  CERN  to Uppsala. The accelerator ring was rebuilt as a cooler and storage ring and given the acronym CELSIUS (Cooling with ELectrons and Storing of Ions from the Uppsala Synchrocyclotron)."}
{"_id": "WikiPedia_Radiology$$$corpus_728", "text": "From 1994 until 2004 The Svedberg Laboratory was a national research facility funded to a large fraction from the Swedish Natural Science Research Council ( Swedish Research Council ). It was open for research groups from universities and institutes in Sweden and abroad. The laboratory had a nationally recruited board and an international program advisory committee, which gave recommendations concerning the research program by examining proposals from the user groups.  Uppsala University  was acting as the host of the Laboratory."}
{"_id": "WikiPedia_Radiology$$$corpus_729", "text": "The TSL was in 2004 converted from a national laboratory into a university facility and new instructions for the laboratory came into operation July 1, 2004. The main activity of TSL is based on an agreement between  Uppsala University Hospital  and  Uppsala University  about continued  proton therapy . The beamtime not used for proton therapy is devoted to commercial neutron and proton irradiation projects. There is still some time for basic (academic) research and in this case the experiments should be associated to Uppsala University or to EU projects."}
{"_id": "WikiPedia_Radiology$$$corpus_730", "text": "The proton beam extracted from the cyclotron may have exclusive advantages in treatment of certain human malignant tumours and some other disorders where conventional  radiation therapy  or surgery is not feasible. The depth dose distribution, with the  Bragg peak , and the relatively sharp penumbra, enables the concentration of radiation to the target volume and minimizes the dose to normal tissue surrounding the target. Proton beam irradiation may lead to cure or shrinkage of tumour burden in cases where other treatment modalities fail.\nAll patients are carefully investigated by computerized tomography and/or magnetic resonance imaging in order to obtain a detailed knowledge of the position and size of the tumour.  Angiography  and  positron emission tomography  will be used in certain cases. Before the treatments, careful  radiation treatment planning  is performed to ensure an optimal dose distribution.\nTreatments:"}
{"_id": "WikiPedia_Radiology$$$corpus_731", "text": "In June 2015 the  Uppsala University Hospital  will finish their treatments at TSL and move over to Skandion, [ 7 ]  a new dedicated clinic for  proton therapy  in Uppsala, Sweden."}
{"_id": "WikiPedia_Radiology$$$corpus_732", "text": "At TSL there are facilities with high-energy particle beams for different purposes.\nThe users mostly use them for testing reliability of electronic equipment under radiation exposure, accelerated radiation testing.\nOther use has also been seen, such as biomedical research, material science and production of filters and other things."}
{"_id": "WikiPedia_Radiology$$$corpus_733", "text": "The following facilities are available:"}
{"_id": "WikiPedia_Radiology$$$corpus_734", "text": "Simulates the  Cosmic ray  induced neutron field. Designed for Single Event Effects/Soft Error Rate testing."}
{"_id": "WikiPedia_Radiology$$$corpus_735", "text": "Makes it possible to study the energy dependence of neutron-induced effects in electronics."}
{"_id": "WikiPedia_Radiology$$$corpus_736", "text": "For Single Event Effects & Total Ionisation Dose testing"}
{"_id": "WikiPedia_Radiology$$$corpus_737", "text": "During the years the cyclotron have delivered heavy ions for research and industrial projects.\nThe cyclotron then used an external ion source, an ECRIS, for preacceleration of heavy ions."}
{"_id": "WikiPedia_Radiology$$$corpus_738", "text": "Machine Name: Gustaf Werner Cyclotron"}
{"_id": "WikiPedia_Radiology$$$corpus_739", "text": "History \nThe machine was designed in house and constructed during 1946\u201351 with first beam in 1951. The machine was then rebuilt 1977\u201386 with first beam in 1986."}
{"_id": "WikiPedia_Radiology$$$corpus_740", "text": "Characteristic Beams out of the machine\u00a0:\nions / energy(MeV/N) /current(pps)"}
{"_id": "WikiPedia_Radiology$$$corpus_741", "text": "Secondary beam facility:\nneutrons via 7Li(p,n) reaction"}
{"_id": "WikiPedia_Radiology$$$corpus_742", "text": "Transmission Efficiency (source to extracted beam)"}
{"_id": "WikiPedia_Radiology$$$corpus_743", "text": "Technical data \n (a)Magnet (nr 1 in picture)"}
{"_id": "WikiPedia_Radiology$$$corpus_744", "text": "Trim Coils"}
{"_id": "WikiPedia_Radiology$$$corpus_745", "text": "Harmonic Coils"}
{"_id": "WikiPedia_Radiology$$$corpus_746", "text": "Main Coils"}
{"_id": "WikiPedia_Radiology$$$corpus_747", "text": "Power"}
{"_id": "WikiPedia_Radiology$$$corpus_748", "text": "(b)RF (nr 3 in picture) \nAcceleration"}
{"_id": "WikiPedia_Radiology$$$corpus_749", "text": "Voltage"}
{"_id": "WikiPedia_Radiology$$$corpus_750", "text": "(c)Injection"}
{"_id": "WikiPedia_Radiology$$$corpus_751", "text": "(d)Extraction \nElements, Characteristic"}
{"_id": "WikiPedia_Radiology$$$corpus_752", "text": "El. stat. defl. 65 kV, aperture 5\u00a0mm, septum 0.5\u00a0mm, El. magn.\nchannel 4.7 kA, 5\u00a0mm septum passive focusing channel"}
{"_id": "WikiPedia_Radiology$$$corpus_753", "text": "passive peeler, regenerator\nTypical Efficiency (%): 50\nBest Efficiency (%): 80"}
{"_id": "WikiPedia_Radiology$$$corpus_754", "text": "(e)Vacuum (nr 4 in picture) \nPumps:"}
{"_id": "WikiPedia_Radiology$$$corpus_755", "text": "Achieved Vacuum: 10-5 Pa (10-7 mbar)"}
{"_id": "WikiPedia_Radiology$$$corpus_756", "text": "There are several beamlines at TSL:\nThe A-line was used for nuclide production, has not been used for several years but is in running condition. The B-line is in commonly use for delivering proton beam for irradiation testing. The C-line is used for biomedical research with different heavy ions. The D-line is commonly used for delivering proton beam for production of neutron beams for irradiation testing. The G-line is commonly used for delivering proton beam for  proton therapy ."}
{"_id": "WikiPedia_Radiology$$$corpus_757", "text": "The company Scanditronix AB, which later was acquired by  General Electric Healthcare  in 1991, design cyclotrons partially based on research at TSL. [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_758", "text": "59\u00b051\u203213\u2033N   17\u00b037\u203231\u2033E \ufeff / \ufeff 59.8537\u00b0N 17.6254\u00b0E \ufeff /  59.8537; 17.6254"}
{"_id": "WikiPedia_Radiology$$$corpus_759", "text": "The  Swedish Radiation Safety Authority  ( Swedish :  Str\u00e5ls\u00e4kerhetsmyndigheten ) is the Swedish government authority responsible for  radiation protection . It sorts under the  Ministry of the Environment ."}
{"_id": "WikiPedia_Radiology$$$corpus_760", "text": "It was created on 1 July 2008 with the merging of the  Swedish Nuclear Power Inspectorate  and the  Swedish Radiation Protection Authority . It employs 300 people and is located in Stockholm, with an annual budget of about 400 million  Swedish krona ."}
{"_id": "WikiPedia_Radiology$$$corpus_761", "text": "Its Director-General is  Nina Cromnier ."}
{"_id": "WikiPedia_Radiology$$$corpus_762", "text": "On the first of March 2022, the Swedish Radiation Safety Authority increased their readiness to handle an \"radiological emergency\" in the wake of  Russian invasion of Ukraine . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_763", "text": "This  Sweden -related article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Radiology$$$corpus_764", "text": "This  nuclear physics  or  atomic physics \u2013related article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Radiology$$$corpus_765", "text": "The  University of Texas Health Science Center at San Antonio Department of Radiology  is the second largest academic department in Radiological Sciences in the United States. [ 1 ]   Its Graduate Program in Radiological Sciences offers graduate training in various tracks, including  Medical Physics ,  radiation biology , Medical  Health Physics , and  Neuroimaging .  In addition the educational enterprise includes an accredited radiology residency program and a number of fellowships."}
{"_id": "WikiPedia_Radiology$$$corpus_766", "text": "The department was historically the first program in the United States to establish a Ph.D. program for radiology residents, which is known as the \"Human Imaging\" graduate program. [ 2 ]  While the Radiology Department is part of the  School of Medicine , the graduate program is housed administratively within the  UTHSCSA Graduate School of Biomedical Sciences  (GSBS)."}
{"_id": "WikiPedia_Radiology$$$corpus_767", "text": "With a minimum of 55 graduate students and over 60 fixed and adjunct faculty members, the program is currently one of the largest graduate programs in  medical physics  in the United States, and is one of only 17 programs in  North America  accredited by the Commission on the Accreditation of Medical Physics Education Programs (CAMPEP)."}
{"_id": "WikiPedia_Radiology$$$corpus_768", "text": "Graduate students research training is conducted in three primary locations within the UTHSCSA complex:"}
{"_id": "WikiPedia_Radiology$$$corpus_769", "text": "The Department also has clinical training facilities at  Brooke Army Medical Center ,  South Texas Medical Center  including the  University Hospital System  and the  Audie Murphy  Memorial Veterans Hospital, Texas Cancer Clinic, Medical and Radiation Physics, Inc. (MARP) and International Medical Physics Services."}
{"_id": "WikiPedia_Radiology$$$corpus_770", "text": "RFA, UFE, Cancer therapy, Dialysis work, PAD, AVMs"}
{"_id": "WikiPedia_Radiology$$$corpus_771", "text": "29\u00b030\u203227\u2033N   98\u00b034\u203231\u2033W \ufeff / \ufeff 29.507494\u00b0N 98.575385\u00b0W \ufeff /  29.507494; -98.575385"}
{"_id": "WikiPedia_Radiology$$$corpus_772", "text": "Abdominal Radiology  is a monthly  peer-reviewed   medical journal  published by  Springer Science+Business Media  and an official journal of the  Society of Abdominal Radiology . [ 1 ]  According to the  Journal Citation Reports , the journal has a 2023  impact factor  of 2.3. [ 2 ]  The journal was formerly known as  Abdominal Imaging . [ 3 ]  The  editor-in-chief  is  Neeraj Lalwani . [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_773", "text": "Acta Radiologica  is a  peer-reviewed   medical journal  covering the field of  radiology , including  diagnostic  and  interventional radiology ,  clinical radiology , experimental investigations in animals, and all other research related to  imaging  procedures. [ 1 ]   Acta Radiologica  is published by  SAGE Publications  in association with the Nordic Society of Medical Radiology, a federation of societies of Medical Radiology in Denmark, Finland, Iceland, Norway and Sweden. The journal is edited by Arnulf Skjennald ( Ullev\u00e5l University Hospital , Oslo, Norway). [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_774", "text": "Acta Radiologica  was established in 1921 and was originally published in German; it is now in English. It was founded by   G\u00f6sta Forssell , who served as editor until his death in 1950. [ 3 ]  According to the  Journal Citation Reports , it has a 2014  impact factor  of 1.603, ranking it 72nd out of 125 journals in the category \" Radiology , Nuclear Medicine & Medical Imaging\". [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_775", "text": "Examples of published items include:"}
{"_id": "WikiPedia_Radiology$$$corpus_776", "text": "The  American Journal of Neuroradiology  is a monthly  peer-reviewed   medical journal  covering  neuroradiology . It was established in 1980 and is published by the  American Society of Neuroradiology . The  editor-in-chief  is Jeffrey S. Ross ( Mayo Clinic College of Medicine , Phoenix, Arizona)."}
{"_id": "WikiPedia_Radiology$$$corpus_777", "text": "According to the  Journal Citation Reports , the journal has a 2017  impact factor  of 3.653. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_778", "text": "The  American Journal of Roentgenology  ( AJR ) is a monthly  peer-reviewed   journal  that covers topics in  radiology . It is published by the  American Roentgen Ray Society  (ARRS) and is based in  Leesburg, VA .  The current editor-in-chief (August 2020) is Andrew B. Rosenkrantz. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_779", "text": "The publication has undergone several changes throughout its history. The initial publication in 1906 was entitled the  American Quarterly of Roentgenology , and was officially associated with the ARRS in 1909. In 1913, journal was renamed the  American Journal of Roentgenology , and publication frequency was increased to a monthly basis under editor Preston M. Hickey. [ 2 ]  Hickey would remain editor-in-chief for approximately 10 years, and became a pioneering voice for evolution of radiologic education and reporting. With the advent of  radiation therapy  and nuclear medicine under the auspices of radiology, there was a period from 1920 to 1970s during which the ARRS began publishing articles on topics of radiation oncology and  nuclear medicine  in addition to diagnostic radiology.  Accordingly, the journal was renamed  American Journal of Roentgenology and Radium Therapy  in 1922, and later the  American Journal of Roentgenology, Radium Therapy, and Nuclear Medicine.   Finally in 1976, the journal was once again renamed back to  American Journal of Roentgenology  at which time mandatory peer-review was implemented."}
{"_id": "WikiPedia_Radiology$$$corpus_780", "text": "In 1975, publication committee chairman Raymond Gagliardi and editor in chief Melvin Figley founded  The American Journal of Neuroradiology  together with the American Society of  Neuroradiology ."}
{"_id": "WikiPedia_Radiology$$$corpus_781", "text": "The  Biomedical Imaging and Intervention Journal  is a quarterly  open access   peer-reviewed   medical journal  established in July 2005. It is financed by donations from regional and international biomedical imaging industry and the  University of Malaya Research Imaging Centre . The journal also receives support from many regional associations and societies and in turn has become the official publication of them. As of 2009, it is the official publication of the  ASEAN Association of Radiologists ,  ASEAN Society of Interventional Radiology ,  Asia-Oceania Federation of Organizations for Medical Physics ,  Asian Oceania Society of Radiology ,  College of Radiology, Academy of Medicine Malaysia ,  Southeast Asian Federation of Organisations of Medical Physics , and the  South East Asian Association of Academic Radiologists ."}
{"_id": "WikiPedia_Radiology$$$corpus_782", "text": "Shiao Eek Tee said \"It is the first fully electronic imaging journal in the country\" [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_783", "text": "BIIJ is indexed by  Scopus ,  EMBASE ,  Compendex ,  EBSCO ,  Chemical Abstracts ,  PubMed Central , and  Inspec . [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_784", "text": "The journal also publishes video recordings of presentations at selected meetings, conferences, and seminars, which may be used for educational purposes. Since November 2009, the videos are also made available on  SciVee . [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_785", "text": "Biomedical Optics Express  is a monthly  peer-reviewed   scientific journal  published by  Optica . The journal's scope encompasses fundamental research and technology development of optics applied to biomedical studies and clinical applications. The founding and first  editor-in-chief  is  Joseph A. Izatt  ( Duke University ). The current  editor-in-chief  is Ruikang (Ricky) Wang at the  University of Washington , USA. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_786", "text": "The journal is abstracted and indexed by:"}
{"_id": "WikiPedia_Radiology$$$corpus_787", "text": "According to the  Journal Citation Reports , the journal has a 2023  impact factor  of 2.9. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_788", "text": "The British Journal of Radiology  is a monthly  peer-reviewed   medical journal  covering  radiology . [ 1 ]  It is published by the  British Institute of Radiology  and the  editors-in-chief  are Simon Jackson (University Hospitals Plymouth NHS Trust) and Andrew Nisbet ( University College London ). According to the  Journal Citation Reports , the journal has a 2021  impact factor  of 3.629. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_789", "text": "The journal's forerunner, the  Archives of Clinical Skiagraphy  was established by  Sydney Domville Rowland  in May 1896. [ 3 ] [ 4 ]  In July 1897 it was renamed the  Archives of the Roentgen Ray  and reported that it would keep a \"record [of] the proceedings of the recently formed Roentgen Society, and will consist of original communications, notes, and correspondence ... (and) offers itself, not merely as a journal of the new photography, but to some extent as the exponent of an important discovery\". [ 1 ]  It was published quarterly and was the only journal which reported the transactions of the roentgen Society. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_790", "text": "In 1904,  John Hall-Edwards  became editor and in 1924, after 24 volumes, the journal was renamed  The British Journal of Radiology (Roentgen Society Section) The Journal of the Roentgen Society , after a period of being  Archives of Radiology and Electrotherapy  and  The Journal of the British Association of Radiology and Physiotherapy . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_791", "text": "In 1928 the British Institute of Radiology and the  Roentgen Society  combined to form  The British Journal of Radiology . [ 1 ]  Later, supplements were added and the journal became online from 2001. [ 1 ]  Old editions have been digitised. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_792", "text": "The journal published important works on the development of  CT scan  and  MRI  imaging techniques. For example:"}
{"_id": "WikiPedia_Radiology$$$corpus_793", "text": "CardioVascular and Interventional Radiology  is a  peer-reviewed   medical journal  published by  Springer . It is the journal of the  Cardiovascular and Interventional Radiological Society of Europe ."}
{"_id": "WikiPedia_Radiology$$$corpus_794", "text": "It had an  impact factor  of 2.191 in 2016. [ 1 ]  It is abstracted and indexed in  Science Citation Index Expanded ,  Journal Citation Reports /Science Edition,  PubMed / MEDLINE ,  Scopus ,  EMBASE ,  Google Scholar ,  Academic OneFile , CSA Environmental Sciences,  Current Contents /Clinical Medicine,  EmCare ,  Gale ,  Health Reference Center Academic ,  INIS Atomindex , Mosby yearbooks,  OCLC , SCImage, Summon by ProQuest. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_795", "text": "This article about a  cardiology   journal  is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Radiology$$$corpus_796", "text": "Clinical Imaging  is a  peer-reviewed   academic journal  on  medical imaging . It was founded in 1977 and received its current title in 1989. It is published by  Elsevier  on behalf of the  New York Roentgen Society . [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_797", "text": "The journal began publication in 1977 as  Computed Axial Tomography . The founding editor was  Rolf L. Schapiro . [ 3 ]  It was renamed  CT: The Journal of Computed Tomography  in 1978, [ 4 ]  and in 1989 obtained its present title. [ 5 ]  In 2012 it gained the sponsorship of the  New York Roentgen Society . [ 6 ]  As of 2022 [update]  the editor-in-chief is  Elizabeth Kagan Arleo . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_798", "text": "Clinical Imaging  is indexed in: [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_799", "text": "Clinical Radiology  is a  medical journal  that covers the aspects of clinical radiology, including: computed tomography, magnetic resonance imaging, ultrasonography etc. The journal is published by  Elsevier . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_800", "text": "The journal is abstracted and indexed in: [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_801", "text": "According to the  Journal Citation Reports , the journal has a 2021  impact factor  of 3.389. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_802", "text": "Dose\u2013Response  is a quarterly  peer-reviewed   scientific journal  covering research on the  dose-response relationship , especially  hormesis . [ 1 ]  It was established in 2003 as  Nonlinearity in Biology, Toxicology and Medicine , obtaining its current name in 2005. It is published by  SAGE Publications  on behalf of the  International Dose-Response Society , of which it is the official journal. [ 2 ]  Since its founding, the journal's  editor-in-chief  has been  Edward Calabrese  ( University of Massachusetts ). According to the  Journal Citation Reports , the journal has a 2015  impact factor  of 1.855, ranking it 162nd out of 255 journals in the category \"Pharmacology & Pharmacy\" [ 3 ]  and 62nd out of 124 in the category \"Radiology, Nuclear Medicine & Medical Imaging.\" [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_803", "text": "The  European Journal of Nuclear Medicine and Molecular Imaging  ( EJNMMI ) is a  peer-reviewed   medical journal  published by  Springer . It is the official journal of the  European Association of Nuclear Medicine . [ 1 ]  Since 1976, the EJNMMI has published material related to the field of  nuclear medicine , including  dosimetry ,  radiation biology ,  radiochemistry ,  radiopharmacology , molecular imaging probes, reporter gene assays,  cell trafficking , targeting of endogenous gene expression, and antisense methodologies. As of 2021, the EJNMMI has an impact factor of 10.057. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_804", "text": "In summer of 2011, Springer launched  EJNMMI Research , a peer-reviewed  open access  journal, as a companion to the  EJNMMI . It accommodates articles that could not be published in  EJNMMI ."}
{"_id": "WikiPedia_Radiology$$$corpus_805", "text": "European Radiology  is a monthly  peer-reviewed   medical journal  published by  Springer Science+Business Media . It was established in 1991 by J. Lissner and is the official journal of the  European Society of Radiology . [ 1 ]  The current  editor-in-chief  is  Bernd Hamm . The following European societies of sub-disciplines have chosen European Radiology as their official organ:"}
{"_id": "WikiPedia_Radiology$$$corpus_806", "text": "According to the  Journal Citation Reports , the journal has a 2014  impact factor  of 4.014. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_807", "text": "Health Physics  is a monthly  peer-reviewed   medical journal  published by  Lippincott Williams & Wilkins . Its scope includes research into radiation safety and healthcare applications. It is the official journal of the  Health Physics Society . It was established in 1958 and it is edited by Brant Ulsh."}
{"_id": "WikiPedia_Radiology$$$corpus_808", "text": "Operational Radiation Safety  is published as a quarterly supplement to Health Physics."}
{"_id": "WikiPedia_Radiology$$$corpus_809", "text": "According to the  Journal Citation Reports , the journal has a 2014  impact factor  of 1.271. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_810", "text": "IEEE Transactions on Medical Imaging  is a monthly  peer-reviewed   scientific journal  published by the  Institute of Electrical and Electronics Engineers  (IEEE). It covers technological aspects of  medical imaging  techniques. The journal was established in 1982 and since 2019 the  editor-in-chief  is  Leslie Ying  ( University at Buffalo ). It is sponsored by four IEEE societies,  IEEE Engineering in Medicine and Biology Society ,  IEEE Signal Processing Society ,  IEEE Nuclear and Plasma Sciences Society , and  IEEE Ultrasonics, Ferroelectrics & Frequency Control Society . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_811", "text": "According to the  Journal Citation Reports , the journal has a 2020  impact factor  of 10.048, ranking it 5th out of 111 journals in the category \"Computer Science, Interdisciplinary Applications\" [ 5 ]  and 4th out of 133 journals in the category \"Radiology, Nuclear Medicine & Medical Imaging\". [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_812", "text": "Imaging in Medicine  is a quarterly  peer-reviewed   open access   medical journal . It covers  medical imaging ,  radiation therapy ,  radiology , and basic imaging and  nuclear medicine . The journal was established in 2009 by  Future Medicine . It now is published by  Open Access Journals , an  imprint  of the  Pulsus Group , which is on  Jeffrey Beall 's list of \"Potential, possible, or probable\"  predatory open-access publishers  after being acquired by the  OMICS Publishing Group  in 2016. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_813", "text": "The journal is abstracted and indexed in  Chemical Abstracts Service , [ 2 ]   Embase , [ 3 ]  and from 2010 to 2014 and 2016 to 2017 in  Scopus  (discontinued). [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_814", "text": "Imaging  Technology News (ITN )  is a  business-to-business  trade publication serving healthcare professionals in the fields of  radiology ,  radiation oncology ,  women\u2019s health  and  nuclear medicine . [ 1 ]   ITN's print, website, and digital media cover trends in  medical imaging ,  radiation ,  oncology , and technology. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_815", "text": "The print publication had 34,901 subscribers as of July 2013. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_816", "text": "ITN covers and exhibits the following organizations:  Radiological Society of North America , the  American Society for Therapeutic Radiology and Oncology , the  Society of Nuclear Medicine and Molecular Imaging  and the  American Association of Physicists in Medicine ."}
{"_id": "WikiPedia_Radiology$$$corpus_817", "text": "ITN launched in 1961 as  Medical Electronics & Equipment News,  which became MEEN in the 1980s. MEEN became  Imaging Technology News  in September 1999, which then became ITN in September 2011. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_818", "text": "The  Indian Journal of Radiology and Imaging  is a  peer-reviewed   open access   medical journal  published  Medknow Publications  on behalf of the  Indian Radiology and Imaging Association . It covers all aspects of  radiology  and  medical imaging ."}
{"_id": "WikiPedia_Radiology$$$corpus_819", "text": "The journal is abstracted and indexed in  Abstracts on Hygiene and Communicable Diseases ,  CAB Abstracts ,  CINAHL ,  EBSCO databases ,  EmCare ,  Excerpta Medica/Embase ,  Expanded Academic ASAP , and  Scopus ."}
{"_id": "WikiPedia_Radiology$$$corpus_820", "text": "The  International Journal of Radiation Biology  is a monthly  peer-reviewed   medical journal  that covers research into the effects of  ionizing  and  non-ionizing radiation  in biology. The  editor-in-chief  is Professor Gayle Woloschak."}
{"_id": "WikiPedia_Radiology$$$corpus_821", "text": "The title was formerly known as  International Journal of Radiation Biology and Related Studies in Physics, Chemistry and Medicine , having changed its name in 1988."}
{"_id": "WikiPedia_Radiology$$$corpus_822", "text": "The journal is  abstracted and indexed  in:"}
{"_id": "WikiPedia_Radiology$$$corpus_823", "text": "According to the  Journal Citation Reports , the journal has a 2014  impact factor  of 1.687. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_824", "text": "Interventional Neuroradiology  is a bimonthly  peer-reviewed   medical journal  covering  neuroradiology . It was established in 1995 and is published by  SAGE Publications . The  editor-in-chief  is Waleed Brinjikji ( Mayo Clinic ). According to the  Journal Citation Reports , the journal has a 2021  impact factor  of 1.760. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_825", "text": "This article about a  neurology   journal  is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Radiology$$$corpus_826", "text": "Investigative Radiology  is a monthly  peer-reviewed   medical journal  published by  Wolters Kluwer . Its  editor-in-chief  is  Val Murray Runge . [ 1 ]  The journal covers research on  radiology  and  diagnostic imaging , focusing on  magnetic resonance ,  computed tomography ,  ultrasound ,  digital subtraction angiography , and new technologies. An additional focus is that of contrast media research, primarily for diagnostic imaging."}
{"_id": "WikiPedia_Radiology$$$corpus_827", "text": "The journal was established in 1966 with S. David Rockoff as the founding editor until 1976. Other editors have been Richard H. Greenspan (1976-1984), Charles E. Putman (1984-1989), and Bruce J. Hillman (1990-1994). Val M. Runge (Inselspital, Universit\u00e4tsspital Bern) has served as editor since 1994. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_828", "text": "The journal was originally published by J.B. Lippincott (now part of  Wolters Kluwer ). Between 1966 and 1984 the journal appeared bimonthly but the frequency was increased to 9 issues in 1985, and to monthly in 1986. [ 3 ]  Each year, one or more special issues are published focusing on a single topic."}
{"_id": "WikiPedia_Radiology$$$corpus_829", "text": "The journal is abstracted and indexed in the  Science Citation Index ,  Current Contents /Clinical Medicine, Current Contents/Life Sciences,  BIOSIS Previews , [ 4 ]  and  Index Medicus / MEDLINE / PubMed . [ 5 ]  According to the  Journal Citation Reports , the journal has a 2023  impact factor  of 7.0. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_830", "text": "The  Japanese Journal of Radiology  (formerly:  Radiation Medicine ) is a  peer-reviewed  journal, officially published by the  Japan Radiological Society . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_831", "text": "It provides a forum for the publication of papers documenting recent advances and new developments in the field of  radiology  in medicine and biology."}
{"_id": "WikiPedia_Radiology$$$corpus_832", "text": "Editor-in-Chief is N Tamaki."}
{"_id": "WikiPedia_Radiology$$$corpus_833", "text": "ISSN: 1867-1071 (print version)"}
{"_id": "WikiPedia_Radiology$$$corpus_834", "text": "ISSN: 1867-108X (electronic version)"}
{"_id": "WikiPedia_Radiology$$$corpus_835", "text": "The  Journal of Biomedical Optics  is a monthly  peer-reviewed   scientific journal  published by  SPIE . It covers the application of  optical technology  to  health care ,  biomedical research , and  experimental medicine . The  editor-in-chief  is Brian W. Pogue ( University of Wisconsin-Madison )."}
{"_id": "WikiPedia_Radiology$$$corpus_836", "text": "This journal is abstracted and indexed in:"}
{"_id": "WikiPedia_Radiology$$$corpus_837", "text": "According to the  Journal Citation Reports , the journal has a 2014  impact factor  of 2.859, ranking it 12th out of 86 journals in the category \"Optics\", [ 1 ]  31st out of 79 journals in the category \"Biochemical Research Methods\", [ 2 ]  and 31st out of 125 journals in the category \"Radiology, Nuclear Medicine & Medical Imaging\". [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_838", "text": "The  Journal of Clinical Interventional Radiology  is a triannual  open-access   peer-reviewed   medical journal  covering all aspects of vascular and non-vascular  interventional radiology . It is published by  Thieme Medical Publishers  on behalf of the  Indian Society of Vascular and Interventional Radiology . It was established in 2017 and the  editor-in-chief  is Naveen Kalra ( Postgraduate Institute of Medical Education and Research, Chandigarh ), who was preceded by Shyamkumar Nidugala Keshava."}
{"_id": "WikiPedia_Radiology$$$corpus_839", "text": "The journal is abstracted and indexed in  Embase [ 1 ]  and  Scopus . [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_840", "text": "The  Journal of Computer Assisted Tomography , abbreviated  JCAT , is a bimonthly  peer-reviewed   medical journal  covering  medical imaging , with a particular focus on  CT scans  and  magnetic resonance imaging . It was established in 1977 and is published by  Wolters Kluwer Health . It is the official journal of SABI, the Society for Advanced Body Imaging."}
{"_id": "WikiPedia_Radiology$$$corpus_841", "text": "The  editor-in-chief  is Eric P. Tamm, MD ( University of Texas  and  MD Anderson Cancer Center ). According to the  Journal Citation Reports , the journal has a 2020  impact factor  of 1.826."}
{"_id": "WikiPedia_Radiology$$$corpus_842", "text": "The journal's title has often been mistakenly represented (in mentions and citations) as \"Journal of Computed Assisted Tomography\"."}
{"_id": "WikiPedia_Radiology$$$corpus_843", "text": "The  Journal of Diagnostic Medical Sonography  (JDMS) is the bimonthly,  peer-reviewed   medical journal  of the  Society of Diagnostic Medical Sonography  (SDMS), and has been in publication since 1985. JDMS publishes peer-reviewed manuscripts supporting the translational use of  medical ultrasound  for diagnosis, intervention, and other clinical applications by a  sonographer , sonologist, or other  health care provider . The JDMS provides research, clinical, and educational content for all specialties, including but not limited to abdominal, women's health, pediatric, cardiovascular, musculoskeletal, and other emerging sonography practice areas. The journal's scope also includes research on instrumentation, physics, and technical advancements of  ultrasonography , as well as research on  sonographer  education and other professional issues, including ergonomics and the prevention of work-related injuries."}
{"_id": "WikiPedia_Radiology$$$corpus_844", "text": "JDMS accepts Original Research, Literature Reviews, Case Studies, Symposia (related to education, policy, technology, or professional issues), and Letters to the Editor. Author resources, editorial board information, and subscription and advertising opportunities are available on the  SDMS website ."}
{"_id": "WikiPedia_Radiology$$$corpus_845", "text": "The  Journal of Diagnostic Medical Sonography  received its first  impact factor  listed within the  Journal Citation Reports  in 2022. The journal is also abstracted and indexed in:"}
{"_id": "WikiPedia_Radiology$$$corpus_846", "text": "Journal of Medical Imaging  is a  peer-reviewed   scientific journal  published bimonthly by  SPIE . It covers fundamental, applied and translational research on  medical imaging . It was established in 2014 and its  editor-in-chief  is Bennett A. Landman ( Vanderbilt University ). [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_847", "text": "According to the  Journal Citation Reports , the journal has a 2022  impact factor  of 2.4. [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_848", "text": "Journal of Medical Imaging and  Radiation Oncology  (formerly:  Australasian Radiology ; print:  ISSN \u00a0 1754-9477 , online:  ISSN \u00a0 1754-9485 ) is the official journal of the  Royal Australian and New Zealand College of Radiologists . It is a  bimonthly   medical journal  covering  radiological  practice and  research  in  Australasia . It is published by  Wiley-Blackwell  and was established in 1957."}
{"_id": "WikiPedia_Radiology$$$corpus_849", "text": "According to the  Journal Citation Reports , its 2009  impact factor  is 0.602, ranking it 96th out of 104 journals in the category \"Radiology, Nuclear Medicine & Medical Imaging\"."}
{"_id": "WikiPedia_Radiology$$$corpus_850", "text": "This article about an  oncology   journal  is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Radiology$$$corpus_851", "text": "The  Journal of Nuclear Cardiology  is a  peer-reviewed   medical journal  covering research in  nuclear   cardiology . It is published by  Springer Science+Business Media  and is the official journal of the American Society of Nuclear Cardiology. [ 1 ]  The  editor-in-chief  is Ami E. Iskandrian ( The University of Alabama at Birmingham ). The founding editor was  Barry L. Zaret  ( Yale University School of Medicine ). According to the  Journal Citation Reports , the journal has a 2016  impact factor  of 3.930. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_852", "text": "This journal is indexed by the following services:"}
{"_id": "WikiPedia_Radiology$$$corpus_853", "text": "The  Journal of Nuclear Medicine Technology  is a quarterly  peer-reviewed   medical journal  published by the  Society of Nuclear Medicine and Molecular Imaging  that focuses entirely on technology crucial to  nuclear medicine , including  quality assurance ,  radiation safety , and clinical applications of nuclear medicine. The journal was established in 1973 and the  editor-in-chief  is Kathy Thomas."}
{"_id": "WikiPedia_Radiology$$$corpus_854", "text": "The Journal of Nuclear Medicine  is a monthly  peer-reviewed   medical journal  published by  Society of Nuclear Medicine and Molecular Imaging [ 1 ]  that covers research on all aspects of  nuclear medicine , including  molecular imaging ."}
{"_id": "WikiPedia_Radiology$$$corpus_855", "text": "The journal is abstracted and indexed in  Science Citation Index ,  Current Contents /Clinical Medicine, Current Contents/Life Sciences,  BIOSIS Previews , [ 2 ]  and  MEDLINE / PubMed . [ 3 ]  According to the  Journal Citation Reports , the journal has a 2020  impact factor  of 10.057, ranking it 3rd out of 134 journals in the category \"Radiology, Nuclear Medicine & Medical Imaging\". [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_856", "text": "The  Journal of Radiation Research  is a bimonthly  peer-reviewed   scientific journal  covering research on  radiation  and  oncology . It was established in 1960 and is published by  Oxford University Press . Its  editor-in-chief  is Kenshi Komatsu ( University of Kyoto )."}
{"_id": "WikiPedia_Radiology$$$corpus_857", "text": "It is an affiliated journal of the  Japan Radiation Research Society  and the  Japanese Society for Radiation Oncology . In 1998 the journal absorbed the Japanese Society for Radiation Oncology's former title, the  Journal of JASTRO . This extended the scope of the journal to include medical and oncology research."}
{"_id": "WikiPedia_Radiology$$$corpus_858", "text": "According to the  Journal Citation Reports , the journal has a 2019  impact factor  of 2.014. 5 year Impact Factor 2.063  [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_859", "text": "This article about a  scientific journal  is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Radiology$$$corpus_860", "text": "The  Journal of the American College of Radiology  (sometimes abbreviated  JACR ) is a monthly  peer-reviewed   medical journal  covering  radiology . It was established in 2004 and is published by  Elsevier  on behalf of the  American College of Radiology , of which it is the official journal. The journal's founding  editor-in-chief  was Bruce J. Hillman ( University of Virginia ) with Ruth C. Carlos ( University of Michigan ) succeeding Hillman on January 1, 2019. [ 1 ]  It is sometimes called the \"blue journal\". [ 2 ]  According to the  Journal Citation Reports , the journal has a 2020  impact factor  of 5.532. [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_861", "text": "The  Journal of Vascular and Interventional Radiology  is a monthly  peer-reviewed   medical journal  covering the field of  interventional radiology . It was established in 1990 and is published by  Elsevier  on behalf of the  Society of Interventional Radiology . The  editor-in-chief  is Daniel Y. Sze. The journal is  abstracted and indexed  in the  Science Citation Index Expanded ,  Biotechnology Research Abstracts ,  CINAHL ,  Embase ,  MEDLINE , and  Scopus . According to the  Journal Citation Reports , the journal has a 2021  impact factor  of 3.682. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_862", "text": "Magnetic Resonance Imaging  is a  peer-reviewed   scientific journal  published by  Elsevier , encompassing biology, physics, and clinical science as they relate to the development and use of  magnetic resonance imaging  technology.  Magnetic Resonance Imaging  was established in 1982 and the current  editor-in-chief  is John C. Gore. The journal produces 10 issues per year."}
{"_id": "WikiPedia_Radiology$$$corpus_863", "text": "Magnetic Resonance in Medicine  is a monthly  peer-reviewed   medical journal  covering research on all aspects of the development and use of  nuclear magnetic resonance  and  electron paramagnetic resonance  techniques for medical applications. It was established in 1984 and is published by  Wiley  on behalf of the  International Society for Magnetic Resonance in Medicine . Since 2019, the editor-in-chief of Magnetic Resonance in Medicine is  Oxford  professor  Peter Jezzard ."}
{"_id": "WikiPedia_Radiology$$$corpus_864", "text": "Molecular Imaging and Biology is published by  Springer Science+Business Media  as the official journal of the  World Molecular Imaging Society (WMIS)  in collaboration with the  European Society for Molecular Imaging (ESMI) . It publishes original research contributions on the utilization of molecular imaging in problems of relevance to biology and medicine."}
{"_id": "WikiPedia_Radiology$$$corpus_865", "text": "According to the  Journal Citation Reports , the journal has a 2018  impact factor  of 3.341. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_866", "text": "The Neuroradiology Journal   is a bimonthly  peer-reviewed   medical journal  covering diagnostic  neuroradiology . It was established in 1994 and is published by  SAGE Publications .  The  editor-in-chief  is  Luca_Saba  ( University_of_Cagliari )."}
{"_id": "WikiPedia_Radiology$$$corpus_867", "text": "NMR in Biomedicine  is a monthly  peer-reviewed   medical journal  published since 1988 by  John Wiley & Sons . It publishes original full-length papers, rapid communications, and  review articles  in which  magnetic resonance spectroscopy  or imaging methods are used to investigate physiological, biochemical, biophysical, or medical problems. The current  editor-in-chief  is  John R. Griffiths  ( Cancer Research UK )."}
{"_id": "WikiPedia_Radiology$$$corpus_868", "text": "The following articles have been cited most frequently: [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_869", "text": "NMR in Biomedicine  is abstracted and indexed in:"}
{"_id": "WikiPedia_Radiology$$$corpus_870", "text": "According to the  Journal Citation Reports , the journal has a 2014  impact factor  of 3.044, ranking it 9th out of 44 journals in the category \"Spectroscopy\", [ 1 ]  24th out of 125 journals in the category \"Radiology Nuclear Medicine & Medical Imaging\", [ 2 ]  and 27th out of 73 journals in the category \"Biophysics\". [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_871", "text": "Onkologia i Radioterapia  (English:  Oncology and Radiotherapy ) is a monthly  peer-reviewed   open-access   medical journal  covering  oncology  and  radiology  published by Medical Project Poland. The  editor-in-chief  is Ludmila Grzybowska-Szatkowska ( Medical University of Lublin ). The journal was established in 2007 and is an official journal of the  Polish Oncological Society ,  Polish Oncology Radiotherapy Society , and the Oncology Orthopedics Section of the  Polish Orthopedic and Traumatological Society . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_872", "text": "The journal is abstracted and indexed in  Embase [ 2 ]  and  Scopus . [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_873", "text": "Oral Surgery, Oral Medicine, Oral Pathology, and Oral Radiology  is a monthly  peer-reviewed   medical journal  that covers research in  oral surgery ,  medicine ,  pathology ,  radiology , and  endodontics  published by  Mosby . It was originally established as  Oral Surgery, Oral Medicine, and Oral Pathology  in 1948, changing its name to  Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology  in 1995, and acquiring its current name in 2012. It is an official journal of the  American College of Oral and Maxillofacial Surgery ,  American Academy of Oral and Maxillofacial Radiology ,  American Academy of Oral Medicine , and the  American Academy of Oral and Maxillofacial Pathology . According to the  Journal Citation Reports , the journal has a 2020  impact factor  of 2.589. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_874", "text": "Pediatric Radiology  is a  peer-reviewed   medical journal  covering all areas of pediatric imaging and related fields published by  Springer Nature . It is the official journal of the  European Society of Paediatric Radiology ,  Society for Pediatric Radiology ,  Asian and Oceanic Society for Pediatric Radiology , and the  Latin American Society of Pediatric Radiology . The  editors in chief  are Professor Amaka C Offiah (Sheffield, UK) and Professor Geetika Khanna (Atlanta, Georgia)."}
{"_id": "WikiPedia_Radiology$$$corpus_875", "text": "The journal is abstracted and indexed in  Academic OneFile ,  Cengage ,  Proquest ,  Current Contents /Clinical Medicine,  EBSCO databases ,  Embase ,  INIS Atomindex ,  PubMed / MEDLINE ,  Science Citation Index ,  Scopus , and  Summon by Serial Solutions . According to the  Journal Citation Reports , the journal has a 2021  impact factor  of 3.005 ."}
{"_id": "WikiPedia_Radiology$$$corpus_876", "text": "This article about a  pediatrics   journal  is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Radiology$$$corpus_877", "text": "Radiation and Environmental Biophysics  is a quarterly  peer-reviewed   scientific journal  covering research in  biophysics  and  radiation biology . It is published by  Springer Science+Business Media  and the  editors-in-chief  are Anna A. Friedl ( Ludwig-Maximilian University ), Werner R\u00fchm ( Helmholtz Zentrum M\u00fcnchen ), and Andrzej Wojcik ( Stockholm University )."}
{"_id": "WikiPedia_Radiology$$$corpus_878", "text": "It was established in 1974, by continuing in part the former title  Biophysik ."}
{"_id": "WikiPedia_Radiology$$$corpus_879", "text": "According to the  Journal Citation Reports , the journal has a 2020  impact factor  of 1.925. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_880", "text": "This article about a  biophysics  journal is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Radiology$$$corpus_881", "text": "Radiation Protection Dosimetry  is a monthly  peer-reviewed   scientific journal  covering  radiobiology , especially  dosimetry  and  radiation monitoring  for both  ionizing  and  non-ionizing radiation . The  editor-in-chief  is J. Hans Zoetelief ( Delft University of Technology )."}
{"_id": "WikiPedia_Radiology$$$corpus_882", "text": "According to the  Journal Citation Reports , the journal had a 2019  impact factor  of 0.773. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_883", "text": "Radiography  is a  peer-reviewed   medical journal  covering  diagnostic  and therapeutic  radiography . The journal is published by  Elsevier  and was established in 1995. The founding  editor-in-chief  was H. Brian Bentley from 1995 until 2003. [ 1 ]  The current editor-in-chief is Julie Nightingale ( University of Salford ). The journal was preceded by an insert in the  British Journal of Radiology  starting in 1927. [ 2 ]  In 1935, the current journal's predecessor, which was also known as  Radiography  was first published. [ 3 ]  It is the official journal of the  Society and College of Radiographers  and the  European Federation of Radiographer Societies . [ 4 ]  Besides regular issues, the journal occasionally publishes special issues. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_884", "text": "Radiology  is a monthly,  peer reviewed ,  medical journal , owned and published by the  Radiological Society of North America . The editor is Linda Moy, MD. The focus of  Radiology  is imaging research articles in radiology and medical imaging. [ 2 ] [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_885", "text": "Publishing formats are  original research  articles (3000 words), research letters (600 words),  technical developments (2000), invited perspectives (2500)   review articles  (4500), special report, invited  editorial , statements and guidelines (3000), Images in Radiology, Radiology Diagnosis Please, and  letter to the editor . [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_886", "text": "According to the  Journal Citation Reports ,  Radiology  has a 2021  impact factor  of 29.146. In addition, the journal is indexed in the following databases: [ 2 ] [ 6 ] [ 7 ] [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_887", "text": "Skeletal Radiology  is a  peer-reviewed   medical journal  published by  Springer Science+Business Media , covering disorders of the  musculoskeletal system , including the  spine . It is the official journal of  The International Skeletal Society . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_888", "text": "The journal is abstracted and indexed in  Current Contents /Clinical Medicine,  EMBASE ,  PASCAL ,  PubMed / Medline ,  Science Citation Index , and  Scopus . [ 2 ]  According to the  Journal Citation Reports , the journal has a 2016  impact factor  of 1.737. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_889", "text": "Ultrasound in Medicine and Biology  is a monthly  peer-reviewed   medical journal  published by  Elsevier  on behalf of the  World Federation for Ultrasound in Medicine and Biology . It covers  ultrasound technology  in  clinical   diagnostic ,  interventional  and  therapeutic  applications, including the  physics ,  engineering , and  technology  of  ultrasound  in  medicine  and  biology . It was established in 1973. The  editor-in-chief  is   Paul S. Sidhu  ( King's College Hospital ) since 2021. The founding editor was Denis N. White, who served from 1973 to 1992 and was succeeded by  Peter N. T. Wells ."}
{"_id": "WikiPedia_Radiology$$$corpus_890", "text": "According to the  Journal Citation Reports , the journal has a 2023  impact factor  of 2.4. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_891", "text": "Journal of Ultrasound in Medicine  is a  medical journal  that covers aspects of medical ultrasound, mainly its direct application to patient care but also relevant basic science, and biological effects etc. The journal is published by  Wiley . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_892", "text": "According to the  Journal Citation Reports , the journal has a 2021  impact factor  of 2.754. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_893", "text": "Ultrasound Quarterly  is a quarterly  peer-reviewed   medical journal  covering research on  medical ultrasound . It was established in 1988 and is published by  Lippincott Williams & Wilkins  on behalf of the  Society of Radiologists in Ultrasound , of which it is the official journal. The  editor-in-chief  is Theodore J. Dubinsky. According to the  Journal Citation Reports , the journal has a 2017  impact factor  of 1.021, ranking it 108th out of 126 journals in the category \"Radiology, Nuclear Medicine, and Medical Imaging\". [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_894", "text": "The  absent bowtie sign  is a  radiologic sign  indicative of a  meniscal tear  in the knee joint. On sagittal  magnetic resonance  (MR) images, the body of the meniscus normally looks like a bow tie, with two distinct segments. The  absent bowtie sign  is present when there is a lack of two segments seen on consecutive sagittal MR images. [ 1 ]  This sign can be used to diagnose \"bucket-handle\" tears of the mensici, which are longitudinal tears with displaced fragment(s). The \"handle\" is created when the inner meniscal fragment is displaced into the intercondylar notch. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_895", "text": "The  anteater nose sign  is a  radiologic sign  characterized by a tubular extension of the anterior process of the  calcaneus  bone that either extends towards or overlaps the  navicular  bone. This sign indicates the presence of a calcaneonavicular  tarsal coalition , which is an inherited  congenital  malformation of the foot. In this condition, there are abnormal bony, cartilaginous, or fibrous connections between the bones of the hindfoot, midfoot, or both regions. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_896", "text": "The  aortic nipple sign  is a  radiologic sign  that describes the appearance of the left  superior intercostal vein  on  chest radiography.  The left superior intercostal vein is located next to the  aortic arch , appearing on radiographs as a small mass (or \"nipple\") projecting from the arch. [ 1 ]  This sign is seen in a small number of individuals and may be mistaken for  lymphadenopathy  or a  neoplasm . [ 2 ]  The  aortic nipple sign  may be helpful in identifying certain thoracic pathologies, such as  pneumomediastinum , [ 2 ]  as it may change in size due to changes in intrathoracic pressure. [ 1 ]  Its appearance is also affected by changes in posture and vascular flow. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_897", "text": "The  bear paw sign  is a  radiologic sign  that describes the appearance of xanthogranulomatous pyelonephritis on computer tomography (CT) scans. Xanthogranulomatous pyelonephritis is a rare type of chronic  pyelonephritis  where the damaged areas of the kidneys are replaced by  foam cells . On CT, multiloculated hypoattenuating masses with bright rim enhancement may be seen in the renal parenchyma, resembling the toe pads of a bear's paw. These masses are indicative of dilated renal  calyces  and  xanthomas . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_898", "text": "The Royal College of Radiologists (RCR)  is the professional body responsible for the specialties of clinical  oncology  and  clinical radiology  throughout the  United Kingdom . Its role is to advance the science and practice of radiology and oncology, further public education, and set appropriate professional standards of practice. The college sets and monitors the educational curriculum for those training to enter the profession and administers the Fellowship of the Royal College of Radiologists exams. It is a  registered charity  in the United Kingdom (no. 211540). [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_899", "text": "The RCR has 2 faculties, representing Clinical Oncology and Clinical Radiology. It publishes two academic journals,  Clinical Oncology  and  Clinical Radiology ."}
{"_id": "WikiPedia_Radiology$$$corpus_900", "text": "The RCR has been based at 63 Lincoln's Inn Fields in London since July 2013."}
{"_id": "WikiPedia_Radiology$$$corpus_901", "text": "A series of bodies has represented practitioners of radiological medicine in the UK, starting in 1897 with the foundation of the  Roentgen Society  (named for the  physicist   Wilhelm Conrad R\u00f6ntgen ). Subsequently, the British Association of Radiologists was founded in 1934. In 1935, The Society of Radiotherapists of Great Britain and Ireland was set up for doctors specializing in the treatment of cancers using X-rays and radium. The latter two bodies amalgamated in 1939 to form the Faculty of Radiologists, which was granted a Royal Charter in 1953. In 1975, a Supplemental Charter was granted, and the faculty became the Royal College of Radiologists. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_902", "text": "In 1950, the first issue of the  Clinical Radiology Journal  was published by the Faculty of Radiologists. The first issue of  Clinical Oncology  was published in September 1989. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_903", "text": "In May 2021, the RCR launched the first national radiotherapy consent forms to help standardize and strengthen the informed consent process for adult cancer patients undergoing radiotherapy. Standardized consent forms with tailored information regarding radiotherapy for different tumor sites were released, and digital versions developed in collaboration with digital consent company Concentric Health. [ 2 ]  Welsh language versions of the consent forms were published in June 2022. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_904", "text": "Candidates are examined against the Specialty Training Curriculum for Clinical Radiology. The specialty trainees are expected to complete their First FRCR examination before progressing to ST2. During their ST3 training year they are expected to pass the Final FRCR Part A examination and must complete this before progressing to ST4. During ST4, trainees are expected to pass the Final FRCR Part B examination. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_905", "text": "The fellowship examinations start at the beginning of the Specialty Training Year 1 (ST1). The First FRCR examination expects candidates to have gained a knowledge of the physical principles that underpin diagnostic medical imaging and of the anatomy needed to perform and interpret radiological studies. [ 4 ] [ 5 ]  The First FRCR examination comprises two modules: Physics and Anatomy. The anatomy modules is a 90-minute exam comprising 100 images, where each image has several annotations, each of which in turn has a single related question. [ 6 ]  The physics module is a 120-minute multiple choice question paper comprising 40 questions, each with five true or false answers. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_906", "text": "The Final FRCR Part A examination comprises the single best of answers, split into two separate papers for the purposes of delivery. Each paper contains 120 questions and examining candidates on all aspects of clinical radiology and the basic sciences of physics, anatomy and techniques. [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_907", "text": "The main areas examined are:"}
{"_id": "WikiPedia_Radiology$$$corpus_908", "text": "1. Cardiothoracic and Vascular"}
{"_id": "WikiPedia_Radiology$$$corpus_909", "text": "2. Musculoskeletal and Trauma"}
{"_id": "WikiPedia_Radiology$$$corpus_910", "text": "3. Gastro-intestinal"}
{"_id": "WikiPedia_Radiology$$$corpus_911", "text": "4. Genito-urinary, Adrenal, Obstetrics & Gynecology and Breast"}
{"_id": "WikiPedia_Radiology$$$corpus_912", "text": "5. Pediatric"}
{"_id": "WikiPedia_Radiology$$$corpus_913", "text": "6. Central Nervous and Head & Neck"}
{"_id": "WikiPedia_Radiology$$$corpus_914", "text": "During the ST4 training, the specialty trainees are expected to complete the Final FRCR Part B. The Final FRCR (Part B) examination consists of a reporting session, a rapid reporting session and an oral examination. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_915", "text": "The extensive examination provided by the RCR ensures the high quality and standard of radiology consultants. It has been deemed as one of the hardest examinations in the medical profession, along with the  FRCA  and  FRCPath . [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_916", "text": "51\u00b030\u203258\u2033N   0\u00b007\u203207\u2033W \ufeff / \ufeff 51.51615\u00b0N 0.11866\u00b0W \ufeff /  51.51615; -0.11866"}
{"_id": "WikiPedia_Radiology$$$corpus_917", "text": "Radiology  ( / \u02cc r e\u026a d \u026a \u02c8 \u0252 l \u0259 d\u0292 i /   rey-dee-ol-uh-jee ) is the medical specialty that uses  medical imaging  to diagnose  diseases  and guide treatment within the bodies of humans and other animals. It began with  radiography  (which is why its name has a root referring to  radiation ), but today it includes all imaging modalities. This includes technologies that use no ionizing electromagnetic radiation, such as  ultrasonography  and  magnetic resonance imaging ), as well as others that do use radiation, such as  computed tomography  (CT),  fluoroscopy , and  nuclear medicine  including  positron emission tomography  (PET).  Interventional radiology  is the performance of usually  minimally invasive  medical procedures with the guidance of imaging technologies such as those mentioned above."}
{"_id": "WikiPedia_Radiology$$$corpus_918", "text": "The modern practice of radiology involves a team of several different healthcare professionals. A radiologist, who is a medical doctor with specialized post-graduate training, interprets medical images, communicates these findings to other physicians through reports or verbal communication, and uses imaging to perform minimally invasive medical procedures [ 1 ] [ 2 ]  The  nurse  is involved in the care of patients before and after imaging or procedures, including administration of medications, monitoring of vital signs and monitoring of sedated patients. [ 3 ]  The  radiographer , also known as a \"radiologic technologist\" in some countries such as the  United States  and  Canada , is a specially trained healthcare professional that uses sophisticated technology and positioning techniques to produce medical images for the radiologist to interpret. Depending on the individual's training and country of practice, the radiographer may specialize in one of the above-mentioned imaging modalities or have expanded roles in image reporting. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_919", "text": "Radiographs  (originally called roentgenographs, named after the discoverer of  X-rays ,  Wilhelm Conrad R\u00f6ntgen ) are produced by transmitting X-rays through a patient. The X-rays are projected through the body onto a detector; an image is formed based on which rays pass through (and are detected) versus those that are absorbed or scattered in the patient (and thus are not detected). R\u00f6ntgen discovered X-rays on November 8, 1895, and received the first  Nobel Prize in Physics  for his discovery in 1901. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_920", "text": "In film-screen radiography, an X-ray tube generates a beam of X-rays, which is aimed at the patient. The X-rays that pass through the patient are filtered through a device called a grid or  X-ray filter , to reduce scatter, and strike an undeveloped film, which is held tightly to a screen of light-emitting phosphors in a light-tight cassette. The film is then developed chemically and an image appears on the film. Film-screen radiography is being replaced by  phosphor plate radiography  but more recently by  digital radiography  (DR) and the  EOS imaging . [ 5 ]  In the two latest systems, the X-rays strike sensors that converts the signals generated into digital information, which is transmitted and converted into an image displayed on a computer screen. In  digital radiography  the sensors shape a plate, but in the EOS system, which is a slot-scanning system, a linear sensor vertically scans the patient. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_921", "text": "Plain radiography was the only imaging modality available during the first 50 years of radiology. Due to its availability, speed, and lower costs compared to other modalities, radiography is often the first-line test of choice in radiologic diagnosis. Also despite the large amount of data in CT scans, MR scans and other digital-based imaging, there are many disease entities in which the classic diagnosis is obtained by plain radiographs. Examples include various types of arthritis and pneumonia, bone tumors (especially benign bone tumors), fractures, congenital skeletal anomalies, and certain kidney stones. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_922", "text": "Mammography  and  DXA  are two applications of low energy projectional radiography, used for the evaluation for  breast cancer  and  osteoporosis , respectively. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_923", "text": "Fluoroscopy and  angiography  are special applications of  X-ray  imaging, in which a fluorescent screen and image intensifier tube is connected to a closed-circuit television system. [ 6 ] :\u200a26\u200a  This allows real-time imaging of structures in motion or augmented with a  radiocontrast  agent. Radio contrast agents  are usually administered by swallowing or injecting into the body of the patient to delineate anatomy and functioning of the blood vessels, the  genitourinary system , or the  gastrointestinal tract  (GI tract). Two radiocontrast agents are presently in common use. Barium sulfate (BaSO 4 ) is given orally or rectally for evaluation of the GI tract. Iodine, in multiple proprietary forms, is given by oral, rectal, vaginal, intra-arterial or intravenous routes. These radiocontrast agents strongly absorb or scatter X-rays, and in conjunction with the real-time imaging, allow demonstration of dynamic processes, such as  peristalsis  in the digestive tract or blood flow in arteries and veins. Iodine contrast may also be concentrated in abnormal areas more or less than in normal tissues and make abnormalities ( tumors ,  cysts ,  inflammation ) more conspicuous. Additionally, in specific circumstances, air can be used as a contrast agent for the gastrointestinal system and carbon dioxide can be used as a contrast agent in the venous system; in these cases, the contrast agent attenuates the X-ray radiation less than the surrounding tissues. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_924", "text": "CT imaging uses X-rays in conjunction with computing  algorithms  to image the body. [ 7 ] \nIn CT, an X-ray tube opposite an X-ray detector (or detectors) in a ring-shaped apparatus rotate around a patient, producing a computer-generated cross-sectional image (tomogram). [ 8 ]  CT is acquired in the  axial  plane, with coronal and sagittal images produced by computer reconstruction. Radiocontrast agents are often used with CT for enhanced delineation of anatomy. Although radiographs provide higher spatial resolution, CT can detect more subtle variations in attenuation of X-rays (higher contrast resolution). CT exposes the patient to significantly more ionizing radiation than a radiograph. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_925", "text": "Spiral multidetector CT uses 16, 64, 254 or more detectors during continuous motion of the patient through the radiation beam to obtain fine detail images in a short exam time. With rapid administration of intravenous contrast during the CT scan, these fine detail images can be reconstructed into three-dimensional (3D) images of carotid, cerebral, coronary or other arteries. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_926", "text": "The introduction of computed tomography in the early 1970s revolutionized diagnostic radiology by providing front-line clinicians with detailed images of anatomic structures in three dimensions. CT scanning has become the test of choice in diagnosing some urgent and emergent conditions, such as cerebral hemorrhage,  pulmonary embolism  (clots in the arteries of the lungs),  aortic dissection  (tearing of the aortic wall),  appendicitis ,  diverticulitis , and obstructing kidney stones. Before the development of CT imaging, risky and painful  exploratory surgery  was often the only way to obtain a definitive diagnosis of the cause of severe abdominal pain which could not be otherwise ascertained from external observation. [ 9 ]  Continuing improvements in CT technology, including faster scanning times and improved resolution, have dramatically increased the accuracy and usefulness of CT scanning, which may partially account for increased use in medical diagnosis. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_927", "text": "Medical ultrasonography uses ultrasound (high-frequency sound waves) to visualize soft tissue structures in the body in real time. No  ionizing radiation  is involved, but the quality of the images obtained using ultrasound is highly dependent on the skill of the person (ultrasonographer) performing the exam and the patient's body size. Examinations of larger,  overweight  patients may have a decrease in image quality as their  subcutaneous fat  absorbs more of the sound waves. This results in fewer sound waves penetrating to organs and reflecting back to the transducer, resulting in loss of information and a poorer quality image. Ultrasound is also limited by its inability to image through air pockets (lungs, bowel loops) or bone. Its use in medical imaging has developed mostly within the last 30 years. The first ultrasound images were static and two-dimensional (2D), but with modern ultrasonography, 3D reconstructions can be observed in real time, effectively becoming \"4D\". [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_928", "text": "Because ultrasound imaging techniques do not employ ionizing radiation to generate images (unlike radiography, and CT scans), they are generally considered safer and are therefore more common in  obstetrical imaging . The progression of pregnancies can be thoroughly evaluated with less concern about damage from the techniques employed, allowing early detection and diagnosis of many fetal anomalies. Growth can be assessed over time, important in patients with chronic disease or pregnancy-induced disease, and in multiple pregnancies (twins, triplets, etc.). Color-flow Doppler ultrasound measures the severity of  peripheral vascular disease  and is used by cardiologists for dynamic evaluation of the heart, heart valves and major vessels.  Stenosis , for example, of the  carotid arteries  may be a warning sign for an impending  stroke . A  clot , embedded deep in one of the inner veins of the legs, can be found via ultrasound before it dislodges and travels to the lungs, resulting in a potentially fatal  pulmonary embolism . Ultrasound is useful as a guide to performing  biopsies  to minimize damage to surrounding tissues and in drainages such as  thoracentesis . Small, portable ultrasound devices now replace  peritoneal lavage  in  trauma  wards by non-invasively assessing for the presence of internal  bleeding  and any internal organ damage. Extensive internal bleeding or injury to the major organs may require surgery and repair."}
{"_id": "WikiPedia_Radiology$$$corpus_929", "text": "MRI uses strong magnetic fields to align  atomic nuclei  (usually  hydrogen   protons ) within body tissues, then uses a radio signal to disturb the axis of rotation of these nuclei and observes the  radio frequency  signal generated as the nuclei return to their baseline states. [ 10 ]   The radio signals are collected by small antennae, called coils, placed near the area of interest. An advantage of MRI is its ability to produce images in  axial ,  coronal ,  sagittal  and multiple oblique planes with equal ease. MRI scans give the best soft tissue contrast of all the imaging modalities. With advances in scanning speed and spatial resolution, and improvements in computer 3D algorithms and hardware, MRI has become an important tool in musculoskeletal radiology and neuroradiology. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_930", "text": "One disadvantage is the patient has to hold still for long periods of time in a noisy, cramped space while the imaging is performed. Claustrophobia (fear of closed spaces) severe enough to terminate the MRI exam is reported in up to 5% of patients. Recent improvements in magnet design including stronger magnetic fields (3  teslas ), shortening exam times, wider, shorter magnet bores and more open magnet designs, have brought some relief for claustrophobic patients. However, for magnets with equivalent field strengths, there is often a trade-off between image quality and open design. MRI has great benefit in imaging the brain, spine, and musculoskeletal system. The use of MRI is currently contraindicated for patients with pacemakers, cochlear implants, some indwelling medication pumps, certain types of cerebral aneurysm clips, metal fragments in the eyes, some metallic hardware due to the powerful magnetic fields, and strong fluctuating radio signals to which the body is exposed. Areas of potential advancement include functional imaging, cardiovascular MRI, and MRI-guided therapy."}
{"_id": "WikiPedia_Radiology$$$corpus_931", "text": "Nuclear medicine imaging involves the administration into the patient of radiopharmaceuticals consisting of substances with affinity for certain body tissues labeled with radioactive tracer. The most commonly used tracers are technetium-99m, iodine-123, iodine-131, gallium-67, indium-111, thallium-201 and  fludeoxyglucose ( 18 F)  ( 18 F-FDG). The  heart ,  lungs ,  thyroid ,  liver ,  brain ,  gallbladder , and bones are commonly evaluated for particular conditions using these techniques. While  anatomical  detail is limited in these studies, nuclear medicine is useful in displaying  physiological  function. The excretory function of the kidneys, iodine-concentrating ability of the thyroid, blood flow to heart muscle, etc. can be measured. The principal imaging devices are the  gamma camera  and the PET Scanner, which detect the radiation emitted by the tracer in the body and display it as an image. With computer processing, the information can be displayed as axial, coronal and sagittal images (single-photon emission computed tomography - SPECT or Positron-emission tomography - PET). In the most modern devices, nuclear medicine images can be fused with a CT scan taken quasisimultaneously, so the  physiological  information can be overlaid or coregistered with the anatomical structures to improve diagnostic accuracy. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_932", "text": "Positron emission tomography  (PET) scanning deals with positrons instead of gamma rays detected by  gamma cameras . The positrons annihilate to produce two opposite traveling gamma rays to be detected coincidentally, thus improving resolution. In PET scanning, a radioactive, biologically active substance, most often  18 F-FDG, is injected into a patient and the radiation emitted by the patient is detected to produce multiplanar images of the body. Metabolically more active tissues, such as cancer, concentrate the active substance more than normal tissues. PET images can be combined (or \"fused\") with anatomic (CT) imaging, to more accurately localize PET findings and thereby improve diagnostic accuracy. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_933", "text": "The fusion technology has gone further to combine PET and MRI similar to PET and CT.  PET/MRI  fusion, largely practiced in academic and research settings, could potentially play a crucial role in fine detail of brain imaging, breast cancer screening, and small joint imaging of the foot. The technology recently blossomed after passing the technical hurdle of altered positron movement in strong magnetic field thus affecting the resolution of PET images and attenuation correction. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_934", "text": "Interventional radiology (IR or sometimes VIR for vascular and interventional radiology) is a subspecialty of radiology in which minimally invasive procedures are performed using image guidance. Some of these procedures are done for purely diagnostic purposes (e.g.,  angiogram ), while others are done for treatment purposes (e.g.,  angioplasty ). [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_935", "text": "The basic concept behind interventional radiology is to diagnose or treat  pathologies , with the most minimally invasive technique possible. Minimally invasive procedures are currently performed more than ever before. These procedures are often performed with the patient fully awake, with little or no sedation required. Interventional radiologists and interventional radiographers [ 11 ]  diagnose and treat several disorders, including  peripheral vascular disease ,  renal artery stenosis ,  inferior vena cava  filter placement,  gastrostomy  tube placements,  biliary   stents  and  hepatic  interventions. Radiographic images, fluoroscopy, and ultrasound modalities are used for guidance, and the primary instruments used during the procedure are specialized needles and  catheters . The images provide maps that allow the clinician to guide these instruments through the body to the areas containing disease. By minimizing the physical trauma to the patient, peripheral interventions can reduce infection rates and recovery times, as well as hospital stays. To be a trained interventionalist in the United States, an individual completes a five-year residency in radiology and a one- or two-year fellowship in IR. [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_936", "text": "The basic technique is optical density evaluation (i.e. histogram analysis). It is then described that a region has a different optical density, e.g. a cancer metastasis to bone can cause radiolucency. The development of this is the digital radiological subtraction. It consists in overlapping two radiographs of the same examined region and subtracting the optical densities  Comparison of changes in dental and bone radiographic densities in the presence of different soft-tissue simulators using pixel intensity and digital subtraction analyses . The resultant image only contains the time-dependent differences between the two examined radiographs. The advantage of this technique is the precise determination of the dynamics of density changes and the place of their occurrence. However, beforehand the geometrical adjustment and general alignment of optical density should be done  Noise in subtraction images made from pairs of intraoral radiographs: a comparison between four methods of geometric alignment .\nAnother possibility of radiographic image analysis is to study second order features, e.g. digital texture analysis  Basic research Textural entropy as a potential feature for quantitative assessment of jaw bone healing process   Comparative Analysis of Three Bone Substitute Materials Based on Co-Occurrence Matrix  or fractal dimension  Using fractal dimension to evaluate alveolar bone defects treated with various bone substitute materials . On this basis, it is possible to assess the places where bio-materials are implanted into the bone for the purpose of guided bone regeneration. They take an intact bone image sample (region of interest, ROI, reference site) and a sample of the implantation site (second ROI, test site) can be assessed numerically/objectively to what extent the implantation site imitates a healthy bone and how advanced is the process of bone regeneration  Fast-Versus Slow-Resorbable Calcium Phosphate Bone Substitute Materials\u2014Texture Analysis after 12 Months of Observation   New Oral Surgery Materials for Bone Reconstruction\u2014A Comparison of Five Bone Substitute Materials for Dentoalveolar Augmentation . It is also possible to check whether the bone healing process is influenced by some systemic factors  Influence of General Mineral Condition on Collagen-Guided Alveolar Crest Augmentation ."}
{"_id": "WikiPedia_Radiology$$$corpus_937", "text": "Teleradiology is the transmission of radiographic images from one location to another for interpretation by an appropriately trained professional, usually a radiologist or reporting radiographer. It is most often used to allow rapid interpretation of emergency room, ICU and other emergent examinations after hours of usual operation, at night and on weekends. In these cases, the images can be sent across time zones (e.g. to Spain, Australia, India) with the receiving Clinician working his normal daylight hours. However, at present, large private teleradiology companies in the U.S. currently provide most after-hours coverage employing night-working radiologists in the U.S. Teleradiology can also be used to obtain consultation with an expert or subspecialist about a complicated or puzzling case. In the U.S., many hospitals outsource their radiology departments to radiologists in India due to the lowered cost and availability of high speed internet access. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_938", "text": "Teleradiology requires a sending station, a high-speed internet connection, and a high-quality receiving station. At the transmission station, plain  radiographs  are passed through a digitizing machine before transmission, while CT, MRI, ultrasound and nuclear medicine scans can be sent directly, as they are already digital data. The computer at the receiving end will need to have a high-quality display screen that has been tested and cleared for clinical purposes. Reports are then transmitted to the requesting clinician."}
{"_id": "WikiPedia_Radiology$$$corpus_939", "text": "The major advantage of teleradiology is the ability to use different time zones to provide real-time emergency radiology services around-the-clock. The disadvantages include higher costs, limited contact between the referrer and the reporting Clinician, and the inability to cover for procedures requiring an onsite reporting Clinician. Laws and regulations concerning the use of teleradiology vary among the states, with some requiring a license to practice medicine in the state sending the radiologic exam. In the U.S., some states require the teleradiology report to be preliminary with the official report issued by a hospital staff radiologist. Lastly, a benefit of teleradiology is that it might be automated with modern  machine learning  techniques. [ 13 ] [ 14 ] [ 15 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_940", "text": "Some radiologists, like teleradiologists, have no interaction with patients. Other radiologists, like interventional radiologists, primarily interact with patients and spend less time analyzing images.  Diagnostic radiologists tend to spend the majority of their time analyzing images and a minority of their time interacting with patients. Compared to the healthcare provider who sends the patient to have images interpreted by a diagnostic radiologist, the radiologist usually does not know as much about the patient's clinical status or have as much influence on what action should be taken based on the images. Thus, the diagnostic radiologist reports image findings directly to that healthcare provider and often provides recommendations, who then takes the appropriate next steps for recommendations about medical management. Because radiologists undergo training regarding risks associated with different types of imaging tests and image-guided procedures, [ 16 ]  radiologists are the healthcare providers who generally educate patients about those risks to enable informed consent, not the healthcare provider requesting the test or procedure. [ 17 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_941", "text": "Radiology is a field in medicine that has expanded rapidly after 2000 due to advances in computer technology, which is closely linked to modern imaging techniques. Applying for residency positions in radiology has become highly competitive. Applicants are often near the top of their medical school classes, with high  USMLE  (board) examination scores. [ 18 ]  Diagnostic radiologists must complete prerequisite undergraduate education, four years of medical school to earn a medical degree ( D.O.  or  M.D. ), one year of internship, and four years of residency training. [ 19 ]  After residency, most radiologists pursue one or two years of additional specialty fellowship training."}
{"_id": "WikiPedia_Radiology$$$corpus_942", "text": "The  American Board of Radiology  (ABR) administers professional certification in Diagnostic Radiology, Radiation Oncology and Medical Physics as well as subspecialty certification in neuroradiology, nuclear radiology, pediatric radiology and vascular and interventional radiology. \"Board Certification\" in diagnostic radiology requires successful completion of two examinations. The Core Exam is given after 36 months of residency. Although previously taken  in Chicago or Tucson, Arizona, beginning in February 2021, the computer test transitioned permanently to a remote format. It encompasses 18 categories. A passing score is 350 or above. A fail on one to five categories was previously a Conditioned exam, however beginning in June 2021, the conditioned category will no longer exist and the test will be graded as a whole. The Certification Exam, can be taken 15 months after completion of the Radiology residency. This computer-based examination consists of five modules and graded pass-fail. It is given twice a year in Chicago and Tucson. Recertification examinations are taken every 10 years, with additional required continuing medical education as outlined in the Maintenance of Certification document. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_943", "text": "Certification may also be obtained from the  American Osteopathic Board of Radiology  (AOBR) and the American Board of Physician Specialties. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_944", "text": "Following completion of residency training, radiologists may either begin practicing as a general diagnostic radiologist or enter into subspecialty training programs known as fellowships. Examples of subspeciality training in radiology include abdominal imaging, thoracic imaging, cross-sectional/ultrasound,  MRI ,  musculoskeletal  imaging,  interventional radiology ,  neuroradiology ,  interventional neuroradiology ,  paediatric radiology , nuclear medicine, emergency radiology, breast imaging and women's imaging. Fellowship training programs in radiology are usually one or two years in length. [ 20 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_945", "text": "Some medical schools in the US have started to incorporate a basic radiology introduction into their core MD training.  New York Medical College , the  Wayne State University School of Medicine ,  Weill Cornell Medicine , the Uniformed Services University, and the University of South Carolina School of Medicine offer an introduction to radiology during their respective MD programs. [ 21 ] [ 22 ] [ 23 ]   Campbell University School of Osteopathic Medicine  also integrates imaging material into their curriculum early in the first year. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_946", "text": "Radiographic exams are usually performed by  radiographers . Qualifications for radiographers vary by country, but many radiographers now are required to hold a degree. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_947", "text": "Veterinary radiologists are veterinarians who specialize in the use of X-rays, ultrasound, MRI and nuclear medicine for diagnostic imaging or treatment of disease in animals. They are certified in either diagnostic radiology or radiation oncology by the American College of Veterinary Radiology. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_948", "text": "Radiology is an extremely competitive speciality in the UK, attracting applicants from a broad range of backgrounds. Applicants are welcomed directly from the  Foundation Programme , as well as those who have completed higher training. Recruitment and selection into training post in clinical radiology posts in England, Scotland and Wales is done by an annual nationally coordinated process lasting from November to March. In this process, all applicants are required to pass a Specialty Recruitment Assessment (SRA) test. [ 24 ]  Those with a test score above a certain threshold are offered a single interview at the London and the South East Recruitment Office. [ 25 ]  At a later stage, applicants declare what programs they prefer, but may in some cases be placed in a neighbouring region. [ 25 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_949", "text": "The training programme lasts for a total of five years. During this time, doctors rotate into different subspecialities, such as paediatrics, musculoskeletal or neuroradiology, and breast imaging. During the first year of training, radiology trainees are expected to pass the first part of the Fellowship of the  Royal College of Radiologists  (FRCR) exam. This comprises a medical physics and anatomy examination. Following completion of their part 1 exam, they are then required to pass six written exams (part 2A), which cover all the subspecialities. Successful completion of these allows them to complete the FRCR by completing part 2B, which includes rapid reporting, and a long case discussion."}
{"_id": "WikiPedia_Radiology$$$corpus_950", "text": "After achieving a  certificate of completion of training  (CCT), many fellowship posts exist in specialities such as neurointervention and vascular intervention, which would allow the doctor to work as an Interventional radiologist. In some cases, the CCT date can be deferred by a year to include these fellowship programmes."}
{"_id": "WikiPedia_Radiology$$$corpus_951", "text": "UK radiology registrars are represented by the Society of Radiologists in Training (SRT), which was founded in 1993 under the auspices of the Royal College of Radiologists. [ 26 ]  The society is a nonprofit organisation, run by radiology registrars specifically to promote radiology training and education in the UK. Annual meetings are held by which trainees across the country are encouraged to attend."}
{"_id": "WikiPedia_Radiology$$$corpus_952", "text": "Currently, a shortage of radiologists in the UK has created opportunities in all specialities, and with the increased reliance on imaging, demand is expected to increase in the future.  Radiographers , and less frequently  Nurses , are often trained to undertake many of these opportunities in order to help meet demand. Radiographers often may control a \"list\" of a particular set of procedures after being approved locally and signed off by a consultant radiologist. Similarly, radiographers may simply operate a list for a radiologist or other physician on their behalf. Most often if a radiographer operates a list autonomously then they are acting as the operator and practitioner under the Ionising Radiation (Medical Exposures) Regulations 2000. Radiographers are represented by a variety of bodies; most often this is the  Society and College of Radiographers . Collaboration with nurses is also common, where a list may be jointly organised between the nurse and radiographer."}
{"_id": "WikiPedia_Radiology$$$corpus_953", "text": "After obtaining medical licensure, German radiologists complete a five-year residency, culminating with a board examination (known as  Facharztpr\u00fcfung )."}
{"_id": "WikiPedia_Radiology$$$corpus_954", "text": "Italian radiologists complete a four-year residency program, after completing the six-year MD program."}
{"_id": "WikiPedia_Radiology$$$corpus_955", "text": "Dutch radiologists complete a five-year residency program, after completing the six-year MD program."}
{"_id": "WikiPedia_Radiology$$$corpus_956", "text": "In India, one must obtain a bachelor's degree which requires 4.5 years of training, along with 1 year internship, followed by NEET PG examination which is one of the hardest examinations in India. Previous rank data shows only top rankers take radiology which means if the score is less, one might get accepted into other branches, but not radiology. The radiology program is a post graduate 3-year program (MD/DNB Radiology) or a 2-year diploma (DMRD). [ 27 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_957", "text": "Radiologists in Singapore complete a five-year undergraduate MD program, followed by a one-year  internship , and then a five-year residency program. Some radiologists may elect to complete a one or two-year fellowship for further sub-specialization in fields such as  interventional radiology ."}
{"_id": "WikiPedia_Radiology$$$corpus_958", "text": "Slovenia"}
{"_id": "WikiPedia_Radiology$$$corpus_959", "text": "After finishing a six-year study of medicine and passing the emergency medicine internship, MDs can apply for radiology residency. Radiology is a five-year post-graduate program that involves all fields of radiology with a final board exam."}
{"_id": "WikiPedia_Radiology$$$corpus_960", "text": "France"}
{"_id": "WikiPedia_Radiology$$$corpus_961", "text": "To become a radiologist, after having validated the common core of medical studies, one must obtain a DES (Specialized Studies Diploma) in radiology and medical imaging (specialized studies in 5 years), or a DES in advanced interventional radiology (specialized studies in 6 years). At the end of his DES, once validated, the future doctor will have to defend his \u201cpractice thesis\u201d in order to validate his DE (State Diploma) as a doctor of medicine (common to all doctors of medicine therefore) and to be able to practice in France."}
{"_id": "WikiPedia_Radiology$$$corpus_962", "text": "Training for interventional radiology occurs in the residency portion of  medical education , and has gone through developments."}
{"_id": "WikiPedia_Radiology$$$corpus_963", "text": "In 2000, the  Society of Interventional Radiology  (SIR) created a program named \"Clinical Pathway in IR\", which modified the \"Holman Pathway\" that was already accepted by the American Board of Radiology to including training in IR; this was accepted by ABR but was not widely adopted. In 2005 SIR proposed and ABR accepted another pathway called \"DIRECT (Diagnostic and Interventional Radiology Enhanced Clinical Training) Pathway\" to help trainees coming from other specialities learn IR; this too was not widely adopted.  In 2006 SIR proposed a pathway resulting in certification in IR as a speciality; this was eventually accepted by the ABR in 2007 and was presented to the  American Board of Medical Specialities  (ABMS) in 2009, which rejected it because it did not include enough  diagnostic radiology  (DR) training. The proposal was reworked, at the same time that overall DR training was being revamped, and a new proposal that would lead to a dual DR/IR specialization was presented to the ABMS and was accepted in 2012 and eventually was implemented in 2014. [ 28 ] [ 29 ] [ 30 ]  By 2016 the field had determined that the old IR fellowships would be terminated by 2020. [ 30 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_964", "text": "A handful of programs have offered interventional radiology  fellowships  that focus on training in the treatment of children. [ 31 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_965", "text": "In Europe the field followed its own pathway; for example in Germany the parallel interventional society began to break free of the DR society in 2008. [ 32 ]  In the UK, interventional radiology was approved as a sub-specialty of clinical radiology in 2010. [ 33 ] [ 34 ]  While many countries have an interventional radiology society, there is also the European-wide  Cardiovascular and Interventional Radiological Society of Europe , whose aim is to support teaching, science, research and clinical practice in the field by hosting meetings, educational workshops and promoting patient safety initiatives. Furthermore, the Society provides an examination, the European Board of Interventional Radiology (EBIR), which is a highly valuable qualification in interventional radiology based on the European Curriculum and Syllabus for IR."}
{"_id": "WikiPedia_Radiology$$$corpus_966", "text": "Four-dimensional computed tomography  ( 4DCT ) is a type of  CT scanning  which records multiple images over time. It allows playback of the scan as a video, so that  physiological  processes can be observed and internal movement can be tracked. The name is derived from the addition of time (as the  fourth dimension ) to traditional  3D  computed  tomography . Alternatively, the phase of a particular process, such as  respiration , may be considered the fourth dimension. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_967", "text": "Fluoroscopy  is a similar technique to 4DCT, however it refers to the introduction of a time element to  2D   planar radiography , rather than to 3D CT. [ 2 ] [ 3 ] [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_968", "text": "4DCT is used in  radiation therapy  planning to reduce doses to healthy organs such as the heart or lungs. Most radiation therapy is  planned  using the results of a 3D CT scan. A 3D scan largely presents a snapshot of the body at a particular point in time, however due to the time of the acquisition, in which the patient is likely to have moved in some way (even if only breathing), there will be an element of blurring or averaging in the 3D scan. [ 6 ]  When it comes to treatment planning, this motion can mean there is less accuracy in the positioning of treatment beams, and reduce the likelihood of a repeatable set-up on the  linear accelerator  when it comes to treatment. [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_969", "text": "To minimise physical movements of the patient, some sort of immobilisation is typically used. To overcome physiological motion, such as breathing, 4DCT acquires images at a range of times and positions, allowing the extent of motion to be visualised (e.g. from maximum inspiration to maximum exhalation). The treatment plan can then be designed with a knowledge of the full range of possible positions of important organs, and the tumour (target) itself. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_970", "text": "4DCT will usually involve a  gating  technique, such as breathing tracking, so that image acquisition is automatically triggered at set points. [ 9 ]  This gating can also be applied at treatment, where the radiotherapy beam is only switched on at certain points in the breathing cycle (as in the  deep inspiration breath-hold  technique). [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_971", "text": "4DCT has started to be used for  diagnostic radiology  procedures, for example looking at  joint  problems, the  cardiac cycle  and parathyroid washout of  contrast . Downsides of 4DCT for diagnostic purposes include large and complex datasets, and increased  radiation dose  to the patient. [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_972", "text": "4DCT aims to visualise the temporal dynamics of a 3D sample with a sufficiently high  temporal  and  spatial resolution . Successive time frames are typically obtained by sequential scanning, followed by independent reconstruction of each 3D dataset. Such an approach requires a large number of projections for each scan to obtain images with sufficient quality (in terms of artefacts and  SNR ). Hence, there is a clear trade-off\nbetween the rotation speed of the gantry (i.e. time resolution) and the quality of the reconstructed images.\nMotion vector based  Iterative  Techniques are available which reconstruct a particular time frame by including the projections of neighbouring time frames as well. Such a strategy allows to improve the trade-off between the rotation speed and the SNR.\n [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_973", "text": "For  fluid dynamics , specialized reconstruction algorithms have been developed that model the attenuation course throughout time. [ 13 ]  An example of such fluid dynamics is  perfusion CT  in which the propagation of  contrast agent  is modelled and simultaneously estimated with the CT images. \n [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_974", "text": "Acute radiation syndrome  ( ARS ), also known as  radiation sickness  or  radiation poisoning , is a collection of health effects that are caused by being exposed to high  amounts  of  ionizing radiation  in a short period of time. [ 1 ]  Symptoms can start within an hour of exposure, and can last for several months. [ 1 ] [ 3 ] [ 5 ]  Early symptoms are usually nausea, vomiting and loss of appetite. [ 1 ]  In the following hours or weeks, initial symptoms may appear to improve, before the development of additional symptoms, after which either recovery or death follow. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_975", "text": "ARS involves a total dose of greater than 0.7  Gy  (70  rad ), that generally occurs from a source outside the body, delivered within a few minutes. [ 1 ]  Sources of such radiation can occur accidentally or intentionally. [ 6 ]  They may involve  nuclear reactors ,  cyclotrons , certain devices used in  cancer therapy ,  nuclear weapons , or  radiological weapons . [ 4 ]  It is generally divided into three types: bone marrow, gastrointestinal, and neurovascular syndrome, with bone marrow syndrome occurring at 0.7 to 10\u00a0Gy, and neurovascular syndrome occurring at doses that exceed 50\u00a0Gy. [ 1 ] [ 3 ]  The  cells  that are most affected are generally those that are rapidly dividing. [ 3 ]  At high doses, this causes DNA damage that may be irreparable. [ 4 ]  Diagnosis is based on a history of exposure and symptoms. [ 4 ]  Repeated  complete blood counts  (CBCs) can indicate the severity of exposure. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_976", "text": "Treatment of ARS is generally  supportive care . This may include  blood transfusions ,  antibiotics ,  colony-stimulating factors , or  stem cell transplant . [ 3 ]  Radioactive material remaining on the skin or in the stomach should be removed. If  radioiodine  was inhaled or ingested,  potassium iodide  is recommended. Complications such as  leukemia  and other  cancers  among those who survive are managed as usual. Short-term outcomes depend on the dose exposure. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_977", "text": "ARS is generally rare. [ 3 ]  A single event can affect a large number of people, [ 7 ]  as happened in the  atomic bombings of Hiroshima and Nagasaki  and the  Chernobyl nuclear power plant disaster . [ 1 ]  ARS differs from  chronic radiation syndrome , which occurs following prolonged exposures to relatively low doses of radiation. [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_978", "text": "Classically, ARS is divided into three main presentations:  hematopoietic ,  gastrointestinal , and  neuro vascular . These syndromes may be preceded by a  prodrome . [ 3 ]  The speed of symptom onset is related to radiation exposure, with greater doses resulting in a shorter delay in symptom onset. [ 3 ]  These presentations presume whole-body exposure, and many of them are markers that are invalid if the entire body has not been exposed. Each syndrome requires that the tissue showing the syndrome itself be exposed (e.g., gastrointestinal syndrome is not seen if the stomach and intestines are not exposed to radiation). Some areas affected are:"}
{"_id": "WikiPedia_Radiology$$$corpus_979", "text": "Early symptoms of ARS typically include nausea, vomiting, headaches, fatigue,  fever , and a short period of  skin reddening . [ 3 ]  These symptoms may occur at radiation doses as low as 0.35 grays (35\u00a0rad). These symptoms are common to many illnesses, and may not, by themselves, indicate acute radiation sickness. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_980", "text": "A similar table and description of symptoms (given in  rems , where 100 rem = 1  Sv ), derived from data from the effects on humans subjected to the  atomic bombings of Hiroshima and Nagasaki , the indigenous peoples of the  Marshall Islands  subjected to the  Castle Bravo  thermonuclear bomb, animal studies and lab experiment accidents, have been compiled by the  U.S. Department of Defense . [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_981", "text": "A person who was less than 1 mile (1.6\u00a0km) from the atomic bomb  Little Boy 's   hypocenter  at Hiroshima, Japan, was found to have absorbed about 9.46 grays (Gy) of ionizing radiation. [ 13 ] [ 14 ] [ 15 ] [ 16 ]  The doses at the hypocenters of the Hiroshima and Nagasaki atomic bombings were 240 and 290 Gy, respectively. [ 17 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_982", "text": "Cutaneous radiation syndrome  (CRS) refers to the skin symptoms of radiation exposure. [ 1 ]  Within a few hours after irradiation, a transient and inconsistent  redness  (associated with  itching ) can occur. Then, a latent phase may occur and last from a few days up to several weeks, when intense reddening,  blistering , and  ulceration  of the irradiated site is visible. In most cases, healing occurs by regenerative means; however, very large skin doses can cause permanent hair loss, damaged  sebaceous  and  sweat glands ,  atrophy ,  fibrosis  (mostly  keloids ), decreased or increased skin pigmentation, and ulceration or  necrosis  of the exposed tissue. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_983", "text": "As seen at  Chernobyl , when skin is irradiated with high energy  beta particles , moist  desquamation  (peeling of skin) and similar early effects can heal, only to be followed by the collapse of the dermal vascular system after two months, resulting in the loss of the full thickness of the exposed skin. [ 20 ]  Another example of skin loss caused by high-level exposure of radiation is during the  1999 Tokaimura nuclear accident , where technician Hisashi Ouchi had lost a majority of his skin due to the high amounts of radiation he absorbed during the irradiation. This effect had been demonstrated previously with pig skin using high energy beta sources at the Churchill Hospital Research Institute, in  Oxford . [ 21 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_984", "text": "ARS is caused by exposure to a large dose of ionizing radiation (>\u00a0~0.1\u00a0Gy) over a short period of time (>\u00a0~0.1\u00a0Gy/h). Alpha and beta radiation have low penetrating power and are unlikely to affect vital internal organs from outside the body. Any type of ionizing radiation can cause burns, but alpha and beta radiation can only do so if  radioactive contamination  or  nuclear fallout  is deposited on the individual's skin or clothing."}
{"_id": "WikiPedia_Radiology$$$corpus_985", "text": "Gamma and neutron radiation can travel much greater distances and penetrate the body easily, so whole-body irradiation generally causes ARS before skin effects are evident. Local gamma irradiation can cause skin effects without any sickness. In the early twentieth century, radiographers would commonly calibrate their machines by irradiating their own hands and measuring the time to onset of  erythema . [ 26 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_986", "text": "Accidental exposure may be the result of a  criticality  or  radiotherapy  accident. There have been  numerous  criticality accidents dating back to  atomic testing  during World War II, while computer-controlled radiation therapy machines such as  Therac-25  played a major part in radiotherapy accidents. The latter of the two is caused by the failure of equipment software used to monitor the radiational dose given. Human error has played a large part in accidental exposure incidents, including some of the criticality accidents, and larger scale events such as the  Chernobyl disaster . Other events have to do with  orphan sources , in which radioactive material is unknowingly kept, sold, or stolen. The  Goi\u00e2nia accident  is an example, where a forgotten radioactive source was taken from a hospital, resulting in the deaths of 4 people from ARS. [ 27 ]   Theft and attempted theft  of radioactive material by clueless thieves has also led to lethal exposure in at least one incident. [ 28 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_987", "text": "Exposure may also come from routine spaceflight and  solar flares  that result in radiation effects on earth in the form of  solar storms . During spaceflight, astronauts are exposed to both  galactic cosmic radiation  (GCR) and  solar particle event  (SPE) radiation. The exposure particularly occurs during flights beyond  low Earth orbit  (LEO). Evidence indicates past SPE radiation levels that would have been lethal for unprotected astronauts. [ 29 ]  GCR levels that might lead to acute radiation poisoning are less well understood. [ 30 ]  The latter cause is rarer, with an event possibly occurring during the  solar storm of 1859 ."}
{"_id": "WikiPedia_Radiology$$$corpus_988", "text": "Intentional exposure is controversial as it involves the use of  nuclear weapons ,  human experiments , or is given to a victim in an act of murder. The intentional atomic bombings of Hiroshima and Nagasaki resulted in tens of thousands of casualties; the survivors of these bombings are known today as  hibakusha . Nuclear weapons emit large amounts of  thermal radiation  as visible, infrared, and ultraviolet light, to which the atmosphere is largely transparent. This event is also known as \"flash\", where radiant heat and light  are bombarded  into any given victim's exposed skin, causing radiation burns. [ 31 ]  Death is highly likely, and radiation poisoning is almost certain if one is caught in the open with no terrain or building masking-effects within a radius of 0\u20133\u00a0km from a 1 megaton airburst. The  50% chance of death  from the blast extends out to ~8\u00a0km from a 1 megaton atmospheric explosion. [ 32 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_989", "text": "Scientific testing on humans within the United States occurred extensively throughout the atomic age. Experiments took place on a range of subjects including, but not limited to; the disabled, children, soldiers, and incarcerated persons, with the level of understanding and consent given by subjects varying from complete to none. Since 1997 there have been requirements for patients to give informed consent, and to be notified if experiments were classified. [ 33 ]  Across the world, the  Soviet nuclear program  involved human experiments on a large scale, which is still [ as of? ]  kept secret by the Russian government and the  Rosatom  agency. [ 34 ] [ 35 ]  The human experiments that fall under intentional ARS exclude those that involved  long term exposure . Criminal activity has involved murder and attempted murder carried out through abrupt victim contact with a radioactive substance such as  polonium  or  plutonium ."}
{"_id": "WikiPedia_Radiology$$$corpus_990", "text": "The most commonly used predictor of ARS is the whole-body  absorbed dose . Several related quantities, such as the  equivalent dose ,  effective dose , and  committed dose , are used to gauge long-term stochastic biological effects such as cancer incidence, but they are not designed to evaluate ARS. [ 36 ]  To help avoid confusion between these quantities, absorbed dose is measured in units of  grays  (in  SI , unit symbol  Gy ) or  rad  (in  CGS ), while the others are measured in  sieverts  (in SI, unit symbol  Sv ) or  rem  (in CGS). 1\u00a0rad = 0.01\u00a0Gy and 1\u00a0rem = 0.01\u00a0Sv. [ 37 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_991", "text": "In most of the acute exposure scenarios that lead to radiation sickness, the bulk of the radiation is external whole-body gamma, in which case the absorbed, equivalent, and effective doses are all equal. There are exceptions, such as the Therac-25 accidents and the 1958  Cecil Kelley criticality accident , where the absorbed doses in Gy or rad are the only useful quantities, because of the targeted nature of the exposure to the body."}
{"_id": "WikiPedia_Radiology$$$corpus_992", "text": "Radiotherapy  treatments are typically prescribed in terms of the local absorbed dose, which might be 60\u00a0Gy or higher. The dose is fractionated to about 2\u00a0Gy per day for  curative  treatment, which allows normal tissues to undergo  repair , allowing them to tolerate a higher dose than would otherwise be expected. The dose to the targeted tissue mass must be averaged over the entire body mass, most of which receives negligible radiation, to arrive at a whole-body absorbed dose that can be compared to the table above. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_993", "text": "Exposure to high doses of radiation causes  DNA  damage, later creating serious and even lethal  chromosomal aberrations  if left unrepaired. Ionizing radiation can produce  reactive oxygen species , and does directly damage cells by causing localized ionization events. The former is very damaging to DNA, while the latter events create clusters of DNA damage. [ 38 ] [ 39 ]  This damage includes loss of  nucleobases  and breakage of the sugar-phosphate backbone that binds to the nucleobases. The DNA organization at the level of  histones ,  nucleosomes , and  chromatin  also affects its susceptibility to  radiation damage . [ 40 ]  Clustered damage, defined as at least two lesions within a helical turn, is especially harmful. [ 39 ]  While DNA damage happens frequently and naturally in the cell from endogenous sources, clustered damage is a unique effect of radiation exposure. [ 41 ]  Clustered damage takes longer to repair than isolated breakages, and is less likely to be repaired at all. [ 42 ]  Larger radiation doses are more prone to cause tighter clustering of damage, and closely localized damage is increasingly less likely to be repaired. [ 39 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_994", "text": "Somatic mutations cannot be passed down from parent to offspring, but these mutations can propagate in cell lines within an organism. Radiation damage can also cause chromosome and  chromatid  aberrations, and their effects depend on in which stage of the mitotic cycle the cell is when the irradiation occurs. If the cell is in  interphase , while it is still a single strand of chromatin, the damage will be replicated during the S1 phase of the  cell cycle , and there will be a break on both chromosome arms; the damage then will be apparent in both  daughter cells . If the irradiation occurs after replication, only one arm will bear the damage; this damage will be apparent in only one daughter cell. A damaged chromosome may cyclize, binding to another chromosome, or to itself. [ 43 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_995", "text": "Diagnosis is typically made based on a history of significant radiation exposure and suitable clinical findings. [ 3 ]  An  absolute lymphocyte count  can give a rough estimate of radiation exposure. [ 3 ]  Time from exposure to vomiting can also give estimates of exposure levels if they are less than 10\u00a0Gy (1000\u00a0rad). [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_996", "text": "A guiding principle of radiation safety is  as low as reasonably achievable  (ALARA). [ 44 ]  This means try to avoid exposure as much as possible and includes the three components of time, distance, and shielding. [ 44 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_997", "text": "The longer that humans are subjected to radiation the larger the dose will be. The advice in the  nuclear war  manual entitled  Nuclear War Survival Skills  published by  Cresson Kearny  in the  U.S.  was that if one needed to leave the shelter then this should be done as rapidly as possible to minimize exposure. [ 45 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_998", "text": "In chapter\u00a012, he states that \"[q]uickly putting or dumping wastes outside is not hazardous once fallout is no longer being deposited. For example, assume the shelter is in an area of heavy fallout and the dose rate outside is 400\u00a0 roentgen (R)  per hour, enough to give a potentially fatal dose in about an hour to a person exposed in the open. If a person needs to be exposed for only 10\u00a0seconds to dump a bucket, in this 1/360 of an hour he will receive a dose of only about 1\u00a0R. Under war conditions, an additional 1-R dose is of little concern.\" In peacetime, radiation workers are taught to work as quickly as possible when performing a task that exposes them to radiation. For instance, the recovery of a radioactive source should be done as quickly as possible."}
{"_id": "WikiPedia_Radiology$$$corpus_999", "text": "Usually, matter attenuates radiation, so placing any mass (e.g., lead, dirt, sandbags, vehicles, water, even air) between humans and the source will reduce the radiation dose. This is not always the case, however; care should be taken when constructing shielding for a specific purpose. For example, although high atomic number materials are very effective in shielding  photons , using them to shield  beta particles  may cause higher radiation exposure due to the production of  bremsstrahlung  x-rays, and hence low atomic number materials are recommended. Also, using material with a high  neutron activation   cross section  to shield neutrons will result in the shielding material itself becoming radioactive and hence more dangerous than if it were not present. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1000", "text": "There are many types of shielding strategies that can be used to reduce the effects of radiation exposure. Internal contamination protective equipment such as respirators are used to prevent internal deposition as a result of inhalation and ingestion of radioactive material. Dermal protective equipment, which protects against external contamination, provides shielding to prevent radioactive material from being deposited on external structures. [ 46 ]  While these protective measures do provide a barrier from radioactive material deposition, they do not shield from externally penetrating gamma radiation. This leaves anyone exposed to penetrating gamma rays at high risk of ARS."}
{"_id": "WikiPedia_Radiology$$$corpus_1001", "text": "Naturally, shielding the entire body from high energy gamma radiation is optimal, but the required mass to provide adequate attenuation makes functional movement nearly impossible. In the event of a radiation catastrophe, medical and security personnel need  mobile protection equipment  in order to safely assist in containment, evacuation, and many other necessary public safety objectives."}
{"_id": "WikiPedia_Radiology$$$corpus_1002", "text": "Research has been done exploring the feasibility of partial body shielding, a radiation protection strategy that provides adequate attenuation to only the most radio-sensitive organs and tissues inside the body. Irreversible stem cell damage in the bone marrow is the first life-threatening effect of intense radiation exposure and therefore one of the most important bodily elements to protect. Due to the regenerative property of  hematopoietic stem cells , it is only necessary to protect enough bone marrow to repopulate the exposed areas of the body with the shielded supply. [ 47 ]  This concept allows for the development of lightweight mobile radiation protection equipment, which provides adequate protection, deferring the onset of ARS to much higher exposure doses. One example of such equipment is the  360 gamma , a radiation protection belt that applies selective shielding to protect the bone marrow stored in the pelvic area as well as other radio sensitive organs in the abdominal region without hindering functional mobility."}
{"_id": "WikiPedia_Radiology$$$corpus_1003", "text": "Where radioactive contamination is present, an  elastomeric respirator ,  dust mask , or good hygiene practices may offer protection, depending on the nature of the contaminant.  Potassium iodide  (KI) tablets can reduce the risk of cancer in some situations due to slower uptake of ambient radioiodine. Although this does not protect any organ other than the thyroid gland, their effectiveness is still highly dependent on the time of ingestion, which would protect the gland for the duration of a twenty-four-hour period. They do not prevent ARS as they provide no shielding from other environmental radionuclides. [ 48 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1004", "text": "If an intentional dose is broken up into a number of smaller doses, with time allowed for recovery between irradiations, the same total dose causes less  cell death . Even without interruptions, a reduction in dose rate below 0.1\u00a0Gy/h also tends to reduce cell death. [ 36 ]  This technique is routinely used in radiotherapy. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1005", "text": "The human body contains many types of  cells  and a human can be killed by the loss of a single type of cells in a vital organ. For many short term radiation deaths (3\u201330\u00a0days), the loss of two important types of cells that are constantly being regenerated causes death. The loss of cells forming  blood cells  ( bone marrow ) and the cells in the digestive system ( microvilli , which form part of the wall of the  intestines ) is fatal. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1006", "text": "Treatment usually involves supportive care with possible symptomatic measures employed. The former involves the possible use of  antibiotics ,  blood products ,  colony stimulating factors , and  stem cell transplant . [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1007", "text": "There is a direct relationship between the degree of the  neutropenia  that emerges after exposure to radiation and the increased risk of developing infection. Since there are no controlled studies of therapeutic intervention in humans, most of the current recommendations are based on animal research. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1008", "text": "The  treatment  of established or suspected infection following exposure to radiation (characterized by neutropenia and fever) is similar to the one used for other febrile neutropenic patients. However, important differences between the two conditions exist. Individuals that develop neutropenia after exposure to radiation are also susceptible to irradiation damage in other tissues, such as the gastrointestinal tract, lungs and central nervous system. These patients may require therapeutic interventions not needed in other types of neutropenic patients. The response of irradiated animals to antimicrobial therapy can be unpredictable, as was evident in experimental studies where  metronidazole [ 49 ]  and  pefloxacin [ 50 ]  therapies were detrimental."}
{"_id": "WikiPedia_Radiology$$$corpus_1009", "text": "Antimicrobials that reduce the number of the strict  anaerobic  component of the gut flora (i.e., metronidazole) generally should not be given because they may enhance systemic infection by aerobic or  facultative bacteria , thus facilitating mortality after irradiation. [ 51 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1010", "text": "An empirical regimen of antimicrobials should be chosen based on the pattern of bacterial susceptibility and  nosocomial infections  in the affected area and medical center and the degree of neutropenia. Broad-spectrum empirical therapy (see below for choices) with high doses of one or more antibiotics should be initiated at the onset of fever. These antimicrobials should be directed at the eradication of Gram-negative aerobic bacilli (i.e.,  Enterobacteriaceae ,  Pseudomonas ) that account for more than three quarters of the isolates causing sepsis. Because aerobic and facultative Gram-positive bacteria (mostly  alpha-hemolytic streptococci ) cause  sepsis  in about a quarter of the victims, coverage for these organisms may also be needed. [ 52 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1011", "text": "A standardized management plan for people with neutropenia and fever should be devised. Empirical regimens contain antibiotics broadly active against Gram-negative aerobic bacteria ( quinolones : i.e.,  ciprofloxacin ,  levofloxacin , a third- or fourth-generation cephalosporin with pseudomonal coverage: e.g.,  cefepime ,  ceftazidime , or an aminoglycoside: i.e.  gentamicin ,  amikacin ). [ 53 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1012", "text": "The prognosis for ARS is dependent on the exposure dose, with anything above 8 Gy being almost always lethal, even with medical care. [ 4 ] [ 54 ]   Radiation burns  from lower-level exposures usually manifest after 2 months, while reactions from the burns occur months to years after radiation treatment. [ 55 ] [ 56 ]  Complications from ARS include an increased risk of developing radiation-induced cancer later in life. According to the controversial but commonly applied  linear no-threshold model , any exposure to ionizing radiation, even at doses too low to produce any symptoms of radiation sickness, can induce cancer due to cellular and genetic damage. The probability of developing cancer is a linear function with respect to the  effective radiation dose . Radiation cancer may occur after ionizing radiation exposure following a latent period averaging 20 to 40 years. [ 57 ] [ 55 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1013", "text": "Acute effects of ionizing radiation were first observed when  Wilhelm R\u00f6ntgen  intentionally subjected his fingers to X-rays in 1895. He published his observations concerning the burns that developed that eventually healed, and misattributed them to ozone. R\u00f6ntgen believed the  free radical  produced in air by X-rays from the ozone was the cause, but other free radicals produced within the body are now understood to be more important. David Walsh first established the symptoms of radiation sickness in 1897. [ 58 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1014", "text": "Ingestion of radioactive materials caused many  radiation-induced cancers  in the 1930s, but no one was exposed to high enough doses at high enough rates to bring on ARS."}
{"_id": "WikiPedia_Radiology$$$corpus_1015", "text": "The  atomic bombings of Hiroshima and Nagasaki  resulted in high acute doses of radiation to a large number of Japanese people, allowing for greater insight into its symptoms and dangers. Red Cross Hospital Surgeon  Terufumi Sasaki  led intensive research into the syndrome in the weeks and months following the Hiroshima and Nagasaki bombings. Sasaki and his team were able to monitor the effects of radiation in patients of varying proximities to the blast itself, leading to the establishment of three recorded stages of the syndrome. Within 25\u201330\u00a0days of the explosion, Sasaki noticed a sharp drop in white blood cell count and established this drop, along with symptoms of fever, as prognostic standards for ARS. [ 59 ]   Actress  Midori Naka , who was present during the atomic bombing of Hiroshima, was the first incident of radiation poisoning to be extensively studied. Her death on 24\u00a0August 1945 was the first death ever to be officially certified as a result of ARS (or \"Atomic bomb disease\")."}
{"_id": "WikiPedia_Radiology$$$corpus_1016", "text": "There are two major databases that track radiation accidents: The American  ORISE  REAC/TS and the European  IRSN  ACCIRAD. REAC/TS shows 417\u00a0accidents occurring between 1944 and 2000, causing about 3000 cases of ARS, of which 127 were fatal. [ 60 ]  ACCIRAD lists 580 accidents with 180 ARS fatalities for an almost identical period. [ 61 ]  The two deliberate bombings are not included in either database, nor are any possible radiation-induced cancers from low doses. The detailed accounting is difficult because of confounding factors. ARS may be accompanied by conventional injuries such as steam burns, or may occur in someone with a pre-existing condition undergoing radiotherapy. There may be multiple causes for death, and the contribution from radiation may be unclear. Some documents may incorrectly refer to radiation-induced cancers as radiation poisoning, or may count all overexposed individuals as survivors without mentioning if they had any symptoms of ARS."}
{"_id": "WikiPedia_Radiology$$$corpus_1017", "text": "The following table includes only those known for their attempted survival with ARS. These cases exclude chronic radiation syndrome such as  Albert Stevens , in which radiation is exposed to a given subject over a long duration. The table also necessarily excludes cases where the individual was exposed to so much radiation that death occurred before medical assistance or dose estimations could be made, such as an attempted cobalt-60 thief who reportedly died 30 minutes after exposure. [ 62 ]  The result column represents the time of exposure to the time of death attributed to the short and long term effects attributed to initial exposure. As ARS is measured by a whole-body  absorbed dose , the exposure column only includes units of gray (Gy)."}
{"_id": "WikiPedia_Radiology$$$corpus_1018", "text": "Thousands of scientific experiments have been performed to study ARS in animals. [ citation needed ]  There is a simple guide for predicting survival and death in mammals, including humans, following the acute effects of inhaling radioactive particles. [ 69 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1019", "text": "Aidoc Medical  is an Israeli technology company that develops  computer-aided simple triage  and notification systems. Aidoc has obtained  FDA  and  CE mark  approval for its stroke,  pulmonary embolism ,  cervical fracture , intracranial hemorrhage,  intra-abdominal free gas , and  incidental pulmonary embolism  algorithms. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1020", "text": "Aidoc algorithms are in use in more than 900 hospitals and imaging centers, including  Montefiore Nyack Hospital ,  LifeBridge Health , LucidHealth,  Yale New Haven Hospital , Cedars-Sinai Medical Center,  University of Rochester Medical Center , and  Sheba Medical Center . [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1021", "text": "Aidoc was founded in 2016 by Elad Walach as the CEO, [ 5 ]  Michael Braginsky as the CTO and Guy Reiner as the VP. In April 2017, the company raised $7M, led by TLV Partners, [ 6 ]  and in April 2019, the company raised another $27M, led by Square Peg capital. [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1022", "text": "In August 2018, Aidoc gained FDA clearance for its  intracranial hemorrhage  system, [ 8 ]  and in May 2019 it received clearance for the  pulmonary embolism  system. [ 9 ] [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1023", "text": "In January 2020, the system for detecting large- vessel occlusions  (LVOs) in head CTA examinations obtained FDA clearance. [ 11 ] [ 12 ] [ 13 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1024", "text": "Aidoc has developed a suite of artificial intelligence products that flag both time-sensitive and time-consuming (for the radiologist) abnormalities across the body. The algorithms are developed with large quantities of data to provide diagnostic aid for a broad set of pathologies. The company offers an array of algorithms that span across the body, including for intracranial hemorrhage, spine fractures (C, T & L), free air in the abdomen, pulmonary embolism, and more. It developed \"Always-on AI\", a term coined by Elad Walach that refers to a type of artificial intelligence that is \"Always-on\u2014constantly running in the background and automatically analyzing medical imaging data, identifying urgent findings, and sparing radiologists from \"drowning\" in vast amounts of irrelevant data. [ 14 ] [ 15 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1025", "text": "Aidoc's solutions cover medical conditions prevalent in all settings ( ED / inpatient / outpatient ), including  level 1 trauma centers , outpatient imaging centers,  teleradiology  groups and, are set up in over 200 medical centers worldwide. Notable customers include the  University of Rochester Medical Center [ 16 ]  and Global Diagnostics Australia. [ 17 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1026", "text": "A clinical study on Aidoc\u2019 accuracy of deep  convolutional neural networks  for the detection of pulmonary embolism (PE) on CT pulmonary angiograms (CTPAs) was performed by the University Hospital of Basel and presented at the European Congress of Radiology, showing that the Aidoc algorithm reached 93% sensitivity and 95% specificity. [ 18 ] [ 19 ] [ 20 ]  Clinical research has also been performed to test the diagnostic performance of Aidoc's deep learning-based triage system for the flagging of acute findings in abdominal computed tomography (CT) examinations. Overall, the algorithm achieved 93% sensitivity (91/98, 7 false negatives) and 97% specificity (93/96, 3 false-positive) in the detection of acute abdominal findings. [ 21 ] [ 22 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1027", "text": "Additional clinical research on Aidoc's Intracranial hemorrhage algorithm accuracy was presented at the European Congress of Radiology by Antwerp University Hospital, evaluating the use of its deep learning algorithm for the detection of intracranial hemorrhage on non-contrast enhanced  CT  of the  brain . [ 23 ]  The University of Washington completed a study on the accuracy of Aidoc's intracranial hemorrhage algorithm. [ 24 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1028", "text": "In  medical imaging , an  anti-scatter grid  (also known as a  Bucky-Potter grid ) is a device for limiting the amount of scattered  radiation  reaching the detector, [ 1 ] [ 2 ]  thereby improving the quality of diagnostic  medical x-ray  images.  The grid is positioned on the opposite side of the patient from the  x-ray  source, and between the patient and the  X-ray detector  or film.  Reducing the amount of scattered x-rays increases the image's contrast resolution, and consequently the visibility of  soft tissues ."}
{"_id": "WikiPedia_Radiology$$$corpus_1029", "text": "The device was first invented by German  radiologist   Gustav Peter Bucky , who showed in 1913 that a grid can be used to 'reject' scattered x-rays before they reach the detector.  It was later improved by American radiologist Hollis E. Potter by introducing moving grid. The Bucky-Potter grid facilitated the transition from small glass photographic plates to film in a variety of sizes. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1030", "text": "Scattered x-rays do not travel in parallel to rays that pass directly through the patient. The quantity of scattering depends on several factors including: x-ray beam area, x-ray photon energies (determined by tube voltage setting), thickness of the tissue, and the composition of the tissue. [ 4 ]  By 'rejecting' scattered x-rays before they reach the detector, the Bucky-Potter grid improves recorded contrast."}
{"_id": "WikiPedia_Radiology$$$corpus_1031", "text": "The grid is constructed of a series of alternating parallel strips of  lead  and a  radiolucent  substance such as a  plastic ,  carbon fibre ,  aluminium , even paper.  The grid is placed between the  patient  and the detector during the exposure. Radiation which has travelled straight through the patient from the x-ray source moves directly through the radiolucent portions of the grid and strikes the detector.  Radiation which has been scattered while travelling through the patient strikes the lead strips at an angle, and is either attenuated or further scattered.  As a result, only radiation which has travelled directly through the patient is imaged on the detector, increasing contrast."}
{"_id": "WikiPedia_Radiology$$$corpus_1032", "text": "The single most important parameter that influences the performance of an anti-scatter grid is the grid ratio. [ 5 ]  The grid ratio is the ratio of the height to the width of the interspaces (not the grid bars) in the grid. Grid ratios of 8:1, 10:1, and 12:1 are most. A 5:1 grid is most common for  mammography . [ 5 ]  The grid is essentially a one-dimensional  Collimator  and increasing the grid ratio increases the degree of collimation. Higher grid ratios provide better scatter cleanup, but they also result in greater radiation doses to the patient. [ 5 ]  In addition, though higher ratios are possible, they require greater radiation intensity increases when used, require more precise positioning, and are more expensive to produce. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1033", "text": "Grids are used particularly in examinations where a large quantity of scatter is created, i.e., those involving a large volume of tissue being irradiated and those requiring low energy i.e.  voltage . The scatter would otherwise degrade the image by reducing the  contrast  and  resolution . Use of a grid, however, requires a greater radiation exposure to the patient as a good deal of primary beam is also attenuated by the lead slats, and for this reason grids are not used for all examinations, particularly in pediatric practice."}
{"_id": "WikiPedia_Radiology$$$corpus_1034", "text": "One drawback of a fixed radiographic grid is that it creates grid lines on the image. Hollis Potter (1880-1964) showed in 1920 that these grid lines could be eliminated by moving the grid at right angles to the grid lines during the exposure. If the range and speed of motion is sufficient, the grid lines will be blurred out. The motion may be oscillating, vibrating, or reciprocating and must be continuous and smooth. The motion must also begin before exposure and continue until after exposure."}
{"_id": "WikiPedia_Radiology$$$corpus_1035", "text": "Aortopulmonary window (APW)  is a faulty connection between the  aorta  and the main  pulmonary artery  that results in a significant  left-to-right shunt . [ 2 ]  The aortopulmonary window is the rarest of  septal defects , accounting for 0.15-0.6% of all congenital heart malformations. [ 4 ]  An aortopulmonary window can develop alone or in up to 50% of cases\u00a0alongside\u00a0other cardiac defects such as  interrupted aortic arch ,\u00a0 coarctation of the aorta ,  transposition of great\u00a0vessels , and  tetralogy of Fallot . [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1036", "text": "A  left-to-right shunt  can cause  heart failure , with symptoms such as  tachypnea , poor eating, and  diaphoresis .  Dyspnea  and indications of laborious breathing can be caused by low lung compliance and increased  airway resistance . Infants may have  failure to thrive  as well as recurrent  pneumonia . [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1037", "text": "Findings among individuals with an isolated aortopulmonary window vary based on\u00a0the size of the defect and the  pulmonary vascular resistance . Cardiac examination typically indicates a parasternal lift resulting from  right ventricular  overload, a loud single second  heart sound  induced by  pulmonary hypertension , and increased peripheral pulses. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1038", "text": "When the defect is larger,\u00a0 pulmonary vascular resistance  may continue to be elevated in the initial weeks or months of life, and there is a modest\u00a0amount of pulmonary overcirculation. A rather faint  basal systolic ejection murmur  without a diastolic element and a loud single second heart sound develop due to mild overcirculation. As the  pulmonary vascular resistance  decreases throughout the first few months, the left-to-right shunting of blood into the lungs increases, and the  systolic murmur  becomes more intense and longer, eventually extending into diastole and becoming a continuous murmur. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1039", "text": "Because there is a pressure gradient from the  aorta  to the  pulmonary artery  throughout systole and diastole, a small aortopulmonary defect may produce a  murmur  similar to a  patent ductus arteriosus . [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1040", "text": "When a large defect is left unrepaired,  Eisenmenger syndrome \u00a0 will develop\u00a0with reversal of the shunt. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1041", "text": "Untreated cases with major malformations have a poor prognosis, with 40% dying within their first year of life. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1042", "text": "Physical examination findings,  ECG , and imaging are used to diagnose aortopulmonary window. An electrocardiogram reveals  right ventricular hypertrophy  or biventricular hypertrophy.  Cardiomegaly , a big main  pulmonary artery  segment, and enhanced  pulmonary vascular  marking are all visible on a\u00a0 chest x-ray . [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1043", "text": "The appearance of aortopulmonary window has similarities to that of  truncus arteriosus ,  ventricular septal defect , and large  patent ductus arteriosus . A two-dimensional  echocardiogram  can detect and distinguish between these problems. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1044", "text": "Corrective heart surgery, which is normally performed in the first year of life, is\u00a0the definitive intervention for an\u00a0aortopulmonary window. If the patient's symptoms don't\u00a0allow for corrective surgery, medical therapy of  congestive heart failure  is the\u00a0second choice.  Permanent alterations in the pulmonary vasculature can be prevented\u00a0with early\u00a0intervention. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1045", "text": "Bone age  is the degree of a person's  skeletal  development. In children, bone age serves as a measure of physiological maturity and aids in the diagnosis of growth abnormalities, endocrine disorders, and other medical conditions. [ 1 ] [ 2 ] [ 3 ]  As a person grows from  fetal  life through childhood,  puberty , and finishes growth as a young adult, the bones of the  skeleton  change in size and shape. These changes can be seen by  x-ray  and other imaging techniques. A comparison between the appearance of a patient's bones to a standard set of bone images known to be representative of the average bone shape and size for a given age can be used to assign a \"bone age\" to the patient."}
{"_id": "WikiPedia_Radiology$$$corpus_1046", "text": "Bone age is distinct from an individual's biological or chronological age, which is the amount of time that has elapsed since  birth . Discrepancies between bone age and biological age can be seen in people with stunted growth, where bone age may be less than biological age. Similarly, a bone age that is older than a person's chronological age may be detected in a child growing faster than normal. A delay or advance in bone age is most commonly associated with normal variability in growth, but significant deviations between bone age and biological age may indicate an underlying medical condition that requires treatment. A child's current height and bone age can be used to predict adult height. [ 4 ]  Other uses of bone age measurements include assisting in the diagnosis of medical conditions affecting children, such as  constitutional growth delay ,  precocious puberty ,  thyroid dysfunction ,  growth hormone deficiency , and other causes of abnormally short or tall stature."}
{"_id": "WikiPedia_Radiology$$$corpus_1047", "text": "In the United States, the most common technique for estimating a person's bone age is to compare an x-ray of the patient's left hand and wrist to a reference atlas containing x-ray images of the left hands of children considered to be representative of how the skeletal structure of the hand appears for the average person at a given age. [ 2 ]  A  paediatric radiologist  specially trained in estimating bone age assesses the patient's x-ray for growth, shape, size, and other bone features. The image in the reference atlas that most closely resembles the patient's x-ray is then used to assign a bone age to the patient. [ 5 ]  Other techniques for estimating bone age exist, including x-ray comparisons of the bones of the knee or elbow to a reference atlas and  magnetic resonance imaging  approaches. [ 1 ] [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1048", "text": "Estimating the bone age of a living child is typically performed by comparing images of their bones to images of models of the average skeleton for a given age and sex acquired from healthy children and compiled in an atlas. [ 7 ] [ 8 ]  Features of bone development assessed in determining bone age include the presence of bones (have certain bones  ossified  yet), the size and shape of bones, the amount of mineralization (also called  ossification ), and the degree of fusion between the  epiphyses  and  metaphyses . [ 5 ] [ 9 ]  The first atlas published in 1898 by John Poland consisted of x-ray images of the left hand and wrist. [ 10 ] [ 11 ]  Since then, updated atlases of the left hand and wrist have appeared, [ 12 ] [ 5 ]  along with atlases of the foot and ankle, [ 13 ]  knee, [ 14 ]  and elbow. [ 15 ]  An alternative approach to the atlas method just described is the so-called \"single-bone method\" where maturity scales are assigned to individual bones. [ 7 ] [ 8 ]  Here, a selection of bones are given a score based on their perceived development, a sum is totaled based on the individual bone scores, and the sum is correlated to a final bone age. [ 7 ] [ 8 ] [ 16 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1049", "text": "The two most common techniques for estimating bone age are based on a posterior-anterior x-ray of a patient's left hand, fingers, and  wrist . [ 5 ] [ 17 ]  The reason for imaging only the left hand and wrist are that a hand is easily x-rayed with minimal radiation [ 18 ]  and shows many bones in a single view. [ 19 ]  Further, most people are right-hand dominant and the left hand is therefore less likely to be deformed due to trauma. [ 17 ] [ 20 ]  Finally, only the wrist and hand are imaged out of a desire to minimize the amount of potentially harmful ionizing radiation delivered to a child. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1050", "text": "In the United States, bone age is usually determined by comparing an x-ray of the patient's left hand and wrist to a set of reference images contained in the Greulich and Pyle atlas. [ 5 ] [ 2 ] [ 3 ] [ 1 ]  Drs. William Walter Greulich and Sarah Idell Pyle published the first edition of their standard reference atlas of x-ray images of the left hands and wrists of boys and girls in 1950. [ 12 ]  The Greulich and Pyle atlas contains x-ray images of the left hands and wrists of different children deemed to be good models of the average appearance of the bones of the hand at a given age. The atlas has a set of images arranged in chronological order by age for males ranging from 3 months to 19 years and for females ranging from 3 months to 18 years in varying intervals of 3 months to 1 year. [ 3 ] [ 21 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1051", "text": "Images in the Greulich and Pyle atlas came from healthy white boys and girls enrolled in the Brush Foundation Study for Human Growth and Development between the years 1931 and 1942. [ 2 ] [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1052", "text": "To assign a bone age to the patient under review, a radiologist compares the patient's hand and wrist x-ray to images in the Greulich and Pyle atlas. Assessment of the carpals, metacarpals, and phalanges are used to find the closest match in the atlas; the chronological age of the patient in the atlas becomes the bone age assigned to the patient under review. [ 3 ]  If a patient's x-ray is found to be very close in appearance to two contiguous images in the atlas, then an average of the chronological ages in the atlas may be used as the patient's bone age, although some evaluators choose to interpolate the closest age while others report a range of possible bone ages. [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1053", "text": "A drawback associated with the Greulich and Pyle method of assessing bone age is that it relies on x-ray imaging and therefore requires exposing the patient to ionizing radiation. Further, there can be moderate levels of variability in the bone ages assigned to the same patient by different assessors. [ 21 ]  Other downsides are that the atlas has not been updated since 1959 and the images in the atlas were acquired from healthy white children living in Cleveland, Ohio in the 1930s and 1940s and therefore may not yield accurate bone age assignments when applied to non-white patients or unhealthy children. [ 1 ] [ 2 ] [ 21 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1054", "text": "The Tanner-Whitehouse (TW) technique of estimating bone is a \"single-bone method\" based on an x-ray image of a patient's left hand and wrist. There have been two updates since the first publication of the TW method in 1962: the TW2 method in 1975 and the TW3 method in 2001. [ 16 ] [ 22 ]  The TW methods consist of evaluating individual bones and assigning a letter grade to each bone based on its degree of maturation. Next, the scores for all evaluated bones are compiled into a sum, and that sum is correlated to bone age through a lookup table for males or females depending on the sex of the patient. [ 16 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1055", "text": "The bones considered in the TW3 method include the distal radius and ulna, the metacarpals and phalanges of the 1st, 3rd, and 5th fingers, and all of the carpal bones except the pisiform. [ 8 ] [ 16 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1056", "text": "An atlas based on knee maturation has also been compiled. [ 1 ] [ 14 ] [ 23 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1057", "text": "The bones in the hand a wrist in a newborn do not change much in the first year of life. [ 3 ]  However, most pediatric radiologists still use the Greulich and Pyle technique for estimating bone age in infancy. [ 11 ] [ 7 ]  Alternative techniques for estimating bone age in infancy include tallying the number of ossification centers present in the left half of the infant's body requiring a hemiskeleton x-ray. [ 11 ] [ 7 ]  One common method based on x-rays of the hemiskeleton is the Sontag method. [ 24 ]  This technique was created to avoid errors in estimating bone age thought to arise from focusing on only one area of the body. [ 24 ]  The Sontag method uses x-rays of all the bones and joints of the upper and lower limbs on the left side of the body. [ 24 ]  Then, a radiologist counts the number of ossification centers present and uses a chart to convert the sum of ossification centers to a bone age. There is a chart for males and another for females with possible bone ages ranging from 1 month to 5 years. [ 24 ]  Since most of the ossification centers counted using this technique appear early in life, this method is only valid for measuring bone age up to around 5 years of age. [ 24 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1058", "text": "Lamparski (1972) [ 25 ]  used the cervical vertebrae and found them to be as reliable and valid as the hand-wrist area for assessing skeletal age.\u00a0He developed a series of standards for the assessment of skeletal age for both males and females.\u00a0This method has the advantage of eliminating the need for additional radiographic exposure in cases where the vertebrae have already been recorded on a lateral cephalometric radiographic. [ 26 ]  This method is called the  Cervical vertebral maturation method"}
{"_id": "WikiPedia_Radiology$$$corpus_1059", "text": "Hassel &\u00a0Farman (1995) [ 27 ]  developed an index based on the second, third, and fourth cervical vertebrae (C2, C3, C4) and proved that atlas maturation was highly correlated with skeletal maturation of the hand-wrist.  Several smartphone applications have been developed to facilitate the use of vertebral methods such as  Easy Age ."}
{"_id": "WikiPedia_Radiology$$$corpus_1060", "text": "Assessment of a patient's bone age is used in pediatric medicine to help determine if a child is growing normally. [ 3 ]  Large differences between a person's bone age and their chronological age may indicate a growth disorder. [ 5 ]  For example, a patient's bone age may be less than their chronological age suggesting a delay in growth as may be caused by a growth hormone deficiency. In the case of too much growth hormone, a child may have a bone age that is older than their chronological age suggesting that they are growing abnormally fast. Since bone age measurements are inherently approximations, they are conventionally reported with a standard deviation which serves as an estimate of the associated error. For a child's bone age to be considered abnormal, the chronological age must differ from the assigned bone age by more than 2  standard deviations . [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1061", "text": "Bone age acts as a surrogate for physiological development because growth and maturation of the skeletal system depend on the presence of hormones like growth hormone, sex steroids (e.g., estrogen and testosterone), and thyroxine. [ 2 ] [ 5 ]  Studies of bone age in children allow physicians to correlate a child's current height and bone age to their predicted future maximum height in adulthood. [ 3 ] [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1062", "text": "Not only can bone age help in diagnosing a child with a growth abnormality, but it can also play a role in treatment. [ 3 ]  In certain instances, abnormal growth conditions may be treated with supplemental hormone therapy. The best time to start and stop such therapies can be determined based on a patient's bone age."}
{"_id": "WikiPedia_Radiology$$$corpus_1063", "text": "Statistics have been compiled to indicate the percentage of height growth remaining at a given bone age. By simple arithmetic, a predicted adult height can be computed from a child's height and bone age. Separate tables are used for boys and girls because of the sex difference in timing of puberty, and slightly different percentages are used for children with unusually advanced or delayed bone maturation. These tables, the Bayley-Pinneau tables, are included as an appendix in the Greulich and Pyle atlas."}
{"_id": "WikiPedia_Radiology$$$corpus_1064", "text": "In several conditions involving atypical growth, bone age height predictions are less accurate. For example, in children born small for gestational age who remain short after birth, bone age is a poor predictor of adult height. [ 28 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1065", "text": "For the average person with average puberty, the bone age would match the person's chronological age. In terms of height growth and height growth related to bone age, average females stop growing taller two years earlier than average males. Peak height velocity (PHV) occurs at the average age of 11 years for girls and at the average age of 13 years for boys. [ 29 ]  While there is no exact age for the culmination of bone maturity, modern research suggests a range of between 15-17 years for bone maturity in boys and 14-16 years for girls. [ 30 ] [ 31 ] [ 32 ] [ 33 ] [ 34 ] [ 35 ] [ 36 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1066", "text": "There are exceptions with people who have an  advanced  bone age (bone age is older than chronological age) due to being an early bloomer (someone starting puberty and hitting PHV earlier than average), being an early bloomer with precocious puberty, or having another condition. There are also exceptions with people who have a  delayed  bone age (bone age is younger than chronological age) due to being a late bloomer (someone starting puberty and hitting PHV later than average), being a late bloomer with  delayed puberty , or having another condition. [ 37 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1067", "text": "An  advanced  bone age is common when a child has had prolonged elevation of  sex steroid  levels, as in  precocious puberty  or  congenital adrenal hyperplasia . The bone age is often marginally advanced with premature  adrenarche , when a child is overweight from a young age or when a child has lipodystrophy. Those with an advanced bone age typically hit a growth spurt early on but stop growing at an earlier age. Bone age may be significantly advanced in genetic overgrowth syndromes, such as  Sotos syndrome ,  Beckwith-Wiedemann syndrome  and  Marshall-Smith syndrome . [ 38 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1068", "text": "Bone maturation is  delayed  with the variation of normal development termed  constitutional  delay of growth and puberty, but delay also accompanies growth failure due to  growth hormone deficiency  and  hypothyroidism . [ 39 ] [ 40 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1069", "text": "Recent studies show that organs like the liver can also be used to estimate age and sex, because of the unique feature of liver. [ 41 ]  Liver weight increases with age and is different between males and females. Thus, the liver can be employed in special medico-legal cases of skeletal deformities or mutilation."}
{"_id": "WikiPedia_Radiology$$$corpus_1070", "text": "A table of possible causes of abnormal stature and the expected bone age associated with each condition is provided below."}
{"_id": "WikiPedia_Radiology$$$corpus_1071", "text": "Formation of the human skeletal system begins in fetal life with the development of a loosely ordered connective tissue known as  mesenchyme . [ 43 ]  The cells of the mesenchyme can become bone by one of two primary methods: (1)  intramembranous ossification  where mesenchymal cells differentiate directly into bone or (2)  endochondral ossification  where  mesenchymal cells become a cartilaginous model of chondrocytes which then become bone. [ 44 ] [ 45 ]  The bones of the limbs form and lengthen through endochondral ossification beginning by the 12th week after fertilization. [ 43 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1072", "text": "At birth, only the  metaphyses  of the \" long bones \" are present. The long bones are those that grow primarily by elongation at an  epiphysis  at one end of the growing bone. The long bones include the  femurs ,  tibias , and  fibulas  of the lower limb, the  humeri ,  radii , and  ulnas  of the upper limb (arm + forearm), and the  phalanges  of the  fingers  and  toes . The long bones of the leg comprise nearly half of adult height. The other primary skeletal component of height is the  spine  and  skull ."}
{"_id": "WikiPedia_Radiology$$$corpus_1073", "text": "As a child grows the epiphyses become calcified and appear on x-rays, as do the carpal and tarsal bones of the  hands  and feet, separated on x-rays by a layer of invisible  cartilage  where most of the growth is occurring. As  sex steroid  levels rise during puberty, bone maturation accelerates. As growth nears conclusion and attainment of adult height, bones begin to approach the size and shape of adult bones. The remaining cartilaginous portions of the epiphyses become thinner. As these cartilaginous zones become obliterated, the epiphyses are said to be \" closed \" and no further lengthening of the bones will occur. A small amount of spinal growth concludes an adolescent's growth."}
{"_id": "WikiPedia_Radiology$$$corpus_1074", "text": "The carpal bones arise from primary ossification centers and continue their calcification in an outward manner. The emergence of the primary ossification centers of the carpal bones appear in a predictable order that can help in determining bone age. First the capitate forms at an average age of 2 months, followed shortly by the hamate, then the triquetrum around 14 months, and so on. [ 46 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1075", "text": "A  bone scan  or  bone scintigraphy   / s \u026a n \u02c8 t \u026a \u0261 r \u0259 f i /  is a  nuclear medicine  imaging technique used to help diagnose and assess different bone diseases. These include  cancer of the bone  or  metastasis , location of bone  inflammation  and  fractures  (that may not be visible in traditional  X-ray images ), and bone infection (osteomyelitis). [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1076", "text": "Nuclear medicine provides functional imaging and allows visualisation of  bone metabolism  or  bone remodeling , which most other imaging techniques (such as X-ray  computed tomography , CT) cannot. [ 2 ] [ 3 ]  Bone  scintigraphy  competes with  positron emission tomography  (PET) for imaging of abnormal metabolism in bones, but is considerably less expensive. [ 4 ]  Bone scintigraphy has higher  sensitivity  but lower specificity than CT or MRI for diagnosis of  scaphoid fractures  following negative  plain radiography . [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1077", "text": "Some of the earliest investigations into skeletal metabolism were carried out by  George de Hevesy  in the 1930s, using  phosphorus-32  and by  Charles Pecher  in the 1940s. [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1078", "text": "In the 1950s and 1960s calcium-45 was investigated, but as a  beta emitter  proved difficult to image. Imaging of  positron  and  gamma emitters  such as  fluorine-18  and  isotopes of strontium  with  rectilinear scanners  was more useful. [ 8 ] [ 9 ]  Use of  technetium-99m  ( 99m Tc) labelled  phosphates ,  diphosphonates  or similar agents, as in the modern technique, was first proposed in 1971. [ 10 ] [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1079", "text": "The most common  radiopharmaceutical  for bone scintigraphy is  99m Tc with  methylene diphosphonate  (MDP). [ 12 ]  Other bone radiopharmaceuticals include  99m Tc with HDP, HMDP and DPD. [ 13 ] [ 14 ]  MDP  adsorbs  onto the crystalline  hydroxyapatite  mineral of bone. [ 15 ]  Mineralisation occurs at  osteoblasts , representing sites of bone growth, where MDP (and other diphosphates) \"bind to the hydroxyapatite crystals in proportion to local blood flow and  osteoblastic  activity and are therefore markers of bone turnover and bone perfusion\". [ 16 ] [ 17 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1080", "text": "The more active the  bone turnover , the more radioactive material will be seen. Some  tumors ,  fractures  and  infections  show up as areas of increased uptake. [ 18 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1081", "text": "Note that the technique depends on the osteoblastic activity during remodelling and repair processes following initial osteolytic activity. This leads to a limitation of the applicability of this imaging technique with diseases not featuring this osteoblastic (reactive) activity, for example with  multiple myeloma . Scintigraphic images remain falsely negative for a long period of time and therefore have only limited diagnostic value. In these cases CT or MRI scans are preferred for diagnosis and staging."}
{"_id": "WikiPedia_Radiology$$$corpus_1082", "text": "In a typical bone scan technique, the patient is injected (usually into a vein in the arm or hand, occasionally the foot) with up to 740\u00a0 MBq  of  technetium-99m-MDP  and then scanned with a  gamma camera , which captures planar  anterior  and posterior or  single photon emission computed tomography  (SPECT) images. [ 19 ] [ 14 ]  In order to view small lesions SPECT imaging technique may be preferred over planar scintigraphy. [ 20 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1083", "text": "In a single phase protocol (skeletal imaging alone), which will primarily highlight osteoblasts, images are usually acquired 2\u20135 hours after the injection (after four hours 50\u201360% of the activity will be fixed to bones). [ 19 ] [ 14 ] [ 21 ]  A two or three phase protocol utilises additional scans at different points after the injection to obtain additional diagnostic information. A dynamic (i.e. multiple acquired frames) study immediately after the injection captures  perfusion  information. [ 21 ] [ 22 ]  A second phase \"blood pool\" image following the perfusion (if carried out in a three phase technique) can help to diagnose inflammatory conditions or problems of blood supply. [ 23 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1084", "text": "A typical  effective dose  obtained during a bone scan is 6.3  millisieverts  (mSv). [ 24 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1085", "text": "Although bone scintigraphy generally refers to gamma camera imaging of  99m Tc radiopharmaceuticals, imaging with  positron emission tomography  (PET) scanners is also possible, using  fluorine-18   sodium fluoride  ([ 18 F]NaF)."}
{"_id": "WikiPedia_Radiology$$$corpus_1086", "text": "For  quantitative  measurements,  99m Tc-MDP has some advantages over [ 18 F]NaF. MDP renal clearance is not affected by urine flow rate and simplified data analysis can be employed which assumes  steady state  conditions. It has negligible tracer uptake in  red blood cells , therefore correction for plasma to whole blood ratios is not required unlike [ 18 F]NaF. However, disadvantages include higher rates of protein binding (from 25% immediately after injection to 70% after 12 hours leading to the measurement of freely available MDP over time), and less  diffusibility  due to higher  molecular weight  than [ 18 F]NaF, leading to lower  capillary permeability . [ 25 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1087", "text": "There are several advantages of the PET technique, which are common to PET imaging in general, including improved  spatial resolution  and more developed  attenuation  correction techniques. Patient experience is improved as imaging can be started much more quickly following radiopharmaceutical injection (30\u201345 minutes, compared to 2\u20133 hours for MDP/HDP). [ 26 ] [ 27 ]  [ 18 F]NaF PET is hampered by high demand for scanners, and limited tracer availability. [ 28 ] [ 29 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1088", "text": "Caldwell's view  (or  Occipitofrontal view ) is a radiographic view of the skull where the X-ray plate is perpendicular to the  orbitomeatal line . The rays pass from behind the head and are angled at 15-20\u00b0 to the radiographic plate. It is commonly used to get better view of the ethmoid and  frontal sinuses . [ 1 ]    It is named after the noted American radiologist  Eugene W. Caldwell , who described it in 1907. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1089", "text": "A  collimator  is a device which narrows a beam of particles or waves. To narrow can mean either to cause the directions of motion to become more aligned in a specific direction (i.e., make  collimated light  or  parallel  rays), or to cause the spatial  cross section  of the beam to become smaller ( beam limiting device )."}
{"_id": "WikiPedia_Radiology$$$corpus_1090", "text": "The English physicist  Henry Kater  was the inventor of the  floating collimator , which rendered a great service to practical astronomy. He reported about his invention in January 1825. [ 1 ]  In his report, Kater mentioned previous work in this area by  Carl Friedrich Gauss  and  Friedrich Bessel ."}
{"_id": "WikiPedia_Radiology$$$corpus_1091", "text": "In  optics , a collimator may consist of a  curved mirror  or  lens  with some type of light source and/or an image at its  focus . This can be used to replicate a target focused at  infinity  with little or no  parallax ."}
{"_id": "WikiPedia_Radiology$$$corpus_1092", "text": "In  lighting , collimators are typically designed using the principles of  nonimaging optics . [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1093", "text": "Optical collimators can be used to calibrate other optical devices, [ 3 ]  to check if all elements are aligned on the  optical axis , to set elements at proper focus, or to align two or more devices such as  binoculars  or  gun barrels  and  gunsights . [ 4 ]  A surveying camera may be collimated by setting its  fiduciary markers  so that they define the principal point, as in  photogrammetry ."}
{"_id": "WikiPedia_Radiology$$$corpus_1094", "text": "Optical collimators are also used as  gun sights  in the  collimator sight , which is a simple optical collimator with a cross hair or some other  reticle  at its focus. The viewer only sees an image of the reticle. They have to use it either with both eyes open and one eye looking into the collimator sight, with one eye open and moving the head to alternately see the sight and the target, or with one eye to partially see the sight and target at the same time. [ 5 ] [ clarification needed ]  Adding a  beam splitter  allows the viewer to see the reticle and the  field of view , making a  reflector sight ."}
{"_id": "WikiPedia_Radiology$$$corpus_1095", "text": "Collimators may be used with  laser diodes  and  CO 2  cutting lasers . Proper collimation of a laser source with long enough  coherence length  can be verified with a  shearing interferometer ."}
{"_id": "WikiPedia_Radiology$$$corpus_1096", "text": "In  X-ray optics ,  gamma ray  optics, and  neutron  optics, a  collimator  is a device that filters a stream of rays so that only those traveling parallel to a specified direction are allowed through. Collimators are used for X-ray, gamma-ray, and neutron imaging because it is difficult to focus these types of radiation into an image using lenses, as is routine with  electromagnetic radiation  at optical or near-optical wavelengths. Collimators are also used in radiation detectors in  nuclear power stations  to make them directionally sensitive."}
{"_id": "WikiPedia_Radiology$$$corpus_1097", "text": "The figure to the right illustrates how a S\u00f6ller collimator is used in neutron and X-ray machines. The upper panel shows a situation where a collimator is not used, while the lower panel introduces a collimator. In both panels the source of radiation is to the right, and the image is recorded on the gray plate at the left of the panels."}
{"_id": "WikiPedia_Radiology$$$corpus_1098", "text": "Without a collimator, rays from all directions will be recorded; for example, a ray that has passed through the top of the specimen (to the right of the diagram) but happens to be travelling in a downwards direction may be recorded at the bottom of the plate. The resultant image will be so blurred and indistinct as to be useless."}
{"_id": "WikiPedia_Radiology$$$corpus_1099", "text": "In the lower panel of the figure, a collimator has been added (blue bars). This may be a sheet of lead or other material opaque to the incoming radiation with many tiny holes bored through it or in the case of neutrons it can be a sandwich arrangement (which can be up to several feet long; see  ENGIN-X ) with many layers alternating between neutron absorbing material (e.g.,  gadolinium ) with neutron transmitting material. This can be something simple, such as air; alternatively, if mechanical strength is needed, a material such as aluminium may be used. If this forms part of a rotating assembly, the sandwich may be curved. This allows energy selection in addition to collimation; the curvature of the collimator and its rotation will present a straight path only to one energy of neutrons. Only rays that are travelling nearly parallel to the holes will pass through them\u2014any others will be absorbed by hitting the plate surface or the side of a hole. This ensures that rays are recorded in their proper place on the plate, producing a clear image."}
{"_id": "WikiPedia_Radiology$$$corpus_1100", "text": "For  industrial radiography  using gamma radiation sources such as  iridium-192  or  cobalt-60 , a collimator (beam limiting device) allows the radiographer to control the exposure of radiation to expose a film and create a radiograph, to inspect materials for defects. A collimator in this instance is most commonly made of  tungsten , and is rated according to how many half value layers it contains, i.e., how many times it reduces undesirable radiation by half. For instance, the thinnest walls on the sides of a 4 HVL tungsten collimator 13\u00a0mm (0.52\u00a0in) thick will reduce the intensity of radiation passing through them by 88.5%. The shape of these collimators allows emitted radiation to travel freely toward the specimen and the x-ray film, while blocking most of the radiation that is emitted in undesirable directions such as toward workers."}
{"_id": "WikiPedia_Radiology$$$corpus_1101", "text": "Although collimators improve  resolution , they also reduce  intensity  by blocking incoming radiation, which is undesirable for remote sensing instruments that require high sensitivity. For this reason, the  gamma ray spectrometer  on the  Mars Odyssey  is a non-collimated instrument. Most lead collimators let less than 1% of incident photons through. Attempts have been made to replace collimators with electronic analysis.  [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1102", "text": "Collimators (beam limiting devices) are used in  linear accelerators  used for  radiotherapy  treatments. They help to shape the beam of radiation emerging from the machine and can limit the maximum field size of a beam."}
{"_id": "WikiPedia_Radiology$$$corpus_1103", "text": "The treatment head of a linear accelerator consists of both a primary and secondary collimator. The primary collimator is positioned after the electron beam has reached a vertical orientation. When using photons, it is placed after the beam has passed through the X-ray target. The secondary collimator is positioned after either a flattening filter (for photon therapy) or a scattering foil (for electron therapy). The secondary collimator consists of two jaws which can be moved to either enlarge or minimize the size of the treatment field."}
{"_id": "WikiPedia_Radiology$$$corpus_1104", "text": "New systems involving  multileaf collimators  (MLCs) are used to further shape a beam to localise treatment fields in radiotherapy. MLCs consist of approximately 50\u2013120 leaves of heavy, metal collimator plates which slide into place to form the desired field shape."}
{"_id": "WikiPedia_Radiology$$$corpus_1105", "text": "To find the spatial resolution of a parallel hole collimator with a hole length,  \n \n \n \n l \n \n \n {\\displaystyle l} \n \n , a hole diameter  \n \n \n \n D \n \n \n {\\displaystyle D} \n \n  and a distance to the imaged object  \n \n \n \n s \n \n \n {\\displaystyle s} \n \n , the following formula can be used\n \n \n \n \n \n R \n \n collimator \n \n \n = \n D \n + \n \n \n \n D \n s \n \n \n l \n \n effective \n \n \n \n \n \n \n {\\displaystyle R_{\\text{collimator}}=D+{\\frac {Ds}{l_{\\text{effective}}}}} \n \n \nwhere the effective length is defined as\n \n \n \n \n \n l \n \n effective \n \n \n = \n l \n \u2212 \n \n \n 2 \n \u03bc \n \n \n \n \n {\\displaystyle l_{\\text{effective}}=l-{\\frac {2}{\\mu }}} \n \n \nWhere  \n \n \n \n \u03bc \n \n \n {\\displaystyle \\mu } \n \n  is the linear attenuation coefficient of the material from which the collimator is made."}
{"_id": "WikiPedia_Radiology$$$corpus_1106", "text": "Companion shadow  is a term used in describing  radiographs  that denotes the appearance of a smooth, homogenous, radiodensity with a well-defined margin that runs parallel with a bony landmark.  Companion shadows represent  soft tissue  that overlies the respective bony landmark in profile. They are not seen in every radiograph and can be misinterpreted as  pathology ."}
{"_id": "WikiPedia_Radiology$$$corpus_1107", "text": "Computational human phantoms  are models of the  human body  used in  computerized analysis . Since the 1960s, the  radiological science  community has developed and applied these models for  ionizing radiation   dosimetry  studies. These models have become increasingly accurate with respect to the internal structure of the human body."}
{"_id": "WikiPedia_Radiology$$$corpus_1108", "text": "As computing evolved, so did the  phantoms . Graduating from phantoms based on simple  quadratic equations  to  voxelized  phantoms, which were based on actual  medical images  of the human body, was a major step. The newest models are based on more advanced mathematics, such as  non-uniform rational B-spline  (NURBS) and  polygon meshes , which allow for  4-D  phantoms where simulations can take place not only  3-dimensional space  but in time as well."}
{"_id": "WikiPedia_Radiology$$$corpus_1109", "text": "Phantoms have been developed for a wide variety of humans, from children to adolescents to adults, male and female, as well as pregnant women. With such a variety of phantoms, many kinds of  simulations  can be run, from  dose  received from medical imaging procedures to  nuclear medicine . Over the years, the results of these simulations have created an assortment of standards that have been adopted in the  International Commission on Radiological Protection  (ICRP) recommendations. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1110", "text": "The very first generation computational phantoms were developed to address the need to better assess  organ   doses  from internally deposited  radioactive materials  in workers and patients.  Until the late 1950s, the ICRP still used very simple models. [ 2 ]  In these calculations, each organ of the body was assumed to be represented as a  sphere  with an \"effective  radius \". The  radionuclide  of interest was assumed to be located at the center of the sphere and the \"effective absorbed energy\" was calculated for each organ. Phantoms such as the  Shepp-Logan Phantom  were used as models of a human head in the development and testing of  image reconstruction  algorithms. [ 3 ] [ 4 ] [ 5 ] [ 6 ]  However, scientists attempted to model individual organs of the body and ultimately the entire human body in a realistic manner, the efforts of which led to stylized  anthropomorphic  phantoms that resemble the  human anatomy ."}
{"_id": "WikiPedia_Radiology$$$corpus_1111", "text": "In general, stylized computational phantom is a mathematical representation of the human body which, when coupled with a  Monte Carlo   radiation transport   computer code , can be used to track the radiation interactions and energy deposition in the body. The feature of stylized computational phantom is finely tuned by adjusting individual parameters of the  mathematical equations , which describes the volume, position, and shape of individual  organs . Stylized computational phantom has a long history of development through the 1960s to 1980s."}
{"_id": "WikiPedia_Radiology$$$corpus_1112", "text": "The MIRD phantom [ 7 ]  was developed by Fisher and Snyder at  Oak Ridge National Laboratory  (ORNL) in the 1960s with 22  internal organs  and more than 100 sub-regions. [ 8 ] [ 9 ]  It is the first anthropomorphic phantom representing a  hermaphrodite  adult for internal  dosimetry ."}
{"_id": "WikiPedia_Radiology$$$corpus_1113", "text": "Based on MIRD phantom, many derivations of phantoms were developed for the following decades. The major types of phantom include: stylized \"Family\" phantom series developed in the 1980s by Cristy and Eckerman; \"ADAM and EVA\" developed by GSF, Germany; CAM (Computerized Anatomical Man) phantom developed by  NASA  unknown by the mainstream radiation protection dosimetry community, etc."}
{"_id": "WikiPedia_Radiology$$$corpus_1114", "text": "Although many efforts were undertaken to diversify and extend its applications in  radiation protection ,  radiation therapy , and  medical imaging , one cannot overcome its inborn limitation. The representation of  internal organs  in this mathematical phantom was crude, by capturing only the most general description of the position and  geometry  of each organ. With the powerful computer and  tomographic  imaging technologies became available in the late 1980s, the history launched a new era of  voxel  phantoms."}
{"_id": "WikiPedia_Radiology$$$corpus_1115", "text": "The stylized phantoms provided only basic information with a large degree of error.  More accurate methods of simulating a human body were necessary to advance.  To allow further research, the computer technology had to become more powerful and more readily available.  This did not occur until the 1980s.  The real breakthrough occurred when  computed tomography  (CT) and  magnetic resonance imaging  (MRI) devices could generate highly accurate images of internal organs in three dimensions and in digital format.  Researchers discovered that they could take that  diagnostic  data and transform it into a  voxel  (volumetric pixel) format, essentially re-creating the human body in digital form in 3D.  Today there are over 38 human phantoms in voxel format, for many different uses. [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1116", "text": "Two major issues with development of the reference phantoms are difficulty in obtaining useful images and handling the large amount of  data  created from these images.  CT scans give the human body a large  dose  of  ionizing radiation  \u2013 something the computational phantom was designed to circumvent in the first place.  MRI images take a long time to process.  Furthermore, most scans of a single subject cover only a small portion of the body, whereas a full scan series is needed for useful data.  Handling this data is also difficult.  While the newer computers had hard drives large enough to store the data, the memory requirements for processing the images to the desired voxel size were often too steep. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1117", "text": "While there have been many voxel phantoms developed, they have all followed a similar path to completion.  First, they must obtain the raw data, from CT scans, MRI imaging, or direct imaging through photography.  Second, the components of the body must be segmented, or identified and separated from the rest. Third, the density of each component must be identified, along with the composition of each. Lastly, the data must be unified into a single 3D structure so it may be used for analysis."}
{"_id": "WikiPedia_Radiology$$$corpus_1118", "text": "The earliest work on voxelized phantoms occurred independently at about the same time by Dr. Gibbs, of  Vanderbilt University , and Dr. Zankl at the  National Research Center for Environment and Health  (GSF) in Germany. [ 12 ] [ 13 ]  This occurred about 1982.  Dr. Gibb's work started with  X-ray  images, not CT or MRI images, for the reconstruction of a human phantom which was used for medical dose  simulations . M. Zankl and team did use CT imaging to create 12 phantoms, ranging from BABY to VISIBLE HUMAN."}
{"_id": "WikiPedia_Radiology$$$corpus_1119", "text": "A computational framework was presented, based on statistical shape modelling, for construction of race-specific organ models for internal radionuclide dosimetry and other nuclear-medicine applications. The proposed technique used to create the race-specific statistical phantom maintains anatomic realism and provides the statistical parameters for application to radionuclide dosimetry. [ 32 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1120", "text": "Boundary representation  (BREP) phantoms are computational human models that contain exterior and interior anatomical features of a human body using boundary representation method. In the realm of  health and medical physics  they are primarily used for  ionizing radiation   dosimetry ."}
{"_id": "WikiPedia_Radiology$$$corpus_1121", "text": "In the development of computational human phantoms, of particular interest is the concept of a  \"deformable\"  phantom whose  geometry  can be conveniently transformed to fit particular physical organ shapes, volumes, or body postures. Design of this type of phantom is realized by Non-Uniform Rational B-Spline (NURBS) method or polygonal mesh method, which are usually collectively called BREP methods. Compared to the voxel phantoms, BREP phantoms are better suited for geometry deformation and adjustment,  because a larger set of computerized operations are available, such as  extrusion ,  chamfering , blending,  drafting ,  shelling  and  tweaking . A major advantage of BREP phantoms is their ability to morph into an existing reference phantom or into the anatomy of a real worker or patient, which makes individual-specific dose calculation possible. [ 33 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1122", "text": "Surfaces of a  non-uniform rational B-spline  (NURBS)-based phantom are defined by NURBS equations which are formulated by a set of control points. The shape and volume of a NURBS surface vary with the coordinates of  control points . This feature is useful in designing a time-dependent  4D  human body modeling. [ 33 ]   An example is given by NCAT phantoms by Segars et al., which is used to simulate cardiac and respiratory motions with more realistic modeling of the cardiac system."}
{"_id": "WikiPedia_Radiology$$$corpus_1123", "text": "A  polygonal mesh  is composed of a set of  vertices ,  edges , and  faces  that specify the shape of a  polyhedral object  in  3D space . The surfaces of the phantom are defined by a large amount of polygonal meshes, most commonly triangles. The polygonal mesh has three remarkable advantages in developing whole-body phantoms. Firstly, mesh surfaces depicting human anatomy can be conveniently obtained from real patient images or commercial human anatomy mesh models. Secondly, the polygonal mesh-based phantom has considerable flexibility in adjusting and fine-tuning its geometry, allowing the simulation of very complex anatomies. Thirdly, many commercial  computer aided design  (CAD) software, such as  Rhinoceros ,  AutoCAD ,  Visualization Toolkit  (VTK), provide built-in functions able to rapidly convert polygonal mesh into NURBS. [ 33 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1124", "text": "Segars was the precursor of applying NURBS to phantom design. In 2001 his  doctoral thesis  described the method of developing a dynamic NURBS-based cardiac-torso (NCAT) phantom in detail. The phantom has a 4D beating heart model which was derived from 4D tagged (MRI) data. The remaining organs in the torso of the phantom were designed based on the  Visible Human Project  CT data set and were composed of 3D NURBS surfaces. Respiratory motion was also incorporated into this phantom."}
{"_id": "WikiPedia_Radiology$$$corpus_1125", "text": "In 2005, Xu et al. at Rensselaer Polytechnic Institute used the 3D VIP-Man phantom to simulate respiratory motions by adopting the gated respiratory motion data of the NCAT phantom. [ 35 ]  The 4D VIP-Man Chest phantom was used to study  external-beam treatment  planning for a  lung cancer  patient. [ 36 ]  In 2007, Xu's research group reported creation of a series of polygon-based phantoms representing a pregnant woman and her  fetus  at the end of 3, 6, and 9 month  gestations  (RPI Pregnant Females). [ 37 ]  The mesh data were initially obtained from separate anatomical information sources including a non-pregnant female, a 7-month pregnant woman CT data set, and a mesh model of the fetus. In 2008, two triangular mesh-based phantoms were created, named as RPI Deformable Adult Male and Female (RPI-AM, RPI-FM). [ 38 ] [ 39 ]  The anatomic parameters of the phantoms were made consistent with two datasets: the mass and density of internal organs originated from ICRP-23 and ICRP-89, and the whole-body height and weight percentile data were obtained from the  National Health and Nutrition Examination Survey  (NHANES 1999\u20132002). Later on, to study the relationship between breast size and lung dosimetry, a new group of phantoms were produced by altering the breast geometry of RPI-AF. [ 39 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1126", "text": "From 2006 to 2009, researchers at the  University of Florida  designed a total of twelve \"hybrid\" male and female phantoms, representing newborn, 1-, 5-, 10-, and 15-year-old and adult male/females. [ 40 ] [ 41 ] [ 42 ]  The phantoms are addressed as \" hybrid \" because most organs and tissues were modeled by NURBS surfaces whereas the skeleton, brain and extra-thoracic airways were modeled by polygonal surfaces. [ 43 ]  Anatomic parameters of the phantoms were adjusted to match 4 reference datasets, i.e., standard  anthropometric  data, reference organ masses from ICRP Publication 89, reference elemental compositions provided in ICRP 89 as well as ICRU Report 46, and reference data on the alimentary tract organs given in ICRP Publications 89 and 100."}
{"_id": "WikiPedia_Radiology$$$corpus_1127", "text": "In 2008, researchers at  Vanderbilt University , in collaboration with researchers from  Duke University , developed a family of adult and pediatric phantoms by adapting the NURBS-based NCAT adult male and female phantoms. [ 43 ]  ICRP-89 reference body and organ values were used to adjust NURBS surfaces."}
{"_id": "WikiPedia_Radiology$$$corpus_1128", "text": "In 2009 Cassola et al. [ 44 ]  at the  Federal University of Pernambuco , Brazil, developed a pair of polygonal mesh-based phantoms in standing posture, FASH (Female Adult meSH) and MASH (Male Adult meSH). The methodology is very similar but not entirely identical to the one implemented in the designing of RPI-AM and RPI-FM."}
{"_id": "WikiPedia_Radiology$$$corpus_1129", "text": "In 2010, based on existing RPI-AM, researchers at  RPI  continued to create 5 more phantoms with different  body mass index  (BMI) ranging from 23 to 44\u00a0kg\u2219m-2. [ 45 ]  These phantoms are used to study the correlation between BMI and organ doses resulting from CT and  positron emission tomography  (PET) examinations."}
{"_id": "WikiPedia_Radiology$$$corpus_1130", "text": "In 2011 researchers at  Hanyang University , Korea, reported a polygon-surface reference Korean male phantom (PSRK-Man). [ 46 ]  This phantom was constructed by converting the Visible Korean Human-Man (VKH-man) into a polygonal mesh-based phantom. The height, weight, geometry of organs and tissues were adjusted to match the Reference Korean data. Without voxelization the PSRK-man could be directly implemented in  Geant4   Monte Carlo  simulation using a built-in function, but the  computation  time was 70~150 times longer than that required by High Definition Reference Korean-Man (HDRK-Man), a voxelized phantom derived also from VKH-man."}
{"_id": "WikiPedia_Radiology$$$corpus_1131", "text": "In 2012, researchers at  RPI  developed the Computational Human for Animated Dosimetry (CHAD) phantom, structured such that its posture could be adjusted in conjunction with data obtained using a  motion capture  system. [ 47 ]  This phantom can be used to simulate the movement of a worker involved in an occupational of nuclear accident scenario, allowing researchers to gain an understanding of the impact of changing posture in the course of worker movement on radiation dose."}
{"_id": "WikiPedia_Radiology$$$corpus_1132", "text": "A  computed tomography scan  ( CT scan ),  formerly called  computed axial tomography scan  ( CAT scan ), is a  medical imaging  technique used to obtain detailed internal images of the body. [ 2 ]  The personnel that perform CT scans are called  radiographers  or radiology technologists. [ 3 ] [ 4 ] \nCT scanners use a rotating  X-ray tube  and a row of detectors placed in a  gantry  to measure X-ray  attenuations  by different tissues inside the body. The multiple  X-ray  measurements taken from different angles are then processed on a computer using  tomographic reconstruction  algorithms to produce  tomographic  (cross-sectional) images (virtual \"slices\") of a body. CT scans can be used in patients with metallic implants or pacemakers, for whom  magnetic resonance imaging  (MRI) is  contraindicated ."}
{"_id": "WikiPedia_Radiology$$$corpus_1133", "text": "Since its development in the 1970s, CT scanning has proven to be a versatile imaging technique. While CT is most prominently used in  medical diagnosis , it can also be used to form images of non-living objects. The 1979  Nobel Prize in Physiology or Medicine  was awarded jointly to South African-American physicist  Allan MacLeod Cormack  and British electrical engineer  Godfrey Hounsfield  \"for the development of computer-assisted tomography\". [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1134", "text": "On the basis of image acquisition and procedures, various type of scanners are available in the market."}
{"_id": "WikiPedia_Radiology$$$corpus_1135", "text": "Sequential CT, also known as step-and-shoot CT, is a type of scanning method in which the CT table moves stepwise. The table increments to a particular location and then stops which is followed by the  X-ray tube  rotation and acquisition of a slice. The table then increments again, and another slice is taken. The table movement stops while taking slices. This results in an increased time of scanning. [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1136", "text": "Spinning tube, commonly called  spiral CT , or helical CT, is an imaging technique in which an entire  X-ray tube  is spun around the central axis of the area being scanned. These are the dominant type of scanners on the market because they have been manufactured longer and offer a lower cost of production and purchase. The main limitation of this type of CT is the bulk and inertia of the equipment (X-ray tube assembly and detector array on the opposite side of the circle) which limits the speed at which the equipment can spin. Some designs use two X-ray sources and detector arrays offset by an angle, as a technique to improve temporal resolution. [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1137", "text": "Electron beam tomography  (EBT) is a specific form of CT in which a large enough X-ray tube is constructed so that only the path of the  electrons , travelling between the  cathode  and  anode  of the X-ray tube, are spun using  deflection coils . [ 10 ]  This type had a major advantage since sweep speeds can be much faster, allowing for less blurry imaging of moving structures, such as the heart and arteries. [ 11 ]  Fewer scanners of this design have been produced when compared with spinning tube types, mainly due to the higher cost associated with building a much larger X-ray tube and detector array and limited anatomical coverage. [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1138", "text": "Dual Energy CT, also known as Spectral CT, is an advancement of Computed Tomography in which two energies are used to create two sets of data. [ 13 ]  A Dual Energy CT may employ Dual source, Single source with dual detector layer, Single source with energy switching methods to get two different sets of data. [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1139", "text": "CT perfusion imaging is a specific form of CT to assess flow through  blood vessels  whilst injecting a  contrast agent . [ 21 ]  Blood flow, blood transit time, and organ blood volume, can all be calculated with reasonable  sensitivity and specificity . [ 21 ]  This type of CT may be used on the  heart , although sensitivity and specificity for detecting abnormalities are still lower than for other forms of CT. [ 22 ]  This may also be used on the  brain , where CT perfusion imaging can often detect poor brain perfusion well before it is detected using a conventional spiral CT scan. [ 21 ] [ 23 ]  This is better for  stroke  diagnosis than other CT types. [ 23 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1140", "text": "Positron emission tomography\u2013computed tomography is a hybrid CT modality which combines, in a single gantry, a  positron emission tomography  (PET) scanner and an X-ray computed tomography (CT) scanner, to acquire sequential images from both devices in the same session, which are combined into a single superposed ( co-registered ) image. Thus,  functional imaging  obtained by PET, which depicts the spatial distribution of metabolic or biochemical activity in the body can be more precisely aligned or correlated with anatomic imaging obtained by CT scanning. [ 24 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1141", "text": "PET-CT gives both anatomical and functional details of an organ under examination and is helpful in detecting different type of cancers. [ 25 ] [ 26 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1142", "text": "Since its introduction in the 1970s, [ 27 ]  CT has become an important tool in  medical imaging  to supplement conventional  X-ray  imaging and  medical ultrasonography . It has more recently been used for  preventive medicine  or  screening  for disease, for example,  CT colonography  for people with a high risk of  colon cancer , or full-motion heart scans for people with a high risk of heart disease. Several institutions offer  full-body scans  for the general population although this practice goes against the advice and official position of many professional organizations in the field primarily due to the  radiation dose  applied. [ 28 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1143", "text": "The use of CT scans has increased dramatically over the last two decades in many countries. [ 29 ]  An estimated 72 million scans were performed in the United States in 2007 and more than 80 million in 2015. [ 30 ] [ 31 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1144", "text": "CT scanning of the head is typically used to detect  infarction  ( stroke ),  tumors ,  calcifications ,  haemorrhage , and bone  trauma . [ 32 ]  Of the above,  hypodense  (dark) structures can indicate  edema  and infarction, hyperdense (bright) structures indicate calcifications and haemorrhage and bone trauma can be seen as disjunction in bone windows. Tumors can be detected by the swelling and anatomical distortion they cause, or by surrounding edema. CT scanning of the head is also used in CT- guided   stereotactic surgery  and  radiosurgery  for treatment of intracranial tumors,  arteriovenous malformations , and other surgically treatable conditions using a device known as the  N-localizer . [ 33 ] [ 34 ] [ 35 ] [ 36 ] [ 37 ] [ 38 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1145", "text": "Contrast CT  is generally the initial study of choice for  neck masses  in adults. [ 39 ]   CT of the thyroid  plays an important role in the evaluation of  thyroid cancer . [ 40 ]  CT scan often incidentally finds thyroid abnormalities, and so is often the preferred investigation modality for thyroid abnormalities. [ 40 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1146", "text": "A CT scan can be used for detecting both acute and chronic changes in the  lung parenchyma , the tissue of the  lungs . [ 41 ]  It is particularly relevant here because normal two-dimensional X-rays do not show such defects. A variety of techniques are used, depending on the suspected abnormality. For evaluation of chronic interstitial processes such as  emphysema , and  fibrosis , [ 42 ]  thin sections with high spatial frequency reconstructions are used; often scans are performed both on inspiration and expiration. This special technique is called  high resolution CT  that produces a sampling of the lung, and not continuous images. [ 43 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1147", "text": "Bronchial wall thickening  can be seen on lung CTs and generally (but not always) implies inflammation of the  bronchi . [ 44 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1148", "text": "An  incidentally  found nodule in the absence of symptoms (sometimes referred to as an  incidentaloma ) may raise concerns that it might represent a tumor, either  benign  or  malignant . [ 45 ]  Perhaps persuaded by fear, patients and doctors sometimes agree to an intensive schedule of CT scans, sometimes up to every three months and beyond the recommended guidelines, in an attempt to do surveillance on the nodules. [ 46 ]  However, established guidelines advise that patients without a prior history of cancer and whose solid nodules have not grown over a two-year period are unlikely to have any malignant cancer. [ 46 ]  For this reason, and because no research provides supporting evidence that intensive surveillance gives better outcomes, and because of risks associated with having CT scans, patients should not receive CT screening in excess of those recommended by established guidelines. [ 46 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1149", "text": "Computed tomography angiography  (CTA) is a type of  contrast CT  to visualize the  arteries  and  veins  throughout the body. [ 47 ]  This ranges from arteries serving the  brain  to those bringing blood to the  lungs ,  kidneys ,  arms  and  legs . An example of this type of exam is  CT pulmonary angiogram  (CTPA) used to diagnose  pulmonary embolism  (PE). It employs computed tomography and an  iodine-based contrast agent  to obtain an image of the  pulmonary arteries . [ 48 ] [ 49 ] [ 50 ]  CT scans can reduce the risk of angiography by providing clinicians with more information about the positioning and number of clots prior to the procedure. [ 51 ] [ 52 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1150", "text": "A CT scan of the heart is performed to gain knowledge about cardiac or coronary anatomy. [ 53 ]  Traditionally, cardiac CT scans are used to detect, diagnose, or follow up  coronary artery disease . [ 54 ]  More recently CT has played a key role in the fast-evolving field of  transcatheter structural heart interventions , more specifically in the transcatheter repair and replacement of heart valves. [ 55 ] [ 56 ] [ 57 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1151", "text": "The main forms of cardiac CT scanning are:"}
{"_id": "WikiPedia_Radiology$$$corpus_1152", "text": "To better visualize the anatomy, post-processing of the images is common. [ 54 ]  Most common are multiplanar reconstructions (MPR) and  volume rendering . For more complex anatomies and procedures, such as heart valve interventions, a true  3D reconstruction  or a 3D print is created based on these CT images to gain a deeper understanding. [ 62 ] [ 63 ] [ 64 ] [ 65 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1153", "text": "CT is an accurate technique for diagnosis of  abdominal  diseases like  Crohn's disease , [ 66 ]  GIT bleeding, and diagnosis and staging of cancer, as well as follow-up after cancer treatment to assess response. [ 67 ]  It is commonly used to investigate  acute abdominal pain . [ 68 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1154", "text": "Non-contrast-enhanced CT scans are the gold standard for diagnosing  kidney stone disease . [ 69 ]  They allow clinicians to estimate the size, volume, and density of stones, helping to guide further treatment; with size being especially important in predicting the time to spontaneous passage of a stone. [ 70 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1155", "text": "For the  axial skeleton  and  extremities , CT is often used to image complex  fractures , especially ones around joints, because of its ability to reconstruct the area of interest in multiple planes. Fractures, ligamentous injuries, and  dislocations  can easily be recognized with a 0.2\u00a0mm resolution. [ 71 ] [ 72 ]  With modern dual-energy CT scanners, new areas of use have been established, such as aiding in the diagnosis of  gout . [ 73 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1156", "text": "CT is used in  biomechanics  to quickly reveal the geometry, anatomy,  density  and  elastic moduli  of biological tissues. [ 74 ] [ 75 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1157", "text": "Industrial CT scanning  (industrial computed tomography) is a process which uses X-ray equipment to produce 3D representations of components both externally and internally. Industrial CT scanning has been used in many areas of industry for internal inspection of components. Some of the key uses for CT scanning have been flaw detection, failure analysis, metrology, assembly analysis, image-based finite element methods [ 76 ]  and reverse engineering applications. CT scanning is also employed in the imaging and conservation of museum artifacts. [ 77 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1158", "text": "CT scanning has also found an application in transport security (predominantly  airport security ) where it is currently used in a materials analysis context for explosives detection  CTX (explosive-detection device) [ 78 ] [ 79 ] [ 80 ] [ 81 ]  and is also under consideration for automated baggage/parcel security scanning using  computer vision  based object recognition algorithms that target the detection of specific threat items based on 3D appearance (e.g. guns, knives, liquid containers). [ 82 ] [ 83 ] [ 84 ]  Its usage in airport security pioneered at  Shannon Airport  in March 2022 has ended the ban on liquids over 100\u00a0ml there, a move that  Heathrow Airport  plans for a full roll-out on 1 December 2022 and the TSA spent $781.2 million on an order for over 1,000 scanners, ready to go live in the summer."}
{"_id": "WikiPedia_Radiology$$$corpus_1159", "text": "X-ray CT is used in geological studies to quickly reveal materials inside a drill core. [ 85 ]  Dense minerals such as pyrite and barite appear brighter and less dense components such as clay appear dull in CT images. [ 86 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1160", "text": "Traditional methods of studying fossils are often destructive, such as the use of thin sections and physical preparation. X-ray CT is used in paleontology to non-destructively visualize fossils in 3D. [ 87 ]  This has many advantages. For example, we can look at fragile structures that might never otherwise be able to be studied. In addition, one can freely move around models of fossils in virtual 3D space to inspect it without damaging the fossil."}
{"_id": "WikiPedia_Radiology$$$corpus_1161", "text": "X-ray CT and  micro-CT  can also be used for the conservation and preservation of objects of cultural heritage. For many fragile objects, direct research and observation can be damaging and can degrade the object over time. Using CT scans, conservators and researchers are able to determine the material composition of the objects they are exploring, such as the position of ink along the layers of a scroll, without any additional harm. These scans have been optimal for research focused on the workings of the  Antikythera mechanism  or the text hidden inside the charred outer layers of the  En-Gedi Scroll . However, they are not optimal for every object subject to these kinds of research questions, as there are certain artifacts like the  Herculaneum papyri  in which the material composition has very little variation along the inside of the object. After scanning these objects, computational methods can be employed to examine the insides of these objects, as was the case with the virtual unwrapping of the  En-Gedi scroll  and the  Herculaneum papyri . [ 88 ]  Micro-CT has also proved useful for analyzing more recent artifacts such as still-sealed historic correspondence that employed the technique of  letterlocking  (complex folding and cuts) that provided a \"tamper-evident locking mechanism\". [ 89 ] [ 90 ]  Further examples of use cases in archaeology is imaging the contents of sarcophagi or ceramics. [ 91 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1162", "text": "Recently, CWI in Amsterdam has collaborated with Rijksmuseum to investigate art object inside details in the framework called IntACT. [ 92 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1163", "text": "Varied types of fungus can degrade wood to different degrees, one Belgium research group has been used X-ray CT 3 dimension with sub-micron resolution unveiled fungi can penetrate micropores of 0.6 \u03bcm [ 93 ]  under certain conditions."}
{"_id": "WikiPedia_Radiology$$$corpus_1164", "text": "Sawmills use industrial CT scanners to detect round defects, for instance knots, to improve total value of timber productions. Most sawmills are planning to incorporate this robust detection tool to improve productivity in the long run, however initial investment cost is high. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1165", "text": "The result of a CT scan is a volume of  voxels , which may be presented to a human observer by various methods, which broadly fit into the following categories:"}
{"_id": "WikiPedia_Radiology$$$corpus_1166", "text": "Technically, all volume renderings become projections when viewed on a  2-dimensional display , making the distinction between projections and volume renderings a bit vague. The epitomes of volume rendering models feature a mix of for example coloring and shading in order to create realistic and observable representations. [ 98 ] [ 99 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1167", "text": "Two-dimensional CT images are conventionally rendered so that the view is as though looking up at it from the patient's feet. [ 100 ]  Hence, the left side of the image is to the patient's right and vice versa, while anterior in the image also is the patient's anterior and vice versa. This left-right interchange corresponds to the view that physicians generally have in reality when positioned in front of patients. [ 101 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1168", "text": "Pixels  in an image obtained by CT scanning are displayed in terms of relative  radiodensity . The pixel itself is displayed according to the mean  attenuation  of the tissue(s) that it corresponds to on a scale from +3,071 (most attenuating) to \u22121,024 (least attenuating) on the  Hounsfield scale . A  pixel  is a two dimensional unit based on the matrix size and the field of view. When the CT slice thickness is also factored in, the unit is known as a  voxel , which is a three-dimensional unit. [ 102 ]  Water has an attenuation of 0  Hounsfield units  (HU), while air is \u22121,000\u00a0HU, cancellous bone is typically +400\u00a0HU, and cranial bone can reach 2,000\u00a0HU. [ 103 ]  The attenuation of metallic implants depends on the atomic number of the element used: Titanium usually has an amount of +1000\u00a0HU, iron steel can completely block the X-ray and is, therefore, responsible for well-known line-artifacts in computed tomograms. Artifacts are caused by abrupt transitions between low- and high-density materials, which results in data values that exceed the dynamic range of the processing electronics. [ 104 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1169", "text": "CT data sets have a very high  dynamic range  which must be reduced for display or printing. This is typically done via a process of \"windowing\", which maps a range (the \"window\") of pixel values to a grayscale ramp. For example, CT images of the brain are commonly viewed with a window extending from 0 HU to 80 HU. Pixel values of 0 and lower, are displayed as black; values of 80 and higher are displayed as white; values within the window are displayed as a gray intensity proportional to position within the window. [ 105 ]  The window used for display must be matched to the X-ray density of the object of interest, in order to optimize the visible detail. [ 106 ]  Window width and window level parameters are used to control the windowing of a scan. [ 107 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1170", "text": "Multiplanar reconstruction (MPR) is the process of converting data from one  anatomical plane  (usually  transverse ) to other planes. It can be used for thin slices as well as projections. Multiplanar reconstruction is possible as present CT scanners provide almost  isotropic  resolution. [ 108 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1171", "text": "MPR is used almost in every scan. The spine is frequently examined with it. [ 109 ]  An image of the spine in axial plane can only show one vertebral bone at a time and cannot show its relation with other vertebral bones. By reformatting the data in other planes, visualization of the relative position can be achieved in sagittal and coronal plane. [ 110 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1172", "text": "New software allows the reconstruction of data in non-orthogonal (oblique) planes, which help in the visualization of organs which are not in orthogonal planes. [ 111 ] [ 112 ]  It is better suited for visualization of the anatomical structure of the bronchi as they do not lie orthogonal to the direction of the scan. [ 113 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1173", "text": "Curved-plane reconstruction (or curved planar reformation = CPR) is performed mainly for the evaluation of vessels. This type of reconstruction helps to straighten the bends in a vessel, thereby helping to visualize a whole vessel in a single image or in multiple images. After a vessel has been \"straightened\", measurements such as cross-sectional area and length can be made. This is helpful in preoperative assessment of a surgical procedure. [ 114 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1174", "text": "For 2D projections used in  radiation therapy  for quality assurance and planning of  external beam radiotherapy , including digitally reconstructed radiographs, see  Beam's eye view ."}
{"_id": "WikiPedia_Radiology$$$corpus_1175", "text": "A threshold value of radiodensity is set by the operator (e.g., a level that corresponds to bone). With the help of  edge detection  image processing algorithms a 3D model can be constructed from the initial data and displayed on screen. Various thresholds can be used to get multiple models, each anatomical component such as muscle, bone and cartilage can be differentiated on the basis of different colours given to them. However, this mode of operation cannot show interior structures. [ 116 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1176", "text": "Surface rendering is limited technique as it displays only the surfaces that meet a particular threshold density, and which are towards the viewer. However, In volume rendering, transparency, colours and  shading  are used which makes it easy to present a volume in a single image. For example, Pelvic bones could be displayed as semi-transparent, so that, even viewing at an oblique angle one part of the image does not hide another. [ 117 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1177", "text": "An important issue within radiology today is how to reduce the radiation dose during CT examinations without compromising the image quality. In general, higher radiation doses result in higher-resolution images, [ 118 ]  while lower doses lead to increased image noise and unsharp images. However, increased dosage raises the adverse side effects, including the risk of  radiation-induced cancer  \u2013 a four-phase abdominal CT gives the same radiation dose as 300 chest X-rays. [ 119 ]  Several methods that can reduce the exposure to ionizing radiation during a CT scan exist. [ 120 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1178", "text": "Although images produced by CT are generally faithful representations of the scanned volume, the technique is susceptible to a number of  artifacts , such as the following: [ 124 ] [ 125 ] Chapters 3 and 5"}
{"_id": "WikiPedia_Radiology$$$corpus_1179", "text": "CT scanning has several advantages over traditional  two-dimensional  medical  radiography . First, CT eliminates the superimposition of images of structures outside the area of interest. [ 140 ]  Second, CT scans have greater  image resolution , enabling examination of finer details. CT can distinguish between  tissues  that differ in   radiographic density  by 1% or less. [ 141 ]  Third, CT scanning enables multiplanar reformatted imaging: scan data can be visualized in the  transverse (or axial) ,  coronal , or  sagittal  plane, depending on the diagnostic task. [ 142 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1180", "text": "The improved resolution of CT has permitted the development of new investigations. For example, CT  angiography  avoids the invasive insertion of a  catheter . CT scanning can perform a  virtual colonoscopy  with greater accuracy and less discomfort for the patient than a traditional  colonoscopy . [ 143 ] [ 144 ]  Virtual colonography is far more accurate than a  barium enema  for detection of tumors and uses a lower radiation dose. [ 145 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1181", "text": "CT is a moderate-to-high  radiation  diagnostic technique. The radiation dose for a particular examination depends on multiple factors: volume scanned, patient build, number and type of scan protocol, and desired resolution and image quality. [ 146 ]  Two helical CT scanning parameters, tube current and pitch, can be adjusted easily and have a profound effect on radiation. CT scanning is more accurate than two-dimensional radiographs in evaluating anterior interbody fusion, although they may still over-read the extent of fusion. [ 147 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1182", "text": "The  radiation  used in CT scans can damage body cells, including  DNA molecules , which can lead to  radiation-induced cancer . [ 148 ]  The radiation doses received from CT scans is variable. Compared to the lowest dose X-ray techniques, CT scans can have 100 to 1,000 times higher dose than conventional X-rays. [ 149 ]  However, a lumbar spine X-ray has a similar dose as a head CT. [ 150 ]  Articles in the media often exaggerate the relative dose of CT by comparing the lowest-dose X-ray techniques (chest X-ray) with the highest-dose CT techniques. In general, a routine abdominal CT has a radiation dose similar to three years of average  background radiation . [ 151 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1183", "text": "Large scale population-based studies have consistently demonstrated that low dose radiation from CT scans has impacts on cancer incidence in a variety of cancers. [ 152 ] [ 153 ] [ 154 ] [ 155 ]  For example, in a large population-based Australian cohort it was found that up to 3.7% of brain cancers were caused by CT scan radiation. [ 156 ]  Some experts project that in the future, between three and five percent of all cancers would result from medical imaging. [ 149 ]  An Australian study of 10.9\u00a0million people reported that the increased incidence of cancer after CT scan exposure in this cohort was mostly due to irradiation. In this group, one in every 1,800 CT scans was followed by an excess cancer. If the lifetime risk of developing cancer is 40% then the absolute risk rises to 40.05% after a CT. The risks of CT scan radiation are especially important in patients undergoing recurrent CT scans within a short time span of one to five years. [ 157 ] [ 158 ] [ 159 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1184", "text": "Some experts note that CT scans are known to be \"overused,\" and \"there is distressingly little evidence of better health outcomes associated with the current high rate of scans.\" [ 149 ]  On the other hand, a recent paper analyzing the data of patients who received high  cumulative doses  showed a high degree of appropriate use. [ 160 ]  This creates an important issue of cancer risk to these patients. Moreover, a highly significant finding that was previously unreported is that some patients received >100 mSv dose from CT scans in a single day, [ 158 ]  which counteracts existing criticisms some investigators may have on the effects of protracted versus acute exposure."}
{"_id": "WikiPedia_Radiology$$$corpus_1185", "text": "There are contrarian views and the debate is ongoing. Some studies have shown that publications indicating an increased risk of cancer from typical doses of body CT scans are plagued with serious methodological limitations and several highly improbable results, [ 161 ]  concluding that no evidence indicates such low doses cause any long-term harm. [ 162 ] [ 163 ] [ 164 ] \nOne study estimated that as many as 0.4% of cancers in the United States resulted from CT scans, and that this may have increased to as much as 1.5 to 2% based on the rate of CT use in 2007. [ 148 ]  Others dispute this estimate, [ 165 ]  as there is no consensus that the low levels of radiation used in CT scans cause damage. Lower radiation doses are used in many cases, such as in the investigation of renal colic. [ 166 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1186", "text": "A person's age plays a significant role in the subsequent risk of cancer. [ 167 ]  Estimated lifetime cancer mortality risks from an abdominal CT of a one-year-old is 0.1%, or 1:1000 scans. [ 167 ]  The risk for someone who is 40 years old is half that of someone who is 20 years old with substantially less risk in the elderly. [ 167 ]  The  International Commission on Radiological Protection  estimates that the risk to a fetus being exposed to 10  mGy  (a unit of radiation exposure) increases the rate of cancer before 20 years of age from 0.03% to 0.04% (for reference a CT pulmonary angiogram exposes a fetus to 4\u00a0mGy). [ 168 ]  A 2012 review did not find an association between medical radiation and cancer risk in children noting however the existence of limitations in the evidences over which the review is based. [ 169 ]  CT scans can be performed with different settings for lower exposure in children with most manufacturers of CT scans as of 2007 having this function built in. [ 170 ]  Furthermore, certain conditions can require children to be exposed to multiple CT scans. [ 148 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1187", "text": "Current recommendations are to inform patients of the risks of CT scanning. [ 171 ]  However, employees of imaging centers tend not to communicate such risks unless patients ask. [ 172 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1188", "text": "In the United States half of CT scans are  contrast CTs  using intravenously injected  radiocontrast agents . [ 173 ]  The most common reactions from these agents are mild, including nausea, vomiting, and an itching rash. Severe life-threatening reactions may rarely occur. [ 174 ]  Overall reactions occur in 1 to 3% with  nonionic contrast  and 4 to 12% of people with  ionic contrast . [ 175 ]  Skin rashes may appear within a week to 3% of people. [ 174 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1189", "text": "The old  radiocontrast agents  caused  anaphylaxis  in 1% of cases while the newer, low-osmolar agents cause reactions in 0.01\u20130.04% of cases. [ 174 ] [ 176 ]  Death occurs in about 2 to 30 people per 1,000,000 administrations, with newer agents being safer. [ 175 ] [ 177 ] \nThere is a higher risk of mortality in those who are female, elderly or in poor health, usually secondary to either anaphylaxis or  acute kidney injury . [ 173 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1190", "text": "The contrast agent may induce  contrast-induced nephropathy . [ 178 ]  This occurs in 2 to 7% of people who receive these agents, with greater risk in those who have preexisting  kidney failure , [ 178 ]  preexisting  diabetes , or reduced intravascular volume. People with mild kidney impairment are usually advised to ensure full hydration for several hours before and after the injection. For moderate kidney failure, the use of  iodinated contrast  should be avoided; this may mean using an alternative technique instead of CT. Those with severe  kidney failure  requiring  dialysis  require less strict precautions, as their kidneys have so little function remaining that any further damage would not be noticeable and the dialysis will remove the contrast agent; it is normally recommended, however, to arrange dialysis as soon as possible following contrast administration to minimize any adverse effects of the contrast."}
{"_id": "WikiPedia_Radiology$$$corpus_1191", "text": "In addition to the use of intravenous contrast, orally administered contrast agents are frequently used when examining the abdomen. [ 179 ]  These are frequently the same as the intravenous contrast agents, merely diluted to approximately 10% of the concentration. However, oral alternatives to iodinated contrast exist, such as very dilute (0.5\u20131% w/v)  barium sulfate  suspensions. Dilute barium sulfate has the advantage that it does not cause allergic-type reactions or kidney failure, but cannot be used in patients with suspected bowel perforation or suspected bowel injury, as leakage of barium sulfate from damaged bowel can cause fatal  peritonitis . [ 180 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1192", "text": "Side effects from  contrast agents , administered  intravenously  in some CT scans, might impair  kidney  performance in patients with  kidney disease , although this risk is now believed to be lower than previously thought. [ 181 ] [ 178 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1193", "text": "The table reports average radiation exposures; however, there can be a wide variation in radiation doses between similar scan types, where the highest dose could be as much as 22 times higher than the lowest dose. [ 167 ]  A typical plain film X-ray involves radiation dose of 0.01 to 0.15\u00a0mGy, while a typical CT can involve 10\u201320\u00a0mGy for specific organs, and can go up to 80\u00a0mGy for certain specialized CT scans. [ 184 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1194", "text": "For purposes of comparison, the world average dose rate from naturally occurring sources of  background radiation  is 2.4\u00a0 mSv  per year, equal for practical purposes in this application to 2.4\u00a0mGy per year. [ 182 ]  While there is some variation, most people (99%) received less than 7\u00a0mSv per year as background radiation. [ 186 ]  Medical imaging as of 2007 accounted for half of the radiation exposure of those in the United States with CT scans making up two thirds of this amount. [ 167 ]  In the United Kingdom it accounts for 15% of radiation exposure. [ 168 ]  The average radiation dose from medical sources is \u22480.6\u00a0mSv per person globally as of 2007. [ 167 ]  Those in the nuclear industry in the United States are limited to doses of 50\u00a0mSv a year and 100\u00a0mSv every 5 years. [ 167 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1195", "text": "Lead  is the main material used by radiography personnel for  shielding  against scattered X-rays."}
{"_id": "WikiPedia_Radiology$$$corpus_1196", "text": "The radiation dose reported in the  gray or mGy  unit is proportional to the amount of energy that the irradiated body part is expected to absorb, and the physical effect (such as DNA  double strand breaks ) on the cells' chemical bonds by X-ray radiation is proportional to that energy. [ 187 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1197", "text": "The  sievert  unit is used in the report of the  effective dose . The sievert unit, in the context of CT scans, does not correspond to the actual radiation dose that the scanned body part absorbs but to another radiation dose of another scenario, the whole body absorbing the other radiation dose and the other radiation dose being of a magnitude, estimated to have the same probability to induce cancer as the CT scan. [ 188 ]  Thus, as is shown in the table above, the actual radiation that is absorbed by a scanned body part is often much larger than the effective dose suggests. A specific measure, termed the  computed tomography dose index  (CTDI), is commonly used as an estimate of the radiation absorbed dose for tissue within the scan region, and is automatically computed by medical CT scanners. [ 189 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1198", "text": "The  equivalent dose  is the effective dose of a case, in which the whole body would actually absorb the same radiation dose, and the sievert unit is used in its report. In the case of non-uniform radiation, or radiation given to only part of the body, which is common for CT examinations, using the local equivalent dose alone would overstate the biological risks to the entire organism. [ 190 ] [ 191 ] [ 192 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1199", "text": "Most adverse health effects of radiation exposure may be grouped in two general categories:"}
{"_id": "WikiPedia_Radiology$$$corpus_1200", "text": "The added lifetime risk of developing cancer by a single abdominal CT of 8 mSv is estimated to be 0.05%, or 1 one in 2,000. [ 195 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1201", "text": "Because of increased susceptibility of fetuses to radiation exposure, the radiation dosage of a CT scan is an important consideration in the choice of  medical imaging in pregnancy . [ 196 ] [ 197 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1202", "text": "In October, 2009, the US  Food and Drug Administration  (FDA) initiated an investigation of brain perfusion CT (PCT) scans, based on  radiation burns  caused by incorrect settings at one particular facility for this particular type of CT scan. Over 200 patients were exposed to radiation at approximately eight times the expected dose for an 18-month period; over 40% of them lost patches of hair. This event prompted a call for increased CT quality assurance programs. It was noted that \"while unnecessary radiation exposure should be avoided, a medically needed CT scan obtained with appropriate acquisition parameter has benefits that outweigh the radiation risks.\" [ 167 ] [ 198 ]  Similar problems have been reported at other centers. [ 167 ]  These incidents are believed to be due to  human error . [ 167 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1203", "text": "CT scan procedure varies according to the type of the study and the organ being imaged. The patient is made to lie on the CT table and the centering of the table is done according to the body part. The IV line is established in case of contrast-enhanced CT. After selecting proper [ clarification needed ]  and rate of contrast from the pressure injector, the scout is taken to localize and plan the scan. Once the plan is selected, the contrast is given. The raw data is processed according to the study and proper windowing is done to make scans easy to diagnose. [ 199 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1204", "text": "Patient preparation may vary according to the type of scan. The general patient preparation includes. [ 199 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1205", "text": "Computed tomography operates by using an  X-ray generator  that rotates around the object;  X-ray detectors  are positioned on the opposite side of the circle from the X-ray source. [ 202 ]  As the X-rays pass through the patient, they are attenuated differently by various tissues according to the tissue density. [ 203 ]  A visual representation of the raw data obtained is called a sinogram, yet it is not sufficient for interpretation. [ 204 ]  Once the scan data has been acquired, the data must be processed using a form of  tomographic reconstruction , which produces a series of cross-sectional images. [ 205 ]  These cross-sectional images are made up of small units of pixels or voxels. [ 206 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1206", "text": "Pixels  in an image obtained by CT scanning are displayed in terms of relative  radiodensity . The pixel itself is displayed according to the mean  attenuation  of the tissue(s) that it corresponds to on a scale from +3,071 (most attenuating) to \u22121,024 (least attenuating) on the  Hounsfield scale . A  pixel  is a two dimensional unit based on the matrix size and the field of view. When the CT slice thickness is also factored in, the unit is known as a  voxel , which is a three-dimensional unit. [ 206 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1207", "text": "Water has an attenuation of 0  Hounsfield units  (HU), while air is \u22121,000\u00a0HU, cancellous bone is typically +400\u00a0HU, and cranial bone can reach 2,000\u00a0HU or more (os temporale) and can cause  artifacts . The attenuation of metallic implants depends on the atomic number of the element used: Titanium usually has an amount of +1000\u00a0HU, iron steel can completely extinguish the X-ray and is, therefore, responsible for well-known line-artifacts in computed tomograms. Artifacts are caused by abrupt transitions between low- and high-density materials, which results in data values that exceed the dynamic range of the processing electronics. Two-dimensional CT images are conventionally rendered so that the view is as though looking up at it from the patient's feet. [ 100 ]  Hence, the left side of the image is to the patient's right and vice versa, while anterior in the image also is the patient's anterior and vice versa. This left-right interchange corresponds to the view that physicians generally have in reality when positioned in front of patients."}
{"_id": "WikiPedia_Radiology$$$corpus_1208", "text": "Initially, the images generated in CT scans were in the  transverse  (axial)  anatomical plane , perpendicular to the long axis of the body. Modern scanners allow the scan data to be reformatted as images in other  planes .  Digital geometry processing  can generate a  three-dimensional  image of an object inside the body from a series of two-dimensional  radiographic  images taken by  rotation around a fixed axis . [ 124 ]  These cross-sectional images are widely used for medical  diagnosis  and  therapy . [ 207 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1209", "text": "Contrast media  used for X-ray CT, as well as for  plain film X-ray , are called  radiocontrasts . Radiocontrasts for CT are, in general, iodine-based. [ 208 ]  This is useful to highlight structures such as blood vessels that otherwise would be difficult to delineate from their surroundings. Using contrast material can also help to obtain functional information about tissues. Often, images are taken both with and without radiocontrast. [ 209 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1210", "text": "The history of X-ray computed tomography goes back to at least 1917 with the mathematical theory of the  Radon transform . [ 210 ] [ 211 ]  In October 1963,  William H. Oldendorf  received a U.S. patent for a \"radiant energy apparatus for investigating selected areas of interior objects obscured by dense material\". [ 212 ]  The first commercially viable CT scanner was invented by  Godfrey Hounsfield  in 1972. [ 213 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1211", "text": "It is often claimed that revenues from the sales of The Beatles' records in the 1960s helped fund the development of the first CT scanner at EMI. The first production X-ray CT machines were in fact called EMI scanners. [ 214 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1212", "text": "The word  tomography  is derived from the  Greek   tome  'slice' and  graphein  'to write'. [ 215 ]  Computed tomography was originally known as the \"EMI scan\" as it was developed in the early 1970s at a research branch of  EMI , a company best known today for its music and recording business. [ 216 ]  It was later known as  computed axial tomography  ( CAT  or  CT scan ) and  body section r\u00f6ntgenography . [ 217 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1213", "text": "The term  CAT scan  is no longer in technical use because current CT scans enable for multiplanar reconstructions. This makes  CT scan  the most appropriate term, which is used by  radiologists  in common vernacular as well as in textbooks and scientific papers. [ 218 ] [ 219 ] [ 220 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1214", "text": "In  Medical Subject Headings  (MeSH),  computed axial tomography  was used from 1977 to 1979, but the current indexing explicitly includes  X-ray  in the title. [ 221 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1215", "text": "The term  sinogram  was introduced by Paul Edholm and Bertil Jacobson in 1975. [ 222 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1216", "text": "In response to increased concern by the public and the ongoing progress of best practices, the Alliance for Radiation Safety in Pediatric Imaging was formed within the  Society for Pediatric Radiology . In concert with the  American Society of Radiologic Technologists , the  American College of Radiology  and the  American Association of Physicists in Medicine , the Society for Pediatric Radiology developed and launched the Image Gently Campaign which is designed to maintain high-quality imaging studies while using the lowest doses and best radiation safety practices available on pediatric patients. [ 224 ]  This initiative has been endorsed and applied by a growing list of various professional medical organizations around the world and has received support and assistance from companies that manufacture equipment used in Radiology."}
{"_id": "WikiPedia_Radiology$$$corpus_1217", "text": "Following upon the success of the  Image Gently  campaign, the American College of Radiology, the Radiological Society of North America, the American Association of Physicists in Medicine and the American Society of Radiologic Technologists have launched a similar campaign to address this issue in the adult population called  Image Wisely . [ 225 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1218", "text": "The  World Health Organization  and  International Atomic Energy Agency  (IAEA) of the United Nations have also been working in this area and have ongoing projects designed to broaden best practices and lower patient radiation dose. [ 226 ] [ 227 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1219", "text": "Use of CT has increased dramatically over the last two decades. [ 29 ]  An estimated 72\u00a0million scans were performed in the United States in 2007, [ 30 ]  accounting for close to half of the total per-capita dose rate from radiologic and nuclear medicine procedures. [ 228 ]  Of the CT scans, six to eleven percent are done in children, [ 168 ]  an increase of seven to eightfold from 1980. [ 167 ]  Similar increases have been seen in Europe and Asia. [ 167 ]  In Calgary, Canada, 12.1% of people who present to the emergency with an urgent complaint received a CT scan, most commonly either of the head or of the abdomen. The percentage who received CT, however, varied markedly by the  emergency physician  who saw them from 1.8% to 25%. [ 229 ]  In the emergency department in the United States, CT or  MRI  imaging is done in 15% of people who present with  injuries  as of 2007 (up from 6% in 1998). [ 230 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1220", "text": "The increased use of CT scans has been the greatest in two fields: screening of adults (screening CT of the lung in smokers, virtual colonoscopy, CT cardiac screening, and whole-body CT in asymptomatic patients) and CT imaging of children. Shortening of the scanning time to around 1 second, eliminating the strict need for the subject to remain still or be sedated, is one of the main reasons for the large increase in the pediatric population (especially for the diagnosis of  appendicitis ). [ 148 ]  As of 2007, in the United States a proportion of CT scans are performed unnecessarily. [ 170 ]  Some estimates place this number at 30%. [ 168 ]  There are a number of reasons for this including: legal concerns, financial incentives, and desire by the public. [ 170 ]  For example, some healthy people avidly pay to receive full-body CT scans as  screening . In that case, it is not at all clear that the benefits outweigh the risks and costs. Deciding whether and how to treat  incidentalomas  is complex, radiation exposure is not negligible, and the money for the scans involves  opportunity cost . [ 170 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1221", "text": "Major manufacturers of CT scanning devices and equipment are: [ 231 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1222", "text": "Photon-counting computed tomography  is a CT technique currently under development. [ as of? ]  Typical CT scanners use energy integrating detectors; photons are measured as a voltage on a capacitor which is proportional to the X-rays detected. However, this technique is susceptible to noise and other factors which can affect the linearity of the voltage to X-ray intensity relationship. [ 232 ]  Photon counting detectors (PCDs) are still affected by noise but it does not change the measured counts of photons. PCDs have several potential advantages, including improving signal (and contrast) to noise ratios, reducing doses, improving spatial resolution, and through use of several energies, distinguishing multiple contrast agents. [ 233 ] [ 234 ]  PCDs have only recently become feasible in CT scanners due to improvements in detector technologies that can cope with the volume and rate of data required. As of February 2016, photon counting CT is in use at three sites. [ 235 ]  Some early research has found the dose reduction potential of photon counting CT for breast imaging to be very promising. [ 236 ]  In view of recent findings of high cumulative doses to patients from recurrent CT scans, there has been a push for scanning technologies and techniques that reduce ionising radiation doses to patients to sub- milliSievert  (sub-mSv in the literature) levels during the CT scan process, a goal that has been lingering. [ 237 ] [ 158 ] [ 159 ] [ 160 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1223", "text": "Computed tomography enterography  ( CT enterography ,  CTE ) is a medical imaging technique which uses  computed tomography  scanner and  contrast media  to examine the  small bowel . [ 1 ]  It was first introduced by  Raptopoulos et al. in 1997. [ 2 ]  CT Enterography can be used to assess a variety of problems involving the small bowel, however it is mainly used to diagnose and assess severity of  Crohn's disease . [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1224", "text": "CT enterography  should not be confused with  CT enteroclysis . In CT enterography contrast media is given orally, and in CT enteroclysis contrast media is administered through a  fluoroscopy -guided positioned  nasojejunal tube . [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1225", "text": "CTE provides enough distention of the bowel not present during normal CT imaging to increase the ability to examine in lumen and internal lining of the small intestines. [ 4 ]  When the small bowel is not properly distended it can be difficult to see if there is a problem in that area. [ 5 ]   CTE also provides better visualization of extraenteric findings, as well as acute inflammation, of  Crohn's disease . These extraenteric findings include, but no limited to,  fistulas  and  abscesses . [ 5 ]  Additionally, compared with CT enteroclysis, the patient does not need to be sedated for CTE nor requires the invasive step of placing the nasojejunal tube. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1226", "text": "While CTE's main use is in the diagnosis and follow up in  Crohn's disease , many of the findings on Crohn's disease found on CTE can be caused by a wide variety of other conditions. [ 5 ]  Spasm and collapse of the small intestine, which can happen in Crohn's disease, can obscure imaging of that portion of the bowel even with CTE. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1227", "text": "At least four hours of no intake of solid foods, patient may have clear liquids.  Metoclopramide  (Reglan) will be administered to assist with emptying the stomach and increase movement through the small intestines. Large amounts of an oral contrast agent are given to the patient. Neutral contrast agents are preferred over positive contrast agents such as  barium . The neutral agents are vitally important for the effective visualization of the lining of the small intestine. Use of positive contrast agents could make it difficult to see any inflammation in the lining. Neutral agents include water, EG electrolyte solution,  sugar alcohols , and  methylcellulose . Patients are usually able to drink the large of amounts of these agents required for the study without major difficulty. [ 5 ]  This step is given at increments of 0, 20, 40, and 55 minutes after Reglan dose.  Glucagon  is given to patient five minutes before they enter the CT scanner to counter act the previous medication and attempt to slow down bowel activity. \u00a0Intravenous contrast is also given when the patient is on the scanner. The patient will then enter the scanner for the image to be captured. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1228", "text": "CTE is preferred for the examination of  Crohn's disease  due to its increased spatial resolution and better ability to examine the wall of the small intestine than traditional CT studies of the abdomen and pelvis. [ 5 ]  Findings on CTE that indicate active inflammation in the small bowel, possibly caused by Crohn's disease, include:"}
{"_id": "WikiPedia_Radiology$$$corpus_1229", "text": "CTE is also used in examining if bowel inflammation improves after therapy and if the disease is progressing in a concerning way. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1230", "text": "Computer-aided detection  ( CADe ), also called  computer-aided diagnosis  ( CADx ), are systems that assist doctors in the interpretation of  medical images . Imaging techniques in  X-ray ,  MRI ,  endoscopy , and  ultrasound  diagnostics yield a great deal of information that the  radiologist  or other medical professional has to analyze and evaluate comprehensively in a short time. CAD systems process digital images or videos for typical appearances and to highlight conspicuous sections, such as possible diseases, in order to offer input to support a decision taken by the professional."}
{"_id": "WikiPedia_Radiology$$$corpus_1231", "text": "CAD also has potential future applications in  digital pathology  with the advent of whole-slide imaging and  machine learning  algorithms. So far its application has been limited to quantifying  immunostaining  but is also being investigated for the standard  H&E stain . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1232", "text": "CAD is an  interdisciplinary  technology combining elements of  artificial intelligence  and  computer vision  with radiological and  pathology  image processing. A typical application is the detection of a tumor. For instance, some hospitals use CAD to support preventive medical check-ups in  mammography  (diagnosis of breast cancer), the detection of polyps in  colonoscopy , and  lung cancer ."}
{"_id": "WikiPedia_Radiology$$$corpus_1233", "text": "Computer-aided detection (CADe) systems are usually confined to marking conspicuous structures and sections. Computer-aided diagnosis (CADx) systems evaluate the conspicuous structures. For example, in mammography CAD highlights microcalcification clusters and hyperdense structures in the soft tissue. This allows the radiologist to draw conclusions about the condition of the pathology. Another application is CADq, which quantifies,  e.g. , the size of a tumor or the tumor's behavior in contrast medium uptake.  Computer-aided simple triage (CAST)  is another type of CAD, which performs a fully automatic initial interpretation and  triage  of studies into some meaningful categories ( e.g.  negative and positive). CAST is particularly applicable in emergency diagnostic imaging, where a prompt diagnosis of critical, life-threatening condition is required."}
{"_id": "WikiPedia_Radiology$$$corpus_1234", "text": "Although CAD has been used in clinical environments for over 40 years, CAD usually does not substitute the doctor or other professional, but rather plays a supporting role. The professional (generally a radiologist) is generally responsible for the final interpretation of a medical image. [ 2 ]  However, the goal of some CAD systems is to detect earliest signs of abnormality in patients that human professionals cannot, as in  diabetic retinopathy , architectural distortion in mammograms, [ 3 ] [ 4 ]  ground-glass nodules in thoracic CT, [ 5 ] [ 6 ]  and non-polypoid (\u201cflat\u201d) lesions in CT colonography. [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1235", "text": "In the late 1950s, with the dawn of modern computers researchers in various fields started exploring the possibility of building computer-aided medical diagnostic (CAD) systems. [ 8 ]  These first CAD systems used flow-charts, statistical pattern-matching, probability theory, or knowledge bases to drive their decision-making process. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1236", "text": "In the early 1970s, some of the very early CAD systems in medicine, which were often referred as \u201c expert systems \u201d in medicine, were developed and used mainly for educational purposes. Examples include the  MYCIN  expert system, [ 10 ]  the  Internist-I  expert system [ 11 ]  and the  CADUCEUS (expert system) . [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1237", "text": "During the beginning of the early developments, the researchers were aiming at building entirely automated CAD / expert systems. The expectated capability of computers was unrealistically optimistic among these scientists. However, after the breakthrough paper, \u201cReducibility among Combinatorial Problems\u201d by  Richard M. Karp , [ 13 ]  it became clear that there were limitations but also potential opportunities when one develops algorithms to solve groups of important computational problems. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1238", "text": "As result of the new understanding of the various algorithmic limitations that Karp discovered in the early 1970s, researchers started realizing the serious limitations that CAD and expert systems in medicine have. [ 9 ]  The recognition of these limitations brought the investigators to develop new kinds of CAD systems by using advanced approaches. Thus, by the late 1980s and early 1990s the focus sifted in the use of  data mining  approaches for the purpose of using more advanced and flexible CAD systems."}
{"_id": "WikiPedia_Radiology$$$corpus_1239", "text": "In 1998, the first commercial CAD system for mammography, the ImageChecker system, was approved by the US Food and Drug Administration (FDA). In the following years several commercial CAD systems for analyzing mammography, breast MRI, medical imagining of lung, colon, and heart also received FDA approvals. Currently, CAD systems are used as a diagnostic aid to provide physicians for better medical decision-making. [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1240", "text": "CAD is fundamentally based on highly complex  pattern recognition . X-ray or other types of images are scanned for suspicious structures. Normally a few thousand images are required to optimize the algorithm. Digital image data are copied to a CAD server in a  DICOM -format and are prepared and analyzed in several steps."}
{"_id": "WikiPedia_Radiology$$$corpus_1241", "text": "1. Preprocessing  for"}
{"_id": "WikiPedia_Radiology$$$corpus_1242", "text": "2.  Segmentation  for"}
{"_id": "WikiPedia_Radiology$$$corpus_1243", "text": "3. Structure/ROI (Region of Interest) Analyze \nEvery detected region is analyzed individually for special characteristics:"}
{"_id": "WikiPedia_Radiology$$$corpus_1244", "text": "4. Evaluation / classification \nAfter the structure is analyzed, every ROI is evaluated individually (scoring) for the probability of a TP. The following procedures are examples of classification algorithms."}
{"_id": "WikiPedia_Radiology$$$corpus_1245", "text": "If the detected structures have reached a certain threshold level, they are highlighted in the image for the radiologist. Depending on the CAD system these markings can be permanently or temporary saved. The latter's advantage is that only the markings which are approved by the radiologist are saved. False hits should not be saved, because an examination at a later date becomes more difficult then."}
{"_id": "WikiPedia_Radiology$$$corpus_1246", "text": "CAD systems seek to highlight suspicious structures. Today's CAD systems cannot detect 100% of pathological changes. The hit rate ( sensitivity ) can be up to 90% depending on system and application. [ 24 ]  A correct hit is termed a True Positive (TP), while the incorrect marking of healthy sections constitutes a False Positive (FP). The less FPs indicated, the higher the  specificity  is. A low specificity reduces the acceptance of the CAD system because the user has to identify all of these wrong hits. The FP-rate in lung overview examinations (CAD Chest) could be reduced to 2 per examination. In other segments ( e.g.  CT lung examinations) the FP-rate could be 25 or more. In  CAST  systems the FP rate must be extremely low (less than 1 per examination) to allow a meaningful study  triage ."}
{"_id": "WikiPedia_Radiology$$$corpus_1247", "text": "The absolute detection rate of a radiologist is an alternative metric to sensitivity and specificity. Overall, results of clinical trials about sensitivity, specificity, and the absolute detection rate can vary markedly. Each study result depends on its basic conditions and has to be evaluated on those terms. The following facts have a strong influence:"}
{"_id": "WikiPedia_Radiology$$$corpus_1248", "text": "Despite the many developments that CAD has achieved since the dawn of computers, there are still certain challenges that CAD systems face today. [ 25 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1249", "text": "Some challenges are related to various algorithmic limitations in the procedures of a CAD system including input data collection, preprocessing, processing and system assessments. Algorithms are generally designed to select a single likely diagnosis, thus providing suboptimal results for patients with multiple, concurrent disorders. [ 26 ]  Today input data for CAD mostly come from  electronic health records  (EHR). Effective designing, implementing and analyzing for EHR is a major necessity on any CAD systems. [ 25 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1250", "text": "Due to the massive availability of data and the need to analyze such data,  big data  is also one of the biggest challenges that CAD systems face today. The increasingly vast amount of patient data is a serious problem. Often the patient data are complex and can be semi-structured or  unstructured data . It requires highly developed approaches to store, retrieve and analyze them in reasonable time. [ 25 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1251", "text": "During the preprocessing stage, input data must be normalized. The  normalization  of input data includes  noise reduction  and filtering."}
{"_id": "WikiPedia_Radiology$$$corpus_1252", "text": "Processing may contain a few sub-steps depending on applications. Basic three sub-steps on medical imaging are segmentation,  feature extraction  / selection, and classification. These sub-steps require advanced techniques to analyze input data with less computational time. Although much effort has been devoted to creating innovative techniques for these procedures of CAD systems, no single best algorithm has emerged for any individual step. Ongoing studies in building innovative algorithms for all the aspects of CAD systems is essential. [ 25 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1253", "text": "There is also a lack of standardized assessment measures for CAD systems. [ 25 ]  This fact may cause the difficulty for obtaining approval for commercial use from governing bodies such as the  FDA . Moreover, while many positive developments of CAD systems have been proven, studies for validating their algorithms for clinical practice have not been confirmed. [ 27 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1254", "text": "Other challenges are related to the problem for healthcare providers to adopt new CAD systems in clinical practice. Some negative studies may discourage the use of CAD. In addition, the lack of training of health professionals on the use of CAD sometimes brings the incorrect interpretation of the system outcomes. [ a ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1255", "text": "CAD is used in the diagnosis of  breast cancer ,  lung cancer ,  colon cancer ,  prostate cancer ,  bone metastases ,  coronary artery disease ,  congenital heart defect , pathological brain detection, fracture detection,  Alzheimer's disease , and  diabetic retinopathy ."}
{"_id": "WikiPedia_Radiology$$$corpus_1256", "text": "CAD is used in screening  mammography  (X-ray examination of the female breast). Screening mammography is used for the early detection of breast cancer. CAD systems are often utilized to help classify a tumor as malignant (cancerous) or benign (non-cancerous). CAD is especially established in the US and the Netherlands and is used in addition to human evaluation, usually by a radiologist."}
{"_id": "WikiPedia_Radiology$$$corpus_1257", "text": "The first CAD system for mammography was developed in a research project at the  University of Chicago . Today it is commercially offered by iCAD and  Hologic . However, while achieving high sensitivities, CAD systems tend to have very low specificity and the benefits of using CAD remain uncertain. A 2008 systematic review on computer-aided detection in screening mammography concluded that CAD does not have a significant effect on cancer detection rate, but does undesirably increase recall rate ( i.e.  the rate of false positives). However, it noted considerable heterogeneity in the impact on recall rate across studies. [ 28 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1258", "text": "Recent advances in  machine learning ,  deep-learning  and  artificial intelligence  technology have enabled the development of CAD systems that are clinically proven to assist  radiologists  in addressing the challenges of reading  mammographic  images by improving cancer detection rates and reducing false positives and unnecessary patient recalls, while significantly decreasing reading times. [ 29 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1259", "text": "Procedures to evaluate mammography based on  magnetic resonance imaging  (MRI) exist too."}
{"_id": "WikiPedia_Radiology$$$corpus_1260", "text": "In the diagnosis of lung cancer,  computed tomography  with special three-dimensional CAD systems are established and considered as appropriate second opinions. [ 30 ]  At this a volumetric dataset with up to 3,000 single images is prepared and analyzed. Round lesions ( lung cancer , metastases and benign changes) from 1\u00a0mm are detectable. Today all well-known vendors of medical systems offer corresponding solutions."}
{"_id": "WikiPedia_Radiology$$$corpus_1261", "text": "Early detection of lung cancer is valuable. However, the random detection of lung cancer in the early stage (stage 1) in the X-ray image is difficult. Round lesions that vary from 5\u201310\u00a0mm are easily overlooked. [ 31 ]  The routine application of CAD Chest Systems may help to detect small changes without initial suspicion. A number of researchers developed CAD systems for detection of lung nodules (round lesions less than 30\u00a0mm) in chest radiography [ 32 ] [ 33 ] [ 34 ]  and CT, [ 35 ] [ 36 ]  and CAD systems for diagnosis ( e.g. , distinction between malignant and benign) of lung nodules in CT. Virtual dual-energy imaging [ 37 ] [ 38 ] [ 39 ] [ 40 ]  improved the performance of CAD systems in chest radiography. [ 41 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1262", "text": "CAD is available for detection of  colorectal polyps  in the  colon  in CT colonography. [ 42 ] [ 43 ]  Polyps are small growths that arise from the inner lining of the colon. CAD detects the polyps by identifying their characteristic \"bump-like\" shape. To avoid excessive false positives, CAD ignores the normal colon wall, including the  haustral  folds."}
{"_id": "WikiPedia_Radiology$$$corpus_1263", "text": "State-of-the-art methods in cardiovascular computing, cardiovascular informatics, and mathematical and  computational modeling  can provide valuable tools in clinical decision-making. [ 44 ]  CAD systems with novel image-analysis-based markers as input can aid vascular physicians to decide with higher confidence on best suitable treatment for  cardiovascular disease  patients."}
{"_id": "WikiPedia_Radiology$$$corpus_1264", "text": "Reliable early-detection and risk-stratification of  carotid atherosclerosis  is of outmost importance for predicting  strokes  in asymptomatic patients. [ 45 ]  To this end, various noninvasive and low-cost markers have been proposed, using  ultrasound -image-based features. [ 46 ]  These combine  echogenicity , texture, and  motion [ 47 ] [ 48 ] [ 49 ] [ 50 ]  characteristics to assist clinical decision towards improved prediction, assessment and management of cardiovascular risk. [ 51 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1265", "text": "CAD is available for the automatic detection of significant (causing more than 50%  stenosis )  coronary artery disease  in coronary CT angiography (CCTA) studies. [ 52 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1266", "text": "Early detection of pathology can be the difference between life and death. CADe can be done by  auscultation  with a digital stethoscope and specialized software, also known as  computer-aided auscultation . Murmurs, irregular heart sounds, caused by blood flowing through a defective heart, can be detected with high sensitivity and specificity. Computer-aided auscultation is sensitive to external noise and bodily sounds and requires an almost silent environment to function accurately."}
{"_id": "WikiPedia_Radiology$$$corpus_1267", "text": "Chaplot et al. was the first to use  Discrete Wavelet Transform  (DWT) coefficients to detect pathological brains. [ 53 ]  Maitra and Chatterjee employed the Slantlet transform, which is an improved version of DWT. Their feature vector of each image is created by considering the magnitudes of Slantlet transform outputs corresponding to six spatial positions chosen according to a specific logic. [ 54 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1268", "text": "In 2010, Wang and Wu presented a forward neural network (FNN) based method to classify a given MR brain image as normal or abnormal. The parameters of FNN were optimized via adaptive chaotic particle swarm optimization (ACPSO). Results over 160 images showed that the classification accuracy was 98.75%. [ 55 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1269", "text": "In 2011, Wu and Wang proposed using DWT for feature extraction, PCA for feature reduction, and FNN with scaled chaotic artificial bee colony (SCABC) as classifier. [ 56 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1270", "text": "In 2013, Saritha et al. were the first to apply wavelet entropy (WE) to detect pathological brains. Saritha also suggested to use spider-web plots. [ 57 ]  Later, Zhang et al. proved removing spider-web plots did not influence the performance. [ 58 ]  Genetic pattern search method was applied to identify abnormal brain from normal controls. Its classification accuracy was reported as 95.188%. [ 59 ]  Das et al. proposed to use Ripplet transform. [ 60 ]  Zhang et al. proposed to use particle swarm optimization (PSO). [ 61 ]  Kalbkhani et al. suggested to use GARCH model. [ 62 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1271", "text": "In 2014, El-Dahshan et al. suggested the use of pulse coupled neural network. [ 63 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1272", "text": "In 2015, Zhou et al. suggested application of naive  Bayes classifier  to detect pathological brains. [ 64 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1273", "text": "CADs can be used to identify subjects with Alzheimer's and mild cognitive impairment from normal elder controls."}
{"_id": "WikiPedia_Radiology$$$corpus_1274", "text": "In 2014, Padma  et al . used combined wavelet statistical texture features to segment and classify AD benign and malignant tumor slices. [ 57 ]  Zhang et al. found kernel support vector machine decision tree had 80% classification accuracy, with an average computation time of 0.022s for each image classification. [ 65 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1275", "text": "In 2019, Signaevsky  et al . have first reported a trained Fully Convolutional Network (FCN) for detection and quantification of  neurofibrillary tangles  (NFT) in Alzheimer's disease and an array of other tauopathies. The trained FCN achieved high precision and recall in naive  digital whole slide image  (WSI) semantic segmentation, correctly identifying NFT objects using a SegNet model trained for 200 epochs. The FCN reached near-practical efficiency with average processing time of 45 min per WSI per  graphics processing unit (GPU) , enabling reliable and reproducible large-scale detection of NFTs. The measured performance on test data of eight naive WSI across various tauopathies resulted in the  recall, precision , and an  F1 score  of 0.92, 0.72, and 0.81, respectively. [ 66 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1276", "text": "Eigenbrain is a novel brain feature that can help to detect AD, based on  principal component analysis (PCA) [ 67 ]  or  independent component analysis  decomposition. [ 68 ]  Polynomial kernel SVM has been shown to achieve good accuracy. The polynomial KSVM performs better than linear SVM and RBF kernel SVM. [ 69 ]  Other approaches with decent results involve the use of texture analysis, [ 70 ]  morphological features, [ 71 ]  or high-order statistical features [ 72 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1277", "text": "CADx is available for nuclear medicine images. Commercial CADx systems for the diagnosis of bone metastases in whole-body bone scans and coronary artery disease in myocardial perfusion images exist. [ 73 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1278", "text": "With a high sensitivity and an acceptable false lesions detection rate, computer-aided automatic lesion detection system is demonstrated as useful and will probably in the future be able to help nuclear medicine physicians to identify possible bone lesions. [ 74 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1279", "text": "Diabetic retinopathy is a disease of the retina that is diagnosed predominantly by fundoscopic images. Diabetic patients in industrialised countries generally undergo regular screening for the condition. Imaging is used to recognize early signs of abnormal retinal blood vessels. Manual analysis of these images can be time-consuming and unreliable. [ 75 ] [ 76 ]  CAD has been employed to enhance the accuracy, sensitivity, and specificity of automated detection method. The use of some CAD systems to replace human graders can be safe and cost effective. [ 76 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1280", "text": "Image pre-processing, and feature extraction and classification are two main stages of these CAD algorithms. [ 77 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1281", "text": "Image normalization  is minimizing the variation across the entire image. Intensity variations in areas between periphery and central macular region of the eye have been reported to cause inaccuracy of vessel segmentation. [ 78 ]  Based on the 2014 review, this technique was the most frequently used and appeared in 11 out of 40 recently (since 2011) published primary research. [ 77 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1282", "text": "Histogram equalization  is useful in enhancing contrast within an image. [ 80 ]  This technique is used to increase  local contrast.  At the end of the processing, areas that were dark in the input image would be brightened, greatly enhancing the contrast among the features present in the area. On the other hand, brighter areas in the input image would remain bright or be reduced in brightness to equalize with the other areas in the image. Besides vessel segmentation, other features related to diabetic retinopathy can be further separated by using this pre-processing technique. Microaneurysm and hemorrhages are red lesions, whereas exudates are yellow spots. Increasing contrast between these two groups allow better visualization of lesions on images. With this technique, 2014 review found that 10 out of the 14 recently (since 2011) published primary research. [ 77 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1283", "text": "Green channel filtering  is another technique that is useful in differentiating lesions rather than vessels. This method is important because it provides the maximal contrast between diabetic retinopathy-related lesions. [ 81 ]  Microaneurysms and hemorrhages are red lesions that appear dark after application of green channel filtering. In contrast, exudates, which appear yellow in normal image, are transformed into bright white spots after green filtering. This technique is mostly used according to the 2014 review, with appearance in 27 out of 40 published articles in the past three years. [ 77 ]  In addition, green channel filtering can be used to detect center of optic disc in conjunction with double-windowing system. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1284", "text": "Non-uniform illumination correction  is a technique that adjusts for non-uniform illumination in fundoscopic image. Non-uniform illumination can be a potential error in automated detection of diabetic retinopathy because of changes in statistical characteristics of image. [ 77 ]  These changes can affect latter processing such as feature extraction and are not observable by humans. Correction of non-uniform illumination (f') can be achieved by modifying the pixel intensity using known original pixel intensity (f), and average intensities of local (\u03bb) and desired pixels (\u03bc) (see formula below). [ 82 ]  Walter-Klein transformation is then applied to achieve the uniform illumination. [ 82 ]  This technique is the least used pre-processing method in the review from 2014."}
{"_id": "WikiPedia_Radiology$$$corpus_1285", "text": "f \n \u2032 \n \n = \n f \n + \n \u03bc \n \u2212 \n \u03bb \n \n \n {\\displaystyle f'=f+\\mu -\\lambda }"}
{"_id": "WikiPedia_Radiology$$$corpus_1286", "text": "Morphological operations  is the second least used pre-processing method in 2014 review. [ 77 ]  The main objective of this method is to provide contrast enhancement, especially darker regions compared to background."}
{"_id": "WikiPedia_Radiology$$$corpus_1287", "text": "After pre-processing of funduscopic image, the image will be further analyzed using different computational methods. However, the current literature agreed that some methods are used more often than others during vessel segmentation analyses. These methods are SVM, multi-scale, vessel-tracking, region growing approach, and model-based approaches."}
{"_id": "WikiPedia_Radiology$$$corpus_1288", "text": "Support vector machine  is by far the most frequently used classifier in vessel segmentation, up to 90% of cases. [ citation needed ]  SVM is a supervised learning model that belongs to the broader category of pattern recognition technique. The algorithm works by creating a largest gap between distinct samples in the data. The goal is to create the largest gap between these components that minimize the potential error in classification. [ 83 ]  In order to successfully segregate blood vessel information from the rest of the eye image, SVM algorithm creates support vectors that separate the blood vessel pixel from the rest of the image through a supervised environment. Detecting blood vessel from new images can be done through similar manner using support vectors. Combination with other pre-processing technique, such as green channel filtering, greatly improves the accuracy of detection of blood vessel abnormalities. [ 77 ]  Some beneficial properties of SVM include [ 83 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1289", "text": "Multi-scale  approach is a multiple resolution approach in vessel segmentation. At low resolution, large-diameter vessels can first be extracted. By increasing resolution, smaller branches from the large vessels can be easily recognized. Therefore, one advantage of using this technique is the increased analytical speed. [ 75 ]  Additionally, this approach can be used with 3D images. The surface representation is a surface normal to the curvature of the vessels, allowing the detection of abnormalities on vessel surface. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1290", "text": "Vessel tracking  is the ability of the algorithm to detect \"centerline\" of vessels. These centerlines are maximal peak of vessel curvature. Centers of vessels can be found using directional information that is provided by Gaussian filter. [ citation needed ]  Similar approaches that utilize the concept of centerline are the skeleton-based and differential geometry-based. [ 75 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1291", "text": "Region growing  approach is a method of detecting neighboring pixels with similarities. A seed point is required for such method to start. Two elements are needed for this technique to work: similarity and spatial proximity. A neighboring pixel to the seed pixel with similar intensity is likely to be the same type and will be added to the growing region. One disadvantage of this technique is that it requires manual selection of seed point, which introduces bias and inconsistency in the algorithm. [ 75 ]  This technique is also being used in optic disc identification. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1292", "text": "Model-based  approaches employ representation to extract vessels from images. Three broad categories of model-based are known: deformable, parametric, and template matching. [ 75 ]  Deformable methods uses objects that will be deformed to fit the contours of the objects on the image. Parametric uses geometric parameters such as tubular, cylinder, or ellipsoid representation of blood vessels. Classical snake contour in combination with blood vessel topological information can also be used as a model-based approach. [ 84 ]  Lastly, template matching is the usage of a template, fitted by stochastic deformation process using Hidden Markov Mode 1."}
{"_id": "WikiPedia_Radiology$$$corpus_1293", "text": "Automation of medical diagnosis labor (for example,  quantifying red blood cells ) has some historical precedent. [ 85 ]  The  deep learning  revolution of the 2010s has already produced AI that are more accurate in many areas of visual diagnosis than radiologists and dermatologists, and this gap is expected to grow."}
{"_id": "WikiPedia_Radiology$$$corpus_1294", "text": "Some experts, including many doctors, are dismissive of the effects that AI will have on medical specialties."}
{"_id": "WikiPedia_Radiology$$$corpus_1295", "text": "In contrast, many economists and artificial intelligence experts believe that fields such as radiology will be massively disrupted, with unemployment or downward pressure on the wages of radiologists; hospitals will need fewer radiologists overall, and many of the radiologists who still exist will require substantial retraining.  Geoffrey Hinton , the \"Godfather of deep learning\", argues that in light of the likely advances expected in the next five or ten years, hospitals should immediately stop training radiologists, as their time-consuming and expensive training on visual diagnosis will soon be mostly obsolete, leading to a glut of traditional radiologists. [ 86 ] [ 87 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1296", "text": "An op-ed in  JAMA  argues that pathologists and radiologists should merge into a single \" information specialist \" role, and state that \"To avoid being replaced by computers, radiologists must allow themselves to be displaced by computers.\" Information specialists would be trained in \" Bayesian logic ,  statistics ,  data science \", and some  genomics  and  biometrics ; manual visual pattern recognition would be greatly de-emphasized compared with current onerous radiology training. [ 88 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1297", "text": "Computer-aided simple triage  ( CAST ) are computerized methods or systems that assist physicians in initial interpretation and classification of medical images. CAST is a sub-class of  computer-aided diagnosis  (CAD). CAST  software  systems perform a fully automatic initial  triage  (classification) of diagnostic  medical imaging  studies. CAST is primarily intended for  emergency   diagnostic imaging , where a prompt  diagnosis  of critical, life-threatening condition is required. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1298", "text": "Computer-aided simple triage (CAST) is a combination of  computer-aided diagnosis  (CAD) and  simple triage and rapid treatment  (START).\nCAST performs a fully automatic initial interpretation of a study \u2013 a \"wet read\". Studies are automatically classified into some meaningful categories, e.g. positive/negative, critical/minor/normal, difficult/simple/non-diagnostic, etc. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1299", "text": "CAST is primarily intended for  emergency  diagnostic imaging. Unlike traditional CAD, mainly used to detect malignant lesions, CAST deals with acute, life-threatening conditions, when a prompt diagnosis is time\ncritical. While the primary goal of the traditional  CAD  is improving the diagnostic accuracy of a human reader, the CAST addresses two other problems:"}
{"_id": "WikiPedia_Radiology$$$corpus_1300", "text": "As with the traditional CAD, CAST does not substitute the physician. It only alerts about the possibility of acute, critical condition, or suggests that the study is free of severe disease. In both cases, the diagnosis should be verified by a trained physician. \nThe clinical benefit is achieved:"}
{"_id": "WikiPedia_Radiology$$$corpus_1301", "text": "Traditional CAD system usually plays the role of a \"second reader\" and is used  after or during  the interpretation\nperformed by physician. CAST, on the other hand, analyzes the study  before  the physician, in a background, fully automatic mode. By the time physician comes to read the study, the initial triage or \"wet read\" prepared by CAST is already available. CAST system can send a message to a physician to report an urgent case requiring immediate attention."}
{"_id": "WikiPedia_Radiology$$$corpus_1302", "text": "Like any CAD system, CAST, in general, cannot guarantee 100% diagnostic accuracy. \nSince CAST operates in a fully automated mode, the system is expected to exhibit very high  sensitivity  \u2013 usually above 90%. Moreover, the need to provide a diagnosis at \"per study\" level dictates stringent requirements for CAST  specificity  as well. The average of one or more  false alarms  per study, tolerable for a traditional CAD, is not acceptable for CAST, as almost every study would be reported as positive. Therefore, for most clinical applications, CAST specificity should be higher than 60-70% to make it useful."}
{"_id": "WikiPedia_Radiology$$$corpus_1303", "text": "Since CAST operates in a fully automatic mode, it should be able to deal with any study, regardless of image quality, patient anatomy, etc. Therefore, CAST systems should implement a quality control mechanism to ensure the high confidence level of the diagnosis. If the system decides (based on the evaluated image quality, detected  artifacts , anatomical anomalies, etc.) that no reliable diagnosis can be automatically achieved, it reports a failure."}
{"_id": "WikiPedia_Radiology$$$corpus_1304", "text": "CAST approach is applicable for the automatic detection of acute, life-threatening conditions from diagnostic medical images, such as:"}
{"_id": "WikiPedia_Radiology$$$corpus_1305", "text": "CAST system can analyze images acquired with various modalities, including  x-ray ,  CT ,  MRI ,  ultrasound  and others."}
{"_id": "WikiPedia_Radiology$$$corpus_1306", "text": "CAST system is available for the detection of significant (>50%)  coronary   stenosis  in coronary  CT angiography  (cCTA) studies. The system exhibits \"per study\"  specificity  of 60\u201370%, while keeping the  sensitivity  above 90%. [ 3 ] [ 4 ] [ 5 ] [ 6 ] [ 7 ] \nIt can be used for chest pain patient triage in emergency room."}
{"_id": "WikiPedia_Radiology$$$corpus_1307", "text": "A deep learning system is available for automatic detection of  Intracranial Hemorrhages  in acute care settings. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1308", "text": "Contrast-induced nephropathy  (CIN) is a purported form of  kidney damage  in which there has been recent exposure to  medical imaging contrast  material without another clear cause for the acute kidney injury."}
{"_id": "WikiPedia_Radiology$$$corpus_1309", "text": "Despite extensive speculation, the actual occurrence of contrast-induced nephropathy has not been demonstrated in the literature. [ 1 ]  Analysis of  observational studies  has shown that radiocontrast use in  CT scanning  is not  causally  related to changes in  kidney function . [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1310", "text": "Given the increasing doubts about the contribution of radiocontrast to acute kidney injury, the  American College of Radiology  has proposed the name contrast-associated acute kidney injury (CA-AKI) (formerly referred to as post-contrast acute kidney injury; PC-AKI) because it does not imply a  causal role , with the name contrast-induced acute kidney injury (CI-AKI) (formerly referred to as contrast-induced nephropathy; CIN) reserved for the rare cases where radiocontrast is likely to be causally related. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1311", "text": "There are multiple risk factors of contrast-induced nephropathy, whereof a 2016 review emphasized  chronic kidney disease ,  diabetes mellitus ,  high blood pressure , reduced  intravascular volume , and  old age . [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1312", "text": "European guidelines classify a pre-existing decreased  kidney function  to be a risk factor of contrast-induced nephropathy in the following cases: [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1313", "text": "To calculate  estimated GFR  (a measure of kidney function) from creatinine, European guidelines use the CKD-EPI formula in adults \u2265 18 years, and the revised Schwartz formula in children. [ 5 ]  Swedish guidelines recommends no specific formula in children because of lack of evidence, but on the other hand recommends GFR based on  cystatin C  rather than creatinine in those with abnormal  muscle mass ,  liver failure , or  cirrhosis . [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1314", "text": "The Mehran score is a  clinical prediction rule  to estimate probability of CIN which includes the following risk factors: systolic  blood pressure  <80\u00a0mm Hg for at least one hour requiring  inotropic  support,  intra-aortic balloon pump ,  congestive heart failure  with  New York Heart Association Functional Classification  class III or worse, history of  pulmonary edema , age >75 years,  hematocrit  level <39% for men and <35% for women,  diabetes mellitus , contrast media volume, decreased kidney function (serum creatinine level >1.5 g/dL or decreased estimated  glomerular filtration rate ). [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1315", "text": "European guidelines include the following procedure-related risk factors: [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1316", "text": "Swedish guidelines list the following additional risk factors: [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1317", "text": "The main alternatives in people with a risk of contrast-induced nephropathy are: [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1318", "text": "According to European guidelines, the ratio of the contrast dose (in grams of iodine) divided by the absolute estimated  glomerular filtration rate  (GFR) should be less than 1.1 g/(ml/min) for intra-arterial contrast medium administration with first-pass renal exposure (not passing lungs or peripheral tissue before reaching the kidneys). [ 5 ]  Swedish guidelines are more restrictive, recommending a ratio of less than 0.5 g/(ml/min) in patients with risk factors and irrespective of route of administration, and even more caution in first-pass renal exposure. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1319", "text": "Hydration by  drinking  or intravenous  volume expander , either before or after contrast administration, decreases the risk of contrast-induced nephropathy. [ 8 ]  Evidence also supports the use of  N-acetylcysteine  with intravenous saline among those getting low molecular weight contrast. [ 9 ] [ dubious  \u2013  discuss ]  The use of  statins  with N-acetylcysteine and intravenous saline is also supported. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1320", "text": "CIN is classically defined as a  serum creatinine  increase of at least 25% and/or an absolute increase in serum creatinine of 0.5\u00a0mg/dL [ 17 ]  after using iodine  contrast agent  without another clear cause for acute kidney injury, [ 4 ]  but other definitions have also been used. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1321", "text": "The  American College of Radiology  recommends the usage of the AKIN criteria for the diagnosis of CIN or PC-AKI. The AKIN criteria states that the diagnosis is made if within 48 hours from intravascular  contrast medium  exposure one of the following occurs: [ 18 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1322", "text": "The mechanism of contrast-induced nephropathy is not entirely understood, but is thought to include a combination of direct  renal tubule  damage from the contrast agent and reductions in blood flow to areas of the kidney. [ 19 ]  The contrast agent directly damages renal tubule cells by a variety of mechanisms, one proposed mechanism is by causing changes in cell polarity. The  sodium potassium pump  (also known as the Na+/K+ ATPase) is redistributed from the basal surface to the luminal surface of renal tubule cells. [ 19 ]  This causes sodium to be transported into the lumen where it is delivered to the distal renal tubule. This sodium load being delivered to the distal renal tubule leads to renal vasoconstriction via tubuloglomerular feedback, with the vasoconstriction and restriction of blood flow leading to injury of tubular cells. [ 19 ]  Contrast agents cause damage to renal tubular cells in other ways specific to the type of contrast agent, leading to  apoptosis  and necrosis of the tubular cells. [ 19 ]  The damaged renal tubular cells detach from the basement membrane and accumulate in the tubules which causes an increase in tubular pressure, reduced glomerular filtration rate and luminal blockage. [ 19 ]  The viscosity of contrast filtered into the tubule may also contribute to increases in tubular pressure. [ 19 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1323", "text": "Contrast agents may also cause renal tubular injury by causing renal vasoconstriction mediated by inhibition of vasodilators such as  nitric oxide  and  prostaglandins  and activation of  endothelin . This renal vasoconstriction, along with increases in blood viscosity caused by the contrast agents themselves, leads to renal vasoconstriction and reduced blood flow to metabolically active areas of the kidneys thus causing kidney damage. [ 19 ]  Changes in blood osmolality due to the contrast agents may lead to reduced red blood cell elasticity, thus leading to microthrombi development in the small blood vessels of the kidney thus further reducing glomerular blood flow. [ 19 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1324", "text": "It is unclear if CIN causes persisting decline in renal function since few studies has followed patients for more than 72 hours. [ 18 ]  In one meta-analysis the decline in renal function was shown to persist in 1.1\u00a0% of the patients with CIN. [ 20 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1325", "text": "Doubts regarding the significance of the phenomenon appeared in the scientific literature. Several studies have shown that intravenous contrast material administration was not associated with excess risk of  acute kidney injury , dialysis, or death, even among patients with comorbidities reported to predispose them to nephrotoxicity. [ 1 ]  Moreover, hydration, the most established prevention measure to prevent contrast-induced nephropathy was shown to be ineffective in the POSEIDON trial, [ 21 ]  raising further doubts regarding the significance of this disease state. [ 22 ]  A meta-analysis of 28 studies of AKI after CT with radiocontrast showed no causal relationship between the use of radiocontrast and AKI. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1326", "text": "Digital X-ray radiogrammetry   is a method for measuring  bone mineral density  (BMD). Digital X-ray radiogrammetry is based on the old technique of  radiogrammetry . In DXR, the  cortical  thickness of the three middle  metacarpal bones  of the hand is measured in a digital X-ray image. [ 1 ]  Through a geometrical operation the thickness is converted to bone mineral density. The BMD is corrected for  porosity  of the bone, estimated by a texture analysis performed on the cortical part of the bone. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1327", "text": "Like other technologies for estimating the bone mineral density, the outputs are an areal BMD value, a  T-score  and a  Z-score  for assessing  osteoporosis  and the risk of bone fracture. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1328", "text": "Digital X-ray radiogrammetry is primarily used in combination with  digital mammography  for osteoporosis screening, where same mammography machine that is used to acquire breast X-ray images is also used to acquire a hand image for BMD measurement. Due to high  precision , DXR is also used for monitoring change in bone mineral density over time. [ 5 ]  Recent studies have suggested that DXR is a promising alternative for DXA for determining low bone quality in children with suspected secondary low bone quality or osteoporosis. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1329", "text": "This  medical  diagnostic article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Radiology$$$corpus_1330", "text": "Dual X-ray absorptiometry and laser technique  (DXL) in the area of  bone density studies  for  osteoporosis  assessment is an improvement to the  DXA Technique , adding an exact laser measurement of the thickness of the region scanned. The addition of object thickness adds a third input to the two  x-ray  energies used by DXA, better solving the equation for bone and excluding more efficiently these soft tissues components."}
{"_id": "WikiPedia_Radiology$$$corpus_1331", "text": "The body consists of three main components:  bone mineral , lean soft tissue (skin, blood, water and skeletal muscle) and  adipose tissue  (fat and yellow bone marrow). These different components have different  x-ray attenuating  properties. The standard in bone mineral density scanning developed in the 1980s is called  Dual X-ray Absorptiometry , known as DXA. The DXA technique uses two different x-ray energy levels to estimate  bone density . DXA scans assume a constant relationship between the amounts of lean soft tissue and adipose tissue. This assumption leads to measurement errors, with an impact on accuracy as well as precision."}
{"_id": "WikiPedia_Radiology$$$corpus_1332", "text": "To reduce soft-tissue errors in DXA, DXL technology was developed in the late 1990s by a team of Swedish researchers led by Prof. Ragnar Kullenberg. With DXL technology, the  region of interest  is scanned using low and high energy x-rays as with a DXA scan. The improvement to DXA with DXL is that, for each pixel scanned by DXA, the exact  thickness of the measured object is also measured using lasers. The DXL results allow for a more accurate estimation of bone density by using three separate inputs (low and high x-ray energies plus thickness) rather than two for each pixel in the measuring region."}
{"_id": "WikiPedia_Radiology$$$corpus_1333", "text": "Using the DXL technique, for each measuring point (or pixel) the following equations apply:"}
{"_id": "WikiPedia_Radiology$$$corpus_1334", "text": "N1 = N01\u22c5exp(-(\u03bdb1\u22c5tb\u22c5\u03c3b + \u03bds1\u22c5ts\u22c5\u03c3s + \u03bdf1\u22c5tf\u22c5\u03c3f))"}
{"_id": "WikiPedia_Radiology$$$corpus_1335", "text": "N2 = N02\u22c5exp(-(\u03bdb2\u22c5tb\u22c5\u03c3b + \u03bds2\u22c5ts\u22c5\u03c3s + \u03bdf2\u22c5tf\u22c5\u03c3f))"}
{"_id": "WikiPedia_Radiology$$$corpus_1336", "text": "T = tb + ts + tf"}
{"_id": "WikiPedia_Radiology$$$corpus_1337", "text": "Where:"}
{"_id": "WikiPedia_Radiology$$$corpus_1338", "text": "tb * \u03c3b is the unknown bone density that one wants to calculate, e.g. areal mass (g/cm2)."}
{"_id": "WikiPedia_Radiology$$$corpus_1339", "text": "The DXL technique is used in the bone densitometry system  DXL Calscan , manufactured and marketed by the company Demetech AB, T\u00e4by, Sweden. Many published studies have evaluated the DXL technique using the DXL Calscan system, which scans the subject's heel. Several published fracture studies have shown that heel scans using DXL Calscan have an ability to predict fractures as well or better than the DXA technique scanning the hip. [ 1 ] [ 2 ] [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1340", "text": "Dual-energy X-ray absorptiometry  ( DXA , or  DEXA [ 1 ] ) is a means of measuring  bone mineral density  (BMD) using  spectral imaging . Two  X-ray  beams, with different  energy levels , are aimed at the patient's  bones . When  soft tissue  absorption is subtracted out, the  bone mineral density  (BMD) can be determined from the absorption of each beam by bone. Dual-energy X-ray absorptiometry is the most widely used and most thoroughly studied bone density measurement technology."}
{"_id": "WikiPedia_Radiology$$$corpus_1341", "text": "The DXA scan is typically used to diagnose and follow  osteoporosis , as contrasted to the nuclear  bone scan , which is sensitive to certain metabolic diseases of bones in which bones are attempting to heal from infections, fractures, or tumors. It is also sometimes used to assess  body composition ."}
{"_id": "WikiPedia_Radiology$$$corpus_1342", "text": "Soft tissue and bone have different  attenuation coefficients  to X-rays.  A single X-ray beam passing through the body will be attenuated by both soft tissue and bone, and it is not possible to determine, from a single beam, how much attenuation was attributable to the bone.  However, the attenuation coefficients vary with the energy of the X-rays, and, crucially, the ratio of the attenuation coefficients also varies.  DXA uses two energies of X-ray.  The difference in total absorption between the two can be used, by suitable weighting, to subtract out the absorption by soft tissue, leaving just the absorption by bone, which is related to bone density."}
{"_id": "WikiPedia_Radiology$$$corpus_1343", "text": "One type of DXA scanner uses a  cerium  filter with a  tube voltage  of 80  kV , resulting in effective photon energies of about 40 and 70  keV . [ 2 ]  There is also a DXA scanner type using a  samarium  filter with a tube voltage of 100 kV, resulting in effective energies of 47 and 80 keV. [ 2 ]  Also, the tube voltage can be continuously switched between a low (for example 70 kV) and high (for example 140 kV) value in synchronism with the\nfrequency of the electrical mains, resulting in effective energies alternating between 45 and 100 keV. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1344", "text": "The combination of  dual X-ray absorptiometry and laser  uses the laser to measure the thickness of the region scanned, allowing for varying proportions of lean soft tissue and  adipose tissue  within the soft tissue to be controlled for and improving the accuracy."}
{"_id": "WikiPedia_Radiology$$$corpus_1345", "text": "The  U.S. Preventive Services Task Force  recommends that women over the age of 65 should get a DXA scan. [ 3 ]  The date at which men should be tested is uncertain [ 3 ]  but some sources recommend age 70. [ 4 ]  At risk women should consider getting a scan when their risk is equal to that of a normal 65-year-old woman."}
{"_id": "WikiPedia_Radiology$$$corpus_1346", "text": "A person's risk can be measured using the University of Sheffield's  FRAX  calculator, which includes many different clinical risk factors including prior fragility fracture, use of  glucocorticoids , heavy smoking, excess alcohol intake, rheumatoid arthritis, history of parental hip fracture, chronic renal and liver disease, chronic respiratory disease, long-term use of phenobarbital or phenytoin, celiac disease, inflammatory bowel disease, and other risks. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1347", "text": "The World Health Organization has defined the following categories based on bone density in white women:"}
{"_id": "WikiPedia_Radiology$$$corpus_1348", "text": "Bone densities are often given to patients as a T score or a Z score. A T score tells the patient what their bone mineral density is in comparison to a young adult of the same gender with peak bone mineral density. A normal T score is -1.0 and above, low bone density is between -1.0 and -2.5, and osteoporosis is -2.5 and lower. A Z score is just a comparison of what a patient's bone mineral density is in comparison to the average bone mineral density of a male or female of their age and weight."}
{"_id": "WikiPedia_Radiology$$$corpus_1349", "text": "The WHO committee did not have enough data to create definitions for men or other ethnic groups. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1350", "text": "Special considerations are involved in the use of DXA to assess bone mass in children. Specifically, comparing the bone mineral density of children to the reference data of adults (to calculate a T-score) will underestimate the BMD of children, because children have less bone mass than fully developed adults. This would lead to an over-diagnosis of  osteopenia  for children. To avoid an overestimation of bone mineral deficits, BMD scores are commonly compared to reference data for the same gender and age (by calculating a  Z-score )."}
{"_id": "WikiPedia_Radiology$$$corpus_1351", "text": "Also, there are other variables in addition to age that are suggested to confound the interpretation of BMD as measured by DXA. One important confounding variable is bone size. DXA has been shown to overestimate the bone mineral density of taller subjects and underestimate the bone mineral density of smaller subjects. This error is due to the way by which DXA calculates BMD. In DXA, bone mineral content (measured as the attenuation of the X-ray by the bones being scanned) is divided by the area (also measured by the machine) of the site being scanned."}
{"_id": "WikiPedia_Radiology$$$corpus_1352", "text": "Because DXA calculates BMD using area (aBMD: areal Bone Mineral Density), it is not an accurate measurement of true bone mineral density, which is  mass  divided by a  volume . In order to distinguish DXA BMD from  volumetric  bone-mineral density, researchers sometimes refer to DXA BMD as an areal bone mineral density (aBMD). The confounding effect of differences in bone size is due to the missing depth value in the calculation of bone mineral density. Despite DXA technology's problems with estimating volume, it is still a fairly accurate measure of bone mineral content. Methods to correct for this shortcoming include the calculation of a volume that is approximated from the projected area measure by DXA. DXA BMD results adjusted in this manner are referred to as the bone mineral apparent density (BMAD) and are a  ratio  of the bone mineral content versus a  cuboidal  estimation of the volume of bone. Like the results for aBMD, BMAD results do not accurately represent true bone mineral density, since they use approximations of the bone's volume. BMAD is used primarily for research purposes and is not yet used in clinical settings."}
{"_id": "WikiPedia_Radiology$$$corpus_1353", "text": "Other imaging technologies such as  quantitative computed tomography  (QCT) are capable of measuring the bone's volume, and are, therefore, not susceptible to the confounding effect of bone-size in the way that DXA results are susceptible."}
{"_id": "WikiPedia_Radiology$$$corpus_1354", "text": "It is important for patients to get repeat BMD measurements done on the same machine each time, or at least a machine from the same manufacturer. Error between machines, or trying to convert measurements from one manufacturer's standard to another can introduce errors large enough to wipe out the sensitivity of the measurements. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1355", "text": "DXA results need to be adjusted if the patient is taking  strontium  supplements. [ 6 ] [ better\u00a0source\u00a0needed ] [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1356", "text": "DXA can also used to measure  trabecular bone score ."}
{"_id": "WikiPedia_Radiology$$$corpus_1357", "text": "DXA is, by far, the most widely used technique for bone mineral density measurements, since it is considered to be cheap, accessible, easy to use, and able to provide an accurate estimation of bone mineral density in adults. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1358", "text": "The official position of the  International Society for Clinical Densitometry  (ISCD) is that a patient may be tested for BMD if they have a condition that could precipitate bone loss, is going to be prescribed pharmaceuticals known to cause bone loss, or is being treated and needs to be monitored. The ISCD states that there is no clearly understood correlation between BMD and the risk of a child's sustaining a fracture; the diagnosis of osteoporosis in children cannot be made using the basis of a densitometry criteria. T-scores are prohibited with children and should not even appear on DXA reports. Thus, the WHO classification of osteoporosis and osteopenia in adults cannot be applied to children, but Z-scores can be used to assist diagnosis. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1359", "text": "Some clinics may routinely carry out DXA scans on pediatric patients with conditions such as nutritional  rickets ,  lupus , and  Turner syndrome . [ 10 ]  DXA has been demonstrated to measure skeletal maturity [ 11 ]  and body fat composition [ 12 ]  and has been used to evaluate the effects of pharmaceutical therapy. [ 13 ]  It may also aid pediatricians in diagnosing and monitoring treatment of disorders of bone mass acquisition in childhood. [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1360", "text": "However, it seems that DXA is still in its early days in pediatrics, and there are widely acknowledged limitations and disadvantages with DXA. A view exists [ 15 ]  that DXA scans for diagnostic purposes should not even be performed outside specialist centers, and, if a scan is done outside one of these centers, it should not be interpreted without consultation with an expert in the field. [ 15 ]  Furthermore, most of the pharmaceuticals given to adults with low bone mass can be given to children only in strictly monitored clinical trials."}
{"_id": "WikiPedia_Radiology$$$corpus_1361", "text": "Whole-body  calcium  measured by DXA has been validated in adults using  in-vivo   neutron activation  of total body calcium [ 16 ] [ 17 ]  but this is not suitable for paediatric subjects and studies have been carried out on paediatric-sized animals. [ 16 ] [ 17 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1362", "text": "DXA scans can also be used to measure total  body composition  and  fat content  with a high degree of accuracy comparable to  hydrostatic weighing  with a few important caveats. [ 18 ] [ specify ]  From the DXA scans, a low resolution \"fat shadow\" image can also be generated, which gives an overall impression of fat distribution throughout the body. [ 19 ]  It has been suggested that, while very accurately measuring minerals and lean soft tissue (LST), DXA may provide skewed results due to its method of indirectly calculating fat mass by subtracting it from the LST and/or body cell mass (BCM) that DXA actually measures. [ 20 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1363", "text": "DXA scans have been suggested as useful tools to diagnose conditions with an abnormal fat distribution, such as  familial partial lipodystrophy . [ 21 ] [ 22 ] [ 19 ]  They are also used to assess adiposity in children, especially to conduct clinical research. [ 23 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1364", "text": "DXA uses X-rays to measure bone mineral density. The  radiation  dose of current DEXA systems is small, [ 24 ]  as low as 0.001  mSv , much less than a standard chest or dental x-ray. [ 25 ] [ 26 ]  However, the dose delivered by older DEXA radiation sources (that used  radioisotopes  rather than  x-ray generators ) could  be as high as 35 mGy, [ 27 ] [ 28 ] [ 29 ]  considered a significant dose by  radiological health  standards."}
{"_id": "WikiPedia_Radiology$$$corpus_1365", "text": "The quality of DXA operators varies widely. DXA is not regulated like other radiation-based imaging techniques because of its low dosage. Each US state has a different policy as to what certifications are needed to operate a DXA machine.  California , for example, requires coursework and a state-run test, whereas  Maryland  has no requirements for DXA technicians. Many states require a training course and certificate from the International Society of Clinical Densitometry (ISCD)."}
{"_id": "WikiPedia_Radiology$$$corpus_1366", "text": "In Australia, regulation differs according to the applicable state or territory. For example, in Victoria, an individual performing DXA scans is required to completed a recognised course in safe use of bone mineral densitometers. [ 30 ]  In NSW and QLD a DXA technician only requires prior study in science, nursing or other related undergraduate study. The Environmental Protection Agency (EPA) oversees licensing of technicians, however, this is far from rigorous and regulation is non-existent. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1367", "text": "Echocardiography , also known as  cardiac ultrasound , is the use of  ultrasound  to examine the  heart . It is a type of  medical imaging , using standard ultrasound or  Doppler ultrasound . [ 1 ]  The visual image formed using this technique is called an  echocardiogram , a  cardiac echo , or simply an  echo ."}
{"_id": "WikiPedia_Radiology$$$corpus_1368", "text": "Echocardiography is routinely used in the diagnosis, management, and follow-up of patients with any suspected or known  heart diseases . It is one of the most widely used diagnostic imaging modalities in cardiology. It can provide a wealth of helpful information, including the size and shape of the heart (internal chamber size quantification), pumping capacity, location and extent of any tissue damage, and assessment of valves. An echocardiogram can also give physicians other estimates of heart function, such as a calculation of the  cardiac output ,  ejection fraction , and  diastolic  function (how well the heart relaxes)."}
{"_id": "WikiPedia_Radiology$$$corpus_1369", "text": "Echocardiography is an important tool in assessing wall motion abnormality in patients with suspected cardiac disease. It is a tool which helps in reaching an early diagnosis of  myocardial infarction , showing regional wall motion abnormality. Also, it is important in treatment and follow-up in patients with  heart failure , by assessing  ejection fraction . [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1370", "text": "Echocardiography can help detect  cardiomyopathies , such as  hypertrophic cardiomyopathy , and dilated cardiomyopathy. The use of stress echocardiography may also help determine whether any chest pain or associated symptoms are related to heart disease."}
{"_id": "WikiPedia_Radiology$$$corpus_1371", "text": "The most important advantages of echocardiography are that it is not invasive (does not involve breaking the skin or entering body cavities) and has no known risks or side effects. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1372", "text": "Not only can an echocardiogram create ultrasound images of heart structures, but it can also produce accurate assessment of the blood flowing through the heart by Doppler echocardiography, using pulsed- or continuous-wave Doppler ultrasound. This allows assessment of both normal and abnormal blood flow through the heart. Color Doppler, as well as spectral Doppler, is used to visualize any abnormal communications between the left and right sides of the heart, as well as any leaking of blood through the valves (valvular regurgitation), and can also estimate how well the valves open (or do not open in the case of valvular stenosis). The Doppler technique can also be used for tissue motion and velocity measurement, by  tissue Doppler echocardiography ."}
{"_id": "WikiPedia_Radiology$$$corpus_1373", "text": "Echocardiography was also the first ultrasound subspecialty to use intravenous contrast. Echocardiography is performed by  cardiac sonographers , cardiac physiologists (UK), or physicians trained in echocardiography."}
{"_id": "WikiPedia_Radiology$$$corpus_1374", "text": "Recognized as the \"Father of Echocardiography\", the Swedish physician  Inge Edler  (1911\u20132001), a graduate of  Lund University , was the first of his profession to apply ultrasonic pulse echo imaging in diagnosing cardiac disease, which the acoustical physicist  Floyd Firestone  had developed to detect defects in metal castings. In fact, Edler in 1953 produced the first echocardiographs using an industrial Firestone-Sperry Ultrasonic Reflectoscope. In developing echocardiography, Edler worked with the physicist  Carl Hellmuth Hertz , the son of the  Nobel laureate   Gustav Hertz  and grandnephew of  Heinrich Rudolph Hertz . [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1375", "text": "Health societies recommend the use of echocardiography for initial diagnosis when a change in the patient's clinical status occurs and when new data from an echocardiogram would result in the physician changing the patient's care. [ 7 ]  Diagnostic criteria for numerous cardiac diseases are based on echocardiography studies. For example, the differentiation of mild, moderate, and severe valvular disease is based upon measured criteria. Another example is the estimation of heart function by the left ventricular ejection fraction (LVEF) has vast uses including classification of heart failure and cut offs for implantation of  implantable cardioverter-defibrillators ."}
{"_id": "WikiPedia_Radiology$$$corpus_1376", "text": "Health societies do not recommend routine testing when the patient has no change in clinical status or when a physician is unlikely to change care for the patient based on the results of testing. [ 7 ]  A common example of overuse of echocardiography when not indicated is the use of routine testing in response to a patient diagnosis of mild  valvular heart disease . [ 8 ]  In this case, patients are often asymptomatic for years before the onset of deterioration and the results of the echocardiogram would not result in a change in care without other change in clinical status. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1377", "text": "Echocardiography has a vast role in  pediatrics , diagnosing patients with valvular heart disease and other congenital abnormalities. An emerging branch is  fetal echocardiography , which involves echocardiography of an unborn fetus. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1378", "text": "There are three primary types of echocardiography: transthoracic, transesophageal, and intracardic.\nStress testing utilizes tranthoracic echo in combination with an exercise modality (e.g., a treadmill).\nIntravascular ultrasound is included below, but is as the name indicates more \"ultrasound\" than \"echocardiography\" as it is imaging the walls of a vessel rather than the heart."}
{"_id": "WikiPedia_Radiology$$$corpus_1379", "text": "A standard echocardiogram is also known as a transthoracic echocardiogram (TTE) or cardiac ultrasound, and it is used for rapid evaluation of a patient at their bedside. [ 9 ] [ 10 ]  In this case, the echocardiography transducer (or probe) is placed on the chest wall (or  thorax ) of the subject, and images are taken through the chest wall. This is a non-invasive, highly accurate, and quick assessment of the overall function of the heart."}
{"_id": "WikiPedia_Radiology$$$corpus_1380", "text": "TTE utilizes several \"windows\" to image the heart from different perspectives. Each window has advantages and disadvantages for viewing specific structures within the heart and, typically, numerous windows are utilized within the same study to fully assess the heart. Parasternal long and parasternal short axis windows are taken next to the sternum, the apical two/three/four chamber windows are taken from the apex of the heart (lower left side), and the subcostal window is taken from underneath the edge of the last rib."}
{"_id": "WikiPedia_Radiology$$$corpus_1381", "text": "TTE utilizes one- (\"M mode\"), two-, and three-dimensional ultrasound (time is implicit and not included) from the different windows. These can be combined with pulse wave or continuous wave Doppler to visualize the velocity of blood flow and structure movements. Images can be enhanced with \"contrast\" that are typically some sort of micro bubble suspension that reflect the ultrasound waves."}
{"_id": "WikiPedia_Radiology$$$corpus_1382", "text": "A transesophageal echocardiogram is an alternative way to perform an echocardiogram. A specialized probe containing an ultrasound transducer at its tip is passed into the patient's  esophagus  via the mouth, allowing image and Doppler evaluation from a location directly behind the heart. It is most often used when transthoracic images are suboptimal and when a clearer and more precise image is needed for assessment. This test is performed in the presence of a cardiologist, anesthesiologist, registered nurse, and ultrasound technologist. Conscious sedation and/or localized numbing medication may be used to make the patient more comfortable during the procedure."}
{"_id": "WikiPedia_Radiology$$$corpus_1383", "text": "TEE, unlike TTE, does not have discrete \"windows\" to view the heart. The entire esophagus and stomach can be utilized, and the probe advanced or removed along this dimension to alter the perspective on the heart. Most probes include the ability to deflect the tip of the probe in one or two dimensions to further refine the perspective of the heart. Additionally, the ultrasound crystal is often a two-dimension crystal and the ultrasound plane being used can be rotated electronically to permit an additional dimension to optimize views of the heart structures. Often, movement in all of these dimensions is needed."}
{"_id": "WikiPedia_Radiology$$$corpus_1384", "text": "TEE can be used as stand-alone procedures, or incorporated into catheter- or surgical-based procedures. For example, during a  valve replacement  surgery the TEE can be used to assess the valve function immediately before repair/replacement and immediately after. This permits revising the valve mid-surgery, if needed, to improve outcomes of the surgery."}
{"_id": "WikiPedia_Radiology$$$corpus_1385", "text": "A stress echocardiogram, also known as a stress echo, uses ultrasound imaging of the heart to assess the wall motion in response to physical stress. First, images of the heart are taken \"at rest\" to acquire a baseline of the patient's wall motion at a resting heart rate. The patient then walks on a treadmill or uses another exercise modality to increase the heart rate to his or her target heart rate, or 85% of the age-predicted maximum heart rate (220 \u2212 patient's age). Finally, images of the heart are taken \"at stress\" to assess wall motion at the peak heart rate. A stress echo assesses wall motion of the heart; it does not, however, create an image of the coronary arteries directly. Ischemia of one or more coronary arteries could cause a wall motion abnormality, which could indicate coronary artery disease. The gold standard test to directly create an image of the coronary arteries and directly assess for stenosis or occlusion is a cardiac catheterization. A stress echo is not invasive and is performed in the presence of a licensed medical professional, such as a cardiologist, and a cardiac sonographer."}
{"_id": "WikiPedia_Radiology$$$corpus_1386", "text": "Intracardiac echocardiography (ICE) is specialized form of echocardiography that uses catheters to insert the ultrasound probe inside the heart to view structures from within the heart.\nICE is often used as a part of the cardiac procedure of crossing the  interatrial septum  with a transseptal puncture to permit catheter access from the right atrium to the left atrium; alternative access to the left heart would be retrograde through the  aorta  and across the  aortic valve  into the left ventricle."}
{"_id": "WikiPedia_Radiology$$$corpus_1387", "text": "ICE has the benefit over transthoracic echocardiography in that an operator who is performing a sterile procedure can also operate the ICE catheter and it is not limited to visibility problems that can arise with transthoracic or transesophageal echo. Though, there are image quality limitations due to size constraints of the probe being limited to a catheter."}
{"_id": "WikiPedia_Radiology$$$corpus_1388", "text": "ICE is often inserted through the femoral vein and into the right atrium.\nFrom the right atrium, visualization of the interatrial septum, all four cardiac chambers, all four valves, and the pericardial space (for an effusion) can be readily visualized.\nIt can also be advanced across the atrial septum into the left atrium to visualize the left atrial appendage during  left atrial appendage occlusion  device deployment."}
{"_id": "WikiPedia_Radiology$$$corpus_1389", "text": "Utilization of ICE imagery can be incorporated into the 3-D models built with  electroanatomic mapping  systems."}
{"_id": "WikiPedia_Radiology$$$corpus_1390", "text": "Intravascular ultrasound (IVUS) is a specialized form of echocardiography that uses a catheter to insert the ultrasound probe inside blood vessels. This is commonly used to measure the size of blood vessels and to measure the internal diameter of the blood vessel. For example, this can be used in a  coronary angiogram  to assess the narrowing of the coronary artery. If the catheter is retraced in a controlled manner, then an internal map can be generated to see the contour of the vessel and its branches."}
{"_id": "WikiPedia_Radiology$$$corpus_1391", "text": "The various modes describe how the ultrasound crystals are used to obtain information. These modes are common to all types of echocardiography."}
{"_id": "WikiPedia_Radiology$$$corpus_1392", "text": "A-scan or one dimensional ultrasound represents over half the standard ECHO exam.  For example, it is how aortic stenosis valve area (or any obstruction).  It is also how pressures are calculated in the heart such as right ventricle systolic pressure (RVSP).  It is usually used in the form of Doppler measurements.  There are two forms, pulse and continuous.  Pulsed allows velocities to be calculated in a specific place, but has a limited velocity range is can be used.  Continuous wave allows the velocity to be measured from zero to the fastest blood velocities a diseased heart can generate.  However, it can not tell you where in the A-scan the high velocity is coming from.  Continuous wave would be used to calculate aortic stenosis because you know the high velocity is coming from the stenosis region.  Pulsed would be used to find a ventricular septal defect where there should be no velocity across the septum and the pulsed tells you the location."}
{"_id": "WikiPedia_Radiology$$$corpus_1393", "text": "Brightness mode is often synonymous with \"2D\" and is very commonly used in echocardiography."}
{"_id": "WikiPedia_Radiology$$$corpus_1394", "text": "Motion mode is infrequently used in modern echocardiography. It has specific uses and has the benefit of very high temporal fidelity (e.g., measuring LV size at end diastole)."}
{"_id": "WikiPedia_Radiology$$$corpus_1395", "text": "Strain rate imaging is an ultrasound method for imaging regional differences in contraction (dyssynergy) in for instance  ischemic heart disease  or dyssynchrony due to  Bundle branch block . Strain rate imaging measures either regional systolic deformation (strain) or the rate of regional deformation (strain rate). The methods used are either  tissue Doppler  or  Speckle tracking echocardiography ."}
{"_id": "WikiPedia_Radiology$$$corpus_1396", "text": "Three-dimensional echocardiography (also known as  four-dimensional  echocardiography when the picture is moving) is possible using a matrix array ultrasound probe and an appropriate processing system. It enables detailed anatomical assessment of cardiac pathology, particularly valvular defects, [ 11 ]  and cardiomyopathies. [ 12 ]  The ability to slice the virtual heart in infinite planes in an anatomically appropriate manner and to reconstruct three-dimensional images of anatomic structures make it unique for the understanding of the congenitally malformed heart. [ 13 ]  Real-time three-dimensional echocardiography can be used to guide the location of  bioptomes  during right ventricular endomyocardial biopsies, placement of catheter-delivered valvular devices, and in many other intraoperative assessments. [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1397", "text": "Three-dimensional echocardiography technology may feature anatomical intelligence, or the use of organ-modeling technology, to automatically identify anatomy based on generic models.  All generic models refer to a dataset of anatomical information that uniquely adapts to variability in patient anatomy to perform specific tasks. Built on feature recognition and segmentation algorithms, this technology can provide patient-specific three-dimensional modeling of the heart and other aspects of the anatomy, including the brain, lungs, liver, kidneys, rib cage, and vertebral column. [ 15 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1398", "text": "Contrast echocardiography or contrast-enhanced ultrasound is the addition of an ultrasound contrast medium, or imaging agent, to traditional ultrasonography. The ultrasound contrast is made up of tiny microbubbles filled with a gas core and protein shell. This allows the microbubbles to circulate through the cardiovascular system and return the ultrasound waves, creating a highly reflective image. There are multiple applications in which contrast-enhanced ultrasound can be useful. The most commonly used application is in the enhancement of LV endocardial borders for assessment of global and regional systolic function. Contrast may also be used to enhance visualization of wall thickening during stress echocardiography, for the assessment of LV thrombus, or for the assessment of other masses in the heart. Contrast echocardiography has also been used to assess blood perfusion throughout myocardium in the case of coronary artery disease."}
{"_id": "WikiPedia_Radiology$$$corpus_1399", "text": "Echocardiography can at many times be subjective, meaning that the person reading the echo may have personal input that affects the interpretation of the findings, leading to so-called \"inter-observer variability\", where different echocardiographers might produce different reports when examining the same images. [ 16 ] [ 17 ]  It necessitated the development of accreditation programs around the world. The aim of such programs is to standardize the practice of echocardiography and to ensure that practitioners have the proper training prior to practicing echocardiography which will eventually limit inter-observer variability. [ 18 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1400", "text": "At the European level  [ 19 ]  individual and laboratory accreditation is provided by the European Association of Echocardiography (EAE). There are three subspecialties for individual accreditation: Adult Transthoracic Echocardiography ( TTE ), Adult Transesophageal Echocardiography ( TEE ) and Congenital Heart Disease Echocardiography (CHD)."}
{"_id": "WikiPedia_Radiology$$$corpus_1401", "text": "In the UK, accreditation is regulated by the British Society of Echocardiography. Accredited radiographers, sonographers, or other professionals are required to pass a mandatory exam. [ 20 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1402", "text": "The \"Intersocietal Accreditation Commission for Echocardiography\" (IAC) sets standards for echo labs across the US. Cardiologists and sonographers who wish to have their laboratory accredited by IAC must comply with these standards. The purpose of accreditation is to maintain quality and consistency across echocardiography labs in the United States. Accreditation is offered in adult and pediatric transthoracic and transesophageal echocardiography, as well as adult stress and fetal echo. Accreditation is a two-part process. Each facility will conduct a detailed self-evaluation, paying close attention to the IAC Standards and Guidelines. The facility will then complete the application and submit actual case studies to the board of directors for review. Once all requirements have been met, the lab will receive certification. IAC certification is a continual process and must be maintained by the facility: it may include audits or site visits by the IAC. There are several states in which Medicare and/or private insurance carriers require accreditation (credentials) of the laboratory and/or sonographer for reimbursement of echocardiograms."}
{"_id": "WikiPedia_Radiology$$$corpus_1403", "text": "There are two credentialing bodies in the United States for sonographers, the  Cardiovascular Credentialing International  (CCI), established in 1968, and the  American Registry for Diagnostic Medical Sonography  (ARDMS), established in 1975. Both CCI and ARDMS have earned the prestigious  ANSI-ISO 17024  accreditation for certifying bodies from the International Organization for Standardization ( ISO ). [ citation needed ]  Accreditation is granted through the American National Standards Institute (ANSI). Recognition of ARDMS programs in providing credentials has also earned the ARDMS accreditation with the National Commission for Certifying Agencies (NCCA). The NCCA is the accrediting arm of the National Organization for Competency Assurance (NOCA)."}
{"_id": "WikiPedia_Radiology$$$corpus_1404", "text": "Under both credentialing bodies, sonographers must first document completion of prerequisite requirements, which contain both didactic and hands-on experience in the field of ultrasound. Applicants must then take a comprehensive exam demonstrating knowledge in both the physics of ultrasound and the clinical competency related to their specialty. Credentialed sonographers are then required to maintain competency in their field by obtaining a certain number of Continuing Medical Education credits, or CME's."}
{"_id": "WikiPedia_Radiology$$$corpus_1405", "text": "In 2009, New Mexico and Oregon became the first two states to require licensure of sonographers. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1406", "text": "The  American Society of Echocardiography  (ASE) is a professional organization made up of physicians, sonographers, nurses, and scientists involved in the field of echocardiography. One of the most important roles that the ASE plays is providing their recommendations through the ASE Guidelines and Standards, providing resource and educational opportunities for sonographers and physicians in the field."}
{"_id": "WikiPedia_Radiology$$$corpus_1407", "text": "There have been various institutes who are working on use of  Artificial intelligence  in Echo but they are at a very early stage and still needs full development. [ 21 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1408", "text": "The most commonly used terminology in echocardiography diagnostics are:"}
{"_id": "WikiPedia_Radiology$$$corpus_1409", "text": "Effective dose  is a dose quantity in the  International Commission on Radiological Protection  (ICRP) system of  radiological protection . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1410", "text": "It is the tissue-weighted sum of the  equivalent doses  in all specified tissues and organs of the human body and represents the  stochastic  health risk to the whole body, which is the  probability  of  cancer induction  and genetic effects, of low levels of  ionizing radiation . [ 2 ] [ 3 ]  It takes into account the type of radiation and the nature of each organ or tissue being irradiated, and enables summation of organ doses due to varying levels and types of radiation, both internal and external, to produce an overall calculated effective dose."}
{"_id": "WikiPedia_Radiology$$$corpus_1411", "text": "The SI unit for effective dose is the  sievert  (Sv) which represents a 5.5% chance of developing cancer. [ 4 ]  The effective dose is not intended as a measure of  deterministic  health effects, which is the  severity  of acute tissue damage that is certain to happen, that is measured by the quantity  absorbed dose . [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1412", "text": "The concept of effective dose was developed by Wolfgang Jacobi and published in 1975, and was so convincing that the ICRP incorporated it into their 1977 general recommendations (publication 26) as \"effective dose equivalent\". [ 6 ]  The name \"effective dose\" replaced the name \"effective dose equivalent\" in 1991. [ 7 ]  Since 1977 it has been the central quantity for dose limitation in the ICRP international system of  radiological protection . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1413", "text": "According to the ICRP, the main uses of effective dose are the prospective dose assessment for planning and optimisation in radiological protection, and demonstration of compliance with dose limits for regulatory purposes. The effective dose is thus a central dose quantity for regulatory purposes. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1414", "text": "The ICRP also says that effective dose has made a significant contribution to radiological protection as it has enabled doses to be summed from whole and partial body exposure from external radiation of various types and from intakes of radionuclides. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1415", "text": "The calculation of effective dose is required for partial or non-uniform irradiation of the human body because  equivalent dose  does not consider the tissue irradiated, but only the radiation type. Various body tissues react to ionising radiation in different ways, so the ICRP has assigned sensitivity factors to specified tissues and organs so that the effect of partial irradiation can be calculated if the irradiated regions are known. [ 10 ]   A radiation field irradiating only a portion of the body will carry lower risk than if the same field irradiated the whole body. To take this into account, the effective doses to the component parts of the body which have been irradiated are calculated and summed. This becomes the effective dose for the whole body, dose quantity  E . It is a \"protection\" dose quantity which can be calculated, but cannot be measured in practice."}
{"_id": "WikiPedia_Radiology$$$corpus_1416", "text": "An effective dose will carry the same effective risk to the whole body regardless of where it was applied, and it will carry the same effective risk as the same amount of equivalent dose applied uniformly to the whole body."}
{"_id": "WikiPedia_Radiology$$$corpus_1417", "text": "Effective dose can be calculated for  committed dose  which is the internal dose resulting from inhaling, ingesting, or injecting radioactive materials."}
{"_id": "WikiPedia_Radiology$$$corpus_1418", "text": "The dose quantity used is:"}
{"_id": "WikiPedia_Radiology$$$corpus_1419", "text": "Committed effective dose,   E( t )  is the sum of the products of the committed organ or tissue equivalent doses and the appropriate tissue weighting factors  W T , where  t  is the integration time in years following the intake. The commitment period is taken to be 50 years for adults, and to age 70 years for children. [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1420", "text": "Ionizing radiation deposits energy in the matter being irradiated. The quantity used to express this is the  absorbed dose , a physical dose quantity that is dependent on the level of incident radiation and the absorption properties of the irradiated object. Absorbed dose is a physical quantity, and is not a satisfactory indicator of biological effect, so to allow consideration of the stochastic radiological risk, the dose quantities equivalent dose and effective dose were devised by the  International Commission on Radiation Units and Measurements  (ICRU) and the ICRP to calculate the biological effect of an absorbed dose."}
{"_id": "WikiPedia_Radiology$$$corpus_1421", "text": "To obtain an effective dose, the calculated absorbed organ dose  D T  is first corrected for the radiation type using factor  W R  to give a weighted average of the equivalent dose quantity  H T  received in irradiated body tissues, and the result is further corrected for the tissues or organs being irradiated using factor  W T , to produce the effective dose quantity  E ."}
{"_id": "WikiPedia_Radiology$$$corpus_1422", "text": "The sum of effective doses to all organs and tissues of the body represents the effective dose for the whole body. If only part of the body is irradiated, then only those regions are used to calculate the effective dose. The tissue weighting factors summate to 1.0, so that if an entire body is radiated with uniformly penetrating external radiation, the effective dose for the entire body is equal to the equivalent dose for the entire body."}
{"_id": "WikiPedia_Radiology$$$corpus_1423", "text": "The ICRP tissue weighting factors are given in the accompanying table, and the equations used to calculate from either absorbed dose or equivalent dose are also given."}
{"_id": "WikiPedia_Radiology$$$corpus_1424", "text": "Some tissues like bone marrow are particularly sensitive to radiation, so they are given a weighting factor that is disproportionately large relative to the fraction of body mass they represent. Other tissues like the hard bone surface are particularly insensitive to radiation and are assigned a disproportionally low weighting factor."}
{"_id": "WikiPedia_Radiology$$$corpus_1425", "text": "Calculating from the equivalent dose:"}
{"_id": "WikiPedia_Radiology$$$corpus_1426", "text": "Calculating from the absorbed dose:"}
{"_id": "WikiPedia_Radiology$$$corpus_1427", "text": "Where"}
{"_id": "WikiPedia_Radiology$$$corpus_1428", "text": "The ICRP tissue weighting factors are chosen to represent the fraction of health risk, or biological effect, which is attributable to the specific tissue named. These weighting factors have been revised twice, as shown in the chart above."}
{"_id": "WikiPedia_Radiology$$$corpus_1429", "text": "The United States  Nuclear Regulatory Commission  still uses the ICRP's 1977 tissue weighting factors in their regulations, despite the ICRP's later revised recommendations. [ 15 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1430", "text": "Ionizing radiation is generally harmful and potentially lethal to living things but can have health benefits in  radiation therapy  for the treatment of cancer and  thyrotoxicosis . Its most common impact is the  induction of cancer  with a  latent period  of years or decades after exposure. High doses can cause visually dramatic  radiation burns , and/or rapid fatality through  acute radiation syndrome . Controlled doses are used for  medical imaging  and  radiotherapy ."}
{"_id": "WikiPedia_Radiology$$$corpus_1431", "text": "The UK  Ionising Radiations Regulations 1999  defines its usage of the term effective dose; \"Any reference to an effective dose means the sum of the effective dose to the whole body from external radiation and the committed effective dose from internal radiation.\" [ 19 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1432", "text": "The US  Nuclear Regulatory Commission  has retained in the US regulation system the older term  effective dose equivalent  to refer to a similar quantity to the ICRP effective dose. The NRC's  total effective dose equivalent  (TEDE) is the sum of external effective dose with internal committed dose; in other words all sources of dose."}
{"_id": "WikiPedia_Radiology$$$corpus_1433", "text": "In the US, cumulative equivalent dose due to external whole-body exposure is normally reported to nuclear energy workers in regular dosimetry reports."}
{"_id": "WikiPedia_Radiology$$$corpus_1434", "text": "The concept of effective dose was introduced in 1975 by Wolfgang Jacobi (1928\u20132015) in his publication \"The concept of an effective dose: a proposal for the combination of organ doses\". [ 6 ] [ 20 ]  It was quickly included in 1977 as \u201ceffective dose equivalent\u201d into Publication 26 by the ICRP. In 1991, ICRP publication 60 shortened the name to \"effective dose.\" [ 21 ]  This quantity is sometimes incorrectly referred to as the \"dose equivalent\" because of the earlier name, and that misnomer in turn causes confusion with  equivalent dose . The tissue weighting factors were revised in 1990 and 2007 due to new data."}
{"_id": "WikiPedia_Radiology$$$corpus_1435", "text": "At the ICRP 3rd International Symposium on the System of Radiological Protection in October 2015, ICRP Task Group 79 reported on the \"Use of Effective Dose as a Risk-related Radiological Protection Quantity\"."}
{"_id": "WikiPedia_Radiology$$$corpus_1436", "text": "This included a proposal to discontinue use of equivalent dose as a separate protection quantity. This would avoid confusion between equivalent dose, effective dose and dose equivalent, and to use absorbed dose in Gy as a more appropriate quantity for limiting deterministic effects to the eye lens, skin, hands & feet. [ 22 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1437", "text": "It was also proposed that effective dose could be used as a rough indicator of possible risk from medical examinations. These proposals will need to go through the following stages:"}
{"_id": "WikiPedia_Radiology$$$corpus_1438", "text": "M.A. Boyd.  \"The Confusing World of Radiation Dosimetry - 9444\"   (PDF) .  US Environmental Protection Agency . Archived from  the original   (PDF)  on 2016-12-21 . Retrieved  2014-05-26 . \u00a0\u2013  an account of chronological differences between USA and ICRP dosimetry systems"}
{"_id": "WikiPedia_Radiology$$$corpus_1439", "text": "Electron resonance imaging  ( ERI ) is a  preclinical imaging  method, together with  positron emission tomography  (PET),  computed tomography scan  (CT scan),  magnetic resonance imaging  (MRI), and other techniques. ERI is dedicated to imaging small laboratory animals, and its unique feature is the ability to detect  free radicals . [ 1 ] [ 2 ]  This technique could also be used for other purposes, such as material science, quality of food, etc. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1440", "text": "For  in vivo  imaging purposes, ERI is a minimally invasive method. It requires an intravenous injection of external substances called  spin probes [ 4 ]  (usually nitroxide or triarylmethyl compounds). The main advantage of ERI modality is the ability to map the tissue microenvironment parameters, e.g., oxygen partial pressure (pO2), redox status,  oxidative stress , thiol concentration,  pH , inorganic phosphorus, viscosity, etc. [ 5 ] [ 6 ] [ 7 ] [ 8 ]  ERI is commonly used to research in the areas of  oncology ,  neurodegenerative disorders , and drug development."}
{"_id": "WikiPedia_Radiology$$$corpus_1441", "text": "ERI is a preclinical application of electron paramagnetic resonance imaging (EPRI). [ 9 ] [ 2 ]  The term \"ERI\" was introduced to distinguish a commercial device from EPRI devices normally used in the academic domain."}
{"_id": "WikiPedia_Radiology$$$corpus_1442", "text": "Electron paramagnetic resonance  (EPR) spectroscopy is dedicated to researching substances with unpaired electrons. It was first introduced in 1944, approximately the same time as a similar phenomenon -  nuclear magnetic resonance  (NMR). [ 10 ] [ 11 ]  Owing to hardware and software limitations, EPR was not developing as rapidly as NMR. This led to a huge gap between these two methods. Therefore, to underline a breakthrough in preclinical imaging by presenting EPRI as a complementary method to the present ones, the term \"ERI\" was introduced. [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1443", "text": "One of the many possible applications of ERI is the ability to measure the absolute value of oxygen. [ 12 ]  The width of the EPR signal from oxygen-sensitive spin probes depends linearly on tissue oxygen concentration. [ 13 ]  Therefore, the information about the oxygen value is collected directly from the examined areas. Oxygen mapping is commonly used to plan and improve the effectiveness of radiotherapy treatments. [ 14 ] [ 15 ]  Trityl spin probes are the most suitable for use in oxygen imaging. [ 16 ] [ 17 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1444", "text": "The unique property of ERI is the ability to track  reactive oxygen species  (ROS). [ 18 ]  Those particles are versatile and are constantly generated in living organisms. ROS plays a special role in oxidative and reduction mechanisms. In a normal physiological state, the number of ROS is controlled by  antioxidants . Factors that increase the number of ROS (e.g., ionizing radiation, metal ions, etc.) will cause their overproduction. Therefore, this state leads to an imbalance between those particles and is called oxidative stress. [ 19 ] [ 20 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1445", "text": "ERI allows for dynamic measurements and 3D tracking of the spin probe. [ 6 ]  In this case, the term \"dynamics\" refers to the fast repetition of the imaging process and the tracking of changes in the signal intensity for each location imaged over time. Due to the method's high temporal resolution and sensitivity, it is possible to distinguish both the inflow and outflow phases of the spin probe, the bio-distribution, and the time to reach a maximum concentration of the spin probe. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1446", "text": "In natural conditions, free radicals are characterised by an extremely short lifespan, so to capture the EPR signal, an external molecule with a stable free radical must be delivered. Usually, it happens when an injection is made into the animal's body. Two main classes of spin probes are used for imaging: nitroxide and triaryl methyl (TAM, trityl) radicals."}
{"_id": "WikiPedia_Radiology$$$corpus_1447", "text": "Nitroxide radicals are sensitive to oxygen concentration, pH, thiol concentrations, viscosity, and polarity. [ 2 ]  The issue with these spin probes is their fast reduction, which sometimes leads to loss of the EPR signal. Triarylmethyl radicals are characterised by far longer lifespans and increased stability towards reducing and oxidising biological agents. They are perfect for measuring oxygen concentration, pH, thiol concentrations, inorganic phosphate, and redox status."}
{"_id": "WikiPedia_Radiology$$$corpus_1448", "text": "Although the aforementioned spin probes are the most popular choice, many more can be used in ERI. One of many examples is  melanin  \u2013 a polymeric pigment that contains a mixture of eumelanin and pheomelanin. [ 21 ] [ 22 ]  This is the only substance that occurs in natural conditions and allows for the registration of the EPR signal without the need to deliver extraneous spin probes."}
{"_id": "WikiPedia_Radiology$$$corpus_1449", "text": "The  empty delta sign  is a  radiologic sign  seen on brain imaging which is associated with  cerebral venous sinus thrombosis . It is usually seen on  magnetic resonance imaging  (MRI) or  computed tomography  (CT) scans with contrast. It is seen as  dural wall  enhancement in the absence of intra-sinus enhancement (there is no enhancement in the lumen of the dural sinus). [ 1 ]   This is due to the presence of a  blood clot  in the  dural venous sinuses . The dural venous sinuses drain blood from the  brain  to the  internal jugular veins , which in turn drains blood to the heart. It has been proposed that the empty delta sign occurs in dural venous thromboses due to contrast material filling the dural venous collateral circulation immediately surrounding the dura whilst being unable to fill the intra-dural sinus space due to the presence of a blood clot. [ 2 ]  The  superior sagittal sinus  is most commonly affected, but the radiologic sign may also be seen in the  transverse sinuses . [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1450", "text": "This  neuroscience  article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Radiology$$$corpus_1451", "text": "EOS  is a  medical imaging  system designed to provide frontal and lateral  radiography  images, while limiting the  X-ray   dose absorbed  by the patient in a sitting or standing position. The system relies on the high sensitivity of a detector ( multi-wire chamber ) invented by  Georges Charpak , which earned him the 1992  Nobel prize . This technology not only enhances patient safety but also improves diagnostic accuracy, making EOS particularly valuable in monitoring musculoskeletal conditions and guiding orthopedic treatments."}
{"_id": "WikiPedia_Radiology$$$corpus_1452", "text": "EOS is commercialized by the French company  EOS imaging  as an  orthopedic  application whose main feature is the 3D visualization of the  vertebral column  and/or lower limbs of the patients. The device develops statistical models by collecting anteroposterior and lateral 2D images of an individuals entire body.  [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1453", "text": "EOS focuses on using an approach that centers around precision medicine, or a medical approach that considers a patient's genetics, environmental factors, and health habits in order to create a more personalized treatment or diagnosis for disease.  [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1454", "text": "These images can be used to image the electrical activity within the cells of hearts. [ 3 ]  Richard Barr, a Duke University biomedical engineer, created a computer program  that creates a simulation environment to model the electrical activity within cardiac cells. This allows for medical professionals to gain a deeper understanding of the heart's functionality without an incision needing to be made, because activity among these cells is non-linear and unpredictable. By visualizing the behavior of cardiac cells, this program helps improve our understanding of the human heart, which will improve our ability to develop personalized treatment for heart disease."}
{"_id": "WikiPedia_Radiology$$$corpus_1455", "text": "Another technique, coined by Elizabeth Bucholz, focuses on a four-dimensional imaging technique using pre-existing MRI technology for mice. This technique involves injecting the liposomal agent into the bloodstream, and then the tool captures images of the heart over time. Once the images are collected, a 4D model of the heart is created, allowing the researchers to analyze the heart's performance and other important health factors. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1456", "text": "EOS offers many more advantages over any other medical imaging techniques. For example, the ability to create 3D reconstructions from its data, a lower dose of radiation, and whole body imaging.  [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1457", "text": "EOS imaging  is a medical device company based in  Paris, France , that designs, develops, and markets EOSedge and the EOS system, innovative, orthopedic medical imaging systems, associated with several orthopedic solutions along the patient care pathway \u2013 from  diagnosis  to post-operative treatments. The EOS platform targets  musculoskeletal disorders  and  orthopedic surgical care  through 2D  X-ray  scans and 3D skeletal models from stereo-radiographic images of patients in a seated or standing position."}
{"_id": "WikiPedia_Radiology$$$corpus_1458", "text": "The philosophy of EOS imaging surrounds three main principles: reduction of the  radiation  dose emitted by the technology, relevance and manipulability of calculated clinical parameters, and optimization of the patient care workflow. Currently, over 300 EOS systems are installed in medical centers in 51 different countries, including the United States, Japan, Korea, China, and throughout the European Union."}
{"_id": "WikiPedia_Radiology$$$corpus_1459", "text": "The EOS imaging technology stems from the scientific findings of  Georges Charpak  ( Nobel Prize in Physics , 1992) concerning radiation detection and  particle physics , especially the  multi-wire chamber . [ 1 ]  Since then, physicists, engineers, radiologists, and surgeons have collaborated to transform these findings into a new technology called the EOS system."}
{"_id": "WikiPedia_Radiology$$$corpus_1460", "text": "EOS imaging began in 1989 as Biospace Med, a medical company founded by Georges Charpak for the development of his detection technology. In 1999, Marie Meynadier became the CEO of Biospace Med; she developed the company's first subsidiary dedicated to imaging solutions for pre-clinical research \u2013 the EOS system."}
{"_id": "WikiPedia_Radiology$$$corpus_1461", "text": "In 2004, hospitals in Paris, France and Brussels, Belgium finished running clinical tests on the EOS prototype, and in 2005, the first fundraising efforts commenced with the company's first venture capital round."}
{"_id": "WikiPedia_Radiology$$$corpus_1462", "text": "From 2007 to 2011, the company obtained  CE marking  in Europe and  FDA  approval to market the EOS system and the sterEOS 2D/3D workstation in the United States."}
{"_id": "WikiPedia_Radiology$$$corpus_1463", "text": "The first installations of EOS in European and North American hospitals and clinics occurred from 2008 to 2010. In 2011, the EOS system was being integrated into clinical routines of medical centers in 10 countries, including the United States, Canada, and Australia."}
{"_id": "WikiPedia_Radiology$$$corpus_1464", "text": "In 2010, Biospace Med changed its name to EOS imaging."}
{"_id": "WikiPedia_Radiology$$$corpus_1465", "text": "In 2012, EOS imaging entered the  Euronext Paris  stock exchange (name: EOSI) and had its first installation in Asia."}
{"_id": "WikiPedia_Radiology$$$corpus_1466", "text": "In 2013, EOS acquired the medical company oneFIT Medical (see Acquisition of oneFIT Medical).\nIn 2014, EOS provided the EOS system in the Vietnam market (Medic - Medic Hoa Hao) through Bluelight."}
{"_id": "WikiPedia_Radiology$$$corpus_1467", "text": "In 2015, the CFDA certification in China and the NECA designation in Korea were obtained, allowing the company to further expand its market."}
{"_id": "WikiPedia_Radiology$$$corpus_1468", "text": "In 2016, the company entered into the Latin American market with the signing of its first contract in Brazil."}
{"_id": "WikiPedia_Radiology$$$corpus_1469", "text": "In 2019, the company launched EOSedge, its new generation imaging system powered by photon-counting technology."}
{"_id": "WikiPedia_Radiology$$$corpus_1470", "text": "While based in Paris, France, EOS imaging has five other corporate locations in various regions around the world:  Besan\u00e7on, France ;  St. Paul, Minnesota , US;  Montreal, Quebec , Canada;  Frankfurt, Germany , and in  Singapore ."}
{"_id": "WikiPedia_Radiology$$$corpus_1471", "text": "In 2013, EOS imaging acquired oneFIT Medical (based in Besan\u00e7on, France), a  medical software  engineering and manufacturing company dedicated to the development of  surgical planning  software for spine, hip, and knee surgeries and patient-specific orthopedic surgical cutting guides. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1472", "text": "EOS imaging platforms\u2014EOSedge and EOS\u2014deliver unique and specific capabilities that are used in conjunction with EOS Advanced Orthopedic Solutions to generate highly accurate 3D representations of patient anatomy and enable a seamless surgical planning experience."}
{"_id": "WikiPedia_Radiology$$$corpus_1473", "text": "The EOS examination takes place in an upright scanning cabin where the patient can either stand or sit. With a vertically traveling arm supporting two fine X-ray beams perpendicular to one another, the EOS system acquires frontal and lateral, weight-bearing images of the patient in a functional \u2013 standing or sitting \u2013 position. These biplanar images are then used to create a 3D model of the patient's skeleton."}
{"_id": "WikiPedia_Radiology$$$corpus_1474", "text": "The ALARA principle (As Low As Reasonably Achievable) represents a movement to \u201cminimize radiation doses and releases of radioactive materials\u201d by minimizing the time of exposure to radiation, increasing the distance between the human body and the radiation source, and using absorber materials to shield the body from  beta particles , X-rays, and  gamma rays . [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1475", "text": "EOS imaging aligns itself with this principle, providing reduced exam times and amounts of radiation in comparison with conventional imaging systems. [ 4 ] [ 5 ]  Furthermore, EOS developed a Micro Dose option that further reduced the radiation exposure by 5.5 times compared to a typical low-dose EOS exam protocol, resulting in a nearly negligible radiation dose. [ 6 ]  Additionally, with Flex Dose technology, EOSedge can deliver up to an 80% overall radiation reduction compared to same acquisition without Flex Dose."}
{"_id": "WikiPedia_Radiology$$$corpus_1476", "text": "Having reduced-radiation options available for patients has become critical in the world of medical imaging as radiation exposure from artificial sources, such as medical imaging, has increased over the last two decades, [ 7 ]  and many patients require multiple examinations throughout the course of their medical treatment."}
{"_id": "WikiPedia_Radiology$$$corpus_1477", "text": "The sterEOS workstation enables the generation of patient-specific 3D models of the spine and/or lower limbs from weight-bearing low dose or Micro Dose EOS exams. Once the models are created, clinical parameters are automatically calculated and may be exported as a patient report including 2D images and 3D captures. This report is used by physicians for diagnosis, post-operative assessment, and patient follow-up. sterEOS also enables the exportation of 3D anatomical biomarkers for pre-operative planning."}
{"_id": "WikiPedia_Radiology$$$corpus_1478", "text": "The EOSapps (kneeEOS, hipEOS, and spineEOS) are online, 3D surgical planning solutions based on the weight-bearing EOS images. Frontal and lateral EOS images are uploaded to the EOS Portal, where the EOS 3DServices team prepares the 3D models and dataset and makes the planning case available online. Surgeons can have access to the patient's anatomy information in 3D, with which they can plan and simulate the effect of different implant selections and positions in 3D. spineEOS is used to plan spine surgeries, hipEOS is used for the planning of  total hip arthroplasty , and kneeEOS is geared towards the planning of  total knee arthroplasty ."}
{"_id": "WikiPedia_Radiology$$$corpus_1479", "text": "The  European Day of Radiology  (EDoR) is an annual day of action that will take place for the first time on February 10, 2011. The day is an initiative of the  European Society of Radiology , an organisation that represents the interests of radiology and its practitioners throughout Europe and also hosts the  European Congress of Radiology ."}
{"_id": "WikiPedia_Radiology$$$corpus_1480", "text": "The European Day of  Radiology  will be held for the first time on February 10, 2011, in honour of the anniversary of the death of  Wilhelm Conrad R\u00f6ntgen , who first discovered  x-rays .\nThe goal of the EDoR is to celebrate the achievements and benefits of  radiology  from its beginnings up to the present day and to raise public awareness."}
{"_id": "WikiPedia_Radiology$$$corpus_1481", "text": "National radiological societies from Austria, Belgium, the Czech Republic, Croatia, France, Georgia, Hungary, Ireland, Italy, Lithuania, the Netherlands, Poland, Portugal, Romania, Spain, Sweden, Switzerland, Turkey and the United Kingdom are taking part in this initiative."}
{"_id": "WikiPedia_Radiology$$$corpus_1482", "text": "In Ireland, the First European Day of Radiology will be celebrated by the Faculty of Radiologists,  Royal college of Surgeons , and in the UK by the  Royal College of Radiologists . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1483", "text": "The  International Day of Radiology  is the successor to the European Day of Radiology which was established in 2011. The first and only European Day of Radiology was held on February 10, 2011, to commemorate the anniversary of  R\u00f6ntgen's  death."}
{"_id": "WikiPedia_Radiology$$$corpus_1484", "text": "In  diagnostic radiology , the  F-factor  is the  conversion factor  between  exposure  to  ionizing radiation  and the  absorbed dose  from that radiation. In other words, it converts between the amount of  ionization  in air ( roentgens  or, in  SI units ,  coulombs  per kilogram of absorber material) and the absorbed dose in air ( rads  or  grays ).  The two determinants of the F-factor are the  effective atomic number  (Z) of the material and the type of ionizing radiation being considered.  Since the effective Z of air and  soft tissue  is approximately the same, the F-factor is approximately 1 for many  x-ray imaging  applications.  However,  bone  has an F-factor of up to 4, due to its higher effective Z."}
{"_id": "WikiPedia_Radiology$$$corpus_1485", "text": "Bushberg et al.,  2002.   The Essential Physics of Medical Imaging.   Philadelphia: Lippincott Williams & Wilkins. (p.\u00a055)"}
{"_id": "WikiPedia_Radiology$$$corpus_1486", "text": "Focal spot blooming  is the unwanted change in the focal spot size of an  X-ray tube  during change in exposure. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1487", "text": "Focal spot blooming is caused due to increased  mAs . When high exposure setting are used, the electron beam from the cathode fail to focus on a particular point because of electrostatic repulsion. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1488", "text": "Forensic radiology  is the discipline which comprises the performance, interpretation and reportage of the  radiological  examinations and procedures which are needed in court procedures or  law enforcement . [ 1 ]  Radiological methods are widely used in  identification ,  age estimation  and establishing  cause of death . \nComparison of ante mortem and post mortem radiographs is one of the means of identification. [ 2 ]  The scanning of baggage, vehicles and individuals have many applications."}
{"_id": "WikiPedia_Radiology$$$corpus_1489", "text": "Tools like multislice helical computed tomography can be used for detailed documentation of injuries, tissue damage and complications like  air embolism  and  pulmonary aspiration  of blood. These types of digital autopsies offer certain advantages when compared to traditional  autopsies . [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1490", "text": "G-arm medical imaging  systems are based on  fluoroscopic X-ray  and are used for a variety of  diagnostic imaging  and minimally invasive  surgical procedures . The name is derived from the G-shaped arm used to connect two  X-ray generators  and two X-ray detectors,  image intensifiers  or digital  flat panel detectors , to one another. The main advantage of the G-arm, compared to a conventional  C-arm system , is that it combines a pair of X-ray chains facilitating simultaneous views in two  perpendicular  planes, also called G-arm imaging."}
{"_id": "WikiPedia_Radiology$$$corpus_1491", "text": "Fluoroscopic X-ray  is used for a variety of  diagnostic imaging  and minimally invasive  surgical procedures . For surgery it is practical to use a mobile C-arm system where the  x-ray generator  and  x-ray detector  are placed on a C-shaped arm positioned directly opposite from and aligned centrally to each other. The C-arm can be moved horizontally, vertically and around the swivel axes, so that X-ray images of the patient can be produced from different angles. The disadvantage of the C-arm is that imaging is limited to only one plane at a time."}
{"_id": "WikiPedia_Radiology$$$corpus_1492", "text": "For precision  surgery procedures , for example in  orthopedics , [ 1 ]  it is necessary to generate a view of the surgical site from two  perpendicular  viewing positions, usually a  frontal  and a  lateral  view. With a C-arm system this can only be achieved by manually repositioning the C-arm for the second view. This can be challenging due to the presence of  sterile drapes  and other surgical devices. Bringing the x-ray generator from a  non-sterile area , underneath the  operating table  to a horizontal position close do the patient can compromise the sterility of the surgical area and increase the risks of  infections .\nShifting the C-arm must normally be done many times during the surgical procedure, taking additional time and increasing the  radiation exposure  to patient and staff. \nWith the G-arm the stand can stay in a fixed position during the entire surgical procedure as both imaging planes can be viewed simultaneously. Benefits are shorter procedures, [ 2 ] [ 3 ]  higher accuracy, [ 4 ] [ 5 ] [ 6 ]  and  lower radiation exposure. [ 7 ] [ 8 ] [ 9 ]  The fixed position of the stand also ensures a better  sterility."}
{"_id": "WikiPedia_Radiology$$$corpus_1493", "text": "A G-arm medical imaging system is typically composed by the following basic elements:"}
{"_id": "WikiPedia_Radiology$$$corpus_1494", "text": "A .\tA movable stand"}
{"_id": "WikiPedia_Radiology$$$corpus_1495", "text": "B .\tX-ray source and detector for the frontal view."}
{"_id": "WikiPedia_Radiology$$$corpus_1496", "text": "C. \tX-ray source and detector for the lateral view"}
{"_id": "WikiPedia_Radiology$$$corpus_1497", "text": "D. \tPatient table with extensions (here shown in position for a hip surgery)"}
{"_id": "WikiPedia_Radiology$$$corpus_1498", "text": "E. \tControl unit with post-processing image software [ 10 ]  and displays for the two perpendicular imaging planes"}
{"_id": "WikiPedia_Radiology$$$corpus_1499", "text": "X-ray detectors, the height of the stand and the angle of the G-Arm may be motorized or manually moved for fine adjustment of the  iso-center  of the x-ray beams."}
{"_id": "WikiPedia_Radiology$$$corpus_1500", "text": "Due to the benefits resulting from the ability to simultaneously view two perpendicular planes G-arm Medical Imaging systems are mainly used for  orthopedic  and  traumatic surgery  procedures, such as  hips ,  knees  and  spine ."}
{"_id": "WikiPedia_Radiology$$$corpus_1501", "text": "The G-Arm Imaging system is originating from a patented invention [ 11 ]  from 1970 by the Swedish company  Saab AB , an aerospace and automobile manufacturer who at that time also was active within   the field of medical devices.\nIn the original product the two x-ray chains were placed in an annular stand. The product, called Multiplane, had some practical disadvantages due to the closed form of the stand. Later a part of the annular stand was cut out and the G-arm was born."}
{"_id": "WikiPedia_Radiology$$$corpus_1502", "text": "The G-Arm concept has been gradually developed to its current form. In 2002 the concept was acquired by the company Scanflex Healthcare AB based in Stockholm, Sweden who has refined the product and is marketing it worldwide under the trademark, Biplanar (trademark registration cancelled 2011). [ 12 ]  The G-Arm concept was also adopted in 2011 by Beijing East Whale Imaging Tech Co., who hold the registered trademarks for G-Arm and MultiScan G-Arm System under this category [ 13 ] [ 14 ]  and a number of related patents. [ 15 ]  The company was founded in 1998 and is based in Beijing, China. Whale Imaging Inc, its R&D and marketing headquarters, is based near Boston, USA. [ 16 ]  The Whale G-Arm received a Spine Technology award in 2014. [ 17 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1503", "text": "Global radiology , a subspecialty of  diagnostic radiology , [ 1 ]  comprises the study and practice of improving access to radiology resources in poor and developing countries, and addressing global health inequities through the application of radiology. [ 2 ]  Similar to the fields of  public health  and  global health , global radiology draws on and encourages collaboration with nonmedical specialties relevant to disease patterns and the provision of medical services, including  economic development ,  biomedical technology ,  engineering  and  social sciences . [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1504", "text": "According to the  World Health Organization , [ 3 ]  one half to two-thirds of the  global population  lacks access to radiological services due primarily to shortages in diagnostic equipment and trained personnel. The practice of global outreach radiology, as well as education and training programs related to global radiology, have been spearheaded by organizations including the  American College of Radiology , [ 4 ]  the  Radiological Society of North America , [ 5 ]  the  American Roentgen Ray Society , [ 6 ]  the  Royal College of Radiologists , [ 7 ]  the  International Union of Interventional Radiologists ,  Imaging the World  and the  World Federation of Pediatric Imaging . Growing interest in  global health  among radiology  resident  physicians [ 8 ]  has spurred some radiology  residency  programs to offer global health training. [ 9 ] [ 10 ] [ 11 ]  In 2014, the  American College of Radiology  proposed a formal \u201cglobal health imaging curriculum\u201d for residents. [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1505", "text": "The academic component of global radiology involves the study of obstacles to obtaining access to imaging services and technology, and research on efforts to improve  global health  through  radiology . This work encompasses both  original research  using data collected through radiology outreach projects in specific locales, [ 13 ]  and broader  epidemiological  assessments informed by imaging data. [ 14 ]  Conferences, such as the world congresses hosted by the  International Society of Radiographers and Radiological Technologists , offer academics and non-academics involved in global radiology an opportunity to \u201cdiscuss data, experiences, and models pertaining to radiology in the developing world and to evaluate potential opportunities for future collaboration.\u201d [ 15 ]  While much of the research published has appeared in various radiology journals, in 2014 the  Journal of Global Radiology ,  founded by Dr. Sarwat Hussain of  University of Massachusetts Medical School , became the first journal dedicated to global radiology. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1506", "text": "The  gloved finger sign  is a  radiologic sign  observed on  chest radiographs  or  CT scans  that indicates the presence of mucoid impaction in the lungs. Mucoid impaction occurs when  bronchi  become dilated and filled with mucus. This abnormality appears as branching tubular opacities projecting out from the  hila  towards the periphery of the lungs, resembling gloved fingers. [ 1 ]  The gloved finger sign has been observed in the imaging of several conditions, including bronchial atresia,  cystic fibrosis ,  bronchiectasis ,  allergic bronchopulmonary aspergillosis ,  foreign body aspiration , benign tumors, and malignancies. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1507", "text": "GXMO  (also fashioned as  GxMO  or  GxmO [ 1 ] ) is an  acronym  for  G eneral  X -Ray  M achine  O perator license. [ 2 ]  It may also refer to the licensing exam. [ 1 ]  Persons who possess this license may add this acronym after their name to demonstrate their qualification."}
{"_id": "WikiPedia_Radiology$$$corpus_1508", "text": "The  Hirtz compass  is a medical device previously used to determine the location and aid the removal of  bullets  and  shrapnel  in a patient's body. [ 1 ] [ 2 ]  The device would be used by a  surgeon  who would, with the help of  x-ray photographs , precisely remove the foreign object. [ 2 ]  The device would usually give a location within 1 or 2 millimeters of the foreign object. [ 3 ]  At its peak, the  average  rate of projectile removal when the device was used by local surgeons reached approximately 90%. [ 4 ]  The device was extensively used during  World War I ."}
{"_id": "WikiPedia_Radiology$$$corpus_1509", "text": "The Hirtz compass was invented in 1907 by  E. J. Hirtz , a  French   radiologist  working at a military hospital. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1510", "text": "First, the compass is carefully secured and the penetration needle is brought in contact with the skin. The compass will then give the location of the incision and the depth and direction of the projectile. The compass is then removed and an incision is made in the indicated direction. The surgeons left index finger is put into the wound and the compass is secured in place above the surgeon's left hand. The indicator needle is then pressed into the route prepared by the left index. At the point where the indicator needle ends, the surgeon should be able to feel the bullet which can then be removed. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1511", "text": "The procedure requires a large area of skin to be left uncovered, which is sometimes an inconvenience for the surgeon. The main problem with the device is the fact that the patient's soft body parts can change shape and thus give inaccurate results. When the projectile is to be extracted from muscular tissue, the procedure must be done with completely relaxed muscles, therefore needing complete anesthesia. Otherwise, the contractions would displace the foreign object making removal with the aid of the compass difficult. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1512", "text": "The  history of radiation protection  begins at the turn of the 19th and 20th centuries with the realization that  ionizing radiation  from natural and artificial sources can have harmful effects on living organisms. As a result, the study of radiation damage also became a part of this history."}
{"_id": "WikiPedia_Radiology$$$corpus_1513", "text": "While  radioactive materials  and X-rays were once handled carelessly, increasing awareness of the dangers of  radiation  in the 20th century led to the implementation of various preventive measures worldwide, resulting in the establishment of radiation protection regulations. Although  radiologists  were the first victims, they also played a crucial role in advancing radiological progress and their sacrifices will always be remembered. Radiation damage caused many people to suffer amputations or die of cancer. The use of radioactive substances in everyday life was once fashionable, but over time, the health effects became known. Investigations into the causes of these effects have led to increased awareness of protective measures. The dropping of  atomic bombs  during  World War II  brought about a drastic change in attitudes towards radiation. The effects of natural  cosmic radiation , radioactive substances such as  radon  and  radium  found in the environment, and the potential health hazards of non-ionizing radiation are well-recognized. Protective measures have been developed and implemented worldwide, monitoring devices have been created, and radiation protection laws and regulations have been enacted."}
{"_id": "WikiPedia_Radiology$$$corpus_1514", "text": "In the 21st century, regulations are becoming even stricter. The permissible limits for ionizing radiation intensity are consistently being revised downward. The concept of radiation protection now includes regulations for the handling of  non-ionizing  radiation."}
{"_id": "WikiPedia_Radiology$$$corpus_1515", "text": "In the Federal Republic of Germany, radiation protection regulations are developed and issued by the  Federal Ministry for the Environment, Nature Conservation, Nuclear Safety and Consumer Protection  (BMUV). The  Federal Office for Radiation Protection  is involved in the technical work. [ 2 ]  In  Switzerland , the Radiation Protection Division of the  Federal Office of Public Health  is responsible, [ 3 ]  and in  Austria , the  Ministry of Climate Action and Energy . [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1516", "text": "The discovery of  X-rays  by  Wilhelm Conrad R\u00f6ntgen  (1845-1923) in 1895 led to extensive experimentation by scientists, physicians, and inventors. The first X-ray machines produced extremely unfavorable radiation spectra for imaging with extremely high skin doses. [ 5 ]  In February 1896, John Daniel and  William Lofland Dudley  (1859\u20131914) of  Vanderbilt University  conducted an experiment in which Dudley's head was X-rayed, resulting in hair loss.  Herbert D. Hawks , a graduate of  Columbia University , suffered severe burns on his hands and chest during demonstration experiments with X-rays. [ 6 ] [ 7 ]   Burns  and  hair loss  were reported in scientific journals.  Nikola Tesla  (1856\u20131943) was one of the first researchers to explicitly warn of the potential dangers of X-rays in the  Electrical Review  on May 5, 1897 - after initially claiming them to be completely harmless. He suffered massive radiation damage after his experiments. [ 8 ]  Nevertheless, some doctors at the time still claimed that X-rays had no effect on humans. [ 9 ]  Until the 1940s, X-ray machines were operated without any protective safeguards. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1517", "text": "R\u00f6ntgen himself was spared the fate of the other X-ray users by habit. He always carried the unexposed photographic plates in his pockets and found that they were exposed if he remained in the same room during the exposure. So he regularly left the room when he took X-rays. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1518", "text": "The use of X-rays for diagnostic purposes in  dentistry  was made possible by the pioneering work of  C. Edmund Kells  (1856-1928), a New Orleans dentist who demonstrated them to dentists in Asheville, North Carolina, in July 1896. [ 10 ]  Kells committed suicide after suffering from radiation-induced cancer for many years. He had been amputated one finger at a time, later his entire hand, followed by his forearm and then his entire arm."}
{"_id": "WikiPedia_Radiology$$$corpus_1519", "text": "Otto Walkhoff  (1860-1934), one of the most important German dentists in history, took X-rays of himself in 1896 and is considered a pioneer in dental radiology. He described the required exposure time of 25 minutes as an \"ordeal\". Braunschweig's medical community later commissioned him to set up and supervise a central X-ray facility. In 1898, the year radium was discovered, he also tested the  use of radium  in medicine in a self-experiment using an amount of 0.2 grams of  radium bromide . Walkhoff observed that cancerous mice exposed to radium radiation died significantly later than a control group of untreated mice. He thus initiated the development of radiation research for the treatment of  tumors . [ 11 ] [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1520", "text": "The Armenian-American radiologist  Mihran Krikor Kassabian  (1870-1910), vice president of the  American Roentgen Ray Society  (ARRS), was concerned about the irritating effects of X-rays. In a publication, he mentioned his increasing problems with his hands. Although Kassabian recognized X-rays as the cause, he avoided making this reference so as not to hinder the progress of radiology. In 1902, he suffered a severe radiation burn on his hand. Six years later, the hand became  necrotic  and two fingers of his left hand were amputated. Kassabian kept a diary and photographed his hands as the tissue damage progressed. He died of cancer in 1910. [ 13 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1521", "text": "Many of the early X-ray and radioactivity researchers went down in history as \"martyrs for science.\" In her article,  The Miracle and the Martyrs , Sarah Zobel of the  University of Vermont  tells of a 1920 banquet held to honor many of the pioneers of X-rays. Chicken was served for dinner: \"Shortly after the meal was served, it could be seen that some of the participants were unable to enjoy the meal. After years of working with X-rays, many of the participants had lost fingers or hands due to radiation exposure and were unable to cut the meat themselves\". [ 14 ]  The first American to die from radiation exposure was  Clarence Madison Dally  (1845-1904), an assistant to  Thomas Alva Edison  (1847-1931). Edison began studying X-rays almost immediately after R\u00f6ntgen's discovery and delegated the task to Dally. Over time, Dally underwent more than 100 skin operations due to radiation damage. Eventually, both of his arms had to be amputated. His death led Edison to abandon all further X-ray research in 1904."}
{"_id": "WikiPedia_Radiology$$$corpus_1522", "text": "One of the pioneers was the Austrian  Gustav Kaiser  (1871-1954), who in 1896 succeeded in photographing a double toe with an exposure time of 1\u00bd-2 hours. Due to the limited knowledge at the time, he also suffered severe radiation damage to his hands, losing several fingers and his right metacarpal. His work was the basis for, among other things, the construction of lead rubber aprons. [ 15 ]   Heinrich Albers-Sch\u00f6nberg  (1865-1921), the world's first professor of radiology, recommended gonadal protection for testicles and ovaries in 1903. He was one of the first to protect germ cells not only from acute radiation damage but also from small doses of radiation that could accumulate over time and cause late damage. Albers-Sch\u00f6nberg died at the age of 56 from radiation damage, [ 16 ]  as did  Guido Holzknecht  and  Elizabeth Fleischman ."}
{"_id": "WikiPedia_Radiology$$$corpus_1523", "text": "Since April 4, 1936, a  radiology memorial  in the garden of the  of Hamburg's St. Georg Hospital has commemorated the 359 victims from 23 countries who were among the first medical users of X-rays. [ 17 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1524", "text": "In 1896, the engineer Wolfram Fuchs, based on his experience with numerous X-ray examinations, recommended keeping the exposure time as short as possible, staying away from the tube, and covering the skin with  Vaseline . [ 18 ]  In 1897, Chicago doctors William Fuchs and Otto Schmidt became the first users to have to pay compensation to a patient for radiation damage. [ 19 ] [ 20 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1525", "text": "In 1901, dentist  William Herbert Rollins  (1852-1929) called for using  lead-glass   goggles  when working with X-rays, for the X-ray tube to be encased in lead, and for all areas of the body to be covered with lead aprons. He published over 200 articles on the potential dangers of X-rays, but his suggestions were long ignored. A year later, Rollins wrote in despair that his warnings about the dangers of X-rays were not being heeded by either the industry or his colleagues. By this time, Rollins had demonstrated that X-rays could kill laboratory animals and induce  miscarriages  in guinea pigs. Rollins' achievements were not recognized until later. Since then, he has gone down in the history of radiology as the \"father of radiation protection. He became a member of the  Radiological Society of North America  and its first treasurer. [ 21 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1526", "text": "Radiation protection continued to develop with the invention of new measuring devices such as the  chromoradiometer  by Guido Holzknecht (1872-1931) in 1902, [ 22 ]  the  radiometer  by  Raymond Sabouraud  (1864-1938) and  Henri Noir\u00e9  (1878\u20131937) [ 23 ]  in 1904/05, and the  quantimeter  by  Robert Kienb\u00f6ck  (1873-1951) in 1905, [ 24 ]  which made it possible to determine maximum doses at which there was a high probability that no skin changes would occur.  Radium  was also included by the  British Roentgen Society , which published its first memorandum on radium protection in 1921."}
{"_id": "WikiPedia_Radiology$$$corpus_1527", "text": "Since the 1920s,  pedoscopes  have been installed in many shoe stores in North America and Europe, more than 10,000 in the U.S. alone, following the invention of Jacob Lowe, a Boston physicist. They were X-ray machines used to check the fit of shoes and to promote sales, especially to children. Children were particularly fascinated by the sight of their footbones. X-rays were often taken several times daily to evaluate the fit of different shoes. Most were available in shoe stores until the early 1970s. The  energy dose absorbed  by the customer was up to 116  rads , or 1.16 grays. In the 1950s, when medical knowledge of the health risks was already available, pedoscopes came with warnings that shoe-buyers should not be scanned more than three times a day and twelve times a year. [ 25 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1528", "text": "By the early 1950s, several professional organizations issued warnings against the continued use of shoe-mounted fluoroscopes, including the American Conference of Governmental Industrial Hygienists, the American College of Surgeons, the New York Academy of Medicine, and the American College of Radiology. At the same time, the  District of Columbia  enacted regulations requiring that shoe-mounted fluoroscopes be operated only by a licensed physical therapist. A few years later, the state of  Massachusetts  passed regulations stating that these machines could only be operated by a licensed physician. In 1957, the use of shoe-mounted fluoroscopes was banned by court order in  Pennsylvania . By 1960, these measures and pressure from insurance companies led to the disappearance of the shoe-mounted fluoroscope, at least in the United States. [ 26 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1529", "text": "In Switzerland, there were 1,500 shoe-mounted fluoroscopes in use, 850 were required to be inspected by the  Swiss Electrotechnical Association  by a decree of the  Federal Department of Home Affairs  on October 7, 1963. The last one was decommissioned in 1990. [ 27 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1530", "text": "In Germany, the machines were not banned until 1976.\u00a0 \u00a0The fluoroscopy machine emitted uncontrolled X-rays, which continuously exposed children, parents, and sales staff. The all-wood cabinet of the machine did not prevent the X-rays from passing through, resulting in particularly high cumulative radiation levels for the cashier when the pedoscope was placed near the cash register. The all-wood cabinet of the machine did not prevent the X-rays from passing through, resulting in particularly high cumulative radiation levels for the cashier when the pedoscope was placed near the cash register. It is clear that the machine was not designed with proper safety measures in place, leading to dangerous levels of radiation exposure. The well-established long-term effects of X-rays, including genetic damage and carcinogenicity, suggest that the use of pedoscopes worldwide over several decades may have contributed to health effects.The well-established long-term effects of X-rays, including genetic damage and carcinogenicity, suggest that the use of pedoscopes worldwide over several decades may have contributed to health effects. However, it cannot be definitively proven that they were the sole cause. [ 28 ] [ 29 ]  For example, a direct link has been discussed in the case of basal cell carcinoma of the foot. [ 30 ]  In 1950, a case was published in which a shoe model had to have a leg amputated as a result. [ 31 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1531", "text": "In 1896, Viennese dermatologist  Leopold Freund  (1868-1943) used X-rays to treat patients for the first time. He successfully irradiated the  hairy nevus  of a young girl. In 1897, Hermann Gocht (1869\u20131931) published the treatment of  trigeminal neuralgia  with X-rays, and  Alexei Petrovich Sokolov  (1854-1928) wrote about radiotherapy for  arthritis  in the oldest radiology journal, Advances in the field of X-rays ( R\u00f6Fo ). In 1922, X-rays were recommended as safe for many diseases and for diagnostic purposes. Radiation protection was limited to recommending doses that would not cause  erythema  (reddening of the skin). For example, X-rays were promoted as an alternative to  tonsillectomy . It was also boasted that in 80% of cases of  diphtheria  carriers,  Corynebacterium diphtheriae  was no longer detectable within two to four days. [ 32 ]  In the 1930s,   G\u00fcnther von Pannewitz  (1900\u20131966), a radiologist from Freiburg, Germany, perfected what he called  X-ray stimulation radiation  for degenerative diseases. Low-dose radiation reduces the inflammatory response of tissues. Until about 1960, children with diseases such as  ankylosing spondylitis  or  favus  (head fungus) were irradiated, which was effective but led to increased cancer rates among patients decades later. [ 33 ] [ 34 ]  In 1926, the American pathologist  James Ewing  (1866-1943) was the first to observe bone changes as a result of radiotherapy, [ 35 ]  which he described as  radiation osteitis ( now  Osteoradionecrosis ). [ 36 ]  In 1983, Robert E. Marx stated that osteoradionecrosis is radiation-induced aseptic bone necrosis. [ 37 ] [ 38 ]  The acute and chronic inflammatory processes of osteoradionecrosis are prevented by the administration of steroidal anti-inflammatory drugs. In addition, the administration of  pentoxifylline  and antioxidant treatments, such as  superoxide dismutase  and  tocopherol  (vitamin E) are recommended. [ 39 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1532", "text": "Sonography  (ultrasound diagnostics) is a versatile and widely used imaging modality in medical diagnostics.  Ultrasound  is also used in  therapy . However, it uses  mechanical waves  and no ionizing or non-ionizing radiation. Patient safety is ensured if the recommended limits for avoiding  cavitation  and overheating are observed, see also  Safety Aspects of Sonography ."}
{"_id": "WikiPedia_Radiology$$$corpus_1533", "text": "Even devices that use alternating  magnetic fields  in the  radiofrequency range , such as  magnetic resonance imaging  (MRI), do not use ionizing radiation. MRI was developed as an imaging technique in 1973 by  Paul Christian Lauterbur  (1929-2007) with significant contributions from Sir  Peter Mansfield  (1933-2017). [ 40 ]  Jewelry or piercings can become very hot; on the other hand, a high tensile force is exerted on the jewelry, which in the worst case can cause it to be torn out. To avoid pain and injury, jewelry containing  ferromagnetic  metals should be removed beforehand.  Pacemakers ,  defibrillator  systems, and large  tattoos  in the examination area that contain metallic  color pigments  may heat up or cause second-degree burns or malfunction of the implants. [ 41 ] [ 42 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1534", "text": "Photoacoustic Tomography  (PAT) is a hybrid imaging modality that utilizes the photoacoustic effect without the use of ionizing radiation. It works without contact with very fast laser pulses that generate ultrasound in the tissue under examination. The local absorption of the light leads to sudden local heating and the resulting thermal expansion. The result is broadband acoustic waves. The original distribution of absorbed energy can be reconstructed by measuring the outgoing ultrasound waves with appropriate ultrasound transducers."}
{"_id": "WikiPedia_Radiology$$$corpus_1535", "text": "In order to better assess radiation protection, the number of X-ray examinations, including the dose, has been recorded annually in Germany since 2007. However, the  Federal Statistical Office  does not have complete data for conventional X-ray examinations. In 2014, the total number of X-ray examinations in Germany was estimated to be about 135 million, of which about 55 million were dental X-ray examinations. The average effective dose from x-ray examinations per inhabitant in Germany in 2014 was about 1.55 mSv (about 1.7 x-ray examinations per inhabitant per year). The proportion of dental X-rays is 41%, but accounts for only 0.4% of the collective effective dose. [ 43 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1536", "text": "In Germany, Section 28 of the X-ray Ordinance (R\u00f6V) has required since 2002 that the attending physician must have an X-ray pass available for X-ray examinations and offer it to the patient. The pass contains information about the patient's X-rays to avoid unnecessary examinations and to allow comparison with previous images. With the entry into force of the new Radiation Protection Ordinance on December 31, 2018, this obligation no longer applies. In Austria and Switzerland, x-ray passports have so far been available voluntarily. [ 44 ] [ 45 ]  In principle, there must always be both a justifiable indication for the use of X-rays and the informed consent of the patient. In the context of medical treatment, informed consent refers to the patient's agreement to all types of interventions and other medical measures."}
{"_id": "WikiPedia_Radiology$$$corpus_1537", "text": "\u00a7 630d\nAct of (in German)"}
{"_id": "WikiPedia_Radiology$$$corpus_1538", "text": "Over the years, there have been increasing efforts to reduce radiation exposure to therapists and patients."}
{"_id": "WikiPedia_Radiology$$$corpus_1539", "text": "Following Rollins' discovery in 1920 that lead aprons protected against X-rays, lead aprons with a lead thickness of 0.5\u00a0mm were introduced. Due to their weight, lead-free and lead-reduced aprons were subsequently developed. In 2005, it was recognized that in some cases the protection was significantly less than wearing lead aprons. [ 46 ]  The lead-free aprons contain  tin ,  antimony  and  barium , which have the property of producing intense radiation ( X-ray fluorescence  radiation) when irradiated. In Germany, the Radiology Standards Committee has taken up the issue and introduced a German standard (DIN 6857-1) in 2009. The international standard IEC 61331-3:2014 was finally published in 2014. Protective aprons that do not comply with DIN 6857-1 of 2009 or the new IEC 61331-1 [ 47 ]  of 2014 may result in higher exposures. There are two classes of lead equivalency classes: 0.25\u00a0mm and 0.35\u00a0mm. The manufacturer must specify the area weight in kg/m 2  at which the protective effect of a pure lead apron of 0.25 or 0.35\u00a0mm Pb is achieved. The protective effect of an apron shall be appropriate to the energy range used, up to 110 kV for low energy aprons and up to 150 kV for high energy aprons. [ 48 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1540", "text": "If necessary, lead glass panels must also be used, with the front panels having a lead equivalent of 0.5-1.0\u00a0mm, depending on the application, and the side shields having a lead equivalent of 0.5-0.75\u00a0mm."}
{"_id": "WikiPedia_Radiology$$$corpus_1541", "text": "Outside the useful beam, radiation exposure is primarily caused by scattered radiation from the tissue being scanned. During examinations of the head and torso, this scattered radiation can spread throughout the body and is difficult to shield with radiation protective clothing. Fears that a lead apron will prevent radiation from leaving the body are unfounded, however, because lead absorbs radiation rather than scattering it. [ 49 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1542", "text": "When preparing an  orthopantomogram  (OPG) for a dental overview radiograph, it is sometimes recommended not to wear a lead apron, as it does little to shield scattered radiation from the jaw area, but may hinder the rotation of the imaging device. [ 50 ]  However, according to the 2018 X-ray regulation, it is still mandatory to wear a lead apron when taking an OPG."}
{"_id": "WikiPedia_Radiology$$$corpus_1543", "text": "In the same year as the discovery of X-rays,  Mihajlo Idvorski Pupin  (1858-1935) invented the method of placing a sheet of paper coated with  fluorescent  substances on the  photographic plate , drastically reducing the exposure time and thus the radiation exposure. 95% of the film was blackened by the intensifying film and only the remaining 5% was directly blackened by the X-rays. Thomas Alva Edison identified the blue-emitting  calcium tungstate  (CaWO4) as a suitable phosphor, which quickly became the standard for X-ray intensifying film. In the 1970s, calcium tungstate was replaced by even better and finer intensifying films with rare  earth-based phosphors  ( terbium -activated  lanthanum oxybromide ,  gadolinium oxysulfide ). [ 51 ]  The use of intensifying films in dental film production did not become widespread because of the loss of image quality. [ 52 ]  The combination with  high-sensitivity films  further reduced radiation exposure."}
{"_id": "WikiPedia_Radiology$$$corpus_1544", "text": "An  anti-scatter grid  is a device in X-ray technology that is placed in front of the image receiver ( screen ,  detector , or film) and reduces the incidence of diffuse radiation on it. The first diffusion radiation grid was developed in 1913 by  Gustav Peter Bucky  (1880-1963). The US radiologist Hollis Elmer Potter (1880-1964) improved it in 1917 by adding a moving device. [ 53 ]  The radiation dose must be increased when using scattered radiation grids. For this reason, the use of scattered radiation equipment should not be used on children. In digital radiography, a grid may be omitted under certain conditions to reduce radiation exposure to the patient. [ 54 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1545", "text": "Radiation protection measures may also be necessary against scattered radiation, which occurs during tumor irradiation of the head and neck on metal parts of the dentition ( dental fillings ,  bridges , etc.). Since the 1990s, soft tissue retractors known as  radiation protection splints  have been used to prevent or reduce  mucositis , an inflammation of the mucous membranes. It is the most significant adverse acute side effect of radiation. [ 55 ]  The radiation protection splint is a spacer that keeps the mucosa away from the teeth and reduces the amount of scattered radiation that hits the mucosa according to the square law of distance. Mucositis, which is extremely painful, is one of the most significant detriments to a patient's quality of life and often limits radiation therapy, thereby reducing the chances of tumor cure. [ 56 ]  The splint reduces oral mucosal reactions that typically occur in the second and third third of a radiation series and are irreversible."}
{"_id": "WikiPedia_Radiology$$$corpus_1546", "text": "The Japanese  Hisatugu Numata  developed the first panoramic radiograph in 1933/34. This was followed by the development of intraoral panoramic X-ray units, in which the X-ray tube is placed intraorally (inside the mouth) and the  X-ray film  extraorally (outside the mouth). At the same time, Horst Beger from Dresden in 1943 and the Swiss dentist Walter Ott in 1946 worked on the Panoramix (Koch & Sterzel), Status X ( Siemens ) and Oralix ( Philips ). [ 57 ]  Intraoral panoramic devices were discontinued at the end of the 1980s because the radiation exposure was too high in direct contact with the tongue and  oral mucosa  due to the intraoral tube."}
{"_id": "WikiPedia_Radiology$$$corpus_1547", "text": "Eastman Kodak  filed the first patent for  digital radiography  in 1973. [ 58 ]  The first commercial CR (Computed Radiology) solution was offered by  Fujifilm  in Japan in 1983 under the device name CR-101. [ 59 ]  X-ray imaging plates are used in X-ray diagnostics to record the shadow image of X-rays. The first commercial digital X-ray system for use in dentistry was introduced in 1986 by  Trophy Radiology  (France) under the name Radiovisiography. [ 60 ]  Digital x-ray systems help reduce radiation exposure. Instead of film, the machines contain a  scintillator  that converts the incident X-ray photons either into visible light or directly into electrical impulses."}
{"_id": "WikiPedia_Radiology$$$corpus_1548", "text": "In 1972, the first commercial  CT  scanner for clinical use went into operation at Atkinsons Morley Hospital in London. Its inventor was the English engineer  Godfrey Newbold Hounsfield  (1919-2004), who shared the 1979  Nobel Prize in Medicine  with  Allan McLeod Cormack  (1924-1998) for his pioneering work in the field of computed tomography. The first steps toward dose reduction were taken in 1989 in the era of single-slice spiral CT. The introduction of multi-slice spiral computed tomography in 1998 and its continuous development made it possible to reduce the dose by means of dose modulation. The tube current is adjusted, for example by reducing the power for images of the lungs compared to the  abdomen . The tube current is modulated during rotation. Because the human body has an approximately oval cross-section, radiation intensity is reduced when radiation is delivered from the front or back, and is increased when radiation is delivered from the side. This dose control also depends on the  body mass index . For example, the use of dose modulation in the head and neck region reduces total exposure and organ doses to the  thyroid  and  eye lens  by up to 50% without significantly compromising diagnostic image quality. [ 61 ]  The  Computed Tomography Dose Index  (CTDI) is used to measure radiation exposure during a CT scan. The CTDI was first defined by the  Food and Drug Administration  (FDA) in 1981. The unit of measurement for the CTDI is the mGy (milli- Gray ). Multiplying the CTDI by the length of the examination volume yields the dose-length product (DLP), which quantifies the total radiation exposure to the patient during a CT scan. [ 62 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1549", "text": "An X-ray room must be shielded on all sides with 1\u00a0mm lead equivalent shielding.  Calcium silicate  or solid brick  masonry  is recommended. A steel  jamb  should be used, not only because of the weight of the heavy shielding door but also because of the shielding; wooden frames must be shielded separately. The shielding door must be covered with a 1\u00a0mm thick lead foil and a  lead glass  window must be installed as a visual connection. A keyhole shall be avoided. All installations (sanitary or electrical), that interrupt the radiation protection, must be leaded ("}
{"_id": "WikiPedia_Radiology$$$corpus_1550", "text": "\u00a7 20\n \u00a7 20 R\u00f6ntgenverordnung  (r\u00f6v_1987)  [\u00a7 20 X-ray Ordinance]  (in German)\nand"}
{"_id": "WikiPedia_Radiology$$$corpus_1551", "text": "\u00a7 Annex+2\n Annex 2 (to \u00a7\u00a08 para.\u00a01 sentence 1 R\u00f6V)  (r\u00f6v_1987) (in German)\nDepending on the application,  nuclear medicine  requires even more extensive protective measures, up to and including concrete walls several meters thick. [ 63 ]  In addition, from December 31, 2018, when the latest amendments to Section 14 (1) No. 2b of the Radiation Protection Act"}
{"_id": "WikiPedia_Radiology$$$corpus_1552", "text": "\u00a7 14\n Strahlenschutzgesetz \u2013 StrlSchG   [Radiation Protection Act (StrlSchG)]  (in German)"}
{"_id": "WikiPedia_Radiology$$$corpus_1553", "text": "come into force, an  expert in medical physics  for X-ray diagnostics and therapy must be consulted for the optimization and quality assurance of the application and for advice on radiation protection issues."}
{"_id": "WikiPedia_Radiology$$$corpus_1554", "text": "Each facility operating an x-ray unit shall have sufficient personnel with appropriate expertise. The person responsible for radiation protection or one or more  Radiation Safety Officers  shall have appropriate qualifications, which shall be regularly updated. X-ray examinations may be technically performed by any other staff member of a medical or dental practice if they are under the direct supervision and responsibility of the person responsible and if they have knowledge of radiation protection."}
{"_id": "WikiPedia_Radiology$$$corpus_1555", "text": "This knowledge of radiation protection has been required since the amendment of the X-ray Ordinance in 1987; medical and  dental assistants  (then called medical assistants or dental assistants) received this additional training in 1990. [ 64 ]  The regulations for the specialty of radiology were tightened by the Radiation Protection Act, which came into force on October 1, 2017. [ 65 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1556", "text": "The handling of radioactive substances and ionizing radiation (if not covered by the X-ray Ordinance) is regulated by the Radiation Protection Ordinance ( StrlSchV ). Section 30 StrlSchV"}
{"_id": "WikiPedia_Radiology$$$corpus_1557", "text": "\u00a7 30\n StrlSchV  (in German)\ndefines the \"Required expertise and knowledge in radiation protection\"."}
{"_id": "WikiPedia_Radiology$$$corpus_1558", "text": "The  Association of German Radiation Protection Physicians  ( VDS\u00c4 ) was formed in the late 1950s from a  working group of radiation protection physicians of the German Red Cross  and was founded in 1964. It was dedicated to the promotion of radiation protection and the representation of medical, dental, and veterinary radiation protection concerns to the public and the health care system. In 2017, it was merged into the Professional Association for Radiation Protection. The  Austrian Association for Radiation Protection  ( \u00d6VS ), [ 66 ]  founded in 1966, pursues the same goals as the Association for Medical Radiation Protection in Austria. [ 67 ]  The  Professional Association for Radiation Protection  for Germany and Switzerland is networked worldwide. [ 68 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1559", "text": "In radiotherapy, radiation protection is often overlooked in favor of structural safeguards and therapist protection. The benefit/risk assessment should prioritize both the therapeutic goal of treating the patient's cancer and the safety of all involved. However, it is crucial to ensure that radiation is delivered only where it is needed through appropriate treatment planning. By employing strong radiation protection measures, we can confidently provide effective treatment while minimizing potential risks. Linear accelerators replaced cobalt and caesium emitters in routine therapy due to their superior technical characteristics and risk profile. They have been available since about 1970. The presence of a medical physicist responsible for technical quality control is required for linear accelerators, unlike X-rays and telecurie systems. It is important to note that radiation necrosis is the necrosis of cells in an organism caused by the effects of ionizing radiation. Radionecrosis is a serious complication of radiosurgical treatment that becomes clinically apparent months or years after irradiation. [ 69 ]  Radiation therapy has significantly reduced the incidence of radionecrosis since its early days. Modern radiation techniques prioritize the sparing of healthy tissue while irradiating as much of the area around the tumor as possible to prevent recurrence. It is important to note that patients undergoing radiotherapy face a certain level of radiation risk."}
{"_id": "WikiPedia_Radiology$$$corpus_1560", "text": "While there is limited literature on radiation injury to animals, there is no evidence of other types of radiation injury. Diagnostic radiation has been shown to cause local burns in animals, typically resulting from prolonged exposure of body parts or sparks from old x-ray tubes. It is important to note that the frequency of injury to veterinary staff and veterinarians is significantly lower than that in human medicine, highlighting the safety of diagnostic radiation in veterinary practice. In veterinary medicine, fewer images are taken compared to human medicine, particularly fewer CT scans. However, due to the manual restraint of animals to avoid anesthesia, at least one person is present in the control area, resulting in significantly higher radiation exposure than that of human medical staff. It is important to note that since the 1970s, dosimeters have been used to measure the radiation exposure of veterinary personnel, ensuring their safety."}
{"_id": "WikiPedia_Radiology$$$corpus_1561", "text": "Feline hyperthyroidism  (overactive thyroid) is a common disease in older cats.  Radioiodine  therapy is considered by many authors to be the treatment of choice. Following the administration of radioactive iodine, cats are kept in an isolation pen. The cat's radioactivity is measured to determine the time of discharge, which is typically 14 days after the start of therapy. The therapy requires significant radiation protection measures and is currently only offered at two veterinary facilities in Germany (as of 2010). After the start of treatment, cats must be kept indoors for four weeks, and contact with pregnant women and children under the age of 16 must be avoided due to residual radioactivity. [ 70 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1562", "text": "Just like a medical practice, any veterinary practice operating an X-ray machine must have sufficient staff with the appropriate expertise, as required by Section 18 of the X-Ray Ordinance 2002. The corresponding training for  paraveterinary workers  (then called veterinary nurses) took place in 1990. [ 64 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1563", "text": "In 2017,  Linsengericht  (Hesse) opened Europe's first clinic for horses with cancer. Radiation therapy is administered in a treatment room that is eight meters wide, on a specially designed table that can withstand heavyweight. The surrounding area is protected from radiation by three-meter thick walls. Mobile equipment is used to irradiate tumors in small animals at various locations. [ 71 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1564", "text": "Radon is a naturally occurring radioactive  noble gas  discovered in 1900 by  Friedrich Ernst Dorn  (1848-1916) and is considered  carcinogenic . Radon is increasingly found in areas with high levels of  uranium  and  thorium  in the soil. These are mainly areas with high  granitic rock deposits . According to studies by the  World Health Organization , the incidence of  lung cancer  increases significantly at radiation levels of 100-200  Bq  per cubic meter of indoor air. The likelihood of developing lung cancer increases by 10% with each additional 100 Bq/m 3  of indoor air. [ 72 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1565", "text": "Elevated radon levels have been measured in numerous areas in Germany, particularly in southern Germany, Austria and Switzerland."}
{"_id": "WikiPedia_Radiology$$$corpus_1566", "text": "The Federal Office for Radiation Protection has developed a radon map of Germany. [ 73 ]  The EU Directive 2013/59/Euratom (Radiation Protection Basic Standards Directive) introduced  reference levels  and the possibility for workers to have their workplace tested for radon exposure. In Germany, it was implemented in the Radiation Protection Act (Chapter 2 or Sections 124-132 StrlSchG)"}
{"_id": "WikiPedia_Radiology$$$corpus_1567", "text": "\u00a7 124-132 \n StrlSchG  (in German)\nand the amended Radiation Protection Ordinance (Part 4 Chapter 1, Sections 153-158 StrlSchV)."}
{"_id": "WikiPedia_Radiology$$$corpus_1568", "text": "\u00a7 153-158 \nAct of (in German)\nThe new radon protection regulations for workplaces and new residential buildings have been binding since January 2019. Extensive radon contamination and radon precautionary areas have been determined by the ministries of the environment of the federal states (as of June 15, 2021). [ 74 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1569", "text": "The highest radon concentrations in Austria were measured in 1991 in the municipality of Umhausen in Tyrol. Umhausen has about 2300 inhabitants and is located in the \u00d6tztal valley. Some of the houses there were built on a bedrock of  granite gneiss . From this porous  subsoil , the radon present in the rock seeped freely into the unsealed cellars, which were contaminated with up to 60,000 Becquerels of radon per cubic meter of air. [ 75 ]  Radon levels in the apartments in Umhausen have been systematically monitored since 1992. Since then, extensive radon mitigation measures have been implemented in the buildings: New buildings, sealing of cellar floors, forced ventilation of cellars or relocation. Queries in the  Austrian Health Information System  ( \u00d6GIS ) have shown that the incidence of new cases of lung cancer has declined sharply since then. The Austrian National Radon Project (\u00d6NRAP) has studied radon exposure throughout the country. [ 76 ]  Austria also has a Radiation Protection Act as a legal basis. [ 77 ]  Indoor limits were set in 2008  [ 78 ]  The Austrian Ministry of the Environment states that"}
{"_id": "WikiPedia_Radiology$$$corpus_1570", "text": "\"Precautionary measures in radiation protection use the generally accepted model that the risk of lung cancer increases uniformly (linearly) with radon concentration. This means that an increased risk of lung cancer does not only occur above a certain value, but that a guideline or limit value only adjusts the magnitude of the risk in a meaningful way to other existing risks. Achieving a guideline or limit therefore means taking a risk that is still (socially) acceptable. It therefore makes perfect sense to take simple measures to reduce radon levels, even if they are below the guideline values.\""}
{"_id": "WikiPedia_Radiology$$$corpus_1571", "text": "In Austria, the Radon Protection Ordinance in its version of September 10, 2021 is currently in force, which also defines the radon protection areas and radon precautionary areas. [ 79 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1572", "text": "The aim of the Radon Action Plan 2012-2020 in Switzerland was to incorporate the new international recommendations into the Swiss strategy for protection against radon and thus reduce the number of lung cancer cases attributable to radon in buildings. [ 80 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1573", "text": "On 1 January 2018, the limit value of 1000 Bq/m 3  was replaced by a reference value of 300 becquerels per cubic meter (Bq/m 3 ) for the radon gas concentration averaged over a year in \"rooms in which people regularly spend several hours a day\"."}
{"_id": "WikiPedia_Radiology$$$corpus_1574", "text": "Subsequently, on May 11, 2020, the  Federal Office of Public Health  FOPH issued the Radon Action Plan 2021-2030. [ 81 ]  The provisions on radon protection are primarily laid down in the Radiation Protection Ordinance (RPO). [ 82 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1575", "text": "In 1879,  Walther Hesse  (1846-1911) and  Friedrich Hugo H\u00e4rting  published the study \"Lung Cancer, the Miners' Disease in the Schneeberg Mines\". Hesse, a  pathologist , was shocked by the poor health and young age of the miners. [ 83 ]  This particular form of  bronchial carcinoma  was given the name  Schneeberg  disease  because it occurred among miners in the  Schneeberg  mines (Saxon Erz Mountains)."}
{"_id": "WikiPedia_Radiology$$$corpus_1576", "text": "When Hesse's report was published, radioactive radiation and the existence of radon were unknown. It was not until 1898 that  Marie Curie-Sk\u0142odowska  (1867-1934) and her husband  Pierre Curie  (1859-1906) discovered radium and created the concept of  radioactivity . [ 84 ]  Beginning in the fall of 1898, Marie Curie suffered from inflammation of the fingertips, the first known symptoms of  radiation sickness ."}
{"_id": "WikiPedia_Radiology$$$corpus_1577", "text": "In the  J\u00e1chymov  mines, where silver and  non-ferrous metals  were mined from the 16th to the 19th century,  uranium  ore was mined in abundance in the 20th century. It was only during the  Second World War  that restrictions were imposed on ore mining in the Schneeberg and J\u00e1chymov mines. After World War II,  uranium mining  was accelerated for the  Soviet atomic bomb project  and the emerging Soviet  nuclear industry.  Forced labor was used. Initially, these were German prisoners of war and displaced persons, and after the  February Revolution of 1948 , political prisoners were imprisoned by the  Communist Party regime in Czechoslovakia , as well as conscripted civilian workers. [ 85 ]  Several \"Czechoslovak  gulags \" were established in the area to house these workers. In all, about 100,000 political prisoners and more than 250,000 forced laborers passed through the camps. About half of them probably did not survive the mining work. [ 86 ]  Uranium mining ceased in 1964. We can only speculate about other victims who died as a result of radiation. Radon-bearing springs discovered during the mining in the early 20th century established a spa industry that is still important today, as well as the town's status as the oldest radium brine spa in the world."}
{"_id": "WikiPedia_Radiology$$$corpus_1578", "text": "The approximately 200,000 uranium miners employed by  Wismut AG  in the former Soviet occupation zone of East Germany were exposed to very high levels of radiation, particularly between 1946 and 1955, but also in later years. This exposure was caused by the inhalation of radon and its radioactive by-products, which were deposited to a considerable extent in the inhaled dust. Radiation exposure was expressed in the historical unit of  working level month  (WLM). This unit of measurement was introduced in the 1950s specifically for occupational safety in  uranium mines  in the U.S. [ 87 ]  to record radiation exposure resulting from radioactive exposure to radon and its decay products in the air we breathe. [ 88 ]  Approximately 9000 workers at Wismut AG have been diagnosed with lung cancer."}
{"_id": "WikiPedia_Radiology$$$corpus_1579", "text": "Until the 1930s, radium compounds were not only considered relatively harmless, but also beneficial to health, and were advertised as medicines for a variety of ailments or used in products that glowed in the dark. Processing took place without any safeguards."}
{"_id": "WikiPedia_Radiology$$$corpus_1580", "text": "Until the 1960s, radioactivity was often handled naively and carelessly. From 1940 to 1945, the Berlin-based  Auergesellschaft , founded by  Carl Auer von Welsbach  (1858-1929,  Osram ), produced a  radioactive  toothpaste called  Doramad  that contained  thorium-X  and was sold internationally. It was advertised with the statement, \"Its radioactive radiation strengthens the defenses of the teeth and gums. The  cells  are charged with new life energy and the destructive effect of  bacteria  is inhibited. This gave the claim of  radiant white teeth  a double meaning. By 1930, there were also bath additives and  eczema  ointments under the brand name \"Thorium-X\". Radium was also added to toothpastes, such as  Kolynos toothpaste . After World War I, radioactivity became a symbol of modern achievement and was considered \"chic\". Radioactive substances were added to mineral water, condoms, and cosmetic powders. Even chocolate laced with radium was sold. [ 89 ]  The toy manufacturer  M\u00e4rklin  in the Swabian town of G\u00f6ppingen tested the sale of an X-ray machine for children. [ 90 ]  At upper-class parties, people \"photographed\" each other's bones for fun. A system called  Trycho  ( Ancient Greek :  \u03c4\u03c1\u03b9\u03c7\u03bf- ,  romanized :\u00a0 tricho- ,  lit. \u2009 'concerning the hair') for  epilation  (hair removal) of the face and body was  franchised  in the USA. As a result, thousands of women suffered skin burns,  ulcers  and tumors. [ 25 ]  It was not until the  atomic bombings of Hiroshima and Nagasaki  that the public became aware of the dangers of  ionizing radiation  and these products were banned. [ 91 ] [ 92 ] [ 93 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1581", "text": "A radium industry developed, using radium in creams, beverages, chocolates, toothpastes, and soaps. [ 94 ] [ 95 ]  It took a relatively long time for radium and its decay product radon to be recognized as the cause of the observed effects.  Radithor , a radioactive agent consisting of triple- distilled water  in which the radium  isotopes   226 Ra and  228 Ra were dissolved so that it had an  activity  of at least one  microcurie , was marketed in the United States. [ 96 ]  It was not until 1932, when the prominent American athlete  Eben Byers , who by his own account had taken about 1,400 vials of Radithor as medicine on the recommendation of his physician, fell seriously ill with cancer, lost many of his teeth, and died shortly thereafter in great agony, that strong doubts were raised about the healing powers of Radithor and radium water. [ 97 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1582", "text": "1908 saw a boom in the use of radioactive water for therapeutic purposes. The discovery of springs in Oberschlema and  Bad Brambach  paved the way for the establishment of radium spas, which relied on the healing properties of radium. During the cures, people bathed in radium water, drank cures with radium water, and inhaled radon in emanatoriums. The baths were visited by tens of thousands of people every year, hoping for  hormesis ."}
{"_id": "WikiPedia_Radiology$$$corpus_1583", "text": "To this day, therapeutic applications are carried out in spas and healing tunnels. The natural release of radon from the ground is used. According to the German Spa Association, the activity in water must be at least 666 Bq/liter. The requirement for inhalation treatments is at least 37,000 Bq/m 3  of air. This form of therapy is not scientifically accepted and the potential risk of radiation exposure is criticized. The equivalent dose of a radon cure in Germany is given by the individual health resorts as about one to two millisieverts, depending on the location. In 2010, doctors in Erlangen, using the (outdated)  LNT (Linear, No-Threshold) model , concluded that five percent of all lung cancer deaths in Germany are caused by radon. [ 98 ]  There are radon baths in  Bad Gastein ,  Bad Hofgastein  and  Bad Zell  in Austria, in  Ni\u0161ka Banja  in Serbia, in the radon revitalization bath in  Menzenschwand  and in  Bad Brambach ,  Bad M\u00fcnster  am  Stein-Ebernburg ,  Bad Schlema ,  Bad Steben ,  Bad Schmiedeberg  and  Sibyllenbad  in Germany, in  J\u00e1chymov  in the Czech Republic, in  H\u00e9v\u00edz  in Hungary, in  \u015awierad\u00f3w-Zdr\u00f3j  (Bad Flinsberg) in Poland, in Naretschen and  Kostenez  in Bulgaria and on the island of  Ischia  in Italy. There are radon tunnels in  Bad Kreuznach  and  Bad Gastein . [ 99 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1584", "text": "The dangers of radium were recognized in the early 1920s and first described in 1924 by New York dentist and oral surgeon Theodor Blum (1883-1962). [ 100 ]  He was particularly aware of the use of radium in the watch industry, where it was used for luminous dials. He published an article on the clinical picture of the so-called  radium jaw . He observed this disease in female patients who, as dial painters, came into contact with luminous paint whose composition was similar to Radiomir, a luminous material invented in 1914 consisting of a mixture of  zinc sulfide  and  radium bromide . As they painted, they used their lips to form the tip of the phosphorus-laden brush into the desired pointed shape, and this is how the radioactive radium entered their bodies. In the U.S. and Canada alone, about 4,000 workers were affected over the years. [ 101 ]  In retrospect, the factory workers were called the  Radium Girls . They also played with the paint, painting their fingernails, teeth and faces. This made them glow at night to the surprise of their companions."}
{"_id": "WikiPedia_Radiology$$$corpus_1585", "text": "After  Harrison Stanford Martland  (1883-1954), chief medical examiner in  Essex County , detected the radioactive noble gas radon (a decay product of radium) in the breath of the Radium Girls, he turned to  Charles Norris  (1867-1935) and  Alexander Oscar Gettler  (1883-1968). In 1928, Gettler was able to detect a high concentration of radium in the bones of Amelia Maggia, one of the young women, even five years after her death. [ 102 ] [ 103 ]  In 1931, a method was developed for determining radium dosage using a film dosimeter. A standard preparation is irradiated through a hardwood cube onto an X-ray film, which is then blackened. For a long time, the  cube minute  was an important unit of radium dosage. [ 104 ]  It was calibrated by ionometric measurements. The radiologists  Hermann Georg Holthusen  (1886-1971) and  Anna Hamann  (1894-1969) found a calibration value of 0.045 r/min in 1932/1935. The calibration film receives the y-ray dose of 0.045 r per minute through the wooden cube from the preparation of 13.33\u00a0mg. In 1933, the physicist  Robley D. Evans  (1907-1995) made the first measurements of radon and radium in the excretions of female workers. [ 105 ]  On this basis, the National Bureau of Standards, the predecessor to the  National Institute of Standards and Technology  (NIST), set the limit for radium at 0.1  microcuries  (about 3.7  kilobecquerels ) in 1941."}
{"_id": "WikiPedia_Radiology$$$corpus_1586", "text": "A  Radium Action Plan 2015-2019  aims to solve the problem of radiological contamination in Switzerland, mainly in the  Jura Mountains , due to the use of radium luminous paint in the watch industry until the 1960s. [ 106 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1587", "text": "In France, a line of cosmetics called  Tho-Radia , which contained both thorium and radium, was created in 1932 and lasted until the 1960s. [ 107 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1588", "text": "Terrestrial radiation  is the ubiquitous radiation on Earth caused by  radionuclides  in the ground that were formed billions of years ago by stellar  nucleosynthesis  and have not yet decayed due to their long  half-lives . Terrestrial radiation is caused by natural radionuclides that occur naturally in the Earth's soil, rocks,  hydrosphere , and  atmosphere . Natural radionuclides can be divided into  cosmogenic  and  primordial nuclides . Cosmogenic nuclides do not contribute significantly to the terrestrial ambient radiation at the Earth's surface. The sources of terrestrial radiation are the natural radioactive nuclides found in the uppermost layers of the Earth, in the water and in the air. These include in particular [ 108 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1589", "text": "According to the  World Nuclear Association ,  coal  from all deposits contains traces of various radioactive substances, particularly radon, uranium and thorium. These substances are released during coal mining, especially from surface mines, through power plant emissions, or power plant ash, and contribute to terrestrial radiation exposure through their exposure pathways. [ 109 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1590", "text": "In December 2009, it was revealed that  oil  and  gas production  generates millions of tons of radioactive waste each year, much of which is improperly disposed of without detection, including  226 Radium  and  210 Polonium . [ 110 ] [ 111 ]  The specific activity of the waste ranges from 0.1 to 15,000 becquerels per gram. In Germany, according to the  Radiation Protection Ordinance  of 2001, the material is subject to monitoring at one Becquerel per gram and would have to be disposed of separately. The implementation of this regulation has been left to the industry, which has disposed of the waste carelessly and improperly for decades."}
{"_id": "WikiPedia_Radiology$$$corpus_1591", "text": "Every building material contains traces of natural radioactive substances, especially  238 uranium,  232 thorium, and their decay products, and  40 potassium. Solidified and effusive rocks such as  granite ,  tuff , and  pumice  have higher levels of radioactivity. In contrast, sand,  gravel ,  limestone , and natural  gypsum  ( calcium sulfate  dihydrate) have low levels of radioactivity. The European Union's  Activity Concentration Index  (ACI), developed in 1999, can be used to assess radiation exposure from building materials. [ 112 ]  It replaces the Leningrad summation formula, which was used in 1971 in Leningrad (St. Petersburg) to determine how much radiation exposure from building materials is permissible for humans. The ACI is calculated from the sum of the weighted activities of  40 potassium,  226 radium, and  232 thorium. The  weighting  takes into account the relative harmfulness to humans. According to official recommendations, building materials with a European ACI value greater than \"1\" should not be used in large quantities. [ 113 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1592", "text": "Uranium  pigments  are used to color ceramic tiles with  uranium glazes  (red, yellow, brown), where 2\u00a0mg of uranium per cm 2  is allowed. Between 1900 and 1943, large quantities of uranium-containing ceramics were produced in the United States, as well as in Germany and Austria. It is estimated that between 1924 and 1943, 50-150  tons  of  uranium (V,VI) oxide  were used annually in the U.S. to produce uranium-containing glazes. In 1943, the U.S. government imposed a ban on the civilian use of uranium-containing substances, which remained in effect until 1958. Beginning in 1958, the U.S. government, and in 1969 the  United States Atomic Energy Commission , sold depleted uranium in the form of  uranium(VI) fluoride  for civilian use. [ 114 ]  In Germany, uranium-glazed ceramics were produced by the  Rosenthal  porcelain factory and were commercially available until the early 1980s. [ 115 ]  Uranium-glazed ceramics should only be used as collector's items and not for everyday use due to possible abrasion."}
{"_id": "WikiPedia_Radiology$$$corpus_1593", "text": "The Federal Office for Radiation Protection's monitoring network measures natural radiation exposure through the local dose rate (ODL), expressed in microsieverts per hour (\u03bcSv/h).\u00a0 In Germany, the natural ODL ranges from approximately 0.05 to 0.18 \u03bcSv/h, depending on local conditions. The ODL monitoring network has been operational since 1973 and currently comprises 1800 fixed, automatically operating measuring points. Its primary function is to provide early warning for the rapid detection of increased radiation from radioactive substances in the air in Germany. Spectroscopic probes have been successfully utilized since 2008 to determine the contribution of artificial radionuclides in addition to the local dose rate, showcasing the network's advanced capabilities. [ 116 ]  In addition to the ODL monitoring network of the Federal Office for Radiation Protection, there are other federal monitoring networks at the  Federal Maritime and Hydrographic Agency  and the  Federal Institute of Hydrology , which measure gamma radiation in water; the  German Meteorological Service  measures air activity with aerosol samplers. [ 117 ]  To monitor  nuclear facilities , the relevant federal states operate their own ODL monitoring networks. The data from these monitoring networks are automatically fed into the  Integrated Measurement and Information System  (IMIS), where they are used to analyze the current situation."}
{"_id": "WikiPedia_Radiology$$$corpus_1594", "text": "Many countries operate their own ODL monitoring networks to protect the public. In Europe, these data are collected and published on the EURDEP platform of the  European Atomic Energy Community . The European monitoring networks are based on Articles 35 and 37 of the  Euratom Treaty . [ 118 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1595", "text": "Nuclear medicine  is the use of open radionuclides for diagnostic and therapeutic purposes ( radionuclide therapy ). [ 119 ]  It also includes the use of other radioactive substances and  nuclear physics  techniques for functional and localization diagnostics.  George de Hevesy  (1885-1966) lived as a lodger and in 1923 suspected that his landlady was offering him pudding that he had not eaten the following week. He mixed a small amount of a radioactive isotope into the leftovers. When she served him the pudding a week later, he was able to detect radioactivity in a sample of the casserole. When he showed this to his landlady, she immediately gave him notice. The method he used made him the  father of nuclear medicine . It became known as the  tracer method , which is still used today in nuclear medicine diagnostics. [ 120 ]  A small amount of a radioactive substance, its distribution in the organism, and its path through the human body can be tracked externally. This provides information about various  metabolic functions  of the body. The continuous development of radionuclides has improved radiation protection. For example, the mercury compounds  203 chloro-merodrin and  197 chloro-merodrin were abandoned in the 1960s as substances were developed that allowed a higher  photon  yield with less radiation exposure. Beta emitters such as  131 I and  90 Y are used in radionuclide therapy. In nuclear medicine diagnostics, the beta+ emitters  18 F,  11 C,  13 N, and  15 O are used as radioactive markers for tracers in  positron emission tomography  (PET). [ 121 ]   Radiopharmaceuticals  (isotope-labeled drugs) are being developed on an ongoing basis."}
{"_id": "WikiPedia_Radiology$$$corpus_1596", "text": "Radiopharmaceutical residues, such as empty application syringes and contaminated residues from the patient's toilet, shower and washing water, are collected in tanks and stored until they can be safely pumped into the sewer system. The storage time depends on the half-life and ranges from a few weeks to a few months, depending on the radionuclide. Since 2001, by"}
{"_id": "WikiPedia_Radiology$$$corpus_1597", "text": "\u00a7 29 \n StrlSchV  (in German)\nof the  Radiation Protection Ordinance , the specific radioactivity in the waste containers has been recorded in release  measuring stations  and the release time is calculated automatically. This requires measurements of the sample activity in Bq/g and the surface contamination in Bq/cm 2 . In addition, the behavior of the patients after their discharge from the clinic is prescribed. [ 122 ]  To protect personnel, syringe filling systems, borehole measurement stations for nuclide-specific measurement of low-activity, small volume individual samples, a lift system into the measurement chamber to reduce radiation exposure when handling highly active samples, probe measurement stations, ILP (isolated limb perfusion) measurement stations to monitor activity with one or more detectors during surgery and report leakage to the surgical  oncologist ."}
{"_id": "WikiPedia_Radiology$$$corpus_1598", "text": "Radioiodine Therapy  (RIT) is a nuclear medicine procedure used to treat thyroid hyperfunction,  Graves' disease , thyroid enlargement, and certain forms of thyroid cancer. The radioactive  iodine isotope  used is  131 Iodine, a predominant  beta emitter  with a half-life of eight days, which is only stored in thyroid cells in the human body. In 1942,  Saul Hertz  (1905-1950) of the Massachusetts General Hospital and the physicist Arthur Roberts published their report on the first radioiodine therapy (1941) for Graves' disease, [ 123 ] [ 124 ]  at that time still predominantly using the  130 iodine isotope with a half-life of 12.4 hours. [ 125 ]  At the same time,  Joseph Gilbert Hamilton  (1907-1957) and  John Hundale Lawrence  (1904-1991) performed the first therapy with  131 iodine, the isotope still used today. [ 125 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1599", "text": "Radioiodine therapy is subject to special legal regulations in many countries, and in Germany may only be performed on an inpatient basis. There are approximately 120 treatment centers in Germany (as of 2014), performing approximately 50,000 treatments per year. [ 126 ]  In Germany, the minimum length of stay is 48 hours. Discharge depends on the residual activity remaining in the body. In 1999, the limit for residual activity was raised. The dose rate may not exceed 3.5  \u03bcSv  per hour at a distance of 2 meters from the patient, which means that a radiation exposure of 1 mSv may not be exceeded within one year at a distance of 2 meters. This corresponds to a residual activity of about 250  MBq . Similar regulations exist in Austria."}
{"_id": "WikiPedia_Radiology$$$corpus_1600", "text": "In Switzerland, a maximum radiation exposure of 1 mSv per year and a maximum of 5 mSv per year for the patient's relatives may not be exceeded. [ 127 ]  After discharge following radioiodine therapy, a maximum dose rate of 5 \u03bcSv per hour at a distance of 1 meter is permitted, which corresponds to a residual activity of approximately 150 MBq. [ 128 ]  In the event of early discharge, the supervisory authority must be notified up to a dose rate of 17.5 \u03bcSv/h; above 17.5 \u03bcSv/h, permission must be obtained. If the patient is transferred to another ward, the responsible  radiation protection officer  must ensure that appropriate radiation protection measures are taken there, e.g. that a temporary  control area  is set up."}
{"_id": "WikiPedia_Radiology$$$corpus_1601", "text": "Scintigraphy  is a nuclear medicine procedure in which low-level radioactive substances are injected into the patient for diagnostic purposes. These include  bone scintigraphy ,  thyroid scintigraphy ,  octreotide scintigraphy , and, as a further development of the procedure, single photon emission computed tomography (SPECT). For example,  201 Tl  thallium(I) chloride , technetium compounds ( 99m Tc tracer,  99m technetium tetrofosmin), PET tracers (with radiation exposure of 1100 MBq each with  15 O-water, 555 MBq with  13 N  ammonia , or 1850 MBq with  82 Rb  rubidium chloride ) are used in myocardial scintigraphy to diagnose blood flow conditions and function of the heart muscle (myocardium). The examination with 74 MBq  201 Thallium Chloride causes a radiation exposure of about 16 mSv (effective dose equivalent), the examination with 740 MBq  99m Technetium-MIBI about 7 mSv. [ 129 ]  Metastable  99m Tc is by far the most important nuclide used as a tracer in scintigraphy because of its short half-life, the 140  keV  gamma radiation it emits, and its ability to bind to many active biomolecules. Most of this radiation is excreted after the examination. The remaining  99m Tc  decays rapidly to  99 Tc with a half-life of 6 hours. This has a long half-life of 212,000 years and, because of the relatively weak beta radiation released during its decay, contributes only a small amount of additional radiation exposure over the remaining lifetime. [ 130 ]  In the United States alone, approximately seven million individual doses of  99m Tc are administered each year for diagnostic purposes."}
{"_id": "WikiPedia_Radiology$$$corpus_1602", "text": "To reduce radiation exposure, the  American Society of Nuclear Cardiology  (ASNC) issued dosage recommendations in 2010. The effective dose is 2.4 mSv for  13 N-ammonia, 2.5 mSv for  15 O-water, 7 mSv for  18 F- fluorodeoxyglucose , and 13.5 mSv for  82 Rb-rubidium chloride. [ 131 ]  Compliance with these recommendations is expected to reduce the average radiation exposure to = 9 mSv. The  Ordinance on Radioactive Drugs or Drugs Treated with Ionizing Radiation"}
{"_id": "WikiPedia_Radiology$$$corpus_1603", "text": "\u00a7 2 \n AMRadV  (in German)\nregulates the approval procedures for the marketability of radioactive drugs. [ 132 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1604", "text": "Brachytherapy  is used to place a sealed radioactive source inside or near the body to treat cancer, such as prostate cancer. Afterloading brachytherapy is often combined with  teletherapy , which is external radiation delivered from a greater distance than brachytherapy. It is not classified as a nuclear medicine procedure, although like nuclear medicine, it uses the radiation emitted by radionuclides. After initial interest in brachytherapy in the early 20th century, its use declined in the mid-20th century because of the radiation exposure to physicians from manual handling of the radiation sources. [ 133 ] [ 134 ]  It was not until the development of remote-controlled afterloading systems and the use of new radiation sources in the 1950s and 1960s that the risk of unnecessary radiation exposure to physicians and patients was reduced. [ 135 ]  In the afterloading procedure, an empty, tubular applicator is inserted into the target volume (e.g., the  uterus ) before the actual therapy and, after checking the position, loaded with a radioactive preparation. The preparation is located at the tip of a steel wire that is advanced and retracted step by step under computer control. After the pre-calculated time, the source is withdrawn into a safe and the applicator is removed. The procedure is used for breast cancer, bronchial carcinoma or oral floor carcinoma, among others.  Beta emitters  such as  90 Sr or  106 Ru or  192 Ir are used. As a precaution, patients undergoing permanent brachytherapy are advised not to hold small children immediately after treatment and not to be in the vicinity of pregnant women, since low-dose radioactive sources (seeds) remain in the body after treatment with permanent brachytherapy. This is to protect the particularly radiation-sensitive tissues of a fetus or infant."}
{"_id": "WikiPedia_Radiology$$$corpus_1605", "text": "Radioactive  thorium  was used in the 1950s and 60s to treat tuberculosis and other benign diseases (including children), with serious consequences (see Peteosthor). A stabilized  suspension  of  colloidal   thorium(IV) oxide , co-developed by  Ant\u00f3nio Egas Moniz  (1874-1954), [ 136 ]  was used from 1929 under the trade name  Thorotrast  as an X-ray contrast agent for  angiography  in several million patients worldwide until it was banned in the mid-1950s. It accumulates in the  reticulohistiocytic system  and can lead to cancer due to locally increased radiation exposure. The same is true for  cholangiocarcinoma  and  angiosarcoma  of the liver, two rare liver cancers. Carcinomas of the  paranasal sinuses  have also been described following administration of Thorotrast. Typical onset of disease is 30\u201335 years after exposure. The  biological half-life  of Thorotrast is approximately 400 years. [ 137 ] [ 138 ]  The largest study in this area was conducted in Germany in 2004 and showed a particularly high mortality rate among patients exposed in this way. The  median   life expectancy  over a seventy-year observation period was 14 years shorter than in the comparison group. [ 139 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1606", "text": "After the U.S. atomic bombs were dropped on Hiroshima and Nagasaki on August 6 and 9, 1945, an additional 130,000 people - in addition to the 100,000 immediate victims - died from the effects of radiation by the end of 1945. Some experienced the so-called  walking ghost phase , an acute radiation sickness caused by a high equivalent dose of 6 to 20 Sievert after a lethal whole-body dose. The phase describes the period of apparent recovery of a patient between the onset of the first massive symptoms and the inevitable death. [ 140 ]  In the years that followed, a number of deaths from radiation-induced diseases were added. In Japan, the radiation-damaged survivors are called  hibakusha  ( Japanese :  \u88ab\u7206\u8005 ,  lit. \u2009 ''Explosion victim'') and are conservatively estimated to number about 100,000. [ 141 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1607", "text": "In 1946, the  Atomic Bomb Casualty Commission  (ABCC) was established by the  National Research Council  of the  National Academy of Sciences  by order of U.S. President  Harry S. Truman  to study the long-term effects of radiation on survivors of the atomic bombings. In 1975, the ABCC was replaced by the Radiation Effects Research Foundation (RERF). [ 142 ]  Organizations such as the  United Nations Scientific Committee on the Effects of Atomic Radiation  (UNSCEAR), founded in 1955, [ 143 ]  and the  National Academy of Sciences - Advisory Committee on the Biological Effects of Ionizing Radiation  (BEIR Committee), [ 144 ]  founded in 1972, analyze the effects of radiation exposure on humans on the basis of atomic bomb victims who have been examined and, in some cases, medically monitored for decades. They determine the course of the  mortality  rate as a function of the age of the radiation victims in comparison with the spontaneous rate, and also the dose-dependency of the number of additional deaths. To date, 26 UNSCEAR reports have been published and are available online, most recently in 2017 on the effects of the Fukushima nuclear accident. [ 145 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1608", "text": "By 1949, Americans felt increasingly threatened by the possibility of nuclear war with the Soviet Union and sought ways to survive a nuclear attack. The U.S. Federal Civil Defense Administration (USFCDA) was created by the government to educate the public on how to prepare for such an attack. In 1951, with the help of this agency, a children's educational film was produced in the U.S. called  Duck and Cover , in which a turtle demonstrates how to protect oneself from the immediate effects of an atomic bomb explosion by using a coat, tablecloths, or even a newspaper. [ 146 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1609", "text": "Recognizing that existing medical capacity would not be sufficient in an emergency, dentists were called upon to either assist physicians in an emergency or, if necessary, to provide assistance themselves. To mobilize the profession with the help of a prominent representative, dentist Russell Welford Bunting (1881-1962), dean of the  University of Michigan  Dental School, was recruited in July 1951 as a dental consultant to the USFCDA. [ 147 ] [ 148 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1610", "text": "The American physicist  Karl Ziegler Morgan  (1907-1999) was one of the founders of radiation health physics. In later life, after a long career with the Manhattan Project and  Oak Ridge National Laboratory  (ORNL), he became a critic of nuclear power and nuclear weapons production. Morgan was Director of Health Physics at ORNL from the late 1940s until his retirement in 1972. In 1955, he became the first president of the  Health Physics Society  and served as editor of the journal Health Physics from 1955 to 1977. [ 149 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1611", "text": "Nuclear fallout shelters  are designed to protect for an extended period. Due to the nature of nuclear warfare, such shelters must be completely self-sufficient for long periods. In particular, because of the radioactive contamination of the surrounding area, such a facility must be able to survive for several weeks. In 1959, top-secret construction began in Germany on a government bunker in the  Ahr  valley. In June 1964, 144 test persons survived for six days in a civilian nuclear bunker. The bunker in Dortmund had been built during the Second World War and had been converted at great expense in the early 1960s into a nuclear-weapon-proof building. However, it would be impossible to build a bunker for millions of German citizens. [ 150 ]  The Swiss Army built about 7800 nuclear fallout shelters in 1964. In the United States in particular, but also Europe, citizens built private fallout shelters in their front yards on their initiative. This construction was largely kept secret because the owners feared that third parties might take possession of the bunker in the event of a crisis."}
{"_id": "WikiPedia_Radiology$$$corpus_1612", "text": "On July 16, 1945, the first  atomic bomb test  took place near the town of  Alamogordo  (New Mexico, USA). As a result of the atmospheric nuclear weapons tests carried out by the United States, the Soviet Union, France, Great Britain, and China, the Earth's atmosphere became increasingly contaminated with fission products from these tests from the 1950s onwards. The  radioactive fallout  landed on the earth's surface and ended up in plants and, via animal feed, in food of animal origin. Ultimately, they entered the human body and could be detected in bones and teeth as strontium-90, among other things. [ 152 ]  The radioactivity in the field was measured with a gamma scope, as shown at the  air raid  equipment exhibition  in Bad Godesberg in 1954. [ 153 ]  Around 180 tests were carried out in 1962 alone. The extent of the radioactive contamination of the food sparked worldwide protests in the early 1960s."}
{"_id": "WikiPedia_Radiology$$$corpus_1613", "text": "During World War II and the Cold War, the  Hanford Site  produced plutonium for U.S. nuclear weapons for more than 50 years. The  plutonium  for the first plutonium bomb, Fat Man, also came from there. Hanford is considered the most radioactively contaminated site in the Western Hemisphere. [ 154 ]  A total of 110,000 tons of nuclear fuel was produced there. In 1948, a radioactive cloud leaked from the plant. The amount of  131 I  alone was 5500  curies . Most of the reactors at Hanford were shut down in the 1960s, but no disposal or decontamination was done. After preliminary work, the world's largest  decontamination  operation began at Hanford in 2001 to safely dispose of the radioactive and toxic waste. In 2006, some 11,000 workers were still cleaning up contaminated buildings and soil to reduce radiation levels at the site to acceptable levels. This work is expected to continue until 2052. [ 155 ]  It is estimated that more than four million liters of radioactive liquid have leaked from storage tanks."}
{"_id": "WikiPedia_Radiology$$$corpus_1614", "text": "It was only after the two superpowers agreed on a Partial Test Ban Treaty in 1963, which allowed only underground nuclear weapons testing, that the level of radioactivity in food began to decline.  Shields Warren  (1896-1980), one of the authors of a report on the effects of the atomic bombs dropped on Japan, was criticized for downplaying the effects of residual radiation in Hiroshima and Nagasaki, [ 156 ]  but later warned of the dangers of fallout. Fallout refers to the spread of radioactivity in the context of a given meteorological situation. A model experiment was conducted in 2008. [ 157 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1615", "text": "The  International Campaign to Abolish Nuclear Weapons  (ICAN) is an international alliance of non-governmental organizations committed to the elimination of all nuclear weapons through a binding international treaty - a Nuclear Weapons Convention. ICAN was founded in 2007 by IPPNW ( International Physicians for the Prevention of Nuclear War ) and other organizations at the  Nuclear Non-Proliferation Treaty  Conference in Vienna and launched in twelve countries. Today, 468 organizations in 101 countries are involved in the campaign (as of 2017). [ 158 ]  ICAN was awarded the 2017  Nobel Peace Prize . [ 159 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1616", "text": "A radioprotector is a  pharmacon  that, when administered, selectively protects healthy cells from the toxic effects of  ionizing radiation . The first work with radioprotectors began as part of the  Manhattan Project , a military research project to develop and build an atomic bomb."}
{"_id": "WikiPedia_Radiology$$$corpus_1617", "text": "Iodine  absorbed by the body is almost completely stored in the  thyroid gland  and has a biological  half-life  of about 120 days. If the iodine is radioactive ( 131 I), it can irradiate and damage the thyroid gland in high doses during this time. Because the thyroid gland can only absorb a limited amount of iodine, prophylactic administration of non-radioactive iodine may result in iodine blockade.  Potassium iodide  in tablet form (colloquially known as \"iodine tablets\") reduces the uptake of radioactive iodine into the thyroid by a factor of 90 or more, thus acting as a radioprotector. [ 160 ]  All other radiation damage remains unaffected by taking iodine tablets. In Germany, the Potassium Iodide Ordinance (KIV) was enacted in 2003 to ensure \"the supply of the population with potassium iodide-containing  medicines  in the event of radiological incidents\"."}
{"_id": "WikiPedia_Radiology$$$corpus_1618", "text": "\u00a7 1 \n kiv  (in German)\nPotassium iodide is usually stored in communities near nuclear facilities for distribution to the population in the event of a disaster. [ 161 ]  People over the age of 45 should not take iodine tablets because the risk of side effects is higher than the risk of developing thyroid cancer. In Switzerland, as a precautionary measure, tablets have been distributed every five years since 2004 to the population living within 20\u00a0km of nuclear power plants (from 2014, 50\u00a0km). [ 162 ] [ 163 ]  In Austria, large stocks of iodine tablets have been kept in pharmacies, kindergartens, schools, the army and the  federal reserve  since 2002. [ 164 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1619", "text": "Thanks to the protective function of radioprotectors, the dose of radiation used to treat malignant tumors (cancer) can be increased, thereby increasing the effectiveness of the therapy. [ 165 ]  There are also  radiosensitizers , which increase the sensitivity of malignant tumor cells to ionizing radiation. [ 166 ]  As early as 1921, the German radiologist  Hermann Holthusen  (1886-1971) described that oxygen increases the sensitivity of cells. [ 167 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1620", "text": "Founded in 1957 as a sub-organization of the  Organization for Economic Cooperation and Development  (OECD), the  Nuclear Energy Agency  (NEA) pools the scientific and financial resources of participating countries' nuclear research programs. It operates various databases and also manages the  International Reporting System for Operating Experience  (IRS or IAEA/NEA Incident Reporting System) of the  International Atomic Energy Agency  (IAEA). The IAEA records and investigates radiation accidents that have occurred worldwide in connection with nuclear medical procedures and the disposal of related materials. [ 168 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1621", "text": "The  International Nuclear and Radiological Event Scale  (INES) is a scale for safety-related events, in particular nuclear incidents and accidents in nuclear facilities. It was developed by an international group of experts and officially adopted in 1990 by the International Atomic Energy Agency (IAEA) and the Nuclear Energy Agency of the Organization for Economic Cooperation and Development (OECD). [ 169 ]  The purpose of the scale is to inform the public quickly about the safety significance of an event by means of a comprehensible classification of events."}
{"_id": "WikiPedia_Radiology$$$corpus_1622", "text": "At the end of its useful life, the proper disposal of the remaining high activity is of paramount importance. Improper disposal of the radionuclide  cobalt-60 , used in  cobalt guns  for radiotherapy, has led to serious radiation accidents, such as the  Ciudad Ju\u00e1rez (Mexico) radiological accident  in 1983/84, [ 170 ]  the  Goi\u00e2nia (Brazil) accident  in 1987, the  Samut Prakan (Thailand) nuclear accident  in 2000, and the Mayapuri (India) accident in 2010. [ 171 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1623", "text": "Eleven  Therac-25   linear accelerators  were built by the Canadian company  Atomic Energy of Canada Limited  (AECL) between 1982 and 1985 and installed in clinics in the United States and Canada.  Software errors  and a lack of quality assurance led to a serious malfunction that killed three patients and seriously injured three others between June 1985 and 1987 before appropriate countermeasures were taken. The radiation exposure in the six cases was subsequently estimated to be between 40 and 200  Gray ; normal treatment is equivalent to a dose of less than 2 Gray. [ 172 ] [ 173 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1624", "text": "Around 1990, about one hundred cobalt guns were still in use in Germany. In the meantime,  electron linear accelerators  were introduced and the last cobalt gun was decommissioned in 2000. [ 174 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1625", "text": "The  Fukushima nuclear accident  in 2011 reinforced the need for proper safety management and the derivation of safety indicators regarding the frequency of errors and incorrect actions by personnel, i.e., the  human factor . [ 175 ]  The  Nuclear Safety Commission of Japan  ( Japanese :  \u539f\u5b50\u529b\u5b89\u5168\u59d4\u54e1\u4f1a ) was a body of scientists that advised the Japanese government on nuclear safety issues. The commission was established in 1978, [ 176 ]  but was dissolved after the Fukushima nuclear disaster on September 19, 2012, and replaced by the  Genshiryoku Kisei Iinkai [ 177 ]  ( Japanese :  \u539f\u5b50\u529b\u898f\u5236\u59d4\u54e1\u4f1a ,  lit. \u2009 'Nuclear Regulatory Committee'). It is an independent agency ( gaikyoku , \"external office\") of the Japanese  Ministry of the Environment  that regulates and monitors the safety of Japan's  nuclear power plants  and related facilities."}
{"_id": "WikiPedia_Radiology$$$corpus_1626", "text": "As a result of the  Chernobyl nuclear disaster  in 1986, the IAEA coined the term \" safety culture \" for the first time in 1991 to draw attention to the importance of human and organizational issues for the safe operation of nuclear power plants."}
{"_id": "WikiPedia_Radiology$$$corpus_1627", "text": "After this nuclear disaster, the sand in children's playgrounds in Germany was removed and replaced with uncontaminated sand to protect children who were most vulnerable to radioactivity. Some families temporarily left Germany to escape the fallout.  Infant mortality  increased significantly by 5% in 1987, the year after Chernobyl. [ 178 ]  In total, 316 more newborns died that year than statistically expected. In Germany, the  caesium 137  inventories from the Chernobyl nuclear disaster in soil and food decrease by 2-3% each year; however, the contamination of game and mushrooms was still comparatively high in 2015, especially in Bavaria; there are several cases of  game meat , especially  wild boar , exceeding the limits. [ 179 ]  However, controls are insufficient. [ 180 ] [ 181 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1628", "text": "\"In particular, wild boars in southern Bavaria are repeatedly found to have a very high radioactive contamination of over 10,000 Becquerel/kg. The limit is 600 Becquerel/kg. For this reason, the Bavarian Consumer Center advises against eating wild boar from the Bavarian Forest and south of the Danube too often. Whoever buys wild boar from a hunter, should ask for the measurement protocol.\""}
{"_id": "WikiPedia_Radiology$$$corpus_1629", "text": "Between 1969 and 1982,  conditioned  low- and intermediate-level radioactive waste was disposed of in the Atlantic Ocean at a depth of about 4,000 meters under the supervision of the  Nuclear Energy Agency  (NEA) of the  Organization for Economic Cooperation and Development  (OECD) in accordance with the provisions of the European Convention on the Prevention of Marine Pollution by Dumping of Waste of All Kinds (London Dumping Convention of June 11, 1974). This was carried out jointly by several European countries. [ 27 ]  Since 1993, international treaties have prohibited the dumping of radioactive waste in the oceans. [ 183 ]  For decades, this dumping of  nuclear waste  went largely unnoticed by the public until  Greenpeace  denounced it in the 1980s."}
{"_id": "WikiPedia_Radiology$$$corpus_1630", "text": "Since the commissioning of the first commercial nuclear power plants (USA 1956, Germany 1962), various final storage concepts for radioactive materials have been proposed in the following decades, of which only storage in  deep geological formations  appeared to be safe and feasible within a reasonable period of time and was pursued further. Due to the high activity of the short-lived fission products,  spent fuel  is initially handled only under water and stored for several years in a decay pool. The water is used for cooling and also shields much of the emitted radiation. This is followed either by  reprocessing  or by decades of interim storage. Waste from reprocessing must also be stored temporarily until the heat has decreased enough to allow final disposal.  Casks  are special  containers  for the storage and transport of highly radioactive materials. Their maximum permissible dose rate is 0.35 mSv/h, of which a maximum of 0.25 mSv/h is due to neutron radiation. The safety of these transport containers has been discussed every three years since 1980 at the International Symposium on the Packaging and Transportation of Radioactive Materials (PATRAM). [ 184 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1631", "text": "Following various experiments, such as the Gorleben exploratory mine or the  Asse mine , a working group on the selection procedure for repository sites (AkEnd) developed recommendations for a new selection procedure for repository sites between 1999 and 2002. [ 185 ]  In Germany, the  Site Selection Act  was passed in 2013 and the  Act on the Further Development of the Site Search  was passed on March 23, 2017. A suitable site is to be sought throughout Germany and identified by 2031. In principle, crystalline (granite), salt or clay rock types can be considered for a repository. There will be no \"ideal\" site. The \"best possible\" site will be sought. Mining areas and regions where volcanoes have been active or where there is a risk of earthquakes are excluded. Internationally, experts are advocating storage in rock formations several hundred meters below the earth's surface. This involves building a repository mine and storing the waste there. It is then permanently sealed. Geological and technical barriers surrounding the waste are designed to keep it safe for thousands of years. For example, 300 meters of rock will separate the repository from the earth's surface. [ 186 ]  It will be surrounded by a 100-meter-thick layer of granite, salt or clay. The first waste is not expected to be stored until 2050. [ 187 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1632", "text": "The Federal Office for the Safety of Nuclear Waste Management (BfE) took up its activities on September 1, 2004. [ 188 ]  Its remit includes tasks relating to nuclear safety, the safety of nuclear waste management, the site selection procedure including research activities in these areas and, later on, further tasks in the area of licensing and supervision of repositories."}
{"_id": "WikiPedia_Radiology$$$corpus_1633", "text": "In the USA,  Yucca Mountain  was initially selected as the final storage site, but this project was temporarily halted in February 2009. Yucca Mountain was the starting point for an investigation into atomic semiotics."}
{"_id": "WikiPedia_Radiology$$$corpus_1634", "text": "The operation of nuclear power plants and other nuclear facilities produces radioactive materials that can have lethal health effects for thousands of years. It is important to note that there is no institution capable of maintaining the necessary knowledge of the dangers over such periods, and of ensuring that warnings about the dangers of nuclear waste in nuclear repositories will be understood by posterity in the distant future. A few years ago, even the capsules of the radionuclide cobalt-60, which were appropriately labeled, went unnoticed. Improper disposal led to the opening of these capsules, resulting in fatal consequences. The dimensions of time exceed previous human standards. For instance, cuneiform writing, which is only about 5000 years old (about 150 human generations), can only be understood after a long period of research and by experts. In 1981, research into the development of atomic semiotics began in the USA, [ 189 ]  in the German-speaking world,  Roland Posner  (1942-2020) of the Center for Semiotics at  Technische Universit\u00e4t Berlin  worked on this in 1982/83. [ 190 ]  In the USA, the time horizon for such warning signs was set at 10,000 years; later, as in Germany, it was set at a period of one million years, which would correspond to about 30,000 (human) generations. To date, no satisfactory solution to this problem has been found."}
{"_id": "WikiPedia_Radiology$$$corpus_1635", "text": "In 1912,  Victor Franz Hess  (1883-1964) discovered (secondary)  cosmic rays  in the Earth's atmosphere using balloon flights. For this discovery he received the  Nobel Prize in Physics  in 1936. He was also one of the \"martyrs\" of early radiation research and had to undergo a thumb amputation and  larynx  surgery due to radium burns. [ 191 ]  In the United States and the Soviet Union, balloon flights to altitudes of about 30\u00a0km, followed by  parachute jumps from the stratosphere , were conducted before 1960 to study human exposure to cosmic radiation in space. The American  Manhigh  and  Excelsior  projects with  Joseph Kittinger  (1928-2022) became particularly well known, but the Soviet parachutist  Yevgeny Andreyev  (1926-2000) also set new records. [ 192 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1636", "text": "High-energy radiation from  space  is much stronger at high altitudes than at sea level. The radiation exposure of flight crews and air travelers is therefore increased. The  International Commission on Radiological Protection  (ICRP) has issued recommendations for dose limits, which were incorporated into European law in 1996 and into the German Radiation Protection Ordinance in 2001. Radiation exposure is particularly high when flying in the polar regions or over the  polar route . [ 193 ]  The average annual effective dose for aviation personnel was 1.9 mSv in 2015 and 2.0 mSv in 2016. The highest annual personal dose was 5.7 mSv in 2015 and 6.0 mSv in 2016. [ 194 ]  The collective dose for 2015 was about 76 person-Sv. This means that  flight personnel  are among the occupational groups in Germany with the highest radiation exposure in terms of collective dose and average annual dose. [ 195 ]  This group also includes  frequent flyers , with Thomas Stuker holding the \"record\" - also in terms of radiation exposure - by reaching the 10 million mile mark with  United Airlines  MileagePlus on 5,900 flights between 1982 and the summer of 2011. [ 196 ]  In 2017, he passed the 18 million mile mark."}
{"_id": "WikiPedia_Radiology$$$corpus_1637", "text": "The program  EPCARD  (European Program Package for the Calculation of Aviation Route Dose) was developed at the  University of Siegen  and the  Helmholtz Munich  and can be used to calculate the dose from all components of natural penetrating cosmic radiation on any flight route and flight profile - also online. [ 197 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1638", "text": "From the earliest  crewed space flights  to the first  moon landing  and the construction of the  International Space Station  (ISS), radiation protection has been a major concern.  Spacesuits  used for extravehicular activities are coated on the outside with  aluminum , which largely protects against cosmic radiation. The largest international research project to determine the  effective dose  or effective dose equivalent was the  Matryoshka experiment  in 2010, named after the Russian  Matryoshka  dolls, because it uses a human-sized phantom that can be cut into slices. [ 198 ]  As part of Matroshka, an  anthropomorphic  phantom was exposed to the outside of the space station for the first time to simulate an  astronaut  performing an  extravehicular activity  (spacewalk) and determine their exposure to radiation. [ 199 ] [ 200 ] Microelectronics  on  satellites  must also be protected from radiation."}
{"_id": "WikiPedia_Radiology$$$corpus_1639", "text": "Japanese scientists from the  Japan Aerospace Exploration Agency  (JAXA) have discovered a huge cave on the moon with their  Kaguya  lunar probe, which could offer astronauts protection from dangerous radiation during future lunar landings, especially during the planned stopover of a Mars mission. [ 201 ] [ 202 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1640", "text": "As part of a  human mission to Mars , astronauts must be protected from cosmic radiation. During  Curiosity 's mission to Mars, a  Radiation Assessment Detector  (RAD) was used to measure radiation exposure. [ 203 ]  The radiation exposure of 1.8 millisieverts per day was mainly due to the constant presence of high-energy galactic particle radiation. In contrast, radiation from the sun accounted for only about three to five percent of the radiation levels measured during Curiosity's flight to Mars. On the way to Mars, the RAD instrument detected a total of five major radiation events caused by  solar flares . [ 204 ]  To protect the astronauts, a  plasma   bubble  will surround the spacecraft as an energy shield and its  magnetic field  will protect the crew from cosmic radiation. This would eliminate the need for conventional radiation shields, which are several centimeters thick and correspondingly heavy. [ 205 ]  In the Space Radiation Superconducting Shield (SR2S) project, which was completed in December 2015,  magnesium diboride  was found to be a suitable material for generating a suitable  force field . [ 206 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1641", "text": "Dosimeters  are instruments used to measure radiation dose - as absorbed dose or dose equivalent - and are an important cornerstone of radiation protection."}
{"_id": "WikiPedia_Radiology$$$corpus_1642", "text": "At the October 1907 meeting of the  American Roentgen Ray Society ,  Rome Vernon Wagner , an X-ray tube manufacturer, reported that he had begun carrying a photographic plate in his pocket and developing it every evening. This allowed him to determine how much radiation he had been exposed to. This was the forerunner of the  film dosimeter . His efforts came too late, as he had already developed cancer and died six months after the conference."}
{"_id": "WikiPedia_Radiology$$$corpus_1643", "text": "In the 1920s, the  physical chemist  John Eggert (1891-1973) played a key role in the introduction of  film dosimetry  for routine personal monitoring. Since then, it has been successively improved and, in particular, the evaluation technique has been automated since the 1960s. [ 207 ]  At the same time,  Hermann Joseph Muller  (1890-1967) discovered  mutations  as genetic consequences of X-rays, for which he was awarded the Nobel Prize in 1946. At the same time, the  roentgen  (R) was introduced as a unit for quantitative measurement of radiation exposure."}
{"_id": "WikiPedia_Radiology$$$corpus_1644", "text": "A dosimeter for film is divided into multiple segments, each containing a light- or radiation-sensitive film surrounded by layers of copper and lead with varying thickness. The degree of radiation penetration determines whether the segment is not blackened or blackened to varying degrees. The absorbed radiation effect during the measurement time is summed up, and the radiation dose can be determined from the blackening. Guidelines for evaluation exist, with those for Germany being published in 1994 and last updated on December 8, 2003. [ 208 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1645", "text": "With the invention of the Geiger  gaseous ionization detector  in 1913, which became the Geiger-M\u00fcller gaseous ionization detector in 1928 - named after the physicists  Hans Geiger  (1882-1945) and Walther M\u00fcller (1905-1979) - the individual particles or quanta of ionizing radiation could be detected and measured. Detectors developed later, such as proportional counters or  scintillation counters , which not only \"count\" but also measure energy and distinguish between types of radiation, also became important for radiation protection. Scintillation measurement is one of the oldest methods of detecting ionizing radiation or X-rays; originally, a  zinc sulfide screen  was held in the path of the beam and the scintillation events were either counted as flashes or, in the case of X-ray diagnostics, viewed as an image. A scintillation counter known as a  spinthariscope  was developed in 1903 by  William Crookes  (1832-1919) [ 209 ]  and used by  Ernest Rutherford  (1871-1937) to study the scattering of alpha particles from atomic nuclei."}
{"_id": "WikiPedia_Radiology$$$corpus_1646", "text": "Lithium fluoride  had already been proposed in the USA in 1950 by  Farrington Daniels  (1889-1972), Charles A. Boyd and  Donald F. Saunders  (1924-2013) for solid-state dosimetry using  thermoluminescent dosimeters . The intensity of the thermoluminescent light is proportional to the amount of radiation previously absorbed. This type of dosimetry has been used since 1953 in the treatment of cancer patients and wherever people are occupationally exposed to radiation. [ 210 ]  The thermoluminescence dosimeter was followed by OSL dosimetry, which is not based on heat but on  optically stimulated luminescence  and was developed by  Zenobia Jacobs  and Richard Roberts at the  University of Wollongong  (Australia). [ 211 ]  The detector emits the stored energy as light. The light output, measured with  photomultipliers , is then a measure of the dose. [ 212 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1647", "text": "Since 2003,  whole-body counters  have been used in radiation protection to monitor the absorption (incorporation) of radionuclides in people who handle gamma-emitting open radioactive materials and who may be contaminated through food, inhalation of dusts and gases, or open wounds. ( \u03b1  and  \u03b2  emitters are not measurable). [ 213 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1648", "text": "Constancy testing is the verification of reference values as part of  quality assurance  in  x-ray diagnostics ,  nuclear medicine  diagnostics, and  radiotherapy . National regulations specify [ 214 ] [ 215 ]  which parameters are to be tested, which limits are to be observed, which test methods are to be used, and which test samples are to be used. In Germany, the Radiation Protection in Medicine Directive and the relevant DIN 6855 standard in nuclear medicine require regular (in some cases daily) constancy testing.  Test sources  are used to check the response of probe measuring stations as well as  in vivo  and  in vitro  measuring stations. Before starting the tests, the background count rate and the setting of the energy window must be checked every working day, and the settings and the yield with reproducible geometry must be checked at least once a week with a suitable test source, e.g. 137Caesium (DIN 6855-1). [ 216 ]  The reference values for the constancy test are determined during the acceptance test."}
{"_id": "WikiPedia_Radiology$$$corpus_1649", "text": "Compact test specimens for medical X-ray images were not created until 1982. Prior to this, the patient himself often served as the object for producing X-ray test images. Prototypes of such an X-ray phantom with integrated structures were developed by Thomas Bronder at the  Physikalisch-Technische Bundesanstalt . [ 217 ] [ 218 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1650", "text": "A water phantom is a Plexiglas container filled with distilled water that is used as a substitute for living tissue to test electron linear accelerators used in radiation therapy. According to regulatory requirements, water phantom testing must be performed approximately every three months to ensure that the radiation dose delivered by the treatment system is consistent with the  radiation planning . [ 219 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1651", "text": "The Alderson-Rando phantom, invented by  Samuel W. Alderson  (1914-2005), has become the standard X-ray phantom. It was followed by the Alderson Radio Therapy (ART) phantom, which he patented in 1967. The ART phantom is cut horizontally into 2.5\u00a0cm thick slices. Each slice has holes sealed with bone-equivalent, soft-tissue-equivalent, or lung-equivalent pins that can be replaced by thermoluminescent dosimeters. Alderson is also known as the inventor of the  crash test dummy . [ 220 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1652", "text": "As a result of accidents or improper use and disposal of radiation sources, a significant number of people are exposed to varying degrees of radiation. Radioactivity and  local dose measurements  are not sufficient to fully assess the effects of radiation. To retrospectively determine the individual radiation dose, measurements are made on teeth, i.e. on biological, endogenous materials.  Tooth enamel  is particularly suitable for the detection of ionizing radiation due to its high mineral content ( hydroxyapatite ), which has been known since 1968 thanks to the research of John M. Brady, Norman O. Aarestad and Harold M. Swartz. [ 221 ]  The measurements are performed on  milk teeth , preferably molars, using  electron paramagnetic resonance spectroscopy  (ESR, EPR). The concentration of  radicals  generated by ionizing radiation is measured in the mineral part of the tooth. Due to the high stability of the radicals, this method can be used for dosimetry of long past exposures. [ 222 ] [ 223 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1653", "text": "Since about 1988, in addition to physical dosimetry, biological dosimetry has made it possible to reconstruct the individual dose of ionizing radiation. This is especially important for unforeseen and accidental exposures, where radiation exposures occur without physical dose monitoring. Biological markers, particularly cytogenetic markers in blood lymphocytes, are used for this purpose. Techniques for detecting radiation damage include analyzing dicentric chromosomes after acute radiation exposure. Dicentric chromosomes result from defective repair of chromosome breaks in two chromosomes, resulting in two centromeres instead of one like undamaged chromosomes. Symmetric translocations, detected through fluorescence in situ hybridization (FISH), are used after chronic or long-term exposure to radiation. The micronucleus test and the premature chromosome condensation (PCC) test are available to measure acute exposure. [ 224 ] [ 225 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1654", "text": "In principle, reducing the exposure of the human organism to ionizing radiation to zero is not possible and perhaps not even sensible. The human organism has been accustomed to natural radioactivity for thousands of years and ultimately this also triggers  mutations  (changes in  genetic material ), which are the cause of the development of life on earth. The mutation-inducing effect of high-energy radiation was first demonstrated in 1927 by  Hermann Joseph Muller  (1890-1967). [ 226 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1655", "text": "Three years after its establishment in 1958, the United Nations Scientific Committee on the Effects of Atomic Radiation adopted the Linear No-Threshold  (LNT) model  - a linear dose-effect relationship without a threshold - largely at the instigation of the Soviet Union. The dose-response relationship measured at high doses was extrapolated linearly to low doses. There would be no threshold, since even the smallest amounts of ionizing radiation would trigger some biological effect. [ 227 ]  The LNT model ignores not only possible  radiation hormesis , but also the known ability of  cells  to repair  genetic damage  and the ability of the organism to remove damaged cells. [ 228 ] [ 229 ] [ 230 ]  Between 1963 and 1969,  John W. Gofman  (1918-2007) and  Arthur R. Tamplin  of the  University of California, Berkeley , conducted research for the  United States Atomic Energy Commission  (USAEC, 1946-1974) investigating the relationship between radiation doses and cancer incidence. Their findings sparked a fierce controversy in the United States beginning in 1969. Starting in 1970,  Ernest J. Sternglass , a radiologist at the  University of Pittsburgh , published several studies describing the effect of radiation from nuclear tests and the vicinity of nuclear power plants on infant mortality. In 1971, the UASEC reduced the maximum allowable radiation dose by a factor of 100. Subsequently, nuclear technology was based on the principle of \"As Low As Reasonably Achievable\" ( ALARA ). This was a coherent principle as long as it was assumed that there was no threshold and that all doses were additive. In the meantime, a transition to \"As High As Reasonably Safe\" (AHARS) is increasingly being discussed. For the question of evacuation after accidents, a transition to AHARS seems absolutely necessary. [ 231 ]  In both the Chernobyl and Fukushima cases, hasty, poorly organized and poorly communicated evacuations caused psychological and physical damage to those affected - including documented deaths in the case of Fukushima. [ 232 ] [ 233 ] [ 234 ]  By some estimates, this damage is greater than would have been expected had the evacuation not taken place. [ 235 ] [ 236 ] [ 237 ]  Voices such as Geraldine Thomas therefore question such evacuations in principle and call for a transition to shelter-in-place wherever possible. [ 238 ] [ 239 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1656", "text": "The British physicist and radiologist and founder of  radiobiology   Louis Harold Gray  (1905-1965) introduced the unit  Rad  (acronym for radiation absorbed dose) in the 1930s, which was renamed  Gray  (Gy) after him in 1978. One gray is a mass-specific quantity and corresponds to the energy of one  joule  absorbed by one kilogram of body weight. Acute whole-body exposures in excess of four Gy are usually fatal to humans."}
{"_id": "WikiPedia_Radiology$$$corpus_1657", "text": "The different types of radiation  ionize  to different degrees. Ionization is any process in which one or more electrons are removed from an atom or molecule, leaving the atom or molecule as a positively charged ion ( cation ). Each type of radiation is therefore assigned a dimensionless weighting factor that expresses its biological effectiveness. For X-rays,  gamma  and beta radiation, the factor is one, alpha radiation reaches a factor of twenty, and for  neutron radiation  it is between five and twenty, depending on the energy."}
{"_id": "WikiPedia_Radiology$$$corpus_1658", "text": "Multiplying the absorbed dose in Gy by the weighting factor gives the  equivalent dose , expressed in Sievert (Sv). It is named after the Swedish physician and physicist  Rolf Maximilian Sievert  (1896-1966). Sievert was the founder of radiation protection research and developed the Sievert chamber in 1929 to measure the intensity of X-rays. He founded the  International Commission on Radiation Units and Measurements  (ICRU) and later became chairman of the  International Commission on Radiological Protection  (ICRP). [ 240 ]  The ICRU and ICRP specify differently defined weighting factors that apply to environmental measurements (quality factor) and body-related dose equivalent data (radiation weighting factor)."}
{"_id": "WikiPedia_Radiology$$$corpus_1659", "text": "In relation to the body, the relevant dose term is the  Organ Equivalent Dose  (formerly \"Organ Dose\"). This is the dose equivalent averaged over an organ. Multiplied by organ-specific tissue weighting factors and summed over all organs, the  effective dose  is obtained, which represents a dose balance. In relation to environmental measurements, the ambient dose equivalent or local dose is relevant. Its increase over time is called the local dose rate."}
{"_id": "WikiPedia_Radiology$$$corpus_1660", "text": "Even at very low effective doses, stochastic effects (genetic and cancer risk) are expected. At effective doses above 0.1 Sv, deterministic effects also occur (tissue damage up to radiation sickness at very high doses). Correspondingly high radiation doses are now only given in units of Gy. Natural radiation exposure in Germany, with an annual average effective dose of about 0.002 Sv, is well below this range. [ 241 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1661", "text": "In 1931, the U.S. Advisory Committee on X-Ray and Radium Protection (ACXRP, now the National Council on Radiation Protection and Measurements, NCRP), founded in 1929, published the results of a study on the so-called tolerance dose, on which a scientifically based radiation protection guideline was based. Exposure limits were gradually lowered. In 1936 the tolerance dose was 0.1 R/day. [ 9 ]  The unit \"R\" (the X-ray) from the  CGS unit system  has been obsolete since the end of 1985. Since then, the  SI  unit of ion dose has been \" coulomb  per kilogram\"."}
{"_id": "WikiPedia_Radiology$$$corpus_1662", "text": "After World War II, the concept of tolerance dose was replaced by that of maximum permissible dose and the concept of relative biological effectiveness was introduced. The limit was set in 1956 by the  National Council on Radiation Protection & Measurements  (NCRP) and the  International Commission on Radiological Protection  (ICRP) at 5 rem (50  mSv ) per year for radiation workers and 0.5 rem per year for the general population. The unit  Rem  as a physical measure of radiation dose (from the English roentgen equivalent in man) was replaced by the unit Sv (sievert) in 1978. This was due to the advent of nuclear energy and its associated dangers. [ 242 ]  Prior to 1991, the equivalent dose was used both as a measure of dose and as a term for the body dose that determines the course and survival of radiation sickness. ICRP Publication 60 [ 243 ]  introduced the radiation weighting factor  \n \n \n \n \n w \n \n R \n \n \n \n \n {\\displaystyle w_{R}} \n \n  was introduced. For examples of equivalent doses as body doses, see"}
{"_id": "WikiPedia_Radiology$$$corpus_1663", "text": "The origin of the concept of using a banana equivalent dose (BED) as a benchmark is unknown. In 1995, Gary Mansfield of the  Lawrence Livermore National Laboratory  found the Banana Equivalent Dose (BED) to be very useful in explaining radiation risks to the public. [ 244 ]  It is not a formally used dose."}
{"_id": "WikiPedia_Radiology$$$corpus_1664", "text": "The banana equivalent dose is the dose of ionizing radiation to which a person is exposed by eating one banana. Bananas contain  potassium . Natural potassium consists of 0.0117% of the  radioactive isotope   40 K (potassium-40) and has a specific activity of 30,346 becquerels per kilogram, or about 30 becquerels per gram. The radiation dose from eating a banana is about 0.1 \u03bcSv. [ 244 ]  The value of this reference dose is given as \"1\" and thus becomes the \"unit of measurement\" banana equivalent dose. Consequently, other radiation exposures can be compared to the consumption of one banana. For example, the average daily total radiation exposure of a person is 100 banana equivalent doses."}
{"_id": "WikiPedia_Radiology$$$corpus_1665", "text": "At 0.17 mSv per year, almost 10 percent of natural  radioactive exposure  in Germany (an average of 2.1 mSv per year) is caused by the body's own (vital) potassium. [ 245 ] [ 246 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1666", "text": "The banana equivalent dose does not take into account the fact that no radioactive nuclide is  accumulated  in the body through the consumption of potassium-containing foods. The potassium content of the body is in  homeostasis  and is kept constant. [ 247 ] [ 248 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1667", "text": "The  Trinity test  was the first nuclear weapon explosion conducted as part of the US  Manhattan Project . There were no warnings to residents about the fallout, nor information about shelters or possible evacuations. [ 249 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1668", "text": "This was followed in 1946 by tests in the  Marshall Islands  (Operation Crossroads), [ 250 ]  as recounted by chemist Harold Carpenter Hodge (1904-1990), toxicologist for the Manhattan Project, in his lecture (1947) as president of the International Association for Dental Research. [ 251 ]  Hodge's reputation was severely damaged by historian Eileen Welsome's 1999  Pulitzer Prize -winning book The Plutonium Files - America's Secret Medical Experiments in the Cold War. She documents horrific human experiments in which the subjects (including Hodge) were unaware that they were being used as \"guinea pigs\" to test the safety limits of uranium and plutonium. The experiments on the unidentified subjects were continued by the  United States Atomic Energy Commission  (AEC) into the 1970s. [ 252 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1669", "text": "The abuse of radiation continues to this day. [ 253 ]  During the Cold War, ethically reprehensible radiation experiments were conducted in the United States on untrained human subjects to determine the detailed effects of radiation on human health. Between 1945 and 1947, 18 people were injected with  plutonium  by Manhattan Project doctors. In Nashville, pregnant women were given radioactive mixtures. In Cincinnati, about 200 patients were irradiated over a 15-year period. In Chicago, 102 people received injections of  strontium  and  caesium  solutions. In Massachusetts, 57 children with developmental disorders were given  oatmeal  with radioactive markers. These radiation experiments were not stopped until 1993 under President  Bill Clinton . But the injustice committed was not atoned for. [ 254 ] [ 255 ]  For years,  uranium hexafluoride  caused radiation damage at a  DuPont  Company plant and to local residents. [ 256 ]  At times, the plant even deliberately released uranium hexafluoride in its heated gaseous state into the surrounding area to study the effects of the radioactive and chemically aggressive gas."}
{"_id": "WikiPedia_Radiology$$$corpus_1670", "text": "Between 1978 and 1989, vehicles were checked with  137 Cs  gamma sources at 17 border crossings between the German Democratic Republic and the Federal Republic of Germany. According to the Transit Agreement, vehicles could only be screened if there was reasonable suspicion. For this reason, the  Ministry for State Security  (Stasi) installed and operated a secret  radioactive screening technology , codenamed \"Technik V,\" which was generally used to screen all transit passengers to detect \" deserters from the Republic .\" Ordinary GDR customs officers were unaware of the secret radioactive screening technology and were subject to strict \"entry regulations\" designed to \"protect\" them as much as possible from radiation exposure. Lieutenant General  Heinz Fiedler  (1929-1993), as the highest ranking border guard of the MfS, was responsible for all radiation controls. [ 257 ]  On February 17, 1995, the Radiation Protection Commission published a statement in which it said: \"Even if we assume that individual persons stopped more frequently in the radiation field and that a fluoroscopy lasting up to three minutes increases the annual radiation exposure by one to a few mSv, this does not result in a dose that is harmful to health\". [ 258 ]  In contrast, the designer of this type of border control calculated 15 nSv per crossing. Lorenz of the former State Office for Radiation Protection and Nuclear Safety of the GDR came up with a dose estimate of 1000 nSv, which was corrected to 50 nSv a few weeks later. [ 257 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1671", "text": "Radar equipment  is used at airports, in airplanes, at  missile sites , on tanks, and on ships. The radar technology commonly used in the 20th century produced X-rays as a technically unavoidable by-product in the  high-voltage electronics  of the equipment. [ 259 ]  In the 1960s and 1970s, German soldiers and technicians were largely unaware of the dangers, as were those in the GDR's  National People's Army . [ 259 ]  The problem had been known internationally since the 1950s, and to the German Armed Forces since at least 1958. [ 260 ]  However, no radiation protection measures were taken, such as the wearing of lead aprons. Until about the mid-1980s, radiation shielding was inadequate, especially for pulse switch tubes. [ 259 ]  Particularly affected were maintenance technicians (radar mechanics) who were exposed to the X-ray generating parts for hours without any protection. The permissible annual limit value could be exceeded after just 3 minutes. It was not until 1976 that warning notices were put up and protective measures taken in the German Navy, and not until the early 1980s in general. [ 259 ]  As late as the 1990s, the German Armed Forces denied any connection between radar equipment and cancer or genetic damage. [ 261 ]  The number of victims amounted to several thousand. The connection was later acknowledged by the German Armed Forces and in many cases a supplementary pension was paid. In 2012, a foundation was set up to provide unbureaucratic compensation for the victims. [ 262 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1672", "text": "The harmful effects of X-rays were recognized during the  National Socialist  era. The function of the  gonads  ( ovaries  or  testicles ) was destroyed by ionizing radiation, leading to  infertility . In July 1942,  Heinrich Himmler  (1900-1945) decided to conduct forced sterilization experiments at the  Auschwitz-Birkenau concentration camp , which were carried out by  Horst Schumann  (1906-1983), previously a doctor in  Aktion T4 . [ 263 ]  Each test victim had to stand between two X-ray machines, which were arranged in such a way that the test victim had just enough space between them. Opposite the x-ray machines was a booth with lead walls and a small window. From the booth, Schumann could direct X-rays at the test victims' sexual organs without endangering himself. [ 264 ]  Human radiation castration experiments were also conducted in  concentration camps  under the direction of  Viktor Brack  (1904-1948). As part of the \"Law for the Prevention of Hereditary Diseases,\" people were often subjected to radiation castration during interrogations without their knowledge. [ 265 ]  Approximately 150 radiologists from hospitals throughout Germany participated in the forced castration of approximately 7,200 people using X-rays or radium. [ 266 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1673", "text": "On November 23, 2006,  Alexander Alexanderovich Litvinenko  (1962-2006) was murdered under unexplained circumstances as a result of radiation sickness caused by  polonium . [ 267 ]  This was also briefly suspected in the case of  Yasser Arafat  (1929-2004), who died in 2004."}
{"_id": "WikiPedia_Radiology$$$corpus_1674", "text": "The misuse of ionizing radiation is a radiation offence under  German criminal law . The use of ionizing radiation to harm persons or property is punishable. Since 1998, the regulations can be found in"}
{"_id": "WikiPedia_Radiology$$$corpus_1675", "text": "\u00a7 309 \n StGB  (in German)\n(previously \u00a7 311a StGB old version); the regulations go back to \u00a7 41 AtG old version. In the Austrian Criminal Code, relevant criminal offenses are defined in the seventh section, \" Criminal acts dangerous to the public \" and \" Criminal acts against the environment \". In Switzerland, endangerment by nuclear energy, radioactive substances or ionizing radiation is punishable under Art. 326 of the Swiss Criminal Code and disregard of safety regulations under Chapter 9 of the Nuclear Energy Act of 21 March 2003."}
{"_id": "WikiPedia_Radiology$$$corpus_1676", "text": "Originally, the term radiation protection referred only to ionizing radiation. Today, non-ionizing radiation is also included and is the responsibility of the Federal Office for Radiation Protection, the Radiation Protection Division [ 2 ]  of the  Federal Office of Public Health [ 3 ]  and the  Ministry of Climate Action and Energy (Austria) . [ 4 ]  The project collected, evaluated and compared data on the legal situation in all European countries (47 countries plus Germany) and major non-European countries (China, India, Australia, Japan, Canada, New Zealand and the USA) regarding electric, magnetic and electromagnetic fields (EMF) and optical radiation (OS). The results were very different and in some cases deviated from the recommendations of the  International Commission on Non-Ionizing Radiation Protection  (ICNIRP). [ 268 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1677", "text": "For many centuries, the  Inuit  ( Eskimos ) have used  snow goggles  with narrow slits, carved from seal bones or reindeer antlers, to protect against snow blindness (photokeratitis)."}
{"_id": "WikiPedia_Radiology$$$corpus_1678", "text": "In the 1960s, Australia - particularly  Queensland  - launched the first awareness campaign on the dangers of  ultraviolet (UV) radiation  in the spirit of primary prevention. In the 1980s, many countries in Europe and overseas initiated similar UV protection campaigns. UV radiation has a thermal effect on the skin and eyes and can lead to skin cancer (malignant melanoma) and eye inflammation or cataracts. [ 269 ]  To protect the skin from harmful UV radiation, such as  photodermatosis ,  acne aestivalis ,  actinic keratosis  or urticaria solaris, normal clothing, special UV protective clothing (SPF 40-50) and high SPF sunscreen can be used. The Australian-New Zealand Standard (AS/NZS 4399) of 1996 measures new textile materials in an unstretched and dry state for the manufacture of protective clothing worn while bathing, especially by children, and for the manufacture of shading textiles (sunshades, awnings). The UV Standard 801 assumes a maximum radiation intensity with the solar spectrum in Melbourne, Australia, on January 1 of a year (at the height of the Australian summer), the most sensitive skin type of the wearer, and under wearing conditions. As the  solar spectrum  in the  northern hemisphere  differs from that in Australia, the measurement method according to the European standard EN 13758-1 is based on the solar spectrum of  Albuquerque  (New Mexico, USA), which corresponds approximately to that of southern Europe. [ 270 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1679", "text": "To protect your eyes, wear sunglasses with UV protection or special goggles that also shield the sides to prevent snow blindness. A defensive reaction of the skin is the formation of a light callus, the skin's own sun protection, which corresponds to a protection factor of about 5. At the same time, the production of brown skin pigments ( melanin ) in the corresponding cells ( melanocytes ) is stimulated."}
{"_id": "WikiPedia_Radiology$$$corpus_1680", "text": "A  solar control film  is usually a film made of  polyethylene terephthalate  (PET) that is applied to windows to reduce the light and heat from the sun's rays. The film filters UV-A and UV-B radiation. Polyethylene terephthalate goes back to an invention by the two Englishmen  John Rex Whinfield  (1902-1966) and  James Tennant Dickson  in 1941."}
{"_id": "WikiPedia_Radiology$$$corpus_1681", "text": "The fact that UV-B radiation (Dorno radiation, after  Carl Dorno  (1865-1942)) is a proven carcinogen, but is also required for the body's own synthesis of  vitamin-D 3  (cholecalciferol), leads to internationally conflicting recommendations regarding health-promoting UV exposure. [ 271 ]  In 2014, based on the scientific evidence of the last decades, 20 scientific authorities, professional societies and associations from the fields of radiation protection, health, risk assessment, medicine and nutrition published a recommendation on \"UV exposure for the formation of the body's own vitamin D\". It was the first interdisciplinary recommendation on this topic worldwide. Using a  solarium  for the first time at a young age (<35 years) almost doubles the risk of developing malignant melanoma. In Germany, the use of tanning beds by minors has been prohibited by law since March 2010. As of August 1, 2012, sunbeds must not exceed a maximum irradiance of 0.3 watts per square meter of skin. Sunbeds must be labeled accordingly. The new irradiance limit corresponds to the highest UV dose that can be measured on Earth at 12 noon under a cloudless sky at the equator. [ 272 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1682", "text": "The minimum erythema dose (MED) is determined for medical applications. The MED is defined as the lowest dose of radiation that produces a barely visible erythema. It is determined 24 hours after the test irradiation. It is performed with the type of lamp intended for the therapy by applying so-called light stairs to skin that is not normally exposed to light (for example, on the buttocks). [ 273 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1683", "text": "Richard K\u00fcch (1860-1915) was able to melt  quartz glass  - the basis for UV radiation sources - for the first time in 1890 and founded the  Heraeus Quarzschmelze . He developed the first quartz lamp (sun lamp) for generating UV radiation in 1904, thus laying the foundation for this form of light therapy."}
{"_id": "WikiPedia_Radiology$$$corpus_1684", "text": "Despite the dosage problems, doctors increasingly used quartz lamps in the early 20th century.  Internal medicine  specialists and  dermatologists  were among the most eager testers. After successful treatment of  skin tuberculosis , internal medicine began to treat tuberculous  pleurisy , glandular tuberculosis and intestinal tuberculosis. In addition, doctors tested the effect of quartz lamps on other infectious diseases such as  syphilis ,  metabolic diseases ,  cardiovascular diseases , nerve pain such as  sciatica , or  nervous diseases  such as  neurasthenia  and  hysteria . In dermatology,  fungal diseases ,  ulcers  and wounds,  psoriasis ,  acne , freckles and hair loss were also treated with quartz lamps, while in gynecology, abdominal diseases were treated with quartz lamps. Rejuvenation specialists used artificial high-altitude sunlight to stimulate gonadal activity and treated infertility,  impotentia generandi  (inability to conceive), and  lack of sexual desire  by irradiating the genitals. For this purpose, Philipp Keller (1891-1973) developed an erythema dosimeter with which he measured the amount of radiation not in Finsen units (UV radiation with a wavelength \u03bb of 296.7\u00a0nm and an irradiance E of 10 \u22125  W/m 2 ), but in height solar units (HSE). It was the only instrument in use around 1930, but it was not widely accepted in medical circles. [ 274 ] [ 275 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1685", "text": "Treatment of acne with ultraviolet radiation is still controversial. Although UV radiation can have an antibacterial effect, it can also induce  proliferative hyperkeratosis . This can lead to the formation of  comedones  (\"blackheads\").  Phototoxic  effects may also occur. In addition, it is carcinogenic and promotes skin aging. UV therapy is increasingly being abandoned in favor of  photodynamic therapy . [ 276 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1686", "text": "The  ruby laser  was developed in 1960 by  Theodore Maiman  (1927-2007) as the first  laser  based on the  ruby maser . Soon after, the dangers of lasers were discovered, especially for the eyes and skin, due to the laser's low penetration depth. Lasers have numerous applications in technology and research as well as in everyday life, from simple  laser pointers  to  distance measuring devices , cutting and  welding tools , reproduction of  optical storage media  such as CDs, DVDs and Blu-ray discs, communication, laser scalpels and other devices using laser light in everyday medical practice. The Radiation Protection Commission requires that laser applications on human skin be performed only by a specially trained physician. Lasers are also used for show effects in discotheques and at events."}
{"_id": "WikiPedia_Radiology$$$corpus_1687", "text": "Lasers can cause biological damage due to the properties of their radiation and their sometimes extremely concentrated electromagnetic power. For this reason, lasers must be labeled with standardized warnings depending on the  laser class . The classification is based on the  DIN standard EN 60825-1 , which distinguishes between ranges of  wavelengths  and exposure times that lead to characteristic injuries and injury thresholds for power or  energy density ."}
{"_id": "WikiPedia_Radiology$$$corpus_1688", "text": "The  CO 2 -Laser  was developed in 1964 by the Indian electrical engineer and physicist  Chandra Kumar Naranbhai Patel  (*1938) [ 277 ]  at the same time as the  Nd:YAG laser  (neodymium-doped yttrium aluminum garnet laser) at  Bell Laboratories  by  LeGrand Van Uitert  (1922-1999) and Joseph E. Geusic (*1931) and the  Er:YAG laser  (erbium-doped yttrium aluminum garnet laser) and has been used in dentistry since the early 1970s. In the hard laser field, two systems in particular are emerging for use in the oral cavity: the CO2 laser for use in soft tissue and the Er:YAG laser for use in dental hard and soft tissue. The goal of  soft laser treatment  is to achieve  biostimulation  with low energy densities. [ 278 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1689", "text": "The Commission on Radiological Protection strongly recommends that the possession and purchase of class 3B and 4 laser pointers be regulated by law to prevent misuse. [ 279 ]  This is due to the increase in dangerous dazzle attacks caused by high-power laser pointers. In addition to pilots, these include truck and car drivers, train operators, soccer players, referees, and even spectators at soccer games. [ 280 ]  Such glare can lead to serious accidents and, in the case of pilots and truck drivers, to occupational disability due to eye damage. The first accident prevention regulation was published on April 1, 1988 as BGV B2, followed on January 1, 1997 by DGUV Regulation 11 of the German Social Accident Insurance. [ 281 ]  Between January and mid-September 2010, the  German Federal Aviation Office  registered 229 dazzle attacks on helicopters and airplanes of German airlines nationwide. [ 282 ]  On October 18, 2017, a perpetrator of a dazzle attack on a federal police helicopter was sentenced to one year and six months in prison without parole. [ 283 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1690", "text": "Electrosmog is colloquially understood as the exposure of humans and the environment to electric, magnetic and  electromagnetic fields , some of which are believed to have undesirable biological effects. [ 284 ]  Electromagnetic environmental compatibility (EMC) refers to the effects on living organisms, some of which are considered  electrosensitive . Fears of such effects have existed since the beginning of technological use in the mid-19th century. In 1890, for example, officials of the Royal General Directorate in Bavaria were forbidden to attend the opening ceremony of Germany's first alternating current power plant, the Reichenhall Electricity Works, or to enter the machine room. With the establishment of the first radio  telegraphy  and its telegraph stations, the U.S. magazine The Atlanta Constitution reported in April 1911 on the potential dangers of radio telegraph waves, which, in addition to \"tooth loss,\" were said to cause hair loss and make people \"crazy\" over time. [ 285 ]  Full-body protection was recommended as a preventive measure."}
{"_id": "WikiPedia_Radiology$$$corpus_1691", "text": "During the second half of the 20th century, other sources of electromagnetic fields have become the focus of health concerns, such as power lines,  photovoltaic systems , microwave ovens, computer and television screens, security devices, radar equipment, and more recently, cordless telephones ( DECT ), cell phones, their  base stations ,  energy-saving lamps , and  Bluetooth  connections. Electrified railroad lines, tram overhead lines and subway tracks are also strong sources of electrosmog. In 1996, the  World Health Organization  (WHO) launched the EMF (ElectroMagnetic Fields) Project to bring together current knowledge and available resources from key international and national organizations and scientific institutions on electromagnetic fields. [ 286 ] [ 287 ]   The German Federal Office for Radiation Protection  ( BfS ) published the following recommendation in 2006:"}
{"_id": "WikiPedia_Radiology$$$corpus_1692", "text": "\"In order to avoid possible health risks, the German Federal Office for Radiation Protection recommends that you minimize your personal exposure to radiation through your own initiative.\""}
{"_id": "WikiPedia_Radiology$$$corpus_1693", "text": "As of 2016, the EMF Guideline 2016 of EUROPAEM ( European Academy For Environmental Medicine ) on the prevention, diagnosis and treatment of EMF-related complaints and diseases applies. [ 289 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1694", "text": "A  microwave oven , invented in 1950 by U.S. researcher  Percy Spencer  (1894-1970), is used to quickly heat food using  microwave  radiation at a frequency of 2.45 gigahertz. In an intact microwave oven,  leakage radiation  is relatively low due to the  shielding  of the cooking chamber. An \"emission limit of five milliwatts per square centimeter (equivalent to 50 watts per square meter) at a distance of five centimeters from the surface of the appliance\" (radiation density or power flux density) is specified. Children should not stand directly in front of or next to the appliance while food is being prepared. In addition, the  Federal Office for Radiation Protection  lists pregnant women as particularly at risk. [ 290 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1695", "text": "In microwave therapy, electromagnetic waves are generated for heat treatment. The penetration depth and energy distribution vary depending on the frequency of application (short waves, ultra short waves, microwaves). To achieve greater penetration, pulsed microwaves are used, each of which delivers high energy to the tissue. A pulse pause ensures that no burns occur. Metal  implants  and  pacemakers  are contraindications. [ 291 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1696", "text": "The discussion about possible  health risks from mobile phone radiation  has been controversial to date, although there are currently no valid results. According to the German Federal Office for Radiation Protection"}
{"_id": "WikiPedia_Radiology$$$corpus_1697", "text": "\"there are still uncertainties in the risk assessment that could not be completely eliminated by the German Mobile Telecommunication Research Program, in particular possible health risks of long-term exposure to high-frequency electromagnetic fields from cell phone calls in adults (intensive cell phone use over more than 10 years) and the question of whether the use of cell phones by children could have an effect on health. For these reasons, the Federal Office for Radiation Protection still considers preventive health protection (precaution) to be necessary: exposure to electromagnetic fields should be kept as low as possible.\""}
{"_id": "WikiPedia_Radiology$$$corpus_1698", "text": "The German Federal Office for Radiation Protection recommends, among other things, mobile phones with a low  SAR  (Specific Absorption Rate) [ 292 ] [ 293 ]  and the use of headsets or hands-free devices to keep the mobile phone away from the head. There is some discussion that mobile phone radiation may increase the incidence of  acoustic neuroma , a benign tumor that arises from the  vestibulocochlear nerve . It should therefore be reduced. [ 294 ]  In everyday life, a mobile phone transmits at maximum power only in exceptional cases. As soon as it is near a cell where maximum power is no longer needed, it is instructed by that cell to reduce its power. Electrosmog or cell phone radiation filters built into cell phones are supposed to protect against radiation. The effect is doubtful from the point of view of electromagnetic environmental compatibility, because the radiation intensity of the cell phone is increased disproportionately in order to obtain the necessary power. The same is true for use in a car without an external antenna, as the necessary radiation can only penetrate through the windows, or in areas with poor network coverage. Since 2004, radio network  repeaters  have been developed for mobile phone networks ( GSM ,  UMTS ,  Tetrapol ) that can amplify the reception of a mobile phone  cell  in shaded buildings. This reduces the SAR value of the mobile phone when making calls."}
{"_id": "WikiPedia_Radiology$$$corpus_1699", "text": "The SAR value of a  WLAN   router  is only a tenth of that of a cell phone, although this drops by a further 80% at a distance of just one meter. The router can be set so that it switches off when not in use, for example at night. [ 295 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1700", "text": "Until now, electrical energy has been transported from the power plant to the consumer almost exclusively via  high-voltage lines , in which  alternating current  flows at a frequency of 50  Hertz . As part of the  energy transition ,  high-voltage direct current  (HVDC) transmission systems are also planned in Germany. Since the amendment of the 26th Federal Immission Control Ordinance (BImSchV) in 2013, emissions from HVDC systems are also regulated by law. The limit is set to prevent interference with electronic implants caused by static  magnetic fields . No limit has been set for static electric fields."}
{"_id": "WikiPedia_Radiology$$$corpus_1701", "text": "Ground fault interrupters are available to reduce  electric fields  and (in the case of  current  flow) magnetic fields from residential electrical installations. In  plaster  installations, only a small part of the electric field can escape from the wall. However, a mains disconnect switch automatically disconnects the relevant line as long as no electrical load is switched on; as soon as a load is switched on, the  mains voltage  is also switched on. [ 296 ]  Ground fault interrupters were introduced in 1973 and have been continuously improved over the decades. [ 297 ]  In 1990, for example, it became possible to disconnect the PEN conductor (formerly known as the neutral conductor). [ 298 ]  Circuit breakers can be installed in several different circuits, preferably in those that supply bedrooms. However, they only turn off when no continuous current consumers such as air conditioners, fans, humidifiers, electric alarm clocks, night lights, standby devices, alarm systems, chargers, and similar devices are turned on. Instead of the mains voltage, a  low voltage  (2-12 volts) is applied, which can be used to detect when a consumer is switched on."}
{"_id": "WikiPedia_Radiology$$$corpus_1702", "text": "Rooms can also be shielded with copper wallpaper or special wall paints containing metal, thus applying the  Faraday cage  principle."}
{"_id": "WikiPedia_Radiology$$$corpus_1703", "text": "Since about 2005,  body scanners  have been used primarily at airports for security (passenger) screening. Passive scanners detect the natural radiation emitted by a person's body and use it to locate objects worn or concealed on the body. Active systems also use artificial radiation to improve detection by analyzing the  backscatter . A distinction is made between body scanners that use ionizing radiation (usually X-rays) and those that use non-ionizing radiation ( terahertz radiation )."}
{"_id": "WikiPedia_Radiology$$$corpus_1704", "text": "The integrated components operating in the lower terahertz range emit less than 1\u00a0mW (-3 dBm), [ 299 ]  so no health effects are expected. There are conflicting studies from 2009 on whether genetic damage can be detected as a result of terahertz radiation. [ 300 ]  In the U.S., backscatter x-ray scanners make up the majority of devices used. Scientists fear that a future increase in cancer could pose a greater threat to the life and limb of passengers than terrorism itself. [ 301 ]  It is not clear to the passenger whether the body scanners used during a particular checkpoint use only terahertz or also X-ray radiation."}
{"_id": "WikiPedia_Radiology$$$corpus_1705", "text": "According to the Federal Office for Radiation Protection, the few available results from investigations in the frequency range of active whole-body scanners that work with  millimeter wave  or terahertz radiation do not yet allow a conclusive assessment from a radiation protection perspective (as of 24 May 2017). [ 302 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1706", "text": "In the vicinity of the plant, where employees or other third parties may be present, the limit value of the permissible annual dose for a single person in the population of one millisievert (1 mSv, including pregnant women and children) is not exceeded, even in the case of permanent presence."}
{"_id": "WikiPedia_Radiology$$$corpus_1707", "text": "In the case of X-ray scanners for hand luggage, it is not necessary to set up a radiation protection area by Section \u00a719  R\u00f6V , as the radiation exposure during a hand luggage check for passengers does not exceed 0.2 microsievert (\u03bcSv), even under unfavorable assumptions. For this reason, employees involved in baggage screening are not considered to be occupationally exposed to radiation in accordance with Section \u00a731 X-ray Ordinance and therefore do not have to wear a dosimeter. [ 303 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1708", "text": "Electromagnetic alternating fields  have been used in medicine since 1764, [ 304 ]  mainly for heating and increasing  blood circulation  ( diathermy ,  short-wave therapy ) to improve wound and bone healing. [ 305 ]  The relevant radiation protection is regulated by the Medical Devices Act together with the Medical Devices Operator Ordinance. [ 306 ]  The Medical Devices Act came into force in Germany on January 14, 1985. It divided the medical devices known at that time into groups according to their degree of risk to the patient. The Medical Devices Ordinance regulated the handling of medical devices until January 1, 2002, when it was replaced by the Medical Devices Act. When ionizing radiation is used in medicine, the benefit must outweigh the potential risk of tissue damage (justifiable indication). For this reason, radiation protection is of great importance. The design should be optimized according to the ALARA (As Low As Reasonably Achievable) principle as soon as an application is described as suitable. Since 1996, the European ALARA Network (EAN), founded by the  European Commission , has been working on the further implementation of the ALARA principle in radiation protection. [ 307 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1709", "text": "Discovered around 1800 by the German-British astronomer, engineer and musician  Friedrich Wilhelm Herschel  (1738-1822),  infrared radiation  primarily produces heat. If the increase in body temperature and the duration of exposure exceed critical limits, heat damage and even  heat stroke  can result. Due to the still unsatisfactory data situation and the partly contradictory results, it is not yet possible to give clear recommendations for radiation protection with regard to infrared radiation. However, the findings regarding the acceleration of skin aging by infrared radiation are sufficient to describe the use of infrared radiation against wrinkles as counterproductive. [ 308 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1710", "text": "In 2011, the  Institute for Occupational Safety and Health of the German Social Accident Insurance  established exposure limit values to protect the skin from burns caused by  thermal radiation . The IFA recommends that, in addition to the limit specified in EU Directive 2006/25/EC to protect the skin from burns for exposure times up to 10 seconds, a limit for exposure times between 10 and 1000 seconds should be applied. In addition, all radiation components in the wavelength range from 380 to 20000\u00a0nm should be considered for comparison with the limit values. [ 309 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1711", "text": "A leaflet published by the German Radiological Society (DRG) in 1913 was the first systematic approach to  radiation protection . [ 310 ] [ 311 ]  The physicist and co-founder of the society, Bernhard Walter (1861-1950), was one of the pioneers of radiation protection."}
{"_id": "WikiPedia_Radiology$$$corpus_1712", "text": "The  International Commission on Radiological Protection  (ICRP) and the  International Commission on Radiation Units and Measurements  (ICRU) were established at the Second International Congress of Radiology in Stockholm in 1928. In the same year, the first international radiation protection recommendations were adopted and each country represented was asked to develop a coordinated radiation control program. The United States representative,  Lauriston Taylor  of the US  Bureau of Standards  (NSB), formed the Advisory Committee on X-Ray and Radium Protection, later renamed the  National Committee on Radiation Protection and Measurements  (NCRP). The NCRP received a Congressional charter in 1964 and continues to develop guidelines to protect individuals and the public from excessive radiation. In the years that followed, numerous other organizations were established by almost every president. [ 312 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1713", "text": "Individuals in professions such as pilots, nuclear physicians, and nuclear power plant workers are regularly exposed to ionizing radiation. In Germany, over 400,000 workers undergo occupational radiation monitoring to safeguard against the harmful effects of radiation. Approximately 70,000 individuals employed across various industries possess a radiation pass (distinct from an X-ray pass - see below). Individuals who may receive an annual effective dose of more than 1 millisievert during their work are required to undergo radiation protection monitoring. In Germany, the effective dose from natural radiation is 2.1 millisieverts per year. Radiation dose is measured using dosimeters, and the occupational dose limit is 20 millisieverts per year. [ 313 ]  Monitoring also applies to buildings, plant components or (radioactive) substances. These are exempted from the scope of the Radiation Protection Ordinance by a special administrative act, the exemption in radiation protection. To this end, it must be ensured that the resulting radiation exposure for an individual member of the public does not exceed 10 \u03bcSv per calendar year and that the resulting collective dose does not exceed 1 person sievert per year. [ 314 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1714", "text": "According to"}
{"_id": "WikiPedia_Radiology$$$corpus_1715", "text": "\u00a7 170 \n StrlSchG   [Radiation Protection Act]  (in German)\nall occupationally exposed persons and holders of radiation passports require a radiation protection register number (SSR number or SSRN), a unique personal identification number, as of December 31, 2018. The SSR number facilitates and improves the allocation and balancing of individual dose values from occupational radiation exposure in the radiation protection register. It replaces the former radiation passport number. It is used to monitor dose limits. Companies are obliged to deploy their employees in such a way that the  radiation dose  to which they are exposed does not exceed the limit of 20  millisieverts  per calendar year. In Germany, about 440,000 people were classified as occupationally exposed to radiation in 2016. According to"}
{"_id": "WikiPedia_Radiology$$$corpus_1716", "text": "\u00a7 145 \n StrlSchG   [German Radiation Protection Act]  (in German)\nparagraph 1, Sentence 1, \"in the case of remediation and other measures to prevent and reduce exposure at radioactively contaminated sites, the person who carries out the measures himself or has them carried out by workers under his supervision must carry out an assessment of the body dose of the workers before starting the measures\". Applications for SSR numbers must be submitted to the Federal Office for Radiation Protection ( BfS ) by March 31, 2019 for all employees currently under surveillance. [ 315 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1717", "text": "The application for the SSR number at the Federal Office and the transmission of the necessary data must be ensured following"}
{"_id": "WikiPedia_Radiology$$$corpus_1718", "text": "\u00a7 170 \n StrlSchG   [German Radiation Protection Act]  (in German)\nparagraph 4 sentence 4 by"}
{"_id": "WikiPedia_Radiology$$$corpus_1719", "text": "\u00a7 131 \n StrlSchG  (in German) paragraph 1 or"}
{"_id": "WikiPedia_Radiology$$$corpus_1720", "text": "\u00a7 145 \n StrlSchG  (in German) paragraph 1 sentence 1 or by"}
{"_id": "WikiPedia_Radiology$$$corpus_1721", "text": "\u00a7 115 \n StrlSchG  (in German) paragraph 2 or"}
{"_id": "WikiPedia_Radiology$$$corpus_1722", "text": "\u00a7 153 \n StrlSchG  (in German) paragraph 1.\nThe SSR numbers must then be available for further use as part of normal communication with monitoring stations or radiation pass authorities. [ 316 ]  The SSR number is derived from the social security number and personal data using non-traceable encryption. The transmission takes place online. Approximately 420,00 persons are monitored for radiation protection in Germany (as of 2019)."}
{"_id": "WikiPedia_Radiology$$$corpus_1723", "text": "Emergency responders (including volunteers) who are not occupationally exposed persons within the meaning of the Radiation Protection Act also require an SSR number retrospectively, i.e. after an operation in which they were exposed to radiation above the limits specified in the Radiation Protection Ordinance, as all relevant exposures must be recorded in the Radiation Protection Register."}
{"_id": "WikiPedia_Radiology$$$corpus_1724", "text": "Radiation protection areas  are spatial areas in which either people can receive certain body doses during their stay or in which a certain local dose rate is exceeded. They are defined in \u00a7 36 of the Radiation Protection Ordinance and in \u00a7\u00a7 19 and 20 of the X-Ray Ordinance. According to the Radiation Protection Ordinance, radiation protection areas are divided into restricted areas (local dose rate \u2265 3 mSv/hour), control areas (effective dose > 6 mSv/year) and monitoring areas (effective dose > 1 mSv/year), depending on the hazard."}
{"_id": "WikiPedia_Radiology$$$corpus_1725", "text": "Germany, Austria and Switzerland, among many other countries, have early warning systems in place to protect the population."}
{"_id": "WikiPedia_Radiology$$$corpus_1726", "text": "The local dose rate measurement network (ODL measurement network) is a measurement system for radioactivity operated by the German Federal Office for Radiation Protection, which determines the local dose rate at the measurement site. [ 317 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1727", "text": "In Austria, the Radiation Early Warning System is a measurement and reporting system established in the late 1970s to provide early detection of elevated levels of ionizing radiation in the country and to enable the necessary measures to be taken. The readings are automatically sent to the central office at the Ministry, where they can be accessed by the relevant departments, such as the Federal Warning Center or the warning centers of the federal states. [ 318 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1728", "text": "NADAM (Network for Automatic Dose Alerting and Measurement) is the gamma radiation monitoring network of the Swiss National Emergency Operations Center. The monitoring network is complemented by the MADUK stations (Monitoring Network for Automatic Dose Rate Monitoring in the Environment of Nuclear Power Plants) of the Swiss Federal Nuclear Safety Inspectorate (ENSI)."}
{"_id": "WikiPedia_Radiology$$$corpus_1729", "text": "In 2011-2014, the NERIS-TP project aimed to discuss the lessons learned from the European EURANOS project on nuclear emergency response with all relevant  stakeholders . [ 319 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1730", "text": "The European PREPARE project aims to fill gaps in nuclear and radiological emergency preparedness identified after the Fukushima accident. The project aims to review emergency response concepts for long-lived releases, to address issues of measurement methods and food safety in the case of transboundary contamination, and to fill gaps in decision support systems (source term reconstruction, improved dispersion modeling, consideration of aquatic dispersion pathways in European river systems). [ 320 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1731", "text": "Environmental radioactivity  has been monitored in Germany since the 1950s. Until 1986, this was carried out by various authorities that did not coordinate with each other. Following the confusion during the Chernobyl reactor disaster in April 1986, measurement activities were pooled in the IMIS (Integrated Measurement and Information System) project, an environmental information system for monitoring radioactivity in Germany. [ 321 ]  Previously, the measuring equipment was affiliated to the warning offices under the name  WADIS  (\"Warning service information system\")."}
{"_id": "WikiPedia_Radiology$$$corpus_1732", "text": "The aim of the CONCERT (European Joint Programme for the Integration of Radiation Protection Research) project is to establish a joint European program for radiation protection research in Europe in 2018, based on the current strategic research programs of the European research platforms MELODI (radiation effects and radiation risks), ALLIANCE (radioecology), NERIS (nuclear and radiological emergency response), EURADOS (radiation dosimetry) and EURAMED (medical radiation protection). [ 322 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1733", "text": "The REWARD (Real time wide area radiation surveillance system) project was established to address the threats of nuclear terrorism, missing radioactive sources, radioactive contamination and nuclear accidents. The consortium developed a mobile system for real time wide area radiation monitoring based on the integration of new miniaturized solid state sensors. Two sensors are used: a  cadmium zinc telluride  (CdZnTe) detector for gamma radiation and a high efficiency neutron detector based on novel silicon technologies. The gamma and neutron detectors are integrated into a single monitoring device called a tag. The sensor unit includes a wireless communication interface to remotely transmit data to a monitoring base station, which also uses a  GPS  system to calculate the tag's position. [ 323 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1734", "text": "The  Nuclear Emergency Support Team  (NEST) is a US program for all types of nuclear emergencies of the National Nuclear Security Administration (NNSA) of the United States Department of Energy and is also a counter-terrorism unit that responds to incidents involving radioactive materials or nuclear weapons in US possession abroad. [ 324 ] [ 325 ]  It was founded in 1974/75 under US President  Gerald Ford  and renamed the Nuclear Emergency Support Team in 2002. [ 326 ] [ 327 ]  In 1988, a secret agreement from 1976 between the USA and the Federal Republic of Germany became known, which stipulates the deployment of NEST in the Federal Republic. In Germany, a similar unit has existed since 2003 with the name Central Federal Support Group for Serious Cases of Nuclear-Specific Emergency Response ( ZUB ). [ 328 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1735", "text": "As early as 1905, the Frenchman  Viktor Hennecart [ 329 ]  called for special legislation to regulate the use of X-rays. In England, Sidney Russ (1879-1963) suggested to the British Roentgen Society in 1915 that it should develop its own set of safety standards, which it did in July 1921 with the formation of the British X-Ray and Radium Protection Committee. [ 330 ]  In the United States, the American X-Ray Society developed its own guidelines in 1922. In the German Reich, a special committee of the German X-Ray Society under  Franz Maximilian Groedel  (1881-1951),  Hans Liniger  (1863-1933) and  Heinz Lossen  (1893-1967) formulated the first guidelines after the First World War. In 1953, the employers' liability insurance associations issued the accident prevention regulation \"Use of X-rays in medical facilities\" based on the legal basis in \u00a7 848a of the Reich Insurance Code (RVG). In the GDR, the Occupational Safety and Health Regulation (ASAO) 950 was in effect from 1954 to 1971. It was replaced by ASAO 980 on April 1, 1971."}
{"_id": "WikiPedia_Radiology$$$corpus_1736", "text": "The European Atomic Energy Community (EURATOM) was founded on March 25, 1957, by the Treaty of Rome between France, Italy, the Benelux countries and the Federal Republic of Germany, and remains almost unchanged to this day. Chapter 3 of the Euratom Treaty regulates measures to protect the health of the population. Article 35 requires facilities for the continuous monitoring of soil, air and water for radioactivity. As a result, monitoring networks have been set up in all Member States and the data collected is sent to the EU's central database (EURDEP, European Radiological Data Exchange Platform). [ 331 ]  The platform is part of the EU's ECURIE system for the exchange of information in the event of radiological emergencies and became operational in 1995. [ 332 ]  Switzerland also participates in this information system. [ 333 ] [ 334 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1737", "text": "In Germany, the first X-ray regulation ( RGBl . I p.\u00a088) was issued in 1941 and originally applied to non-medical companies. The first medical regulations were issued in October 1953 by the Main Association of Industrial Employer's Liability Insurance Associations as accident prevention regulations for the Reich Insurance Code. Basic standards for radiation protection were introduced by directives of the European Atomic Energy Community ( EURATOM ) on February 2, 1959. The Atomic Energy Act of December 23, 1959 is the national legal basis for all radiation protection legislation in the Federal Republic of Germany (West) with the Radiation Protection Ordinance of June 24, 1960 (only for radioactive substances), the Radiation Protection Ordinance of July 18, 1964 (for the medical sector) and the X-ray Ordinance of March 1, 1973. [ 335 ]  Radiation protection was formulated in \u00a7 1, according to which  life, health and property are to be protected from the dangers of nuclear energy and the harmful effects of ionizing radiation and damage caused by nuclear energy or ionizing radiation is to be compensated.  The Radiation Protection Ordinance sets dose limits for the general population and for occupationally exposed persons. In general, any use of ionizing radiation must be justified and radiation exposure must be kept as low as possible even below the limit values. To this end, physicians, dentists and veterinarians, for example, must provide proof every five years - by Section 18a (2) X-ray Ordinance .  in the version dated April 30, 2003 - that their specialist knowledge in radiation protection has been updated and must complete a full-day course with a final examination. Specialist knowledge in radiation protection is required by the Technical Knowledge Guideline according to X-ray Ordinance .  - R3 for persons who work with baggage screening equipment, industrial measuring equipment and interfering emitters. Since 2019, the regulatory areas of the previous X-ray and radiation protection ordinances have been merged in the amended Radiation Protection Ordinance."}
{"_id": "WikiPedia_Radiology$$$corpus_1738", "text": "The  Radiation Protection Commission  ( SSK ) was founded in 1974 as an  advisory body  to the  Federal Ministry of the Interior. [ 336 ]  It emerged from Commission IV \"Radiation Protection\" of the German Atomic Energy Commission, which was founded on January 26, 1956. After the Chernobyl nuclear disaster in 1986, the  Federal Ministry for the Environment, Nature Conservation, Nuclear Safety and Consumer Protection  was established in the Federal Republic of Germany. The creation of this ministry was primarily a response to the perceived lack of coordination in the political response to the Chernobyl disaster and its aftermath. On December 11, 1986, the German Bundestag passed the Precautionary Radiation Protection Act ( StrVG ) to protect the population, to monitor radioactivity in the environment, and to minimize human exposure to radiation and  radioactive contamination  of the environment in the event of radioactive accidents or incidents. The last revision of the X-Ray Ordinance was issued on January 8, 1987. As part of a comprehensive modernization of German radiation protection law, [ 337 ]  which is largely based on Directive 2013/59/Euratom, [ 338 ]  the provisions of the X-Ray Ordinance have been incorporated into the revised Radiation Protection Ordinance."}
{"_id": "WikiPedia_Radiology$$$corpus_1739", "text": "Among many other measures, contaminated food was withdrawn from the market on a large scale. Parents were strongly advised not to let their children play in sandboxes. Some of the contaminated sand was replaced. In 1989, the Federal Office for Radiation Protection was incorporated into the Ministry of the Environment. On April 30, 2003, a new precautionary radiation protection law was promulgated to implement two EU directives on the health protection of persons against the dangers of ionizing radiation during medical exposure. [ 339 ] [ 340 ]  The protection of workers from optical radiation (infrared radiation (IR), visible light (VIS) and ultraviolet radiation (UV)), which falls under the category of  non-ionizing radiation, is regulated by the Ordinance on the Protection of Workers from Artificial Optical Radiation of 19 July 2010 . [ 341 ]  It is based on the  EU Directive  2006/25/EC of April 27, 2006. [ 342 ]  On March 1, 2010, the \"Act on the Protection of Humans from Non-Ionizing Radiation\" ( NiSG ), [ 343 ]   BGBl . I p.\u00a02433, came into force, according to which the use of sunbeds by minors has been prohibited since August 4, 2009, in accordance with"}
{"_id": "WikiPedia_Radiology$$$corpus_1740", "text": "\u00a7 4 \n NiSG   [Network and Information Systems Security Ordinance \u2013 NIS Ordinance]  (in German)\nA new Radiation Protection Act came into force in Germany on October 1, 2017. [ 344 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1741", "text": "In Germany, a radiation protection officer directs and supervises activities to ensure radiation protection when handling radioactive materials or ionizing radiation. Their duties are described in"}
{"_id": "WikiPedia_Radiology$$$corpus_1742", "text": "\u00a7 31-33 \n StrlSchV  (in German)\nof the Radiation Protection Ordinance and"}
{"_id": "WikiPedia_Radiology$$$corpus_1743", "text": "\u00a7 13-15 \n R\u00f6V  (in German)\nof the X-Ray Ordinance. They are appointed by the radiation protection officer, who is responsible for ensuring that all radiation protection regulations are observed."}
{"_id": "WikiPedia_Radiology$$$corpus_1744", "text": "Since 2002, an x-ray pass is a document in which the examining physician or dentist must enter information about the x-ray examinations performed on the patient. The main aim was to avoid unnecessary repeat examinations. According to the new Radiation Protection Ordinance ( StrlSchV ), [ 345 ]  practices and clinics are no longer obliged to offer their patients X-ray passports and to enter examinations in them. The Radiation Protection Ordinance came into force on December 31, 2018, together with the Radiation Protection Act (StrlSchG) passed in 2017, replacing the previous Radiation Protection Ordinance and the X-ray Ordinance. The  Federal Office for Radiation Protection  ( BfS ) continues to advise patients to keep records of their own radiation diagnostic examinations. On its website, the BfS provides a downloadable document that can be used for personal documentation. [ 346 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1745", "text": "In Switzerland, institutionalized radiation protection began in 1955 with the issuance of  guidelines for protection against ionizing radiation in medicine, laboratories, industry and manufacturing plants , although these were only recommendations. The legal basis was created by a new constitutional article (Art. 24), according to which the federal government issues regulations on protection against the dangers of ionizing radiation. On this basis, a corresponding federal law entered into force on July 1, 1960. The first Swiss ordinance on radiation protection entered into force on May 1, 1963. On October 7, 1963, the  Federal Department of Home Affairs  (EDI) issued the following decrees to supplement the ordinance:"}
{"_id": "WikiPedia_Radiology$$$corpus_1746", "text": "Another 40 regulations followed. The monitoring of such facilities took many years due to a lack of personnel. From 1963, dosimeters were to be used for personal protection, but this met with great resistance. It was not until 1989 that an updated radiation protection law was passed, accompanied by radiation protection training for the people concerned. [ 347 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1747", "text": "The legal basis for radiation protection in Austria is the Radiation Protection Act (BGBl. 277/69 as amended) of June 11, 1969. [ 348 ]  The tasks of radiation protection extend to the fields of medicine, commerce and industry, research, schools, worker protection and food. The General Radiation Protection Ordinance, Federal Law Gazette II No. 191/2006, has been in force since June 1, 2006. [ 349 ]  Based on the Radiation Protection Act, it regulates the handling of radiation sources and measures for protection against ionizing radiation. The Optical Radiation Ordinance ( VOPST ) is a detailed ordinance to the Occupational Safety and Health Act ( ASchG )."}
{"_id": "WikiPedia_Radiology$$$corpus_1748", "text": "On August 1, 2020, a new radiation protection law came into force, which largely harmonized the radiation protection regulations for artificial radioactive substances and terrestrial natural radioactive substances. They are now enshrined in the General Radiation Protection Ordinance 2020. Companies that carry out activities with naturally occurring radioactive substances are now subject to the licensing or notification requirements pursuant to Sections 15 to 17 of the Radiation Protection Act 2020, unless an exemption provision pursuant to Sections 7 or 8 of the General Radiation Protection Ordinance 2020 applies. Cement production including maintenance of  clinker  kilns, production of primary iron and tin, lead and copper smelting are included in the scope. If a company falls within the scope of the General Radiation Protection Ordinance 2020, its owner must commission an officially authorized monitoring body. The mandate includes dose assessment for workers who may be exposed to increased radiation exposure and, if necessary, determination of the activity concentration of residues and radioactive substances discharged with the air or waste water. [ 350 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1749", "text": "The  Hounsfield scale  ( / \u02c8 h a\u028a n z f i\u02d0 l d /   HOWNZ -feeld ), named after Sir  Godfrey Hounsfield , is a quantitative scale for describing  radiodensity . It is frequently used in  CT scans , where its value is also termed  CT number ."}
{"_id": "WikiPedia_Radiology$$$corpus_1750", "text": "The Hounsfield unit (HU) scale is a linear transformation of the original  linear attenuation coefficient  measurement into one in which the  radiodensity  of  distilled water  at standard  pressure  and  temperature  ( STP ) is defined as 0 Hounsfield units (HU), while the radiodensity of  air  at STP is defined as \u22121000 HU. In a  voxel  with average linear attenuation coefficient  \n \n \n \n \u03bc \n \n \n {\\displaystyle \\mu } \n \n , the corresponding HU value is therefore given by: [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1751", "text": "H \n U \n = \n 1000 \n \u00d7 \n \n \n \n \u03bc \n \u2212 \n \n \u03bc \n \n \n water \n \n \n \n \n \n \n \u03bc \n \n \n water \n \n \n \n \u2212 \n \n \u03bc \n \n \n air \n \n \n \n \n \n \n \n \n {\\displaystyle HU=1000\\times {\\frac {\\mu -\\mu _{\\textrm {water}}}{\\mu _{\\textrm {water}}-\\mu _{\\textrm {air}}}}}"}
{"_id": "WikiPedia_Radiology$$$corpus_1752", "text": "where  \n \n \n \n \n \u03bc \n \n \n water \n \n \n \n \n \n {\\displaystyle \\mu _{\\textrm {water}}} \n \n  and  \n \n \n \n \n \u03bc \n \n \n air \n \n \n \n \n \n {\\displaystyle \\mu _{\\textrm {air}}} \n \n  are respectively the linear attenuation coefficients of water and air."}
{"_id": "WikiPedia_Radiology$$$corpus_1753", "text": "Thus, a change of one Hounsfield unit (HU) represents a change of 0.1% of the attenuation coefficient of water since the attenuation coefficient of air is nearly zero. [ 3 ] :\u200a259"}
{"_id": "WikiPedia_Radiology$$$corpus_1754", "text": "Calibration tests of HU with reference to water and other materials may be done to ensure standardised response. This is particularly important for CT scans used in  radiotherapy   treatment planning , where HU is converted to  electron density . [ 4 ]  Variation in the measured values of reference materials with known composition, and variation between and within slices may be used as part of test procedures. [ 3 ] :\u200a283\u200a [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1755", "text": "The above standards were chosen as they are universally available references and suited to the key application for which computed axial tomography was developed: imaging the internal anatomy of living creatures based on organized water structures and mostly living in air,  e.g.   humans . [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1756", "text": "HU-based differentiation of material applies to  medical-grade   dual-energy CT scans  but not to  cone beam computed tomography  (CBCT) scans, as CBCT scans provide  unreliable HU readings . [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1757", "text": "Values reported here are  approximations . Different dynamics are reported from one study to another. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1758", "text": "Exact HU dynamics can vary from one CT acquisition to another due to CT acquisition and reconstruction parameters (kV, filters, reconstruction algorithms, etc.). The use of  contrast agents  modifies HU as well in some body parts (mainly blood)."}
{"_id": "WikiPedia_Radiology$$$corpus_1759", "text": "A practical application of this is in evaluation of tumors, where, for example, an  adrenal tumor  with a radiodensity of less than 10 HU is rather fatty in composition and almost certainly a benign  adrenal adenoma . [ 30 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1760", "text": "In  medical or research imaging , an  incidental imaging finding  (also called an  incidentaloma ) is an unanticipated finding which is not related to the original diagnostic inquiry. As with other types of  incidental medical findings , they may represent a diagnostic, ethical, and philosophical dilemma because their significance is unclear. While some coincidental findings may lead to beneficial diagnoses, others may lead to  overdiagnosis  that results in unnecessary testing and treatment, sometimes called the \"cascade effect\". [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1761", "text": "Incidental findings are common in imaging. For instance, around 1 in every 3 cardiac  MRIs  result in an incidental finding. [ 2 ]  Incidence is similar for chest  CT scans  (~30%). [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1762", "text": "As the use of medical imaging increases, the number of incidental findings also increases. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1763", "text": "Incidental adrenal masses on imaging are common (0.6 to 1.3% of all abdominal CT). Differential diagnosis include  adenoma ,  myelolipoma , cyst,  lipoma ,  pheochromocytoma ,  adrenal cancer ,  metastatic cancer ,  hyperplasia , and  tuberculosis . [ 3 ]   Some of these lesions are easily identified by radiographic appearance; however, it is often adenoma vs. cancer/metastasis that is most difficult to distinguish.  Thus, clinical guidelines have been developed to aid in diagnosis and decision-making. [ 4 ]  Although adrenal incidentalomas are common, they are not commonly cancerous - less than 1% of all adrenal incidentalomas are malignant. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1764", "text": "The first considerations are size and radiographic appearance of the mass.  Suspicious adrenal masses or those \u22654\u00a0cm are recommended for complete removal by adrenalectomy.  Masses <4\u00a0cm may also be recommended for removal if they are found to be hormonally active, but are otherwise recommended for observation. [ 5 ]   All adrenal masses should receive hormonal evaluation. Hormonal evaluation includes: [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1765", "text": "On CT scan, benign  adenomas  typically are of low  radiodensity  (due to fat content). A radiodensity equal to or below 10  Hounsfield units  (HU) is considered diagnostic of an adenoma. [ 7 ]  An adenoma also shows rapid  radiocontrast washout  (50% or more of the contrast medium washes out at 10 minutes). If the hormonal evaluation is negative and imaging suggests benign lesion, follow up may be considered. Imaging at 6, 12, and 24 months and repeat hormonal evaluation yearly for 4 years is often recommended, [ 6 ]  but there exists controversy about harm/benefit of such screening as there is a high subsequent false-positive rate (about 50:1) and overall low incidence of adrenal carcinoma. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1766", "text": "Autopsy  series have suggested that  pituitary  incidentalomas may be quite common. It has been estimated that perhaps 10% of the adult population may harbor such  endocrinologically  inert lesions. [ 9 ]  Most of these lesions, especially those which are small, will not grow. However, some form of long-term surveillance has been recommended based on the size and presentation of the lesion. [ 10 ]  With pituitary adenomas larger than 1\u00a0cm, a baseline pituitary hormonal function test should be done, including measurements of serum levels of  TSH ,  prolactin ,  IGF-1  (as a test of  growth hormone  activity), adrenal function (i.e. 24 hour urine cortisol, dexamethasone suppression test),  testosterone  in men, and  estradiol  in  amenorrheic  women. [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1767", "text": "Incidental  thyroid  masses may be found in 9% of patients undergoing bilateral carotid duplex ultrasonography. [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1768", "text": "Some experts [ 13 ]  recommend that nodules > 1\u00a0cm (unless the  TSH  is suppressed) or those with ultrasonographic features of malignancy should be biopsied by  fine needle aspiration .  Computed tomography   is inferior to  ultrasound  for evaluating thyroid nodules. [ 14 ]  Ultrasonographic markers of malignancy are: [ 15 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1769", "text": "Incidental  parathyroid  masses may be found in 0.1% of patients undergoing bilateral carotid duplex ultrasonography. [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1770", "text": "The American College of Radiology  recommends the following workup for thyroid nodules as incidental imaging findings on  CT ,  MRI  or  PET-CT : [ 16 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1771", "text": "Studies of whole body screening  computed tomography  find abnormalities in the lungs of 14% of patients. [ 17 ]   Clinical practice guidelines  by the  American College of Chest Physicians  advise on the evaluation of the  solitary pulmonary nodule . [ 18 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1772", "text": "Most  renal cell carcinomas  are now found incidentally. [ 19 ]  Tumors less than 3\u00a0cm in diameter less frequently have aggressive  histology . [ 20 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1773", "text": "A  CT scan  is the first choice modality for workup of solid masses in the kidneys. Nevertheless, hemorrhagic cysts can resemble renal cell carcinomas on CT, but they are easily distinguished with  Doppler ultrasonography  (Doppler US). In renal cell carcinomas, Doppler US often shows vessels with high velocities caused by neovascularization and arteriovenous shunting. Some renal cell carcinomas are hypovascular and not distinguishable with Doppler US. Therefore, renal tumors without a Doppler signal, which are not obvious simple cysts on US and CT, should be further investigated with  contrast-enhanced ultrasound , as this is more sensitive than both Doppler US and CT for the detection of hypovascular tumors. [ 21 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1774", "text": "The increasing use of MRI, often during diagnostic work-up for back or lower extremity pain, has led to a significant increase in the number of incidental findings that are most often clinically inconsequential.  The most common include: [ 22 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1775", "text": "Sometimes normally asymptomatic findings can present with symptoms and these cases when identified cannot then be considered as incidentalomas. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1776", "text": "The concept of the \"incidentaloma\" has been criticized, as such lesions do not have much in common other than the history of an incidental identification and the assumption that they are clinically inert. It has been proposed just to say that such lesions have been \"incidentally found.\" [ 23 ]  The underlying pathology shows no unifying histological concept. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1777", "text": "The  International Day of Radiology  (IDoR) is an  annual event  promoting the role of medical imaging in modern  healthcare . It is celebrated on  November 8  each year and coincides with the anniversary of the discovery of  x-rays . It was first introduced in 2012, as a joint initiative of the  European Society of Radiology  (ESR), the  Radiological Society of North America  (RSNA), and the  American College of Radiology  (ACR). [ 1 ]  The International Day of Radiology is acknowledged and celebrated by nearly 200 national, sub-speciality, and related societies around the world."}
{"_id": "WikiPedia_Radiology$$$corpus_1778", "text": "The International Day of Radiology is a successor to the  European Day of Radiology  which was launched in 2011. The first and only European Day of Radiology (EDoR) was held on February 10, 2011, to commemorate the anniversary of R\u00f6ntgen's death and was organised by the  European Society of Radiology (ESR). Due to the success of the EDoR, the ESR entered into cooperation with the RSNA and the ACR to establish the International Day of Radiology. It was also decided that the date of the celebration should be moved from the anniversary of R\u00f6ntgen's death to that of his discovery of the  x-ray . The day was officially confirmed by the three founding societies during the annual RSNA meeting in Chicago on November 28, 2011."}
{"_id": "WikiPedia_Radiology$$$corpus_1779", "text": "On November 8, 1895  Wilhelm Conrad R\u00f6ntgen  discovered  x-rays  by chance while investigating cathode rays, effectively laying the foundation for the medical discipline of  radiology . This discovery would grow to include various methods of imaging and establish itself as a crucial element of modern medicine. November 8 was eventually chosen as the appropriate day to mark the celebrations which are observed by radiological societies the world over. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1780", "text": "In addition to the general recognition of radiology, a theme is chosen every year, focusing on various specialities and sub-specialities of radiology. [ 3 ]  These themes have included:"}
{"_id": "WikiPedia_Radiology$$$corpus_1781", "text": "In and around November 8 of every year, international radiological societies all over the world celebrate the day with their own organised events. These celebrations come in the form of exhibitions, workshops, lectures, and social media campaigns which invite radiologists as well as the general public to participate and learn more about radiology."}
{"_id": "WikiPedia_Radiology$$$corpus_1782", "text": "In 2018, various radiological and partner societies organised events to draw attention to radiology and that year's theme of cardiac imaging. Examples include:"}
{"_id": "WikiPedia_Radiology$$$corpus_1783", "text": "In further support of the day, the  European Society of Radiology  publishes a book every year on the selected theme. In 2018, the book,  The HEART revealed,  was published as a free pdf download on the IDoR website. The book, authored by professional radiologists, contains descriptions of various cardiac diseases where imaging is helpful in diagnosis, treatment, and follow-up. [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1784", "text": "Other published texts addressing the yearly theme include:"}
{"_id": "WikiPedia_Radiology$$$corpus_1785", "text": "In addition to the themed publications, the  European Society of Radiology  in collaboration with the International Society for the History of Radiology published a three-volume series on the history of radiology,  The Story of Radiology ."}
{"_id": "WikiPedia_Radiology$$$corpus_1786", "text": "The  International Subarachnoid Aneurysm Trial  ( ISAT ) was a large  multicenter  prospective  randomized   clinical medical trial  comparing the safety and efficacy of  endovascular coil  treatment and  surgical clipping  for the treatment of  brain aneurysms . The study began in 1994 with the first results being published in  The Lancet  in 2002, and the 10-year data were published again in  The Lancet  in early September 2005. A total of 2,143 study participants were mostly drawn from  U.K.  hospitals with the rest drawn from North American and European hospitals."}
{"_id": "WikiPedia_Radiology$$$corpus_1787", "text": "The study found superior results with  endovascular  coil treatment compared to surgical clipping. However, subsequent studies have questioned this conclusion. [ 1 ]  The study was criticized by many clinicians and not well accepted by surgeons. [ 2 ]  Primary criticisms were related to the study's generalizability and the long-term prognosis of coil embolization. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1788", "text": "ISAT sought to measure outcomes of  cerebral aneurysm  patients at 2 and 12 months using a type of a  Rankin scale . [ 4 ] :\u200a114\u200a  The study was prematurely terminated in 2002 after the oversight committee determined there was increased morbidity with surgical clipping compared to  endovascular  coiling. [ 4 ] :\u200a114"}
{"_id": "WikiPedia_Radiology$$$corpus_1789", "text": "ISAT was criticized on several factors related to the randomization of the patient population. The randomized patient population in the ISAT was younger on average, the majority had aneurysms under 10mm and in anterior circulation compared to the population of  subarachnoid hemorrhage  patients in the U.S. and Japan. [ 1 ] [ 5 ] :\u200a210\u200a  In response to these criticisms, a facility that participated in ISAT compared the clinical outcomes of their patients who were not selected for the study to those who were. They reported similar outcomes to the ISAT. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1790", "text": "Although the initial ISAT analysis appeared to favor endovascular coiling over microsurgical clipping, subsequent meta-analysis have questioned that conclusion finding higher incidences [ spelling? ]  of recurrence. [ 6 ]  A large meta-analysis from  Johns Hopkins University  published in  Neurosurgery  concluded that \"there is no clear consensus in these two studies or in the 45 observational studies included.\" [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1791", "text": "Updated data from the ISAT group in March 2008 shows that the higher aneurysm rate of recurrence is also associated with a higher re-bleeding rate, given that the re-bleed rate of coiled aneurysms appears to be 8 times higher than that of aneurysms treated with surgical clipping in this study. [ 7 ]  The ISAT authors conclude that \"when treating ruptured cerebral aneurysms, the advantage of coil embolization over clip ligation cannot be assumed for patients younger than 40 years old.\" [ 7 ]  Other studies have directly questioned the ISAT's conclusions. [ 8 ]  This conclusion is based on a number of methodological assumptions itself and other authors have cautioned about extending it to other patient populations. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1792", "text": "It appears that although endovascular coiling is associated with a shorter recovery period as compared to surgical clipping, it is also associated with a significantly higher  recurrence  rate after treatment. The long-term data for unruptured  aneurysms  are still being gathered."}
{"_id": "WikiPedia_Radiology$$$corpus_1793", "text": "The  John Thomas sign , [ 1 ]  also known as the  Throckmorton sign , [ 2 ]  is a slang or joke term used in the field of  radiology . It refers to the position of a  penis  as it relates to  pathology  on an  X-ray  of a  pelvis . When the penis (visible on the X-ray as a shadow) points towards the same side as a unilateral medical condition such as a broken bone, this is considered a \"positive John Thomas sign,\" and if the shadow points to the other side, it is a \"negative John Thomas sign.\" [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1794", "text": "Studies have shown that the \"sign\" is no better than chance at identifying the location of a  hip fracture . [ 4 ] [ 5 ]  In those cases where the John Thomas sign is positive, it has been proposed that a person with a displaced hip fracture may try to lie on the injured side to immobilize the fracture and reduce pain; the penis then inclines toward the downward (injured) side. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1795", "text": "Andy Murray , British professional  tennis  player, released a picture of his pelvic  X-ray  following his hip resurfacing surgery on January 29, 2019 [ 7 ]  clearly demonstrating an example of a negative John Thomas or Throckmorton sign where his penis pointed away from the site of injury. The release of the X-ray image with visible genitalia was discussed by  Piers Morgan  on  Good Morning Britain , prompting Murray, who was watching at the time, to message the show, stating, \"Please can you stop discussing my genitals on national TV, I was heavily medicated at the time of posting.\" [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1796", "text": "Laboratory Unit for Computer Assisted Surgery   is a system used for virtual  surgical planning . Starting with 1998, LUCAS was developed at the  University of Regensburg, Germany , with the support of the  Carl Zeiss Company . The resulting surgical planning is then  reproduced  onto the patient by using a  navigation system . In fact, LUCAS is integrated into the same  platform  together with the  Surgical Segment Navigator (SSN) , the Surgical Tool Navigator (STN), the Surgical Microscope Navigator (SMN) and the 6 DOF  Manipulator (or, in German, \"Mehrkoordinatenmanipulator\" - MKM), also from the  Carl Zeiss Company ."}
{"_id": "WikiPedia_Radiology$$$corpus_1797", "text": "Data from separate  bidimensional  slices generated by a  CT  or  MRI  scan are uploaded into the LUCAS system. The resulting  dataset  is then processed, in order to eliminate  image noise , and to enhance the anatomical contours and also the general contrast of the images. The next step is to create a virtual  3D  model from the gathered collection of  2D  images. The bone segment that is to be repositioned is marked, on the 3D grid reconstructed model; then, the actual repositioning of that bone segment is done on the virtual model, until the optimal anatomical position is obtained. The criteria for the optimal position of the bone segment are: symmetry with the opposite side, the continuity of the normal bone contours, or the normal volume of an anatomical region (such as the  Orbit . Afterwards, a  textured  final image is rendered. The calculated vectors for the bone segment repositioning, together with the whole virtual model are finally transferred to the  Surgical Segment Navigator ."}
{"_id": "WikiPedia_Radiology$$$corpus_1798", "text": "A  limited radiology technician  perform  x-rays  of patients and deliver the images to requester. They make no  diagnosis  but still work closely with patients, explaining procedures, operating the X-ray and other associated equipment. Technical aspects include positioning patients for X-rays, determining appropriate angle and height of X-ray equipment, and calculating  radiation  dosages needed to create X-rays of the appropriate density, detail, and contrast, enabling the  physician  to make an accurate diagnosis."}
{"_id": "WikiPedia_Radiology$$$corpus_1799", "text": "The  Lubberts effect  is the non-uniform response of an  imaging system  to  X-rays  that are absorbed at different depths within the input  phosphor .  It indicates an input phosphor depth-dependent response of the imaging system. It is named [ 1 ]  for G. Lubberts, who published a report of it in 1968 while working at  Kodak . [ 2 ]  The Lubberts effect is related to the  Swank effect , which relates the  signal-to-noise ratio  of a scintillator-based imaging system to the amount of random variation in the strength of the emitted photons. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1800", "text": "Magnetic resonance imaging  ( MRI ) is a  medical imaging  technique used in  radiology  to generate  pictures of the  anatomy  and the  physiological  processes inside the body.  MRI scanners  use strong  magnetic fields , magnetic field gradients, and  radio waves  to form images of the organs in the body. MRI does not involve  X-rays  or the use of  ionizing radiation , which distinguishes it from  computed tomography  (CT) and  positron emission tomography  (PET) scans. MRI is a  medical application  of  nuclear magnetic resonance  (NMR) which can also be used for imaging in other  NMR applications , such as  NMR spectroscopy . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1801", "text": "MRI is widely used in hospitals and clinics for  medical diagnosis ,  staging  and follow-up of disease. Compared to CT, MRI provides better  contrast  in images of soft tissues, e.g. in the  brain  or abdomen. However, it may be perceived as less comfortable by patients, due to the usually longer and louder measurements with the subject in a long, confining tube, although \"open\" MRI designs mostly relieve this. Additionally,  implants  and other non-removable metal in the body can pose a risk and may exclude some patients from undergoing an MRI examination safely."}
{"_id": "WikiPedia_Radiology$$$corpus_1802", "text": "MRI was originally called NMRI (nuclear magnetic resonance imaging), but \"nuclear\" was dropped to avoid  negative associations . [ 2 ]  Certain  atomic nuclei  are able to absorb  radio frequency  (RF) energy when placed in an external  magnetic field ; the resultant evolving  spin polarization  can induce an RF signal in a radio frequency coil and thereby be detected. [ 3 ]  In other words, the nuclear magnetic spin of protons in the hydrogen nuclei resonates with the RF incident waves and emit coherent radiation with compact direction, energy (frequency) and phase. This coherent amplified radiation is easily detected by RF antennas close to the subject being examined. It is a process similar to  masers . In clinical and research MRI,  hydrogen atoms  are most often used to generate a macroscopic polarized radiation that is detected by the antennas. [ 3 ]  Hydrogen atoms are  naturally abundant in humans  and other biological organisms, particularly in  water  and  fat . For this reason, most MRI scans essentially map the location of water and fat in the body. Pulses of radio waves excite the  nuclear spin  energy transition, and magnetic field gradients localize the polarization in space. By varying the parameters of the  pulse sequence , different contrasts may be generated between tissues based on the  relaxation  properties of the hydrogen atoms therein."}
{"_id": "WikiPedia_Radiology$$$corpus_1803", "text": "Since its development in the 1970s and 1980s, MRI has proven to be a versatile imaging technique. While MRI is most prominently used in  diagnostic medicine  and biomedical research, it also may be used to form images of non-living objects, such as  mummies .  Diffusion MRI  and  functional MRI  extend the utility of MRI to capture neuronal tracts and blood flow respectively in the nervous system, in addition to detailed spatial images. The sustained increase in demand for MRI within  health systems  has led to concerns about  cost effectiveness  and  overdiagnosis . [ 4 ] [ 5 ] [ dubious  \u2013  discuss ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1804", "text": "In most medical applications,  hydrogen  nuclei, which consist solely of a  proton , that are in tissues create a signal that is processed to form an image of the body in terms of the density of those nuclei in a specific region. Given that the protons are affected by fields from other atoms to which they are bonded, it is possible to separate responses from hydrogen in specific compounds. To perform a study, the person is positioned within an  MRI scanner  that forms a strong  magnetic field  around the area to be imaged. First, energy from an  oscillating  magnetic field is temporarily applied to the patient at the appropriate  resonance  frequency. Scanning with X and Y gradient coils causes a selected region of the patient to experience the exact magnetic field required for the energy to be absorbed. The atoms are  excited  by a  RF  pulse and the resultant signal is measured by a  receiving coil . The RF signal may be processed to deduce position information by looking at the changes in RF level and phase caused by varying the local magnetic field using  gradient coils . As these coils are rapidly switched during the excitation and response to perform a moving line scan, they create the characteristic repetitive noise of an MRI scan as the windings move slightly due to  magnetostriction . The contrast between different tissues is determined by the rate at which excited atoms return to the  equilibrium state .  Exogenous   contrast agents  may be given to the person to make the image clearer. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1805", "text": "The major components of an MRI scanner are the main  magnet , which polarizes the sample, the  shim coils  for correcting shifts in the  homogeneity  of the main magnetic field, the gradient system which is used to localize the region to be scanned and the RF system, which excites the sample and detects the resulting NMR signal. The whole system is controlled by one or more computers."}
{"_id": "WikiPedia_Radiology$$$corpus_1806", "text": "MRI requires a magnetic field that is both strong and  uniform  to a few parts per million across the scan volume. The field strength of the magnet is measured in  teslas  \u2013 and while the majority of systems operate at 1.5 T, commercial systems are available between 0.2 and 7 T.  3T MRI  systems, also called 3 Tesla MRIs, have stronger magnets than 1.5 systems and are considered better for images of organs and soft tissue. [ 7 ]  Whole-body MRI systems for research applications operate in e.g. 9.4T, [ 8 ] [ 9 ]  10.5T, [ 10 ]  11.7T. [ 11 ]  Even higher field whole-body MRI systems e.g. 14 T and beyond are in conceptual proposal [ 12 ]  or in engineering design. [ 13 ]  Most clinical magnets are  superconducting  magnets, which require  liquid helium  to keep them at low temperatures. Lower field strengths can be achieved with permanent magnets, which are often used in \"open\" MRI scanners for  claustrophobic  patients. [ 14 ]  Lower field strengths are also used in a  portable MRI  scanner approved by the FDA in 2020. [ 15 ]  Recently, MRI has been demonstrated also at ultra-low fields, i.e., in the microtesla-to-millitesla range, where sufficient signal quality is made possible by prepolarization (on the order of 10\u2013100 mT) and by measuring the  Larmor precession  fields at about 100 microtesla with highly sensitive superconducting quantum interference devices ( SQUIDs ). [ 16 ] [ 17 ] [ 18 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1807", "text": "Each tissue returns to its equilibrium state after excitation by the independent relaxation processes of T 1  ( spin-lattice ; that is, magnetization in the same direction as the static magnetic field) and T 2  ( spin-spin ; transverse to the static magnetic field).\nTo create a T 1 -weighted image, magnetization is allowed to recover before measuring the MR signal by changing the  repetition time  (TR). This image weighting is useful for assessing the cerebral cortex, identifying fatty tissue, characterizing focal liver lesions, and in general, obtaining morphological information, as well as for  post-contrast  imaging.\n \nTo create a T 2 -weighted image, magnetization is allowed to decay before measuring the MR signal by changing the  echo time  (TE). This image weighting is useful for detecting  edema  and inflammation, revealing  white matter lesions , and assessing zonal anatomy in the  prostate  and  uterus ."}
{"_id": "WikiPedia_Radiology$$$corpus_1808", "text": "The information from MRI scans comes in the form of  image contrasts  based on differences in the rate of relaxation of  nuclear spins  following their perturbation by an oscillating magnetic field (in the form of radiofrequency pulses through the sample). [ 19 ]  The relaxation rates are a measure of the time it takes for a signal to decay back to an equilibrium state from either the longitudinal or transverse plane."}
{"_id": "WikiPedia_Radiology$$$corpus_1809", "text": "Magnetization  builds up along the z-axis in the presence of a magnetic field, B 0 , such that the  magnetic dipoles  in the sample will, on average, align with the z-axis summing to a total magnetization M z . This magnetization along z is defined as the equilibrium magnetization; magnetization is defined as the sum of all magnetic dipoles in a sample. Following the equilibrium magnetization, a 90\u00b0 radiofrequency (RF) pulse flips the direction of the magnetization vector in the xy-plane, and is then switched off. The initial magnetic field B 0 , however, is still applied. Thus, the spin magnetization vector will slowly return from the xy-plane back to the equilibrium state. The time it takes for the magnetization vector to return to its equilibrium value, M z , is referred to as the longitudinal relaxation time, T 1 . [ 20 ]  Subsequently, the rate at which this happens is simply the reciprocal of the relaxation time:  \n \n \n \n \n \n 1 \n \n T \n 1 \n \n \n \n = \n R \n 1 \n \n \n {\\displaystyle {\\frac {1}{T1}}=R1} \n \n . Similarly, the time in which it takes for M xy  to return to zero is T 2 , with the rate  \n \n \n \n \n \n 1 \n \n T \n 2 \n \n \n \n = \n R \n 2 \n \n \n {\\displaystyle {\\frac {1}{T2}}=R2} \n \n . [ 21 ]  Magnetization as a function of time is defined by the  Bloch equations ."}
{"_id": "WikiPedia_Radiology$$$corpus_1810", "text": "T 1  and T 2  values are dependent on the chemical environment of the sample; hence their utility in MRI. Soft tissue and muscle tissue relax at different rates, yielding the image contrast in a typical scan."}
{"_id": "WikiPedia_Radiology$$$corpus_1811", "text": "The standard display of MR images is to represent fluid characteristics in  black-and-white  images, where different tissues turn out as follows:"}
{"_id": "WikiPedia_Radiology$$$corpus_1812", "text": "MRI has a wide range of applications in  medical diagnosis  and around 50,000 scanners are estimated to be in use worldwide. [ 25 ]  MRI affects diagnosis and treatment in many specialties although the effect on improved health outcomes is disputed in certain cases. [ 26 ] [ 27 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1813", "text": "MRI is the investigation of choice in the preoperative  staging  of  rectal  and  prostate cancer  and has a role in the diagnosis, staging, and follow-up of other tumors, [ 28 ]  as well as for determining areas of tissue for sampling in biobanking. [ 29 ] [ 30 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1814", "text": "MRI is the investigative tool of choice for neurological cancers over CT, as it offers better visualization of the  posterior cranial fossa , containing the  brainstem  and the  cerebellum . The contrast provided between  grey  and  white matter  makes MRI the best choice for many conditions of the  central nervous system , including  demyelinating diseases ,  dementia ,  cerebrovascular disease ,  infectious diseases ,  Alzheimer's disease  and  epilepsy . [ 31 ] [ 32 ] [ 33 ]  Since many images are taken milliseconds apart, it shows how the brain responds to different stimuli, enabling researchers to study both the functional and structural brain abnormalities in psychological disorders. [ 34 ]  MRI also is used in  guided   stereotactic surgery  and  radiosurgery  for treatment of intracranial tumors, arteriovenous malformations, and other surgically treatable conditions using a device known as the  N-localizer . [ 35 ] [ 36 ] [ 37 ]  New tools that implement  artificial intelligence in healthcare  have demonstrated higher image quality and morphometric analysis in  neuroimaging  with the application of a denoising system. [ 38 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1815", "text": "The record for the highest spatial resolution of a whole intact brain (postmortem) is 100 microns, from Massachusetts General Hospital. The data was published in NATURE on 30 October 2019. [ 39 ] [ 40 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1816", "text": "Though MRI is used widely in research on mental disabilities, based on a 2024 systematic literature review and meta analysis commissioned by the Patient-Centered Outcomes Research Institute (PCORI), available research using MRI scans to diagnose ADHD showed great variability. [ 41 ]  The authors conclude that MRI cannot be reliably used to assist in making a clinical diagnosis of ADHD. [ 41 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1817", "text": "Cardiac MRI is complementary to other imaging techniques, such as  echocardiography ,  cardiac CT , and  nuclear medicine . It can be used to assess the structure and the function of the heart. [ 42 ]  Its applications include assessment of  myocardial ischemia and viability ,  cardiomyopathies ,  myocarditis ,  iron overload , vascular diseases, and  congenital heart disease . [ 43 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1818", "text": "Applications in the musculoskeletal system include  spinal imaging , assessment of  joint  disease, and  soft tissue tumors . [ 44 ]  Also, MRI techniques can be used for diagnostic imaging of\n systemic muscle diseases  including genetic muscle diseases. [ 45 ] [ 46 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1819", "text": "Swallowing movement of throat and oesophagus can cause motion artifact over the imaged spine. Therefore, a saturation pulse [ clarification needed ]  applied over this region the throat and oesophagus can help to avoid this artifact. Motion artifact arising due to pumping of the heart can be reduced by timing the MRI pulse according to heart cycles. [ 47 ]  Blood vessels flow artifacts can be reduced by applying saturation pulses above and below the region of interest. [ 48 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1820", "text": "Hepatobiliary  MR is used to detect and characterize lesions of the  liver ,  pancreas , and  bile ducts . Focal or diffuse disorders of the liver may be evaluated using  diffusion-weighted , opposed-phase imaging and  dynamic contrast enhancement  sequences. Extracellular contrast agents are used widely in liver MRI, and newer hepatobiliary contrast agents also provide the opportunity to perform functional biliary imaging. Anatomical imaging of the bile ducts is achieved by using a heavily T2-weighted sequence in magnetic resonance cholangiopancreatography (MRCP). Functional imaging of the pancreas is performed following administration of  secretin . MR enterography provides non-invasive assessment of inflammatory bowel disease and small bowel tumors. MR-colonography may play a role in the detection of large polyps in patients at increased risk of colorectal cancer. [ 49 ] [ 50 ] [ 51 ] [ 52 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1821", "text": "Magnetic resonance  angiography  (MRA) generates pictures of the arteries to evaluate them for  stenosis  (abnormal narrowing) or  aneurysms  (vessel wall dilatations, at risk of rupture). MRA is often used to evaluate the arteries of the neck and brain, the thoracic and abdominal aorta, the renal arteries, and the legs (called a \"run-off\"). A variety of techniques can be used to generate the pictures, such as administration of a  paramagnetic  contrast agent ( gadolinium ) or using a technique known as \"flow-related enhancement\" (e.g., 2D and 3D time-of-flight sequences), where most of the signal on an image is due to blood that recently moved into that plane (see also  FLASH MRI ). [ 53 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1822", "text": "Techniques involving phase accumulation (known as phase contrast angiography) can also be used to generate flow velocity maps easily and accurately. Magnetic resonance venography (MRV) is a similar procedure that is used to image veins. In this method, the tissue is now excited inferiorly, while the signal is gathered in the plane immediately superior to the excitation plane\u2014thus imaging the venous blood that recently moved from the excited plane. [ 54 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1823", "text": "MRI for imaging anatomical structures or blood flow do not require contrast agents since the varying properties of the tissues or blood provide natural contrasts. However, for more specific types of imaging,  exogenous  contrast agents may be given  intravenously ,  orally , or  intra-articularly . [ 6 ]  Most contrast agents are either paramagnetic (e.g.: gadolinium, manganese, europium), and are used to shorten T1 in the tissue they accumulate in, or super-paramagnetic (SPIONs), and are used to shorten T2 and T2* in healthy tissue reducing its signal intensity (negative contrast agents). The most commonly used intravenous contrast agents are based on  chelates  of  gadolinium , which is highly paramagnetic. [ 55 ]  In general, these agents have proved safer than the iodinated contrast agents used in X-ray radiography or CT.  Anaphylactoid reactions  are rare, occurring in approx. 0.03\u20130.1%. [ 56 ]  Of particular interest is the lower incidence of nephrotoxicity, compared with iodinated agents, when given at usual doses\u2014this has made contrast-enhanced MRI scanning an option for patients with renal impairment, who would otherwise not be able to undergo  contrast-enhanced CT . [ 57 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1824", "text": "Gadolinium-based contrast reagents are typically  octadentate  complexes of  gadolinium(III) . The complex is  very stable  (log K > 20) so that, in use, the concentration of the un-complexed Gd 3+  ions should be below the toxicity limit. The 9th place in the metal ion's  coordination sphere  is occupied by a water molecule which exchanges rapidly with water molecules in the reagent molecule's immediate environment, affecting the magnetic resonance  relaxation time . [ 58 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1825", "text": "In December 2017, the  Food and Drug Administration  (FDA) in the  United States  announced in a drug safety communication that new warnings were to be included on all gadolinium-based contrast agents (GBCAs). The FDA also called for increased patient education and requiring gadolinium contrast vendors to conduct additional animal and clinical studies to assess the safety of these agents. [ 59 ] \nAlthough gadolinium agents have proved useful for patients with kidney impairment, in patients with severe  kidney failure  requiring dialysis there is a risk of a rare but serious illness,  nephrogenic systemic fibrosis , which may be linked to the use of certain gadolinium-containing agents. The most frequently linked is  gadodiamide , but other agents have been linked too. [ 60 ]  Although a causal link has not been definitively established, current guidelines in the  United States  are that dialysis patients should only receive gadolinium agents where essential and that  dialysis  should be performed as soon as possible after the scan to remove the agent from the body promptly. [ 61 ] [ 62 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1826", "text": "In Europe, where more gadolinium-containing agents are available, a classification of agents according to potential risks has been released. [ 63 ] [ 64 ]  In 2008, a new contrast agent named  gadoxetate , brand name Eovist (US) or Primovist (EU), was approved for diagnostic use: This has the theoretical benefit of a dual excretion path. [ 65 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1827", "text": "An  MRI sequence  is a particular setting of radiofrequency pulses and gradients, resulting in a particular image appearance. [ 66 ]  The  T1 and T2  weighting can also be described as MRI sequences."}
{"_id": "WikiPedia_Radiology$$$corpus_1828", "text": "edit This table does not include  uncommon and experimental sequences ."}
{"_id": "WikiPedia_Radiology$$$corpus_1829", "text": "Standard foundation and comparison for other sequences"}
{"_id": "WikiPedia_Radiology$$$corpus_1830", "text": "Magnetic resonance spectroscopy  (MRS) is used to measure the levels of different  metabolites  in body tissues, which can be achieved through a variety of single voxel or imaging-based techniques. [ 96 ]  The MR signal produces a spectrum of resonances that corresponds to different molecular arrangements of the isotope being \"excited\". This signature is used to diagnose certain metabolic disorders, especially those affecting the brain, [ 97 ]  and to provide information on tumor  metabolism . [ 98 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1831", "text": "Magnetic resonance spectroscopic imaging (MRSI) combines both spectroscopic and imaging methods to produce spatially localized spectra from within the sample or patient. The spatial resolution is much lower (limited by the available  SNR ), but the spectra in each voxel contains information about many metabolites. Because the available signal is used to encode spatial and spectral information, MRSI requires high SNR achievable only at higher field strengths (3 T and above). [ 99 ]  The high procurement and maintenance costs of MRI with extremely high field strengths [ 100 ]  inhibit their popularity. However, recent  compressed sensing -based software algorithms ( e.g. ,  SAMV [ 101 ] ) have been proposed to achieve  super-resolution  without requiring such high field strengths."}
{"_id": "WikiPedia_Radiology$$$corpus_1832", "text": "Real-time magnetic resonance imaging  (RT-MRI) refers to the continuous monitoring of moving objects in real time. Traditionally, real-time MRI was possible only with low image quality or low temporal resolution. An  iterative reconstruction  algorithm removed limitations. Radial  FLASH MRI  (real-time) yields a temporal resolution of 20 to 30 milliseconds for images with an in-plane resolution of 1.5 to 2.0\u00a0mm. [ 103 ]  Real-time MRI adds information about diseases of the  joints  and the  heart . In many cases MRI examinations become easier and more comfortable for patients, especially for the patients who cannot calm their breathing [ 104 ]  or who have  arrhythmia ."}
{"_id": "WikiPedia_Radiology$$$corpus_1833", "text": "The lack of harmful effects on the patient and the operator make MRI well-suited for  interventional radiology , where the images produced by an MRI scanner guide minimally invasive procedures. Such procedures use no  ferromagnetic  instruments. [ 105 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1834", "text": "A specialized growing subset of  interventional MRI  is  intraoperative MRI , in which an MRI is used in surgery. Some specialized MRI systems allow imaging concurrent with the surgical procedure. More typically, the surgical procedure is temporarily interrupted so that MRI can assess the success of the procedure or guide subsequent surgical work. [ 106 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1835", "text": "In guided therapy,  high-intensity focused ultrasound  (HIFU) beams are focused on a tissue, that are controlled using MR thermal imaging. Due to the high energy at the focus, the temperature rises to above 65  \u00b0C  (150\u00a0\u00b0F) which completely destroys the tissue. This technology can achieve precise  ablation  of diseased tissue. MR imaging provides a three-dimensional view of the target tissue, allowing for the precise focusing of ultrasound energy. The MR imaging provides quantitative, real-time, thermal images of the treated area. This allows the physician to ensure that the temperature generated during each cycle of ultrasound energy is sufficient to cause thermal ablation within the desired tissue and if not, to adapt the parameters to ensure effective treatment. [ 107 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1836", "text": "Hydrogen has the most frequently imaged  nucleus  in MRI because it is present in biological tissues in great abundance, and because its high  gyromagnetic ratio  gives a strong signal. However, any nucleus with a net  nuclear spin  could potentially be imaged with MRI. Such nuclei include  helium-3 ,  lithium-7 ,  carbon-13 ,  fluorine -19,  oxygen-17 ,  sodium -23,  phosphorus -31 and  xenon-129 .  23 Na and  31 P are naturally abundant in the body, so they can be imaged directly. Gaseous isotopes such as  3 He or  129 Xe must be  hyperpolarized  and then inhaled as their nuclear density is too low to yield a useful signal under normal conditions.  17 O  and  19 F can be administered in sufficient quantities in liquid form (e.g.  17 O -water) that hyperpolarization is not a necessity. [ 108 ]  Using helium or xenon has the advantage of reduced background noise, and therefore increased contrast for the image itself, because these elements are not normally present in biological tissues. [ 109 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1837", "text": "Moreover, the nucleus of any atom that has a net nuclear spin and that is bonded to a hydrogen atom could potentially be imaged via heteronuclear magnetization transfer MRI that would image the high-gyromagnetic-ratio hydrogen nucleus instead of the low-gyromagnetic-ratio nucleus that is bonded to the hydrogen atom. [ 110 ]  In principle, heteronuclear magnetization transfer MRI could be used to detect the presence or absence of specific chemical bonds. [ 111 ] [ 112 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1838", "text": "Multinuclear imaging is primarily a research technique at present. However, potential applications include functional imaging and imaging of organs poorly seen on  1 H MRI (e.g., lungs and bones) or as alternative contrast agents. Inhaled hyperpolarized  3 He can be used to image the distribution of air spaces within the lungs. Injectable solutions containing  13 C or stabilized bubbles of hyperpolarized  129 Xe have been studied as contrast agents for angiography and perfusion imaging.  31 P can potentially provide information on bone density and structure, as well as functional imaging of the brain. Multinuclear imaging holds the potential to chart the distribution of lithium in the human brain, this element finding use as an important drug for those with conditions such as bipolar disorder. [ 113 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1839", "text": "MRI has the advantages of having very high spatial resolution and is very adept at morphological imaging and functional imaging. MRI does have several disadvantages though. First, MRI has a sensitivity of around 10 \u22123   mol/L   to 10 \u22125  mol/L, which, compared to other types of imaging, can be very limiting. This problem stems from the fact that the population difference between the nuclear spin states is very small at room temperature. For example, at 1.5  teslas , a typical field strength for clinical MRI, the difference between high and low energy states is approximately 9 molecules per 2\u00a0million. Improvements to increase MR sensitivity include increasing magnetic field strength and  hyperpolarization  via optical pumping or dynamic nuclear polarization. There are also a variety of signal amplification schemes based on chemical exchange that increase sensitivity. [ 114 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1840", "text": "To achieve molecular imaging of disease biomarkers using MRI, targeted MRI  contrast agents  with high specificity and high relaxivity (sensitivity) are required. To date, many studies have been devoted to developing targeted-MRI contrast agents to achieve molecular imaging by MRI. Commonly, peptides, antibodies, or small ligands, and small protein domains, such as HER-2 affibodies, have been applied to achieve targeting. To enhance the sensitivity of the contrast agents, these targeting moieties are usually linked to high payload MRI contrast agents or MRI contrast agents with high relaxivities. [ 115 ]  A new class of gene targeting MR contrast agents has been introduced to show gene action of unique mRNA and gene transcription factor proteins. [ 116 ] [ 117 ]  These new contrast agents can trace cells with unique mRNA, microRNA and virus; tissue response to inflammation in living brains. [ 118 ]  The MR reports change in gene expression with positive correlation to TaqMan analysis, optical and electron microscopy. [ 119 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1841", "text": "It takes time to gather MRI data using sequential applications of magnetic field gradients. Even for the most streamlined of  MRI sequences , there are physical and physiologic limits to the rate of gradient switching. Parallel MRI circumvents these limits by gathering some portion of the data simultaneously, rather than in a traditional sequential fashion. This is accomplished using arrays of radiofrequency (RF) detector coils, each with a different 'view' of the body. A reduced set of gradient steps is applied, and the remaining spatial information is filled in by combining signals from various coils, based on their known spatial sensitivity patterns. The resulting acceleration is limited by the number of coils and by the signal to noise ratio (which decreases with increasing acceleration), but two- to four-fold accelerations may commonly be achieved with suitable coil array configurations, and substantially higher accelerations have been demonstrated with specialized coil arrays. Parallel MRI may be used with most  MRI sequences ."}
{"_id": "WikiPedia_Radiology$$$corpus_1842", "text": "After a number of early suggestions for using arrays of detectors to accelerate imaging went largely unremarked in the MRI field, parallel imaging saw widespread development and application following the introduction of the SiMultaneous Acquisition of Spatial Harmonics (SMASH) technique in 1996\u20137. [ 120 ]  The SENSitivity Encoding (SENSE) [ 121 ]  and Generalized Autocalibrating Partially Parallel Acquisitions (GRAPPA) [ 122 ]  techniques are the parallel imaging methods in most common use today. The advent of parallel MRI resulted in extensive research and development in image reconstruction and RF coil design, as well as in a rapid expansion of the number of receiver channels available on commercial MR systems. Parallel MRI is now used routinely for MRI examinations in a wide range of body areas and clinical or research applications."}
{"_id": "WikiPedia_Radiology$$$corpus_1843", "text": "Most MRI focuses on qualitative interpretation of MR data by acquiring spatial maps of relative variations in signal strength which are \"weighted\" by certain parameters. [ 123 ]  Quantitative methods instead attempt to determine spatial maps of accurate tissue relaxometry parameter values or magnetic field, or to measure the size of certain spatial features."}
{"_id": "WikiPedia_Radiology$$$corpus_1844", "text": "Examples of quantitative MRI methods are:"}
{"_id": "WikiPedia_Radiology$$$corpus_1845", "text": "Quantitative MRI aims to increase the  reproducibility  of MR images and interpretations, but has historically require longer scan times. [ 123 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1846", "text": "Quantitative MRI (or qMRI) sometimes more specifically refers to multi-parametric quantitative MRI, the mapping of multiple tissue relaxometry parameters in a single imaging session. [ 128 ] \nEfforts to make multi-parametric quantitative MRI faster have produced sequences which map multiple parameters simultaneously, either by building separate encoding methods for each parameter into the sequence, [ 129 ] \nor by fitting MR signal evolution to a multi-parameter model. [ 130 ] [ 131 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1847", "text": "Traditional MRI generates poor images of lung tissue because there are fewer water molecules with protons that can be excited by the magnetic field. Using hyperpolarized gas an MRI scan can identify ventilation defects in the lungs. Before the scan, a patient is asked to inhale hyperpolarized  xenon  mixed with a buffer gas of helium or nitrogen. The resulting lung images are much higher quality than with traditional MRI."}
{"_id": "WikiPedia_Radiology$$$corpus_1848", "text": "MRI is, in general, a safe technique, although injuries may occur as a result of failed safety procedures or human error. [ 132 ]   Contraindications  to MRI include most  cochlear implants  and  cardiac pacemakers ,  shrapnel , and metallic  foreign bodies  in the  eyes .  Magnetic resonance imaging in pregnancy  appears to be safe, at least during the second and third  trimesters  if done without contrast agents. [ 133 ]  Since MRI does not use any ionizing radiation, its use is generally favored in preference to  CT  when either modality could yield the same information. [ 134 ]  Some patients experience claustrophobia and may require sedation or shorter MRI protocols. [ 135 ] [ 136 ]  Amplitude and rapid switching of gradient coils during image acquisition may cause peripheral nerve stimulation. [ 137 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1849", "text": "MRI uses powerful magnets and can therefore cause  magnetic materials  to move at great speeds, posing a projectile risk, and may cause fatal accidents. [ 138 ]  However, as millions of MRIs are performed globally each year, [ 139 ]  fatalities are extremely rare. [ 140 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1850", "text": "MRI machines can produce loud noise, up to 120  dB(A) . [ 141 ]  This can cause  hearing loss ,  tinnitus  and  hyperacusis , so appropriate  hearing protection  is essential for anyone inside the MRI scanner room during the examination."}
{"_id": "WikiPedia_Radiology$$$corpus_1851", "text": "Medical societies issue guidelines for when physicians should use MRI on patients and recommend against overuse. MRI can detect health problems or confirm a diagnosis, but medical societies often recommend that MRI not be the first procedure for creating a plan to diagnose or manage a patient's complaint. A common case is to use MRI to seek a cause of  low back pain ; the  American College of Physicians , for example, recommends against imaging (including MRI) as unlikely to result in a positive outcome for the patient. [ 26 ] [ 27 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1852", "text": "An  MRI artifact  is a  visual artifact , that is, an anomaly during visual representation. Many different artifacts can occur during magnetic resonance imaging (MRI), some affecting the diagnostic quality, while others may be confused with pathology. Artifacts can be classified as patient-related, signal processing-dependent and hardware (machine)-related. [ 142 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1853", "text": "MRI is used industrially mainly for routine analysis of chemicals. The  nuclear magnetic resonance  technique is also used, for example, to measure the ratio between water and fat in foods, monitoring of flow of corrosive fluids in pipes, or to study molecular structures such as catalysts. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1854", "text": "Being non-invasive and non-damaging, MRI can be used to study the anatomy of plants, their water transportation processes and water balance. [ 143 ]  It is also applied to veterinary radiology for diagnostic purposes. Outside this, its use in zoology is limited due to the high cost; but it can be used on many species. [ 144 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1855", "text": "In palaeontology it is used to examine the structure of fossils. [ 145 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1856", "text": "Forensic  imaging provides graphic documentation of an  autopsy , which manual autopsy does not. CT scanning provides quick whole-body imaging of skeletal and  parenchymal  alterations, whereas MR imaging gives better representation of soft tissue  pathology . [ 146 ]  All that being said, MRI is more expensive, and more time-consuming to utilize. [ 146 ]  Moreover, the quality of MR imaging deteriorates below 10\u00a0\u00b0C. [ 147 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1857", "text": "In 1971 at  Stony Brook University ,  Paul Lauterbur  applied magnetic field gradients in all three dimensions and a back-projection technique to create NMR images. He published the first images of two tubes of water in 1973 in the journal  Nature , [ 148 ]  followed by the picture of a living animal, a clam, and in 1974 by the image of the thoracic cavity of a mouse. Lauterbur called his imaging method zeugmatography, a term which was replaced by (N)MR imaging. [ 1 ]  In the late 1970s, physicists  Peter Mansfield  and  Paul Lauterbur  developed MRI-related techniques, like the  echo-planar imaging  (EPI) technique. [ 149 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1858", "text": "Raymond Damadian 's work into  nuclear magnetic resonance  (NMR) has been incorporated into MRI, having built one of the first scanners. [ 150 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1859", "text": "Advances in  semiconductor  technology were crucial to the development of practical MRI, which requires a large amount of  computational power . This was made possible by the rapidly increasing number of  transistors  on a single  integrated circuit  chip. [ 151 ]  Mansfield and Lauterbur were awarded the 2003  Nobel Prize in Physiology or Medicine  for their \"discoveries concerning magnetic resonance imaging\". [ 152 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1860", "text": "Marie Curie, une femme sur le front  (English: Marie Curie, a woman on the front) is a Franco-Belgian drama historical television film directed by  Alain Brunard \u00a0[ fr ]  and starring  Dominique Reymond . [ 2 ] [ 3 ]  It was broadcast on April 25, 2014 on  RTBF [ 4 ]  and November 11, 2014 on  France 2 . [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1861", "text": "The fictional scenes are interspersed with many sequences from filmed archives including, at the end of the movie, several sequences where Marie Curie herself appears. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1862", "text": "Marie Curie ,  Nobel laureate in physics  and  chemistry , directs the  Radium Institute  when  World War I  breaks out in 1914. She equips a first van with  X-ray  equipment and goes to the site of the  Battle of the Marne . The  field hospital  she takes care of becomes notable for the few deaths recorded. In addition to the help of Doctor  Claudius Regaud , one of her collaborators who works on the treatment of cancer by radiotherapy, Marie Curie receives that of her 17-year-old daughter,  Ir\u00e8ne . She quickly equips other vehicles, nicknamed by the soldiers \u201cthe  Little Curies \u00a0[ fr ] \u201d. Following the different fronts, her work becomes recognised and  radiography , which until then was mainly an amusement for the public, became a precious aid for medicine."}
{"_id": "WikiPedia_Radiology$$$corpus_1863", "text": "The movie participated to the  Luchon TV Festival \u00a0[ fr ] [ 6 ] [ 7 ]  and was awarded the Audience Award for Best TV Movie, while Dominique Reymond obtained the Best Actress Award. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1864", "text": "In  mammography ,  mean glandular dose  ( MGD ) is a quantity used to describe the  absorbed dose  of  radiation  to the  breast . It is based on a measurement of  air kerma  and conversion factors. MGD can be calculated from measurements made with  poly(methyl methacrylate)  (PMMA) blocks. It is often used to compare typical doses to patients between different centres or internationally, and is the preferred measure of the potential risk from mammography. [ 1 ] [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1865", "text": "MGD can be calculated from a measured incident air kerma at the top of the breast,  \n \n \n \n K \n \n \n {\\displaystyle K} \n \n , as follows: [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1866", "text": "D \n = \n K \n g \n c \n s \n \n \n {\\displaystyle D=Kgcs}"}
{"_id": "WikiPedia_Radiology$$$corpus_1867", "text": "g \n \n \n {\\displaystyle g} \n \n  converts from incident air kerma to MGD, with a glandularity of 50%, based on breast thickness and  HVL .  \n \n \n \n c \n \n \n {\\displaystyle c} \n \n  corrects for glandularity other than 50%, depending on the breast thickness and HVL, with two versions for ages 50\u201364 and 40\u201349.  \n \n \n \n s \n \n \n {\\displaystyle s} \n \n  corrects for the x-ray  spectra  in use with a table of target/ filter  combinations. [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1868", "text": "MGD is typically used to define limits on mammography exposures by national and international organisations such as the  European Union  and  International Atomic Energy Agency , at <2.5  milligray  (mGy) per exposure to a standard breast (4.5\u00a0cm PMMA). [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1869", "text": "In routine quality assurance testing of mammographic equipment, MGD measurements for a range of effective breast thicknesses with PMMA, and from real patient exposures, is widely recommended. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1870", "text": "Neuroimaging  is the use of quantitative (computational) techniques to study the  structure  and function of the  central nervous system , developed as an objective way of scientifically studying the healthy human brain in a non-invasive manner. Increasingly it is also being used for quantitative research studies of brain disease and psychiatric illness.  Neuroimaging is highly multidisciplinary involving neuroscience, computer science, psychology and statistics, and is not a medical specialty.  Neuroimaging is sometimes confused with neuroradiology."}
{"_id": "WikiPedia_Radiology$$$corpus_1871", "text": "Neuroradiology  is a medical specialty that uses non-statistical brain imaging in a clinical setting, practiced by radiologists who are medical practitioners. Neuroradiology primarily focuses on recognizing brain lesions, such as vascular diseases, strokes, tumors, and inflammatory diseases. In contrast to neuroimaging, neuroradiology is qualitative (based on subjective impressions and extensive clinical training) but sometimes uses basic quantitative methods.  Functional brain imaging techniques, such as functional magnetic resonance imaging ( fMRI ), are common in neuroimaging but rarely used in neuroradiology.  Neuroimaging falls into two broad categories:"}
{"_id": "WikiPedia_Radiology$$$corpus_1872", "text": "The first chapter of the history of neuroimaging traces back to the Italian neuroscientist  Angelo Mosso  who invented the 'human circulation balance', which could non-invasively measure the redistribution of  blood  during emotional and intellectual activity. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1873", "text": "In 1918, the American neurosurgeon  Walter Dandy  introduced the technique of ventriculography.  X-ray  images of the  ventricular system  within the brain were obtained by injection of filtered air directly into one or both lateral ventricles of the brain. Dandy also observed that air introduced into the subarachnoid space via lumbar spinal puncture could enter the cerebral ventricles and also demonstrate the cerebrospinal fluid compartments around the base of the brain and over its surface.  This technique was called  pneumoencephalography . [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1874", "text": "In 1927,  Egas Moniz  introduced  cerebral angiography , whereby both normal and abnormal blood vessels in and around the brain could be visualized with great precision."}
{"_id": "WikiPedia_Radiology$$$corpus_1875", "text": "In the early 1970s,  Allan McLeod Cormack  and  Godfrey Newbold Hounsfield  introduced  computerized axial tomography  (CAT or CT scanning), and ever more detailed anatomic images of the brain became available for diagnostic and research purposes. Cormack and Hounsfield won the 1979  Nobel Prize for Physiology or Medicine  for their work. Soon after the introduction of CAT in the early 1980s, the development of  radioligands  allowed  single-photon emission computed tomography  (SPECT) and  positron emission tomography  (PET) of the brain."}
{"_id": "WikiPedia_Radiology$$$corpus_1876", "text": "More or less concurrently,  magnetic resonance imaging  (MRI or MR scanning) was developed by researchers including  Peter Mansfield  and  Paul Lauterbur , who were awarded the  Nobel Prize for Physiology or Medicine  in 2003. In the early 1980s MRI was introduced clinically, and during the 1980s a veritable explosion of technical refinements and diagnostic MR applications took place. Scientists soon learned that the large blood flow changes measured by PET could also be imaged by the correct type of MRI.  Functional magnetic resonance imaging  (fMRI) was born, and\nsince the 1990s, fMRI has come to dominate the brain mapping field due to its low invasiveness, lack of radiation exposure, and relatively wide availability."}
{"_id": "WikiPedia_Radiology$$$corpus_1877", "text": "In the early 2000s, the field of neuroimaging reached the stage where limited practical applications of functional brain imaging have become feasible. The main application area is crude forms of  brain\u2013computer interface ."}
{"_id": "WikiPedia_Radiology$$$corpus_1878", "text": "The world record for the spatial resolution of a whole-brain MRI image was a 100-micrometer volume (image) achieved in 2019. The sample acquisition took about 100 hours. [ 2 ]  The spatial world record of a whole human brain of any method was an\nX-ray tomography scan performing at the ESRF (European synchrotron radiation facility), which had a resolution of about 25 microns and requiring about 22 hours. This scan was part of the human organ atlas which has X-ray tomography scans of other organs in the human body with the same resolution. [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1879", "text": "A crucial idea for magnetic resonance imaging is that the net magnetization vector can be moved by exposing the spin system to energy of a frequency equal to the energy difference between the spin states (e.g., by a radio frequency pulse). If enough energy is delivered to the system, it is possible to make the net magnetization vector orthogonal to that of the external magnetic field."}
{"_id": "WikiPedia_Radiology$$$corpus_1880", "text": "Neuroradiology often follows a  neurological examination  in which a physician has found cause to more deeply investigate a patient who has or may have a  neurological disorder ."}
{"_id": "WikiPedia_Radiology$$$corpus_1881", "text": "Common clinical indications for neuroimaging include head trauma, stroke like symptoms e.g.: sudden weakness/numbness in one half of body, difficulty talking or walking; seizures, sudden onset severe headache, sudden change in level of consciousness for unclear reasons."}
{"_id": "WikiPedia_Radiology$$$corpus_1882", "text": "Another indication for neuroradiology is CT-, MRI- and PET- guided   stereotactic surgery  or  radiosurgery  for treatment of intracranial tumors, arteriovenous malformations and other surgically treatable conditions. [ 5 ] [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1883", "text": "One of the more common neurological problems which a person may experience is simple  syncope . [ 8 ] [ 9 ]  In cases of simple  syncope  in which the patient's history does not suggest other neurological symptoms, the diagnosis includes a  neurological examination  but routine neurological imaging is not indicated because the likelihood of finding a cause in the central nervous system is extremely low and the patient is unlikely to benefit from the procedure. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1884", "text": "Neuroradiology is not indicated for patients with stable headaches which are diagnosed as migraine. [ 10 ]  Studies indicate that presence of migraine does not increase a patient's risk for intracranial disease. [ 10 ]  A diagnosis of migraine which notes the absence of other problems, such as  papilledema , would not indicate a need for radiological investigations. [ 10 ]  In the course of conducting a careful diagnosis, the physician should consider whether the headache has a cause other than the migraine and might require radiological investigations. [ 10 ] [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1885", "text": "Computed tomography  (CT) or  Computed Axial Tomography  (CAT) scanning uses a series of  x-rays  of the head taken from many different directions. Typically used for quickly viewing  brain injuries , CT scanning uses a computer program that performs a numerical integral calculation (the inverse  Radon transform ) on the measured x-ray series to estimate how much of an x-ray beam is absorbed in a small volume of the brain. Typically the information is presented as cross-sections of the brain. [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1886", "text": "Magnetic resonance imaging  (MRI) uses magnetic fields and radio waves to produce high quality two- or three-dimensional images of brain structures without the use of ionizing radiation (X-rays) or radioactive tracers."}
{"_id": "WikiPedia_Radiology$$$corpus_1887", "text": "The record for the highest spatial resolution of a whole intact brain (postmortem) is 100 microns, from Massachusetts General Hospital. The data was published in  Scientific Data  on 30 October 2019. [ 13 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1888", "text": "Positron emission tomography  (PET) and  brain positron emission tomography , measure emissions from radioactively labeled metabolically active chemicals that have been injected into the bloodstream. The emission data are computer-processed to produce 2- or 3-dimensional images of the distribution of the chemicals throughout the brain. [ 14 ] :\u200a57\u200a  The  positron  emitting  radioisotopes  used are produced by a  cyclotron , and chemicals are labeled with these radioactive atoms. The labeled compound, called a  radiotracer , is injected into the bloodstream and eventually makes its way to the brain.  Sensors in the PET scanner detect the radioactivity as the compound accumulates in various regions of the brain.  A computer uses the data gathered by the sensors to create multicolored 2- or 3-dimensional images that show where the compound acts in the brain. Especially useful are a wide array of  ligands  used to map different aspects of neurotransmitter activity, with by far the most commonly used PET tracer being a labeled form of glucose (see  Fludeoxyglucose (18F)  (FDG))."}
{"_id": "WikiPedia_Radiology$$$corpus_1889", "text": "The greatest benefit of PET scanning is that different compounds can show blood flow and oxygen and  glucose   metabolism  in the tissues of the working brain.  These measurements reflect the amount of brain activity in the various regions of the brain and allow to learn more about how the brain works.  PET scans were superior to all other metabolic imaging methods in terms of resolution and speed of completion (as little as 30 seconds) when they first became available.  The improved resolution permitted better study to be made as to the area of the brain activated by a particular task. The biggest drawback of PET scanning is that because the radioactivity decays rapidly, it is limited to monitoring short tasks. [ 14 ] :\u200a60\u200a   Before fMRI technology came online, PET scanning was the preferred method of functional (as opposed to structural) brain imaging, and it continues to make large contributions to  neuroscience ."}
{"_id": "WikiPedia_Radiology$$$corpus_1890", "text": "PET scanning is also used for diagnosis of brain disease, most notably brain tumors, epilepsy, and neuron-damaging diseases which cause dementia (such as Alzheimer's disease) all cause great changes in brain metabolism, which in turn causes easily detectable changes in PET scans. PET is probably most useful in early cases of certain dementias (with classic examples being  Alzheimer's disease  and  Pick's disease ) where the early damage is too diffuse and makes too little difference in brain volume and gross structure to change CT and standard MRI images enough to be able to reliably differentiate it from the \"normal\" range of cortical atrophy which occurs with aging (in many but not all) persons, and which does  not  cause clinical dementia."}
{"_id": "WikiPedia_Radiology$$$corpus_1891", "text": "FDG-PET scanning is also often used in assessment of patients with epilepsy who continue to have seizures despite adequate medical treatment. In focal epilepsy, where seizures begin in a small part of the brain before spreading elsewhere, it is one of the many modalities used to identify the region of brain responsible for seizure onset. Typically, the area of brain where seizures begin is dysfunctional even when patient is not having a seizure and uptakes less glucose, hence less FDG compared to healthy brain regions. [ 15 ]  This information can help plan for epilepsy surgery as a treatment for drug resistant epilepsy."}
{"_id": "WikiPedia_Radiology$$$corpus_1892", "text": "Other radiotracers have also been used to identify areas of seizure onset though they are not available commercially for clinical use. These include  11 C-flumazenil, 1 1 C-alpha-methyl-L-tryptophan,  11 C-methionine,  11 C-cerfentanil. [ 15 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1893", "text": "Single-photon emission computed tomography  (SPECT) is similar to PET and uses  gamma ray -emitting  radioisotopes  and a  gamma camera  to record data that a computer uses to construct two- or three-dimensional images of active brain regions. [ 16 ]  SPECT relies on an injection of radioactive tracer, or \"SPECT agent,\" which is rapidly taken up by the brain but does not redistribute. Uptake of SPECT agent is nearly 100% complete within 30 to 60 seconds, reflecting  cerebral blood flow  (CBF) at the time of injection. These properties of SPECT make it particularly well-suited for epilepsy imaging, which is usually made difficult by problems with patient movement and variable seizure types. SPECT provides a \"snapshot\" of cerebral blood flow since scans can be acquired after seizure termination (so long as the radioactive tracer was injected at the time of the seizure). A significant limitation of SPECT is its poor resolution (about 1\u00a0cm) compared to that of MRI. Today, SPECT machines with Dual Detector Heads are commonly used, although Triple Detector Head machines are available in the marketplace.  Tomographic reconstruction , (mainly used for functional \"snapshots\" of the brain) requires multiple projections from Detector Heads which rotate around the human skull, so some researchers have developed 6 and 11 Detector Head SPECT machines to cut imaging time and give higher resolution. [ 17 ] [ 18 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1894", "text": "Like PET, SPECT also can be used to differentiate different kinds of disease processes which produce dementia, and it is increasingly used for this purpose. SPECT scan using Isoflupane labeled with I-123 (also called DaT scan) is useful in differentiating Parkinson's disease from other causes of tremor. [ 19 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1895", "text": "SPECT scan is also used in evaluation of drug resistant epilepsy. This uses Tc 99  labeled hexamethyl-propylene amine oxime (Tc 99 HMPAO) or ethyl cysteinate dimer ( Tc 99  ECD) as the tracers. The radiotracer is injected into the patient's vein as soon as the start of a seizure is detected and scanning is done within few hours after the seizure is over. This technique is called ictal SPECT and relies on the increased CBF in areas of seizure onset during the seizure. Interictal SPECT is a scan done using the same tracers but during a time when the patient is not having a seizure. In between seizures, a reduction in CBF is seen in areas of seizure onset and is not as pronounced as the blood flow increase during the seizure. [ 20 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1896", "text": "Cranial ultrasound  is usually only used in babies, whose open  fontanelles  provide acoustic windows allowing ultrasound imaging of the brain.  Advantages include the absence of  ionising radiation  and the possibility of bedside scanning, but the lack of soft-tissue detail means  MRI  is preferred for some conditions."}
{"_id": "WikiPedia_Radiology$$$corpus_1897", "text": "[ 21 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1898", "text": "Functional magnetic resonance imaging  (fMRI) and  arterial spin labeling  (ASL) relies on the paramagnetic properties of oxygenated and deoxygenated  hemoglobin  to see images of changing blood flow in the brain associated with neural activity. This allows images to be generated that reflect which brain structures are activated (and how) during the performance of different tasks or at resting state. According to the oxygenation hypothesis, changes in oxygen usage in regional cerebral blood flow during cognitive or behavioral activity can be associated with the regional neurons as being directly related to the cognitive or behavioral tasks being attended."}
{"_id": "WikiPedia_Radiology$$$corpus_1899", "text": "Most fMRI scanners allow subjects to be presented with different visual images, sounds and touch stimuli, and to make different actions such as pressing a button or moving a joystick. Consequently, fMRI can be used to reveal brain structures and processes associated with perception, thought and action. The resolution of fMRI is about 2-3 millimeters at present, limited by the spatial spread of the hemodynamic response to neural activity. It has largely superseded PET for the study of brain activation patterns. PET, however, retains the significant advantage of being able to identify specific brain  receptors  (or  transporters ) associated with particular  neurotransmitters  through its ability to image radiolabeled receptor \"ligands\" (receptor ligands are any chemicals that stick to receptors). There is also significant concern regarding the validity of some of the statistics used in fMRI analyses; hence, the validity of conclusions drawn from many fMRI studies. [ 22 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1900", "text": "With between 72% and 90% accuracy where chance would achieve 0.8%, [ 23 ]  fMRI techniques can decide which of a set of known images the subject is viewing. [ 24 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1901", "text": "Recent studies on machine learning in psychiatry have used fMRI to build machine learning models that can discriminate between individuals with or without suicidal behaviour. Imaging studies in conjunction with machine learning algorithms may help identify new markers in neuroimaging that could allow stratification based on patients' suicide risk and help develop the best therapies and treatments for individual patients. [ 25 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1902", "text": "Diffuse optical imaging  (DOI) or diffuse optical tomography (DOT) is a  medical imaging  modality which uses near  infrared  light to generate images of the body. The technique measures the  optical absorption  of  haemoglobin , and relies on the  absorption spectrum  of haemoglobin varying with its oxygenation status.  High-density diffuse optical tomography (HD-DOT) has been compared directly to fMRI using response to visual stimulation in subjects studied with both techniques, with reassuringly similar results. [ 26 ]  HD-DOT has also been compared to fMRI in terms of language tasks and resting state functional connectivity. [ 27 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1903", "text": "Event-related optical signal  (EROS) is a brain-scanning technique which uses infrared light through optical fibers to measure changes in optical properties of active areas of the cerebral cortex. Whereas techniques such as  diffuse optical imaging  (DOT) and near-infrared spectroscopy (NIRS) measure optical absorption of haemoglobin, and thus are based on blood flow, EROS takes advantage of the scattering properties of the neurons themselves and thus provides a much more direct measure of cellular activity. EROS can pinpoint activity in the brain within millimeters (spatially) and within milliseconds (temporally). Its biggest downside is the inability to detect activity more than a few centimeters deep. EROS is a new, relatively inexpensive technique that is non-invasive to the test subject. It was developed at the University of Illinois at Urbana-Champaign where it is now used in the Cognitive Neuroimaging Laboratory of Dr. Gabriele Gratton and Dr. Monica Fabiani."}
{"_id": "WikiPedia_Radiology$$$corpus_1904", "text": "Magnetoencephalography  (MEG) is an imaging technique used to measure the magnetic fields produced by electrical activity in the brain via extremely sensitive devices such as  superconducting quantum interference devices  (SQUIDs) or  spin exchange relaxation-free [ 28 ]  (SERF) magnetometers. MEG offers a very direct measurement of neural electrical activity (compared to fMRI for example) with very high temporal resolution but relatively low spatial resolution. The advantage of measuring the magnetic fields produced by neural activity is that they are likely to be less distorted by surrounding tissue (particularly the skull and scalp) compared to the electric fields measured by  electroencephalography  (EEG).  Specifically, it can be shown that magnetic fields produced by electrical activity are not affected by the surrounding head tissue, when the head is modeled as a set of concentric spherical shells, each being an isotropic homogeneous conductor. Real heads are non-spherical and have largely anisotropic conductivities (particularly white matter and skull). While skull anisotropy has a negligible effect on MEG (unlike EEG), white matter anisotropy strongly affects MEG measurements for radial and deep sources. [ 29 ]  Note, however, that the skull was assumed to be uniformly anisotropic in this study, which is not true for a real head: the absolute and relative thicknesses of  diplo\u00eb  and tables layers vary among and within the skull bones. This makes it likely that MEG is also affected by the skull anisotropy, [ 30 ]  although probably not to the same degree as EEG."}
{"_id": "WikiPedia_Radiology$$$corpus_1905", "text": "There are many uses for MEG, including assisting surgeons in localizing a pathology, assisting researchers in determining the function of various parts of the brain, neurofeedback, and others."}
{"_id": "WikiPedia_Radiology$$$corpus_1906", "text": "Functional ultrasound imaging  (fUS) is a medical ultrasound imaging technique of detecting or measuring changes in neural activities or metabolism, for example, the loci of brain activity, typically through measuring blood flow or hemodynamic changes. Functional ultrasound relies on Ultrasensitive Doppler and ultrafast ultrasound imaging which allows high sensitivity blood flow imaging."}
{"_id": "WikiPedia_Radiology$$$corpus_1907", "text": "In June 2021, researchers reported the development of the first modular quantum brain scanner which uses magnetic imaging and could become a novel whole-brain scanning approach. [ 31 ] [ 32 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1908", "text": "fMRI is commonly classified as a minimally-to-moderate risk due to its non-invasiveness compared to other imaging methods. fMRI uses blood oxygenation level dependent (BOLD)-contrast in order to produce its form of imaging. BOLD-contrast is a naturally occurring process in the body so fMRI is often preferred over imaging methods that require radioactive markers to produce similar imaging. [ 33 ]  A concern in the use of fMRI is its use in individuals with medical implants or devices and metallic items in the body. The magnetic resonance (MR) emitted from the equipment can cause failure of medical devices and attract metallic objects in the body if not properly screened for. Currently, the FDA classifies medical implants and devices into three categories, depending on MR-compatibility: MR-safe (safe in all MR environments), MR-unsafe (unsafe in any MR environment), and MR-conditional (MR-compatible in certain environments, requiring further information). [ 34 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1909", "text": "The CT scan was introduced in the 1970s and quickly became one of the most widely used methods of imaging. A CT scan can be performed in under a second and produce rapid results for clinicians, with its ease of use leading to an increase in CT scans performed in the United States from 3 million in 1980 to 62 million in 2007. Clinicians oftentimes take multiple scans, with 30% of individuals undergoing at least 3 scans in one study of CT scan usage. [ 36 ]  CT scans can expose patients to levels of radiation 100-500 times higher than traditional x-rays, with higher radiation doses producing better resolution imaging. [ 37 ]  While easy to use, increases in CT scan use, especially in asymptomatic patients, is a topic of concern since patients are exposed to significantly high levels of radiation. [ 36 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1910", "text": "In PET scans, imaging does not rely on intrinsic biological processes, but relies on a foreign substance injected into the bloodstream traveling to the brain. Patients are injected with radioisotopes that are metabolized in the brain and emit positrons to produce a visualization of brain activity. [ 33 ]  The amount of radiation a patient is exposed to in a PET scan is relatively small, comparable to the amount of environmental radiation an individual is exposed to across a year. PET radioisotopes have limited exposure time in the body as they commonly have very short half-lives (~2 hours) and decay rapidly. [ 38 ]  Currently, fMRI is a preferred method of imaging brain activity compared to PET, since it does not involve radiation, has a higher temporal resolution than PET, and is more readily available in most medical settings. [ 33 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1911", "text": "The high temporal resolution of MEG and EEG allow these methods to measure brain activity down to the millisecond. Both MEG and EEG do not require exposure of the patient to radiation to function. EEG electrodes detect electrical signals produced by neurons to measure brain activity and MEG uses oscillations in the magnetic field produced by these electrical currents to measure activity. A barrier in the widespread usage of MEG is due to pricing, as MEG systems can cost millions of dollars. EEG is a much more widely used method to achieve such temporal resolution as EEG systems cost much less than MEG systems. A disadvantage of EEG and MEG is that both methods have poor spatial resolution when compared to fMRI. [ 33 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1912", "text": "Owl's eye appearance , also known as  owl's eye sign , is a pattern used in the medical field to describe cells (or cell attributes) that resemble the shape of an actual owl's eye. Using the techniques of  histology  and  radiology , microscopes and other  medical imaging  are used to locate this pattern of \"owl's eye\" shaped cells. The term may be applied to the appearance of the cells themselves, or to aspects of their  morphology , such as reference to an \"owl eye  nucleus \". The presence of \"owl's eye\" cells has been linked to a variety of conditions, such as in the  pathology  of  Hodgkin's lymphoma , a form of cancer. In particular, owl's eye appearance has been used to indicate the presence of  cytomegalovirus (CMV) , a  genus  of virus found in humans and other primates."}
{"_id": "WikiPedia_Radiology$$$corpus_1913", "text": "The description \"owl's eye\" may refer to:"}
{"_id": "WikiPedia_Radiology$$$corpus_1914", "text": "The owl's eye appearance has a relationship with  Reed\u2013Sternberg cells  in regard to  cytomegalovirus infection . [ 3 ]  Owl's eye appearance was used as an indication of the presence of the  cytomegalovirus  for the following case studies."}
{"_id": "WikiPedia_Radiology$$$corpus_1915", "text": "In 1982, a textbook wrote a chapter on cytomegalovirus and elaborated on its further relevance to owl's eye appearances. [ 4 ]  It was stated that the owl's eye had a characteristic of a clear halo that extended towards the cell membrane's nucleus. The cellular structure was found to be relevant to pneumonia which was caused by cytomegalovirus."}
{"_id": "WikiPedia_Radiology$$$corpus_1916", "text": "In a 1986 case study, a journal wrote that an owl's eye appearance was found in a total of 10 out of 10 patients. [ 5 ]  This was apparently due to the cytomegalovirus found in the patients that were also found to be diagnosed with AIDS. [ 5 ]  This case study involved  CT scans  that were used as a proposal as a way to detect the cytomegalovirus; however, the case study found that the cytomegalovirus had little relevance to the ability of CT scans. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1917", "text": "In 1987, a 33-year-old man diagnosed with AIDS was discovered with the cytomegalovirus in his eyes. [ 6 ]  The presence of an owl's eye appearance indicated the hospital that this patient was infected with the cytomegalovirus."}
{"_id": "WikiPedia_Radiology$$$corpus_1918", "text": "In 1990, a case study journal found that the owl's eye appearance correlated with the appearance of  HIV infection . [ 7 ]  This was where the case study involved the study of hospital cases and concluding that HIV plays a role in certain symptoms such as diarrhea. [ 7 ]  In another case study journal, the owl's eye appearances were found within the four patients that were observed. [ 8 ]  These patients were diagnosed with AIDS, and the presence of the owl's eye appearances proved the presence of cytomegalovirus. The confirmation of this virus was by the use of  immunohistochemistry . [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1919", "text": "In a 2000 case study, it was discovered that the owl's eye appearance as a cell body was key for the  histopathological  understanding of the cytomegalovirus. [ 2 ]  The study found a strong relationship with a positive CMV PCR (p < 0.001). [ 2 ]  The discovery led to a result that owl's eye appearances were a strong sign for finding cytomegalovirus inside organs. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1920", "text": "In 2006, a case study journal wrote that owls' eye signs were found in patients with compromised  immune system . [ 9 ]  The purpose of this case study was to identify the features of the cytomegalovirus itself and the appearance of owl's eyes in relevance."}
{"_id": "WikiPedia_Radiology$$$corpus_1921", "text": "In 2009, a case study journal found a 44-year-old male patient to be infected with the cytomegalovirus. [ 10 ]  The presence of an eye's owl appearance found within the infected area, gave the necessary clues to confirm cytomegalovirus infection. [ 10 ]  A different case study found the appearance of an owl's eye in eighteen patients who were induced with drugs with a syndrome. [ 11 ]  The case study concluded that the cytomegalovirus disease was present, as the syndrome caused these patients to compromise their immune system. The case also found that the significant decrease of  white blood cells  was a factor in the preliminary stage of cytomegalovirus infection."}
{"_id": "WikiPedia_Radiology$$$corpus_1922", "text": "In 2011, a second edition textbook found that an owl's eye appearance was found inside a dead  retina . [ 12 ]  It was found due to the cause of the cytomegalovirus [ 12 ]  that had been residing inside an eye causing it to transition from healthy to dead."}
{"_id": "WikiPedia_Radiology$$$corpus_1923", "text": "In 2012, a journal was written on patients with cytomegalovirus infection and was used in mapping out the owl's eye cells using their microscopic technology. [ 13 ]  The patients were two elderly men at ages 75 and 77 years old. The image of the owl's eye appearance was created using the microscope via lasers, and two-dimensional images were created using computer software. The conclusion made by the journal was that the owl's eye had relevance to cytomegalovirus infection."}
{"_id": "WikiPedia_Radiology$$$corpus_1924", "text": "In 2019, a four-year-old boy was found with  acute flaccid paralysis  and was found to have an owl's eye appearance. [ 14 ]  The case also spoke on the presence of  enterovirus . [ 14 ]  The boy was also found to have a compromised immune system, which the enterovirus came through in infection. This case is unique due to the owl's eye appearance in relevance to the enterovirus."}
{"_id": "WikiPedia_Radiology$$$corpus_1925", "text": "Owl's eye appearances were also found within  tissues  and  organs  and are tied with  histopathological  cases. Most of these cases are also relevant to the pathology cases. However, these cases focused more on the specifics of a singular organ or tissue where the owl's eye appeared. These cases also have moderate relevance to the  cytomegalovirus ."}
{"_id": "WikiPedia_Radiology$$$corpus_1926", "text": "In 1983, a journal wrote on a case study that found owl's eye appearance within the human eyes with the presence of potential cytomegalovirus with a deficient immune system. [ 15 ]  This was from the symptoms of  inflammation  that gave the diagnosis of an immune system to be deficient."}
{"_id": "WikiPedia_Radiology$$$corpus_1927", "text": "In 1985, a journal wrote that the appearance of owl's eye signs was due to the presence of  inflammatory bowel disease . [ 16 ]  This finding created a suspicion that the patient, in this case, was, infected with the  cytomegalovirus infection . However, further investigations showed that the patient was leading to a weak immune system. The patient was also identified as an 80-year-old man with a short-term case of diarrhea of blood and mucus, [ 16 ]  which was not contained and resulted in his death. The autopsy found the presence of cytomegalovirus this way."}
{"_id": "WikiPedia_Radiology$$$corpus_1928", "text": "In 2002, a rare case study journal wrote that a range of cytomegalovirus could infect patients diagnosed with AIDS and compromised immune systems. However, it was rare to involve the patient's skin. [ 17 ]  The skin at the cellular level was found to have owl's eye appearance and was concluded after several tests to be the cytomegalovirus infection."}
{"_id": "WikiPedia_Radiology$$$corpus_1929", "text": "In 2007, a journal wrote about the presence of owls' eye appearance as cells found in a transplant to a patient. [ 18 ]  The owl's eye appearance was considered rare for cytomegalovirus infection in the transplant, but was considered concerning. [ 18 ]  The cytomegalovirus infection was found of relevance towards compromised immune patients, as previous cases show that immune problems for patients have a similar case of cytomegalovirus infection."}
{"_id": "WikiPedia_Radiology$$$corpus_1930", "text": "In 2015, a review journal wrote on  herpes infection . It made a finding that owl's eye appearance was found in most organs [ 19 ]  through the investigation of a liver transplant. This provides evidence that the appearance of an owl's eye allowed the doctors to diagnose that cytomegalovirus infection from the liver transplant can be detected through detection tools."}
{"_id": "WikiPedia_Radiology$$$corpus_1931", "text": "In 2019, a case study was conducted on a series of patients that were infected with cytomegalovirus, [ 20 ]  and found the presence of the owl's eye appearance due to the presence of the virus. These owl's eye appearances were able to conclude that high-risk patients had a higher risk of cytomegalovirus."}
{"_id": "WikiPedia_Radiology$$$corpus_1932", "text": "Another particular case in 1957 found that an owl's eye appearance was found by two cells mirroring each other, producing the pattern inside the  histological  case study of  tumors . [ 21 ]  This is essentially what an owl's eye appearance is, however, the symptom did not occur from the presence of  cytomegalovirus  but from a unique case."}
{"_id": "WikiPedia_Radiology$$$corpus_1933", "text": "In another particular case in 1999, a case study was conducted by investigating a series of babies and found a baby with the presence of an owl's sign which was also found to be known as an  eye mask . This had to do with the presence of a rash, not the reality of cytomegalovirus. [ 22 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1934", "text": "In a particular case in 2011, the owl's eye appearance was found within the cellular structure of the  spinal ganglia . [ 23 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1935", "text": "Owl's eye appearance is also found within  radiology  images from  X-rays  and  CT scans . [ 24 ]  They appear as an indication of a clue to be used for analyzing the problem. These scans so far do not indicate that the owl's eye appearance found within radiology has any relevance towards the  cytomegalovirus infection  within patients. [ 25 ]  An example of the appearance of an owl's eye appearing within an image is of a skeleton within the bone structure, especially in the  spinal cord ."}
{"_id": "WikiPedia_Radiology$$$corpus_1936", "text": "In 2009, a journal wrote on the presence of an owl's eye appearance that was found within the  skeletal structure  from the  magnetic resonance imaging  (MRI) scan in regards to compression of the  spinal cord . [ 26 ]  The owl's eye sign indicated that the spinal issues may be similar to other spinal cord cases and can be used to identify future cases."}
{"_id": "WikiPedia_Radiology$$$corpus_1937", "text": "In 2012, a case study journal article was written on a 10-year-old boy and discovered the owl's eye appeared inside the brain from an MRI scan. [ 27 ]  In the findings, it was found that the owl eye's sign was seen when doing  neuroradiology  images. The owl's eye sign was also detected from the spinal cord in spine MRI scans conducted post-treatment for the boy."}
{"_id": "WikiPedia_Radiology$$$corpus_1938", "text": "In 2015, a case study on owl's eye sign was found in a  neuroimaging  via MRI, which was rare due to the patient's diagnosis. [ 28 ]  The patient was found with  Flailing Arm Syndrome ."}
{"_id": "WikiPedia_Radiology$$$corpus_1939", "text": "In June 2016, a journal article was written on a  central pontine myelinolysis  presence. [ 29 ]  And from doing radiology scans within the brain, they were able to find observations of owl's eye signs that also resembled similar to  monkey signs . [ 29 ]  The owl's eye appearance was also used as a sign in the MRI scans conducted in the scanning of the brain to show its relevance to the patient's diagnosed profile. In September 2016, a journal article examined MRI scans relevant to spinal cord conditions. [ 30 ]  These tests found owls' eye appearance as they were relevant to spinal cords in past cases. The journal concluded that the owl's eyes were not a main characteristic of tissue death."}
{"_id": "WikiPedia_Radiology$$$corpus_1940", "text": "A textbook has stated that within radiology, the appearance of an owl's eye can be seen from the  cells  and  neurological disorders . [ 31 ]  This textbook is a clinical review textbook and has provided relevance between owl's eye signs and  neurological imaging ."}
{"_id": "WikiPedia_Radiology$$$corpus_1941", "text": "It was found that a 1986 case study found that  CT scans [ 5 ]  were of little effect when trying to find  cytomegalovirus  in the presence of owl's eye appearance."}
{"_id": "WikiPedia_Radiology$$$corpus_1942", "text": "Paediatric radiology  (or  pediatric radiology ) is a  subspecialty  of  radiology  involving the imaging of fetuses, infants, children, adolescents and young adults. Many paediatric radiologists practice at  children's hospitals ."}
{"_id": "WikiPedia_Radiology$$$corpus_1943", "text": "Although some diseases seen in  paediatrics  are the same as that in adults, there are many conditions which are seen only in infants. The specialty has to take in account the dynamics of a growing body, from  preterm infants  to large  adolescents , where the organs follow growth patterns and phases. These require specialised imaging and treatment which is carried out in a children's hospital, which has all the facilities necessary to treat children and their specific pathologies."}
{"_id": "WikiPedia_Radiology$$$corpus_1944", "text": "To successfully diagnose a  paediatric condition , high-quality images are needed to give a diagnosis. To achieve this requires creating an environment where a child is comfortable. This is one of the most essential elements to paediatric radiology. For imaging departments which specialise in paediatric radiology, rooms can be tailored to suit a child's needs. For example, bright wall designs, visual stimulation and toys. These can be permanent fixtures as the department wouldn't need to cater to any other age range. For departments which only see children occasionally, creating a child-friendly environment is more difficult. It is usually achieved by creating one room as a child-friendly room where murals / stencils can be painted on the wall. Modern children's hospitals are now designed with much glass to allow as much natural light in as possible, the  Evelina Children's Hospital  being one of these."}
{"_id": "WikiPedia_Radiology$$$corpus_1945", "text": "Paediatric radiology comes with many challenges. Unlike adults, children cannot always understand / comprehend a change of environment. Therefore, staff are usually required to wear colourful uniforms, usually  scrubs , as opposed to a normal hospital uniform. It is also important to recognise that when a child is unwell, they follow their instincts, which is usually to cry and stay close to their parents. This presents a huge challenge for the radiographer, who must try to gain the child's trust and gain their co-operation. Once co-operation has been achieved there is another big challenge of keeping the child still for their imaging test. This can be very difficult for children in a lot of pain. Coercion and support from parents is usually enough to achieve this, however, in some extreme cases (such as  MRI  and  CT ), it may be necessary to sedate the child."}
{"_id": "WikiPedia_Radiology$$$corpus_1946", "text": "Another challenge faced is the radiation difference between an adult and child."}
{"_id": "WikiPedia_Radiology$$$corpus_1947", "text": "Medical Use of Radiation : Medicine has used ionising radiation for decades to help diagnose or treat children (and adults). There is no doubt that this imaging has saved lives. Medical imaging use has grown exponentially in the past few years, particularly the use of CAT Scans (also called CT scans). There are approximately 65 million CT scans done in the United States annually with an estimated 8 million in children. However, there is a much higher radiation dose from CT scans than from the traditional radiographs and fluoroscopy tests that radiologists perform and interpret. CT scans provide in general more information about the anatomy and diseases in the body but could be replaced for some orthopedic indications by other low-dose imaging modalities like  EOS . [ 1 ]  To do this, though, they may expose a person to 100 to 250 times the radiation dose compared to a chest x-ray. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1948", "text": "Radiation Safety Issues : There are risks from ionising radiation that are comprehensively studied in the survivors of the atomic bomb in Hiroshima in 1945. Longitudinal studies led by the National Academy of Sciences in the United States have shown increased cancer rates in this population that are dose dependent. From these data, modelling research suggests that even at the lower doses used in medical imaging, there may be an added risk of cancer. [ 3 ]  Last year, two medical physicists suggested that the increasing use of CAT Scans in the United States may increase cancer incidence in the future. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1949", "text": "Paediatric Radiation Protection Issues : Children are more radiosensitive than adults. They also have a longer life expectancy over which they may develop cancer from exposures to ionising radiation. The paediatric radiology and medical community has long had an awareness of this issue and has developed radiation protection policies and practices that reflect this. With the increased use of imaging and in particular, CT scanning, there is increasing attention to this issue by the entire medical and radiology communities. An educational resource for health care providers as well as patients and parents is the Image Gently web site started in 2008. [1]  There is collaboration by several radiology, medical physics, paediatrics, and governmental organisations to increase awareness of radiation safety issues in children and to provide education to all stakeholders caring for children on ways to decrease the ionising radiation exposure in children  [2] . For parents, basic information brochures that can be printed or downloaded that describe what an X ray is, what are its risks and benefits, and what can be done to decrease these risks  [3] . A call to action has been published advocating a reduction of ionising radiation exposure to children by delivering the right imaging exam, the right way with the right dose. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1950", "text": "Equipment adapted for use in paediatric radiology includes:"}
{"_id": "WikiPedia_Radiology$$$corpus_1951", "text": "An example of positioning equipment for X ray scans on infants is the Pigg-O-Stat baby tube. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1952", "text": "Most equipment is the same used for adult imaging, but using lower dose and exposure setting adapted for children."}
{"_id": "WikiPedia_Radiology$$$corpus_1953", "text": "In many countries, paediatric radiology does not officially require a specific training. Where there is, paediatric radiologists have usually completed a  diagnostic radiology   residency , then complete one or two more years of subspecialty fellowship training before they are eligible to take the board examination for official subspecialty certification (e.g. Canada, UK, Switzerland). This then qualifies them in the specialised area of paediatric radiology."}
{"_id": "WikiPedia_Radiology$$$corpus_1954", "text": "Paleoradiology  (ancient radiology) is the study of  archaeological  remains through the use of  radiographic  techniques, such as  X-ray ,  CT  (computer tomography) and  micro-CT  scans. [ 1 ]  It is predominately used by archaeologists and  anthropologists  to examine  mummified  remains due to its non-invasive nature. [ 2 ]  Paleoradiologists can discover post-mortem damage to the body, or any artefacts buried with them, while still keeping the remains intact. Radiological images can also contribute evidence about the person's life, such as their age and cause of death. The first recorded use of paleoradiology (although not by that name) was in 1896, just a year after the R\u014dntgen radiograph was first produced. [ 3 ]  Although this method of viewing ancient remains is advantageous due to its non-invasive manner, many radiologists lack expertise in archeology and very few radiologists can identify ancient diseases which may be present. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1955", "text": "CT scans are most commonly used in paleoradiological studies because they can create images of soft tissue, organs and body cavities of mummified remains without performing an invasive and damaging autopsy. [ 5 ]  This enables archaeologists and anthropologists to digitally unwrap the remains and reveal what they contain. CT scanners create these images by taking multiple radiographic planes (or cuts) of the body at different angles which records the layers of different structures in the remains. This differs from typical  radiographic scans  (X-rays) where all the structural layers are documented in one image, which can create shadows and therefore limit their accuracy. [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1956", "text": "There are several main viewing techniques used in CT imaging. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1957", "text": "After these different views of the remains have been obtained, it is possible to create a three-dimensional reconstruction of the body. This brings into focus details which may have been missed on the axial imagining.  Algorithm  manipulation is used to create the rotational 3D images. [ 6 ] [ 5 ]  In paleoradiology, the 3D images provide a greater understanding of the remains themselves. For example, in 2002, a study of nine Egyptian mummies found that by using the 3D reconstructions they could see the preservation of soft tissues, such as the penis on one male body and braided hair on female remains. The 3D modelling also illustrated discrepancies between the remains, as some had their internal organs removed while others had not. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1958", "text": "Due to their ability to take multiple planes of the remains, CT scans are able to virtually 'fly through' the body to assess internal composition and cavities. [ 2 ]  These techniques are commonly used for diagnostic scans such as  colonoscopy  and  bronchoscopy , and the same method is applied to ancient remains. [ 5 ]  This enables researchers to digitally look through the remains from the top down, as though they were watching a short video of footage from the interior of the body. The technique presents observable data from the hollow cavities in the chest and abdomen regions. It can demonstrate whether there are internal organs present or if, in the case of Egyptian mummies, linen has been packed to maintain the body shape of the remains. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1959", "text": "Micro-CT is a specialised form of CT scan used to create images with pixels in micrometres. These images are frequently used for bone density examinations and produce greater detail for images of bony structures. This radiology technique is often used to examine the teeth from mummified remains. [ 6 ] [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1960", "text": "Radiographs, or X-rays, have been used to study and observe ancient remains since their invention by  Wilhelm R\u00f6ntgen  in 1895. This early form of X-ray, sometimes known as R\u00f6ntgenograms, was immediately used by physicists, anthropologists, anatomists and archaeologists as shown below. [ 3 ] [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1961", "text": "CT scans are the most common radiological technique used in modern archaeology due to their ability to provide more detailed information about ancient remains (such as soft tissue and blood vessels) and to produce 3D images by taking layers of different angled pictures. Archaeologists are able to collect data such as age, sex, the cause of death, socioeconomic status, mummification and burial practices by analysing the CT images. The images can also reveal whether the remains were subject to ancient diseases or post-mortem damage. [ 9 ]  Although paleoradiology practices are used on preserved remains such as European  bog bodies  and frozen bodies from the High Andes, they are more frequently documented in the analysis of Egyptian mummified remains. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1962", "text": "CT scans are used in  Egyptology  to gain insight into mummified bodies without risking damage to the integrity of the remains. Hoffman's recent study of nine Egyptian remains discovered new information regarding the mummification practices of Egyptians. The typical process of  mummification , as written by  Herodotus , involves the removal of the four major internal organs (liver, intestines, lungs and stomach) and placement of them in four  canopic jars . The heart is removed, embalmed and placed back into the body as it is an important feature in the journey to the  Egyptian afterlife . However, Hoffman discovered that this was not the case in all mummies. Through analysis of CT-produced 3D images, the \"fly-through\" technique and a combination of axial and coronal images, it was discovered that four of the remains had not had their internal organs removed and in another four the heart could not be identified. [ 5 ]  Hoffman suggests this may be due to socioeconomic differences between the mummies during the time they were alive. CT scans were further used in Hoffman's study to potentially identify one of the remains as  Ramesses I , a Pharaoh during  New Kingdom Egypt . It was found that the mummification practices of this particular body were in conjunction with those typically used during the New Kingdom period, as images showed rolled linen placed inside the body in order to preserve its shape. The mummy's arms were also found to be placed across the chest as a symbol of nobility. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1963", "text": "Imaging done by Rethy Chhem, in 2004, was able to correct a diagnosis of Ramesses II from X-rays done in 1976. The incorrect diagnosis had been of  ankylosing spondylitis , a form of arthritis. However, Chhem perceived that the pharaoh actually had  diffuse idiopathic skeletal hyperostosis , a calcification of the joints causing ligaments to attach to the spine. [ 6 ]  The CT images provided a clearer and more detailed image of the spine when compared with the early X-rays. This enabled the researchers to provide a greater insight into diseases found in ancient remains and achieve a more accurate diagnosis."}
{"_id": "WikiPedia_Radiology$$$corpus_1964", "text": "A recent CT scan of Tutankhamun in 2006 was able to provide evidence against the 'homicide theory'. [ 2 ] [ 6 ]  A depression fracture noted on the skull from X-rays taken 30 years previously was found to be a post-mortem injury rather than a cause of death. [ 6 ]  The hole in the head had been created in order to continue the embalming process of mummification. [ 10 ]  This CT investigation was also able to confirm Tutankhamun's age of death as nineteen and disprove the idea that the young pharaoh had suffered from  scoliosis ; rather the bend in his spine was from additional post-mortem damage to the body. [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1965", "text": "Although the information and evidence gathered by radiological imaging of ancient remains have been largely beneficial to the fields of archaeology and anthropology, not all of the information can be considered accurate due to the lack of radiologists who specialise in  paleopathology . Instead, to obtain the most information from CT or X-ray images a team must meet to discuss the findings (e.g. for a skeletal study of the remains, an orthopaedic surgeon, bone pathologist and musculoskeletal radiologist would meet). [ 2 ] [ 4 ]  Another disadvantage to this technique is the low contrast resolution. The researcher may be unable to determine a difference between soft tissue and artefacts left from the embalming process. Due to the decomposed state of some of the mummified remains, it can also be difficult to distinguish internal organs due to shrinkage and a lack of preservation. Post-mortem injuries and damage to the body can also hinder the ability of radiological scans to provide accurate information for researchers. For example, in frozen remains, there can difficulty when differentiating whether a CT suggests the body has air-inflated lung tissue or if there is frozen fluid in the lungs. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1966", "text": "Paleoradiology is informative in its ability to assist in determining the age of death of the remains, however, this is not always completely accurate or available information. In a sample of bog bodies, 35% were not able to be identified with any age group and 30% could not be sex determined. A radiological study of an iceman was only able to produce an estimate of 40\u201350 years at age of death. In order to achieve a more accurate time frame, the body would have to be subject to an autopsy or similar physical assessment which would cause irreversible damage to the remains. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1967", "text": "Another disadvantage of paleoradiology is the difficulty in transporting the equipment or the artefact/remains to spaces where the images can be taken. [ 1 ] [ 11 ]  For example, in 2005 the mummy of Tutankhamun was imaged using a CT-scanner which had to be brought from the  Cairo Museum  to  tomb KV62  in the  Valley of the Kings . [ 10 ]  This was due to the fragile state of the remains which were unable to be removed from the climate-controlled tomb. In this study, funding came from  a five-year grant from the  Supreme Council of Antiquities , which was aided by the donation of a Siemens CT-scanner by the  National Geographic Society , [ 10 ]  however typically funding for research can be problematic as equipment is costly and there may not be sufficient interest to prompt donations."}
{"_id": "WikiPedia_Radiology$$$corpus_1968", "text": "Peak kilovoltage  ( kVp ) refers to the maximum  high voltage  applied across an  X-ray tube  to produce the X-rays. During X-ray generation, surface electrons are released from a heated cathode by  thermionic emission . The applied voltage (kV) accelerates these electrons toward an  anode  target, ultimately producing X-rays when the  electrons are stopped  in the anode. Thus, the kVp corresponds to the highest  kinetic energy  of the  electrons  striking the target, and is proportional to the maximum  photon energy  of the resulting  X-ray emission spectrum . [ 1 ]  In early and basic X-ray equipment, the applied voltage varies cyclically, with one, two, or more pulses per  mains AC power cycle . One standard way to measure  pulsating DC  is its  peak amplitude , hence kVp. Most modern X-ray generators apply a constant potential across the X-ray tube; in such systems, the kVp and the steady-state kV are identical."}
{"_id": "WikiPedia_Radiology$$$corpus_1969", "text": "kVp controls the property called \"radiographic contrast\" of an X-ray image (the ratio of transmitted radiation through regions of different thickness or density). Each body part contains a certain type of cellular composition which requires an X-ray beam with a certain kVp to penetrate it. The body part is said to have \"subject contrast\" (that is, different cellular make up: some dense, some not so dense tissues all within a specific body part). For example: bone to muscle to air ratios in the abdomen differ from those of the chest area. So the subject contrast is said to be higher in the chest than in the abdomen. In order to image the body so that the maximum information will result, higher subject contrast areas require a higher kVp so as to result in a low radiographic contrast image, and vice versa."}
{"_id": "WikiPedia_Radiology$$$corpus_1970", "text": "Although the product of tube current and exposure time, measured in  milliampere-seconds  (mA\u00b7s), is the primary controlling factor of radiographic density, kVp also affects the radiographic density indirectly. As the energy (which is proportional to the peak voltage) of the stream of electrons in the X-ray tube increases, the X-ray photons created from those electrons are more likely to penetrate the cells of the body and reach the image receptor (film or plate), resulting in increased film density (compared to lower energy beams that may be absorbed in the body on their way to the  image receptor ). However, scattered X-rays also contribute to increased film density: the higher the kVp of the beam, the more scatter will be produced. Scatter adds unwanted density (that is, density that does not bring pertinent information to the image receptor). This is why kVp is not primarily used to control  film  density \u2013 as the density resulting from increasing kVp exceeds what is needed to penetrate a body part, it only adds useless photons to the image."}
{"_id": "WikiPedia_Radiology$$$corpus_1971", "text": "Increasing mAs causes more photons (radiation) of the particular kVp energy to be produced. This is helpful when larger body parts are imaged, because they require more photons. The more photons that pass through a particular tissue type (whose kVp is interacting at the cellular level), the more photons reach the image receptor. The more photons that pass through a part and reach the image receptor with pertinent information, the more useful the film density on the resulting image. Conversely, lower mAs creates fewer photons, which will decrease film density, but is helpful when imaging smaller parts. The measurement of kVp is done by kV meter. The quality of X-ray tube depends upon the kV applied across the filament at the target. A slight change in kV affects the image significantly. Therefore, it is necessary to measure kV applied to tube accurately."}
{"_id": "WikiPedia_Radiology$$$corpus_1972", "text": "PI-RADS  is an  acronym  for Prostate Imaging Reporting and Data System, defining standards of high-quality clinical service for multi-parametric  magnetic resonance imaging  (mpMRI), including image creation and reporting."}
{"_id": "WikiPedia_Radiology$$$corpus_1973", "text": "In 2007, the AdMeTech Foundation's International Prostate MRI Working Group  [ 1 ]  convened the key global experts, including members of the  European Society of Urogenital Radiology  (ESUR) and the  American College of Radiology  (ACR). In March 2009 in Vienna an ESUR Prostate MRI Committee was formed, with the aim to produce minimal and maximal standards for acquisition and reporting of prostate MRI. This standardization was endorsed by the results of a consensus meeting in London in December 2009 [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1974", "text": "Dr. Jelle Barentsz published with the ESUR Prostate MRI Committee the first PI-RADS (v.1) version in December 2011. [ 3 ]  Following this initiative the ACR, ESUR, and the AdMeTech Foundation formed a Joint Steering Committee, and by 2016 published a second version of PI-RADS (v.2) in European Urology. [ 4 ]  This paper enabled acceptance of the urologists of prostate MRI and was awarded \u201cBest clinical scientific paper of 2016 in European Urology\u201d.  In 2019 the PI-RADS Steering Committee published an updated version: PI-RADS v2.1. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1975", "text": "The aim of prostate MRI using PI-RADS is to assess the risk of clinically significant prostate cancer being present. Furthermore, the PI-RADS v2 system is designed to standardize prostate MRI."}
{"_id": "WikiPedia_Radiology$$$corpus_1976", "text": "Various studies have compared the predictive performance of PI-RADS v1 for detecting significant prostate cancer against either image-guided biopsy results (definitive  pathology ) and/or prostatectomy specimens ( histopathology ). In a 2015 articles in the Journal of Urology, Thompson reported multi-parametric MRI detection of significant prostate cancer had sensitivity of 96%, specificity of 36%, negative predictive value and positive predictive values of 92% and 52%; when PI-RADS was incorporated into a multivariate analysis (PSA, digital rectal exam, prostate volume, patient age) the area under the curve (AUC) improved from 0.776 to 0.879, p<0.001. [ 6 ]   A similar paper in European Radiology found that when correlated with histopathology, PI-RADS v2 correctly identified 94-95% of prostate cancer foci \u22650.5 mL, but was limited for the assessment of GS \u22654+3 (significant) tumors \u22640.5 mL; in their series, DCE-MRI offered limited added value to T2WI+DW-MRI. [ 7 ]   Other applications for which PI-RADS may be useful include prediction of termination of Active Surveillance due to  tumor  progression/aggressiveness, [ 8 ]  detection of extraprostatic extension of prostate cancer, [ 9 ]  and supplemental information when considering whether to re-biopsy patients with a history of previous negative biopsy. [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1977", "text": "PI-RADS v2 is designed to improve detection, characterization and risk stratification in patients suspected of prostate cancer with a goal of better treatment decisions, improved outcomes and simplified reporting. However, multi-center validation trials are needed and expected to lead to modifications in the scoring system. [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1978", "text": "Calculators designed to assist with PI-RADS criteria application have been developed to streamline the evaluation of prostate MRI. These tools, while not officially endorsed by the ACR, are becoming more popular among radiologists for their ability to reduce variability and improve diagnostic efficiency. Examples include PI-RADS v. 2.1 calculators available on independent online platforms, [ 12 ]  which helps in systematically applying the PI-RADS scoring system. These tools are increasingly recognized for their potential to enhance clinical workflow and reporting accuracy."}
{"_id": "WikiPedia_Radiology$$$corpus_1979", "text": "Plesiotherapy  is a  radiation therapy  modality in which a source of ionizing radiation is placed in contact with the exterior surface of the body. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1980", "text": "This is as distinguished from  teletherapy  in which radiation is projected by the source from a distance, from  brachytherapy  in which one or more sealed sources of radiation are placed inside the body, and from  radiopharmaceutical  therapy in which a source is introduced into the body, but that source is unsealed. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1981", "text": "In contrast with teletherapy, where the distance between the source and the patient is exploited to produce a shallow fall-off of beam intensity with depth; in plesiotherapy, the source geometry is exploited to produce a dose fall-off that is steep, for treating superficial areas. [ 2 ] [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1982", "text": "One example of plesiotherapy is use of the  90 Sr  eye applicator in the treatment of  pterygium . [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1983", "text": "This  medical treatment \u2013related article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Radiology$$$corpus_1984", "text": "A  radioactive tracer ,  radiotracer , or  radioactive label  is a  synthetic  derivative of a  natural compound  in which one or more atoms have been replaced by a  radionuclide  (a radioactive atom). By virtue of its  radioactive decay , it can be used to explore the mechanism of chemical reactions by tracing the path that the radioisotope follows from reactants to products.  Radiolabeling  or  radiotracing  is thus the radioactive form of  isotopic labeling . In biological contexts, experiments that use radioisotope tracers are sometimes called  radioisotope feeding  experiments."}
{"_id": "WikiPedia_Radiology$$$corpus_1985", "text": "Radioisotopes of  hydrogen ,  carbon ,  phosphorus ,  sulfur , and  iodine  have been used extensively to trace the path of  biochemical reactions . A radioactive tracer can also be used to track the distribution of a substance within a natural system such as a  cell  or  tissue , [ 1 ]  or as a  flow tracer  to track  fluid flow . Radioactive tracers are also used to determine the location of fractures created by  hydraulic fracturing  in natural gas production. [ 2 ]  Radioactive tracers form the basis of a variety of imaging systems, such as,  PET scans ,  SPECT scans  and  technetium scans .  Radiocarbon dating  uses the naturally occurring  carbon-14  isotope as an  isotopic label ."}
{"_id": "WikiPedia_Radiology$$$corpus_1986", "text": "Isotopes  of a  chemical element  differ only in the mass number. For example, the isotopes of  hydrogen  can be written as  1 H ,  2 H  and  3 H , with the mass number superscripted to the left. When the  atomic nucleus  of an isotope is unstable, compounds containing this isotope are  radioactive .  Tritium  is an example of a radioactive isotope."}
{"_id": "WikiPedia_Radiology$$$corpus_1987", "text": "The principle behind the use of radioactive tracers is that an  atom  in a  chemical compound  is replaced by another atom, of the same chemical element. The substituting atom, however, is a radioactive isotope. This process is often called radioactive labeling. The power of the technique is due to the fact that radioactive decay is much more energetic than chemical reactions. Therefore, the radioactive isotope can be present in low concentration and its presence detected by sensitive  radiation detectors  such as  Geiger counters  and  scintillation counters .  George de Hevesy  won the 1943  Nobel Prize for Chemistry  \"for his work on the use of isotopes as tracers in the study of chemical processes\"."}
{"_id": "WikiPedia_Radiology$$$corpus_1988", "text": "There are two main ways in which radioactive tracers are used"}
{"_id": "WikiPedia_Radiology$$$corpus_1989", "text": "The commonly used radioisotopes have short  half lives  and so do not occur in nature in large amounts. They are produced by  nuclear reactions . One of the most important processes is absorption of a  neutron by an atomic nucleus, in which the mass number of the element concerned increases by 1 for each neutron absorbed. For example,"}
{"_id": "WikiPedia_Radiology$$$corpus_1990", "text": "In this case the atomic mass increases, but the element is unchanged. In other cases the product nucleus is unstable and decays, typically emitting protons, electrons ( beta particle ) or  alpha particles . When a nucleus loses a proton the  atomic number  decreases by 1. For example,"}
{"_id": "WikiPedia_Radiology$$$corpus_1991", "text": "Neutron irradiation is performed in a  nuclear reactor . The other main method used to synthesize radioisotopes is proton bombardment. The proton are accelerated to high energy either in a  cyclotron  or a  linear accelerator . [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1992", "text": "Tritium  (hydrogen-3) is produced by neutron irradiation of  6 Li :"}
{"_id": "WikiPedia_Radiology$$$corpus_1993", "text": "Tritium has a  half-life   4500 \u00b1 8  days (approximately 12.32 years) [ 4 ]  and it decays by  beta decay . The  electrons  produced have an average energy of 5.7\u00a0keV. Because the emitted electrons have relatively low energy, the detection efficiency by scintillation counting is rather low. However, hydrogen atoms are present in all organic compounds, so tritium is frequently used as a tracer in  biochemical  studies."}
{"_id": "WikiPedia_Radiology$$$corpus_1994", "text": "11 C  decays by  positron emission  with a half-life of ca. 20 min.  11 C is one of the isotopes often used in  positron emission tomography . [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1995", "text": "14 C  decays by  beta decay , with a half-life of 5730 years. It is continuously produced in the upper atmosphere of the earth, so it occurs at a trace level in the environment. However, it is not practical to use naturally-occurring  14 C for tracer studies. Instead it is made by neutron irradiation of the isotope  13 C  which occurs naturally in carbon at about the 1.1% level.  14 C has been used extensively to trace the progress of organic molecules through metabolic pathways. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_1996", "text": "13 N  decays by  positron emission  with a half-life of 9.97 min. It is produced by the nuclear reaction"}
{"_id": "WikiPedia_Radiology$$$corpus_1997", "text": "13 N  is used in  positron emission tomography  (PET scan)."}
{"_id": "WikiPedia_Radiology$$$corpus_1998", "text": "15 O  decays by positron emission with a half-life of 122 seconds. It is used in positron emission tomography."}
{"_id": "WikiPedia_Radiology$$$corpus_1999", "text": "18 F  decays predominantly by \u03b2 emission, with a half-life of 109.8 min. It is made by proton bombardment of  18 O  in a cyclotron or  linear particle accelerator . It is an important isotope in the  radiopharmaceutical  industry. For example, it is used to make labeled  fluorodeoxyglucose  (FDG) for application in PET scans. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2000", "text": "32 P  is made by neutron bombardment of  32 S"}
{"_id": "WikiPedia_Radiology$$$corpus_2001", "text": "It decays by beta decay with a half-life of 14.29 days. It is commonly used to study protein phosphorylation by  kinases  in biochemistry."}
{"_id": "WikiPedia_Radiology$$$corpus_2002", "text": "33 P  is made in relatively low yield by neutron bombardment of  31 P . It is also a beta-emitter, with a half-life of 25.4 days. Though more expensive than  32 P , the emitted electrons are less energetic, permitting better resolution in, for example, DNA sequencing."}
{"_id": "WikiPedia_Radiology$$$corpus_2003", "text": "Both isotopes are useful for labeling  nucleotides  and other species that contain a  phosphate  group."}
{"_id": "WikiPedia_Radiology$$$corpus_2004", "text": "35 S  is made by neutron bombardment of  35 Cl"}
{"_id": "WikiPedia_Radiology$$$corpus_2005", "text": "It decays by beta-decay with a half-life of 87.51 days. It is used to label the sulfur-containing  amino-acids   methionine  and  cysteine . When a sulfur atom replaces an oxygen atom in a  phosphate  group on a  nucleotide  a  thiophosphate  is produced, so  35 S can also be used to trace a phosphate group."}
{"_id": "WikiPedia_Radiology$$$corpus_2006", "text": "99m Tc  is a very versatile radioisotope, and is the most commonly used radioisotope tracer in medicine. It is easy to produce in a  technetium-99m generator , by decay of  99 Mo ."}
{"_id": "WikiPedia_Radiology$$$corpus_2007", "text": "The molybdenum isotope has a half-life of approximately 66 hours (2.75 days), so the generator has a useful life of about two weeks. Most commercial  99m Tc generators use  column chromatography , in which  99 Mo in the form of molybdate, MoO 4 2\u2212  is adsorbed onto acid alumina (Al 2 O 3 ). When the  99 Mo decays it forms  pertechnetate  TcO 4 \u2212 , which because of its single charge is less tightly bound to the alumina. Pulling normal saline solution through the column of immobilized  99 Mo elutes the soluble  99m Tc, resulting in a saline solution containing the  99m Tc as the dissolved sodium salt of the pertechnetate. The pertechnetate is treated with a  reducing agent  such as  Sn 2+  and a  ligand . Different ligands form  coordination complexes  which give the technetium enhanced affinity for particular sites in the human body."}
{"_id": "WikiPedia_Radiology$$$corpus_2008", "text": "99m Tc decays by gamma emission, with a half-life: 6.01 hours. The short half-life ensures that the body-concentration of the radioisotope falls effectively to zero in a few days."}
{"_id": "WikiPedia_Radiology$$$corpus_2009", "text": "123 I  is produced by proton irradiation of  124 Xe . The  caesium  isotope produced is unstable and decays to  123 I. The isotope is usually supplied as the iodide and hypoiodate in dilute sodium hydroxide solution, at high isotopic purity. [ 6 ]   123 I has also been produced at Oak Ridge National Laboratories by proton bombardment of  123 Te . [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2010", "text": "123 I decays by  electron capture  with a half-life of 13.22 hours. The emitted 159\u00a0 keV   gamma ray  is used in  single-photon emission computed tomography  (SPECT). A 127\u00a0keV gamma ray is also emitted."}
{"_id": "WikiPedia_Radiology$$$corpus_2011", "text": "125 I  is frequently used in  radioimmunoassays  because of its relatively long half-life (59 days) and ability to be detected with high sensitivity by gamma counters. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2012", "text": "129 I  is present in the environment as a result of the testing of  nuclear weapons  in the atmosphere. It was also produced in the  Chernobyl  and  Fukushima  disasters.  129 I decays with a  half-life  of 15.7 million years, with low-energy  beta  and  gamma  emissions. It is not used as a tracer, though its presence in living organisms, including human beings, can be characterized by measurement of the gamma rays."}
{"_id": "WikiPedia_Radiology$$$corpus_2013", "text": "Many other isotopes have been used in specialized radiopharmacological studies. The most widely used is  67 Ga  for  gallium scans .  67 Ga is used because, like  99m Tc, it is a gamma-ray emitter and various ligands can be attached to the Ga 3+  ion, forming a  coordination complex  which may have selective affinity for particular sites in the human body."}
{"_id": "WikiPedia_Radiology$$$corpus_2014", "text": "An extensive list of radioactive tracers used in hydraulic fracturing can be found below."}
{"_id": "WikiPedia_Radiology$$$corpus_2015", "text": "In  metabolism  research, tritium and  14 C -labeled glucose are commonly used in  glucose clamps  to measure rates of  glucose uptake ,  fatty acid synthesis , and other metabolic processes. [ 9 ]   While radioactive tracers are sometimes still used in human studies,  stable isotope  tracers such as  13 C  are more commonly used in current human clamp studies. Radioactive tracers are also used to study  lipoprotein  metabolism in humans and experimental animals. [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2016", "text": "In  medicine , tracers are applied in a number of tests, such as  99m Tc in  autoradiography  and  nuclear medicine , including  single-photon emission computed tomography  (SPECT), positron emission tomography (PET) and  scintigraphy . The  urea breath test  for  helicobacter pylori  commonly used a dose of  14 C labeled urea to detect h. pylori infection. If the labeled urea was metabolized by h. pylori in the stomach, the patient's breath would contain labeled carbon dioxide. In recent years, the use of substances enriched in the non-radioactive isotope  13 C  has become the preferred method, avoiding patient exposure to radioactivity. [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2017", "text": "In  hydraulic fracturing , radioactive tracer isotopes are injected with hydraulic fracturing fluid to determine the injection profile and location of created fractures. [ 2 ]   Tracers with different half-lives are used for each stage of hydraulic fracturing. In the United States amounts per injection of radionuclide are listed in the US  Nuclear Regulatory Commission  (NRC) guidelines. [ 12 ]   According to the NRC, some of the most commonly used tracers include  antimony-124 ,  bromine-82 ,  iodine-125 ,  iodine-131 ,  iridium-192 , and  scandium-46 . [ 12 ]  A 2003 publication by the  International Atomic Energy Agency  confirms the frequent use of most of the tracers above, and says that  manganese-56 ,  sodium-24 ,  technetium-99m ,  silver-110m ,  argon-41 , and  xenon-133  are also used extensively because they are easily identified and measured. [ 13 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2018", "text": "Radiodensity  (or  radiopacity ) is  opacity  to the  radio wave  and  X-ray  portion of the  electromagnetic spectrum : that is, the relative inability of those kinds of  electromagnetic radiation  to pass through a particular material.  Radiolucency  or  hypodensity  indicates greater passage (greater  transradiancy ) to X-ray  photons [ 1 ]  and is the analogue of  transparency and translucency  with  visible light . Materials that inhibit the passage of electromagnetic radiation are called  radiodense  or  radiopaque , while those that allow radiation to pass more freely are referred to as  radiolucent . Radiopaque volumes of material have white appearance on  radiographs , compared with the relatively darker appearance of radiolucent volumes. For example, on typical radiographs, bones look white or light gray (radiopaque), whereas muscle and skin look black or dark gray, being mostly invisible (radiolucent)."}
{"_id": "WikiPedia_Radiology$$$corpus_2019", "text": "Though the term radiodensity is more commonly used in the context of  qualitative  comparison, radiodensity can also be quantified according to the  Hounsfield scale , a principle which is central to  X-ray computed tomography  (CT scan) applications. On the Hounsfield scale,  distilled water  has a value of 0 Hounsfield units (HU), while air is specified as -1000 HU."}
{"_id": "WikiPedia_Radiology$$$corpus_2020", "text": "In modern medicine, radiodense substances are those that will not allow X-rays or similar radiation to pass.  Radiographic imaging  has been revolutionized by radiodense  contrast media , which can be passed through the bloodstream, the  gastrointestinal tract , or into the cerebral spinal fluid and utilized to highlight CT scan or X-ray images. Radiopacity is one of the key considerations in the design of various devices such as guidewires or  stents  that are used during  radiological  intervention. The radiopacity of a given endovascular device is important since it allows the device to be tracked during the interventional procedure.\nThe two main factors contributing to a material's radiopacity are density and atomic number. Two common radiodense elements used in medical imagery are  barium  and  iodine ."}
{"_id": "WikiPedia_Radiology$$$corpus_2021", "text": "Medical devices often contain a radiopacifier to enhance visualization during implantation for temporary implantation devices, such as catheters or guidewires, or for monitoring the position of permanently implanted medical devices, such as stents, hip and knee implants, and screws. Metal implants usually have sufficient radiocontrast that additional radiopacifier is not necessary. Polymer-based devices, however, usually incorporate materials with high electron density contrast compared to the surrounding tissue. Examples of radiocontrast materials include titanium, tungsten, barium sulfate, [ 2 ]  bismuth oxide [ 3 ]  and zirconium oxide. Some solutions involve direct binding of heavy elements, for instance iodine, to polymeric chains in order to obtain a more homogeneous material which has lower interface criticalities. [ 4 ]  When testing a new medical device for regulatory submission, device manufacturers will usually evaluate the radiocontrast according to  ASTM F640 \"Standard Test Methods for Determining Radiopacity for Medical Use.\""}
{"_id": "WikiPedia_Radiology$$$corpus_2022", "text": "The term  radiogenomics  is used in two contexts: either to refer to the study of genetic variation associated with response to radiation (radiation genomics) or to refer to the correlation between cancer imaging features and gene expression (imaging genomics)."}
{"_id": "WikiPedia_Radiology$$$corpus_2023", "text": "In radiation genomics, radiogenomics is used to refer to the study of  genetic variation  associated with response to  radiation therapy . Genetic variation, such as  single nucleotide polymorphisms , is studied in relation to a cancer patient's risk of developing toxicity following  radiation therapy . [ 1 ] [ 2 ] [ 3 ]     It is also used in the context of studying the  genomics  of tumor response to  radiation therapy . [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2024", "text": "The term radiogenomics was coined in 2002 by Andreassen et al. (2002) [ 6 ]   as an analogy to  pharmacogenomics , which studies the genetic variation associated with drug responses. See also West et al. (2005) [ 7 ]   and Bentzen (2006). [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2025", "text": "In 2009, [ 9 ] [ 10 ]  a Radiogenomics Consortium (RGC) was established to facilitate and promote multi-centre collaboration of researchers linking genetic variants with response to radiation therapy. The Radiogenomics Consortium ( http://epi.grants.cancer.gov/radiogenomics/ ) is a Cancer Epidemiology Consortium supported by the Epidemiology and Genetics Research Program of the National Cancer Institute of the National Institutes of Health. [ 11 ]  RGC researchers have completed numerous clinical studies that identified genetic variants associated with radiation toxicities in patients with prostate, breast, lung, head and neck, and other cancers."}
{"_id": "WikiPedia_Radiology$$$corpus_2026", "text": "Radiological images are used to diagnose disease on a large scale: tissue imaging correlates with tissue  pathology .  The addition of genomic data including  DNA microarrays ,  miRNA ,  RNA-Seq  allows new correlations to be made between cellular genomics and tissue-scale imaging."}
{"_id": "WikiPedia_Radiology$$$corpus_2027", "text": "Radiographers , also known as  radiologic technologists ,  diagnostic radiographers  and  medical radiation technologists [ 1 ]  are  healthcare professionals  who specialise in the  imaging  of  human anatomy  for the  diagnosis  and  treatment  of  pathology . Radiographers are infrequently, and almost always erroneously, known as  x-ray technicians.  In countries that use the title  radiologic technologist  they are often informally referred to as  techs  in the clinical environment; this phrase has emerged in popular culture such as television programmes. [ 2 ]  The term  radiographer  can also refer to a  therapeutic radiographer , also known as a  radiation therapist ."}
{"_id": "WikiPedia_Radiology$$$corpus_2028", "text": "Radiographers are  allied health professionals  who work in both  public healthcare  and private healthcare and can be physically located in any setting where appropriate diagnostic equipment is located, most frequently in  hospitals . The practice varies from country to country and can even vary between hospitals in the same country. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2029", "text": "Radiographers are represented by a variety of organizations worldwide, including the  International Society of Radiographers and Radiological Technologists  which aims to give direction to the profession as a whole through collaboration with national representative bodies. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2030", "text": "For the first three decades of  medical imaging 's existence (1897 to the 1930s), there was no standardized differentiation between the roles that we now differentiate as radiologic technologist (a technician in an  allied health profession  who obtains the images) versus  radiologist  (a  physician  who interprets them). By the 1930s and 1940s, as it became increasingly apparent that proper interpretation of the images required not only a physician but also one who was specifically trained and experienced in doing so, the differentiation between the roles was formalized. Simultaneously, it also became increasingly true that just as a radiologic technologist cannot do the radiologist's job, the radiologist also cannot do the radiologic technologist's job, as it requires some knowledge, skills, experience, and  certifications  that are specific to it."}
{"_id": "WikiPedia_Radiology$$$corpus_2031", "text": "Radiography's origins and  fluoroscopy's origins  can both be traced to 8 November 1895, when German physics professor  Wilhelm R\u00f6ntgen  discovered the X-ray and noted that, while it could pass through human tissue, it could not pass through bone or metal. [ 5 ]  R\u00f6ntgen referred to the radiation as \"X\", to indicate that it was an unknown type of radiation. He received the first  Nobel Prize in Physics  for his discovery. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2032", "text": "There are conflicting accounts of his discovery because R\u00f6ntgen had his lab notes burned after his death, but this is a likely reconstruction by his biographers: [ 7 ] [ 8 ]  R\u00f6ntgen was investigating  cathode rays  using a  fluorescent  screen painted with barium  platinocyanide  and a  Crookes tube  which he had wrapped in black cardboard to shield its fluorescent glow. He noticed a faint green glow from the screen, about 1 metre away. R\u00f6ntgen realized some invisible rays coming from the tube were passing through the cardboard to make the screen glow: they were passing through an opaque object to affect the film behind it. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2033", "text": "R\u00f6ntgen discovered X-rays' medical use when he made a picture of his wife's hand on a photographic plate formed due to X-rays. The photograph of his wife's hand was the first ever photograph of a human body part using X-rays. When she saw the picture, she said, \"I have seen my death.\" [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2034", "text": "The first use of X-rays under clinical conditions was by  John Hall-Edwards  in  Birmingham, England  on 11 January 1896, when he radiographed a needle stuck in the hand of an associate. [ 10 ] [ self-published source? ]  On 14 February 1896, Hall-Edwards also became the first to use X-rays in a surgical operation. [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2035", "text": "The United States saw its first medical X-ray obtained using a  discharge tube  of  Ivan Pulyui 's design. In January 1896, on reading of R\u00f6ntgen's discovery, Frank Austin of  Dartmouth College  tested all of the discharge tubes in the physics laboratory and found that only the Pulyui tube produced X-rays. This was a result of Pulyui's inclusion of an oblique \"target\" of  mica , used for holding samples of  fluorescent  material, within the tube. On 3 February 1896 Gilman Frost, professor of medicine at the college, and his brother Edwin Frost, professor of physics, exposed the wrist of Eddie McCarthy, whom Gilman had treated some weeks earlier for a fracture, to the X-rays and collected the resulting image of the broken bone on  gelatin photographic plates  obtained from Howard Langill, a local photographer also interested in R\u00f6ntgen's work. [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2036", "text": "X-rays were put to diagnostic use very early; for example,  Alan Archibald Campbell-Swinton  opened a radiographic laboratory in the United Kingdom in 1896, before the dangers of ionizing radiation were discovered. Indeed,  Marie Curie  pushed for radiography to be used to treat wounded soldiers in World War I. Initially, many kinds of staff conducted radiography in hospitals, including physicists, photographers, physicians, nurses, and engineers. The medical speciality of radiology grew up over many years around the new technology. When new diagnostic tests were developed, it was natural for the radiographers to be trained in and to adopt this new technology. Radiographers now perform  fluoroscopy ,  computed tomography ,  mammography ,  ultrasound ,  nuclear medicine  and  magnetic resonance imaging  as well. Although a nonspecialist dictionary might define radiography quite narrowly as \"taking X-ray images\", this has long been only part of the work of \"X-ray Departments\", Radiographers, and Radiologists. Initially, radiographs were known as roentgenograms, [ 13 ]  while  Skiagrapher  (from the  Ancient Greek  words for \"shadow\" and \"writer\") was used until about 1918 to mean  Radiographer . [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2037", "text": "The history of  magnetic resonance imaging  includes many researchers who have discovered  NMR  and described  its underlying physics , but it is regarded to be invented by  Paul C. Lauterbur  in September 1971; he published the theory behind it in March 1973. [ 15 ] [ 16 ]  The factors leading to image contrast (differences in tissue relaxation time values) had been described nearly 20 years earlier by Erik Odeblad (doctor and scientist) and Gunnar Lindstr\u00f6m. [ 17 ] [ 18 ] [ 19 ] [ 20 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2038", "text": "In 1950,  spin echoes  and  free induction decay  were first detected by  Erwin Hahn [ 21 ] [ 22 ]  and in 1952,  Herman Carr  produced a one-dimensional NMR spectrum as reported in his Harvard PhD thesis. [ 23 ] [ 24 ] [ 25 ]  In the  Soviet Union ,  Vladislav Ivanov  filed (in 1960) a document with the USSR State Committee for Inventions and Discovery at Leningrad for a Magnetic Resonance Imaging device, [ 26 ] [ 27 ] [ 28 ]  although this was not approved until the 1970s. [ 29 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2039", "text": "By 1959, Jay Singer had studied blood flow by NMR relaxation time measurements of blood in living humans. [ 30 ] [ 31 ]  Such measurements were not introduced into common medical practice until the mid-1980s, although a patent for a whole-body NMR machine to measure blood flow in the human body was already filed by Alexander Ganssen in early 1967. [ 19 ] [ 31 ] [ 32 ] [ 33 ] [ 34 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2040", "text": "In the 1960s and 1970s the results of a very large amount of work on relaxation, diffusion, and chemical exchange of water in cells and tissues of various types appeared in the scientific literature. [ 19 ]  In 1967, Ligon reported the measurement of NMR relaxation of water in the arms of living human subjects. [ 19 ]  In 1968, Jackson and Langham published the first NMR signals from a living animal. [ 19 ] [ 35 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2041", "text": "A radiographer uses their expertise and knowledge of  patient care ,  physics ,  human anatomy ,  physiology ,  pathology  and  radiology  to assess patients, develop optimum radiological techniques and evaluate the resulting radiographic media. [ 36 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2042", "text": "This branch of healthcare is extremely varied, especially between different countries, and as a result radiographers in one country often have a completely different role to that of radiographers in another. However, the base responsibilities of the radiographer are summarised below: [ 37 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2043", "text": "On a basic level, radiographers do not generally interpret diagnostic media, rather they evaluate media and make a decision about its diagnostic effectiveness. In order to make this evaluation radiographers must have a comprehensive but not necessarily exhaustive knowledge of pathology and radiographic appearances; it is for this reason that radiographers often do not interpret or diagnose without further training. Notwithstanding, it is now becoming more common that radiographers have an extended and expanded clinical role, this includes a role in initial radiological diagnosis, diagnosis consultation and what subsequent investigations to conduct. [ 38 ]  It is not uncommon for radiographers to now conduct procedures which would have previously been undertaken by a cardiologist, urologist, radiologist or oncologist autonomously. [ 39 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2044", "text": "Contrary to what could be inferred, radiographers conduct and contribute to investigations which are not necessarily radiological in nature, e.g.  sonography  and  magnetic resonance imaging ."}
{"_id": "WikiPedia_Radiology$$$corpus_2045", "text": "Radiographers often have opportunities to enter military service due to their role in healthcare. As with most other occupations in the medical field many radiographers have rotating shifts that include night duties."}
{"_id": "WikiPedia_Radiology$$$corpus_2046", "text": "Radiography is a deeply diverse profession with many different modalities and specialities. It is not uncommon for radiographers to be specialised in more than one modality and even have expertise of interventional procedures themselves; however this depends on the country in which they operate. As a result of this the typical career pathway for a radiographer is hard to summarise. Upon qualifying it is common for radiographers to focus solely on plain film radiography before specialising in any one chosen modality. After a number of years in the profession, non-imaging based roles often become open and radiographers may then move into these positions. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2047", "text": "Generally, imaging modalities are all diagnostic, all have the potential to be used therapeutically in order to deliver an intervention. Modalities (or specialities) include but are not limited to:"}
{"_id": "WikiPedia_Radiology$$$corpus_2048", "text": "Non-imaging modalities vary, and are often undertaken in addition to imaging modalities. They commonly include:"}
{"_id": "WikiPedia_Radiology$$$corpus_2049", "text": "Education varies worldwide due to legal limitations on scope of practice."}
{"_id": "WikiPedia_Radiology$$$corpus_2050", "text": "The profession of diagnostic radiographer is called \"medical imaging technologist\", it is a regulated healthcare profession. A diploma of a specific professional Bachelor is a requirement for registration and recognition. [ 41 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2051", "text": "Since 2 December 2014, everyone who works at a Medical Imaging department, is obliged to be in possession of the recognition and the visa issued by the Ministry of Health (a professional identity card that is considered a license) [ 42 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2052", "text": "To practice a health care profession with a foreign diploma from within the EEA or equivalent in the EEA, it is necessary to request the recognition for the profession from Government of Flanders (Agency of Care and Health). [ 43 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2053", "text": "It is possible to request the recognition if:"}
{"_id": "WikiPedia_Radiology$$$corpus_2054", "text": "In Germany radiographers must complete a 3-year apprenticeship before they qualify as a 'Medizinisch-technischer Radiologieassistent'. Only after qualifying do radiographers in Germany fulfil the requirements to practise as a fully qualified MTRA."}
{"_id": "WikiPedia_Radiology$$$corpus_2055", "text": "Similar to other countries, they work within the areas of radiography diagnostics ( CT scans ,  magnetic resonance imaging ,  radiography ,  digital subtraction angiography ),  radiation therapy ,  radiation dosimeters  and  nuclear medicine . [ 44 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2056", "text": "Radiographers  in the  Republic of Ireland  (ROI) must be registered with  CORU  before they can practice in the Republic of Ireland. Student radiographers training in the ROI will typically study for 4 years on an approved bachelor's degree program; currently degree programs only exist at  University College Dublin . [ 45 ] [ 46 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2057", "text": "Applicants must have either an approved qualification, a schedule 3 qualification, an appropriate letter of recommendation/accreditation or another qualification which is deemed 'suitably relevant' by registration board in order to successfully fulfil the vocational education requirements to become a Radiographer in the ROI. Applications for registration with qualifications outside of this are considered on an individual basis; typically this includes most international applicants. [ 47 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2058", "text": "The professional body representing Radiographers in the ROI is the  Irish Institute of Radiography and Radiation Therapy (IIRRT) . [ 48 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2059", "text": "To practice as a Radiographer or Radiation Therapist in Ireland, one must register with CORU as of 31 October 2015. [ 49 ]  CORU is Ireland's multi-profession health regulator. Set up under the Health and Social Care Professionals Act 2005, CORU is used to protect the public by promoting high standards of professional conduct, education, training and competence through statutory registration of health and social care professionals. [ 50 ]  If a radiographer commences clinical practice without registration then they may be prosecuted with a fine or an imprisonment of up to six months. [ 49 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2060", "text": "Radiography is a regulated profession in Malta and anyone wanting to practice Diagnostic or Therapeutic Radiography would need to obtain state registration in order to be licensed as a Radiographer, obtained from the Council for Professions Complementary to Medicine (CPCM). [ 51 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2061", "text": "In Malta, in order for an individual to become a Radiographer he/she first has to follow a course offered by the University of Malta. The course is BSc (Hons) Radiography and its duration is of four years. On completion of the course, the graduate will have the conditions to be eligible for registration with the council for professions complementary to Medicine [ 52 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2062", "text": "A foreign radiographer can work in Malta should the necessary documentation and competencies have been obtained and presented. Radiographers working on Malta should abide by the rules of the host country and title of radiographer will be used. [ 53 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2063", "text": "An application form has to be filled along with the necessary authenticated copies of several documents. The application form includes the insertion of personal details of the individual along with the description of qualifications and the university which granted the qualifications. The individual has to declare whether he or she is registered with another Health Care Profession Register in Malta. [ 53 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2064", "text": "Below is a list of the documents needed for a professional to register with the council:"}
{"_id": "WikiPedia_Radiology$$$corpus_2065", "text": "In cases where the professional qualification acquired was not obtained from an Accredited Institution in Malta, a letter is to be submitted, issued from the Malta Qualifications Recognition Information Centre ( MQRIC ), certifying that the Institution from where the qualification was obtained is equivalently accredited and indicate the level of qualification in accordance to the Malta Qualifications Framework. [ 53 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2066", "text": "For applicants from the  European Economic Area  countries, once the application is submitted, it will follow the regulations established on the  Directive 2005/36/EC  on the recognition of qualifications between member states. [ 54 ]  In these cases, the professional document and theoretical and practical training are required to be equivalent to the requirements of Malta, i.e. An EQF Level 6 Bachelor's Degree with an equivalent syllabus to that of the University of Malta and their course is no more than one year shorter. Should the radiographer have a substantial difference between their professional qualifications and those required by CPCM, the radiographer has the right to provide further evidence of competence (including professional experience or CPD), otherwise, the CPCM board should offer the applicant the possibility to do an aptitude test or adaptation period (as chosen by the applicant). A  Flow chart  explaining this procedure for EEA applicants can be found on the government's website. [ 55 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2067", "text": "As a developing country, the health care sector in  Federal Democratic Republic of Nepal  has very limited resources meaning radiological services are rather limited.\nNepal is still struggling to improve and manage conventional radiological examinations. Radiological Services in Nepal commenced in 1923 at Military Hospital by Dr. Rana and Dr Asta Bahadur Shrestha. The first health related training program began in 1933 at the Nepal Rajkiya Ayurved School; the Civil Medical School was later established in 1934. Radiological education in Nepal started in 1923 in a 64 bedded Military Hospital, Tri-ChandraElectro-Medical Institute. The post graduate (MSc) program in physics at TU began in 1965 with only Nuclear Physics specialization. In 1972, the Institute of Medicine (IOM) which is affiliated with TU started the Proficiency Certificate Level (PCL) Radiography course however this has since stopped."}
{"_id": "WikiPedia_Radiology$$$corpus_2068", "text": "Radiotherapy was first introduced at Maternity Hospital in 1976 utilising radium needle treatment. CT and Nuclear Medicine was introduced in 1988 at Bir Hospital. The Radiotherapy unit with Tele Cobalt-60 machine was established at Bir Hospital in 1991."}
{"_id": "WikiPedia_Radiology$$$corpus_2069", "text": "Nepal became a member of IAEA in 2008. Since 2008 onwards diploma level radiography courses have been conducted across the country by the Council for Technical Education and Vocational Training (CTEVT) and other affiliated institutions."}
{"_id": "WikiPedia_Radiology$$$corpus_2070", "text": "In Nepal there are 125 vocational health training institutes however only 15 are conducting radiological technological education. Bachelor level radiography education is taught in two universities & one college whereas master level radiography course is taught\nin one where another university is in pipeline. Until recently, therapeutic radiography courses have not been taught in Nepal;\nradiation therapists are predominantly trained abroad."}
{"_id": "WikiPedia_Radiology$$$corpus_2071", "text": "The Nepal Health Professional Council (NHPC) is the legislative body for registering, accrediting, developing & enforcing quality assurance of Health Professionals, including Radiographers, in Nepal.  [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2072", "text": "Until 1997, radiographers were required to register the Evidence of Competence at the Chief of Medical Inspections. This was mandatory under the Law on Paramedic professions. After innovate the law of Individual Health Care Professions (BIG), the registration requirements for radiographers were cancelled. A voluntary register has been set up in consultation with the Health Care Inspectorate: the Paramedics Quality Register. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2073", "text": "The Paramedics Quality Register comes from the BIG. The purpose of the Paramedics Quality Register is to guarantee the quality of professional practice. Through the registration and re-registration (once in five years) it becomes visible for patients, health insurers etc. that the registered radiographer professional is and remains competent in the field of professional practice. Despite the fact that the quality register is not compulsory according to the law, many hospitals are obliged to do it. The hospitals are obliged to provide good quality care. Health insurers also attach great value to the Paramedics Quality Register because they are also required to provide good care."}
{"_id": "WikiPedia_Radiology$$$corpus_2074", "text": "Radiographers who are in possession of a valid Certificate of Competence, diploma of certificate and endorse the code of professional conduct of the professional association, can be enroll in the Paramedics historical register."}
{"_id": "WikiPedia_Radiology$$$corpus_2075", "text": "The official registration of the radiographer satisfies the educational requirements in the General Administrative Order (AMvB) ex. art. 34 BIG and the quality requirements of the professional group. On the basis of which is carried out radiographer is mentioned in the Diplomaregister Paramedici and / or the Quality Register Paramedics. By registration, the radiographer continues to be traced by, for example, the Health Care Inspectorate (IGZ) and the professional associations. Other organizations also intend the Quality Register Paramedics."}
{"_id": "WikiPedia_Radiology$$$corpus_2076", "text": "To be in the Paramedics Quality Register the radiographer need to request re-registration every five years. The first period of five years is determined on the basis of the diploma date. In case of re-registration, the radiographer must meet the requirements for that period. The start date of the period station local quality criteria. The quality criteria are set every five years by the Paramedics Quality Register, paramedical professional associations. To ensure that the requirements for the patient and the client-oriented exercises and expertise-enhancing activities are safeguarded for the quality of the professional practice. The quality criteria are set up in such a way that paramedics can meet the quality requirements with the set range of expertise-enhancing activities."}
{"_id": "WikiPedia_Radiology$$$corpus_2077", "text": "In  Nigeria , these professionals are generally referred to as  Radiographers  or  Medical Radiographers  to differentiate them from Industrial Radiographers. Radiographers must complete a 5-year undergraduate BSc and a compulsory one year paid internship program in a hospital after graduation before attaining a full licensing by the  Radiographers Registration Board of Nigeria . The board also registers  Radiotherapists  who have undergone the initial 5-year Radiography program before proceeding to the Radiotherapy training.  [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2078", "text": "Radiographers in Nigeria have been striving to extend their practice to include radiographic interpretation and Ultrasound services. They are also on the verge of adopting an official professional title of \"Radr\" or \"Rr\" As of 2015 [update] .\nRadiographers in Nigeria normally proceed for a Masters programme and a PhD programme in the profession.\nThere is a recent rise in the number of radiographers available in the country unlike the situation of shortage between 2000 \u2013 2010. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2079", "text": "In a typical Nigerian Teaching Hospital, radiographers do not undertake sonography examinations, this is left for the radiologists, who, in some areas, have gradually improved their relationship with the radiographers in providing services in other radiographic units. The radiologist is also in charge of specific Fluoroscopic cases where the radiographer assists only with positioning and image acquisition. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2080", "text": "Allied Health Unions (such as 'JOHESU' and 'NUAHP') that Radiographers are members of (with Nurses, Pharmacists, Physiotherapists, Laboratory Scientists, etc.), have over the years gone on strike actions to force the Nigerian government to improve their allowances/salaries in the government owned hospitals. These strikes (when it is not a response on its own) often trigger a response from the Nigerian Medical Association who will also table some requests for the medical doctors. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2081", "text": "Apart from monetary issues, these professional bodies are also in loggerheads over non-doctors requesting to be given top administrative roles in government owned hospitals. Many radiographers, however, do not particularly involve themselves in these movements as working in a private establishment is more lucrative. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2082", "text": "Some Radiographers in Nigeria are also keen on setting up a \"Department of Radiography\" in the government owned hospitals which will not be under the Head of the Radiology Department. Some hospitals however have an understanding between the Radiology head (a Radiologist) and the Chief Radiographer where all radiographers are directly answerable to their Chief, and not the HOD. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2083", "text": "X-Ray Technicians  (\u0641\u0646\u064a \u0627\u0634\u0639\u0629) in  Saudi Arabia  must successfully undertake a degree level program at a recognised higher-level education institution in Nursing before undertaking further study in radiographic imaging at university for typically 2 to 3 years; this must include a year's experience in a hospital. Upon completion, graduates are qualified X-Ray Technicians and can commence clinical practice. [ 56 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2084", "text": "The  SCoR  is the professional body and union for UK radiographers. In the United Kingdom, there is ambiguity in the use of the term  Radiographer  as this does not differentiate between Therapeutic Radiographers (also known as Radiotherapists) and  Diagnostic Radiographers . As a result, all of these titles are protected titles within the United Kingdom and can not be used by any persons who has not undertaken formal study and registered with the  Health and Care Professions Council  (HCPC). In order to practise Radiography in the United Kingdom candidates must now successfully obtain a pass in a degree level programme from an accredited institution. Degrees are offered by universities across the UK and last for at least 3 years in England, Wales and Northern Ireland; and 4 years in Scotland. [ 57 ] [ 58 ]  Student Diagnostic Radiographers spend a significant amount of time working at various hospitals affiliated with their university during their studies to meet the requirement for registration with the HCPC."}
{"_id": "WikiPedia_Radiology$$$corpus_2085", "text": "They specialise in the acquisition of radiographs of General Practitioner referred (GP) patients, Outpatients, Emergency Department (ED) referred patients and Inpatients. They conduct mobile X-rays on wards and in other departments where patients are too critical to be moved and work as part of the operating team in mainly Orthopaedic and Urology cases, offering surgeons live radiographic imaging. Once qualified, Diagnostic Radiographers are able to acquire X-rays without supervision and work as part of the imaging team. They will have basic head examination qualifications in CT and even basic experience of MRI, Ultrasound and Nuclear Medicine."}
{"_id": "WikiPedia_Radiology$$$corpus_2086", "text": "Diagnostic Radiographers can specialise in-house or through a university course as a postgraduate in CT, MRI, Ultrasound or Nuclear Medicine with opportunities to gain an MSc or PhD in their field. Diagnostic Radiographers in the UK are also taking on roles that were typically only undertaken by the Radiologist (a medical doctor who specialised in interpreting X-rays), Urologist or Cardiologist in the past. [ 59 ]  This extended practice includes various interventional procedures not excluding barium enemas, barium meals/swallows, peripheral angioplasties, nerve root injections, central line insertions and many other procedures."}
{"_id": "WikiPedia_Radiology$$$corpus_2087", "text": "The professional body and workers union for Radiographers in the United Kingdom is the  Society and College of Radiographers (SCoR) . The union has been heavily involved in extending practice of Radiographers in the United Kingdom and has helped expand the role of the Radiographer greatly."}
{"_id": "WikiPedia_Radiology$$$corpus_2088", "text": "Radiographers are now able to write reports and diagnose pathologies and/or conditions seen on differing diagnostic media after completing a HCPC and SCoR accredited university course; [ 60 ] [ 61 ]  completing a course in this modality allows the Radiographer to become a reporting Radiographer in their chosen specialty. [ 62 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2089", "text": "Diagnostic Radiographers are able to become supplementary prescribers which allows them the capacity to prescribe medications in partnership with an independent prescriber (a doctor or a dentist); the supplementary prescriber is to implement an agreed Clinical Management Plan for an individual patient with that patient's agreement. [ 63 ]  An accredited university course must be undertaken before this role extension is annotated onto a HCPC registrant's record. [ 64 ]  It is thought that in the future Diagnostic Radiographers in will gain independent prescribing rights, however this is currently limited by their restricted and varied scope of practice. In 2016, the introduction of independent prescribing right was agreed for Therapeutic Radiographers after a consultation by the  Medicines and Healthcare products Regulatory Agency (MHRA) [ 65 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2090", "text": "In the United States, these professionals are known as  Radiologic Technologists . Formal training programs in radiography range in length that leads to a certificate, an associate or a bachelor's degree. The American Registry of Radiologic Technologists (ARRT), the primary credentialing organisation for Radiologic Technologists in the United States, requires that candidates for ARRT Certification Exams must have an associate degree at minimum as of January, 2015, effectively ending non-degree granting diploma programs. [ 66 ]  Accreditation is primarily through The Joint Review Committee on Education in Radiologic Technology (JRCERT), the only agency recognised by the United States Department of Education and the Council for Higher Education Accreditation to grant accreditation to both traditional and online programs in Radiography, Radiation Therapy, Magnetic Resonance Imaging, and Medical Dosimetry. An online page where prospective students can check the accreditation of programs is maintained by JRCERT. [ 67 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2091", "text": "Radiologic Technology students study  anatomy ,  physiology ,  physics ,  radiopharmacology ,  pathology ,  biology , research,  nursing ,  medical imaging ,  diagnosis ,  radiologic instrumentation ,  emergency medical procedures ,  medical imaging techniques ,  patient care ,  medical ethics  and  general chemistry . Schooling also includes significant amounts of documented practicum supervised by Registered Technologists in various clinical settings where the classroom theory is translated to practical knowledge and real world experience. The change from Film to Digital imaging has changed training as film quality assurance and quality control is largely obsolete. The role of computer workstations to produce synthetic images for Radiologists has steadily increased the need for computer skills as has electronic medical record software."}
{"_id": "WikiPedia_Radiology$$$corpus_2092", "text": "After primary training and licensure, continuing education is required to maintain licensure and certification with the ARRT, who sets the accepted national guidelines. The ARRT requires 24 Units of accredited continuing education every two years and the laws and the regulations of most states accept this standard. Continuing formal education or the passing of an advanced practice speciality exam may also be accepted for continuing education credit. The  American Society of Radiologic Technologists  (ASRT), [ 68 ]  a professional association for people in Medical Imaging and Therapy, offers members and others continuing education materials in various media that meet the requirements of the ARRT for continuing education. [ 69 ]  Additional requirements are set forth for technologists who specialise in mammography by the US FDA. [ 70 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2093", "text": "A new and evolving career for Radiologic Technologists is that of the Registered Radiologist Assistant (RRA) [ 71 ]  who is an experienced technologist (a type of Physician Assistant) who has completed additional education, training, and has passed exams to function as radiologist extenders. [ 72 ] [ 73 ]  A list of the 9 currently accredited RRA programs is maintained by the ARRT and can be accessed online. [ 74 ]  Candidates for the RRA certification must possess a bachelor's degree at minimum. [ 75 ]   [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2094", "text": "Registered Radiologist Assistant (RRA), a new advanced practice radiographer career path in the United States for experienced technologists. RRAs do not interpret studies in the manner of the reporting radiographer. [ 76 ]  The role has been accepted by the  American College of Radiology  (ACR). [ 77 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2095", "text": "A  radiological information system  ( RIS ) [ 1 ]  is the core system for the electronic management of  medical imaging  departments. The major functions of the RIS can include patient scheduling,  resource management , examination performance tracking, reporting, results distribution, and procedure billing. [ 2 ]  RIS complements  HIS (hospital information systems)  and  PACS (picture archiving and communication system) , and is critical to efficient workflow to  radiology  practices. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2096", "text": "Radiological information systems commonly support the following features: [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2097", "text": "In addition, a RIS often supports the following: [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2098", "text": "The electronic production of a visual  image  by  ionising radiation  on a  radiation detector  and displayed on a display  monitor  or similar screen. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2099", "text": "This  physics -related article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Radiology$$$corpus_2100", "text": "A  rectilinear scanner  is an  imaging  device, used to capture emission from  radiopharmaceuticals  in  nuclear medicine . The image is created by physically moving a  radiation detector  over the surface of a radioactive patient. It has become obsolete in medical imaging, largely replaced by the  gamma camera  since the late 1960s. [ 1 ] [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2101", "text": "One of the first rectilinear scanners was developed by Benedict Cassen in 1950. Before then hand-held detectors had been used to locate radioactive materials in patients, but the Cassen system (designed for  Iodine-131 ) combined a motor driven  photomultiplier tube  and printing mechanism. [ 2 ] [ 4 ]  Subsequent developments improved the detection systems, movement, display and printing of images. [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2102", "text": "Cassen's original rectilinear scanner used  calcium tungstate  (CaWo 4 ) crystal as the radiation detector. Later systems used a  Sodium iodide  (NaI)  scintillator , as in a gamma camera. [ 7 ]  The detector must be connected by mechanical or electronic means to an output system. This could be a simple light source over  photographic film ,  dot matrix printer ,  oscilloscope  or  television screen . [ 8 ] [ 9 ] [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2103", "text": "The patient is administered with a radioactive pharmaceutical agent, such as radio- iodine  which will naturally collect in the  thyroid . The detector moves in a  raster pattern  over studied area of the patient, making a constant count rate. A  collimator  restricts detection to a small area directly below its position so that by the end of the scan emission from the whole study area has been detected. The output method is designed such that positional and detection information is maintained. For example, when using a light source and film the light is moved in tandem with the detector, and the intensity of light produced increases with an increase in activity, producing dark areas on the film. [ 11 ] [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2104", "text": "Disadvantages include the very long imaging time (several minutes) due to the need to separately cover each target area, unlike a gamma camera which has a much larger  field of view , and the motion artefacts this can result in. [ 13 ] [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2105", "text": "Reed's rules  are a set of guidelines developed by  Joseph O. Reed  in interpretation of  pediatric   radiology . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2106", "text": "Reed's rules are as follows:"}
{"_id": "WikiPedia_Radiology$$$corpus_2107", "text": "Reid's base line  is used for an unambiguous definition of the orientation of the  human skull  in  conventional radiography ,  computer tomography  (CT), and  magnetic resonance imaging  (MRI) studies. [ 1 ]  It is defined as a line drawn from the inferior margin of the orbit ( Orbitale  point) to the auricular point (center of the orifice of the external acoustic meatus,  Auriculare  point) and extending backward to the center of the occipital bone. [ 2 ]  Reid's base line is used as the zero plane in computed tomography. Paediatric base line is an anatomic line that maintains a fixed relation to facial bones throughout the period of growth."}
{"_id": "WikiPedia_Radiology$$$corpus_2108", "text": "In 1962, the World Federation of  Radiology  defined it as the line between the  infraorbital margin  and the upper margin of the  external auditory meatus ."}
{"_id": "WikiPedia_Radiology$$$corpus_2109", "text": "With the head upright, it is typically tilted about 7 degrees nose up with respect to the horizontal plane."}
{"_id": "WikiPedia_Radiology$$$corpus_2110", "text": "Schuller's view  is a lateral  radiographic  view of  skull  principally used for viewing  mastoid cells . [ 1 ]  The central beam of  X-rays  passes from one side of the head and is at an angle of 25\u00b0  caudad  to the radiographic plate. This angulation prevents overlap of images of the two  mastoid bones . The radiograph for each mastoid is taken separately. Schuller's view serves as an alternate view to the  Law  projection which uses a 15\u00b0 angle of patient's face toward the image receptor and a 15\u00b0 caudal angulation of the computed radiography (CR) to achieve the same result, a lateral mastoid air cells view without overlap of the opposite side. Under examination the outer ear ( auricle ) can be taped forward to avoid a  cartilage  shadow around mastoid. Older editions of  Merrill's Atlas of  Radiographic Positioning and Procedures  books have detailed explanation of these and other mastoid positions. [ 2 ]  Newer version of texts often omits this because of the rarity of this exam in lieu of  computed tomography  ( CT  scan scans) studies."}
{"_id": "WikiPedia_Radiology$$$corpus_2111", "text": "https://radiopaedia.org/articles/schullers-view?lang=us"}
{"_id": "WikiPedia_Radiology$$$corpus_2112", "text": "Simultaneous algebraic reconstruction technique  ( SART ) is a  computerized tomography  (CT)  imaging  algorithm useful in cases when the projection data is limited; it was proposed by  Anders Andersen  and  Avinash Kak  in 1984. [ 1 ] \nIt generates a good reconstruction in just one iteration and it is superior to standard  algebraic reconstruction technique  (ART)."}
{"_id": "WikiPedia_Radiology$$$corpus_2113", "text": "As a measure of its popularity, researchers have proposed various extensions to \nSART: OS-SART, FA-SART, VW-OS-SART, [ 2 ]  SARTF, etc. Researchers have also studied how SART can best be implemented on different  parallel processing  architectures. SART and its proposed extensions are used in emission CT in  nuclear medicine , dynamic CT, [ 3 ]  and holographic  tomography , and other reconstruction applications. [ 4 ]   Convergence\nof the SART algorithm was theoretically established in 2004 by Jiang and Wang. [ 5 ]  Further convergence analysis was done by Yan. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2114", "text": "An application of SART to ionosphere was presented by Hobiger et al. [ 7 ]  Their  method does not use matrix algebra and therefore it can be implemented in a low-level programming language. Its convergence speed is significantly higher than that of classical SART. A discrete version of SART called DART was developed by Batenburg and Sijbers. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2115", "text": "Within the  medical  field of  otology , the  Stenvers projection  is a radiological technique that provides an oblique view of the skull and establishes a better perspective on the  petrous bone ,  bony labyrinth , and  internal auditory canal . [ 1 ]  It focuses on the posteroanterior and lateral planes."}
{"_id": "WikiPedia_Radiology$$$corpus_2116", "text": "The Stenvers projection was named after the physician Hendrik Willem Stenvers (1889\u20131973) of Utrecht, who developed it in 1917. [ 2 ]  It was described in 1938 by Sch\u00fctz along with the lateral projection, and later recommended by Muntean and Fink in 1941. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2117", "text": "For the Stenvers projection, a patient is placed facing the film, with the head flexed slightly and rotated 45 degrees away from the side being examined. [ 1 ]  The X-ray beam will be angled 10 to 15 degrees caudal. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2118", "text": "Surgical planning  is the preoperative method of pre-visualising a surgical intervention, in order to predefine the surgical steps and furthermore the  bone segment navigation  in the context of  computer-assisted surgery . [ 1 ] \nThe surgical planning is most important in  neurosurgery  and  oral and maxillofacial surgery . The transfer of the surgical planning to the patient is generally made using a  medical navigation system ."}
{"_id": "WikiPedia_Radiology$$$corpus_2119", "text": "The imagistic  dataset  used for surgical planning is mainly based on a  CT  or  MRI . In  oral and maxillofacial surgery , a different, more \"traditional\" surgical planning can be used for  orthognatic surgery , based on cast models fixed into an  articulator . [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2120", "text": "In order to make a surgical planning, one would need a  3D  image of the patient. The starting point was made by  G. Hounsfield  in the 1970s, by using  CT  in order to record data about the anatomical situation of the patients. [ 2 ]  In the 1980s, advances were made by the radiologist  M. Vannier  and his team, by creating the first computed three-dimensional reconstruction from a  CT  dataset. [ 3 ]  In the early 1990s, the surgical planning was performed by using  stereolithographic models . [ 4 ]  During the late 1990s, the first  full computer-based  virtual surgical planning was made for  osteotomies , and then transferred to the operating theatre by a  navigation system . [ 5 ]  Currently 3D Printed models are also used to plan a procedure and improve patient outcomes. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2121", "text": "The first commercially available neurosurgical planning systems appeared in the 1990s (the StealthStation by  Medtronic , [ 7 ]  the VectorVision by  Brainlab [ 8 ] ). As newer imaging modalities emerged providing increasing anatomical and functional detail for the patient in the 2000s, these surgical planning systems started to incorporate  virtual reality  technology to facilitate the visualisation and manipulation of the 3D data. One example of such systems is the  Dextroscope , manufactured by  Volume Interactions Pte Ltd . The Dextroscope is mostly used in the planning of complex neurosurgical procedures. [ 9 ] [ 10 ] [ 11 ] [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2122", "text": "Teleradiology  is the transmission of radiological patient images from procedures such as  x-rays  photographs,  Computed tomography  (CT), and  MRI  imaging, from one location to another for the purposes of sharing studies with other radiologists and physicians. Teleradiology allows radiologists to provide services without actually having to be at the location of the patient.  This is particularly important when a sub-specialist such as an MRI radiologist, neuroradiologist, pediatric radiologist, or musculoskeletal radiologist is needed, since these professionals are generally only located in large metropolitan areas working during daytime hours. Teleradiology allows for specialists to be available at all times."}
{"_id": "WikiPedia_Radiology$$$corpus_2123", "text": "Teleradiology utilizes standard network technologies such as the  Internet ,  telephone  lines,  wide area networks ,  local area networks  (LAN) and the latest advanced technologies such as  medical cloud computing . Specialized software is used to transmit the images and enable the radiologist to effectively analyze potentially hundreds of images of a given study. Technologies such as advanced graphics processing, voice recognition, artificial intelligence, and image compression are often used in teleradiology. Through teleradiology and mobile  DICOM  viewers, images can be sent to another part of the hospital or to other locations around the world with equal effort. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2124", "text": "Teleradiology is a growth technology given that imaging procedures are growing approximately 15% annually against an increase of only 2% in the radiologist population. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2125", "text": "Teleradiologists can provide a preliminary read for emergency room cases and other emergency cases or a final read for the official patient record and for use in billing."}
{"_id": "WikiPedia_Radiology$$$corpus_2126", "text": "Preliminary reports include all pertinent findings and a telephone call for any critical findings. For some teleradiology services, the turnaround time is rapid with a 30-minute standard turnaround and expedited for critical and stroke studies."}
{"_id": "WikiPedia_Radiology$$$corpus_2127", "text": "Teleradiology final reports can be provided for emergency and non-emergency studies. Final reports include all findings and require access to prior studies and all relevant patient information for a complete diagnosis. Telephone calls with any critical findings are signs of quality services."}
{"_id": "WikiPedia_Radiology$$$corpus_2128", "text": "Teleradiology preliminary or final reports can be provided for all doctors and hospitals overflow studies. Teleradiology can be available for intermittent coverage as an extension of practices and will provide patients with the highest quality care."}
{"_id": "WikiPedia_Radiology$$$corpus_2129", "text": "Some teleradiologists are fellowship trained and have a wide variety of subspecialty expertise including such difficult-to-find areas as neuroradiology, pediatric neuroradiology, thoracic imaging, musculoskeletal radiology, mammography, and nuclear cardiology. [ 3 ] \nThere are also various medical practitioners who are not radiologists that take on studies in radiology to become sub specialists in their respected fields, an example of this is dentistry where  oral and maxillofacial radiology  allows those in dentistry to specialize in the acquisition and interpretation of radiographic imaging studies performed for diagnosis of treatment guidance for conditions affecting the maxillofacial region. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2130", "text": "In the United States,  Medicare  and  Medicaid  laws require the teleradiologist to be on U.S. soil in order to qualify for reimbursement of the Final Read."}
{"_id": "WikiPedia_Radiology$$$corpus_2131", "text": "In addition, advanced teleradiology systems must also be HIPAA compliant, which helps to ensure patients' privacy. HIPAA (Health Insurance Portability and Accountability Act of 1996) is a uniform, federal floor of privacy protections for consumers. It limits the ways that entities can use patients' personal information and protects the privacy of all medical information no matter what form it is in. Quality teleradiology must abide by important HIPAA rules to ensure patients' privacy is protected."}
{"_id": "WikiPedia_Radiology$$$corpus_2132", "text": "Also State laws governing the licensing requirements and medical malpractice insurance coverage required for physicians vary from state to state. Ensuring compliance with these laws is a significant overhead expense for larger multi-state teleradiology groups."}
{"_id": "WikiPedia_Radiology$$$corpus_2133", "text": "Medicare (Australia)  has identical requirements to that of the United States, where the guidelines are provided by the Department of Health and Ageing, and government based payments fall under the Health Insurance Act. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2134", "text": "The regulations in Australia are also conducted at both federal and state levels, ensuring that strict guidelines are adhered to at all times, with regular yearly updates and amendments are introduced (usually around March and November of every year), ensuring that the legislation is kept up to date with changes in the industry."}
{"_id": "WikiPedia_Radiology$$$corpus_2135", "text": "One of the most recent changes to Medicare and radiology / teleradiology in Australia was the introduction of the Diagnostic Imaging Accreditation Scheme (DIAS) on 1 July 2008. DIAS was introduced to further improve the quality of Diagnostic Imaging and to amend the Health Insurance Act. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2136", "text": "Until the late 1990s teleradiology was primarily used by individual radiologists to interpret occasional emergency studies from offsite locations, often in the radiologists home. The connections were made through standard analog phone lines."}
{"_id": "WikiPedia_Radiology$$$corpus_2137", "text": "Teleradiology expanded rapidly as the growth of the internet and broad band combined with new CT scanner technology to become an essential tool in trauma cases in emergency rooms throughout the country. The occasional 2\u20133 x-ray studies a week soon became 3\u201310 CT scans, or more, a night. Because ER physicians are not trained to read CT scans or MRIs, radiologists went from working 8\u201310 hours a day, five and half days a week to a schedule of 24 hours a day, 7 days a week coverage. This became a particularly acute challenge in smaller rural facilities that only had one solo radiologist with no other to share call."}
{"_id": "WikiPedia_Radiology$$$corpus_2138", "text": "These circumstances spawned a post-dot.com boom of firms and groups that provided  medical outsourcing , off-site teleradiology on-call services to hospitals and Radiology Groups around the country. As an example, a teleradiology firm might cover trauma at a hospital in Indiana with doctors based in Texas. Some firms even used overseas doctors in locations like Australia and India. Nighthawk, founded by Paul Berger, was the first to station U.S. licensed radiologists overseas (initially Australia and later Switzerland) to maximize the time zone difference to provide nightcall in U.S. hospitals."}
{"_id": "WikiPedia_Radiology$$$corpus_2139", "text": "Currently, teleradiology firms are facing pricing pressures. Industry consolidation is likely as there are more than 500 of these firms, large and small, throughout the United States."}
{"_id": "WikiPedia_Radiology$$$corpus_2140", "text": "Although teleradiology is flourishing in the developed world, few teleradiological links have been made to the developing world. Generally, barriers to the implementation of radiology services have also complicated setting up reliable links. [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2141", "text": "Several examples of simple, low-cost nonprofit teleradiology solutions have been employed by Satellife and the Swinfen Charitable Trust. Established in 1987 by Nobel Peace Prize laureate,  Bernard Lown , Satellife (Boston) was the first non-profit organization to own and use a low Earth orbit satellite as well as mobile computing devices such as handheld computers and mobile phones for medical data communication. [ 8 ]  Starting in 1998, Swinfen Charitable Trust, a U.K. based nonprofit organization founded by Lord and Lady  Swinfen , gave healthcare personnel in remote places internet access and a digital camera, and also facilitated a low-cost telemedicine service linking doctors at hospitals in the developing world with medical and surgical consultants who gave advice at no cost. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2142", "text": "More complex solutions emerged in 2007. Operated by volunteer radiologists, T\u00e9l\u00e9radiologie sans Fronti\u00e8res (Teleradiology without Borders), a Luxembourg-based nonprofit organization founded  by  Dr Jean-Baptiste Niedercorn and Dr G\u00e9rald Wajnapel, started to provide teleradiology imaging services to developing  countries using a professional cloud  picture archiving and communications system  (PACS). [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2143", "text": "Today, many established private teleradiology practices such as Virtual Radiologic (vRad) are also involved in pilot programs with NGOs, reporting radiographs from rural health centres, free of charge. [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2144", "text": "Thrombus perviousness  is an imaging biomarker which is used to estimate clot permeability from CT imaging. It reflects the ability of artery-occluding thrombi to let fluid seep into and through them. The more pervious a thrombus, the more fluid it lets through. Thrombus perviousness can be measured using radiological imaging routinely performed in the clinical management of acute ischemic stroke:  CT scans  without intravenous contrast (also called non-contrast CT, in short NCCT) combined with CT scans after intravenously administered contrast fluid ( CT-angiography , in short CTA). Pervious thrombi may let more blood pass through to the ischemic brain tissue, and/or have a larger contact surface and histopathology more sensitive for  thrombolytic medication . Thus, patients with pervious thrombi may have less brain tissue damage by stroke. [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 5 ] [ 6 ]  The value of thrombus perviousness in acute ischemic stroke treatment is currently being researched."}
{"_id": "WikiPedia_Radiology$$$corpus_2145", "text": "Emilie Santos et al. introduced the term thrombus perviousness in 2016 to estimate thrombus permeability in ischemic stroke patients. [ 1 ]  Before, Mishra et al. used \u2018residual flow within the clot\u2019, and Fr\u00f6lich et al. used \u2018antegrade flow across incomplete vessel occlusions\u2019 to describe an estimate of thrombus permeability. [ 2 ] [ 3 ]   Permeability  is the physical measure of the ability of a material to transmit fluids over time. To measure thrombus permeability, one needs to measure contrast flow through a clot over time and the pressure drop caused by the occlusion, which is commonly not possible in the acute management of a patient with acute ischemic stroke. Current standard diagnostic protocol for acute ischemic stroke only requires single-phase imaging, visualizing the thrombus at a snapshot in time. Therefore, thrombus perviousness was introduced as a derivative measure of  permeability."}
{"_id": "WikiPedia_Radiology$$$corpus_2146", "text": "The amount of  contrast  that seeps into a thrombus can be quantified by the density difference of thrombi between non-contrast computed tomography (NCCT) and CT angiography (CTA) images. Two measures for thrombus perviousness have been introduced: (1) the void fraction and (2) thrombus attenuation increase (TAI). [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2147", "text": "The void fraction represents the ratio of the void volume within a thrombus, filled with a volume of blood (V blood ) and the volume of thrombus material (V thrombus ): \n \n \n \n \n \u03b5 \n \n = \n \n \n \n \n V \n \n \n blood \n \n \n \n \n V \n \n \n thrombus \n \n \n \n \n \n \n {\\displaystyle {\\text{\u03b5}}={\\frac {{\\text{V}}_{\\text{blood}}}{{\\text{V}}_{\\text{thrombus}}}}} \n \n Void fraction can be estimated by measuring the attenuation increase (\u0394) between NCCT and CTA in the thrombus (\u0394 thrombus ) and in the contralateral artery, filling with contrast on CTA (\u0394 blood ), and subsequently compute the ratio of these \u0394s: \n \n \n \n \n \u03b5 \n \n = \n \n \n \n \n \n \u03c1 \n \n \n CTA \n \n \n \n \n \n thrombus \n \n \n \u2212 \n \n \n \u03c1 \n \n \n NCCT \n \n \n \n \n \n thrombus \n \n \n \n \n \n \n \u03c1 \n \n \n CTA \n \n \n \n \n \n blood \n \n \n \u2212 \n \n \n \u03c1 \n \n \n NCCT \n \n \n \n \n \n blood \n \n \n \n \n \n = \n \n \n \n \n \u0394 \n \n \n thrombus \n \n \n \n \n \u0394 \n \n \n blood \n \n \n \n \n \n \n {\\displaystyle {\\text{\u03b5}}={\\frac {{\\text{\u03c1}}_{\\text{CTA}}\\,^{\\text{thrombus}}-{\\text{\u03c1}}_{\\text{NCCT}}\\,^{\\text{thrombus}}}{{\\text{\u03c1}}_{\\text{CTA}}\\,^{\\text{blood}}-{\\text{\u03c1}}_{\\text{NCCT}}\\,^{\\text{blood}}}}={\\frac {{\\text{\u0394}}_{\\text{thrombus}}}{{\\text{\u0394}}_{\\text{blood}}}}}"}
{"_id": "WikiPedia_Radiology$$$corpus_2148", "text": "To measure TAI, the mean  attenuation  ( density , in  Hounsfield Units ) of a clot is measured on NCCT (\u03c1 thrombus NCCT ) and subtracted from the thrombus density measured on CTA (\u03c1 thrombus CTA ). [ 1 ]  CTA thrombus density increases after administration of the high-density contrast fluid used in CTA:"}
{"_id": "WikiPedia_Radiology$$$corpus_2149", "text": "\u0394 thrombus  = \u03c1 thrombus CTA  \u2013 \u03c1 thrombus NCCT"}
{"_id": "WikiPedia_Radiology$$$corpus_2150", "text": "A manual (volume of interest [ROI]-based) and semi-automated (full thrombus segmentation) method have been described to measure thrombus density."}
{"_id": "WikiPedia_Radiology$$$corpus_2151", "text": "In the manual thrombus perviousness assessment, spherical ROIs with a diameter of 2\u00a0mm are manually placed in the thrombus, both on NCCT and CTA. To improve reflection of possible thrombus heterogeneity, three ROIs are placed per imaging modality rather than one. [ 7 ]  The average of every three ROIs is calculated and used as \u03c1 thrombus NCCT  and \u03c1 thrombus CTA ."}
{"_id": "WikiPedia_Radiology$$$corpus_2152", "text": "In automated measurements, the thrombus on CTA images is semi-automatically segmented in three steps. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2153", "text": "It has been shown that manual measurement tends to overestimate actual entire thrombus density, especially in low-density thrombi. [ 7 ]  Measurements based on the full thrombus show a wider variety of thrombus densities and better discrimination of high- and low-density thrombi and shows a stronger correlation with outcome measures than measurements based on 3 ROIs. [ 7 ] [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2154", "text": "TAI measurements performed on CT scans with thicker slices will be less accurate, because volume averaging results in a reduction of thrombus density on NCCT. [ 10 ]  Therefore, it has been suggested to only use thin-slice CT images (\u22642.5\u00a0mm) to measure thrombus perviousness. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2155", "text": "Alternative measures of similar thrombus permeability characteristics have been introduced and are still being introduced. Mishra et al. introduced the residual flow grade, which distinguishes no contrast penetration (grade 0); contrast permeating diffusely through thrombus (grade 1); and tiny hairline lumen or streak of well-defined contrast within the thrombus extending either through its entire length or part of the thrombus (grade 2)."}
{"_id": "WikiPedia_Radiology$$$corpus_2156", "text": "Currently, treatment for  acute ischemic stroke  due to an occlusion of one of the arteries of the proximal anterior intracranial circulation consists of  intravenous thrombolysis  followed by  endovascular thrombectomy  for patients that arrive at the hospital within 4.5 hours of stroke onset. Patients that arrive later than 4.5 hours after onset, or have contra-indications for intravenous thrombolysis can still be eligible for endovascular thrombectomy only. Even with treatment, not all patients recover after their stroke; many are left with permanent brain damage. Increased thrombus perviousness may decrease brain damage during stroke by allowing more blood to reach the ischemic tissue. [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 5 ] [ 6 ]  Furthermore, level of perviousness may reflect histopathological composition of clots or size of contact surface for thrombolytic medication, thereby influencing effectiveness of thrombolysis. [ 1 ] [ 5 ] [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2157", "text": "A number of studies has been conducted on the effects of thrombus perviousness on NCCT and CTA. [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 5 ] [ 6 ] [ 12 ]  In addition, dynamic imaging modalities have been used to investigate thrombus perviousness/permeability in animal and laboratory studies  [ 13 ] [ 14 ] [ 15 ]  and in humans using digital subtraction angiography (DSA) and CT Perfusion/4D-CTA.  [ 3 ] [ 16 ]  4D-CTA may enable more accurate measurement of TAI, since it overcomes the influence of varying scan timing and contrast arrival in single phase CTA.  [ 16 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2158", "text": "Tomographic reconstruction  is a type of multidimensional  inverse problem  where the challenge is to yield an estimate of a specific system from a finite number of  projections . The mathematical basis for tomographic imaging was laid down by  Johann Radon . A notable example of applications is the  reconstruction  of  computed tomography  (CT) where cross-sectional images of patients are obtained in non-invasive manner. Recent developments have seen the  Radon transform  and its inverse used for tasks related to realistic object insertion required for testing and evaluating computed tomography use in  airport security . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2159", "text": "This article applies in general to reconstruction methods for all kinds of  tomography , but some of the terms and physical descriptions refer directly to the reconstruction of X-ray computed tomography."}
{"_id": "WikiPedia_Radiology$$$corpus_2160", "text": "The projection of an object, resulting from the tomographic measurement process at a given angle  \n \n \n \n \u03b8 \n \n \n {\\displaystyle \\theta } \n \n , is made up of a set of  line integrals  (see Fig. 1). A set of many such projections under different angles organized in 2D is called a sinogram (see Fig. 3). In X-ray CT, the line integral represents the total attenuation of the beam of  X-rays  as it travels in a straight line through the object. As mentioned above, the resulting image is a 2D (or 3D) model of the  attenuation coefficient . That is, we wish to find the image  \n \n \n \n \u03bc \n ( \n x \n , \n y \n ) \n \n \n {\\displaystyle \\mu (x,y)} \n \n . The simplest and easiest way to visualise the method of scanning is the system of  parallel projection , as used in the first scanners. For this discussion we consider the data to be collected as a series of parallel rays, at position  \n \n \n \n r \n \n \n {\\displaystyle r} \n \n , across a projection at angle  \n \n \n \n \u03b8 \n \n \n {\\displaystyle \\theta } \n \n . This is repeated for various angles.  Attenuation  occurs  exponentially  in tissue:"}
{"_id": "WikiPedia_Radiology$$$corpus_2161", "text": "where  \n \n \n \n \u03bc \n ( \n x \n , \n y \n ) \n \n \n {\\displaystyle \\mu (x,y)} \n \n  is the attenuation coefficient as a function of position. Therefore, generally the total attenuation  \n \n \n \n p \n \n \n {\\displaystyle p} \n \n  of a ray at position  \n \n \n \n r \n \n \n {\\displaystyle r} \n \n , on the projection at angle  \n \n \n \n \u03b8 \n \n \n {\\displaystyle \\theta } \n \n , is given by the line integral:"}
{"_id": "WikiPedia_Radiology$$$corpus_2162", "text": "Using the coordinate system of Figure 1, the value of  \n \n \n \n r \n \n \n {\\displaystyle r} \n \n  onto which the point  \n \n \n \n ( \n x \n , \n y \n ) \n \n \n {\\displaystyle (x,y)} \n \n  will be projected at angle  \n \n \n \n \u03b8 \n \n \n {\\displaystyle \\theta } \n \n  is given by:"}
{"_id": "WikiPedia_Radiology$$$corpus_2163", "text": "So the equation above can be rewritten as"}
{"_id": "WikiPedia_Radiology$$$corpus_2164", "text": "where  \n \n \n \n f \n ( \n x \n , \n y \n ) \n \n \n {\\displaystyle f(x,y)} \n \n  represents  \n \n \n \n \u03bc \n ( \n x \n , \n y \n ) \n \n \n {\\displaystyle \\mu (x,y)} \n \n  and  \n \n \n \n \u03b4 \n ( \n ) \n \n \n {\\displaystyle \\delta ()} \n \n  is the  Dirac delta function . This function is known as the  Radon transform  (or  sinogram ) of the 2D object."}
{"_id": "WikiPedia_Radiology$$$corpus_2165", "text": "The  Fourier Transform  of the projection can be written as"}
{"_id": "WikiPedia_Radiology$$$corpus_2166", "text": "where  \n \n \n \n \n g \n \n \u03b8 \n \n \n ( \n x \n cos \n \u2061 \n \u03b8 \n + \n y \n sin \n \u2061 \n \u03b8 \n ) \n \n \n {\\displaystyle g_{\\theta }(x\\cos \\theta +y\\sin \\theta )} \n \n  is the derivative of the  Hilbert transform  of  \n \n \n \n \n p \n \n \u03b8 \n \n \n ( \n r \n ) \n \n \n {\\displaystyle p_{\\theta }(r)}"}
{"_id": "WikiPedia_Radiology$$$corpus_2167", "text": "In theory, the inverse Radon transformation would yield the original image. The  projection-slice theorem  tells us that if we had an infinite number of one-dimensional projections of an object taken at an infinite number of angles, we could perfectly reconstruct the original object,  \n \n \n \n f \n ( \n x \n , \n y \n ) \n \n \n {\\displaystyle f(x,y)} \n \n . However, there will only be a finite number of projections available in practice."}
{"_id": "WikiPedia_Radiology$$$corpus_2168", "text": "Assuming  \n \n \n \n f \n ( \n x \n , \n y \n ) \n \n \n {\\displaystyle f(x,y)} \n \n  has effective diameter  \n \n \n \n d \n \n \n {\\displaystyle d} \n \n  and desired resolution is  \n \n \n \n \n R \n \n s \n \n \n \n \n {\\displaystyle R_{s}} \n \n , a rule of thumb for the number of projections needed for reconstruction is  \n \n \n \n N \n > \n \u03c0 \n d \n \n / \n \n \n R \n \n s \n \n \n \n \n {\\displaystyle N>\\pi d/R_{s}} \n \n [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2169", "text": "Practical reconstruction algorithms have been developed to implement the process of reconstruction of a three-dimensional object from its projections. [ 3 ] [ 2 ]  These  algorithms  are designed largely based on the mathematics of the  X-ray transform , statistical knowledge of the data acquisition process and geometry of the data imaging system."}
{"_id": "WikiPedia_Radiology$$$corpus_2170", "text": "Reconstruction can be made using interpolation. Assume  \n \n \n \n N \n \n \n {\\displaystyle N} \n \n  projections of  \n \n \n \n f \n ( \n x \n , \n y \n ) \n \n \n {\\displaystyle f(x,y)} \n \n  are generated at equally spaced angles, each sampled at the same rate. The  discrete Fourier transform  (DFT) on each projection yields sampling in the frequency domain. Combining all the frequency-sampled projections generates a polar raster in the frequency domain. The polar raster is sparse, so interpolation is used to fill the unknown DFT points, and reconstruction can be done through the  inverse discrete Fourier transform . [ 4 ]  Reconstruction performance may improve by designing methods to change the sparsity of the polar raster, facilitating the effectiveness of interpolation."}
{"_id": "WikiPedia_Radiology$$$corpus_2171", "text": "For instance, a concentric square raster in the frequency domain can be obtained by changing the angle between each projection as follow:"}
{"_id": "WikiPedia_Radiology$$$corpus_2172", "text": "where  \n \n \n \n \n R \n \n 0 \n \n \n \n \n {\\displaystyle R_{0}} \n \n  is highest frequency to be evaluated."}
{"_id": "WikiPedia_Radiology$$$corpus_2173", "text": "The concentric square raster improves computational efficiency by allowing all the interpolation positions to be on rectangular DFT lattice. Furthermore, it reduces the interpolation error. [ 4 ]  Yet, the Fourier-Transform algorithm has a disadvantage of producing inherently noisy output."}
{"_id": "WikiPedia_Radiology$$$corpus_2174", "text": "In practice of tomographic image reconstruction, often a stabilized and  discretized  version of the inverse Radon transform is used, known as the  filtered back projection  algorithm. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2175", "text": "With a sampled discrete system, the inverse Radon transform is"}
{"_id": "WikiPedia_Radiology$$$corpus_2176", "text": "where  \n \n \n \n \u0394 \n \u03b8 \n \n \n {\\displaystyle \\Delta \\theta } \n \n  is the angular spacing between the projections and  \n \n \n \n k \n ( \n t \n ) \n \n \n {\\displaystyle k(t)} \n \n  is a Radon kernel with frequency response  \n \n \n \n \n | \n \n \u03c9 \n \n | \n \n \n \n {\\displaystyle |\\omega |} \n \n ."}
{"_id": "WikiPedia_Radiology$$$corpus_2177", "text": "The name  back-projection  comes from the fact that a one-dimensional projection needs to be filtered by a one-dimensional Radon kernel (back-projected) in order to obtain a two-dimensional signal. The filter used does not contain DC gain, so adding  DC bias  may be desirable. Reconstruction using back-projection allows better resolution than interpolation method described above. However, it induces greater noise because the filter is prone to amplify high-frequency content."}
{"_id": "WikiPedia_Radiology$$$corpus_2178", "text": "The iterative algorithm is computationally intensive but it allows the inclusion of  a priori  information about the system  \n \n \n \n f \n ( \n x \n , \n y \n ) \n \n \n {\\displaystyle f(x,y)} \n \n . [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2179", "text": "Let  \n \n \n \n N \n \n \n {\\displaystyle N} \n \n  be the number of projections and  \n \n \n \n \n D \n \n i \n \n \n \n \n {\\displaystyle D_{i}} \n \n  be the distortion operator for the  \n \n \n \n i \n \n \n {\\displaystyle i} \n \n th projection taken at an angle  \n \n \n \n \n \u03b8 \n \n i \n \n \n \n \n {\\displaystyle \\theta _{i}} \n \n .  \n \n \n \n { \n \n \u03bb \n \n i \n \n \n } \n \n \n {\\displaystyle \\{\\lambda _{i}\\}} \n \n  are a set of parameters to optimize the conversion of iterations."}
{"_id": "WikiPedia_Radiology$$$corpus_2180", "text": "An alternative family of recursive tomographic reconstruction algorithms are the  algebraic reconstruction techniques  and  iterative sparse asymptotic minimum variance ."}
{"_id": "WikiPedia_Radiology$$$corpus_2181", "text": "Use of a noncollimated fan beam is common since a  collimated  beam of radiation is difficult to obtain. Fan beams will generate series of line integrals, not parallel to each other, as projections. The fan-beam system requires a 360-degree range of angles, which imposes mechanical constraints, but it allows faster signal acquisition time, which may be advantageous in certain settings such as in the field of medicine. Back projection follows a similar two-step procedure that yields reconstruction by computing weighted sum back-projections obtained from filtered projections."}
{"_id": "WikiPedia_Radiology$$$corpus_2182", "text": "Deep learning methods are widely applied to image reconstruction nowadays and have achieved impressive results in various image reconstruction tasks, including low-dose denoising, sparse-view reconstruction, limited angle tomography and metal artifact reduction. An excellent overview can be found in the special issue  [ 5 ]  of IEEE Transaction on Medical Imaging. One group of deep learning reconstruction algorithms apply post-processing neural networks to achieve image-to-image reconstruction, where input images are reconstructed by conventional reconstruction methods. Artifact reduction using the U-Net in limited angle tomography is such an example application. [ 6 ]  However, incorrect structures may occur in an image reconstructed by such a completely data-driven method, [ 7 ]  as displayed in the figure. Therefore, integration of known operators into the architecture design of neural networks appears beneficial, as described in the concept of precision learning. [ 8 ]  For example, direct image reconstruction from projection data can be learnt from the framework of filtered back-projection. [ 9 ]  Another example is to build neural networks by unrolling iterative reconstruction algorithms. [ 10 ]  Except for precision learning, using conventional reconstruction methods with deep learning reconstruction prior  [ 11 ]  is also an alternative approach to improve the image quality of deep learning reconstruction."}
{"_id": "WikiPedia_Radiology$$$corpus_2183", "text": "Tomographic systems have significant variability in their applications and geometries (locations of sources and detectors). This variability creates the need for very specific, tailored implementations of the processing and reconstruction algorithms. Thus, most CT manufacturers provide their own custom proprietary software. This is done not only to protect intellectual property, but may also be enforced by a government regulatory agency. Regardless, there are a number of general purpose tomographic reconstruction software packages that have been developed over the last couple decades, both commercial and open-source."}
{"_id": "WikiPedia_Radiology$$$corpus_2184", "text": "Most of the commercial software packages that are available for purchase focus on processing data for benchtop cone-beam CT systems. A few of these software packages include  Volume Graphics ,  InstaRecon ,  iTomography ,  Livermore Tomography Tools (LTT) , and  Cone Beam Software Tools (CST) ."}
{"_id": "WikiPedia_Radiology$$$corpus_2185", "text": "Some noteworthy examples of open-source reconstruction software include: Reconstruction Toolkit (RTK),  [ 12 ]  CONRAD, [ 13 ]  TomoPy, [ 14 ]  the ASTRA toolbox, [ 15 ] [ 16 ]  PYRO-NN, [ 17 ]  ODL, [ 18 ]  TIGRE, [ 19 ]  and LEAP. [ 20 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2186", "text": "Shown in the gallery is the complete process for a simple object tomography and the following tomographic reconstruction based on ART."}
{"_id": "WikiPedia_Radiology$$$corpus_2187", "text": "Transient hepatic attenuation differences  ( THAD ) are areas of  enhancement  during the arterial phase of  contrast CT  of the liver. THAD is thought to be a physiological phenomenon resulting from regional variation in the blood supply by the  portal vein  and/or the  hepatic artery . THAD may in some cases be associated with  liver tumors  such as a  hepatocellular carcinoma . [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2188", "text": "A  vaginogram  is a  medical imaging  method in which a  radiocontrast agent  is injected while  X-ray pictures  are taken, to visualize structures of the  vagina . [ 1 ]  It has been used to visualize  ureterovaginal fistulas . [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2189", "text": "This  gynaecology  article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Radiology$$$corpus_2190", "text": "Waters' view  (also known as the  occipitomental view  or  parietoacanthial projection ) is a radiographic view of the skull. It is commonly used to get a better view of the  maxillary sinuses . An x-ray beam is angled at 45\u00b0 to the  orbitomeatal line . The rays pass from behind the head and are perpendicular to the radiographic plate. Another variation of the waters places the orbitomeatal line at a 37\u00b0 angle to the image receptor. It is named after the American radiologist Charles Alexander Waters."}
{"_id": "WikiPedia_Radiology$$$corpus_2191", "text": "Waters' view can be used to best visualise a number of structures in the skull."}
{"_id": "WikiPedia_Radiology$$$corpus_2192", "text": "The frontal sinus may not show the  frontal sinus  in detail. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2193", "text": "Typically, the x-ray beam is angled at 45\u00b0 to the  orbitomeatal line . [ 3 ]  Another variation of the waters places the orbitomeatal line at a 37\u00b0 angle to the image receptor, [ 4 ]  or 30\u00b0. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2194", "text": "Waters' view is named after the American radiologist Charles Alexander Waters. [ 6 ]  It is also known as the occipitomental view. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2195", "text": "An  X-ray tube  is a  vacuum tube  that converts electrical input power into  X-rays . [ 1 ]  The availability of this controllable source of X-rays created the field of  radiography , the imaging of partly opaque objects with penetrating  radiation . In contrast to other sources of  ionizing radiation , X-rays are only produced as long as the X-ray tube is energized. X-ray tubes are also used in  CT scanners , airport luggage scanners,  X-ray crystallography , material and structure analysis, and for industrial inspection."}
{"_id": "WikiPedia_Radiology$$$corpus_2196", "text": "Increasing demand for high-performance  computed tomography  (CT) scanning and  angiography  systems has driven development of very high-performance medical X-ray tubes."}
{"_id": "WikiPedia_Radiology$$$corpus_2197", "text": "X-ray tubes evolved from experimental  Crookes tubes  with which X-rays were first discovered on November 8, 1895, by the German physicist  Wilhelm Conrad R\u00f6ntgen . The first-generation  cold cathode  or  Crookes  X-ray tubes were used until the 1920s. These tubes work by ionisation of residual gas within the tube. The positive ions bombard the cathode of the tube to release electrons, which are accelerated toward the anode and produce X-rays when they strike it. [ 2 ]  The Crookes tube was improved by  William Coolidge  in 1913. [ 3 ]  The  Coolidge  tube, also called a  hot cathode  tube, uses  thermionic emission , where a tungsten cathode is heated to a sufficiently high temperature to emit electrons, which are then accelerated toward the anode in a near perfect vacuum. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2198", "text": "Until the late 1980s, X-ray generators were merely high-voltage, AC to DC variable power supplies. In the late 1980s a different method of control was emerging, called high-speed switching. This followed the electronics technology of switching power supplies (aka  switch mode power supply ), and allowed for more accurate control of the X-ray unit, higher quality results and reduced X-ray exposures. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2199", "text": "As with any  vacuum tube , there is a  cathode , which emits electrons into the vacuum and an  anode  to collect the electrons, thus establishing a flow of electrical current, known as the  beam , through the tube. A high  voltage  power source, for example 30 to 150  kilovolts  (kV), called the  tube voltage , is connected across cathode and anode to accelerate the electrons. The  X-ray  spectrum depends on the anode material and the accelerating voltage. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2200", "text": "Electrons from the cathode collide with the anode material, usually  tungsten ,  molybdenum  or  copper , and accelerate other electrons, ions and nuclei within the anode material. About 1% of the energy generated is emitted/radiated, usually perpendicular to the path of the electron beam, as X-rays. The rest of the energy is released as heat. Over time, tungsten will be deposited from the target onto the interior surface of the tube, including the glass surface. This will slowly darken the tube and was thought to degrade the quality of the X-ray beam. Vaporized tungsten condenses on the inside of the envelope over the \"window\" and thus acts as an additional filter and decreases the tube's ability to radiate heat. [ 5 ]  Eventually, the tungsten deposit may become sufficiently conductive that at high enough voltages, arcing occurs. The arc will jump from the cathode to the tungsten deposit, and then to the anode. This arcing causes an effect called \" crazing \" on the interior glass of the X-ray window. With time, the tube becomes unstable even at lower voltages and must be replaced. At this point, the tube assembly (also called the \"tube head\") is removed from the X-ray system, and replaced with a new tube assembly. The old tube assembly is shipped to a company that reloads it with a new X-ray tube. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2201", "text": "The two X-ray photon-generating effects are generally called the ' Characteristic effect ' and the  bremsstrahlung  effect, a compound of the German  bremsen  meaning to brake, and  Strahlung  meaning  radiation . [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2202", "text": "The range of  photonic energies  emitted by the system can be adjusted by changing the applied voltage, and installing aluminum filters of varying thicknesses. Aluminum filters are installed in the path of the X-ray beam to remove \"soft\" (non-penetrating) radiation. The number of emitted X-ray photons, or dose, are adjusted by controlling the current flow and exposure time. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2203", "text": "Heat is produced in the focal spot of the anode. Since a small fraction (less than or equal to 1%) of electron energy is converted to X-rays, it can be ignored in heat calculations. [ 7 ] \nThe quantity of heat produced (in Joule) in the focal spot is given by\u00a0:"}
{"_id": "WikiPedia_Radiology$$$corpus_2204", "text": "Heat Unit (HU) was used in the past as an alternative to Joule. It is a convenient unit when a single-phase power source is connected to the X-ray tube. [ 7 ]  With a full-wave rectification of a  sine wave ,  \n \n \n \n w \n \n \n {\\displaystyle w} \n \n = \n \n \n \n \n \n 1 \n \n 2 \n \n \n \n \u2248 \n 0.707 \n \n \n {\\displaystyle {\\frac {1}{\\sqrt {2}}}\\approx 0.707} \n \n , thus the heat unit:"}
{"_id": "WikiPedia_Radiology$$$corpus_2205", "text": "Crookes tubes generated the electrons needed to create X-rays by  ionization  of the residual air in the tube, instead of a heated  filament , so they were partially but not completely  evacuated . They consisted of a  glass  bulb with around 10 \u22126  to 5\u00d710 \u22128   atmospheric pressure  of  air  (0.1 to 0.005  Pa ). They had an  aluminum   cathode  plate at one end of the tube, and a  platinum   anode  target at the other end. The anode surface was angled so that the X-rays would radiate through the side of the tube. The cathode was concave so that the electrons were focused on a small (~1\u00a0mm) spot on the anode, approximating a  point source  of X-rays, which resulted in sharper images. The tube had a third electrode, an anticathode connected to the anode. It improved the X-ray output, but the method by which it achieved this is not understood. A more common arrangement used a copper plate anticathode (similar in construction to the cathode) in line with the anode such that the anode was between the cathode and the anticathode. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2206", "text": "To operate, a  DC  voltage of a few  kilovolts  to as much as 100 kV was applied between the anodes and the cathode, usually generated by an  induction coil , or for larger tubes, an  electrostatic machine . [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2207", "text": "Crookes tubes were unreliable. As time passed, the residual air would be absorbed by the walls of the tube, reducing the pressure. This increased the voltage across the tube, generating 'harder' X-rays, until eventually the tube stopped working. To prevent this, 'softener' devices were used (see picture). A small tube attached to the side of the main tube contained a mica sleeve or chemical that released a small amount of gas when heated, restoring the correct pressure. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2208", "text": "The glass envelope of the tube would blacken with usage due to the X-rays affecting its structure. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2209", "text": "In the Coolidge tube, the electrons are produced by  thermionic effect  from a  tungsten   filament  heated by an electric current. The filament is the cathode of the tube. The high voltage potential is between the cathode and the anode, the electrons are thus  accelerated , then hit the anode. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2210", "text": "There are two designs: end-window tubes and side-window tubes. End window tubes usually have \"transmission target\" which is thin enough to allow X-rays to pass through the target (X-rays are emitted in the same direction as the electrons are moving.) In one common type of end-window tube, the filament is around the anode (\"annular\" or ring-shaped), the electrons have a curved path (half of a toroid). [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2211", "text": "What is special about side-window tubes is an  electrostatic lens  is used to focus the beam onto a very small spot on the anode. The anode is specially designed to dissipate the heat and wear resulting from this intense focused barrage of electrons. The anode is precisely angled at 1-20 degrees off perpendicular to the electron current to allow the escape of some of the X-ray photons which are emitted perpendicular to the direction of the electron current. The anode is usually made of tungsten or molybdenum. The tube has a window designed for escape of the generated X-ray photons. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2212", "text": "The power of a Coolidge tube usually ranges from 0.1 to 18  kW . [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2213", "text": "A considerable amount of heat is generated in the focal spot (the area where the beam of electrons coming from the cathode strike to) of a stationary anode. Rather, a rotating anode lets the electron beam sweep a larger area of the anode, thus redeeming the advantage of a higher intensity of emitted radiation, along with reduced damage to the anode compared to its stationary state. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2214", "text": "The focal spot temperature can reach 2,500\u00a0\u00b0C (4,530\u00a0\u00b0F) during an exposure, and the anode assembly can reach 1,000\u00a0\u00b0C (1,830\u00a0\u00b0F) following a series of large exposures. Typical anodes are a tungsten-rhenium target on a molybdenum core, backed with graphite. The  rhenium  makes the  tungsten  more ductile and resistant to wear from the impact of the electron beams. The  molybdenum  conducts heat from the target. The  graphite  provides thermal storage for the anode, and minimizes the rotating mass of the anode."}
{"_id": "WikiPedia_Radiology$$$corpus_2215", "text": "Some X-ray examinations (such as, e.g.,  non-destructive testing  and  3-D microtomography ) need very high-resolution images and therefore require X-ray tubes that can generate very small focal spot sizes, typically below 50\u00a0\u03bcm in diameter. These tubes are called microfocus X-ray tubes. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2216", "text": "There are two basic types of microfocus X-ray tubes: solid-anode tubes and metal-jet-anode tubes. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2217", "text": "Solid-anode microfocus X-ray tubes  are in principle very similar to the Coolidge tube, but with the important distinction that care has been taken to be able to focus the electron beam into a very small spot on the anode. Many microfocus X-ray sources operate with focus spots in the range 5-20\u00a0\u03bcm, but in the extreme cases spots smaller than 1\u00a0\u03bcm may be produced. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2218", "text": "The major drawback of solid-anode microfocus X-ray tubes is their very low operating power. To avoid melting the anode, the electron-beam power density must be below a maximum value. This value is somewhere in the range 0.4-0.8 W/\u03bcm depending on the anode material. [ 10 ]  This means that a solid-anode microfocus source with a 10\u00a0\u03bcm electron-beam focus can operate at a power in the range 4-8 W."}
{"_id": "WikiPedia_Radiology$$$corpus_2219", "text": "In  metal-jet-anode microfocus X-ray tubes  the solid metal anode is replaced with a jet of liquid metal, which acts as the electron-beam target. The advantage of the metal-jet anode is that the maximum electron-beam power density is significantly increased. Values in the range 3-6 W/\u03bcm have been reported for different anode materials (gallium and tin). [ 11 ] [ 12 ]  In the case with a 10\u00a0\u03bcm electron-beam focus a metal-jet-anode microfocus X-ray source may operate at 30-60 W."}
{"_id": "WikiPedia_Radiology$$$corpus_2220", "text": "The major benefit of the increased power density level for the metal-jet X-ray tube is the possibility to operate with a smaller focal spot, say 5\u00a0\u03bcm, to increase image resolution and at the same time acquire the image faster, since the power is higher (15-30 W) than for solid-anode tubes with 10\u00a0\u03bcm focal spots."}
{"_id": "WikiPedia_Radiology$$$corpus_2221", "text": "Any  vacuum tube  operating at several thousand volts or more can produce X-rays as an unwanted byproduct, raising safety issues. [ 13 ] [ 14 ]  The higher the voltage, the more penetrating the resulting radiation and the more the hazard.  CRT displays , once common in color televisions and computer displays, operate at  3-40  kilovolts  depending on size, [ 15 ]  making them the main concern among household appliances. Historically, concern has focused less on the CRT, since its thick glass envelope is impregnated with several pounds of lead for shielding, than on high voltage (HV)  rectifier  and  voltage regulator  tubes inside earlier TVs. In the late 1960s it was found that a failure in the HV supply circuit of some  General Electric  TVs could leave excessive voltages on the regulator tube, causing it to emit X-rays. The same failure mode was also observed in early revisions of Soviet-made  Rubin  TVs equipped with  GP-5   voltage-regulator tube . The models were recalled and the ensuing scandal caused the US agency responsible for regulating this hazard, the  Center for Devices and Radiological Health  of the  Food and Drug Administration  (FDA), to require that all TVs include circuits to prevent excessive voltages in the event of failure. [ 16 ]  The hazard associated with excessive voltages was eliminated with the advent of all- solid-state  TVs, which have no tubes other than the CRT. Since 1969, the FDA has limited TV X-ray emission to 0.5 mR ( milliroentgen ) per hour. As  other screen technologies  advanced, starting in the 1990s, the production of CRTs was slowly phased out. These other technologies, such as  LED ,  LCD  and  OLED , are incapable of producing x-rays due to the lack of a high voltage transformer. [ 17 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2222", "text": "Interventional neuroradiology (INR)   also known as  neurointerventional surgery (NIS) ,  endovascular therapy (EVT) ,  endovascular neurosurgery , and  interventional neurology  is a medical subspecialty of   neurosurgery ,  neuroradiology ,  intervention radiology  and  neurology  specializing in minimally invasive image-based technologies and procedures used in diagnosis and treatment of diseases of the head, neck, and spine. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2223", "text": "Diagnostic angiography"}
{"_id": "WikiPedia_Radiology$$$corpus_2224", "text": "Cerebral angiography  was developed by Portuguese  neurologist   Egas Moniz  at the  University of Lisbon , in order to identify central nervous system diseases such as tumors or  arteriovenous malformations . He performed the first brain angiography in  Lisbon  in 1927 [ 3 ]  by injecting an  iodinated contrast  medium into the  internal carotid artery  and using the  X-rays  discovered 30 years earlier by  Roentgen  in order to visualize the cerebral vessels. In pre-CT and pre-MRI, it was the only tool to observe the structures within the skull and was also used to diagnose extravascular pathologies."}
{"_id": "WikiPedia_Radiology$$$corpus_2225", "text": "Subsequently, European radiologists further developed the angiographic technique by replacing the traumatic direct puncture with catheterization: in 1953, Swedish physician  Sven Seldinger  introduced the technique of  arterial  and  venous catheterization  still in practice, [ 4 ]  dubbed the  Seldinger Technique.  In 1964, the Norwegian radiologist Per Amudsen was the first to perform a complete brain angiography with a transfemoral approach, as it is performed today; he then moved to San Francisco to teach the technique to American neuroradiologists. [ 5 ]  These two stages, at the basis of modern invasive vascular diagnostics, prepared the way for later therapeutic developments."}
{"_id": "WikiPedia_Radiology$$$corpus_2226", "text": "The first treatments: balloon occlusion"}
{"_id": "WikiPedia_Radiology$$$corpus_2227", "text": "The first to carry out a true endovascular procedure was  Charles Dotter , the father of  angioplasty  and considered by many as the father of all  interventional radiology , as well as the first doctor to have performed endovascular treatment. On January 16, 1964, he performed a therapeutic angioplasty of a superficial  femoral artery  in an 82-year-old woman with an  ischemic  leg refusing  amputation . [ 6 ]  The artery remained open for the next two and a half years, after which the woman died of  pneumonia ."}
{"_id": "WikiPedia_Radiology$$$corpus_2228", "text": "The concept of using balloons to treat  cerebrovascular   lesions  was inspired by a 1959 May Day celebration in Moscow\u2019s Red Square. While watching children use tether lines to manipulate helium balloons, Fedor Serbinenko, a Russian neurosurgeon, began to envision small balloons moving through  tortuous arteries . [ 7 ]  In the 1970s Fedor Serbinenko developed a technique for closing  intracranial aneurysms  with balloons that were released into the internal carotid artery by  occluding  the  lumen . The first treatment was performed in 1970 in Moscow, with the occlusion of an internal carotid to treat a  carotid-cavernous fistula . He can be considered, therefore, the first interventional neuroradiologist. This technique was subsequently refined by neuroradiologists all over the world and mainly in France, where interventional neuroradiology developed and flourished."}
{"_id": "WikiPedia_Radiology$$$corpus_2229", "text": "Parallel to the development of catheters, in the radiology and neuroradiology units, image technology dramatically improved: Charles Mistretta in 1979 invented  digital subtraction angiography  (DSA), the technique currently in use. It consists of performing skull radiography under basic conditions which are then \"subtracted\" to the image after contrast media injection, to provide an image where only brain vessels are displayed, with great improvement in the diagnostic potential."}
{"_id": "WikiPedia_Radiology$$$corpus_2230", "text": "Coils replace balloon occlusion"}
{"_id": "WikiPedia_Radiology$$$corpus_2231", "text": "Between the end of the 1980s and the beginning of the '90s, INR was suddenly revolutionized after the work of two Italian physicians:  Cesare Gianturco  and Guido Guglielmi. The first combined a deep knowledge of diagnostic radiology with a great ability to solve technical and manual problems. He invented Gianturco's coils, which he used to make the first attempts to  embolize  arteries and aneurysms. [ 8 ]  Gianturco also patented the first  endovascular stent  approved by the American FDA; [ 8 ]  a device with a great legacy. In the second half of the 1980s,  Sadek Hilal  was the first in Columbia University to use coils to treat brain aneurysms; but this technique was inaccurate and dangerous because the coils were released with little control with great risk of occluding the vessel from which the aneurysm originated (parent vessel). [ 9 ]  The coil embolization was revolutionized by the work of Guido Guglielmi in UCLA, who realized that electricity could function as a controlled release mechanism for coils; in 1991 he published two works dealing with the embolization of brain aneurysms by means of detachable platinum coils [ 10 ]  ( Guglielmi's coils ). The treatment of aneurysms was thus made more accessible and safe."}
{"_id": "WikiPedia_Radiology$$$corpus_2232", "text": "New techniques: Sole stenting and flow diversion stents"}
{"_id": "WikiPedia_Radiology$$$corpus_2233", "text": "From the early 2000s, intracranial stents were used to prevent the coils inside the aneurysmal sac from protruding into the parent artery. [ 11 ] [ 12 ]  Flow diversion devices were later developed, with the function of reconstructing the vessel's normal anatomy without directly closing the aneurysm neck and therefore preserving side branches and preventing ischemia. [ 13 ]  The  sole stenting [ 14 ]  procedure involves the insertion of a stent only (without any coils) into the vessel that has an aneurysm. [ 15 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2234", "text": "Not just hemorrhages: the treatment of ischemic stroke"}
{"_id": "WikiPedia_Radiology$$$corpus_2235", "text": "The Souers Stroke Institute was founded in 1991 at  Saint Louis University , and its first director,  Camilo R. Gomez , M.D., is often credited with founding interventional neurology as a subspecialty in the United States. [ 16 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2236", "text": "Between January and June 2015, five major randomized trials were published in the  New England Journal of Medicine  ( NEJM ) with the collaboration of interventional neuroradiologists and  stroke  neurologists (in the Netherlands, [ 17 ]  Canada, [ 18 ]  Australia, [ 19 ]  US [ 20 ]  and Spain [ 21 ] ) regarding the role of mechanical  thrombectomy  in the treatment of ischemic stroke, demonstrating that if it is performed in centers with proven experience, intra-arterial mechanical thrombectomy is more effective than traditional treatment (intravenous thrombolytic injection). The promising results of these mechanical thrombectomy trials were highlighted by the  NEJM  in an editorial, which concluded with the statement: \"Endovascular equipoise no longer exists. It's about time.\" [ 22 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2237", "text": "Thrombectomy is currently recommended by the guidelines written by the main American (AHA/ASA) [ 23 ]  and European (ESO-ESNR-ESMINT) [ 24 ]  societies of stroke neurologists and interventional neuroradiologists."}
{"_id": "WikiPedia_Radiology$$$corpus_2238", "text": "The following is a list of diseases and conditions typically treated by neurointerventionalists."}
{"_id": "WikiPedia_Radiology$$$corpus_2239", "text": "Interventional oncology  (abbreviated  IO ) is a subspecialty field of  interventional radiology  that deals with the diagnosis and treatment of  cancer  and cancer-related problems using targeted minimally invasive procedures performed under image guidance. [ 1 ] [ 2 ]  Interventional oncology has developed to a separate pillar of modern oncology and it employs  X-ray ,  ultrasound ,  computed tomography (CT)  or  magnetic resonance imaging (MRI)  to help guide miniaturized instruments (e.g. biopsy needles, ablation electrodes, intravascular catheters) to allow targeted and precise treatment of solid tumours (also known as  neoplasms ) located in various organs of the  human body , including but not limited to the  liver ,  kidneys ,  lungs , and  bones . [ 3 ] [ 4 ]  Interventional oncology treatments are routinely carried out by interventional radiologists in appropriate settings and facilities. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2240", "text": "Interventional oncology procedures are generally divided between  diagnostic  procedures that help obtain tissue diagnosis of suspicious neoplasms and therapeutic ones that aim to cure or palliate the tumour. Therapeutic interventional oncology procedures may be classified further into  ablation  techniques that destroy neoplastic tissues by delivery of some form of heat, cryo or electromagnetic energy and embolization techniques that aim to occlude the blood vessels feeding the tumour and thereby destroy it by means of  ischemia . Both ablation and embolization techniques are minimally invasive treatment, i.e. they may be delivered through the skin (in a  percutaneous  way) without the need for any skin incisions or other form of  open surgery . Hence, most treatments are nowadays offered as day case or  outpatient  appointments and patients may enjoy rapid recovery and minimal pain and discomfort with low rates of complications. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2241", "text": "Uses different types of energy to burn ( radiofrequency ablation (RFA)  and  microwave ablation (MWA) ), deliver electrical fields/electroporate ( irreversible electroporation(IRE) ) or freeze ( cryoablation ) solid tumors resulting in tumor cell death. Ablation techniques can be performed throughout the body such as in the lung, [ 7 ]  liver, [ 8 ] [ 9 ]  kidney, [ 10 ]   prostate, [ 11 ]  breast, [ 12 ]  bone, [ 13 ]  and other organs using image guidance to place a needle/probe through the skin into the target tissue."}
{"_id": "WikiPedia_Radiology$$$corpus_2242", "text": "Uses a machine that emits high frequency sound waves to kill cancer cells and provide relief for tumor-related pain, such as in the bone."}
{"_id": "WikiPedia_Radiology$$$corpus_2243", "text": "Interventional oncology has long been used to provide palliative care for patients. IO procedures can help reduce cancer-related pain and improve patients\u2019 quality of life. Tumours can intrude into various ducts and blood vessels of the body, obstructing the vital passage of food, blood or waste. The interventional radiological treatment known as stenting can be used to re-open blockages, for example of the esophagus or bile ducts in cases of esophageal cancer or cholangiocarcinoma, respectively, considerably relieving the patient's adverse symptoms. [ 22 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2244", "text": "Interventional oncology (IO) procedures are commonly applied to treat primary or  metastatic  cancer. IO treatments may be also offered in combination with any of the above oncological therapies in order to augment the therapeutic outcome in more complex or widespread (metastatic) cancer cases. There is a variety of applications of interventional oncological treatments for tumors that arise in the:"}
{"_id": "WikiPedia_Radiology$$$corpus_2245", "text": "While the  surgical resection  of tumours is generally accepted to offer the best long-term solution, it is often not possible due to the size, number or location of the tumour. IR therapies may be applied to shrink the tumour, making a surgical or interventional treatment possible. Some patient groups may also be too weak to undergo open surgery. IR treatments can be applied in these complex cases to provide effective and milder forms of treatment.\nInterventional oncological techniques can also be used in combination with other treatments to help increase their  efficacy . For example, IO techniques can be used to shrink large tumours making them easier to excise. Chemotherapeutic drugs can also be administered intra-arterially, increasing their potency and removing the harsh effects of system-wide application."}
{"_id": "WikiPedia_Radiology$$$corpus_2246", "text": "Patients can greatly benefit from IO treatments. The minimally invasive nature of the treatments means they cause less pain, fewer side effects and shorter recovery times. Many IO procedures can be performed on an  outpatient  basis, freeing up hospital beds and reducing costs. [ 33 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2247", "text": "Cancer is a multifaceted disease group that requires a multidisciplinary approach to treatment. Numerous studies have shown that cancer patients treated in multidisciplinary environments benefit greatly from the combined expertise. Interventional Radiologists are seen as playing a major role in multidisciplinary cancer teams where they provide innovative solutions to improve combined therapies and to treat complications. [ 34 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2248", "text": "Proper patient selection is the key element for the success of any medical procedure and improper conduct can have fatal consequences. Patient selection protocols must be strictly followed before treating patients with IO procedures."}
{"_id": "WikiPedia_Radiology$$$corpus_2249", "text": "IO treatments are carried out under image guidance. For this reason practitioners must have attained solid training in  radiation protection ."}
{"_id": "WikiPedia_Radiology$$$corpus_2250", "text": "Interventional pulmonology  ( IP , also called  interventional pulmonary medicine ) is a maturing  medical sub-specialty  from its parent specialty of  pulmonary medicine . It deals specifically with minimally invasive  endoscopic  and percutaneous procedures for diagnosis and treatment of  neoplastic  as well as  non-neoplastic diseases  of the airways, lungs, and pleura. Many IP procedures constitute efficacious yet less invasive alternatives to  thoracic surgery ."}
{"_id": "WikiPedia_Radiology$$$corpus_2251", "text": "Before the advent of  optical fibers  and advances in  anesthesiology , interventional pulmonary procedures were mostly limited to foreign body retrieval via rigid bronchoscopy.  Gustav Killian  (June 2, 1860 \u2013 February 24, 1921), a German laryngologist, performed foreign body retrievals from bronchial passages using a rigid  laryngoscope /bronchoscope whereas in the United States,  Chevalier Jackson  (1865 \u2013 1958) was the first to use the rigid  bronchoscope . [ 1 ]  Later, Swedish internist  Hans-Christian Jacobaeus  first introduced  thoracoscopy  in a 1910 paper published in the journal  M\u00fcnch med Wochenschr , before Japanese thoracic surgeon  Shiketo Ikeda  (1925 \u2013 2001) introduced the fiberoptic bronchoscope in the late 20th century. [ 2 ] [ 3 ]  Jean-Francois Dumon from France is credited with modernizing rigid bronchoscopy in the late 20th century by introducing a novel non-metallic airway stent made of silicone, appropriately named the Dumon stent. [ 4 ]  Together, these developments laid the foundation for most of today\u2019s interventional pulmonary techniques."}
{"_id": "WikiPedia_Radiology$$$corpus_2252", "text": "In 1978, Kopen Wang and colleagues at  Johns Hopkins Hospital  described the use of transbronchial needle aspiration (TBNA) through a rigid bronchoscope to diagnose a paratracheal  mediastinal mass . [ 5 ]  Following the advent of  endobronchial ultrasound  (EBUS), which first became available in the early 21st century, EBUS-TBNA swiftly replaced  mediastinoscopy  as the first-line in mediastinal  staging  for lung cancer. [ 6 ]  With these developments, interventional pulmonology became much more firmly established on the map of distinct subspecialties."}
{"_id": "WikiPedia_Radiology$$$corpus_2253", "text": "In 1992, the Association for Bronchology and Interventional Pulmonology (AABIP) was formed as a representative society of interventional pulmonologists based in North America. [ 7 ]  This organization also publishes a journal, namely the  Journal of Bronchology and Interventional Pulmonology . [ 8 ]  The World Association for Bronchology was founded by Dr. Ikeda in 1978 and renamed as the World Association for Bronchology and Interventional Pulmonology (WABIP) in 2010. [ 9 ]  It holds a biennial scientific meeting known as the World Congress for Bronchology and Interventional Pulmonology. The Association for Interventional Pulmonology Program Directors (AIPPD), dedicated to the advancement of IP education in the United States, was created in 2012. [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2254", "text": "In addition to basic bronchoscopic and pleural procedures that are performed by a general pulmonologist, an interventional pulmonologist may perform the following advanced procedures:"}
{"_id": "WikiPedia_Radiology$$$corpus_2255", "text": "For purposes of formal training in interventional pulmonology, dedicated training programs only became available in the early 21st century. The first dedicated program was a 12-month advanced fellowship offered by Dr. Beamis at  Lahey Clinic  in  Boston . [ 11 ]  Currently, there are over 30 IP  fellowship  programs across the country. [ 10 ]  However, training programs have varied considerably in terms of the breadth and depth of procedural training that they offer. [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2256", "text": "To address the issue of inconsistent IP training across fellowship programs, representative members from five professional organizations (AABIP, AIPPD, ACCP, ATS, and APCCMPD) jointly published a list of minimum standards required by July 2019 in order for IP fellowship programs to receive formal accreditation from the AABIP and AIPPD. [ 13 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2257", "text": "To be eligible for this fellowship, applicants must first complete a three-year fellowship in pulmonary &  critical care medicine . Most of these programs select one to two fellow(s) per year, applying though the Interventional Pulmonary Fellow Application Service (IPFAS\u00a9). As with most other medical specialties and subspecialties across the United States, applicants are matched to programs through the  National Resident Matching Program  (NRMP, or the \u201cMatch\u201d). [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2258", "text": "Interventional radiology  ( IR ) is a medical specialty that performs various  minimally-invasive procedures  using medical imaging guidance, such as  x-ray fluoroscopy ,  computed tomography ,  magnetic resonance imaging , or  ultrasound . IR performs both diagnostic and therapeutic procedures  through very small incisions  or  body orifices . Diagnostic IR procedures are those intended to help make a  diagnosis  or guide further medical treatment, and include image-guided biopsy of a tumor or injection of an  imaging contrast agent  into a hollow structure, such as a  blood vessel  or a  duct . By contrast,  therapeutic  IR procedures provide direct treatment\u2014they include catheter-based medicine delivery, medical device placement (e.g., stents), and angioplasty of narrowed structures."}
{"_id": "WikiPedia_Radiology$$$corpus_2259", "text": "The main benefits of IR techniques are that they can reach the deep structures of the body through a  body orifice  or tiny incision using  small needles and wires . This decreases risks, pain, and recovery compared to  open procedures .  Real-time  visualization also allows precision guidance to the abnormality, making the procedure or diagnosis more accurate.  These benefits are weighed against the additional risks of lack of immediate access to internal structures (should bleeding or a perforation occur), and the risks of  radiation exposure  such as cataracts and cancer."}
{"_id": "WikiPedia_Radiology$$$corpus_2260", "text": "Interventional radiology is a set of techniques that allows access to the internal structures of the body through  body orifices  or very small incisions and guidance with  medical imaging .  Regardless of the reason for the intervention, the procedure will likely use common elements such as a  puncture needle  (to pass through the skin),  guidewires  (to guide through structures such as blood vessels or the biliary or urinary systems), a sheath (which slides over the guidewire and holds the path open without injuring it), and  catheters  (that allow fluids to be pushed through them). [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2261", "text": "Also common to all intervention radiology procedures are the medical imaging machines that allow the healthcare provider to see what is occurring within the body.  Some use X-rays (such as  CT  and  fluoroscopy ) and some do not (such as  ultrasound  and  MRI ). [ 1 ]   In each case, the images created may be modified by computer to better visualize the structures as is in the case with  digital subtraction angiography , CT and MRI, or the display of the images improved with  virtual reality  or  augmented reality  presentation. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2262", "text": "Vascular"}
{"_id": "WikiPedia_Radiology$$$corpus_2263", "text": "Biliary intervention [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2264", "text": "Catheter placement"}
{"_id": "WikiPedia_Radiology$$$corpus_2265", "text": "Ablative [ 13 ] [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2266", "text": "Genitourinary [ 16 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2267", "text": "The treatment of  gastrointestinal hemorrhage  can range anywhere from monitoring an asymptomatic bleed to supporting and maintaining the hemodynamic function of the patient. The role for the interventional radiologist is to offer patients an image-guided, minimally invasive procedure to alleviate a condition that could be otherwise be potentially life-threatening. [ 17 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2268", "text": "The avenue for the interventional radiologist to dictate the clinical course of a GI bleed is largely influenced by location of bleed, overall patient health and other conditions the patient may have, most notably heart and liver functions. For most cases, collaboration between the gastroenterologist and interventional radiologist optimizes patient outcome but again, is largely dictated by anatomical location of the GI bleed. If a patient is evaluated and determined to be a candidate for an interventional procedure, then the bleed is often treated by embolization. Embolization is a process in which the interventional radiologist accesses the culprit bleeding vessel via a small catheter and interrupts blood flow to the site of bleeding via various mechanisms. Side effects of this procedure are minimal but there is a risk of bleeding and infection\u2014though much less than the equivalent surgical procedure. When successful, the procedure often eliminates the bleed and patients can walk after a few hours of rest. [ 18 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2269", "text": "A transjugular intrahepatic portosystemic shunt (TIPS) is a procedure an interventional radiologist performs to create a shunt (essentially, a new conduit allowing for blood flow) between the hepatic inferior vena cava and the portal vein, a vessel that returns blood from the intestines to the liver. The portal vein is the site where hypertension (high blood pressure) can produce a myriad of deleterious effects throughout the liver and small or large intestine. [ 19 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2270", "text": "Primarily, a TIPS functions to alleviate two different conditions: an emergent/life-threatening GI bleed or ascites (excessive abdominal fluid) caused by too high of blood pressure in the portal vein that is otherwise uncontrolled by diet and medications. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2271", "text": "The workup for the procedure is straightforward and the interventional radiologist performing the procedure often orders several tests to assess how well the patient will tolerate the procedure. These are often simple blood tests, and an ultrasound of the heart and liver. The procedure is often well tolerated and can result in a permanent reduction or elimination of symptoms. The procedure can take anywhere between 15 minutes to an hour and has lower risks of bleeding or infection compared to an equivalent surgical procedure. [ 19 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2272", "text": "A TIPS may cause temporary confusion or worsening of liver/heart function. The degree of these two side effects largely depends on the health of the patient's heart and liver prior to the procedure and the risk-benefits of the procedure must be thoroughly discussed with their interventional radiologist before beginning. If the post-procedural consequences are more troublesome to the patient than their initial symptoms the artificial conduit created by the procedure can be reversed if the post-procedural side effects outweigh those caused by the prior conditions. [ 19 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2273", "text": "In addition to normal liver tissue, the liver has three main vessels traversing it: arteries, veins and bile ducts. While bile is made in the liver and stored in the gallbladder, the bile eventually passes into the GI tract through the hepatic, cystic and common bile ducts.  Any condition that prevents the normal flow of bile from the liver, through these bile vessels and into the GI tract can cause a condition called  jaundice . [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2274", "text": "While jaundice can be caused by a few viruses that the human body can naturally clear, jaundice in the setting of an obstruction is usually caused by a cancer and can result in intolerable itching and a worsening of liver function that can be life-threatening. Depending on a patient's condition, this type of obstructive jaundice can be alleviated with surgery or chemotherapy but if these measures fail to restore proper flow of bile, an interventional radiologist can perform a procedure called a percutaneous transhepatic cholangiography (PTC). [ 20 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2275", "text": "A PTC is an outpatient procedure lasting anywhere from 15 minutes to an hour where an interventional radiologist accesses the patient's bile duct system with a needle through the skin and liver under imaging guidance. Using fluoroscopy (essentially an X-ray camera) to guide a wire (followed by a catheter over the wire) through the bile duct system and into the GI tract, essentially restoring the normal flow of bile. If the patient's GI tract cannot be accessed due to the obstruction, the catheter can be placed to drain the bile duct system into a bag that the patient can wear during daily activities. Risks of this procedure include bleeding and infection but these are much lower than an equivalent surgical procedure. [ 20 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2276", "text": "Benign prostatic hyperplasia , or BPH, is a noncancerous condition that commonly affects men over the age of 50. The prostate gland enlarges and compresses the adjacent urethra, making it difficult for men to control frequency and/or urgency of urination. [ 21 ]  First-line therapy involves medication, though long-term treatment for symptoms that are persistent despite medical optimization typically involves transurethral resection of the prostate (TURP) as the \"gold standard\" of care. However, TURP can lead to urinary incontinence or permanent male infertility and may not be the ideal procedure for a certain subset of patients. [ 22 ]  For those reasons, a physician may recommend undergoing a treatment known as prostate artery embolization (PAE). [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2277", "text": "Patients typically go home the same day as the procedure and can expect to feel some symptom relief in a matter of days. Though rare, risks of PAE include unintentional embolization of nearby blood vessels, which can result in loss of blood flow to surrounding areas of the bladder or rectum. [ 22 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2278", "text": "Data suggests that TURP may have higher rates of symptom resolution at one and six months, but PAE appears to provide lower risks of complications more commonly associated with surgery, such as infection. [ 22 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2279", "text": "Kidney stones  can be present along any part of the course of the urinary tract from the kidneys to the urethra. The most common symptoms, whether in men or women, are sudden onset, intense flank pain accompanied by blood in the urine. Most kidney stones pass spontaneously, but larger ones (greater than 5\u00a0mm) are less likely to, and can cause severe pain or infection. [ 23 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2280", "text": "The interventional radiologist plays a large clinical role in the treatment of kidney stones that are unlikely to pass on their own. The gold standard of treatment for these types of stones is surgical removal. However, some patients have an infected stone and are simply too ill for an operative surgical removal. In these instances, the mainstay of IR treatment is a percutaneous nephrostomy tube. [ 24 ]  This is a procedure where a small caliber catheter is placed through the skin and into the urinary collecting system upstream of the stone. This procedure not only drains any infection, often bringing about a precipitous improvement in the patient's symptoms but also diverts urine\u2014thus giving the patient more time to recover before definitive surgical treatment. [ 25 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2281", "text": "A  varicocele  is defined as an enlargement of the veins within the scrotum, most commonly occurring on the left side due to anatomical reasons. When this happens, blood can stagnate within these dilated veins and cause temperature fluctuations within the testicle itself. The exact cause to this condition remains unknown and an ill-favored sequela can be male  infertility . [ 26 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2282", "text": "The mainstay of treatment for this condition within the field of interventional radiology is varicocele embolization. An embolization, within the context of this procedure, results in the interruption of venous blood flow. The interruption of blood flow abates venous dilation of blood that can lead to impaired testicular temperature regulation and theoretically improve infertility. [ 27 ]  The physician accesses the dilated scrotal veins with a small catheter via a vein in the groin and embolizes the varicocele. Patients often tolerate this procedure well and are able to return home the same day. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2283", "text": "About 87% of all strokes are  ischemic strokes , in which blood flow to the brain is blocked. [ 28 ]  A clot-busting medication such as  tissue plasminogen activator  (t-PA) can be used in a controlled hospital setting to dissolve the clot and help restore blood flow to the damaged area of the brain. Certain patients with an acute ischemic stroke may be candidates for endovascular therapy. [ 29 ]  Endovascular therapy is a procedure performed by neurointerventionalists to remove or dissolve the  thrombus  (clot) and restore blood flow to parts of the brain. Using a catheter that is directed through the blood vessels in the arm or leg up to the brain, the interventionalist can remove the thrombus or deliver drugs to dissolve the thrombus. [ 29 ]  These procedures are referred to as  mechanical thrombectomy  or  thrombolysis , and several factors are considered before the procedure is completed. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2284", "text": "People who may be eligible for endovascular treatment have a large vessel occlusion, which means the thrombus is in an artery that is large enough to reach and there are no contraindications such as a hemorrhagic stroke (bleeding in the brain), elapsed time of greater than six hours since onset of symptoms, or greater than 24 hours in special cases. Hospitals with comprehensive stroke centers are equipped to treat patients with endovascular care. [ 30 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2285", "text": "Long-term care after an ischemic stroke is focused on rehabilitation and preventing future blood clots using  anticoagulant  therapy. Patients work with specialists from fields such as  physical therapy ,  occupational therapy , and  speech therapy  to complete recovery. [ 31 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2286", "text": "Although there are no clearly defined recommendations on treatment of asymptomatic aneurysms, all symptomatic unruptured brain aneurysms should be treated. Endovascular therapy is an effective treatment for select cases. [ 32 ]  During this treatment, an interventional radiologist inserts a catheter into the patient's leg and uses it to guide a coil through blood vessels to the site of the aneurysm. The coil induces clotting within the aneurysm, which reduces the risk of rupture. Multiple coils may be used depending on the size. [ 33 ]  Imaging studies ( DSA ,  CTA , or  MRA ) help characterize the aneurysm to decide the best course of treatment, whether endovascular coiling or surgical clipping. Endovascular coiling is associated with a reduction in procedural morbidity and mortality over surgical. For cases of ruptured aneurysms, emergent treatment is based on the type of aneurysm, and may use a combination of techniques. Conservative therapy focuses on minimizing modifiable risk factors with blood pressure control and smoking cessation. [ 34 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2287", "text": "Arteriovenous malformations (AVMs) are abnormal blood vessel structures in which an artery connects to a vein via an abnormal channel. This creates a high flow system that puts the vessel at risk of rupture. Ruptured AVMs require emergency management of the patient; unruptured AVMs require expert consultation to discuss the risks and benefits of treatment. [ 35 ]  Current treatment options include conservative management, surgical resection,  stereotactic radiosurgery , endovascular embolization, or combinations of these treatments. [ 36 ]   Endovascular embolization  is a technique used by neurointerventionalists in which particles, glue, or coils are lodged inside the AVM to prevent blood flow through the abnormal channel. During this treatment, an interventional radiologist guides a catheter through a blood vessel accessed from the patient's leg to the site of the AVM. The particles, glue, or coils induce clotting within the malformation, which reduces the risk of rupture. [ 37 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2288", "text": "Utilizing image guidance,  local anesthetics  and/or long-acting steroid medications can be directly delivered to localized sites of pain.  The use of image guidance helps to confirm appropriate needle placement. [ 38 ]  This includes common imaging modalities used in joint injections:  ultrasound ,  fluoroscopy  and  computerized tomography  (CT)."}
{"_id": "WikiPedia_Radiology$$$corpus_2289", "text": "Vertebral augmentation , which includes vertebroplasty and kyphoplasty, are similar spinal procedures in which  bone cement  is injected through a small hole in the skin into a fractured  vertebra  to try to relieve  back pain  caused by a vertebral  compression fractures . It was found ineffective in treating  osteoporosis -related compression fractures of the spine. [ 53 ] [ 54 ]  The people in both the experimental and placebo groups reported improvement in their pain, suggesting that the benefit is related to the  placebo effect . As of 2019 [update] , routine use is thus not recommended. [ 55 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2290", "text": "Interventional oncology (IO) procedures are commonly applied to treat primary or  metastatic  cancer. IO treatments may be also offered in combination with surgery, systemic chemotherapy/immunotherapy, and radiation therapy to augment the therapeutic outcome. A variety of interventional oncological treatments for tumors arise:"}
{"_id": "WikiPedia_Radiology$$$corpus_2291", "text": "Vascular disease  refers to disorders of the vasculature or  circulatory system , most commonly involving the  arteries ,  veins  and  lymphatics . The symptoms related to vascular disease can range from asymptomatic, bothersome symptoms or limb- and/or life-threatening conditions."}
{"_id": "WikiPedia_Radiology$$$corpus_2292", "text": "Vascular and interventional radiologists are at the forefront of treating a wide variety of vascular diseases."}
{"_id": "WikiPedia_Radiology$$$corpus_2293", "text": "Since its development by  Charles Dotter  when he did a percutaneous peripheral vascular revascularization procedure for the first time on January 16, 1964, on Laura Shaw, vascular and interventional radiology (commonly interventional radiology or IR) distinguished itself from earlier approaches to vascular disease by the use of medical imaging to guide endovascular therapies (fixing this from inside the vessel). [ 75 ] [ 76 ]  The  Seldinger technique  is the basic principle that underlies endovascular procedures. Briefly, this involves using a needle to puncture a target vessel, then using a series of small medical guidewires and catheters to pass various tools inside for treatment. [ 77 ] [ 78 ]  When these minimally-invasive techniques can be used, patients avoid the need for larger surgical exposure to treat diseased vessels. Though numerous factors can affect patient's post-operative course, in general an endovascular approach is associated with a more rapid recovery time compared to a traditional open vascular surgery. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2294", "text": "Many endovascular procedures have since been developed and refined. Numerous tools are at the disposal of modern vascular and interventional radiologists to perform these procedures, and developing new tools is a burgeoning focus of international research."}
{"_id": "WikiPedia_Radiology$$$corpus_2295", "text": "While some interventional radiology endovascular procedures are highly specialized, a few standard techniques apply to most:"}
{"_id": "WikiPedia_Radiology$$$corpus_2296", "text": "The goal of endovascular therapy is to  revascularize  an affected or diseased vessel."}
{"_id": "WikiPedia_Radiology$$$corpus_2297", "text": "Arteries  are the component of the  circulatory system  that carry oxygenated blood away from the  heart  to the vital  organs  and  extremities . Arteries have relatively thick, muscular walls, composed of multiple layers, because they transport freshly oxygenated blood through the body at relatively high pressures. Arterial diseases can affect one or multiple layers of the artery wall."}
{"_id": "WikiPedia_Radiology$$$corpus_2298", "text": "The  aorta  is the largest artery in the body, and the major aortic branches continue to divide multiple times, giving way to smaller arteries, muscular  arterioles  and thin-walled  capillaries . In contrast to arteries, capillaries have thin single-layered walls, so oxygen and nutrients can be exchanged with tissues in capillary beds before the de-oxygenated blood is carried away by the venous system."}
{"_id": "WikiPedia_Radiology$$$corpus_2299", "text": "Perfusion  refers to the flow of oxygen and nutrient rich blood into the capillary beds of the muscles and organs, this is critical for their function. The lack of adequate perfusion is referred to as  ischemia  and is typically the cause of symptoms related to vascular disease. The goal of revascularization therapies, whether endovascular or surgical, is to re-establish or optimize perfusion and stop ischemia."}
{"_id": "WikiPedia_Radiology$$$corpus_2300", "text": "Atherosclerosis  refers to a progressive narrowing of the arteries due to  atheroma , derived from the Greek word for 'gruel, porridge'. Atheromatous plaque is a mixture of fat and inflammatory debris that sticks to the inner walls of an artery. Plaque can be soft or become firm as it accrues layers of calcium, a byproduct of chronic inflammation. Atherosclerosis has no single cause but many recognized risk factors. Some risk factors are modifiable, and others are not. Age and genetic predispositions are examples of non-modifiable risk factors. Medical management of atherosclerosis aims to address the many other known modifiable risk factors, such as smoking, diet, and exercise, as well as blood sugar levels in patients with diabetes. Using medications to control blood pressure and cholesterol have also been shown beneficial."}
{"_id": "WikiPedia_Radiology$$$corpus_2301", "text": "Atherosclerosis is described, evaluated, and treated differently depending on the affected artery, as described below. However, multiple studies have shown strong correlations between the different types of atherosclerosis. [ 85 ] [ 86 ] [ 87 ]  In particular, patients with peripheral arterial disease have an increased risk of coronary artery disease, and severe peripheral artery disease symptoms can be a predictor of cardiac-related mortality. The majority of patients begin to develop symptoms from ischemia around middle age, even though vessel narrowing can develop silently and slowly over decades. Unfortunately, sudden cardiac death or stroke can be a patient's first sign of vascular disease. Therefore, controlling risk factors is crucial in those with known atherosclerosis to prevent progression of disease, and screening is recommended by some vascular disease specialists for those at increased risk, such as those with diabetes, smoking or a strong family history of cardiovascular disease."}
{"_id": "WikiPedia_Radiology$$$corpus_2302", "text": "Screening tests typically use the non-invasive evaluation called the  ankle\u2013brachial index , which compares the blood pressure between the arm and the ankle. This can help detect narrowing in the major vessels of the chest, abdomen, pelvis, and legs. CT scans of the heart with evaluations of coronary artery calcium are also used in some instances to stratify risk of coronary artery disease."}
{"_id": "WikiPedia_Radiology$$$corpus_2303", "text": "Historically, open vascular surgical approaches were required for all critically advanced atherosclerotic disease. An  endarterectomy  is a large operation, where blood flow is temporarily stopped using clamps, the vessel is cut open, the plaque removed and then the vessel resealed. If an occlusion is too dense or complex, a bypass could also be performed, where two segments of vessel are bridged by an additional vein or synthetic graft.\nModern endovascular approaches to treating atherosclerosis can include combinations of angioplasty, stenting, and atherectomy (removal of plaque)."}
{"_id": "WikiPedia_Radiology$$$corpus_2304", "text": "There are several systems for staging PAD, but an often used scale is the revised Rutherford classification. [ 75 ] [ 88 ]  Plaque and blood flow can be evaluated using  ultrasound ,  CT angiography , MR angiography, and catheter-based angiography to establish anatomic segments of disease. The severity of ischemia can be evaluated by correlating symptoms and non-invasive physiologic vascular studies including toe pressures, TCPO2, and skin perfusion studies."}
{"_id": "WikiPedia_Radiology$$$corpus_2305", "text": "Certain monitored exercises, such as walking regimens, have been shown to significantly improve walking distance especially when used consistently for at least six months. When medical management fails, vascular interventional radiologists can attempt to restore blood flow to extremities using angioplasty and stenting. Sometimes repeat interventions are required. The goal of therapy is to maintain perfusion, avoid amputation and preserve the limb structure and function."}
{"_id": "WikiPedia_Radiology$$$corpus_2306", "text": "Aneurysm  refers to pathologic dilation of an artery to greater than 1.5 times its normal size.  True vascular aneurysms are due to degenerative processes in the wall of the artery. Aneurysms can be solitary or multiple and are sometimes found in association with various clinical syndromes, including forms of vasculitis or connective tissue diseases. Aneurysms are typically classified by major shapes, either fusiform (tubular) or saccular (eccentric).  Ectasia  is another broad term for an enlarged vessel, but is not necessarily pathological. Rupture is a dreaded complication of aneurysms that can lead to extensive, difficult to control bleeding. Aneurysms can also clot, or  thrombose , and rapidly occlude the involved vessel, leading to acute distal ischemia."}
{"_id": "WikiPedia_Radiology$$$corpus_2307", "text": "A variety of endovascular grafts are available, and each has advantages and disadvantages depending on the characteristics of the aneurysm and patient. [ 89 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2308", "text": "Dissection refers to a tear in the inner layer of the arterial wall. Blood pumps into this defect and dissects its way between the layers in the wall of an artery, creating a false channel separate from the true arterial lumen. Dissections can develop due to trauma, spontaneously due to high blood pressure and native vascular disease, or in some cases as a complication of prior surgical or endovascular treatment."}
{"_id": "WikiPedia_Radiology$$$corpus_2309", "text": "When an arterial dissection expands, it can restrict normal flow through the affected artery or potentially block the origin of a branch vessel\u2014this can compromise distal perfusion in either case. When acute and symptomatic, this is an emergency that requires prompt treatment."}
{"_id": "WikiPedia_Radiology$$$corpus_2310", "text": "However, as medical imaging has improved, chronic, asymptomatic dissections have also been discovered, and in some cases these may be safely managed with blood pressure control, follow-up imaging and proper counseling for the warning signs of potential ischemia."}
{"_id": "WikiPedia_Radiology$$$corpus_2311", "text": "Dissections can occur in any artery and are named for their vessel of origin.  Aortic dissections  can be further classified and treated depending on whether they involve the thoracic aorta, the abdominal aorta or both. Classic pain related to acute aortic dissections is described as \"tearing\" or \"ripping\" and possibly radiating to a patient's back. Acute aortic dissection can be difficult to diagnose but is more common than aortic aneurysm rupture."}
{"_id": "WikiPedia_Radiology$$$corpus_2312", "text": "Thoracic aortic dissections are further characterized with the Stanford classification. [ 92 ]  Type A dissections involve the root and ascending aorta. These require prompt treatment, which currently is mostly surgical in nature.  Type B dissections begin in the distal aortic arch beyond the left subclavian artery origin, and may often be addressed with pain medication and blood pressure control. If the type B aortic dissection results in poor circulation to the intestines, kidneys or legs it often requires urgent endovascular repair with endografts and/or fenestrations. If a type B aortic dissection has ruptured, or has features that indicate impending rupture, they are urgently repaired too."}
{"_id": "WikiPedia_Radiology$$$corpus_2313", "text": "Dissections can also arise in virtually any other artery. Carotid artery dissection, for example, places patients at increased risk for stroke and may extend further into the blood vessels within the brain.  Vertebral artery dissection  are less common but also dangerous for similar reasons. Mesenteric artery dissection may limit the blood supply to the intestines. Renal artery dissections can decrease blood flow to the kidneys and contribute to hypertension. [ 93 ]  Peripheral arterial dissections can be found elsewhere in the arms and legs. These dissections can occur primarily due to focal traumas, underlying vascular disease, or as an extension of a larger, complex aortic dissection that tears further into these smaller branches."}
{"_id": "WikiPedia_Radiology$$$corpus_2314", "text": "Treatment of dissections depends on several factors, including the location, extent, how long it has been developing (acute or chronic) and whether it is limiting perfusion. Surgical approaches to dissections can include reconstructing the aorta, surgical bypass and surgical fenestration.  Like other arterial disorders, endovascular approaches to dissection such as stent-grafting [ 94 ]  and percutaneous fenestration [ 95 ]  can be utilized, either primarily or in combination with surgery depending on the complexity of the dissection."}
{"_id": "WikiPedia_Radiology$$$corpus_2315", "text": "Penetrating aortic ulcer (PAU) is an advanced focal form of atherosclerosis, most often encountered in the aorta. [ 96 ]  It starts as a small plaque in the inner-most layer of the aorta called the intima, but the inflammatory process ulcerates and penetrates through this layer into the media. While PAU is considered a distinct entity, many think this is a precursor lesion to dissection or aneurysm. [ citation needed ]  Along with intramural hematoma, aneurysm and dissection, PAU is recognized as one of several  acute aortic syndromes \u2014a spectrum of related conditions correlated to potential aortic rupture. They thus have a high potential morbidity and mortality, and should at least be followed closely."}
{"_id": "WikiPedia_Radiology$$$corpus_2316", "text": "Acute or active bleeding can occur throughout the human body due to a variety of causes. Interventional radiologists can address bleeding with embolization, usually with small plastic particles, glues or coils. Traumatic rupture of a blood vessel, for example, may be addressed this way if a patient is at risk of fatal bleeding. This has revolutionized medicine and interventional radiologists commonly treat refractory nose bleeds, excessive coughing of blood, intestinal bleeding, post-pregnancy bleeding, spontaneous intra-abdominal on intra-thoracic bleeding, bleeding related to trauma and post-surgical bleeding. In some instances where severe bleeding is anticipated, such as in complex surgery or the excision of a highly vascular tumor, interventional radiologists may embolize certain target blood vessels prior to the operation to prevent major blood loss."}
{"_id": "WikiPedia_Radiology$$$corpus_2317", "text": "Transplant organs rely on healthy blood supply to survive. In some instances, the arteries that feed a transplant may narrow, typically where the donor vessel is sewn to the recipient. Interventional radiologists evaluate the blood supply of these patient's and may use balloons or stents to open narrowed vessels and keep the transplant organ functional."}
{"_id": "WikiPedia_Radiology$$$corpus_2318", "text": "The  veins  of the human body are responsible for returning de-oxygenated blood back to the heart. Like a rock rolling down a hill, blood flows from the highest pressure (the blood in the aorta) to the lower venous pressure (the blood in the vena cava as it empties back to the heart.) Unlike arteries, veins are thin walled and distensible, allowing them to accommodate large volumes of blood without significant changes in pressure. In fact, the venous system is so low pressure that veins have valves to keep blood from flowing backward. The motion of the human body helps pump blood through the veins\u2014squeezing leg muscles while walking, for instance, helps push venous blood back up to the heart against the pull of gravity. Unfortunately, without this extra push some blood can sit stagnant in veins, leading to a multitude of clinical problems. The largest vein in the body is the vena cava. The superior vena cava (SVC) drains blood from the top half of the body while the inferior vena cava (IVC) drains blood from below the diaphragm. Elsewhere in the body, veins can be categorized into superficial, primarily associated with the skin and soft tissues, or deep veins, which drain muscles and organs."}
{"_id": "WikiPedia_Radiology$$$corpus_2319", "text": "Chronic kidney disease  (CKD or chronic renal disease) is a condition in which there is a progressive loss of kidney function. It has numerous recognized causes and risk factors. CKD affects approximately 14% of the world population, and over 600,000 people in the United States alone.  There are five recognized stages of CKD; the fifth stage is also called end-stage renal disease (ESRD) and invariably requires some form of  renal replacement therapy ."}
{"_id": "WikiPedia_Radiology$$$corpus_2320", "text": "Around the turn of the 20th century, breakthroughs in understanding of renal physiology led many to believe that dialysis using  artificial kidneys  was a potential cure for renal disease. Over 100 years later, the only available curative, renal replacement therapy for CKD is kidney transplantation. However, many patients can live for decades utilizing dialysis."}
{"_id": "WikiPedia_Radiology$$$corpus_2321", "text": "Dialyzer technology initially outpaced the ability of clinicians to apply it to patients. In the 1920s, the first dialysis catheter was created using thin fragile glass tubes. Early methods required surgical incision to reach large vessels, which carried a large risk of major bleeding. The first somewhat permanent, reliable dialysis access, the  Scribner Teflon shunt , was invented nearly 40 years later and allowed a patient with  kidney failure  to survive 11 more years. As medicine and surgery have grown more sophisticated, more patients now live with chronic renal disease than ever before. The most common type of dialysis in the United States is hemodialysis, which can be performed through several types of vascular access. The arteriovenous fistula (AVF) is the preferred method.  Arteriovenous fistula are created surgically by directly connecting an artery and a vein, most commonly in the arm. An arteriovenous graft (AVG) relies on the same principle but bridges the gap between the artery and vein with a medical-grade prosthetic shunt. Over time, altered flow mechanics can result in changes within the involved vessels.  Vascular narrowing, thrombosis, aneurysms and pseudoaneurysms are commonly encountered complications over the life of an AVF or AVG. Interventional radiologists can use angiography to evaluate these structures (commonly called a istulogram) and treat dysfunctional access with angioplasty, stenting, and thrombectomy. Most patients require regular evaluation and treatment to keep their access working.  When possible, AVFs are preferred to AVGs due to their relatively lower complication rate and longer patency. The Fistula First initiative works to promote physician and patient awareness about the benefits of first attempting hemodialysis through a fistula. [ 97 ]   There are a few devices (endo AVF) that are being utilized by interventional radiologists to percutaneously create fistulas in a minimally invasive fashion."}
{"_id": "WikiPedia_Radiology$$$corpus_2322", "text": "Dialysis catheters include temporary and tunneled large-bore central venous access lines placed for administering hemodialysis. When possible, these catheters are placed in the right internal jugular vein, but the left internal jugular and femoral veins may also be utilized. Temporary dialysis lines may be placed when patients are hospitalized and either too sick or at a high risk of bleeding. Permanent hemodialysis catheters are longer overall but a segment is tunneled through the skin of the chest, which lets the catheter lie flat and lowers the risk of infection."}
{"_id": "WikiPedia_Radiology$$$corpus_2323", "text": "Central venous access refers to a variety of intravenous catheters placed in patients requiring certain long-term medications. These are much smaller in diameter than dialysis lines, but are larger and longer than a standard intravenous line (IV.) Examples include Hickman catheters, peripherally inserted central cathethers (or PICCs), tunneled small bore central venous catheters, and mediports. These lines differ in where they are inserted but are all placed under imaging guidance and adjusted so the end of the catheter sits in the vena cava adjacent to the heart. These catheters are designed to deliver strong medications, such as chemotherapy or prolonged courses of antibiotics, which are either dosed too frequently to keep placing new IVs or are too irritating to small veins be injected through a standard IV."}
{"_id": "WikiPedia_Radiology$$$corpus_2324", "text": "Angioplasty , also known as  balloon angioplasty  and  percutaneous transluminal angioplasty  ( PTA ), is a  minimally invasive   endovascular   procedure  used to widen narrowed or obstructed arteries or veins, typically to treat arterial  atherosclerosis . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2325", "text": "A deflated balloon attached to a catheter (a  balloon catheter ) is passed over a guide-wire into the  narrowed   vessel  and then inflated to a fixed size. [ 1 ]  The balloon forces expansion of the blood vessel and the surrounding muscular wall, allowing an improved blood flow. [ 1 ]  A  stent  may be inserted at the time of ballooning to ensure the vessel remains open, and the balloon is then deflated and withdrawn. [ 2 ]  Angioplasty has come to include all manner of  vascular  interventions that are typically performed  percutaneously ."}
{"_id": "WikiPedia_Radiology$$$corpus_2326", "text": "A coronary angioplasty is a therapeutic procedure to treat the  stenotic  (narrowed)  coronary arteries  of the  heart  found in  coronary heart disease . [ 1 ]  These stenotic segments of the coronary arteries arise due to the buildup of  cholesterol -laden  plaques  that form in a condition known as  atherosclerosis . [ 3 ]   A  percutaneous coronary intervention  (PCI), or coronary angioplasty with stenting, is a non-surgical procedure used to improve the blood flow to the heart. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2327", "text": "Coronary angioplasty is indicated for coronary artery diseases such as  unstable angina ,  NSTEMI ,  STEMI  and spontaneous coronary artery perforation. [ 1 ]  PCI for stable coronary disease has been shown to significantly relieve symptoms such as  angina , or chest pain, thereby improving functional limitations and quality of life. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2328", "text": "Peripheral angioplasty refers to the use of a balloon to open a blood vessel outside the coronary arteries.  It is most commonly done to treat  atherosclerotic  narrowings of the abdomen, leg and  renal  arteries caused by  peripheral artery disease . Often, peripheral angioplasty is used in conjunction with guide wire, peripheral  stenting  and an  atherectomy . [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2329", "text": "Angioplasty can be used to treat advanced  peripheral artery disease  to relieve the  claudication , or leg pain, that is classically associated with the condition. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2330", "text": "The bypass versus angioplasty in severe ischemia of the leg (BASIL) trial investigated infrainguinal  bypass surgery  first compared to angioplasty first in select patients with severe lower limb ischemia who were candidates for either procedure. The BASIL trial found that angioplasty was associated with less short term morbidity compared with bypass surgery, however long term outcomes favor bypass surgery. [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2331", "text": "Based on the BASIL trial, the ACCF/AHA guidelines recommend balloon angioplasty only for patients with a life expectancy of 2 years or less or those who do not have an  autogenous vein  available. For patients with a life expectancy greater than 2 of years life, or who have an autogenous vein, a bypass surgery could be performed first. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2332", "text": "Renal artery stenosis  is associated with  hypertension  and loss of  renal function . [ 9 ]  Atherosclerotic obstruction of the  renal artery  can be treated with angioplasty with or without  stenting  of the renal artery. [ 10 ]  There is a weak recommendation for renal artery angioplasty in patients with renal artery stenosis and flash edema or congestive heart failure. [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2333", "text": "Carotid artery stenosis  can be treated with angioplasty and  carotid stenting  for patients at high risk for undergoing  carotid endarterectomy  (CEA). [ 11 ]   Although carotid endarterectomy is typically preferred over carotid artery stenting, stenting is indicated in select patients with radiation-induced stenosis or a carotid lesion not suitable for surgery. [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2334", "text": "Angioplasty is used to treat venous stenosis affecting  dialysis  access, with drug-coated balloon angioplasty proving to have better 6 month and 12 month patency than conventional balloon angioplasty. [ 13 ]  Angioplasty is occasionally used to treat residual  subclavian vein  stenosis following  decompression surgery  for  thoracic outlet syndrome . [ 14 ]  There is a weak recommendation for deep venous stenting to treat obstructive chronic venous disease. [ 15 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2335", "text": "Angioplasty requires an access vessel, typically the  femoral  or  radial artery  or  femoral vein , to permit access to the vascular system for the wires and  catheters  used. If no access vessel of sufficient size and quality is available, angioplasty is contraindicated. A small vessel diameter, the presence of posterior calcification, occlusion, hematoma, or an earlier placement of a  bypass origin , may make access to the vascular system too difficult. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2336", "text": "Percutaneous transluminal coronary angioplasty (PTCA) is contraindicated in patients with left main coronary artery disease, due to the risk of spasm of the left main coronary artery during the procedure. [ 16 ]  Also, PTCA is not recommended if there is less than 70% stenosis of the coronary arteries, as the stenosis it is not deemed to be hemodynamically significant below this level. [ 16 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2337", "text": "Access to the vascular system is typically gained  percutaneously  (through the skin, without a large surgical incision). An  introducer sheath  is inserted into the blood vessel via the  Seldinger technique . [ 17 ]   Fluoroscopic guidance  uses magnetic resonance or X-ray fluoroscopy and  radiopaque   contrast dye  to guide angled wires and  catheters  to the region of the body to be treated in real time. [ 18 ]  Tapered guidewire is chosen for small occlusion, followed by intermediate type guidewires for tortuous arteries and difficulty passing through extremely narrow channels, and stiff wires for hard, dense, and blunt occlusions. [ 19 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2338", "text": "To treat a narrowing in a blood vessel, a wire is passed through the  stenosis  in the vessel and a  balloon on a catheter  is passed over the wire and into the desired position. [ 20 ]  The positioning is verified by fluoroscopy and the balloon is inflated using water mixed with contrast dye to 75 to 500 times normal  blood pressure  (6 to 20 atmospheres), with most coronary angioplasties requiring less than 10 atmospheres. [ 21 ]  A  stent  may or may not also be placed."}
{"_id": "WikiPedia_Radiology$$$corpus_2339", "text": "At the conclusion of the procedure, the balloons, wires and catheters are removed and the vessel puncture site is treated either with direct pressure or a  vascular closure device . [ 22 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2340", "text": "Transradial artery access (TRA) and transfemoral artery access (TFA) are two techniques for percutaneous coronary intervention. [ 23 ]  TRA is the technique of choice for management of acute coronary syndrome (ACS) as it has significantly lower incidence of bleeding and vascular complications compared with the TFA approach. [ 23 ]  TRA also has a mortality benefit for high risk ACS patients and high risk bleeding patients. [ 23 ]  TRA was also found to yield improved quality of life, as well as decreased healthcare costs and resources. [ 23 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2341", "text": "Relative to  surgery , angioplasty is a lower-risk option for the treatment of the conditions for which it is used, but there are unique and potentially dangerous risks and complications associated with angioplasty:"}
{"_id": "WikiPedia_Radiology$$$corpus_2342", "text": "Angioplasty may also provide a less durable treatment for atherosclerosis and be more prone to  restenosis  relative to  vascular bypass  or  coronary artery bypass grafting . [ 28 ]  Drug-eluting balloon angioplasty has significantly less restenosis, late lumen loss and target lesion revascularization at both short term and midterm follow-up compared to uncoated balloon angioplasty for femoropopliteal arterial occlusive disease. [ 29 ]   Although angioplasty of the femoropopliteal artery with paclitaxel-coated stents and balloons significantly reduces rates of vessel restenosis and target lesion revascularization, it was also found to have increased risk of death. [ 30 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2343", "text": "After angioplasty, most patients are monitored overnight in the hospital, but if there are no complications, patients are sent home the following day. [ 26 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2344", "text": "The catheter site is checked for bleeding and swelling and the heart rate and blood pressure are monitored to detect late rupture and hemorrhage. [ 26 ]  Post-procedure protocol also involves monitoring urinary output, cardiac symptoms, pain and other signs of systemic problems. [ 26 ]  Usually, patients receive medication that will relax them to protect the arteries against  spasms . Patients are typically able to walk within two to six hours following the procedure and return to their normal routine by the following week. [ 31 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2345", "text": "Angioplasty recovery consists of avoiding physical activity for several days after the procedure. Patients are advised to avoid heavy lifting and strenuous activities for a week. [ 32 ] [ 33 ]  Patients will need to avoid physical stress or prolonged sport activities for a maximum of two weeks after a delicate balloon angioplasty. [ 34 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2346", "text": "After the initial two week recovery phase, most angioplasty patients can begin to safely return to low-level exercise. A graduated exercise program is recommended whereby patients initially perform several short bouts of exercise each day, progressively increasing to one or two longer bouts of exercise. [ 35 ]   As a precaution, all structured exercise should be cleared by a cardiologist before commencing. Exercise-based rehabilitation following percutaneous coronary intervention has shown improvement in recurrent angina, total exercise time, ST-segment decline, and maximum exercise tolerance. [ 36 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2347", "text": "Patients who experience swelling, bleeding or pain at the insertion site, develop  fever , feel faint or weak, notice a change in temperature or color in the arm or leg that was used or have  shortness of breath  or chest pain should immediately seek medical advice."}
{"_id": "WikiPedia_Radiology$$$corpus_2348", "text": "Patients with stents are usually prescribed dual antiplatelet therapy (DAPT) which consists of a  P2Y12 inhibitor , such as  clopidogrel , which is taken at the same time as  acetylsalicylic acid  (aspirin). [ 37 ]  Dual antiplatelet therapy (DAPT) is recommended for 1 month following bare metal stent placement, for 3 months following a second generation drug-eluting stent placement, and for 6\u201312 months following a first generation  drug-eluting stent  placement. [ 1 ]  DAPT's antiplatelet properties are intended to prevent blood clots, however they also increase the risk of bleeding, so it is important to consider each patient's preferences, cardiac conditions, and bleeding risk when determining the duration of DAPT treatment. [ 37 ]  Another important consideration is that concomitant use of  Clopidogrel  and  Proton Pump Inhibitors  following coronary angiography is associated with significantly higher adverse cardiovascular complications such as major adverse cardiovascular events (MACE), stent thrombosis and myocardial infarction. [ 38 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2349", "text": "Angioplasty was first described by the US  interventional radiologist   Charles Dotter  in 1964. [ 39 ]  Dotter pioneered modern medicine with the invention of angioplasty and the catheter-delivered stent, which were first used to treat peripheral arterial disease. On January 16, 1964, Dotter percutaneously dilated a tight, localized stenosis of the  subsartorial artery  in an 82-year-old woman with painful leg ischemia and gangrene who refused leg amputation. After successful dilation of the stenosis with a guide wire and coaxial Teflon catheters, the circulation returned to her leg. The dilated artery stayed open until her death from pneumonia two and a half years later. [ 40 ]  Charles Dotter is commonly known as the \"Father of  Interventional Radiology \" and was nominated for the  Nobel Prize  in medicine in 1978."}
{"_id": "WikiPedia_Radiology$$$corpus_2350", "text": "The first percutaneous coronary angioplasty on an awake patient was performed in Zurich by the German cardiologist  Andreas Gruentzig  on September 16, 1977. [ 41 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2351", "text": "The first percutaneous coronary angioplasties in the United States were performed on the same day (March 1, 1978) by Simon H. Stertzer at Lenox Hill Hospital in New York and Richard K. Myler at St. Mary's Hospital in San Francisco. During the previous year, also at St. Mary's Hospital in San Francisco, Myler and Gruentzig had performed dilatations in the setting of bypass surgery to test the catheter concept before Gruentzig performed the first PTCA in his catheterization lab in Zurich."}
{"_id": "WikiPedia_Radiology$$$corpus_2352", "text": "The initial form of angioplasty was 'plain old balloon angioplasty' (POBA) without stenting, until the invention of bare metal stenting in the mid-1980s to prevent the abrupt closure sometimes seen with POBA. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2353", "text": "Bare metal stents were found to cause in-stent restenosis as a result of  neointimal hyperplasia  and stent thrombosis, which led to the invention of drug-eluting stents with anti-proliferative drugs to combat in-stent restenosis. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2354", "text": "The first coronary angioplasty with a drug delivery stent system was performed by Stertzer and Luis de la Fuente, at the Instituto Argentino de Diagn\u00f3stico y Tratamiento (English: Argentina Institute of Diagnosis and Treatment [ 42 ] ) in Buenos Aires, in 1999."}
{"_id": "WikiPedia_Radiology$$$corpus_2355", "text": "Ingemar Henry Lundquist  invented the over-the-wire balloon catheter that is now used in the majority of angioplasty procedures in the world. [ 43 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2356", "text": "A subset of angioplasty, known as excimer laser coronary angioplasty (ELCA), uses  excimer lasers  to remove small amounts of tissue, including undilatable and uncrossable lesions, in the artery in order to allow the balloon to more effectively compress plaque into the artery walls. [ 44 ]  Such work was first developed in 1984 following earlier work in 1980\u20131983, when  Rangaswamy Srinivasan ,  Samuel Blum  and  James J. Wynne  at  IBM 's  T. J. Watson Research Center  observed the effect of the ultraviolet excimer laser on biological materials. Intrigued, they investigated further, finding that the laser made clean, precise cuts that would be ideal for delicate surgeries.  This resulted in a fundamental patent [ 45 ]  and Srinivasan, Blum and Wynne were elected to the  National Inventors Hall of Fame  in 2002. In 2012, the team members were honored with  National Medal of Technology and Innovation  by the  President   Barack Obama  for their work related to the excimer laser. [ 46 ]  Robert Ginsburg deployed the first used of ELCA in 1984 on a patient with severe stenosis of the deep femoral artery and a threatened limb. [ 47 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2357", "text": "An  angiosome  is a three-dimensional unit of  skin  and  underlying tissues  vascularized by a source  artery , termed an  arteriosome  and drained by a vein termed a  venosome . It is a concept that is used by  plastic surgeons , and other medical disciplines like CMF,  ENT , etc., for the design and harvesting of  free flap  transplants (e.g. fibula free-flap transplant [ 1 ] ), and by  vascular surgeons  and  interventional radiologists  for the  endovascular treatment  of critical  limb ischemia .  It is an alternative model to the traditional \"best vessel\" model. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2358", "text": "An example is the angiosome of the  fibular artery  (also called the  peroneal artery ), that primarily vascularizes the skin of the distal two-thirds of the  lateral-posterior  aspect of the leg. Furthermore, also the underlying  fibula bone  and parts of the local muscles, like the  flexor hallucis longus muscle ."}
{"_id": "WikiPedia_Radiology$$$corpus_2359", "text": "Small arteries, called  arterial perforators , branch off from the larger arteries below the deep body  fascia . These arterial perforators penetrate the deep body fascia in their course towards the skin and further ramify in the  subcutaneous tissue . A three-dimensional unit of tissue, only encompassing skin and the subcutaneous tissue \u2013 but not the tissue from below the body fascia (like muscle and bone) \u2013 primarily supplied by a dominant arterial perforator, is called a  perforasome . Although multiple other arterial perforators may also supply this unit of tissue with arterial blood, it is the dominant arterial perforator that is essential for the survival of the perforasome."}
{"_id": "WikiPedia_Radiology$$$corpus_2360", "text": "Arterial perforators can be further defined by their path, in three categories: direct-cutaneous perforator, septo-cutaneous perforator and musculo-cutaneous perforator, depending on what anatomical structure the perforator progresses through, after branching from the deep source artery."}
{"_id": "WikiPedia_Radiology$$$corpus_2361", "text": "Therefore, generally speaking, one \u201cbig\u201d angiosome can contain multiple \u201csmaller\u201d perforasomes."}
{"_id": "WikiPedia_Radiology$$$corpus_2362", "text": "Atherectomy  is a  minimally invasive  technique for removing  atherosclerosis  from blood vessels within the body. It is an alternative to  angioplasty  for the treatment of  peripheral artery disease , but the studies that exist are not adequate to determine whether it is superior to angioplasty. [ 1 ]  It has also been used to treat  coronary artery disease , albeit without evidence of superiority to angioplasty. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2363", "text": "Atherectomy is used to treat  narrowing  in  arteries  caused by  peripheral artery disease  and  coronary artery disease . [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2364", "text": "The use of atherectomy instead of or in addition to angioplasty remains an area of controversy, as atherectomy typically involves the use of more costly disposable devices, and clear evidence to justify its use is lacking. [ 1 ]  Atherectomy has high physician reimbursement relative to angioplasty alone. [ 3 ]  According to the New York Times, \u2018Medical device makers have bankrolled a cottage industry of doctors and clinics that perform artery-clearing procedures that can lead to amputations.\u2019 [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2365", "text": "Unlike  angioplasty  and  stents , which push plaque into the vessel wall, atherectomy cuts plaque from the wall of the artery. While atherectomy is usually employed to treat  arteries  it can be used in  veins  and  vascular bypass  grafts as well."}
{"_id": "WikiPedia_Radiology$$$corpus_2366", "text": "Atherectomy falls under the general category of  percutaneous   revascularization , which implies re-canalizing blocked vasculature via a needle puncture in the skin. The most common access point is near the groin through the  common femoral artery  (CFA). Other common places are the  brachial artery ,  radial artery ,  popliteal artery ,  dorsalis pedis , and others."}
{"_id": "WikiPedia_Radiology$$$corpus_2367", "text": "There are four types of atherectomy devices: orbital, rotational, laser, and directional."}
{"_id": "WikiPedia_Radiology$$$corpus_2368", "text": "The decision to use which type of device is made by the interventionist, based on a number of factors. They include the type of lesion being treated, the physician's experience with each device, and interpretation of the devices' risks and effectiveness, based on a review of the medical literature."}
{"_id": "WikiPedia_Radiology$$$corpus_2369", "text": "Directional atherectomy is an intravascular procedure guided by  optical coherence tomography  termed as  lumivascular atherectomy . [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2370", "text": "Balloon-occluded retrograde transvenous obliteration  ( BRTO ) is an  endovascular procedure  used for the treatment of  gastric varices . When performing the procedure, an  interventional radiologist  accesses blood vessels using a catheter, inflates a balloon (e.g. balloon occlusion) and injects a substance into the variceal blood vessels that causes blockage of those vessels. To prevent the flow of the agent out of the intended site (variceal blood vessels), a balloon is inflated during the procedure, which occludes."}
{"_id": "WikiPedia_Radiology$$$corpus_2371", "text": "BRTO is used for the treatment of bleeding from gastric varices. In addition to  transjugular intrahepatic portosystemic shunt  (TIPS), BRTO is a first line treatment for the prevention of recurrent bleeding from gastric varices (GOV2 or IGV1). [ 1 ]  BRTO may be used for the treatment of ectopic varices. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2372", "text": "As BRTO results in a blockage of a portosystemic shunt, the procedure may result in increased portal hypertension, which may worsen esophageal varices or ascites. [ 2 ] [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2373", "text": "BRTO was developed as a procedure in the early 1990s. [ 2 ]  Initially, the procedure was performed using  ethanolamine oleate  as a sclerosant. [ 2 ] [ 3 ]  Between 2006 and 2007, American physicians began using  sodium tetradecyl sulfate  (3% STS) as an alternative sclerosing agent. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2374", "text": "Suvro Banerjee  is a consultant interventional  cardiologist , practicing in  Kolkata . He has worked at various hospitals in the  United Kingdom , and is a Fellow of the  Royal College of Physicians  of  London  as well as  Edinburgh . His procedural skills, among others, include coronary and peripheral  angioplasty ,  pacemaker , ICD and CRT implantation. He is the first doctor in Kolkata to successfully use the  ICD  which is the  Implantable Carvioverter Defibrillatorto  to treat a patient's abnormal heart rhythm. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2375", "text": "Banerjee is a clinical examiner for the MRCP (UK) examinations in  India . He is also a postgraduate teacher in  Indira Gandhi Open University  (IGNOU). He was the Steering Committee member for The Indian Consensus Guidance on Stroke Prevention in Atrial Fibrillation (2015) and Joint Convener for the Cardiological Society of India (CSI) Guideline Committee position statement on the management of heart failure (2017). He is a member of the Editorial Advisory Board for Indian Heart Journal Interventions. Currently, he is the Overseas Regional Adviser for East Region of India and West Bengal. [ 3 ]  He has also been involved as Principal Investigator in epidemiological studies with  University of Calgary ,  Canada  and Coventry & Warwickshire NHS Trust, UK. His work on the \"Prevalence, awareness and control of hypertension in the slums of Kolkata\" was carried out in collaboration with Kolkata Municipal Corporation. He has been conferred the fellowship of European Society of Cardiology and the American College of Cardiology. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2376", "text": "He was the Honorary Treasurer of West Bengal Academy of Echocardiography, a post which he has held since 2013. Additionally, he was the Secretary of the Cardiological Society of India, West Bengal Branch (2017-2018)."}
{"_id": "WikiPedia_Radiology$$$corpus_2377", "text": "For his philanthropic and social work, Dr. Banerjee was recognized by Rotary International as a Paul Harris Fellow in 2004. [ 5 ]  He regularly contributes to newspapers on matters of health and heart related diseases. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2378", "text": "A  biopsy  is a  medical test  commonly performed by a  surgeon ,  an interventional radiologist , or an  interventional cardiologist . The process involves the extraction of  sample   cells  or  tissues  for examination to determine the presence or extent of a disease. The tissue is then  fixed, dehydrated, embedded, sectioned, stained and mounted [ 1 ]  before it is generally examined under a  microscope  by a  pathologist ; it may also be analyzed chemically. When an entire lump or suspicious area is removed, the procedure is called an  excisional biopsy . An  incisional biopsy  or  core biopsy  samples a portion of the abnormal tissue without attempting to remove the entire lesion or tumor. When a sample of tissue or fluid is removed with a needle in such a way that cells are removed without preserving the histological architecture of the tissue cells, the procedure is called a  needle aspiration biopsy . Biopsies are most commonly performed for insight into possible  cancerous  or inflammatory conditions."}
{"_id": "WikiPedia_Radiology$$$corpus_2379", "text": "The  Arab  physician  Abulcasis  (1013\u20131107) developed one of the earliest diagnostic biopsies. He used a needle to puncture the  thyroid  and then characterized many types of  goiter . [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2380", "text": "The term  biopsy  reflects the  Greek  words  \u03b2\u03af\u03bf\u03c2   bios , \"life,\" and  \u1f44\u03c8\u03b9\u03c2   opsis , \"a sight.\" [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2381", "text": "The French dermatologist  Ernest Besnier  introduced the word  biopsie  to the medical community in 1879. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2382", "text": "When cancer is suspected, a variety of biopsy techniques can be applied. An  excisional biopsy  is an attempt to remove an entire lesion. When the specimen is evaluated, in addition to diagnosis, the amount of uninvolved tissue around the lesion, the  surgical margin  of the specimen is examined to see if the disease has spread beyond the area biopsied. \"Clear margins\" or \"negative margins\" means that no disease was found at the edges of the biopsy specimen. \"Positive margins\" means that disease was found, and a wider excision may be needed, depending on the diagnosis. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2383", "text": "When intact removal is not indicated for a variety of reasons, a wedge of tissue may be taken in an  incisional biopsy . In some cases, a sample can be collected by devices that \"bite\" a sample. A variety of sizes of needles can collect tissue in the lumen ( core biopsy ). Smaller diameter needles collect cells and cell clusters,  fine needle aspiration biopsy . [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2384", "text": "Pathologic  examination of a biopsy can determine whether a lesion is  benign  or  malignant , and can help differentiate between different types of cancer. In contrast to a biopsy that merely samples a lesion, a larger excisional specimen called a resection may come to a pathologist, typically from a surgeon attempting to eradicate a known lesion from a patient. For example, a pathologist would examine a  mastectomy  specimen, even if a previous nonexcisional breast biopsy had already established the diagnosis of breast cancer. Examination of the full mastectomy specimen would confirm the exact nature of the cancer (subclassification of tumor and histologic \"grading\") and reveal the extent of its spread ( pathologic \"staging\" )."}
{"_id": "WikiPedia_Radiology$$$corpus_2385", "text": "There are two types of liquid biopsy (which is not really a biopsy as they are blood tests that do not require a biopsy of tissue): circulating tumor cell assays or cell-free circulating tumor DNA tests. [ 7 ]  These methods provide a non-invasive alternative to repeat invasive biopsies to monitor cancer treatment, [ 8 ]  test available drugs against the circulating tumor cells, [ 9 ]  evaluate the mutations in cancer and plan individualized treatments. In addition, because cancer is a heterogeneous genetic disease, and excisional biopsies provide only a snapshot in time of some of the rapid, dynamic genetic changes occurring in tumors, liquid biopsies provide some advantages over tissue biopsy-based genomic testing. [ 10 ]  In addition, excisional biopsies are invasive, cannot be used repeatedly, and are ineffective in understanding the dynamics of tumor progression and metastasis. [ 11 ] [ 12 ]  By detecting, quantifying and characterisation vital circulating tumor cells or genomic alterations in CTCs and cell-free DNA in blood, liquid biopsy can provide real-time information on the stage of tumor progression, treatment effectiveness, and cancer metastasis risk. [ 13 ]  This technological development could make it possible to diagnose and manage cancer from repeated blood tests rather than from a traditional biopsy. [ 13 ] [ 14 ] [ 15 ] [ 16 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2386", "text": "Circulating tumor cell tests are already available but not covered by insurance yet at  maintrac  and under development by many pharmaceutical companies. Those tests analyze  circulating tumor cells  (CTCs) [ 14 ] [ 17 ]  Analysis of individual CTCs demonstrated a high level of heterogeneity seen at the single cell level [ 18 ]  for both protein expression and protein localization and the CTCs reflected both the primary biopsy and the changes seen in the metastatic sites. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2387", "text": "Analysis of cell-free circulating tumor DNA (cfDNA) has an advantage over circulating tumor cells assays in that there is approximately 100 times more cell-free DNA than there is DNA in circulating tumor cells. [ 7 ]  These tests analyze fragments of tumor-cell DNA that are continuously shed by tumors into the bloodstream. Companies offering cfDNA next generation sequencing testing include Personal Genome Diagnostics and  Guardant Health . [ 10 ]  These tests are moving into widespread use when a tissue biopsy has insufficient material for DNA testing or when it is not safe to do an invasive biopsy procedure, according to a recent report of results on over 15,000 advanced cancer patients sequenced with the Guardant Health test. [ 19 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2388", "text": "A 2014 study of the blood of 846 patients with 15 different types of cancer in 24 institutions was able to detect the presence of cancer DNA in the body. They found tumor DNA in the blood of more than 80 percent of patients with metastatic cancers and about 47 percent of those with localized tumors. The test does not indicate the tumor site(s) or other information about the tumor. The test did not produce false positives. [ 20 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2389", "text": "Such tests may also be useful to assess whether malignant cells remain in patients whose tumors have been surgically removed. [ 21 ]  Up to 30 percent are expected to relapse because some tumor cells remain. [ 22 ]  Initial studies identified about half the patients who later relapsed, again without false positives. [ 20 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2390", "text": "Another potential use is to track the specific DNA mutations driving a tumor. Many new cancer medications block specific molecular processes. Such tests could allow easier targeting of therapy to tumors. [ 20 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2391", "text": "For easily detected and accessed sites, any suspicious lesions may be assessed. Originally, this was skin or superficial masses.  X-ray , then later  CT ,  MRI , and  ultrasound  along with  endoscopy  extended the range. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2392", "text": "A biopsy of the  temporal arteries  is often performed for suspected  vasculitis .\nIn  inflammatory bowel disease  ( Crohn's disease  and  ulcerative colitis ), frequent biopsies are taken to assess the activity of the disease and to assess changes that precede malignancy. [ 23 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2393", "text": "Biopsy specimens are often taken from part of a  lesion  when the cause of a disease is uncertain or its extent or exact character is in doubt.  Vasculitis , for instance, is usually diagnosed on biopsy."}
{"_id": "WikiPedia_Radiology$$$corpus_2394", "text": "Needle core biopsies or aspirates of the pancreas may be made through the duodenum or stomach. [ 29 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2395", "text": "In the case of  Wilson's disease , clinicians use biopsies to determine the  quantitative   copper  level."}
{"_id": "WikiPedia_Radiology$$$corpus_2396", "text": "After the biopsy is performed, the sample of tissue that was removed from the patient is sent to the  pathology   laboratory . A  pathologist  specializes in diagnosing  diseases  (such as  cancer ) by examining tissue under a  microscope . When the laboratory (see  Histology ) receives the biopsy sample, the tissue is processed and an extremely thin slice of  tissue  is removed from the sample and attached to a glass slide. Any remaining tissue is saved for use in later studies, if required. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2397", "text": "The slide with the tissue attached is treated with dyes that stain the tissue, which allows the individual  cells  in the tissue to be seen more clearly. The slide is then given to the pathologist, who examines the tissue under a microscope, looking for any abnormal findings. The pathologist then prepares a report that lists any abnormal or important findings from the biopsy. This report is sent to the  surgeon  who originally performed the biopsy on the patient. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2398", "text": "Bronchial artery  embolization  is a treatment for  hemoptysis , abbreviated as  BAE . It is a kind of catheter intervention to control hemoptysis (airway bleeding) by embolizing the  bronchial artery , which is a bleeding source. Embolic agents are particulate embolic material such as gelatin sponge or polyvinyl alcohol (PVA), and liquid embolic material such as NBCA, or metallic coils. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2399", "text": "It is said that  hemoptysis  is caused by the formation of anomalous anastomosis (bronchial artery-pulmonary artery shunt) between the  bronchial artery  and the pulmonary artery, and if the bronchial artery is embolized, hemorrhage will cease. [ 1 ]  This is a fundamental concept of BAE. Traditionally, BAE was mostly performed as an emergency hemostatic procedure. Recently, it is often performed as an elective catheter treatment to prevent recurrence after massive hemoptysis, or control chronic repetitive hemoptysis. [ 2 ]  Although it is termed bronchial artery embolization, various systemic arteries other than the bronchial artery (non-bronchial arteries) also form a shunt with the pulmonary artery and cause hemoptysis. Therefore, it is common to embolize such non-bronchial arteries, but the expression of bronchial artery embolization, BAE, rather than the universal expression \"arterial embolization\" is more common. [ 3 ]  The therapeutic outcomes are improving, due to the combined approach such as spreading the treatment target to non-bronchial arteries, development of 3D-CT angiography following the development of MDCT, the advancement of devices such as coils and micro-catheters, and the evolution of therapeutic strategies. BAE has become the gold standard for hemoptysis for its dramatic improvement. [ 4 ] [ 1 ]  Although the hemostatic effect is greatly affected by the underlying disease, some high-volume centers report a hemostatic rate of about 90.4% within one year of treatment, and 85.9% even in two years after treatment. [ 2 ]  The occlusion of the blood vessels in the brain, heart, and kidneys, which are supplied by the end arteries, can cause cerebral, myocardial, and renal infarctions. In BAE, both bronchial mucosal necrosis and pulmonary infarction seldom occur. [ 1 ]  It is presumed that this is because the pulmonary circulation is dually controlled by the bronchial artery and the pulmonary artery; and even if the blood flow in the bronchial artery is lost, blood flow from the pulmonary artery is slightly maintained. [ 1 ] \u00a0With non-bronchial arteries, it is empirically known that some collateral circulations also develop. [ 5 ]  In addition, direct hemorrhage from the pulmonary artery is rare (less than 5%), which requires embolization of the pulmonary artery. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2400", "text": "BAE is effective for hemoptysis in most underlying diseases such as  bronchiectasis ,  nontuberculous mycobacterial disease  (NTM), cryptogenic hemoptysis, pulmonary  aspergillosis , and  pulmonary tuberculosis  sequelae. [ 1 ]  According to Ishikawa who reported long-term treatment results of BAE for 489 hemoptysis patients, each underlying disease's ratio is 34.0%, 23.5%, 18.4%, 13.3%, 6.8%, respectively. [ 2 ]  Other diseases for which BAE is effective include  lung abscess  and pulmonary actinomycosis. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2401", "text": "As for lung cancer, hemoptysis is caused mostly by bleeding from the tumor itself, and not by the bronchial-pulmonary artery shunt mechanism; embolism of the feeding vessels for the tumor causes necrosis of the cancer which may evoke massive hemoptysis. In addition, subsequent chemotherapy and endovascular treatment cannot be performed if the route of anticancer drugs is permanently obstructed. Lung cancer needs a different strategy. Seki et al. reported the usefulness of endovascular treatment for lung cancer hemoptysis. [ 7 ]  Kichang et al. reported BAE for hemoptysis in 84 lung cancer patients, and demonstrated that massive hemoptysis and cavity formation were significantly poor prognosis factors; re-hemoptysis rate was 23.8% in their follow-up period. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2402", "text": "Even though BAE is currently considered the gold standard treatment for hemoptysis, Ishikawa et al. [ 9 ]  found that only 9065 patients (8.4%) out of 107,389 patients hospitalized for hemoptysis between 2010 and 2018 in Japan were treated with BAE. According to Ishikawa basically, all patients with hemoptysis who are admitted to the hospital are eligible for BAE, and the reason why BAE has been performed only in such a small number of patients is that there are still few facilities that can perform BAE,"}
{"_id": "WikiPedia_Radiology$$$corpus_2403", "text": "Besides, among the 660 hospitals that performed BAE, half of them (334 centers) experienced less than one case per year. [ 9 ]  Centralization of hemoptysis treatment facilities will be necessary to increase the performance rate of BAE and to improve the quality of BAE."}
{"_id": "WikiPedia_Radiology$$$corpus_2404", "text": "A  catheter  with a diameter of less than 2\u00a0mm is inserted at the base of the foot ( femoral artery ) or the artery in the wrist ( radial artery ). [ 2 ]  The tip of the catheter is inserted into the orifice of the bronchial artery (normally smaller than 1\u00a0mm) or other non-bronchial hemoptysis-related arteries. Contrast agent is injected through the catheter, and when abnormal findings are observed, such as systemic\u2013pulmonary shunts, proliferations of the capillary vessels, or extravasation of the contrast medium to the lung tissues, they were super selectively embolized using the 3 Fr microcatheter system. [ 5 ]  A thinner microcatheter (about 0.8\u00a0mm) is passed through the catheter into the blood vessel, and then, embolic material is injected into the appropriate site. Thus, hemostasis is performed by ceasing or reducing the pressure applied to a bronchial (or non-bronchial)-pulmonary shunt (abnormal anastomosis). BAE is performed under local anesthesia, and the required time is about 1 hour to 3 hours. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2405", "text": "In the past, BAE was mostly considered a palliative or a bridge therapy to surgical operation owing to the high rate of re-hemoptysis with BAE. But with the improvement in treatment strategy and devices, it is regarded as a permanent therapy for hemoptysis nowadays. [ 1 ] [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2406", "text": "There are few facilities in which sophisticated BAE is feasible, and there are significant disparities between hospitals in the treatment quality and their experience. In most of the facilities, BAE is operated by interventional vascular radiology doctors, [ 10 ]  but in recent years, specialized high volume centers where a trained pulmonologist performs BAE are emerging. [ 11 ] [ 2 ]  It is particularly effective for cryptogenic hemoptysis. Ando, Masuda et al. reported in their article that the hemostatic rate is 97% at 20 months, [ 12 ]  which is equivalent to the results of the article by Ishikawa. [ 2 ]  Ando, Masuda et al. state that micro bronchial aneurysms are involved in 22.9% of cryptogenic hemoptysis [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2407", "text": "For pulmonary aspergillosis, BAE was relatively less effective and was once thought to be contraindicated, but hemostatic rates have improved in recent years. Ando, Masuda et al. demonstrated that the re-hemoptysis rate was significantly higher in cases of disease progression. [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2408", "text": "The hemostatic rate in each underlying disease by Ishikawa is shown below. [ 2 ]  In this paper, both re-hemoptysis and death are defined as composite endpoints, and among these, only re-hemoptysis free rate is shown in the following table. It is originally a long-term performance data for 3 years; In the third year, the 95% confidence interval was too wide except for cryptogenic hemoptysis; hence, they are regarded as statistically unreliable figures. Therefore, the third year result is not posted here except for idiopathic hemoptysis. [ 2 ]  The poorest hemostatic rate after 2 years was observed in nontuberculous mycobacterial disease (NTM). The result shown by Okuda, Masuda et al. was similar (73.8%). [ 13 ]  It is considered to reflect the progressive nature of the disease. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2409", "text": "Below are the treatment results summarized according to underlying diseases based on peer-reviewed papers published by Eishinkai Kishiwada Rehabilitation Hospital Hemoptysis and Pulmonary Circulation Center (EHPC), and The National Hospital Organization Tokyo Hospital Pulmonary Circulation and Hemoptysis Center (Tokyo Hp)\u00a0; the top two representatives of high-volume centers in Japan."}
{"_id": "WikiPedia_Radiology$$$corpus_2410", "text": "In cases of recurrence, re-BAE is possible to perform several times."}
{"_id": "WikiPedia_Radiology$$$corpus_2411", "text": "Furthermore, Takeda et al. showed that the 1, 2, 3, and 5-year hemostatic rates of bronchiectasis (without nontuberculous mycobacteriosis or pulmonary aspergillosis) were 91.3, 84.2, 81.5, and 78.9%, respectively. [ 15 ]  This paper is valuable for its long-term results of 5 years."}
{"_id": "WikiPedia_Radiology$$$corpus_2412", "text": "These include polyvinyl alcohol (PVA), n-butyl-2-cyanoacrylate (NBCA), gelatin sponge, metallic coil, etc. [ 1 ] [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2413", "text": "PVA  - Woo et al. reported 406 cases of BAE long-term results, including 293 cases of PVA and 113 cases of NBCA. [ 16 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2414", "text": "NBCA  - This is a kind of medical instant adhesive. Generally, there are many complications such as non-target blood vessel embolization and adhesion of catheter and vessel wall. However, in the article by Woo et al., major complication rate was 0%. [ 16 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2415", "text": "This kind has many advantages, such as low cost, instantaneous embolization, and very low recanalization rate since it does not depend on the patient's thrombus formation. It appears to be the best indication for traumatic bleeding control, particularly, in the peripheral bronchial aneurysms that the micro-catheter cannot access in BAE procedures, is a very good indication, and Mine, Hasebe et al. reported a technique called B-glue; NBCA combined with a balloon. [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2416", "text": "Gelatin sponge  (GS) is a transient embolic material, and in most cases, it dissolves within one to two weeks, and blood flow resumes. For this reason, it is important for emergency hemostatic purposes such as palliative treatment until surgery, which was the former positioning of BAE. GS is not suitable for the prevention of recurrence after massive hemoptysis or elective BAE for chronic repetitive hemoptysis. Wada et al. demonstrated that hemostatic rate was 24% (median follow-up time was 15 months) in their retrospective analysis of BAE for 33 patients using GS. [ 17 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2417", "text": "There are three kinds of platinum vascular embolic coil. One is a detachable coil, which is expensive, but can be deployed repetitively until electric detach. This enables safest and fully controlled embolization. The second one is pushable coil, which is affordable, and allows for only one deployment. The third one is mechanical detachable coil; it has a moderate price range, and repetitive deployment is feasible. Ishikawa termed BAE with metallic coil as ssBACE, and published the world's largest number of cases of ssBACE long-term results in 2017. [ 2 ]  As described below, there are no reports on spinal cord ischemia in ssBACE, [ 2 ] [ 11 ]  which is considered the most serious complication of BAE. This is one of the strongest merit of ssBACE. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2418", "text": "Despite a rumor that it cannot be re-treated if ssBACE is performed once, Ryuge demonstrated in their article on \"the mechanism of re-hemoptysis\" that the technical success rate in re-BAE was at least 97.7%. [ 18 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2419", "text": "Ryuge classified the re-hemoptysis mechanism after ssBACE into four as shown below. They also demonstrated that for the improvement of the long-term results in ssBACE in the future, suppressing recanalization is necessary. [ 18 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2420", "text": "Some readers misunderstand that 45.2% of the embolized coils recanalized. This, in fact, is the ratio of re-hemoptysis mechanism occurring in 9.6% cases in 1 year, and in 14.1% of those in 2 years. [ 18 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2421", "text": "Recanalization was the main cause of re-hemoptysis, and the suppression of new hemoptysis-related vessels, which is the second cause, cannot be controlled by the BAE procedure itself. It was shown that suppression of the recanalization was the key to improvement in ssBACE result in future. [ 18 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2422", "text": "Chest pain is the most common complication for who had undergone BAE, ranging from 24 to 91%. However, the symptom is temporary due to accidental embolisation of  coronary artery  supplying the heart. [ 19 ] \nIn the past,  paraplegia  caused by spinal cord ischemia due to erroneous embolization of the  anterior spinal artery  was well known as a rare, but serious complication. [ 1 ] [ 20 ]  Super selective BAE using microcatheter reduced the incidence of the spinal ischemia. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2423", "text": "However, according to Ishikawa et al., spinal cord infarction still occurs, with an incidence of 0.19% (16/8563). [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2424", "text": "They also compared it between three embolic agents (GS, NBCA, Coil) and demonstrated that the incidence of spinal cord infarction was significantly lower in coils: 0.06% (1/1577) compared with GS 0.18% (12/6561) and NBCA 0.71% (3/425) (p=0,04)."}
{"_id": "WikiPedia_Radiology$$$corpus_2425", "text": "Major complications reported by Ishikawa et al. are presented below. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2426", "text": "Mediastinal hematoma occurs by injury of hemoptysis-related vessel, mainly by wire, and can easily bail out by proximal coil embolization. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2427", "text": "The majority of research on BAE was the single-center retrospective observational studies. Descriptive epidemiological studies using French medical big data is precious in that aspect. [ 21 ]  From the fall of 2020 to January 2021, a collaborative study led by the Yasunaga Laboratory of the University of Tokyo published two landmark papers using the Japanese medical database. [ 22 ] [ 9 ]  One of them is a study by Ando et al. of the Department of Respiratory Medicine, University of Tokyo, which demonstrated for the first time in the world that early BAE (within three days after endotracheal intubation) significantly reduced in-hospital mortality in patients with severe hemoptysis on ventilators (30 days): 7.5% in the early BAE group vs. 16.8% in the non-early BAE group. (odds ratio, 0.45; 95% CI, 0.28-0.73; p = 0.001). [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2428", "text": "Omachi et al. of the Hemoptysis and Pulmonary Circulation Center, Kishiwada Rehabilitation Hospital, demonstrated for the first time in the world that elective BAE with coils significantly improved the quality of life of hemoptysis patients(single-center prospective observational study). In this study, both physical and mental QOL improved significantly after BAE, especially the latter. [ 23 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2429", "text": "Cholecystostomy  or ( cholecystotomy ) is a medical procedure used to drain the  gallbladder  through either a percutaneous or endoscopic approach. The procedure involves creating a  stoma  in the gallbladder, which can facilitate placement of a tube or stent for  drainage , first performed by American surgeon, Dr.  John Stough Bobbs , in 1867. [ 1 ] [ 2 ] [ 3 ]  It is sometimes used in cases of  cholecystitis  or other gallbladder disease where the person is ill, and there is a need to delay or defer  cholecystectomy . [ 4 ]  The first endoscopic cholecystostomy was performed by Drs.  Todd Baron  and Mark Topazian in 2007 using ultrasound guidance to puncture the stomach wall and place a plastic biliary catheter for gallbladder drainage. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2430", "text": "Cholecystostomy finds its application when the patient has cholecystitis and is not a good candidate for surgery. [ 6 ]  Some indications include:"}
{"_id": "WikiPedia_Radiology$$$corpus_2431", "text": "Contraindications to cholecystostomy include:"}
{"_id": "WikiPedia_Radiology$$$corpus_2432", "text": "Percutaneous cholecystostomy is performed under sedation and guided by  ultrasound  (US) or  computed tomography  (CT) imaging. [ 7 ]  There are 3 major considerations when deciding the approach for this procedure."}
{"_id": "WikiPedia_Radiology$$$corpus_2433", "text": "There are numerous studies comparing the trans-hepatic and trans-peritoneal approaches and their associated complications. Some studies have shown that there is no statistically significant difference in complications between the two approaches and recommend operator preference. A more recent study, however, did suggest greater incidence of hemorrhage with the trans-hepatic approach. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2434", "text": "Before the procedure, a thorough review of the patient's imaging is conducted to evaluate the anatomy of the  gallbladder  and surrounding structures. [ 9 ]  The patient's clinical status, medications, and laboratory values (i.e.  white blood cell count ,  coagulation studies ,  inflammatory markers ,  anticoagulation  therapy, etc.) are reviewed to ensure the patient is stable for the procedure. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2435", "text": "Once the patient is ready, the surgical site is cleaned with an  antiseptic  solution to minimize the risk of infection. [ 9 ]  Local anesthesia, in the form of a topical 1%  lidocaine  injection, is administered. A small incision is made in the right upper quadrant (RUQ) directly above the gallbladder, using a #11 blade. [ 9 ]  At this point, there are 2 main techniques to perform the cholecystostomy."}
{"_id": "WikiPedia_Radiology$$$corpus_2436", "text": "Cholecystostomy is a medical procedure and carries its share of complications and adverse effects. Complications occur in approximately 10% of cases. [ 7 ]  The most common issues encountered are catheter dislodgement, blockage, or a bile leak, which, while frequent, are considered minor complications. [ 10 ]  Major complications, although rare, encompass  sepsis , significant  hemorrhage ,  pneumothorax , and bowel injury. [ 10 ]  Notably, the transhepatic approach offers advantages by reducing the risk of both organ perforation and bile leaks. [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2437", "text": "Once the cholecystostomy tube is placed, it is recommended to keep the tube for 3\u20136 weeks to allow the tract to mature. [ 11 ]  Studies have shown that premature removal (before 21 days) is associated with a higher incidence of bile leaks. [ 11 ]  Once the cholecystitis is resolved and adequate time has passed for tract maturation, a clamp trial can be conducted for 24 hours to assess drainage from the gallbladder. [ 9 ]  If the patient passes the clamp trial (minimal to no drainage after unclamping), the tube is removed. Future management consists of performing a  cholecystectomy  to prevent future episodes of cholecystitis once the patient is stable for surgery. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2438", "text": "An alternative to the percutaneous cholecystostomy is to use the  endoscopic  route. There are 2 primary techniques: endoscopic transpapillary gallbladder drainage (ET-GBD) and endoscopic ultrasound-guided gallbladder drainage (EUS-GBD). These techniques are considered when the patient is a poor candidate for surgical cholecystectomy but can tolerate anesthesia for an endoscopic procedure and does not have a gallbladder perforation. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2439", "text": "This procedure is performed during an  endoscopic retrograde cholangiopancreatography (ERCP) . The  cystic duct  is cannulated and a plastic  stent  is deployed to relieve the blockage and allow for drainage. ET-GBD can be considered when the patient is already undergoing an ERCP for another medical condition (i.e.  choledocholithiasis ). Some drawbacks include an increased risk of  pancreatitis  from the ERCP procedure and a lower success rate compared to EUS-GBD or percutaneous cholecystostomy, particularly when there is evidence of cystic duct obstruction (i.e.  stones ,  adhesions ,  strictures ,  cancer , or other masses). [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2440", "text": "EUS-GBD allows for internal drainage by placing a  lumen-apposing metal stent  (LAMS) into the gallbladder from either the  stomach  or the  duodenum . \u00a0The procedure involves using a cautery-powered LAMS to puncture through the gastric wall and enter the gallbladder. Two flanges on either side of the LAMS are deployed, tethering the stent on the inside walls of the gallbladder and gastric lumen. An important consideration is that the gallbladder must be within 10mm of the gastric puncture site. EUS-GBD is a good option for patients who are unlikely to undergo a future surgical cholecystectomy. It may also be used in patients with a cystic duct occlusion, or a pre-existing uncovered metal biliary stent. Some advantages include a high success rate with few complications and a reduced need for reinterventions. The primary drawback is the risk of stent occlusion with food or gastric contents. This risk is lowered when entering through the duodenum. EUS-GBD also complicates a future surgical cholecystectomy because the patient's anatomy is modified, requiring an additional repair of the choleycystoenteric  fistula . [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2441", "text": "Cryoablation  is a process that uses extreme  cold  to destroy  tissue . Cryoablation is performed using hollow needles (cryoprobes) through which cooled, thermally conductive fluids are circulated. Cryoprobes are positioned adjacent to the target in such a way that the freezing process will destroy the diseased tissue. Once the probes are in place, the attached cryogenic freezing unit removes heat from (\"cools\") the tip of the probe and by extension from the surrounding tissues."}
{"_id": "WikiPedia_Radiology$$$corpus_2442", "text": "Ablation occurs in tissue that has been frozen by at least three mechanisms:"}
{"_id": "WikiPedia_Radiology$$$corpus_2443", "text": "The most common application of cryoablation is to ablate solid tumors found in the lung, liver, breast, kidney and prostate. The use in prostate and renal cryoablation are the most common. Although sometimes applied in  cryosurgery  through  laparoscopic  or open surgical approaches, most often cryoablation is performed percutaneously (through the skin and into the target tissue containing the tumor) by a medical specialist, such as an  interventional radiologist . The term is from  cryo-  +  ablation ."}
{"_id": "WikiPedia_Radiology$$$corpus_2444", "text": "Prostate  cryoablation is moderately effective but, as with any prostate removal process, also can result in impotence. Prostate cryoablation is used in three patient categories:"}
{"_id": "WikiPedia_Radiology$$$corpus_2445", "text": "Cryoablation has been explored as an alternative to  radiofrequency ablation  in the treatment of moderate to severe pain in people with  metastatic bone disease . The area of tissue destruction created by this technique can be monitored more effectively by CT than RFA, a potential advantage when treating tumors adjacent to critical structures. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2446", "text": "Cryoablation has similar outcomes to radiofrequency ablation when treating  renal cell carcinoma . [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2447", "text": "Cryoablation for breast cancer is typically only possible for small tumors. [ 3 ]  Often surgery is used following cryoablation. [ 3 ]  As of 2014 more research is required before it can replace  lumpectomy . [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2448", "text": "Another type of cryoablation is used to restore normal electrical conduction by freezing tissue or heart pathways that interfere with the normal distribution of the heart\u2019s electrical impulses. Cryoablation is used in two types of intervention for the treatment of  arrhythmias : (1)  catheter -based procedures and (2) surgical operations."}
{"_id": "WikiPedia_Radiology$$$corpus_2449", "text": "A catheter is a very thin tube that is inserted into a vein in the patient\u2019s leg and threaded to the heart where it delivers energy to treat the patient\u2019s arrhythmia. In surgical procedures, a flexible probe is used directly on an exposed heart to apply the energy that interrupts the arrhythmia. By cooling the tip of a cryoablation catheter ( cardiology ) or probe ( heart surgery ) to sub-zero temperatures, the cells in the heart responsible for conducting the arrhythmia are altered so that they no longer conduct electrical impulses."}
{"_id": "WikiPedia_Radiology$$$corpus_2450", "text": "Cryoablation is also currently being used to treat  fibroadenomas  of the breast. Fibroadenomas are  benign  breast tumors that are found in approximately 10% of women (primarily ages 15\u201330). [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2451", "text": "In this procedure which has been approved by the U.S.  Food and Drug Administration  (FDA), an ultrasound-guided probe is inserted into the fibroadenoma and extremely cold temperatures are then used to destroy the abnormal cells. [ 5 ]  Over time the cells are reabsorbed into the body. The procedure can be performed in a doctor's office setting with  local anesthesia  and leaves very little scarring compared to open surgical procedures. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2452", "text": "Different catheter-based ablation techniques may be used and they generally fall into two categories: (1) cold-based procedures where tissue cooling is used to treat the arrhythmia, and (2) heat-based procedures where high temperature is used to alter the abnormal conductive tissue in the heart."}
{"_id": "WikiPedia_Radiology$$$corpus_2453", "text": "Cold temperatures are used in cryoablation to chill or freeze cells that conduct abnormal heart rhythms. The catheter removes heat from the tissue to cool it to temperatures as low as -75\u00a0\u00b0C. This causes localized scarring, which cuts undesired conduction paths."}
{"_id": "WikiPedia_Radiology$$$corpus_2454", "text": "This is a much newer treatment for  supraventricular tachycardia  (SVT) involving the atrioventricular (AV) node directly. SVT involving the AV node is often a contraindication for using radiofrequency ablation because of the risk of injuring the AV node, forcing patients to receive a permanent pacemaker. With cryoablation, areas of tissue can be mapped by limited, reversible, freezing (e.g., to -10 C). If the result is undesirable, the tissue can be rewarmed without permanent damage. Otherwise, the tissue can be permanently ablated by freezing it to a lower temperature (e.g., -73 C)."}
{"_id": "WikiPedia_Radiology$$$corpus_2455", "text": "This therapy has revolutionized  AV nodal reentrant tachycardia  (AVNRT) and other AV nodal tachyarrhythmias. It has allowed people who were otherwise not a candidate for radiofrequency ablation to have a chance at having their problem cured. This technology was developed at The Montreal Heart Institute in the late 1990s. The therapy was successfully adopted in Europe in 2001, and in the US in 2004 following the \"Frosty Trial\". [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2456", "text": "In 2004, the technology was pioneered in the midwest United States at Miami Valley Hospital in Dayton, Ohio, by Mark Krebs, MD, FACC, Matthew Hoskins, RN, BSN and Ken Peterman, RN, BSN.  These electrophysiology experts were successful in curing the first 12 candidates in their facility. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2457", "text": "Cryoablation for AVNRT and other arrhythmias do have some drawbacks. A recent study [ 7 ]  concluded that procedure times are slightly higher on average for cryoablation than for traditional radio-frequency (heat-based) ablations. Also, higher rate of equipment failures were recorded using this technique. Finally, even though short term success rate is equivalent to RF treatments, cryoablation appears to have a significantly higher long term recurrence rate."}
{"_id": "WikiPedia_Radiology$$$corpus_2458", "text": "Cryotherapy  is able to produce a temporary electrical block by cooling down the tissue believed to be conducting the arrhythmia. This allows the physician to make sure this is the right site before permanently disabling it. The ability to test a site in this way is referred to as site testing or  cryomapping ."}
{"_id": "WikiPedia_Radiology$$$corpus_2459", "text": "When ablating tissue near the  AV node  (a special conduction center that carries electrical impulses from the atria to the ventricles), there is a risk of producing heart block\u00a0\u2013 that is, normal conduction from the atria cannot be transmitted to the ventricles. Freezing tissue near the AV node is less likely to provoke irreversible heart block than ablating it with heat."}
{"_id": "WikiPedia_Radiology$$$corpus_2460", "text": "As in catheter-based procedures, techniques using heating or cooling temperatures may be used to treat arrhythmias during heart surgery. Techniques also exist where incisions are used in the open heart to interrupt abnormal electrical conduction ( Maze procedure ).  Cryosurgery  involves the use of freezing techniques for the treatment of arrhythmias during surgery."}
{"_id": "WikiPedia_Radiology$$$corpus_2461", "text": "A physician may recommend cryosurgery being used during the course of heart surgery as a secondary procedure to treat any arrhythmia that was present or that may appear during the primary open-chest procedure. The most common heart operations in which cryosurgery may be used in this way are  mitral valve repairs  and  coronary artery bypass grafting . During the procedure, a flexible cryoprobe is placed on or around the heart and delivers cold energy that disables tissue responsible for conducting the arrhythmia."}
{"_id": "WikiPedia_Radiology$$$corpus_2462", "text": "Cryoablation has recently been used to treat low-flow  vascular malformations  such as  venous malformations  (VM) and  fibroadipose vascular anomalies  (FAVA). Cryoablation has proved effective for treating these disorders both as primary treatment and after  sclerotherapy . [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2463", "text": "Cryoimmunotherapy  is an oncological treatment for various cancers that combines cryoablation of tumor with  immunotherapy  treatment. [ 9 ]  In-vivo cryoablation of a tumor alone can induce an immunostimulatory, systemic anti-tumor response, resulting in a cancer vaccine\u00a0\u2013 the  abscopal effect . [ 10 ]  However, cryoablation alone may produce an insufficient immune response, depending on various factors, such as high freeze rate. Combining cryotherapy with immunotherapy enhances the immunostimulating response and has synergistic effects for cancer treatment. [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2464", "text": "The use of cold for pain relief and as an anti-inflammatory has been known since the time of  Hippocrates  (460\u2013377 BC). [ 12 ]  Since then there have been numerous accounts of ice used for pain relief including from the Ancient Egyptians and Avicenna of Persia (AD 982\u20131070). [ 13 ]  Since 1899, Dr. Campbell White used refrigerants for treating a variety of conditions, including: lupus erythematosus, herpes zoster, chancroid, naevi, warts, varicose leg ulcers, carbuncles, carcinomas and epitheliomas. De Quervain successfully used of carbonic snow to treat bladder papillomas and bladder cancers in 1917. Dr. Irving S. Cooper, in 1913, progressed the field of cryotherapy by designing a liquid nitrogen probe capable of achieving temperatures of -196\u00a0\u00b0C, and utilizing it to treat of Parkinson's disease and previously inoperable cancer. Cooper's cryoprobe advanced the practice of cryotherapy, which led to growing interest and practice of cryotherapy. In 1964, Dr. Cahan successfully used his liquid nitrogen probe invention to treat uterine fibroids and cervical cancer. Cryotherapy continued to advance with Dr. Amoils developing a liquid nitrogen probe capable of achieving cooling expansion, in 1967. [ 14 ] [ 15 ] [ 16 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2465", "text": "With the technological cryoprobe advancements in the 1960s came wider acceptance and practice of cryotherapy. Since the 1960s, liver, prostate, breast, bone, and other cancers have been treated with cryoablation in many parts of the world. Japanese physician Dr. Tanaka began treating metastatic  breast cancer  with cryoablation in 1968. [ 17 ]   For the next three decades, Dr. Tanaka successfully treated small and localized as well as advanced and unresectable breast cancer with minimally invasive cryoablation.  All of Dr. Tanaka's breast cancer cases were considered incurable: advanced, unresectable, and resistant to radiotherapy, chemotherapy, and endocrine therapy. [ 17 ]  At the same time, physicians, including Dr. Ablin and Dr. Gage, started utilizing cryoablation for the treatment of prostate and  bone cancer . [ 18 ] [ 19 ]  Dr. Paul J. Wang MD and Dr. Peter L. Friedman MD, PhD invented cryoablation for the heart and cardiac arrhythmia in 1988. Their patents were for the cryoablation catheter and cryogenic mapping (US Patents 5147355A and 5423807A)."}
{"_id": "WikiPedia_Radiology$$$corpus_2466", "text": "The 1980s and 1990s saw dramatic advancement in apparatus and imaging techniques, with the introduction of CMS Cryoprobe, and Accuprobe. [ 20 ]   CT -,  MRI -, and  ultrasound -guided cryoprobes became available and improved the capabilities of cryoprobes in treatment. Excited by the latest advancements in cryotherapy, China embraced cryotherapy in the 1990s to treat many oncological conditions. [ 21 ]  With the benefits well-established, the FDA approved the treatment of prostate cancer with cryoablation in 1998. [ 22 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2467", "text": "Electromagnetic navigation bronchoscopy  ( ENB ) is a medical procedure utilizing  electromagnetic technology  designed to localize and guide  endoscopic  tools or  catheters  through the  bronchial pathways  of the lung.  Using a virtual, three-dimensional (3D) bronchial map from a recently  computed tomography  (CT) chest scan and disposable catheter set, physicians are able to navigate to a desired location within the lung to  biopsy   lesions , stage  lymph nodes , insert markers to guide  radiotherapy  or guide  brachytherapy  catheters.  [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2468", "text": "The ENB system consists of four essential components:"}
{"_id": "WikiPedia_Radiology$$$corpus_2469", "text": "Electromagnetic navigation bronchoscopy consists of two primary phases: planning and navigation. In the planning phase previously acquired CT scans are utilized to mark and plan pathways to targets within the lung. In the navigation phase these previously planned targets and pathways are displayed and can be utilized for navigation and access deep within the lung. Upon arriving at the target ENB enables multiple applications all within the same procedure. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2470", "text": "CT scans of the patient\u2019s chest are loaded into proprietary software that reconstructs the patient\u2019s airways in multiple 3D images. The physician utilizes these images to mark target locations and plan pathways to these target locations within the lungs. [ 1 ] [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2471", "text": "Using the planned pathway created in the Planning Phase and real-time guidance, the physician navigates the steerable sensor probe and extended working channel to the desired target location(s). Once at the desired location, the physician locks the extended working channel in place and the steerable sensor probe is removed. The extended working channel provides access to the target lesion for standard bronchoscopic tools or catheters. [ 1 ] [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2472", "text": "According to the Aetna Clinical Policy Bulletin on ENB, \"In 2004, the FDA cleared for marketing through the 510(k) process the  Medtronic  superDimension/Bronchus system, also known as the inReach system (superDimension, Ltd, Israel), a minimally invasive image-guidance localization and navigation system that uses electromagnetic guidance for the management of peripheral lung lesions. [ 1 ]   The system consists of several components: a guide catheter, a steerable navigation catheter, and planning and navigation software and hardware (i.e., computer and monitor).  Navigation is facilitated by an electromagnetic tracking system that detects a position sensor incorporated into a flexible catheter advanced through a bronchoscope.  Information obtained during bronchoscopy is super-imposed on previously acquired computed tomography (CT) data and 3-dimensional virtual images.  The system was designed to solve the clinical problem of reaching small suspected lesions in the peripheral lung airways and mediastinal lymph nodes and is being proposed as an alternative to open surgical biopsy of distant lung lesions and as an alternative to transthoracic implantation of radiosurgical markers.\" [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2473", "text": "Despite the medical advances of detection, diagnosis and treatment methods throughout the past 50 years, lung cancer causes more deaths than any other cancer in both men and women. [ 5 ]  Currently, lung cancer is the most common form of cancer diagnosed in the United States and a major cause of death, accounting for 14% of all cancers. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2474", "text": "The most effective way of stopping cancer comes at diagnosis and treatment in the early stages. Lung cancer diagnosed in the early stages yields an 88% survival rate at ten years versus 16% at five years when found in the later stages, [ 7 ] [ 8 ]  although 88% rate has only been achieved once. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2475", "text": "Although 1 in 500 chest X-rays show a peripheral lesion, [ 9 ]  65% of traditional bronchoscopes fail to reach these distant lesions. [ 10 ]  More invasive diagnostic techniques are then necessary, posing a greater potential for complications such as pneumothorax. [ 11 ] \nPatients with poor lung function may not tolerate more invasive procedures, leaving them with \"watchful waiting\" as their only option."}
{"_id": "WikiPedia_Radiology$$$corpus_2476", "text": "There are four publications that show that peripheral lung lesions can be diagnosed successfully in 69% to 86% of cases using the  Medtronic   superDimension system. [ 3 ] [ 12 ] [ 13 ] [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2477", "text": "According to the American Journal of Respiratory and Critical Care Medicine, a prospective ... study was conducted to determine the ability of electromagnetic navigation bronchoscopy to sample peripheral lung lesions and mediastinal lymph nodes with standard bronchoscopic instruments and demonstrate safety the ENB.\"  The results provided a \"yield/procedure [rate at] 74% and 100% for peripheral lesions and lymph nodes, respectively.\" Additionally, \"a diagnosis was obtained in 80.4% of bronchoscopic procedures.\" The study concluded that ENB \"is a safe method for sampling peripheral and mediastinal lesions with high diagnostic yield independent of lesion size and location\". [ 15 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2478", "text": "A similar study of 40 patients issued in the  European Respiratory Journal  resulted in an overall 62.5% diagnostic yield and concluded;\n\"electromagnetic navigation bronchoscopy without additional fluoroscopic guidance is a safe and efficient technique for the diagnosis of peripheral pulmonary nodules. The overall diagnostic yield found in the present study is superior to rates reported in most previous studies performed for small peripheral pulmonary nodules with bronchoscopy\". [ 16 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2479", "text": "Virtual bronchoscopy continues to be an active subject for basic engineering research. The Bioelectromagnetics group at  University College Cork  has developed a novel low-cost tracking system for use in electromagnetic navigation bronchoscopy. [ 17 ]  The group is also collaborating with the Surgical Planning Laboratory at  Harvard Medical School  to develop the world's first open-source virtual bronchoscopy module to be implemented in the  3DSlicer  environment. [ 18 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2480", "text": "Embolectomy  is the emergency  interventional  or  surgical  removal of  emboli  which are blocking blood circulation. It usually involves removal of  thrombi  (blood clots), and is then referred to as  thromboembolectomy  or  thrombectomy . Embolectomy is an emergency procedure often as the last resort because permanent occlusion of a significant blood flow to an organ leads to  necrosis . Other involved therapeutic options are  anticoagulation  and  thrombolysis ."}
{"_id": "WikiPedia_Radiology$$$corpus_2481", "text": "Surgical embolectomy for massive pulmonary embolism (PE) has become a rare procedure and is often viewed as a last resort.  Thrombolytic therapy  has become the treatment of choice. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2482", "text": "Surgical or catheter embolectomy is a procedure performed in patients with pulmonary embolism, which is a blockage of an artery in the lung caused by a blood clot. This procedure is typically used for patients who are in a critical condition, such as those who are experiencing persisting shock despite receiving supportive care, and who have an absolute contraindication for thrombolytic therapy. During the procedure, a catheter is inserted into the affected artery, and the clot is removed using a variety of techniques such as mechanical fragmentation or suction. However, it's important to note that there is a risk of complications such as bleeding, infection, and damage to the artery or surrounding tissue. This procedure is done under general anesthesia and with the help of imaging technology like angiography, and it's performed by interventional radiologists or cardiothoracic surgeons. [ 2 ]  And although other treatments have improved urgent surgical embolectomy or catheter embolectomy may be a life saving procedure in severe pulmonary embolism. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2483", "text": "Embolectomies are performed as  limb-sparing techniques  for arterial embolisms in  acute limb ischemia . However, there are also other options, such as  catheter-directed thrombolysis  and  anticoagulation  with observation. [ 4 ]  It can also be used for other ischemias due to embolism for example mesenteric ischemia and  stroke . [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2484", "text": "Typically this is done by inserting a  catheter  with an inflatable balloon attached to its tip into an artery, passing the catheter tip beyond the clot, inflating the balloon, and removing the clot by withdrawing the catheter. The catheter is called Fogarty, named after its inventor  Thomas J. Fogarty . [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2485", "text": "Possible complications of balloon embolectomy include intimal lesions, which can lead to another thrombosis. [ 7 ]  The vessel may also be affected by a  dissection  or rupture. The  procedure may lead to  cholesterol embolism  from atherosclerotic plaques. [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2486", "text": "Catheter embolectomy is also used for aspiration embolectomy, where the thrombus is removed by suction rather than pushing with a balloon. [ 8 ]  It is a rapid and effective way of removing thrombi in thromboembolic occlusions of the limb arteries below the inguinal ligament, [ 8 ]  as in  leg infarction ."}
{"_id": "WikiPedia_Radiology$$$corpus_2487", "text": "Surgical embolectomy is the simple surgical removal of a clot following incision into a vessel by open surgery on the artery. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2488", "text": "Outcome of embolectomy varies with size and location of the embolus. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2489", "text": "In pulmonary embolism recent data shows mortality as being approximately 20%. Although this is a high mortality, it may have life-saving potential in some instances. [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2490", "text": "Emboli  are abnormal masses of material (which can be solid, liquid or gas) that are carried in the blood stream from one part of the circulation to another causing a blockage ( occlusion ) of a  blood vessel  that leads to lack of oxygen supply ( ischemia ) and finally  infarction  of  tissue  downstream of the embolus. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2491", "text": "The most common type of emboli are a blood clot generated by  thrombosis  which has then broken off and is then transported in the blood stream  [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2492", "text": "There are two areas where emboli can form and therefore impact: [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2493", "text": "Embolization  refers to the passage and lodging of an  embolus  within the bloodstream. It may be of natural origin ( pathological ), in which sense it is also called  embolism , for example a  pulmonary embolism ; or it may be artificially induced ( therapeutic ), as a  hemostatic  treatment for bleeding or as a treatment for some types of cancer by deliberately blocking blood vessels to starve the  tumor  cells."}
{"_id": "WikiPedia_Radiology$$$corpus_2494", "text": "In the  cancer management  application, the embolus, besides blocking the blood supply to the tumor, also often includes an ingredient to attack the tumor chemically or with  irradiation . When it bears a  chemotherapy  drug, the process is called chemoembolization.  Transcatheter arterial chemoembolization  (TACE) is the usual form. When the embolus bears a  radiopharmaceutical  for  unsealed source radiotherapy , the process is called radioembolization or  selective internal radiation therapy  (SIRT)."}
{"_id": "WikiPedia_Radiology$$$corpus_2495", "text": "Embolization involves the selective  occlusion  of  blood vessels  by purposely introducing  emboli , in other words deliberately blocking a blood vessel. Embolization is used to treat a wide variety of conditions affecting different organs of the human body."}
{"_id": "WikiPedia_Radiology$$$corpus_2496", "text": "Embolization is commonly used to treat active arterial bleeding. Embolization is rarely used to treat venous bleeding as venous bleeding can stop on its own or with packing or compression. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2497", "text": "The treatment is used to occlude:"}
{"_id": "WikiPedia_Radiology$$$corpus_2498", "text": "The treatment is used to slow or stop blood supply thus reducing the size of the tumour:"}
{"_id": "WikiPedia_Radiology$$$corpus_2499", "text": "It could be useful for managing  malignant hypertension  due to end stage  kidney failure . [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2500", "text": "First developed by  Sadek Hilal  in 1968, embolization is a minimally invasive surgical technique. [ 8 ]  The purpose is to prevent blood flow to an area of the body, which can effectively shrink a tumor or block an aneurysm."}
{"_id": "WikiPedia_Radiology$$$corpus_2501", "text": "The procedure is carried out as an endovascular procedure by an  interventional radiologist  in an interventional suite. It is common for most patients to have the treatment carried out with little or no sedation, although this depends largely on the organ to be embolized. Patients who undergo cerebral embolization or portal vein embolization are usually given a  general anesthetic ."}
{"_id": "WikiPedia_Radiology$$$corpus_2502", "text": "Access to the organ in question is acquired by means of a guidewire and catheter(s). Depending on the organ this can be very difficult and time-consuming. The position of the correct artery or vein supplying the pathology in question is located by  digital subtraction angiography  (DSA). These images are then used as a map for the radiologist to gain access to the correct vessel by selecting an appropriate  catheter  and or wire, depending on the 'shape' of the surrounding anatomy."}
{"_id": "WikiPedia_Radiology$$$corpus_2503", "text": "Once in place, the treatment can begin. The artificial embolus used is usually one of the following:"}
{"_id": "WikiPedia_Radiology$$$corpus_2504", "text": "Once the artificial emboli have been successfully introduced, another set of DSA images are taken to confirm a successful deployment."}
{"_id": "WikiPedia_Radiology$$$corpus_2505", "text": "Liquid embolic agents  \u2013 Used for AVM, these agents can flow through complex vascular structures so the surgeon does not need to target the catheter to every single vessel."}
{"_id": "WikiPedia_Radiology$$$corpus_2506", "text": "Sclerosing agents  \u2013 These will harden the endothelial lining of vessels. They require more time to react than the liquid embolic agents. Therefore, they cannot be used for large or high-flow vessels."}
{"_id": "WikiPedia_Radiology$$$corpus_2507", "text": "Particulate embolic agents  \u2013 These are only used for precapillary arterioles or small arteries. These are also very good for AVM deep within the body. The disadvantage is that they are not easily targeted in the vessel. None of these are radioopaque, so they are difficult to view with radiologic imaging unless they are soaked in contrast prior to injection."}
{"_id": "WikiPedia_Radiology$$$corpus_2508", "text": "Mechanical occlusion devices  \u2013 These fit in all vessels. They also have the advantage of accuracy of location; they are deployed exactly where the catheter ends."}
{"_id": "WikiPedia_Radiology$$$corpus_2509", "text": "Endovascular aneurysm repair  ( EVAR ) is a type of minimally-invasive  endovascular surgery  used to treat  pathology  of the  aorta , most commonly an  abdominal aortic aneurysm  (AAA). When used to treat  thoracic aortic  disease, the procedure is then specifically termed  TEVAR  for \"thoracic endovascular aortic/aneurysm repair.\" EVAR involves the placement of an expandable  stent graft  within the aorta to treat aortic disease without operating directly on the aorta. In 2003, EVAR surpassed  open aortic surgery  as the most common technique for repair of AAA, [ 1 ]  and in 2010, EVAR accounted for 78% of all intact AAA repair in the United States. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2510", "text": "Standard EVAR is appropriate for aneurysms that begin below the  renal arteries , where there exists an adequate length of normal  aorta  (the  \"proximal aortic neck\" ) for reliable attachment of the endograft without leakage of blood around the device (\" endoleak \"). [ 3 ]  If the proximal aortic neck is also involved with the aneurysm, the patient may be a candidate for complex visceral EVAR with a fenestrated or branched EVAR."}
{"_id": "WikiPedia_Radiology$$$corpus_2511", "text": "Patients with aneurysms require elective repair of their aneurysm when it reaches a diameter large enough (typically greater than 5.5\u00a0cm) such that the risk of rupture is greater than the risk of surgery. Repair is also warranted for aneurysms that rapidly enlarge or those that have been the source of  emboli  (debris from the aneurysm that dislodges and travel into other arteries). Lastly, the repair is also indicated for aneurysms that are the source of  pain  and  tenderness , which may indicate impending rupture. The options for repair include traditional  open aortic surgery  or endovascular repair. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2512", "text": "Endovascular procedures aim to reduce the morbidity and mortality of treating arterial disease in a patient population that is increasingly older and less fit than when major open repairs were developed and popularized. Even in the early days, significant risks were accepted in the understanding that the large open operation was the only option. That is not the case in most patients today. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2513", "text": "Studies that assign aneurysm patients to treatment with EVAR or traditional open surgery have demonstrated fewer early complications with the minimally invasive approach. Some studies have also observed a lower mortality rate with EVAR. [ 4 ] [ 5 ]  The reduction in death, however, does not persist long-term. After a few years, the survival after repair is similar to EVAR or open surgery. This observation may be the result of durability problems with early endograft, with a corresponding need for additional procedures to repair endoleaks and other device-related issues. Newer, improved technology may reduce the need for such secondary procedures. If so, the results of EVAR may improve to the point where long-term survival benefit becomes evident. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2514", "text": "EVAR is also used for  rupture  of the abdominal and descending thoracic aorta, and in rare cases used to treat pathology of the  ascending aorta . [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2515", "text": "Endografts have been used in patients with  aortic dissection , noting the extremely complex nature of open surgical repair in these patients. In uncomplicated aortic dissections, no benefit has been demonstrated over medical management alone.\nIn uncomplicated type B aortic dissection, TEVAR does not seem either to improve or compromise 2-year survival and adverse event rates. [ 7 ]  Its use in complicated aortic dissection is under investigation. In the Clinical Practice Guidelines of the European Society for Vascular Surgery, it is recommended that in patients with complicated acute type B aortic dissection, endovascular repair with thoracic endografting should be the first line intervention. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2516", "text": "Before people are deemed to be suitable candidates for this treatment, they have to go through a rigorous set of tests.  These include a CT scan of the complete thorax/abdomen/pelvis and blood tests.  The CT scan gives precise measurements of the aneurysm and the surrounding anatomy. In particular, the calibre/tortuosity of the iliac arteries and the relationship of the neck of the aneurysm to the renal arteries are important determinants of whether the aneurysm is amenable to endoluminal repair. In certain occasions where the renal arteries are too close to the aneurysm, the custom-made fenestrated graft stent is now an accepted alternative to doing open surgery. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2517", "text": "A patient's anatomy can be unsuitable for EVAR in several ways. Most commonly, in an infrarenal aneurysm, a potential EVAR candidate lacks adequate length of the normal-diameter aorta between the aneurysm and the takeoff of the renal arteries, the \"infra-renal neck\". Another relative  contraindications  include prohibitively small  iliac arteries , aneurysmal iliac arteries, prohibitively small  femoral arteries , or circumferential calcification of the femoral or iliac arteries. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2518", "text": "In addition to a short proximal aortic neck, the neck may be angulated, large in diameter, or shaped like a funnel (conical) where the neck diameter at the top is larger than the neck diameter at the bottom. Along with a short proximal aortic neck, necks with any of these characteristics are called \"hostile necks\" and endovascular repair can be either contraindicated or associated with early-late complications of endoleak, or endograft migration, or both. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2519", "text": "Many of the advances in EVAR technique aim to adapt EVAR for these situations, and advanced techniques allow EVAR to be employed in patients who previously were not candidates. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2520", "text": "The procedure is carried out in a sterile environment under  fluoroscopic  guidance.  It is usually carried out by a  vascular surgeon ,  interventional radiologist  or  cardiac surgeon , and occasionally,  general surgeon  or  interventional cardiologist . [ 9 ] [ 10 ] [ 11 ] [ 12 ]  The procedure can be performed under  general ,  regional (spinal or epidural)  or even  local anesthesia . [ 13 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2521", "text": "Access to the patient's femoral arteries can be with surgical incisions or  percutaneously  in the groin on both sides. Vascular sheaths are introduced into the patient's femoral arteries, through which guidewires, catheters, and the endograft are passed. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2522", "text": "Diagnostic angiography images are captured of the aorta to determine the location of the patient's renal arteries, so the stent-graft can be deployed without blocking these. Failure to achieve this will cause  kidney failure . With most devices, the \"main body\" of the endograft is placed first, followed by the \"limbs\" which join the main body and extend to the iliac arteries, effectively protecting the aneurysm sac from blood pressure. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2523", "text": "The abdominal aneurysm extends down to the common iliac arteries in about 25%-30% of patients. In such cases, the iliac limbs can be extended into the external iliac artery to bypass a common iliac aneurysm. Alternatively, a specially designed endograft, (an iliac branch device) can be used to preserve flow to the  internal iliac arteries . The preservation of the hypogastric (internal iliac) arteries is important to prevent buttock  claudication  and  impotence , and every effort should be made to preserve flow to at least one hypogastric artery. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2524", "text": "The endograft acts as an artificial lumen for blood to flow through, protecting the surrounding aneurysm sac. This reduces the pressure in the aneurysm, which itself will usually thrombose and shrink in size over time. [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2525", "text": "Staging such procedures is common, particularly to address aortic branch points near the diseased aortic segment. One example in the treatment of thoracic aortic disease is revascularization of the left common carotid artery and/or the left subclavian artery from the innominate artery or the right common carotid artery to allow treatment of a thoracic aortic aneurysm that encroaches proximally into the aortic arch. These \"extra-anatomic bypasses\" can be performed without an invasive  thoracotomy . Another example in the abdominal aorta is the embolization of the internal iliac artery on one side prior to coverage by an iliac limb device. Continued improvement in stent-graft design, including branched endografts, will reduce but not eliminate multi-stage procedures. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2526", "text": "Standard EVAR involves a surgical cut-down on either the femoral or iliac arteries, with the creation of a 4\u20136\u00a0cm incision. Like many surgical procedures, EVAR has advanced to a more  minimally invasive  technique, by accessing the femoral arteries  percutaneously  In percutaneous EVAR ( PEVAR ), small, sub-centimeter incisions are made over the femoral artery, and endovascular techniques are used to place the device over a wire. Percutaneous EVAR has been systematically compared to the standard EVAR cut-down femoral artery approach. [ 15 ]  Moderate quality evidence suggests that there are no differences in short-term mortality, aneurysm sealing, long and short-term complications, or infections at the wound site. [ 15 ]  Higher quality evidence suggests that there are no differences in post-repair bleeding complications or haematoma between the two approaches. [ 15 ]  The percutaneous approach may have reduced surgical time. [ 15 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2527", "text": "Fenestrated endovascular aortic/aneurysm repair (FEVAR) is performed in the cases where the aneurysm extends near or involves the visceral vessels (such as juxta-renal, para-renal, thoraco-abdominal aortic aneurysms). A custom-made graft with fenestrations (holes on the graft body to maintain the patency of the visceral arteries) is used for the procedure. When the aneurysm involves the visceral arteries, standard EVAR is  contraindicated  due to the lack of suitable infra-aortic segment for the endograft attachment; FEVAR achieves seal between the stent graft and para-visceral segment and/or more proximal segment while preserving the flow of the visceral arteries. FEVAR has been in use in the United Kingdom for over a decade and early results were published in Jun 2012.\n [ 16 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2528", "text": "Thoracoabdominal aortic aneurysms (TAAA) involve the aorta in the chest and abdomen. As such, major branch arteries to the head, arms, spinal cord, intestines, and kidneys may originate from the aneurysm. An endovascular repair of a TAAA is only possible if blood flow to these critical arteries is preserved. Hybrid procedures offer one option, but a more direct approach involves the use of a branched endograft. However, the complex anatomy associated with the supra-aortic vessels is particularly difficult to accommodate with branched endograft devices. [ 17 ]  Dr. Timothy Chuter pioneered this approach, with a completely endovascular solution. After partial deployment of the main body of an endograft, separate endograft limbs are deployed from the main body to each major aortic branch. This procedure is long, technically difficult, and currently only performed in a few centers.\nWhen the aneurysm begins above the renal arteries, neither fenestrated endografts nor \"EndoAnchoring\" of an infrarenal endograft is useful (an open surgical repair may be necessary). Alternatively, a \"branched\" endograft may be used. A branched endograft has graft limbs that branch off of the main portion of the device to directly provide blood flow to the kidneys or the visceral arteries. [ 18 ] [ 19 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2529", "text": "On occasion, there is inadequate length or quality of the proximal or distal aortic neck. In these cases, a fully minimally invasive option is not possible. One solution, however, is a hybrid repair, which combines an open surgical bypass with EVAR or TEVAR. In hybrid procedures, the endograft is positioned over major aortic branches. While such a position would normally cause problems from disruption of blood flow to the covered branches (renal, visceral, or branches to the head or arms), the prior placement of bypass grafts to these critical vessels allowed the deployment of the endograft at a level that would otherwise not be possible. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2530", "text": "If a patient has calcified or narrow femoral arteries that prohibit the introduction of the endograft transfemorally, an iliac conduit may be used. This is typically a piece of PTFE that is sewn directly to the iliac arteries, which are exposed via an open retroperitoneal approach. The endograft is then introduced into the aorta through the conduit. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2531", "text": "In patients with thoracic aortic disease involving the arch and descending aorta, it is not always possible to perform a completely endovascular repair. This is because head vessels of the aortic arch supplying blood to the brain cannot be covered and for this reason, there is often an inadequate landing zone for stent-graft delivery. A hybrid repair strategy offers a reasonable choice for treating such patients. A commonly used hybrid repair procedure is the \"frozen elephant trunk repair\". [ 20 ]  This technique involves midline sternotomy. The aortic arch is transected and the stent-graft device is delivered in an ante-grade fashion in the descending aorta. The aortic arch is subsequently reconstructed and the proximal portion of the stent-graft device is then directly sutured into the surgical graft. Patients with anomalies of the arch and some disease extension into the descending aorta are often ideal candidates. Studies have reported successful use of hybrid techniques for treating Kommerell diverticulum [ 21 ]  and descending aneurysms in patients with previous coarctation repairs. [ 22 ] [ 23 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2532", "text": "In addition, hybrid techniques combining both open and endovascular repair are also used in managing emergency complications in the aortic arch, such as retrograde ascending dissection and endoleaks from previous stent grafting of descending aorta. A \"reverse frozen elephant trunk repair\" is shown to be particularly effective. [ 24 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2533", "text": "The complications of EVAR can be divided into those that are related to the repair procedure and those related to the endograft device. For example, a  myocardial infarction  that occurs immediately after the repair is normally related to the procedure and not the device. By contrast, the development of an endoleak from degeneration of endograft fabric would be a device-related complication. [ 19 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2534", "text": "Durability and problems such as 'endoleaks' may require careful surveillance and adjuvant procedures to ensure the success of the EVAR or EVAR/hybrid procedure. CT angiography (CTA) imaging has, in particular, made a key contribution to planning, success, durability in this complex area of vascular surgery. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2535", "text": "A major cause of complications in EVAR is the failure of the seal between the proximal, infra-renal aneurysm neck and the endovascular graft. [ 27 ] [ 28 ] [ 29 ]  Risk of this form of failure is especially elevated in adverse or challenging proximal neck anatomies, where this seal could be compromised by unsuitable geometric fit between the graft and vessel wall, as well as instability of the anatomy. [ 30 ] [ 31 ] [ 32 ]  New recent techniques have been introduced to address these risks by utilizing a segment of the supra-renal portion of the aorta to increase the sealing zone, such as with fenestrated EVAR, chimneys and snorkels. [ 33 ]  These techniques may be suitable in certain patients with qualifying factors, e.g., configuration of renal arteries, renal function.  However, these are more complex procedures than standard EVAR and may be subject to further complications. [ 34 ] [ 35 ] [ 36 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2536", "text": "An approach that directly augments the fixation and sealing between the graft and aorta to mimic the stability of a surgical anastomosis is EndoAnchoring. [ 37 ] [ 38 ]  EndoAnchors are small, helically shaped implants that directly lock the graft to the aortic wall with the goal to prevent complications of the seal, especially in adverse neck anatomies. [ 39 ] [ 40 ]  These EndoAnchors may also be used to treat identified leaks between the graft and proximal neck. [ 41 ] [ 42 ] [ 43 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2537", "text": "Arterial dissection, contrast-induced kidney failure, thromboembolizaton,  ischemic colitis , groin  hematoma , wound infection, type II endoleaks, myocardial infarction, congestive heart failure, cardiac arrhythmias, respiratory failure. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2538", "text": "Endograft migration, aneurysm rupture, graft limb stenosis/kinking, type I/III/IV endoleaks, stent graft thrombosis, or infection. [ 44 ]  Device infection occurs in 1-5% of aortic prosthesis placements and is a life-threatening complication. [ 45 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2539", "text": "An endoleak is a leak into the aneurysm sac after endovascular repair. Five types of endoleaks exist: [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2540", "text": "Type I and III leaks are considered high-pressure leaks and are more concerning than other leak types. Depending on the aortic anatomy, they may require further intervention to treat. Type II leaks are common and often can be left untreated unless the aneurysm sac continues to expand after EVAR. [ 46 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2541", "text": "Spinal cord injury is a devastating complication after aortic surgery, specifically for thoracoabdominal aortic aneurysm repair; severe injury could lead to urine and fecal incontinence, paresthesia and even paraplegia. [ 47 ]  The risk varies between studies with two metanalysis demonstrating a pooled incidence of spinal cord injury 2.2% [ 48 ]  and 11%. [ 49 ]  Predictive factors include increasing extent of coverage, hypogastric artery occlusion, prior aortic repair and perioperative hypotension. [ 50 ]  Spinal cord injury related to aortic repair occurs due to impaired blood flow to the spine after coverage of blood vessels, important to the blood circulation of the spine, namely intercostal- and lumbar arteries. [ 51 ]  Neuromonitoring appears to be effective in detecting perioperative spinal cord injury risk during TEVAR. While the incidence of spinal cord injury remains variable, identification of risk factors may guide clinical decisions, particularly in high-risk procedures. [ 52 ]  A few methods exist for potentially reversing spinal cord injury, if it arises, elevated blood pressure, increased oxygenation, blood transfusion and cerebrospinal fluid drainage."}
{"_id": "WikiPedia_Radiology$$$corpus_2542", "text": "Cerebrospinal fluid drainage is one of the adjunct methods used to reverse spinal cord injury. With increased drainage of spinal fluid, the intrathecal pressure decreases which allows for increase blood perfusion to the spine, possibly reversing the ischemic injury of the spinal tissue due to lessened blood supply. The benefits of this procedure have been established in open aortic repair [ 53 ]  and suggested in endovascular aortic repair. [ 47 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2543", "text": "As compared to the traditional aortic repair, standard recovery after EVAR is faster with earlier ambulation. However, there is still risk of spinal cord injury early after the procedure. Patients who have undergone EVAR typically spend one night in the hospital to be monitored, although it has been suggested that EVAR can be performed as a same-day procedure. [ 54 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2544", "text": "Patients are advised to slowly return to normal activity. There are no specific activity restrictions after EVAR, however, patients typically are seen by their surgeon within one month after EVAR to begin post-EVAR surveillance. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2545", "text": "There is limited research looking at patients' experience of recovery after more complex and staged EVAR for thoracoabdominal aortic diseases. One qualitative study found that patients with complex aortic diseases struggle with physical and psychological setbacks, continuing years after their operations. [ 55 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2546", "text": "Dr.  Juan C. Parodi  introduced the minimally-invasive endovascular aneurysm repair (EVAR) to the world and performed the first successful endovascular repair of an abdominal aortic aneurysm on 7 September 1990 in Buenos Aires on a friend of  Carlos Menem , the then President of Argentina. The first device was simple, according to Parodi: \"It was a graft I designed with expandable ends, the extra-large Palmaz stent, a Teflon sheath with a valve, a wire, and the valvuloplasty balloon, which I took from the cardiologists.\" Parodi's first patient lived for nine years after the procedure and died from pancreatic cancer. [ 56 ] [ 57 ] \nThe first EVAR performed in the United States was in 1992 by Drs.  Frank Veith ,  Michael Marin ,  Juan Parodi  and  Claudio Schonholz  at  Montefiore Medical Center  affiliated with  Albert Einstein College of Medicine . [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2547", "text": "The modern endovascular device used to repair abdominal aortic aneurysms, which is bifurcated and modular, was pioneered and first employed by Dr. Timothy Chuter while a fellow at the  University of Rochester . [ 58 ]  The first clinical series of his device was published from Nottingham in 1994. [ 59 ]  The first endovascular repair of a ruptured abdominal aortic aneurysm was also reported from Nottingham in 1994. [ 60 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2548", "text": "By 2003, four devices were on the market in the United States. [ 61 ]  Each of these devices has since been either abandoned or further refined to improve its characteristics  in vivo ."}
{"_id": "WikiPedia_Radiology$$$corpus_2549", "text": "Women are known to have smaller aortas on average than men, so are potential candidates for AAA treatment at smaller maximum aneurysm diameters than men. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2550", "text": "As immunosuppressive medications are known to increase the rate of aneurysm growth, transplant candidates are AAA repair candidates at smaller maximum aneurysm diameters than the general population. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2551", "text": "Due to the expense associated with EVAR stent-graft devices and their specificity to human aortic anatomy, EVAR is not used in other animals. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2552", "text": "Endovascular coiling  is an  endovascular  treatment for  intracranial aneurysms  and  bleeding  throughout the body. The procedure reduces blood circulation to an aneurysm or blood vessel through the implantation of detachable platinum wires, with the clinician inserting one or more into the blood vessel or aneurysm until it is determined that blood flow is no longer occurring within the space. It is one of two main treatments for cerebral  aneurysms, the other being  surgical clipping ."}
{"_id": "WikiPedia_Radiology$$$corpus_2553", "text": "Endovascular coiling is typically used to treat  cerebral aneurysms . The main goal is prevention of rupture in unruptured aneurysms, and prevention of rebleeding in ruptured aneurysms by limiting blood circulation to the aneurysm space. Clinically, packing density is recommended to be 20-30% or more of the aneurysm's volume, typically requiring deployment of multiple wires. [ 1 ]  Higher volumes may be difficult due to the delicate nature of the aneurysm; intraoperative rupture rates are as high as 7.6% for this procedure. [ 2 ]  In ruptured aneurysms, coiling is performed quickly after rupture because of the high risk of rebleeding within the first few weeks after initial rupture. The patients most suitable for endovascular coiling are those with aneurysms with a small neck size (preferably <4\u00a0mm), luminal diameter <25\u00a0mm and those that are distinct from the parent vessel. [ 3 ]  Larger aneurysms are subject to compaction of coils, due to both looser packing densities (more coils are needed) and increased blood flow. Coil compaction renders them unsuitable as they are incapable of stemming blood flow. [ 4 ]  However, technological advances have made coiling of many other aneurysms possible as well."}
{"_id": "WikiPedia_Radiology$$$corpus_2554", "text": "A number of studies have questioned the efficacy of endovascular coiling over the more traditional surgical clipping. Most concerns involve the chance of later bleeds or other recanalization. [ 5 ] [ 6 ] [ 7 ]  Due to its less invasive nature, endovascular coiling usually presents faster recovery times than surgical clipping, with one study finding a significant decrease in probability of death or dependency compared to a neurosurgical population. [ 8 ]  Complication rates for coiling as well are generally found to be lower than microsurgery (11.7% and 17.6% for coiling and microsurgery, respectively). Despite this, intraoperative rupture rates for coiling have been documented as being as high as 7.6%. [ 2 ]  Clinical results are found to be similar at a two-month and one year follow-up between coiling and neurosurgery. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2555", "text": "Reported recurrence rates are quite varied, with rates between 20 and 50% of aneurysms recurring within one year of coiling, and with the recurrence rate increasing with time. [ 2 ] [ 10 ]  These results are similar to those previously reported by other endovascular groups. [ 11 ]  Other studies have questioned whether new matrix coils work better than bare platinum coils. [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2556", "text": "The  International Subarachnoid Aneurysm Trial  tested the efficacy of endovascular coiling against the traditional micro-surgical clipping. The study initially found very favorable results for coiling, however its results and methodology were criticized. Since the study's release in 2002, and again in 2005, some studies have found higher recurrence rates with coiling, while others have concluded that there is no clear consensus between which procedure is preferred. [ 13 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2557", "text": "Risks of endovascular coiling include  stroke , aneurysm rupture during the procedure and aneurysm recurrence and rupture after the procedure. [ 3 ]  Additionally in some patients coiling may not be successful. In general, coiling is only performed when the risk of aneurysm rupture is higher than the risks of the procedure itself."}
{"_id": "WikiPedia_Radiology$$$corpus_2558", "text": "Similar to patients who experience neurosurgical procedures, coiling results in an increase in resting energy expenditure, albeit at a slightly reduced rate than their neurosurgery counterpart. This can lead to malnutrition if steps are not taken to compensate for the increased metabolic rate. [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2559", "text": "The treatment works by promoting blood clotting ( thrombosis ) in the aneurysm, eventually sealing it from the blood flow. This is accomplished by decreasing the amount of blood flow going into the aneurysm, increasing the residence time of the blood (thereby lowering the velocity) in the aneurysm space and reducing the  wall shear stress  of the aneurysm wall. This change in the blood flow, or  hemodynamics , is ultimately dependent on several factors, including:"}
{"_id": "WikiPedia_Radiology$$$corpus_2560", "text": "While these factors are crucial to the success of the procedure, thrombosis ultimately is dependent on biological processes, with the coiling only providing the appropriate conditions for the process to occur, and hopefully closing the aneurysm."}
{"_id": "WikiPedia_Radiology$$$corpus_2561", "text": "Endovascular coiling is usually performed by an  interventional neuroradiologist  or neurosurgeon with the patient under general anaesthesia. The whole procedure is performed under  fluoroscopic imaging  guidance. A guiding catheter is inserted through the femoral artery and advanced to a site close to the aneurysm after which angiography is performed to localize and assess the aneurysm. After this, a microcatheter is navigated into the aneurysm."}
{"_id": "WikiPedia_Radiology$$$corpus_2562", "text": "The treatment uses detachable coils made of platinum that are inserted into the aneurysm using the microcatheter. A variety of coils are available, including Guglielmi Detachable Coils (GDC) which are platinum, Matrix coils which are coated with a biopolymer, and hydrogel coated coils. Coils are also available in a variety of diameters, lengths, and cross sections. [ 16 ]  A coil is first inserted along the aneurysm wall to create a frame, with the core then being filled with more coils. [ 17 ]  A series of progressively smaller coils may also be used. Success is determined by injecting a contrast dye into parent artery and qualitatively determining if dye is flowing into the aneurysm space during fluoroscopy. If no flow is observed, the procedure is considered completed. [ 2 ]  In the case of wide-necked aneurysms a  stent  may be used. [ 18 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2563", "text": "Endovascular coiling was a developed through the synthesis of a number of innovations that took place between 1970 and 1990 in the field of electronics, neurosurgery, and  interventional radiology . [ 4 ]  While the procedure itself has been and continues to be compared to surgical clipping, the development of the concept and procedure has resulted in it becoming the gold standard at many centers. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2564", "text": "The first documented technique of using metal coils to induce thrombosis was accomplished by Mullan in 1974. Copper coils were inserted into a giant aneurysm through externally puncturing the aneurysm wall via craniotomy. Five patients died, with ten having satisfactory process. [ 19 ]  It did not gain popularity due to the specialized equipment required, in addition to the technique being unsuitable for many types of aneurysms. [ 4 ]  Later, in 1980, similar techniques were developed by Alksne and Smith using iron suspended in  methyl methacrylate  in a limited set of patients. There were no deaths in 22 consecutive cases with low morbidity. [ 20 ]  This technique also did not gain traction due to advances in clipping. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2565", "text": "As a means of avoiding invasive methods, early endovascular interventions involved the usage of detachable and nondetachable  balloon catheters  to occlude the aneurysm while preserving the  parent artery . [ 21 ]  Despite the innovative approach, the aneurysms were often found to adapt to the shape of the balloon itself resulting in higher incidents of aneurysm rupture. This procedure was deemed \"uncontrollable\" due to its high morbidity and mortality rate, but it demonstrated that the endovascular approach was feasible for many aneurysms. [ 4 ]  Endovascular coils would later be used in 1989 by Hilal et al., but these were short, stiff coils that offered no control, preventing dense packing of the aneurysm. [ 22 ]  Controllable microguidewire systems were later used. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2566", "text": "In 1983 the use of electrically induced thrombosis for intracranial aneurysms was described for the first time. [ 23 ]  A stainless steel electrode  supplied a positive current to the aneurysm to stimulate electrothrombosis. Minimal occlusion was achieved, but the researchers discovered that the erosion of the electrode due to  electrolysis  would be useful as a detachment system. [ 4 ]  Detachable coils were constructed from a platinum coil soldered to a stainless steel delivery wire, first described in 1991 by Guglielmi et al. [ 3 ]  When combined with a controllable microguide wire system, multiple coils could be inserted to fully pack an aneurysm. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2567", "text": "Given the complexity of modeling the vasculature, much research has been devoted towards modeling the hemodynamics of an aneurysm before and after an intervention. Techniques such as  particle image velocimetry  (PIV) and  computational fluid dynamics / finite element analysis  (CFD/FEA) have yielded results that have influenced the direction of research, but no model to date has been able to account for all factors present. [ 2 ] [ 24 ] [ 25 ]  Advantages of the  in-silico  research method include flexibility of selecting variables, but one comparative study has found that simulations tend to over-emphasis results compared to PIV, and are more beneficial for trends than exact values. [ 25 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2568", "text": "Medical images, particularly  CT angiography , can be used to generate 3D reconstructions of patient specific anatomy. When combined with CFD/FEA, hemodynamics can be estimated in patient specific simulations, giving the clinician greater predictive tools for surgical planning and outcome evaluation to best promote thrombus formation. [ 26 ] [ 27 ]  However, most computer models use many assumptions for simplicity, including rigid walls (non-elastic) for vasculature, substituting a porous medium in place of physical coil representations, and  navier-stokes  for fluid behavior. However, new predictive models are being developed as computational power increases, including algorithms for simulations of coil behavior in-vivo. [ 16 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2569", "text": "Ethylene vinyl alcohol  ( EVOH ) is a formal  copolymer  of  ethylene  and  vinyl alcohol .  Because the latter  monomer  mainly exists as its  tautomer   acetaldehyde , the copolymer is prepared by polymerization of ethylene and  vinyl acetate  to give the  ethylene vinyl acetate  (EVA) copolymer followed by hydrolysis.  EVOH copolymer is defined by the mole\u00a0% ethylene content: lower ethylene content grades have higher barrier properties; higher ethylene content grades have lower temperatures for  extrusion ."}
{"_id": "WikiPedia_Radiology$$$corpus_2570", "text": "The  plastic  resin is commonly used as an oxygen barrier in  food packaging .  It is better than other plastics at keeping air out and flavors in, is highly transparent, weather resistant, oil and solvent resistant, flexible, moldable, recyclable, and printable.  Its drawback is that it is difficult to make and therefore more expensive than other food packaging.  Instead of making an entire package out of EVOH, manufacturers keep costs down by coextruding or laminating it as a thin layer between cardboard, foil, or other plastics. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2571", "text": "It is also used as a hydrocarbon barrier in plastic fuel tanks and pipes."}
{"_id": "WikiPedia_Radiology$$$corpus_2572", "text": "Because of the high capital cost to build an EVOH plant, and the complexity of making a food grade product, only a few companies produce EVOH:"}
{"_id": "WikiPedia_Radiology$$$corpus_2573", "text": "Kuraray  produces EVOH resin under the name \"EVAL,\" with a 10,000 ton plant in Okayama, Japan; a 58,000 ton plant in the U.S. (near Houston, TX) under its subsidiary Kuraray America; and a 35,000 ton plant in Belgium under its subsidiary EVAL Europe. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2574", "text": "Nippon Gohsei produces EVOH under the trade name Soarnol.  It has production sites in Mizushima, Japan; La Porte, Texas in the USA; and at  Salt End ,  Hull , England. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2575", "text": "Chang Chun Petrochemical produces EVOH under the trade name EVASIN.  It has a single site in Taipei, Taiwan."}
{"_id": "WikiPedia_Radiology$$$corpus_2576", "text": "Due to its strong barrier against gasses (especially oxygen), odors and flavours, [ 5 ]  food packaging manufacturers use EVOH in their packaging structure to extend the shelf life of food products. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2577", "text": "A downside of EVOH is its relatively high moisture sensitivity, meaning that the barrier capabilities of EVOH decrease in environments with high humidity. [ 7 ]  As such, EVOH is often applied within a multilayer film. Here, one or more inside layers contain EVOH, but the outside layers consist of a different plastic that is less sensitive to moisture, such as  polyethylene ."}
{"_id": "WikiPedia_Radiology$$$corpus_2578", "text": "EVOH is used in a liquid embolic system in  interventional radiology , e.g. in  Onyx . [ 8 ]  Dissolved in  dimethyl sulfoxide  (DMSO) and mixed with a radiopaque substance, ethylene vinyl alcohol copolymer is used to  embolize   blood vessels ."}
{"_id": "WikiPedia_Radiology$$$corpus_2579", "text": "Hemorrhoidal artery embolization  (HAE, or hemorrhoid artery embolization) is a non-surgical treatment of internal  hemorrhoids. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2580", "text": "The procedure involves blocking the abnormal blood flow to the rectal (hemorrhoidal) arteries using microcoils and/or  microparticles  to decrease the size of the hemorrhoids and improve hemorrhoid related symptoms, especially bleeding. [ 2 ]  It is a  minimally invasive therapy  that can be performed as an outpatient procedure. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2581", "text": "HAE begins when a  catheter  is inserted into the femoral or radial artery through a small incision. The catheter is then carefully navigated through the arterial system with  x-ray  guidance until it reaches the branches of the  superior rectal artery  that supply blood to the hemorrhoidal plexus. [ 3 ]  Once in position,  microparticles  and/or microcoils are injected through the catheter to block these arteries, thereby reducing the blood supply to the hemorrhoids. This causes the hemorrhoidal tissue to shrink over time, alleviating symptoms such as pain, bleeding, and swelling. [ 1 ] [ 2 ] [ 4 ]  Post-procedure, patients are monitored for a brief period to ensure stability before being discharged with instructions for managing any minor discomfort or symptoms that may occur during the recovery period."}
{"_id": "WikiPedia_Radiology$$$corpus_2582", "text": "HAE offers several benefits as a minimally invasive treatment for symptomatic hemorrhoids. Firstly, HAE effectively reduces blood flow to the hemorrhoidal tissue, leading to significant shrinkage and resolution of symptoms such as pain, bleeding, and prolapse. [ 2 ] [ 4 ]  This approach has been shown to provide long-lasting relief comparable to surgical methods but with potentially lower complication rates and faster recovery times. [ 5 ]  Additionally, HAE is associated with minimal post-procedural pain and allows for quicker return to daily activities, making it an attractive option for patients seeking less invasive treatment options. [ 5 ]  Moreover, its safety profile and efficacy have been supported by clinical trials, demonstrating its potential as a preferred alternative for managing hemorrhoidal disease. [ 6 ] [ 7 ] [ 8 ]  HAE is very effective at stopping bleeding related symptom with success rate of approximately 90%. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2583", "text": "The incidence of adverse events with HAE is very low. Rare arterial access site complications may occur. [ 2 ]   Although minor anal discomfort can occur in a minority of patients, there have been no reports of anorectal complications when embolization is performed primarily with microcoils [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2584", "text": "Hepatic artery embolization , also known as  trans-arterial embolization (TAE) , is one of the several therapeutic methods to treat primary liver tumors or  metastases  to the liver. The  embolization  therapy can reduce the size of the tumor, and decrease the tumor's impact such its hormone production, effectively decreasing symptoms. The treatment was initially developed in the early 1970s. [ 1 ]  The  several types of hepatic artery treatments are based on the observation that tumor cells get nearly all their nutrients from the hepatic artery, while the normal cells of the liver get about 70-80 percent of their nutrients and 50% their oxygen supply from the portal vein, and thus can survive with the hepatic artery effectively blocked. [ 2 ]  In practice, hepatic artery embolization occludes the blood flow to the tumors, [ 3 ]  achieving significant tumor shrinkage in over 80% of people. [ 3 ]  Shrinkage rates vary. [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2585", "text": "The  several types of  hepatic artery  treatments are based on the observation that  tumor cells  get nearly all their nutrients from the hepatic artery, while the normal cells of the liver get about 70-80 percent of their nutrients and 50% their oxygen supply from the  portal vein , and thus can survive with the hepatic artery effectively blocked. [ 2 ]  In practice,  hepatic artery embolization is an option if the neoplastic growth is mainly within the liver. [ 6 ]  By occluding the blood supply to the tumors, [ 3 ]  achieving significant tumor shrinkage in over 80% of people. [ 3 ]  Shrinkage rates vary. [ 4 ]  The therapy can effectively decrease symptoms by reducing the size of the tumor, or by decreasing the tumor's impact, for example by decreasing the tumor's production of  hormones . [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2586", "text": "Primary liver tumors, metastatic  neuroendocrine tumors  to the liver [ 8 ]  and other  metastases  to the liver [ 9 ] [ 10 ]  may be considered for therapy directed via the hepatic artery."}
{"_id": "WikiPedia_Radiology$$$corpus_2587", "text": "The percutaneous  Seldinger technique  introduces a  catheter , which is a thin flexible tube made of medical grade material, into the  hepatic artery  under radiological control. [ 11 ] [ 12 ]  This approach was developed for  metastatic   neuroendocrine tumors  in the early 1970s. [ 1 ]  Tumor cells get over 90% of their nutrients from the hepatic artery, [ 1 ]  while the normal cells of the liver get about 70-80 percent of their nutrients and 50% their oxygen supply from the portal vein, and thus can survive with the hepatic artery effectively blocked. [ 1 ] [ 2 ]  Once the catheter is carefully placed in the artery or in a selected branch, the blood flow can be occluded by injecting various items, such as plastic particles, glue, metal coils, foam, or by deploying a balloon. [ 11 ]  Additional considerations and procedural details have been reviewed. [ 1 ] [ 13 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2588", "text": "In hepatic artery chemotherapy (HAC), chemotherapy agents are given into the hepatic artery, often by steady infusion over hours or even days. Compared with systemic chemotherapy, a higher proportion of the chemotherapy agents is (in theory) delivered to the lesions in the liver. [ 14 ] [ 15 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2589", "text": "Hepatic artery chemoembolization (HACE), sometimes called  transarterial chemoembolization  (TACE), combines hepatic artery embolization with hepatic artery chemo infusion. In one method, embospheres bound with chemotherapy agents injected into the hepatic artery, lodge in downstream capillaries. The spheres not only block blood flow to the lesions but by halting the chemotherapy agents in the neighborhood of the lesions, they provide a much better targeting leverage than chemo infusion provides."}
{"_id": "WikiPedia_Radiology$$$corpus_2590", "text": "Image-guided radiation therapy  (IGRT) is the process of frequent  imaging , during a course of  radiation treatment , used to direct the treatment, position the patient, and compare to the pre-therapy imaging from the  treatment plan . [ 1 ]  Immediately prior to, or during, a treatment fraction, the patient is localized in the treatment room in the same position as planned from the reference imaging dataset. An example of IGRT would include comparison of a  cone beam computed tomography  (CBCT) dataset, acquired on the treatment machine, with the  computed tomography  (CT) dataset from planning. IGRT would also include matching planar kilovoltage (kV) radiographs or megavoltage (MV) images with digital reconstructed radiographs (DRRs) from the planning CT."}
{"_id": "WikiPedia_Radiology$$$corpus_2591", "text": "This process is distinct from the use of imaging to delineate targets and organs in the planning process of radiation therapy. However, there is a connection between the imaging processes as IGRT relies directly on the imaging modalities from planning as the reference coordinates for localizing the patient. The variety of medical imaging technologies used in planning includes  x-ray computed tomography  (CT),  magnetic resonance imaging  (MRI), and  positron emission tomography  (PET) among others."}
{"_id": "WikiPedia_Radiology$$$corpus_2592", "text": "IGRT can help to reduce errors in set-up and positioning, allow the margins around target tissue when planning to be reduced, and enable treatment to be adapted during its course, with the aim of overall improving outcomes. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2593", "text": "The goal of the IGRT process is to improve the accuracy of the radiation field placement, and to reduce the exposure of healthy tissue during radiation treatments. In years past, larger planning target volume (PTV) margins were used to compensate for localization errors during treatment. [ 4 ]  This resulted in healthy human tissues receiving unnecessary doses of radiation during treatment. PTV margins are the most widely used method to account for geometric uncertainties. By improving accuracy through IGRT, radiation is decreased to surrounding healthy tissues, allowing for increased radiation to the tumour for control. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2594", "text": "Currently, certain radiation therapy techniques employ the process of  intensity-modulated radiotherapy (IMRT) . This form of radiation treatment uses computers and linear accelerators to sculpt a three-dimensional radiation dose map, specific to the target's location, shape and motion characteristics. Because of the level of precision required for  IMRT , detailed data must be gathered about tumour locations. The single most important area of innovation in clinical practice is the reduction of the planning target volume margins around the location. The ability to avoid more normal tissue (and thus potentially employ dose escalation strategies) is a direct by-product of the ability to execute therapy with the most accuracy. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2595", "text": "Modern, advanced radiotherapy techniques such as proton and charged particle radiotherapy enable superior precision in the dose delivery and spatial distribution of the effective dose. Today, those possibilities add new challenges to IGRT, concerning required accuracy and reliability. [ 5 ]  Suitable approaches are therefore a matter of intense research."}
{"_id": "WikiPedia_Radiology$$$corpus_2596", "text": "IGRT increases the amount of data collected throughout the course of therapy. Over the course of time, whether for an individual or a population of patients, this information will allow for the continued assessment and further refinement of treatment techniques. The clinical benefit for the patient is the ability to monitor and adapt to changes that may occur during the course of radiation treatment. Such changes can include tumor shrinkage or expansion, or changes in shape of the tumor and surrounding anatomy. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2597", "text": "The precision of IGRT is significantly improved when technologies that were originally developed for  image-guided surgery , such as the  N-localizer [ 6 ]  and Sturm-Pastyr localizer, [ 7 ]  are used in conjunction with these medical imaging technologies. SRT provides a Non-Surgical Alternative for Non-Melanoma Skin Cancer & an Effective Solution for Keloids."}
{"_id": "WikiPedia_Radiology$$$corpus_2598", "text": "Sensus Healthcare is a manufacturer and distributor of this device With a compact 30\u201dx30\u201d footprint, the mobile unit delivers a precise and calibrated dose of SRT that penetrates only five millimeters below the skin\u2019s surface\u2014making it one of the safest and most effective alternative cancer treatments available. Unlike more powerful radiotherapy devices, the SRT-100\u2122 carefully destroys malignant skin cancer cells while preserving healthy tissue."}
{"_id": "WikiPedia_Radiology$$$corpus_2599", "text": "Radiation therapy is a local treatment that is designed to treat the defined tumour and spare the surrounding normal tissue from receiving doses above specified dose tolerances. There are many factors that may contribute to differences between the planned dose distribution and the delivered dose distribution. One such factor is uncertainty in patient position on the treatment unit. IGRT is a component of the radiation therapy process that incorporates imaging coordinates from the treatment plan to be delivered in order to ensure the patient is properly aligned in the treatment room. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2600", "text": "The localization information provided through IGRT approaches can also be used to facilitate robust treatment planning strategies and enable patient modelling, which is beyond the scope of this article. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2601", "text": "In general, at the time of 'planning' (whether a clinical mark up or a full simulation) the intended area for treatment is outlined by the radiation oncologist. Once the area of treatment was determined, marks were placed on the skin. The purpose of the ink marks was to align and position the patient daily for treatment to improve reproducibility of field placement. By aligning the markings with the radiation field (or its representation) in the radiation therapy treatment room, the correct placement of the treatment field could be identified. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2602", "text": "Over time, with improvement in technology \u2013 light fields with cross hairs, isocentric lasers \u2013 and with the shift to the practice of 'tattooing' \u2013 a procedure where ink markings are replaced with a permanent mark by the application of ink just under the first layer of skin using a needle in documented locations - the reproducibility of the patient's setup improved. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2603", "text": "Portal imaging is the acquisition of images using a radiation beam that is being used for giving radiation treatment to a patient. [ 10 ]  If not all of the radiation beam is absorbed or scattered in the patient, the portion that passes through may be measured and used to produce images of the patient."}
{"_id": "WikiPedia_Radiology$$$corpus_2604", "text": "It is difficult to establish the initial use of portal imaging to define radiation field placement. From the early days of radiation therapy,  X-rays  or  gamma rays  were used to develop large format radiographic films for inspection. With the introduction of  cobalt-60  machines in the 1950s, radiation went deeper inside the body, but with lower contrast and poor subjective visibility. Today, using advancements in digital imaging devices, the use of electronic portal imaging has developed into both a tool for accurate field placement and as a quality assurance tool for review by radiation oncologists during check film reviews. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2605", "text": "Electronic portal imaging is the process of using digital imaging, such as a CCD video camera, liquid ion chamber and amorphous silicon flat panel detectors to create a digital image with improved quality and contrast over traditional portal imaging. The benefit of the system is the ability to capture images, for review and guidance, digitally. [ 11 ]  These systems are in use throughout clinical practice. [ 12 ]  Current reviews of Electronic Portal Imaging Devices (EPID) show acceptable results in imaging irradiations and in most clinical practice, provide sufficiently large fields-of-view. kV is not a portal imaging feature. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2606", "text": "Fluoroscopy is an imaging technique that uses a fluoroscope, in coordination with either a screen or image-capturing device to create real-time images of patients' internal structures."}
{"_id": "WikiPedia_Radiology$$$corpus_2607", "text": "Digital X-ray equipment mounted in the radiation treatment device is often used to picture the patient\u2019s internal anatomy at time before or during treatment, which then can be compared to the original planning CT series. Usage of an orthogonal set-up of two radiographic axes is common, to provide means for highly accurate patient position verification. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2608", "text": "A medical imaging method employing tomography where digital geometry processing is used to generate a three-dimensional image of the internal structures of an object from a large series of two-dimensional X-ray images taken around a single axis of rotation. CT produces a volume of data, which can be manipulated, through a process known as windowing, in order to demonstrate various structures based on their ability to attenuate and prevent transmission of the incident X-ray beam."}
{"_id": "WikiPedia_Radiology$$$corpus_2609", "text": "With the growing recognition of the utility of CT imaging in using guidance strategies to match treatment volume position and treatment field placement, several systems have been designed that place an actual conventional 2-D CT machine in the treatment room alongside the treatment linear accelerator. The advantage is that the conventional CT provides accurate measure of tissue attenuation, which is important for dose calculation (e.g. CT on rails). [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2610", "text": "Cone-beam   computed tomography  (CBCT) based image guided systems have been integrated with medical linear accelerators to great success. With improvements in flat-panel technology, CBCT has been able to provide volumetric imaging, and allows for radiographic or fluoroscopic monitoring throughout the treatment process. Cone beam CT acquires many projections over the entire volume of interest in each projection. Using reconstruction strategies pioneered by Feldkamp, the 2D projections are reconstructed into a 3D volume analogous to the CT planning dataset."}
{"_id": "WikiPedia_Radiology$$$corpus_2611", "text": "Megavoltage computed tomography  (MVCT) is a medical imaging technique that uses the Megavoltage range of X-rays to create an image of bony structures or surrogate structures within the body. The original rational for MVCT was spurred by the need for accurate density estimates for treatment planning. Both patient and target structure localization were secondary uses. A test unit using a single linear detector, consisting of 75 cadmium tungstate crystals, was mounted on the linear accelerator gantry. [ citation needed ]  The test results indicated a spatial resolution of .5mm, and a contrast resolution of 5% using this method. While another approach could involve integrating the system directly into the MLA [ clarification needed ] , it would limit the number of revolutions to a number prohibitive to regular use. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2612", "text": "Optical tracking entails the use of a camera to relay positional information of objects within its inherent coordinate system by means of a subset of the electromagnetic spectrum of wavelengths spanning ultra-violet, visible, and infrared light. Optical navigation has been in use for the last 10 years within  image-guided surgery  (neurosurgery, ENT, and orthopaedic) and has increased in prevalence within radiotherapy to provide real-time feedback through visual cues on graphical user interfaces (GUIs). For the latter, a method of calibration is used to align the camera's native coordinate system with that of the isocentric reference frame of the radiation treatment delivery room.  Optically tracked tools are then used to identify the positions of patient reference set-up points and these are compared to their location within the planning CT coordinate system. A computation based on least-squares methodology is performed using these two sets of coordinates to determine a treatment couch translation that will result in the alignment of the patient's planned isocenter with that of the treatment room. These tools can also be used for intra-fraction monitoring of patient position by placing an optically tracked tool on a region of interest to either initiate radiation delivery (i.e. gating regimes) or action (i.e. repositioning). Alternatively, products such as AlignRT (from Vision RT) allow for real time feedback by imaging the patient directly and tracking the skin surface of the patient."}
{"_id": "WikiPedia_Radiology$$$corpus_2613", "text": "The first clinically active MRI-guided radiation therapy machine, the ViewRay device, was installed in St. Louis, MO, at the  Alvin J. Siteman Cancer Center  at Barnes-Jewish Hospital and Washington University School of Medicine. Treatment of the first patients was announced in February 2014. [ 13 ]  Other radiation therapy machines which incorporate real-time MRI tracking of tumors are currently in development. MRI-guided radiation therapy enables clinicians to see a patient's internal anatomy in real-time using continual soft-tissue imaging and allows them to keep the radiation beams on target when the tumour moves during treatment. [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2614", "text": "Ultrasound is used for daily patient setup. It is useful for soft tissue such as the breast and prostate. The BAT (Best Nomos) and Clarity (Elekta) systems are the two main systems currently being used. The Clarity system has been further developed to enable intra-fraction prostate motion tracking via trans-perineal imaging."}
{"_id": "WikiPedia_Radiology$$$corpus_2615", "text": "While not IGRT per se, electromagnetic transponder systems seek to serve exactly the same clinical function as CBCT or kV X-ray, yet provide for more temporally continuous analysis of setup error analogous to that of the optical tracking strategies. Hence, this technology (although entailing the use of no \"images\") is usually classified as an IGRT approach."}
{"_id": "WikiPedia_Radiology$$$corpus_2616", "text": "There are two basic correction strategies used while determining the most beneficial patient position and beam structure: on-line and off-line correction. Both serve their purposes in the clinical setting, and have their own merits. Generally, a combination of the both strategies is employed. Often, a patient will receive corrections to their treatment via on-line strategies during their first radiation session, and physicians make subsequent adjustments off-line during check film rounds. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2617", "text": "The On-line strategy makes adjustment to patient and beam position during the treatment process, based on continuously updated information throughout the procedure. [ 8 ]  The on-line approach requires a high-level of integration of both software and hardware. The advantage of this strategy is a reduction in both systematic and random errors. An example is the use of a marker-based program in the treatment of prostate cancer at Princess Margaret Hospital. Gold markers are implanted into the prostate to provide a surrogate position of the gland. Prior to each day's treatment, portal imaging system results are returned. If the center of the mass has moved greater than 3mm, then the couch is readjusted and a subsequent reference image is created. [ 4 ]  Other clinics correct for any positional errors, never allowing for >1\u00a0mm error in any measured axes."}
{"_id": "WikiPedia_Radiology$$$corpus_2618", "text": "The Off-line strategy determines the best patient position through accumulated data gathered during treatment sessions, almost always initial treatments. Physicians and staff measure the accuracy of treatment and devise treatment guidelines during using information from the images. The strategy requires greater coordination than on-line strategies. However, the use of off-line strategies does reduce the risk of systematic error. The risk of random error may still persist, however."}
{"_id": "WikiPedia_Radiology$$$corpus_2619", "text": "An  inferior vena cava filter  is a  medical device  made of metal that is  implanted  by  vascular surgeons  or  interventional radiologists  into the  inferior vena cava  to prevent a life-threatening  pulmonary embolism  (PE) or  venous thromboembolism  (VTE). [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2620", "text": "The filter is designed to trap a  blood clot  and prevent its travel to the  lung  where it would form a pulmonary embolism. [ 4 ] [ 3 ]  Their effectiveness and safety profile is well established, and they may be used when  anticoagulant treatment  is not sufficient. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2621", "text": "Results from the PREPIC study and other studies which have shown many long-term complications of IVC filters led to the introduction of retrievable IVC filters. [ 6 ]  The first retrievable IVC filters were approved by FDA in 2003 and 2004. [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2622", "text": "In 2012, the  American College of Chest Physicians  recommended IVC filters for those with  contraindications  to  anticoagulation  who either have acute PE or acute  proximal deep vein thrombosis  (above the knee). [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2623", "text": "The first IVC filter was created by  Kazi Mobin-Uddin  who published his findings in 1969 in the  New England Journal of Medicine . [ 10 ] [ 11 ] [ 12 ] [ 13 ]  The Mobin-Uddin filter was later replaced by the Greenfield filter developed by  Lazar Greenfield  which had a lower rate of filter related complications. [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2624", "text": "While the ability to retrieve a filter does exist for many models, it cannot be guaranteed that all cases of filter placement will allow for, or be indicated for retrieval.  Thus, the requirements and indications for permanent placement of filters is used to decide on when to use both permanent and temporary IVC filters. [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2625", "text": "Long-term risk factors must be considered as well, to include life expectancy of more than six months following insertion, and the ability of the patient to comply with anticoagulation therapy. [ 5 ]  The decision to use a filter that is temporary vs permanent basically is tied to the expected duration of time that protection is needed to prevent pulmonary emboli from passing to the heart and lungs. One such guideline is outlined below: [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2626", "text": "While many  studies have been done on the efficacy of Vena Cava filters, there still have not been any major studies done on the actual placement and removal of the filters regarding standard guidelines.  Which is why the Society of Interventional Radiology created a multidisciplinary panel that developed the following guidelines to see if someone qualifies for implantation: [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2627", "text": "These are patients that should strongly consider having IVC filter placement, as they are at greatest risk of pulmonary embolus."}
{"_id": "WikiPedia_Radiology$$$corpus_2628", "text": "This is a maybe category; normally it represents patients who could benefit from an IVC filter, but may be just fine without one as well. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2629", "text": "These are usually very controversial reasons to do an IVC filter, and most radiologists and doctors generally will not recommend an IVC filter if other options are available instead."}
{"_id": "WikiPedia_Radiology$$$corpus_2630", "text": "There is no current published data confirming the benefit of removing an IVC.  Because of this, the Society of Interventional Radiology created a multidisciplinary panel that developed the following guidelines to see if someone qualifies for removal: [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2631", "text": "An IVC filter, just by doing its job properly (catching embolic material), can eventually fill up with embolic material and cause a circulatory impairment that may warrant revision with vascular surgery (new filter, stent additions, or otherwise). A representative case has been reported in science journalism of the type that reports interesting unusual causes and solutions of symptoms; [ 16 ]  in this instance, the symptom was  orthostatic hypotension . [ 16 ]  Physicians speculate that this problem is uncommon but nonetheless worth consideration in differential diagnosis. [ 16 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2632", "text": "In those with initial acute proximal DVT or acute PE who had IVC filters placed instead of  anticoagulation , and who have their risk of bleeding resolve, the  American College of Chest Physicians  suggested, in 2012, that they receive a standard course of  anticoagulation . [ 8 ] [ 9 ]  While IVC filters are associated with a long term risk of DVT, [ 17 ]  they are not, alone, reason enough to maintain extended anticoagulation. [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2633", "text": "The main function of a vena cava filter is to prevent death from massive pulmonary emboli.  Long-term clinical follow-up studies have shown that this is accomplished in 96% of cases having a standard stainless-steel Greenfield filter. [ 18 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2634", "text": "In August, 2010, the FDA released an Initial Communication on the Risk and Adverse events associated with Long Term use of an inferior vena cava filter. [ 19 ]    Over a period of about 5 years, they identify 921 events.  While not the majority of cases, that number still represents a statistical significance of the use of long-term IVCs."}
{"_id": "WikiPedia_Radiology$$$corpus_2635", "text": "Of these IVC filter side effects, 328 involved device migration, 146 involved embolizations after detachment of device components, 70 involved perforation of the IVC, and 56 involved filter fracture. Much of the medical community believes that this large number of adverse events is related to the heart filter remaining in place for longer than necessary."}
{"_id": "WikiPedia_Radiology$$$corpus_2636", "text": "Common issues relating to failure, to include death (the other 4% of cases) include:"}
{"_id": "WikiPedia_Radiology$$$corpus_2637", "text": "While these side effects are not common (less than 10-20% of patients), many do report issues stemming from the placement and complication of the IVC while inside of the body. [ 20 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2638", "text": "Numerous small published articles and case studies report describe similar issues to the above.  Most notably:"}
{"_id": "WikiPedia_Radiology$$$corpus_2639", "text": "Even though the cases above are the exception, and not the rule, most radiologists object to doing prophylactic filter insertions in patients who do not have thromboembolic diseases. [ 32 ]  For the most part, whenever possible, interventional radiologists would rather start the patient on anticoagulants than use an IVC, even if requested or referred via a doctor. [ 33 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2640", "text": "While most IVC filters are made of non-ferromagnetic materials, there are a few types that are weakly ferromagnetic. Accordingly, IVC filters fall under the MRI Safe and MRI Conditional categories depending mostly on type of material used during construction.  Rarely will one find an MRI Not Safe IVC filter, as most of the steel, and other ferromagnetic material devices have been discontinued via the FDA. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2641", "text": "IVC filters are attached to the vena cava via hooks on their ends. Some are compression springs, which compress outward onto the side wall of the vena cava; however, they still have small hooks that retain their location.  These hooks aid in the anchoring and healing process, as they allow the tissues to 'ingrow' around them, securing the IVC in place.  It is unlikely, then, after 4 to 6 weeks of healing, that an MRI of 1.5 tesla, up to 3 tesla, will cause any level of dislodging to occur to the IVC filter. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2642", "text": "Studies of MR examination of both animals and humans, with implanted IVC filters, have not reported complications or symptomatic filter displacement. [ 34 ] [ 35 ] [ 36 ] [ 37 ] [ 38 ] [ 39 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2643", "text": "Several animal studies have even used \"real-time\" MR for the placement of IVC filters to check for rotation, sheering, and other artifacts. [ 40 ] [ 41 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2644", "text": "As part of the 'routing' survey for MRI studies, patients who have IVC filters will often need verification from the doctor, or medical records, to state that the IVC is safe for the MRI.  Most patients with weakly or non-safe ferromagnetic implants will be given a card, which they keep on their person at all time, that can help isolate if it is safe to do an MRI."}
{"_id": "WikiPedia_Radiology$$$corpus_2645", "text": "For patients who have been denied MRI scans for safety reasons, doctors usually recommend the CT scan with contrast as an alternative."}
{"_id": "WikiPedia_Radiology$$$corpus_2646", "text": "Most IVC filters that have been tested have been labeled as \u201cMRi safe\u201d; the remainder of IVC filters that have been tested are \u201cMR conditional.\u201d Patients who have been treated with nonferromagnetic IVC filters can undergo MR examination any time after filter implantation. In patients who have been treated with a weakly ferromagnetic IVC filter (Gianturco bird nest IVC filter [Cook], stainless steel Greenfield vena cava filter [Boston Scientific]), it is advised that the patient wait at least six weeks before undergoing an MR examination (because these older devices initially may not be anchored as firmly in place as other devices discussed in the present context), unless there is a strong clinical indication to perform the MR examination sooner after implantation, and as long as there is no reason to suspect that the device is not positioned properly or that it is not firmly in place. Most studies of IVC filters have generally been conducted at 1.5 tesla or less, although many IVC filters have now been evaluated at 3 tesla and deemed acceptable for MR examination. [ 42 ] [ 43 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2647", "text": "IVC filters are placed endovascularly, meaning that they are inserted via the blood vessels.  Historically, IVC filters were placed surgically, but with modern filters that can be compressed into much thinner  catheters , access to the venous system can be obtained via the  femoral vein  (the large vein in the groin), the  internal jugular vein  (the large vein in the neck) or the arm veins with one design.  Choice of route depends mainly on the number and location of any  blood clot  within the venous system.  To place the filter, a catheter is guided into the IVC using fluoroscopic guidance, then the filter is pushed through the catheter and deployed into the desired location, usually just below the junction of the IVC and the lowest  renal vein . [ 44 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2648", "text": "Review of prior cross-sectional imaging or a venogram of the IVC is performed before deploying the filter to assess for potential anatomic variations, thrombi within the IVC, or areas of stenoses, as well as to estimate the diameter of the IVC.  Rarely, ultrasound-guided placement is preferred in the setting of contrast allergy,  chronic kidney disease , and when patient immobility is desired.  The size of the IVC may affect which filter is deployed, as some (such as the Birds Nest) are approved to accommodate larger cavae.  There are situations where the filter is placed above the renal veins (e.g. pregnant patients or women of childbearing age, renal or gonadal vein thromboses, etc.).  Also, if there is duplication of the IVC, the filter is placed above the confluence of the two IVCs  [ 45 ]  or a filter can be placed within each IVC. [ 46 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2649", "text": "The concept of a removable IVC filter was first conceived in 1967. [ 47 ]   In 2003 and 2004 that the United States Food and Drug Administration first approved retrievable filters. [ 48 ]   In 2005 that the Society of Interventional Radiology (SIR) convened a multidisciplinary conference to address the clinical application of nonpermanent vena cava filters. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2650", "text": "Retrievable filters are fitted with a device (varying from model to model) that allows them to be easily  snared  and pulled back into a catheter and removed from the body, often through the  jugular vein . Prior to 2004, filters that had been in the IVC for less than three weeks were considered suitable to attempt retrieval, as filters that have been in place longer might have been overgrown by cells from the IVC wall and there was an increased risk of IVC injury if the filter is dislodged. Newer designs, and developments in techniques mean that some filters can now be left in for prolonged periods and retrievals after a year are now being reported. [ 49 ]  This would include the ALN, Bard G2 and G2x, Option, Tulip and Celect filters. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2651", "text": "It is important to note that the clinical exam prior to the removal of the filter is vital in understanding both the risk and pathophysiological effects removing the filter will have on the patient.  Doctors and medical professionals must consider several key factors (see  Indications for removing IVC filters ). [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2652", "text": "Irreversible electroporation  or  IRE  is a soft tissue  ablation  technique using short but strong  electrical fields  to create permanent and hence lethal nanopores in the  cell membrane , to disrupt cellular  homeostasis . The resulting cell death results from induced  apoptosis  or  necrosis  induced by either membrane disruption or secondary breakdown of the membrane due to transmembrane transfer of electrolytes and  adenosine triphosphate . [ 1 ] [ 2 ] [ 3 ] [ 4 ]  The main use of IRE lies in tumor ablation in regions where precision and conservation of the  extracellular matrix , blood flow and nerves are of importance. The first generation of IRE for clinical use, in the form of the NanoKnife System, became commercially available for research purposes in 2009, solely for the surgical ablation of soft tissue tumors. [ 5 ]  Cancerous tissue ablation via IRE appears to show significant cancer specific immunological responses which are currently being evaluated alone and in combination with  cancer immunotherapy . [ 6 ] [ 7 ] [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2653", "text": "First observations of IRE effects go back to 1754. Nollet reported the first systematic observations of the appearance of red spots on animal and human skin that was exposed to electric sparks. [ 10 ]  However, its use for modern medicine began in 1982 with the seminal work of Neumann and colleagues. [ 11 ]  Pulsed electric fields were used to temporarily permeabilize cell membranes to deliver foreign DNA into cells. In the following decade, the combination of high-voltage pulsed electric fields with the chemotherapeutic drug bleomycin and with DNA yielded novel clinical applications:  electrochemotherapy  and  gene electrotransfer , respectively. [ 12 ] [ 13 ] [ 14 ] [ 15 ] [ 16 ]  The use of irreversible electroporation for therapeutic applications was first suggested by Davalos, Mir, and Rubinsky. [ 17 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2654", "text": "Utilizing ultra short pulsed but very strong electrical fields, micropores and nanopores are induced in the  phospholipid bilayers  which form the outer cell membranes. [ citation needed ]  Two kinds of damage can occur:"}
{"_id": "WikiPedia_Radiology$$$corpus_2655", "text": "It should be stated that even though the ablation method is generally accepted to be apoptosis, some findings seem to contradict a pure apoptotic cell death, making the exact process by which IRE causes cell death unclear. [ 18 ] [ 4 ]  In any case, all studies agree that the cell death is an induced one with the cells dying over a varying time period of hours to days and does not rely on local extreme heating and melting of tissue via high energy deposition like most ablation technologies  (see  radiofrequency ablation ,  microwave ablation ,  High-intensity focused ultrasound ). [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2656", "text": "When an electrical field of more than 0.5 V/nm [ 19 ]  is applied to the resting trans-membrane potential, it is proposed that water enters the cell during this dielectric breakdown. Hydrophilic pores are formed. [ 20 ] [ 21 ]  A molecular dynamics simulation by Tarek [ 22 ]  illustrates this proposed pore formation in two steps: [ 23 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2657", "text": "It is proposed that as the applied electrical field increases, the greater is the perturbation of the phospholipid head groups, which in turn increases the number of water filled pores. [ 24 ]  This entire process can occur within a few nanoseconds. [ 22 ]  Average sizes of nanopores are likely cell-type specific. In swine livers, they average around 340-360\u00a0nm, as found using  SEM . [ 23 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2658", "text": "A secondary described mode of cell death was described to be from a breakdown of the membrane due to transmembrane transfer of electrolytes and adenosine triphosphate. [ 3 ]  Other effects like heat [ 25 ]  or electrolysis [ 26 ] [ 27 ]  were also shown to play a role in the currently clinically applied IRE pulse protocols."}
{"_id": "WikiPedia_Radiology$$$corpus_2659", "text": "A number of electrodes, in the form of long needles, are placed around the target volume. The point of penetration for the electrodes is chosen according to anatomical conditions. Imaging is essential to the placement and can be achieved by ultrasound, magnetic resonance imaging or tomography. The needles are then connected to the IRE-generator, which then proceeds to sequentially build up a potential difference between two electrodes. The geometry of the IRE-treatment field is calculated in real time and can be influenced by the user. Depending on the treatment-field and number of electrodes used, the ablation takes between 1 and 10 minutes. In general muscle relaxants are administered, since even under general anesthetics, strong muscle contractions are induced by excitation of the motor end-plate. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2660", "text": "Typical parameters (1st generation IRE system): [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2661", "text": "The shortly pulsed, strong electrical fields are induced through thin, sterile, disposable electrodes. The potential differences are calculated and applied by a computer system between these electrodes in accordance to a previously planned treatment field. [ 39 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2662", "text": "One specific device for the IRE procedure is the  NanoKnife  system manufactured by AngioDynamics, which received FDA 510k clearance on October 24, 2011. [ 40 ]  The NanoKnife system has also received an Investigational Device Exemption (IDE) from the FDA that allows AngioDynamics to conduct clinical trials using this device. [ 40 ]  The Nanoknife system transmits a low-energy direct current from a generator to electrode probes placed in the target tissues for the surgical ablation of soft tissue. In 2011, AngioDynamics received an FDA warning letter for promoting the device for indications for which it had not received approval. [ 41 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2663", "text": "In 2013, the UK National Institute for Health and Clinical Excellence issued a guidance that the safety and efficacy of the use of irreversible electroporation of the treatment of various types of cancer has not yet been established. [ 42 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2664", "text": "Newer generations of Electroporation-based ablation systems are being developed specifically to address the shortcomings of the first generation of IRE but, as of June 2020, none of the technologies are available as a medical device. [ 27 ] [ 43 ] [ 44 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2665", "text": "Potential organ systems, where IRE might have a significant impact due to its properties include the pancreas, liver, prostate and the kidneys, which were the main focus of the studies listed in Table 1-3 (state: June 2020)."}
{"_id": "WikiPedia_Radiology$$$corpus_2666", "text": "None of the potential organ systems, which may be treated for various conditions and tumors, are covered by randomized multicenter trials or long-term follow-ups (state. June 2020)."}
{"_id": "WikiPedia_Radiology$$$corpus_2667", "text": "2016 [ 47 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2668", "text": "3.0\u00a0cm"}
{"_id": "WikiPedia_Radiology$$$corpus_2669", "text": "laparoscopic\n(n = 20)"}
{"_id": "WikiPedia_Radiology$$$corpus_2670", "text": "2013 [ 48 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2671", "text": "CRLM (n = 20),\nOther (n = 10);\n2.5\u00a0cm"}
{"_id": "WikiPedia_Radiology$$$corpus_2672", "text": "(n = 28), open\n(n = 14), laparoscopic\n(n = 2)"}
{"_id": "WikiPedia_Radiology$$$corpus_2673", "text": "2017 [ 49 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2674", "text": "CRLM (n = 23),\nother (n = 7); 2.4\u00a0cm"}
{"_id": "WikiPedia_Radiology$$$corpus_2675", "text": "(n = 30)"}
{"_id": "WikiPedia_Radiology$$$corpus_2676", "text": "(at 6 months)"}
{"_id": "WikiPedia_Radiology$$$corpus_2677", "text": "2014 [ 50 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2678", "text": "2.7\u00a0cm"}
{"_id": "WikiPedia_Radiology$$$corpus_2679", "text": "(n = 28)"}
{"_id": "WikiPedia_Radiology$$$corpus_2680", "text": "2012 [ 51 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2681", "text": "CRLM (n = 21),\nother (n = 5);\n1.0\u00a0cm"}
{"_id": "WikiPedia_Radiology$$$corpus_2682", "text": "(n = 6), open\n(n = 22)"}
{"_id": "WikiPedia_Radiology$$$corpus_2683", "text": "2014 [ 52 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2684", "text": "CRLM (n = 20),\nCCC (n = 5);\n2.7\u00a0cm"}
{"_id": "WikiPedia_Radiology$$$corpus_2685", "text": "(n = 67)"}
{"_id": "WikiPedia_Radiology$$$corpus_2686", "text": "2015 [ 53 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2687", "text": "CRLM (n = 16),\nCCC (n = 6),\nother (n = 4); 1.7\u00a0cm"}
{"_id": "WikiPedia_Radiology$$$corpus_2688", "text": "(n = 25)"}
{"_id": "WikiPedia_Radiology$$$corpus_2689", "text": "2016 [ 54 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2690", "text": "CRLM (n = 22),\nCCC (n = 5),\nother (n = 5); 2.4\u00a0cm"}
{"_id": "WikiPedia_Radiology$$$corpus_2691", "text": "(n = 34)"}
{"_id": "WikiPedia_Radiology$$$corpus_2692", "text": "2017 [ 55 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2693", "text": "CRLM (n = 16),\nCCC (n = 6), other\n(n = 4); 2.3\u00a0cm"}
{"_id": "WikiPedia_Radiology$$$corpus_2694", "text": "(n = 71)"}
{"_id": "WikiPedia_Radiology$$$corpus_2695", "text": "2013 [ 56 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2696", "text": "CRLM (n = 23),\nCCC (n = 2),\nother (n = 22);\n3.8\u00a0cm"}
{"_id": "WikiPedia_Radiology$$$corpus_2697", "text": "(NS) open\n(NS)"}
{"_id": "WikiPedia_Radiology$$$corpus_2698", "text": "2014 [ 57 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2699", "text": "2.4\u00a0cm"}
{"_id": "WikiPedia_Radiology$$$corpus_2700", "text": "2011 [ 58 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2701", "text": "CRLM (n = 15), other\n(n = 31); 2.5\u00a0cm"}
{"_id": "WikiPedia_Radiology$$$corpus_2702", "text": "Hepatic IRE appears to be safe, even when performed near vessels and bile ducts [ 59 ] [ 60 ]  with an overall complication rate of 16%, with most complications being needle related (pneumothorax and hemorrhage).The COLDFIRE-2 trial with 50 patients showed 76% local tumor progression-free survival after 1 year. [ 61 ]  Whilst there are no studies comparing IRE to other ablative therapies yet, thermal ablations have shown a higher efficacy in that matter with around 96% progression free survival. Therefor Bart et al. [ 36 ]  concluded that IRE should currently only be performed for only truly unresectable and non-ablatable tumors."}
{"_id": "WikiPedia_Radiology$$$corpus_2703", "text": "Patients"}
{"_id": "WikiPedia_Radiology$$$corpus_2704", "text": "and Median\nLargest Tumor Diameter"}
{"_id": "WikiPedia_Radiology$$$corpus_2705", "text": "Follow-up"}
{"_id": "WikiPedia_Radiology$$$corpus_2706", "text": "(mo)"}
{"_id": "WikiPedia_Radiology$$$corpus_2707", "text": "Overall\nSurvival (mo)"}
{"_id": "WikiPedia_Radiology$$$corpus_2708", "text": "Recurrence\n(%)"}
{"_id": "WikiPedia_Radiology$$$corpus_2709", "text": "Downstaging\nCaused by IRE"}
{"_id": "WikiPedia_Radiology$$$corpus_2710", "text": "2017 [ 62 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2711", "text": "2019 [ 63 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2712", "text": "(88% after chemotherapy or radiation\ntherapy)"}
{"_id": "WikiPedia_Radiology$$$corpus_2713", "text": "(n = 32), open (n = 1)"}
{"_id": "WikiPedia_Radiology$$$corpus_2714", "text": "10.7 (IRE)"}
{"_id": "WikiPedia_Radiology$$$corpus_2715", "text": "2016 [ 64 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2716", "text": "2016 [ 65 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2717", "text": "percutaneous (n = 2)"}
{"_id": "WikiPedia_Radiology$$$corpus_2718", "text": "2018 [ 66 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2719", "text": "chemotherapy)"}
{"_id": "WikiPedia_Radiology$$$corpus_2720", "text": "2016 [ 67 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2721", "text": "7.0 (IRE)"}
{"_id": "WikiPedia_Radiology$$$corpus_2722", "text": "2019 [ 68 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2723", "text": "2015 [ 69 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2724", "text": "chemo- or radiation\ntherapy)"}
{"_id": "WikiPedia_Radiology$$$corpus_2725", "text": "18 (IRE)"}
{"_id": "WikiPedia_Radiology$$$corpus_2726", "text": "et al., 2016 [ 70 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2727", "text": "(after chemo- or radiation therapy)"}
{"_id": "WikiPedia_Radiology$$$corpus_2728", "text": "14.2 (IRE)"}
{"_id": "WikiPedia_Radiology$$$corpus_2729", "text": "2015 [ 71 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2730", "text": "6.4 (IRE)"}
{"_id": "WikiPedia_Radiology$$$corpus_2731", "text": "2019 [ 72 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2732", "text": "and local recurrence (n = 10), 4.0\u00a0cm (68% after chemotherapy)"}
{"_id": "WikiPedia_Radiology$$$corpus_2733", "text": "9.6 (IRE)"}
{"_id": "WikiPedia_Radiology$$$corpus_2734", "text": "2017 [ 73 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2735", "text": "(52% after chemotherapy)"}
{"_id": "WikiPedia_Radiology$$$corpus_2736", "text": "11.0 (IRE)"}
{"_id": "WikiPedia_Radiology$$$corpus_2737", "text": "2018 [ 74 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2738", "text": "percutaneous, NS"}
{"_id": "WikiPedia_Radiology$$$corpus_2739", "text": "2017 [ 75 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2740", "text": "2016 [ 76 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2741", "text": "2017 [ 77 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2742", "text": "Animal studies have shown the safety and efficacy of IRE on pancreatic tissue. [ 78 ]  The overall survival rates in studies on the use of IRE for pancreatic cancer provide an encouraging nonvariable endpoint and show an additive beneficial effect of IRE compared with standard-of care chemotherapeutic treatment with FOLFIRINOX (a combination of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) (median OS, 12\u201314months). [ 79 ] [ 80 ]  However, IRE appears to be more effective in conjunction with systemic therapy and is not suggested as first-line treatment. [ 68 ]  Despite that IRE makes adjuvant tumor mass reduction therapy for  LAPC  possible, IRE remains, in its current state, a high risk procedure requiring additional safety data before it can be used widely. [ 81 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2743", "text": "Concurrent Treatment"}
{"_id": "WikiPedia_Radiology$$$corpus_2744", "text": "(% of patients)"}
{"_id": "WikiPedia_Radiology$$$corpus_2745", "text": "(no. of patients)"}
{"_id": "WikiPedia_Radiology$$$corpus_2746", "text": "(2010) [ 82 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2747", "text": "3+4: n = 6"}
{"_id": "WikiPedia_Radiology$$$corpus_2748", "text": "4+4: n = 3"}
{"_id": "WikiPedia_Radiology$$$corpus_2749", "text": "urinary incontinence 0% erectile dysfunction 0%"}
{"_id": "WikiPedia_Radiology$$$corpus_2750", "text": "out-of-field occurrence, n = 1"}
{"_id": "WikiPedia_Radiology$$$corpus_2751", "text": "(2016) [ 83 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2752", "text": "4+3: n = 3"}
{"_id": "WikiPedia_Radiology$$$corpus_2753", "text": "4+4: n = 2"}
{"_id": "WikiPedia_Radiology$$$corpus_2754", "text": "4 weeks after IRE"}
{"_id": "WikiPedia_Radiology$$$corpus_2755", "text": "complete fibrosis or necrosis of ablation zone"}
{"_id": "WikiPedia_Radiology$$$corpus_2756", "text": "(2018) [ 84 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2757", "text": "3+4: n = 38"}
{"_id": "WikiPedia_Radiology$$$corpus_2758", "text": "4+3: n = 16"}
{"_id": "WikiPedia_Radiology$$$corpus_2759", "text": "Grade 2: 11%"}
{"_id": "WikiPedia_Radiology$$$corpus_2760", "text": "Grade 3\u20135: 0%"}
{"_id": "WikiPedia_Radiology$$$corpus_2761", "text": "urinary incontinence 0%;"}
{"_id": "WikiPedia_Radiology$$$corpus_2762", "text": "erectile dysfunction 23%"}
{"_id": "WikiPedia_Radiology$$$corpus_2763", "text": "out-of-field recurrence, n = 4"}
{"_id": "WikiPedia_Radiology$$$corpus_2764", "text": "(2019) [ 85 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2765", "text": "3+4/4+3:"}
{"_id": "WikiPedia_Radiology$$$corpus_2766", "text": "n = 225"}
{"_id": "WikiPedia_Radiology$$$corpus_2767", "text": "4+4: n = 68"}
{"_id": "WikiPedia_Radiology$$$corpus_2768", "text": "5+3/3+5: n = 3"}
{"_id": "WikiPedia_Radiology$$$corpus_2769", "text": ">4+4 = 42"}
{"_id": "WikiPedia_Radiology$$$corpus_2770", "text": "prostatectomy (n = 21),"}
{"_id": "WikiPedia_Radiology$$$corpus_2771", "text": "radiation therapy (n = 28),"}
{"_id": "WikiPedia_Radiology$$$corpus_2772", "text": "TURP (n = 17),"}
{"_id": "WikiPedia_Radiology$$$corpus_2773", "text": "HIFU (n = 8)"}
{"_id": "WikiPedia_Radiology$$$corpus_2774", "text": "ADT (n = 29)"}
{"_id": "WikiPedia_Radiology$$$corpus_2775", "text": "erectile dysfunction 3%"}
{"_id": "WikiPedia_Radiology$$$corpus_2776", "text": "local recurrence, n = 20;"}
{"_id": "WikiPedia_Radiology$$$corpus_2777", "text": "out-of-field recurrence, n = 27"}
{"_id": "WikiPedia_Radiology$$$corpus_2778", "text": "(2014) [ 86 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2779", "text": "3+4: n = 19"}
{"_id": "WikiPedia_Radiology$$$corpus_2780", "text": "4+3: n = 5"}
{"_id": "WikiPedia_Radiology$$$corpus_2781", "text": "4+4: n = 1"}
{"_id": "WikiPedia_Radiology$$$corpus_2782", "text": "incontinence 0%;"}
{"_id": "WikiPedia_Radiology$$$corpus_2783", "text": "erectile dysfunction 5%"}
{"_id": "WikiPedia_Radiology$$$corpus_2784", "text": "only one histologic verification. Out-of-field\nrecurrence, NS"}
{"_id": "WikiPedia_Radiology$$$corpus_2785", "text": "(2016) [ 87 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2786", "text": "3+4: n = 15"}
{"_id": "WikiPedia_Radiology$$$corpus_2787", "text": "4+3: n = 8"}
{"_id": "WikiPedia_Radiology$$$corpus_2788", "text": "4+4: n = 0"}
{"_id": "WikiPedia_Radiology$$$corpus_2789", "text": "Grade 2: 29%"}
{"_id": "WikiPedia_Radiology$$$corpus_2790", "text": "erectile dysfunction, unknown"}
{"_id": "WikiPedia_Radiology$$$corpus_2791", "text": "out-of-fieldrecurrence, n = 5 (with histologic verification)"}
{"_id": "WikiPedia_Radiology$$$corpus_2792", "text": "3+4: n = 37"}
{"_id": "WikiPedia_Radiology$$$corpus_2793", "text": "4+3: n = 6"}
{"_id": "WikiPedia_Radiology$$$corpus_2794", "text": "Grade 2: 9"}
{"_id": "WikiPedia_Radiology$$$corpus_2795", "text": "erectile dysfunction 6%"}
{"_id": "WikiPedia_Radiology$$$corpus_2796", "text": "out-of-field recurrence, NS"}
{"_id": "WikiPedia_Radiology$$$corpus_2797", "text": "Focal ablation using IRE for PCa in the distal apex appears safe and feasible."}
{"_id": "WikiPedia_Radiology$$$corpus_2798", "text": "The concept of treating prostate cancer with IRE was first proposed by Gary Onik and Boris Rubinsky in 2007. [ 89 ]  Prostate carcinomas are frequently located near sensitive structures which might be permanently damaged by thermal treatments or radiation therapy. The applicability of surgical methods is often limited by accessibility and precision. Surgery is also associated with a long healing time and high rate of side effects. [ 90 ]  Using IRE, the urethra, bladder, rectum and neurovascular bundle and lower urinary sphincter  can potentially be included in the treatment field without creating (permanent) damage. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2799", "text": "IRE has been in use against prostate cancer since 2011, partly in form of clinical trials, compassionate care or individualized treatment approach. As for all other ablation technologies and also most conventional methods, no studies employed a randomized multi-center approach or targeted  cancer-specific mortality  as endpoint.  Cancer-specific mortality  or  overall survival  are notoriously hard to assess for prostate cancer, as the trials require more than a decade and usually several treatment types are performed during the years making treatment-specific survival advantages difficult to quantify. Therefore, the results of ablation-based treatments and focal treatments in general usually use local recurrences and functional outcome (quality of life) as endpoint. In that regard, the clinical results collected so far and listed in Table 3 shown encouraging results and uniformly state IRE as a safe and effective treatment (at least for focal ablation) but all warrant further studies. The largest cohort presented by Guenther et al. [ 85 ]  with up to 6-year follow-up is limited as a heterogeneous retrospective analysis and no prospective clinical trial. Therefore, despite that several hospitals in Europe have been employing the method for many years with one private clinic even listing more than one thousand treatments as of June 2020, [ 91 ]  IRE for prostate cancer is currently not recommended in treatment guidelines."}
{"_id": "WikiPedia_Radiology$$$corpus_2800", "text": "While nephron-sparing surgery is the gold standard treatment for small, malignant renal masses, ablative therapies are considered a viable option in patients who are poor surgical candidates. Radiofrequency ablation (RFA) and cryoablation have been used since the 1990s; however, in lesions larger than 3\u00a0cm, their efficacy is limited. The newer ablation modalities, such as IRE, microwave ablation (MWA), and high-intensity focused ultrasound, may help overcome the challenges in tumor size. [ 92 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2801", "text": "The first human studies have proven the safety of IRE for the ablation of renal masses; however, the effectiveness of IRE through histopathological examination of an ablated renal tumor in humans is yet to be known. Wagstaff et al. have set out to investigate the safety and effectiveness of IRE ablation of renal masses and to evaluate the efficacy of ablation using MRI and contrast-enhanced ultrasound imaging. In accordance with the prospective protocol designed by the authors, the treated patients will subsequently undergo radical nephrectomy to assess IRE ablation success. [ 93 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2802", "text": "Later phase 2 prospective trials showed good results in terms of safety and feasibility   [ 94 ] [ 95 ]  for small renal masses but the cohort was limited in numbers (7 and 10 patients respectively), hence efficacy is not yet sufficiently determined. IRE appears safe for small renal masses up to 4\u00a0cm. However, the consensus is that current evidence is still inadequate in quality and quantity. [ 36 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2803", "text": "In a prospective, single-arm, multi-center, phase II clinical trial, the safety and efficacy of IRE on lung cancers were evaluated. The trial included patients with primary and secondary lung malignancies and preserved lung function. The expected effectiveness was not met at interim analysis and the trial was stopped prematurely. Complications included pneumothoraces (11 of 23 patients), alveolar hemorrhage not resulting in significant hemoptysis, and needle tract seeding was found in 3 cases (13%). Disease progression was seen in 14 of 23 patients (61%). Stable disease was found in 1 (4%), partial remission in 1 (4%) and complete remission in 7 (30%) patients. The authors concluded that IRE is not effective for the treatment of lung malignancies. [ 96 ]  Similarly poor treatment outcomes have been observed in other studies. [ 97 ] [ 98 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2804", "text": "A major obstacle of IRE in the lung is the difficulty in positioning the electrodes; placing the probes in parallel alignment is made challenging by the interposition of ribs. Additionally, the planned and actual ablation zones in the lung are dramatically different due to the differences in conductivity between tumor, lung parenchyma, and air. [ 99 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2805", "text": "Maor et el have demonstrated the safety and efficiency of IRE as an ablation modality for smooth muscle cells in the walls of large vessels in rat model. [ 100 ]  Therefore, IRE has been suggested as preventive treatment for coronary artery re-stenosis after  percutaneous coronary intervention . [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2806", "text": "Numerous studies in animals have demonstrated the safety and efficiency of IRE as a non-thermal ablation modality for pulmonary veins in the context of  atrial fibrillation  treatment. [ 101 ]  In 2023, irreversible electroporation is being widely used and evaluated in humans, as  cardiac ablation therapy  to kill very small areas of heart muscle. This is done to treat  irregularities of heart rhythm . A  cardiac catheter  delivers trains of high-voltage ultra-rapid electrical pulses that form irreversible pores in cell membranes, resulting in cell death. It is thought to allow better selectivity than the previous techniques, which used heat or cold to kill larger volumes of muscle. [ 102 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2807", "text": "IRE has also been investigated in ex-vivo human eye models for treatment of uveal melanoma [ 103 ]  and in thyroid cancer. [ 104 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2808", "text": "Successful ablations in animal tumor models have been conducted for lung, [ 105 ] [ 106 ]  brain, [ 107 ] [ 108 ]  heart, [ 109 ]  skin, [ 110 ] [ 111 ]  bone, [ 112 ] [ 113 ]  head and neck cancer, [ 114 ]  and blood vessels. [ 115 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2809", "text": "Microwave ablation  is a form of thermal ablation used in  interventional radiology  to treat  cancer . MWA uses  electromagnetic waves  in the microwave energy spectrum (300\u00a0MHz to 300\u00a0GHz) to produce tissue-heating effects. The oscillation of polar molecules produces frictional heating, ultimately generating  tissue necrosis  within solid tumors. It is generally used for the treatment and/or  palliation  of solid tumors in patients who are nonsurgical candidate."}
{"_id": "WikiPedia_Radiology$$$corpus_2810", "text": "For isolated, nonmetastatic  lung tumors , surgical resection remains the reference standard for treatment. However, many patients are precluded from surgery due to poor  cardiopulmonary function , advanced age, or extensive disease burden. For these patients, minimally invasive therapeutic options such as  radiofrequency ablation , microwave ablation, and  cryoablation  have emerged as possible alternatives."}
{"_id": "WikiPedia_Radiology$$$corpus_2811", "text": "Tumor ablation of thoracic malignancies should be considered a viable treatment option for patients with early stage, primary or secondary lung cancers who are not surgical candidates or for patients in whom  palliation  of tumor related symptoms is the intent. MWA is regarded as a particularly efficient option for the treatment of lung tumors since unlike RFA it does not rely on impedance to generate heat, rather electromagnetic microwave waves heat matter by agitating water molecules in the surrounding tissue, producing friction and heat."}
{"_id": "WikiPedia_Radiology$$$corpus_2812", "text": "Another common use for microwave ablation is the treatment of  liver tumors . For nonsurgical patients, local thermal ablation techniques have enabled local control of tumors without resection. In particular, this therapy has grown in use for patients with  hepatocellular carcinoma , since many patients present with advanced disease or compromised liver function."}
{"_id": "WikiPedia_Radiology$$$corpus_2813", "text": "Clinical applications of MWA have also included treatment of renal, adrenal, and bone malignancies. The goals of ablation of thoracic malignancies include: \n1. Ablating the entire tumor and a margin of normal parenchyma surrounding it\n2. Avoiding injury to critical structures\n3. Creating a large ablation area quickly."}
{"_id": "WikiPedia_Radiology$$$corpus_2814", "text": "The most common adverse effects of MWA for lung tumors include pain, fever,  pneumothorax , and  pleural effusions . [6-12]  Rib fractures, following thermal ablation, particularly MWA, have been newly noted in the literature. [13]"}
{"_id": "WikiPedia_Radiology$$$corpus_2815", "text": "One of the limitations of thermal-based ablation therapies, including MWA, is the risk of marginal recurrences and/or residual disease. Residual or recurrent tumor is particularly likely in areas adjacent to heat sinks, such as larger blood vessels or airways. Theoretically, the greater heat intensity generated in MWA compared to other thermal modalities should allow for more complete ablations in larger tumors and thus decreased incidence of residual disease or recurrence at the tumor margins. [3]"}
{"_id": "WikiPedia_Radiology$$$corpus_2816", "text": "MWA allows for flexible treatment approaches, including  percutaneous ,  laparoscopic , and open surgical access. Therapy is generally performed with the patient under  conscious sedation ; however, in cases where intra-procedural pain is problematic a  general anesthetic  may be used. Ablations can be performed using a single MW antenna or a cluster of three to achieve a greater ablation volume. [4]  Tumor temperatures during ablation can be measured with a separate thermal couple; tumors are treated to over 60\u00a0\u00b0C to achieve coagulation necrosis."}
{"_id": "WikiPedia_Radiology$$$corpus_2817", "text": "Currently, there are six MWA systems commercially available in the United States. The systems use either a  915\u00a0MHz  generator (Evident, Covidien, Mansfield, MA; MicrothermX, BSD Medical, Salt Lake City, UT; Avecure, Medwaves, San Diego, CA) or a  2450\u00a0MHz  generator (Certus 140, Neuwave, Madison, WI; Amica, Hospital Service, Rome, Italy; Acculis MTA, AngioDynamics, Latham, NY). The MW antennas used are straight applicators with active tips ranging in lengths from 0.6 to 4.0\u00a0cm. Five of the six available systems require that the antennas are internally cooled with either room-temperature fluid or carbon dioxide to reduce conductive heating and to prevent possible skin damage. [5]"}
{"_id": "WikiPedia_Radiology$$$corpus_2818", "text": "The technique for thermal ablation in the lung by using  radiofrequency ablation  was first described in 1995 for use in animal lung tumor models and then in 2000 in humans. [1-2]  Microwave ablation has emerged as a newer ablation modality and an addition to the arsenal of minimally invasive cancer care."}
{"_id": "WikiPedia_Radiology$$$corpus_2819", "text": "The purported benefits of microwave ablation over other heat-based modalities such as radiofrequency ablation and laser include a larger and faster volume of tissue heating with a given application. Unlike radiofrequency ablation, MWA does not rely on an electrical circuit allowing for multiple applicators to be used simultaneously. [3]"}
{"_id": "WikiPedia_Radiology$$$corpus_2820", "text": "Devi Elizabeth Nampiaparampil  (also known as  Doctor Devi ; born May 13, 1977) is an American  physician  and researcher who specializes in preventing and treating  chronic pain . She performs X-ray-guided invasive spinal procedures for pain, teaches medical students and trainees, comments on medical issues for various platforms, and appears on news and talk shows. She has appeared on the daytime soap opera  General Hospital . Dr. Nampiaparampil also ran as for New York City Public Advocate in the November 2021 general election."}
{"_id": "WikiPedia_Radiology$$$corpus_2821", "text": "Doctor Devi was born at  NYU Medical Center  (where she now teaches [ 1 ] ) to Mary and Joseph Nampiaparampil,  Catholic  Indians who had immigrated to the U.S. from  Kerala , India. She was educated at  Ardsley High School  in New York. Between 1995 and 2002, Nampiaparampil attended the seven-year combined B.A./M.D. program at  Northwestern University , where she double-majored in economics and biology. She completed her specialty and subspecialty medical training at  Harvard Medical School . [ 2 ]  Doctor Devi is board-certified in four specialties including Pain Medicine, Sports Medicine, Physical Medicine and Rehabilitation and Hospice and Palliative Medicine"}
{"_id": "WikiPedia_Radiology$$$corpus_2822", "text": "In 2015, she became an associate professor of  Rehabilitation Medicine at NYU School of Medicine , WNYW-Fox 5 NY's on-air medical contributor, and opened her own private practice,  Metropolis Pain Medicine , in downtown Manhattan. Dr. Devi has also served as a medical legal consultant to Fortune 500 companies."}
{"_id": "WikiPedia_Radiology$$$corpus_2823", "text": "Doctor Devi began working for the  U.S. Department of Veterans Affairs  in 2008 and started the Brain Injury Clinic at the VA Central California in Fresno. She moved to New York City in 2009 to direct and develop the Pain Management program at the VA Hudson Valley. [ 3 ]  She served as the head of the regional Pain Management program for the New York/New Jersey region but stepped down to further develop the VA's Interventional Pain Management program in  New York City . She established the Veterans' Hospital in Manhattan (the VA New York Harbor) as a referral center for invasive pain procedures. [ 4 ]  She was an assistant professor in the Department of Rehabilitation Medicine at  NYU School of Medicine  from 2009 to 2015 and then was promoted to associate professor. [ 5 ]  In 2015, she was elected to the board of the American Society of Interventional Pain Physicians. [ 6 ]  She is also an editor for Pain Physician, an academic journal for pain management specialists. [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2824", "text": "The  U.S. Department of Veterans Affairs  recognized Doctor Devi for \"outstanding service\" during the wars in Iraq and Afghanistan wars and  NYU Langone Medical Center  honored her for her achievements in research and education. The Department of Physical Medicine & Rehabilitation (PM&R) at  Harvard Medical School  honored her for her efforts \"to further the field of PM&R.\" Doctor Devi has won research awards from institutions and organizations such as  Massachusetts General Hospital , Harvard Medical School, the  Massachusetts Medical Society , the  American Pain Society , the  American Medical Association  and the  American Society for Regional Anesthesia and Pain Medicine  for her work on pain and the  opioid crisis . [ 8 ]  Dr. Devi has also been named one of  Caste Connolly's Top Doctors  since 2015. Doctor Devi has also been awarded the Lifetime Achievement Award from the  New York State Senate  for her services and sacrifice during COVID pandemic."}
{"_id": "WikiPedia_Radiology$$$corpus_2825", "text": "Doctor Devi has over 50 peer-reviewed academic publications including  20 publications  in the Journal of the American Medical Association ( JAMA )."}
{"_id": "WikiPedia_Radiology$$$corpus_2826", "text": "Doctor Devi has appeared as a physician on the daytime  soap opera ,  General Hospital , before becoming a physician in her real life. She intermittently appeared on the show between 2002 and 2005. She made her debut as a medical expert on television on  The Dr. Oz Show  when she demonstrated  botox  injections for chronic migraine pain in front of a live audience.  Mehmet Oz  nicknamed her Doctor Devi when she appeared on his show."}
{"_id": "WikiPedia_Radiology$$$corpus_2827", "text": "In 2015, She worked on a short documentary, entitled, \"A Life For A Life: Trading Organs For One More Today,\" [ 15 ]  which won a Jury Award at the  Directors Guild of America  Student Film Awards. She published a related article in  Newsweek  entitled \"How a Death Row Inmate's Request to Give His Organs Kept Him Alive\". [ 16 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2828", "text": "In 2016, Doctor Devi became an  on-air medical contributor  for  Fox 5 , analyzing medical developments for  Good Day NY , Fox 5 News at 5, News at 6, and News at 10. She has appeared in over 350 national news segments for  Fox News Channel ,  MSNBC , and  CNN  among other networks. [ 17 ] [ 18 ]  She also has a master's degree in journalism from the  Columbia University Graduate School of Journalism ."}
{"_id": "WikiPedia_Radiology$$$corpus_2829", "text": "Doctor Devi ran for New York York City  Public Advocate  in the   2021 election . She won the republican primary, losing in the general election to incumbent democrat  Jumaane Williams . [ 19 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2830", "text": "A  nephrostomy  or  percutaneous nephrostomy  is an artificial opening created between the  kidney  and the  skin  which allows for the  urinary diversion  directly from the upper part of the urinary system ( renal pelvis ). [ 2 ]  It is an  interventional radiology / surgical procedure  in which the  renal pelvis  is punctured whilst using imaging as guidance. Images are obtained once an antegrade  pyelogram  (an injection of contrast), with a fine needle, has been performed. A nephrostomy tube may then be placed to allow drainage. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2831", "text": "An  urostomy  is a related procedure performed more distally along the urinary system to provide urinary diversion."}
{"_id": "WikiPedia_Radiology$$$corpus_2832", "text": "A nephrostomy is performed whenever a blockage keeps urine from passing from the kidneys, through the  ureter  and into the  urinary bladder . Without another way for urine to drain, pressure would rise within the urinary system and the kidneys would be damaged. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2833", "text": "The most common cause of blockage necessitating a nephrostomy is  cancer , especially  ovarian cancer  and  colon cancer . Nephrostomies may also be required to treat  pyonephrosis ,  hydronephrosis  and  kidney stones . [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2834", "text": "Percutaneous nephrostomy is used in Whitaker test to differentiate recurrent obstruction or permanent dilatation after an operative surgery that corrects the cause of obstruction. This procedure is also used for  antegrade pyelography  to visualize the upper urinary tract system. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2835", "text": "Percutaneous nephrostomy is also used to treat  hydronephrosis  caused by kidney stones, pregnancy, stricture of the urinary tract, urinary tract/cervical/prostate tumours. Besides, infections such as urosepsis and  pyonephrosis  can also be drained by nephrostomy tube insertion. [ 6 ]  Percutaneous nephrostomy is also useful in divert urine away from diseased site to enhance healing. Examples of conditions that can be treated with such method are malignant/traumatic/inflammatory  fistula , and  haemorrhagic cystitis . [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2836", "text": "Percutaneous nephrostomy is also used to provide access for chemotherapy/antibiotic/antifungal therapy, antegrade urethral stent placement, stone retrieval, and endopyelotomy (endoscopic surgery for the enlargement of the junction of renal pelvis and ureter). [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2837", "text": "Nephrostomies are created either by  surgeons  or  interventional radiologists ."}
{"_id": "WikiPedia_Radiology$$$corpus_2838", "text": "Under interventional radiology, the subject either lies down on the side or in a prone position. An area is selected below the 12th rib, bounded laterally by the posterior axillary line and the muscles of the spine and from below by the pelvic bone. The exact area is then located by ultrasound. Local anesthetic infiltration is used to numb the area. Then a needle would pass through to make the puncture on the kidney. Then, urine from the kidney is aspirated and check for its contents. If the urine is clear, dye will be injected to delineate the  renal pelvis  and  renal calyx . If the urine is turbid, it means the urine is infected. Dye injection is avoided in case of turbid urine to prevent the spread of infection to other parts of the urinary system. [ 6 ]  Then, a guidewire is inserted into the through the needle and parked within the upper renal calyx or within the  ureter  under  fluoroscopy  guidance. Then the puncture tract is dilated using a dilator. [ 6 ]  Various types of catheters such as pigtail catheter [ 7 ]  or Malecot catheter (a catheter that has a special mechanism for preventing blockage in case of thick pus in  pyonephrosis  and not easily dislodged when compared to pigtail catheter) can be used. [ 6 ]  The catheter is inserted through the guidewire and is secured in place by suturing it to the skin. The other end of the catheter is attached to a urine bag for drainage of urine from the kidney. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2839", "text": "Percutaneous nephrostomy is overall a very safe procedure. [ 8 ]  Risks and complications include: [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2840", "text": "Although pneumothorax and colonic injury are more common on subcostal needle insertion, these are rare complications. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2841", "text": "Blood in urine usually clears up after 48 to 72 hours. Bleeding longer than this period may signifies more serious bleeding complication. About 2\u20134% of percutaneous nephrostomy cases require blood transfusion. [ 9 ]  Arteriovenous fistula is a rare complication. [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2842", "text": "The  BMJ  has published original research of this condition and its treatment,"}
{"_id": "WikiPedia_Radiology$$$corpus_2843", "text": "In  interventional radiology ,  Onyx  is a trade name for a copolymer used for  embolisation therapy , [ 1 ]  which involves the occlusion of  blood vessels . It is a  liquid embolic agent . Onyx is produced and sold by Medtronic (previously Covidien, which acquired ev3 Inc., the original developer of Onyx, in 2010)."}
{"_id": "WikiPedia_Radiology$$$corpus_2844", "text": "Onyx consists of  Ethylene Vinyl Alcohol Copolymer , soluted in  Dimethyl-Sulfoxide  (DMSO). Depending on the desired character of the liquid, the concentration can be varied: For example, 6% EVOH (trade name Onyx 18) or 8% EVOH (trade name Onyx 34). Micronized tantalum powder is added in order to maintain  Radiopacity . [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2845", "text": "Onyx was approved as 'Humanitarian Use Device (HUD)' for the treatment of  saccular aneurysms  that are not surgically removable by the  Food and Drug Administration (FDA)  in the United States on April 11, 2007. [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2846", "text": "Paracentesis  (from  Greek  \u03ba\u03b5\u03bd\u03c4\u03ac\u03c9, \"to pierce\") is a form of  body fluid sampling  procedure, generally referring to  peritoneocentesis  (also called  laparocentesis  or  abdominal paracentesis ) in which the  peritoneal cavity  is punctured by a needle to sample  peritoneal fluid . [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2847", "text": "The procedure is used to remove fluid from the peritoneal cavity, particularly if this cannot be achieved with medication. The most common indication is  ascites  that has developed in people with  cirrhosis ."}
{"_id": "WikiPedia_Radiology$$$corpus_2848", "text": "It is used for a number of reasons: [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2849", "text": "The procedure is often performed in a doctor's office or an outpatient clinic. In an expert's hands, it is usually very safe, [ 4 ]  although there is a small risk of infection, excessive bleeding or perforating a loop of bowel. These last two risks can be minimized greatly with the use of ultrasound guidance. [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2850", "text": "The use of  ultrasound  has become the standard of care when preparing a patient for paracentesis. Confirmation of an ascitic effusion reduces the risks associated with a dry or blind tap of the abdomen. Anatomic landmarks, such as the midline  linea alba  approach, were traditionally used as reference points for needle insertion. Phased array or curvilinear ultrasound transducers are typically used in the hospital and outpatient setting to identify ascites in the abdominal cavity. Fluid within the abdominal cavity appears hypoechoic or anechoic (black) on ultrasound.  Morison's pouch  (hepatorenal recess) is a common starting location in concordance with ultrasound FAST ( focused assessment with sonography for trauma ) exam. Fluid collection can occur in a number of different locations and may be difficult to find, especially if the patient only exhibits a small volume of ascites. Measurement of the amount of fluid within the abdominal cavity is not necessary or very successful. Identification of sufficient fluid within the abdominal cavity for fluid analysis or to achieve a therapeutic benefit is all that is required to proceed to paracentesis. Ultrasound guidance of the paracentesis can also be used as an additional safety measure to ensure the needle stays within the ascitic fluid and avoidance of important vessels within the abdominal cavity. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2851", "text": "The patient is requested to urinate before the procedure; alternately, a  Foley catheter  is used to empty the bladder. The patient is positioned in the bed with the head elevated at 45\u201360 degrees to allow fluid to accumulate in lower abdomen. After cleaning the side of the abdomen with an antiseptic solution, the physician numbs a small area of skin and inserts a large-bore needle with a plastic sheath 2 to 5\u00a0cm (1 to 2\u00a0in) in length to reach the peritoneal (ascitic) fluid. The needle is removed, leaving the plastic sheath to allow drainage of the fluid. The fluid is drained by gravity, a syringe, or by connection to a vacuum bottle. Several litres of fluid may be drained during the procedure; however, if more than two litres are to be drained, it will usually be done over the course of several treatments. [ 6 ]  After the desired level of drainage is complete, the plastic sheath is removed and the puncture site bandaged. [ 6 ]  The plastic sheath can be left in place with a flow control valve and protective dressing if further treatments are expected to be necessary. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2852", "text": "If fluid drainage in  cirrhotic  ascites is more than 5 litres, patients may receive  intravenous   serum albumin  (25% albumin, 8\u00a0g/L) to prevent  hypotension  (low blood pressure). [ 7 ]  There has been debate as to whether albumin administration confers benefit, but a recent 2016  meta-analysis  concluded that it can reduce mortality after large-volume paracentesis significantly. [ 8 ]  However, for every end-point investigated, while albumin was favorable as compared to other agents (e.g., plasma expanders, vasoconstrictors), these were not statistically significant and the meta-analysis was limited by the quality of the studies\u2014two of which that were in fact unsuitable\u2014included in it. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2853", "text": "The procedure generally is not painful and does not require  sedation . The patient is usually discharged within several hours following post-procedure observation provided that blood pressure is otherwise normal and the patient experiences no dizziness. [ 1 ] [ 9 ] [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2854", "text": "Paracentesis is known to be a safe procedure when ascitic fluid is readily visible, so complications are typically rare. Possible complications following or during the procedure involve infection, bleeding, the leakage ascitic of fluid, or  bowel perforation . [ 7 ] [ 5 ]  Of these, the most concerning in the immediate setting is bleeding within the peritoneal cavity. [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2855", "text": "The z-tracking technique has held particular importance in performing paracentesis. A z-track is a technique that allows for decreased ascitic fluid leak following the paracentesis by displacing the needle tracks with respect to the  epidermis  and the  peritoneum . [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2856", "text": "The  serum-ascites albumin gradient  can help determine the cause of the ascites. [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2857", "text": "The color of the ascitic fluid can also be useful in analysis. Blood fluid can indicate trauma or  malignancy . A milky appearance of the fluid can indicate  lymphoma  or malignant peritoneal ascites. Cloudy or turbid fluid can indicate possible infection or inflammation within the peritoneal cavity. Straw or light yellow colored fluid indicates more plasma-like and benign causes of peritoneal ascites. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2858", "text": "The ascitic white blood cell count can help determine if the ascites is infected. A count of 250 neutrophils per ml or higher is considered diagnostic for spontaneous bacterial peritonitis. Cultures of the fluid can be taken, but the yield is approximately 40% (72\u201390% if  blood culture  bottles are used). Empiric antibiotics are typically started when  spontaneous bacterial peritonitis  is highly suspected. A third-generation cephalosporin is typically started in these cases to cover the most common organisms,  E. coli  and  Klebsiella , in SBP. [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2859", "text": "Mild hematologic abnormalities do not increase the risk of bleeding. [ 12 ] [ 7 ]  The risk of bleeding may be increased if: [ 13 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2860", "text": "Absolute contraindication is the acute abdomen that requires surgery."}
{"_id": "WikiPedia_Radiology$$$corpus_2861", "text": "Relative contraindications are: [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2862", "text": "Percutaneous intentional extraluminal revascularization   is a percutaneous technique used in  interventional radiology  for limb salvage in patients with  lower limb ischemia  due to long  superficial femoral artery  occlusions. This method is intended for those patients who make poor candidates for infrainguinal arterial   bypass  surgery. [ 1 ]   A  guide wire [ 2 ]  is intentionally introduced in the  subintimal space , after which balloon dilatation is performed to create a new  lumen  for the blood to flow through. [ 3 ]  The technique is not without complications but may serve as a \"temporary bypass\" to provide wound healing and limb salvage. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2863", "text": "Percutaneous intentional extraluminal revascularization, or PIER, is an  endovascular  approach to  revascularization  of peripheral occlusions that may serve as an alternative to  transluminal  angioplasty. It is a minimally invasive procedure requiring only local anesthetic, which proves to be a major advantage over invasive surgical bypass procedures. [ 5 ]  Endovascular approaches, both extraluminal and transluminal, are usually indicated in patients who cannot tolerate the gold-standard treatment of surgical bypass, usually due to comorbid medical conditions that make them unsuitable for surgery. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2864", "text": "Typically, PIER is considered an indication when the transluminal approach is unable to be achieved due to anatomical complexity of the occluding lesion. Research has shown comparable outcomes between extraluminal and transluminal approaches when the extraluminal technique is used in more complex cases, however, the current literature is lacking in data when comparing these two techniques in clinically comparable lesions. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2865", "text": "Risks of the PIER procedure include those associated with all endovascular procedures, with the overall complication rate ranging between 8-17%. [ 7 ]  Some common complications are listed below:"}
{"_id": "WikiPedia_Radiology$$$corpus_2866", "text": "Although variations of the procedure exist depending on physician preference and patient anatomy, a common technique for PIER of the  superficial femoral artery  is briefly outlined below."}
{"_id": "WikiPedia_Radiology$$$corpus_2867", "text": "Entry is made in an antegrade fashion into the common femoral artery near the mid-femoral head using a 5-French rigid catheter with an angulated tip. The catheter is advanced to the proximal portion of the SFA, proximal to the occlusion. The catheter tip is then advanced into the extraluminal, or subintimal, space. Adequate positioning is confirmed with injections of contrast. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2868", "text": "Once the catheter is in the extraluminal space, a guidewire is advanced in a loop configuration which allows for a more rigid structure that can be used to traverse the subintimal dissection plane when compared to the free end of a straight guidewire. The looped guidewire is further advanced towards the patent portion of the artery distal to the occlusion, where re-entry into the true lumen can now be achieved. To avoid bleeding complications in the event of arterial perforation, heparin is only administered once re-entry into the true lumen is confirmed. The false lumen created in the subintimal space is then dilated with a balloon catheter. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2869", "text": "A systematic review of 23 studies investigating subintimal angioplasty performed for occlusions in the femoral, femoropopliteal, and crural arteries found that the extraluminal technique achieves clinically similar outcomes as the transluminal approach. [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2870", "text": "Percutaneous intentional extraluminal revascularization was first described in 1990 as an alternative to transluminal angioplasty. Up until that point, the widely accepted technique was to remain within the lumen of the artery, with accidental entry of the catheter into the subintimal space typically being an indication to abort the procedure. However, the early literature reports a case where accidental entry of the catheter into the subintimal space and subsequent return into the true lumen led to successful revascularization after the  angioplasty balloon  was inflated within the subintimal space. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2871", "text": "Portal vein embolization  ( PVE ) is a preoperative procedure performed in  interventional radiology  to initiate hypertrophy of the anticipated future liver remnant a couple weeks prior to a major  liver resection  procedure. The procedure involves injecting the right or left portal vein with embolic material to occlude portal blood flow. By occluding the blood flow to areas of the liver that will be resected away, the blood is diverted to healthy parts of the liver and induces  hyperplasia . This may allow for a more extensive resection or stage bilateral resections that would otherwise be  contraindicated  resulting in better  oncological  treatment outcomes. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2872", "text": "Indications for PVE depend on the ratio of future liver remnant (FLR) to total estimated liver volume (TELV) and liver condition. Although there is no consensus to the absolute minimum liver volume required for adequate post-resection liver function, a FLR/TELV ratio of at least 25% is recommended in patients with otherwise normal livers. [ 2 ]  The recommendation for those with chronic liver disease such as  cirrhosis  is a FLR/TELV ratio of at least 40%. In these patients a PVE may be indicated to increase the FLR and the FLR/TELV ratio. Preoperative patients receiving extensive chemotherapy with a FLR/TELV less than 30% should also receive PVE prior to resection; conversely, chemotherapy does not preclude subsequent PVE."}
{"_id": "WikiPedia_Radiology$$$corpus_2873", "text": "Other important considerations before a PVE include co-morbidities such as diabetes, procedure type and the extent of planned resection.  Insulin resistance  has been associated with slower rates of regeneration and higher likelihood of inadequate FLR growth after PVE. [ 2 ]  Additionally, if the resection requires more extensive surgery such as a resections of the pancreas or small bowel, a greater FLR/TELV ratio may be needed for safe recovery. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2874", "text": "Preoperative PVE is a very well tolerated procedure with extremely low mortality rates (0.1 percent) and technical failure rates (0.4 percent). [ 3 ]  Complication rates from the procedure are low as well (2\u20133 percent) and include portal vein thrombosis, liver infarction, necrosis, infection,  pneumothorax , and other risks as listed above. [ 3 ]  Success of PVE is determined by degree of regenerative response, which again depends on factors such as baseline liver condition, technical approach and pre-existing co-morbidities. Five-year survival in patients with originally unresectable tumors as a result of inadequate future liver remnant and received PVE with subsequent resection was found in one study to be 29%. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2875", "text": "Originally, there was concern that PVE could promote tumor growth and increase recurrence rates, however a systematic review has found that there was no significant difference observed in postoperative hepatic recurrence or 3 and 5 year overall survival rates. [ 5 ]  This suggests that PVE does not have any significant adverse effects on the risk of oncogenesis. Overall, PVE is an important technique that can allow for patients with inadequate predicted FLR/TELV ratios an opportunity for resection and potential cure of their liver conditions."}
{"_id": "WikiPedia_Radiology$$$corpus_2876", "text": "Portal hypertension  is an absolute contraindication, as these patients are not surgical candidates and are at higher risk of significant complications from PVE. Additionally, complete lobar portal vein occlusion of either lobe would preclude expected increases in FLR from PVE due to already existing diversion of portal flow. Patients with extrahepatic metastatic disease are also not candidates for resection, and therefore PVE is contraindicated. In the past patients with bi-lobar disease were not considered for PVE, however now there may be a role of PVE in combination with a two-stage hepatectomy. [ 2 ] [ 6 ]   Additionally, patients who have an inadequate predicted FLR post PVE should not be considered. Other contraindications include any conditions that make a patient unfit for surgery or intervention (poor cardiopulmonary status,  sepsis ,  kidney failure , etc.)."}
{"_id": "WikiPedia_Radiology$$$corpus_2877", "text": "PVE has been shown to have the following risks: [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2878", "text": "PVE has been shown to have the following benefits:"}
{"_id": "WikiPedia_Radiology$$$corpus_2879", "text": "Portal vein embolization is a preoperative procedure performed in  interventional radiology  to initiate hypertrophy of the anticipated future liver remnant a couple weeks prior to a major liver resection procedure. Future liver remnant (FLR) is defined as the predicted volume of functional liver after resection. There are specific FLR thresholds depending on the status of the liver (otherwise normal, chronic hepatitis, cirrhosis, etc.) that are required for safe liver resection. When the predicted FLR is below threshold, portal vein embolization may increase the FLR and bring it to threshold. [ 1 ]  The majority of preoperative PVEs usually target the right  portal vein  in preparation of a major right-sided resection. Though rare, the left portal vein may be embolized prior to a left-sided resection."}
{"_id": "WikiPedia_Radiology$$$corpus_2880", "text": "The increase in FLR is a result of cellular hyperplasia and not cellular  hypertrophy . This means that it is an increase in the number of hepatocytes that accounts for the growth rather than the increase in size of existing hepatocytes. The liver is unique in that it is an organ with regenerative potential. When blood flow to one section of the liver is occluded in PVE, the flow is diverted to other areas and this increase in blood flow stimulates the regenerative response. [ 7 ]  Regeneration begins within hours of occlusion and factors important to this response include  hepatocyte growth factor ,  epidermal growth factor ,  insulin ,  IL-6  and  TNF-alpha , among others. [ 7 ] [ 8 ]  The expected increase in FLR is approximately 10 percent; greater increases after four to six weeks can be observed, albeit at a lower rate of growth. An increase in FLR of greater than five percent for a normal liver and 10 percent for a cirrhotic liver is considered adequate and is associated with a reduced risk of post-resection liver failure. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2881", "text": "PVE was originally performed using an open approach, but the majority is now done percutaneously under conscious sedation and local anesthesia by an interventional radiologist. This can be done using either a transjugular or transhepatic approach. The most commonly used method is the direct transhepatic puncture of the portal vein. [ 10 ]  Several different  embolization agents  can be used and the choice of agents often depend on the expertise of the physician, availability and cost. As the agents differ in size, occlusive properties and side effect profiles, the choice of agent will also depend on the anatomy and locations of the tumors in a specific case. Some commonly used agents include cyanoacrylate, sodium tetradecyl sulfate foam, gelatin, metallic spherical particles, coils and absolute alcohol. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2882", "text": "To determinate whether there is a need for PVE the FLR needs to be measured. There are various imaging methods used in order to measure the liver volume such as contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) [ 11 ]  and the FLR can be traced either manually or using automatic or semi-automatic segmentation tools. FLR is measured with the chosen imaging method before PVE and then again 1\u20134 weeks after PVE calculating the hypertrophy of the FLR."}
{"_id": "WikiPedia_Radiology$$$corpus_2883", "text": "A technique tested so far in pigs in which a 3:1 mixture of iodinated oil and absolute ethanol was infused via lobar hepatic artery branches and into the portal system via the peribiliary plexus. The degree of FLR hypertrophy seen in the pigs with transarterial PVE compared to traditional percutaneous PVE were found to be nearly double. No significant adverse events were noted. The advantage to this new approach is a better safety profile (does not require direct hepatic puncture). However, this approach may be limited by the amount of embolic agent needed for successful embolization, as the amount needed for humans may exceed the threshold for pulmonary complications."}
{"_id": "WikiPedia_Radiology$$$corpus_2884", "text": "There are times when a patient who has undergone a PVE is no longer able to undergo a resection. In these instances, the patients are left with a permanently occluded portal vein that can exclude them from receiving other therapies. Therefore, PVE with absorbable materials such as powdered gelatin sponge dissolved in a 4:1 mixture of iodinated contrast medium and saline has been used and shown induce FLR hypertrophy. However, whether it can provide the comparable response to traditional PVE must still be studied. In the future, reversible PVE may also play a role in treating patients with chronic hepatic insufficiency to increase functional liver tissue, as opposed to just being used as an adjuvant therapy for liver resection."}
{"_id": "WikiPedia_Radiology$$$corpus_2885", "text": "Studies have shown that bone marrow-derived stem cells (specifically CD133+) play a role in liver regeneration. A study done by Esch, et al. [ 12 ]  showed that patients who received stem cells in addition to PVE had significant increases in both absolute and relative FLR growth than in patients who received PVE only. They found no significant differences between the groups in regards to major complications and mortality. This suggests that adjuvant stem cell transplantation can increase the efficacy of PVE without increasing risk."}
{"_id": "WikiPedia_Radiology$$$corpus_2886", "text": "Radiation lobectomy  is a form of  radiation therapy  used in  interventional radiology  to treat  liver cancer . It is performed in patients that would be surgical candidates for resection, but cannot undergo surgery due to insufficient remaining liver tissue. It consists of injecting small radioactive beads loaded with  yttrium-90  into the hepatic artery feeding the hepatic lobe in which the tumor is located. This is done with the intent of inducing growth in the contralateral hepatic lobe, not dissimilarly from  portal vein embolization  (PVE)."}
{"_id": "WikiPedia_Radiology$$$corpus_2887", "text": "RL is performed in people with liver cancer, both primary such as  hepatocellular carcinoma  and metastatic such as from  colon adenocarcinoma . Surgical resection is considered the only curative treatment for liver cancer (other than liver transplantation for hepatocellular carcinoma) but it can only be performed in patients with sufficient remnant liver after resection (amongst other criteria). Both PVE and RL are performed in patients who are not surgical candidates due to insufficient future liver remnant (FLR), which is advised to be between 20-30% and 30-40% of the native liver volume in healthy and cirrhotic livers, respectively. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2888", "text": "Radiation lobectomy is a relatively new application of  radioembolization  and results are mainly reported in the form of retrospective chart review studies and case reports, without any prospective validation. Most authors report a comparable future liver remnant hypertrophy between portal vein embolization and RL, ranging between 10 and 47% [ 2 ] [ 3 ] [ 4 ] [ 5 ]  with cases reaching up to 119% with RL. [ 6 ]  The main difference between the two is the time interval necessary for appropriate hypertrophy, greater for RL. PVE requires a shorter time frame to achieve comparable results, ranging between 2\u20136 weeks, [ 7 ] [ 8 ]  while the hypertrophy kinetics of RL are slower but more constant, without significant plateau (some studies report continued hypertrophy up to 9 months). [ 2 ]  Some authors have even raised concerns regarding PVE and the potential interval disease progression in the embolized and treatment naive lobes while allowing hypertrophy, which is of less concern with RL due to its added tumoricidal effect. [ 9 ]  Additionally, RL has been demonstrated to aid surgical resection in some cases by inducing a \u201cvascular shift\u201d of tumor masses via necrosis and contraction away from major vascular pedicles, converting patients to resectable status. [ 4 ]  One study has shown preliminary 600-day survival in 12 out of 13 patients who received RL and subsequent resection. [ 4 ]  Ultimately, further studies are needed to prospectively compare survival and recurrence outcomes in patients receiving RL versus PVE. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2889", "text": "Common side effects include fatigue, abdominal pain, nausea and anorexia, usually self-limiting. Post-radioembolization syndrome occurs in 20-70% of patients that undergo traditional radioembolization, presenting with shakes, chills, fatigue, nausea/vomiting, abdominal pain/discomfort, and/or cachexia and possibly hemodynamic changes, rarely requiring admission. Unfortunately, most data, if not all, is derived from traditional radioembolization outcomes studies and more will be needed to assess the actual incidence and risk of post-radioembolization syndrome in RL. [ 10 ] [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2890", "text": "Complications are abscess formation, biliary complications (biloma, radiation induced cholecystitis and cholangitis, biliary necrosis), gastrointestinal complications (diarrhea, radiation induced gastritis and gastrointestinal ulceration), radiation induced pancreatitis, dermatitis, pneumonitis and lymphopenia. [ 10 ] [ 11 ] [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2891", "text": "RL is performed by an interventional radiologist in the  angiography  suite, in a fashion similar to radioembolization. The procedure is composed of two different portions, a planning phase and the actual radiation lobectomy, usually performed in two different sessions: [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2892", "text": "Patients undergo cross-sectional imaging at approximately 30\u201360 days from the procedure for evaluation of the degree of  hypertrophy  undergone by the contralateral side (as assessed by future liver remnant) and to assess tumor burden. At this time, the surgeons and/or a multi-specialty tumor board will convene to determine if the patient can/should undergo safe surgical resection."}
{"_id": "WikiPedia_Radiology$$$corpus_2893", "text": "Radiofrequency ablation  ( RFA ), also called  fulguration , [ 1 ]  is a medical procedure in which part of the  electrical conduction system of the heart ,  tumor ,  sensory nerves  or a dysfunctional  tissue  is  ablated  using the heat generated from  medium frequency   alternating current  (in the range of 350\u2013500\u00a0kHz). [ 2 ] [ 3 ]  RFA is generally conducted in the  outpatient  setting, using either a  local anesthetic [ 3 ]  or  twilight anesthesia . When it is delivered via  catheter , it is called radiofrequency  catheter ablation ."}
{"_id": "WikiPedia_Radiology$$$corpus_2894", "text": "Two advantages of  radio frequency  current (over previously used low frequency AC or pulses of DC) are that it does not directly stimulate nerves or heart muscle, and therefore can often be used without the need for  general anesthesia , and that it is specific for treating the desired tissue without significant collateral damage. [ 3 ] [ 4 ]  Due to this, RFA is an alternative for eligible patients who have  comorbities  or do not want to undergo surgery. [ 3 ] [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2895", "text": "Documented benefits have led to RFA becoming widely used during the 21st century. [ 3 ] [ 5 ] [ 7 ] [ 8 ] [ 9 ]  RFA procedures are performed under image guidance (such as X-ray screening,  CT scan  or  ultrasound ) by an interventional pain specialist (such as an anesthesiologist),  interventional radiologist ,  otolaryngologists , a gastrointestinal or surgical endoscopist, or a  cardiac electrophysiologist , a subspecialty of  cardiologists ."}
{"_id": "WikiPedia_Radiology$$$corpus_2896", "text": "RFA may be performed to treat tumors in the lung, [ 10 ] [ 11 ] [ 12 ]  liver, [ 13 ]  kidney, and bone, as well as other body organs less commonly. Once the diagnosis of tumor is confirmed, a needle-like RFA probe is placed inside the tumor. The radiofrequency waves passing through the probe increase the temperature within tumor tissue, which results in destruction of the tumor. RFA can be used with small tumors, whether these arose within the organ (primary tumors) or spread to the organ ( metastases ). The suitability of RFA for a particular tumor depends on multiple factors. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2897", "text": "RFA can usually be administered as an outpatient procedure, though may at times require a brief hospital stay. RFA may be combined with locally delivered chemotherapy to treat hepatocellular carcinoma (primary liver cancer). A method currently in phase III trials uses the low-level heat (hyperthermia) created by the RFA probe to trigger release of concentrated chemotherapeutic drugs from heat-sensitive liposomes in the margins around the ablated tissue as a treatment for  hepatocellular carcinoma  (HCC). [ 14 ] \nRadiofrequency ablation is also used in pancreatic cancer and bile duct cancer. [ 15 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2898", "text": "RFA has become increasingly important in the care of benign bone tumors, most notably  osteoid osteomas . Since the procedure was first introduced for the treatment of osteoid osteomas in the 1990s, [ 16 ]  it has been shown in numerous studies to be less invasive and expensive, to result in less bone destruction and to have equivalent safety and efficacy to surgical techniques, with 66 to 95% of people reporting freedom from symptoms. [ 17 ] [ 18 ] [ 19 ]  While initial success rates with RFA are high, symptom recurrence after RFA treatment has been reported, with some studies demonstrating a recurrence rate similar to that of surgical treatment. [ 20 ]  RFA is also increasingly used in the palliative treatment of painful  metastatic bone disease  in people who are not eligible or do not respond to traditional therapies ( i.e.  radiation therapy ,  chemotherapy , palliative surgery,  bisphosphonates  or analgesic medications). [ 21 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2899", "text": "Radiofrequency energy is used in heart tissue or normal parts to destroy abnormal electrical pathways that are contributing to a  cardiac arrhythmia . It is used in recurrent  atrial flutter  (Afl),  atrial fibrillation  (AF),  supraventricular tachycardia  (SVT),  atrial tachycardia ,  Multifocal Atrial Tachycardia  (MAT) and some types of  ventricular arrhythmia . The energy-emitting probe (electrode) is at the tip of a catheter which is placed into the heart, usually through a vein. This catheter is called the  ablator . The practitioner first \"maps\" an area of the heart to locate the abnormal electrical activity ( electrophysiology study ) before the responsible tissue is eliminated. Radiofrequency ablation technique can be used in AF, either to block the  atrioventricular node  after implantation of a pacemaker or to block conduction within the  left atrium , especially around the  pulmonary veins . Radiofrequency ablation for AF can be unipolar (one electrode) or bipolar (two electrodes). [ 22 ]  Although bipolar can be more successful, it is technically more difficult, resulting in unipolar being used more often. [ 22 ]  But bipolar is more effective in preventing recurrent atrial arrhythmias. [ 23 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2900", "text": "Ablation is now the standard treatment for SVT and typical atrial flutter, In some conditions, especially forms of intra-nodal re-entry (the most common type of SVT), also called atrioventricular nodal reentrant tachycardia or AVNRT, ablation can also be accomplished by cryoablation (tissue freezing using a coolant which flows through the catheter) which avoids the risk of complete heart block \u2013 a potential complication of radiofrequency ablation in this condition. Recurrence rates with cryoablation are higher, though. [ 24 ]  Microwave ablation, where tissue is ablated by the microwave energy \"cooking\" the adjacent tissue, and ultrasonic ablation, creating a heating effect by mechanical vibration, or laser ablation have also been developed but are not in widespread use. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2901", "text": "A new indication for the use of radiofrequency technology has made news in the last few years.  Hypertension  is a very common condition, with about 1\u00a0billion people over the world, nearly 75 million in the US alone. Complications of inadequately controlled hypertension are many and have both individual and global impact. Treatment options include medications, diet, exercise, weight reduction and meditation. Inhibition of the neural impulses that are believed to cause or worsen hypertension has been tried for a few decades. Surgical sympathectomy has helped but not without significant side effects. Therefore, the introduction of non-surgical means of renal denervation using a radiofrequency ablation catheter was enthusiastically welcomed. Although the initial use of radiofrequency-generated heat to ablate nerve endings in the renal arteries to aid in management of 'resistant hypertension' were encouraging, the most recent phase 3 studying looking at catheter-based renal denervation for the treatment of resistant hypertension failed to show any significant reduction in systolic blood pressure. [ 25 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2902", "text": "Radiofrequency  ablation [ 26 ]  is a dermatosurgical procedure by using various forms of alternating current. Types of radiofrequency are electrosection, electrocoagulation, electrodessication and fulguration. The use of radiofrequency ablation has obtained importance as it can be used to treat most of the skin lesions with minimal side effects and complications. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2903", "text": "Radiofrequency ablation is a minimally invasive procedure used in the treatment of  varicose veins . It is an alternative to the traditional stripping operation. Under ultrasound guidance, a radiofrequency catheter is inserted into the abnormal vein and the vessel treated with radio-energy, resulting in closure of the involved vein. Radiofrequency ablation is used to treat the  great saphenous vein , the  small saphenous vein , and the  perforator veins . The latter are connecting veins that transport blood from the superficial veins to the deep veins. Branch varicose veins are then usually treated with other minimally invasive procedures, such as  ambulatory phlebectomy ,  sclerotherapy , or  foam sclerotherapy . Currently, the VNUS ClosureRFS stylet is the only device specifically cleared by FDA for endovenous ablation of perforator veins. [ 27 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2904", "text": "The possibility of skin burn during the procedure is very small, because the large volumes (500 cc) of dilute Lidocaine (0.1%) tumescent anesthesia injected along the entire vein prior to the application of radiofrequency provide a heat sink that absorbs the heat created by the device. Early studies have shown a high success rate with low rates of complications. [ 28 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2905", "text": "RFA was first studied in  obstructive sleep apnea  (OSA) in a pig model. [ 29 ]  RFA has been recognized as a  somnoplasty  treatment option in selected situations by the  American Academy of Otolaryngology [ 29 ]  but was not endorsed for general use in the  American College of Physicians  guidelines. [ 30 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2906", "text": "The clinical application of  RFA in obstructive sleep apnea  is reviewed in that main article, including controversies and potential advantages in selected  medical situations .\nUnlike other electrosurgical devices, [ 31 ]  RFA allows very specific treatment targeting of the desired tissue with a precise  line of demarcation  that avoids collateral damage, which is crucial in the head and neck region due to its high density of major nerves and blood vessels. RFA also does not require high temperatures. However, overheating from misapplication of RFA can cause harmful effects such as coagulation on the surface of the electrode, boiling within tissue that can leave \"a gaping hole\", tears, or even charring. [ 32 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2907", "text": "RFA, or  rhizotomy , was developed by  Nikolai Bogduk  to treat chronic pain arising from the  facet joints  in the lower ( lumbar ) back.  Radiofrequency waves  are used to produce heat on specifically identified nerves surrounding the  facet joints  called the lumbar medial branches of the  dorsal ramus of the spinal nerves . [ 33 ]   By generating heat around the nerve, the nerve is ablated, thus destroying its ability to transmit signals to the brain."}
{"_id": "WikiPedia_Radiology$$$corpus_2908", "text": "The nerves to be ablated are identified through injections of local anesthesia (such as  lidocaine ) around the medial branches prior to the RFA procedure to first confirm the diagnosis. If the  local anesthesia  injections provide temporary pain relief, the injection is repeated a second time to confirm the diagnosis. Then RFA is performed on the nerve(s) that responded well to the injections."}
{"_id": "WikiPedia_Radiology$$$corpus_2909", "text": "RFA is a minimally invasive procedure which can usually be done in day-surgery clinics, going home shortly after completion of the procedure. The person is awake during the procedure, so risks associated with general anesthesia are avoided. Whether for back or knee pain, a drawback for this procedure is that nerves recover function over time, so the pain relief achieved lasts only temporarily (3\u201315 months) in most people. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2910", "text": "Radiofrequency ablation of sensory nerves in the knee, also called  genicular neurotomy  or  genicular RFA , is clinically preceded by confirming pain reduction upon anesthetizing the main knee sensory nerves in a test procedure called  genicular nerve block . [ 3 ] [ 34 ] [ 35 ]  Genicular nerve block is a short (10-30 minutes), outpatient procedure usually performed weeks before genicular RFA. [ 3 ] [ 36 ] [ 37 ]  The extent of pain reduction by injecting a local anesthetic, such as  bupivacaine , at specific locations of the target genicular nerves, is self-assessed by the person for hours after the procedure, leading to confirmation with the physician of the need for RFA. [ 3 ] [ 37 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2911", "text": "In the procedure for genicular RFA, a guide cannula is first directed under local anesthesia and imaging ( ultrasound  or  fluoroscopy ) to each target genicular nerve, then the radiofrequency electrode is passed through the cannula, and the electrode tip is heated to about 80\u00a0\u00b0C (176\u00a0\u00b0F) for one minute to  cauterize  a small segment of the nerve. [ 3 ] [ 34 ]  The heat destroys that segment of the nerve, which is prevented from sending pain signals to the brain. [ 3 ] [ 34 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2912", "text": "As of 2019, several hundred publications showed promise for substantial, long-term (6 months or longer) reduction of knee pain following genicular RFA. [ 3 ] [ 38 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2913", "text": "The US  Food and Drug Administration  had approved in 2017 a commercial device using cooled RFA, with effects lasting for up to a year of pain relief from  knee arthritis . [ 9 ] [ 39 ]  As of 2023, reviews of clinical outcomes indicated that efficacy for reducing knee pain was achieved by ablating three or more branches of the genicular nerve (one of the  articular  branches of the  tibial nerve ). [ 36 ] [ 38 ] [ 40 ] [ 41 ]  Other sources indicate 4-5 genicular nerve targets may be justified for ablation to optimize pain relief, [ 35 ] [ 36 ]  while a 2022 analysis indicated that as many as 10 genicular nerve targets for RFA would produce better long-term relief of knee pain. [ 42 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2914", "text": "Knee pain relief of 50% or more following genicular RFA may last from several months to two years, [ 3 ] [ 40 ] [ 41 ]  and can be repeated by the same outpatient procedure when pain recurs. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2915", "text": "An anatomical study of  cadaver  knees indicated that ultrasound-guided bony landmarks could be used to effectively target the superior medial geniculate nerve, superior lateral geniculate nerve, and inferior medial geniculate nerve \u2013 the three nerves commonly targeted for knee RFA [ 3 ]  \u2013 with average nerve-to-needle distances of 1.7, 3.2, and 1.8 mm, respectively. [ 43 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2916", "text": "Radiofrequency ablation has been shown to be a safe and effective treatment for  Barrett's esophagus . The balloon-based radiofrequency procedure was invented by Robert A. Ganz, Roger Stern and Brian Zelickson in 1999 (System and Method for Treating Abnormal Tissue in the Human Esophagus). While the person is sedated, a catheter is inserted into the esophagus and radiofrequency energy is delivered to the diseased tissue. This outpatient procedure typically lasts from fifteen to thirty minutes. Two months after the procedure, the physician performs an upper endoscopic examination to assess the esophagus for residual Barrett's esophagus. If any Barrett's esophagus is found, the disease can be treated with a focal RFA device. Between 80 and 90% or greater of people in numerous clinical trials have shown complete eradication of Barrett's esophagus in approximately two to three treatments with a favorable safety profile. The treatment of Barrett's esophagus by RFA is durable for up to 5 years. [ 44 ] [ 45 ] [ 46 ] [ 47 ] [ 48 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2917", "text": "Radiofrequency ablation has been used successfully on benign thyroid nodules for decades, most notably in Europe, South America and Korea. [ citation needed ]  In the United States, the FDA approved the use of RFA techniques for thyroid nodules in 2018. Since then, professional guidelines reflect its use as a viable treatment modality for thyroid nodules, and the procedure is increasingly applied. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2918", "text": "- 2023: the  American Thyroid Association  issued the position statement \"Thyroid ablative procedures provide valid alternative treatment strategies to conventional surgical management for a subset of patients with symptomatic benign thyroid nodules. [ 49 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2919", "text": "- 2022: the  American Association of Clinical Endocrinologists  published an update in Endocrine Practice, stating that the \"new image-guided minimally invasive approaches appear safe and effective alternatives when used appropriately and by trained professionals to treat symptomatic or enlarging thyroid masses\". [ 50 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2920", "text": "- 2018: FDA approved the RFA procedure for treatment of benign thyroid nodules. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2921", "text": "The procedure is similar to a thyroid biopsy, although instead of using a needle to remove cells from the nodule, a probe delivers heat to the interior of the nodule that effectively  cauterizess  the tissue. [ medical citation needed ]  Over the course of 3-6 months, the nodule will continue to shrink, typically achieving a 50-80% reduction total size. [ medical citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2922", "text": "In order to qualify for an RFA procedure, a person must have a clearly benign thyroid nodule, usually proven by two fine needle aspiration biopsies. [ medical citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2923", "text": "As of 2020, RFA is not recommended for the treatment of  malignant  thyroid nodules, although research into this topic is ongoing. [ 51 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2924", "text": "RFA is also used in radiofrequency lesioning for vein closure in areas where intrusive surgery is contraindicated by trauma, and in liver resection to control bleeding (hemostasis) and facilitate the transection process. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2925", "text": "This process has also been used to treat  TRAP sequence  in multiple gestation pregnancies. This has an acceptable success rate for saving the 'pump' twin in recent studies compared to previous methods including laser photocoagulation. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2926", "text": "RFA is used to treat  uterine fibroids  using the heat energy of radio frequency waves to ablate the fibroid tissue. The Acessa device [ 52 ]  obtained FDA approval in 2012. [ 53 ]  The device is inserted via a laparoscopic probe and guided inside the fibroid tissue using an ultrasound probe. The heat shrinks the fibroids. Clinical data on the procedure show an average of 45% shrinkage."}
{"_id": "WikiPedia_Radiology$$$corpus_2927", "text": "RFA is also used in the treatment of  Morton's neuroma [ 54 ]  where the outcome appears to be more reliable than alcohol injections. [ 55 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2928", "text": "Renal sympathetic denervation  (RSDN) is a minimally invasive, endovascular catheter based procedure using  radiofrequency ablation  or ultrasound ablation aimed at treating resistant  hypertension  (high  blood pressure  not controlled by medication). [ 1 ]   Nerves in the wall of the  renal artery  are ablated by applying radiofrequency pulses or ultrasound to the renal arteries. This causes reduction of sympathetic afferent and efferent activity to the  kidney  and blood pressure can be decreased. [ 2 ]  Early data from international clinical trials without sham controls was promising - demonstrating large blood pressure reductions in patients with treatment-resistant hypertension. [ 2 ] [ 3 ]  However, in 2014 a prospective, single-blind, randomized, sham-controlled clinical trial failed to confirm a beneficial effect on blood pressure. [ 4 ]  A 2014 consensus statement from The Joint UK Societies did not recommend the use of renal denervation for treatment of resistant hypertension on current evidence. [ 5 ]   More recent sham-controlled trials suggest renal denervation can lead to lower systolic blood pressure. [ 6 ] [ 7 ] [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2929", "text": "Prior to pharmacological management of hypertension, surgical  sympathectomy  was a recognized treatment for hypertension. [ 9 ]  This was often successful in reducing blood pressure but due to its non-selective nature the side effects of the procedure were poorly tolerated. Side effects included orthostatic hypotension, palpitations, anhydrosis, intestinal disturbances, loss of ejaculation, thoracic duct injuries and atelectasis. [ 10 ]   Modern antihypertensive pharmacological interventions have improved the control of hypertension, but only 34\u201366% of people with hypertension in England, US and Canada have blood pressure at or below target levels. [ 11 ]  Resistant hypertension is defined as blood pressure above target (140/90mm Hg) despite concomitant use of three or more anti-hypertensives \u2013 one of which should be a diuretic. [ 12 ]  It has been estimated that 8\u201310% of people with hypertension fall into this category. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2930", "text": "Several commercial devices exist. [ 13 ]   These include Medtronic's Symplicity Renal Denervation System, St. Jude Medical's EnligHTN System, Boston Scientific's Vessix V2 Renal Denervation System, Covidien's OneShot System, Recor's Paradise System, Terumo's Iberis System and Cordis Corporation's RENLANE Renal Denervation System."}
{"_id": "WikiPedia_Radiology$$$corpus_2931", "text": "In August 2023, the US FDA panel recommended the device from ReCor while rejecting the device from Medtronic. [ 14 ] [ 15 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2932", "text": "The procedure involves  endovascular access   via  the  femoral artery  with advancement of a catheter-mounted device into the renal artery. The device uses radiofrequency or ultrasound to ablate the renal nerves. Typically, numerous ablations are applied at a different longitudinal and rotational positions to ensure maximal denervation. [ 13 ]  The procedure does not involve a permanent implant. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2933", "text": "The most widely discussed studies to date are the Symplicity HTN-1, HTN-2 and HTN-3 trials, conducted with Medtronic's Symplicity RDN System. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2934", "text": "Symplicity HTN-1 [ 3 ]  looked at outcomes in 153 patients that underwent catheter-based renal denervation. Three-year follow-up data have demonstrated an average blood pressure reduction of -33/-19mm Hg."}
{"_id": "WikiPedia_Radiology$$$corpus_2935", "text": "Symplicity HTN-2 was a randomized, [ 2 ]  controlled trial that compared 54 control patients with 52 patients who underwent catheter-based renal denervation. Six month follow-up data demonstrated a blood pressure reduction of -32/12\u00a0mm Hg in the treated group compared with a change of 1/0\u00a0mm Hg in the control group."}
{"_id": "WikiPedia_Radiology$$$corpus_2936", "text": "Meta-analyses of renal denervation have yielded conflicting results. [ 16 ]  Whilst office systolic blood pressure reductions typically average around 30\u00a0mmHg, reductions observed on ambulatory blood pressure monitoring are typically much smaller, around 10 mmHg. [ 17 ]  Explanations offered for this mismatch include renal denervation obliterating the white coat response, thereby disproportionately reducing clinic pressures, [ 16 ]  or inadvertent bias arising from the unblinded design and lack of sham control procedure in almost all renal denervation trial designs to date. [ 17 ] [ 18 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2937", "text": "A study published in 2014, Symplicity HTN-3, was a prospective, single-blind, randomised, sham-controlled trial in which 535 patients with severe resistant hypertension were randomized to undergo renal denervation or a sham procedure (in a 2:1 ratio). The results showed no statistically significant difference between renal denervation and the sham procedure. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2938", "text": "Following the publication of Symplicity HTN-3 the Joint UK Societies produced a consensus statement that did not recommend the use of renal denervation for treatment of resistant hypertension in routine clinical practice. However they advocated further research with better designed randomised studies. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2939", "text": "More recent sham-controlled trials suggest renal denervation can lead to lower systolic blood pressure. [ 6 ] [ 7 ] [ 8 ] [ 19 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2940", "text": "The Symplicity HTN-1, HTN-2 and HTN-3 trials have demonstrated acceptable safety profiles for catheter based renal denervation. Patients may experience pain during application of radiofrequency pulses and intraprocedural  bradycardia  requiring  atropine  has also been reported. [ 2 ]   Other documented procedure related complications include femoral artery  pseudoaneurysm  and renal artery dissection. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2941", "text": "Of particular concern is the theoretical risk of damage to renal arteries during delivery of radiofrequency energy. An animal study using swine showed no damage to the renal arteries at 6 month follow up.  This finding is further supported in human studies in the HTN-1 and HTN-2 trial where follow up imaging has not demonstrated renal vascular damage. [ 20 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2942", "text": "Other diseases may be associated with an overactive sympathetic drive and therefore, in theory, renal denervation could be of benefit. Congestive heart failure (CHF), left ventricular hypertrophy (LVH), atrial fibrillation (AF), obstructive sleep apnea (OSA), and insulin resistance/type 2 diabetes mellitus (DM) all have been associated with increased activity of the sympathetic nervous system. [ citation needed ]  Current clinical trials are examining the effect of renal denervation in these conditions. [ 21 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2943", "text": "Resuscitative endovascular balloon occlusion of the aorta  ( REBOA ) is a minimally-invasive procedure performed during resuscitation of critically-injured trauma patients. Originally developed as a less invasive alternative to  emergency thoracotomy  with aortic cross clamping, REBOA is performed to gain rapid control of non-compressible truncal or junctional hemorrhage. [ 1 ] [ 2 ]  REBOA is performed first by achieving access to the common femoral artery (CFA) and advancing a catheter within the aorta. [ 1 ]  Upon successful catheter placement, an occluding balloon may be inflated either within the descending  thoracic aorta  (Zone 1) or infrarenal  abdominal aorta  (Zone 3). [ 1 ] [ 2 ]  REBOA stanches downstream hemorrhage and improves  cardiac index , cerebral perfusion, and coronary perfusion. [ 1 ] [ 3 ] [ 4 ]  Although REBOA does not eliminate the need for definitive hemorrhage control, it may serve as a temporizing measure during initial resuscitation. [ 1 ]  Despite the benefits of REBOA, there are significant local and systemic ischemic risks. [ 1 ] [ 5 ]  Establishing standardized REBOA procedural indications and mitigating the risk of ischemic injury are topics of ongoing investigation. [ 1 ] [ 4 ]  Although this technique has been successfully deployed in adult patients, it has not yet been studied in children. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2944", "text": "Severe hemorrhagic shock caused by non-compressible traumatic injury to the torso and junctional regions remains a major cause of death among civilian and military trauma victims. [ 1 ] [ 2 ] [ 3 ] [ 4 ]  In contrast to peripheral hemorrhage caused by injury to an extremity, traumatic injuries to the torso and junctional regions are not amendable to direct pressure or  tourniquet  application. [ 1 ] [ 2 ] [ 4 ]  Because non-compressible torso hemorrhages are not amendable to external interventions, these injuries account for approximately 90% of exsanguinating deaths. [ 4 ]  Severe hemorrhage is managed either with vascular embolization or damage control surgical techniques such as abdominal packing or removal of non-essential organs. [ 2 ]  However, in patients with severe hemorrhagic shock at risk for cardiovascular collapse, emergency thoracotomy with aortic cross clamping may be performed though outcomes are typically poor. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2945", "text": "REBOA was developed as a rapidly deployable, minimally invasive alternative to emergency thoracotomy with aortic cross-clamping. Although there is no single indication criteria for the procedure, it is typically performed for patients with either blunt or penetrating traumatic injuries to the torso with severe hemorrhage refractory to blood product resuscitation. [ 7 ]  REBOA is performed by gaining access to the common femoral artery and inserting a small endovascular catheter with an inflatable balloon within the aorta. [ 1 ]  Upon inflation of the occluding balloon, blood flow across the descending aorta is either partially or completely obstructed which subsequently stanches downstream bleeding. [ 1 ] [ 2 ] [ 3 ]  The adjustable catheter design of the REBOA device allows for variable positioning of the occluding balloon within the aorta based on the suspected source of bleeding. [ 1 ] [ 2 ]  Zone 1 positioning in the descending thoracic aorta minimizes blood flow below the diaphragm and significantly reduces bleeding within the abdomen, pelvis, and lower extremities. [ 2 ]  Alternatively, Zone 3 placement within the infrarenal descending abdominal aorta reduces bleeding within the pelvis and lower extremities while preserving blood supply within the abdomen. [ 2 ]  Although REBOA does not replace the need for definitive surgical management, it may act as a temporizing measure by temporarily augmenting cardiac index to preserve cerebral and myocardial perfusion. [ 1 ] [ 3 ] [ 4 ]  Immediately following successful REBOA deployment, patients must be considered for emergent surgical intervention. [ 1 ] [ 2 ] [ 7 ] [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2946", "text": "The safety and efficacy of REBOA in the treatment of severe hemorrhagic shock is an area of ongoing research. Early studies reported conflicting data regarding mortality and failed to establish any clear benefit of REBOA when compared to emergency thoracotomy with aortic cross clamping. [ 1 ] [ 2 ] [ 4 ]  However, design improvements of the REBOA device and continuously evolving patient selection criteria have subsequently improved REBOA outcomes. [ 1 ]  Current literature demonstrates a survival benefit of REBOA deployment in patients with severe hemorrhagic shock who do not require  cardiopulmonary resuscitation (CPR) . [ 1 ]  However, despite REBOA demonstrating its greatest efficacy when deployed prior to cardiovascular collapse, recent data has also shown promise when deployed during CPR. [ 1 ]  Closed cardiopulmonary compressions with the REBOA device deployed has demonstrated improved cardiac compression fraction and end-tidal CO 2  when compared to emergency thoracotomy with aortic cross clamping and cardiac massage. [ 1 ]  Additionally, some centers have promoted REBOA deployment in patients with hypotension at risk for progression to severe hemorrhagic shock but who do not yet meet criteria for emergency thoracotomy with aortic cross clamping. [ 3 ]  The variability in REBOA outcomes likely reflects the variability in institutional patient selection and indications criteria which highlights the need for ongoing evaluation. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2947", "text": "Access to the common femoral artery is first achieved using ultrasound guided, open, or percutaneous technique. [ 1 ]  The REBOA device is then positioned either within Zone 1 (descending thoracic aorta) or Zone 3 (infrarenal abdominal aorta) before the occluding balloon is inflated with saline. [ 1 ]  Upon successful definitive hemorrhage control, the occluding balloon is slowly deflated and the patient is monitored for recurrent bleeding or metabolic derangement. [ 1 ]  Finally, the REBOA sheath is removed and the patient is monitored for access site complications or potential ischemic complications. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2948", "text": "Despite the minimally invasive nature of the REBOA device, there are significant risks associated with its use. Although occlusion of the aorta may temporarily augment cardiac index to preserve cardiac and coronary perfusion, there is a significant risk of downstream ischemia which may lead to local ischemic changes or systemic metabolic derangement. [ 2 ] [ 3 ]  Significant complications such as limb amputation,  metabolic acidosis , and severe  reperfusion injury  have all been reported with REBOA use and are the subjects of ongoing research. [ 1 ] [ 2 ] [ 3 ]  Although there is no definitive consensus within the academic or surgical communities, many centers recommend balloon occlusion times of less than 30 minutes whenever possible to minimize the risk of clinically significant ischemia. [ 3 ]  Alternatively, some institutions have recommended partial aortic occlusion or intermittent balloon deflation to minimize the effect of downstream ischemia. [ 3 ]  Although intermittent balloon deflation is less technically difficult to perform, partial occlusion of the aorta has been demonstrated to reduce uncontrolled hemorrhage while simultaneously limiting distal ischemia and extending safe occlusion times. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2949", "text": "Additional potential complications are listed below:"}
{"_id": "WikiPedia_Radiology$$$corpus_2950", "text": "The  Seldinger technique , also known as  Seldinger wire technique , is a  medical procedure  to obtain safe access to  blood vessels  and other hollow  organs . It is  named after   Sven Ivar Seldinger  (1921\u20131998), a  Swedish   radiologist  who introduced the procedure in 1953. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2951", "text": "The Seldinger technique is used for  angiography , insertion of  chest drains  and  central venous catheters , insertion of  PEG  tubes using the push technique, insertion of the leads for an  artificial pacemaker  or  implantable cardioverter-defibrillator , and numerous other interventional medical procedures."}
{"_id": "WikiPedia_Radiology$$$corpus_2952", "text": "The initial puncture is with a sharp instrument, and this may lead to  hemorrhage  or  perforation  of the organ in question.  Infection  is a possible complication, and hence  asepsis  is practiced during most Seldinger procedures."}
{"_id": "WikiPedia_Radiology$$$corpus_2953", "text": "Loss of the guidewire into the cavity or blood vessel is a significant and generally preventable complication. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2954", "text": "The desired vessel or cavity is punctured with a sharp hollow needle, with  ultrasound  guidance if necessary. A round-tipped guidewire is then advanced through the  lumen  of the needle, and the needle is withdrawn. A sheath or blunt  cannula  can now be passed over the guidewire into the cavity or vessel. Alternatively, drainage tubes are passed over the guidewire (as in chest drains or  nephrostomies ). After passing a sheath or tube, the guidewire is withdrawn. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2955", "text": "An introducer sheath can be used to introduce  catheters  or other devices to perform endoluminal (inside the hollow organ) procedures, such as  angioplasty .  Fluoroscopy  may be used to confirm the position of the catheter and to manoeuvre it to the desired location. Injection of  radiocontrast  may be used to visualize organs. Interventional procedures, such as  thermoablation , angioplasty, embolisation or  biopsy , may be performed."}
{"_id": "WikiPedia_Radiology$$$corpus_2956", "text": "Upon completion of the desired procedure, the sheath is withdrawn. In certain settings, a sealing device may be used to close the hole made by the procedure."}
{"_id": "WikiPedia_Radiology$$$corpus_2957", "text": "A modified technique, known as the accelerated Seldinger technique, has also been described where the needle, guidewire, dilator, and sheath are inserted as one unit. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2958", "text": "Prior to the description of the Seldinger technique, sharp  trocars  were used to create lumens through which devices could be passed. This had a high rate of complications. [ 4 ]  However, with the introduction of the Seldinger technique,  angiography  became a relatively risk-free procedure, and the field of  interventional radiology  blossomed."}
{"_id": "WikiPedia_Radiology$$$corpus_2959", "text": "Building on the work of Seldinger,  Charles Dotter  and  Andreas Gruentzig  developed  angioplasty ."}
{"_id": "WikiPedia_Radiology$$$corpus_2960", "text": "Selective aortic arch perfusion  ( SAAP ) is an experimental treatment for  haemorrhage -induced  traumatic cardiac arrest . It has been shown in animal studies to be superior to Zone 1  REBOA  once cardiac arrest has occurred. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2961", "text": "Selective internal radiation therapy  (SIRT), also known as  transarterial radioembolization  (TARE),  radioembolization  or  intra-arterial micro brachytherapy  is a form of  radionuclide therapy  used in  interventional radiology  to treat  cancer . It is generally for selected patients with surgically unresectable cancers, especially  hepatocellular carcinoma  or  metastasis  to the  liver . The treatment involves injecting tiny  microspheres  of  radioactive  material into the  arteries  that supply the  tumor , where the spheres lodge in the small vessels of the tumor. Because this treatment combines  radiotherapy  with  embolization , it is also called  radioembolization . The chemotherapeutic analogue (combining  chemotherapy  with embolization) is called chemoembolization, of which  transcatheter arterial chemoembolization  (TACE) is the usual form."}
{"_id": "WikiPedia_Radiology$$$corpus_2962", "text": "Radiation therapy  is used to kill cancer cells; however, normal cells are also damaged in the process. Currently, therapeutic doses of radiation can be targeted to tumors with great accuracy using  linear accelerators  in  radiation oncology ; however, when irradiating using  external beam radiotherapy , the beam will always need to travel through healthy tissue, and the normal liver tissue is very sensitive to radiation. [ 1 ]  The radiation sensitivity of the  liver parenchyma  limits the radiation dose that can be delivered via external beam radiotherapy. SIRT, on the other hand, involves the direct insertion of radioactive  microspheres  to a region, resulting in a local and targeted deposition of radioactive dose. It is therefore well-suited for treatment of liver tumors. Due to the local deposition, SIRT is regarded as a type of locoregional therapy (LRT). [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2963", "text": "The liver has a dual blood supply system; it receives blood from both the  hepatic artery  and the  portal vein . The healthy liver tissue is mainly perfused by the portal vein, while most liver malignancies derive their blood supply from the hepatic artery. Therefore, locoregional therapies such as transarterial chemoembolization or radioembolization, can selectively be administered in the arteries that are supplying the tumors and will preferentially lead to deposition of the particles in the tumor, while sparing the healthy liver tissue from harmful side effects. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2964", "text": "In addition, malignancies (including primary and many metastatic liver cancers) are often  hypervascular ; tumor blood supplies are increased compared to those of normal tissue, further leading to preferential deposition of particles in the tumors. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2965", "text": "SIRT can be performed using several techniques, including whole liver treatment, lobar or segmental approaches. Whole liver SIRT targets the entire liver in one treatment and can be used when the disease is spread throughout the liver. Radiation lobectomy targets one of the two  liver lobes  and can be a good treatment option when only a single lobe is involved or when treating the whole liver in two separate treatments, one lobe at the time. The segmental approach, also called radiation  segmentectomy , is a technique where a high dose of radiation is delivered in one or two Couinaud  liver segments  only. The high dose results in eradication of the tumor while damage to healthy liver tissue is contained to the targeted segments only. This approach results in effective  necrosis  of the targeted segments. Segmentectomy is only feasible when the tumor(s) are contained in one or two segments. Which technique is applied is determined by  catheter  placement. The more  distally  the catheter is placed, the more localized the technique. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2966", "text": "Candidates for radioembolization include patients with:"}
{"_id": "WikiPedia_Radiology$$$corpus_2967", "text": "SIRT is currently considered as a salvage therapy. It has been shown to be safe and effective in patients for whom surgery is not possible, and chemotherapy was not effective. [ 4 ] [ 5 ] [ 11 ] [ 7 ] [ 8 ]  Subsequently, several large  phase III trials  have been started to evaluate the efficacy of SIRT when used earlier in the treatment scheme or in combination treatments with systemic therapy."}
{"_id": "WikiPedia_Radiology$$$corpus_2968", "text": "SIRT, when added to first line therapy for patients with metastases of colorectal cancer, was evaluated in the SIRFLOX, [ 12 ]  FOXFIRE [ 13 ]  and FOXFIRE Global [ 14 ]  studies. For primary liver cancer (HCC), two large trials comparing SIRT with standard of care chemotherapy,  Sorafenib , have been completed, namely the SARAH [ 15 ]  and SIRveNIB [ 16 ]  trials."}
{"_id": "WikiPedia_Radiology$$$corpus_2969", "text": "Results of these studies, published in 2017 and 2018, reported no superiority of SIRT over chemotherapy in terms of overall survival (SARAH, [ 17 ]  SIRveNIB, [ 18 ]  FOXFIRE [ 19 ] ). In the SIRFLOX study, better progression-free survival was also not observed. [ 20 ]  These trials did not give direct evidence supporting SIRT as a first-line treatment regime for liver cancer. However, these studies did show that SIRT is generally better tolerated than systemic therapy, with less severe adverse events. Simultaneously, for HCC, data derived from a large retrospective analysis showed promising results for SIRT as an earlier stage treatment, particularly with high dose radiation segmentectomy and lobectomy. [ 21 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2970", "text": "More studies and cohort analyses are underway to evaluate subgroups of patients who benefit from SIRT as a first-line or later treatment, or to evaluate the effect of SIRT in combination with chemotherapy (EPOCH, [ 22 ]  SIR-STEP, [ 23 ]  SORAMIC, [ 24 ]  STOP HCC [ 25 ] )."}
{"_id": "WikiPedia_Radiology$$$corpus_2971", "text": "For HCC patients currently ineligible for liver transplant, SIRT can sometimes be used to decreases tumor size allowing patients to be candidates for curative treatment. This is sometimes called bridging therapy. [ 26 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2972", "text": "When comparing SIRT with transarterial chemoembolization (TACE), several studies have shown favorable results for SIRT, such as longer time to progression, [ 27 ]  higher complete response rates and longer progression-free survival. [ 28 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2973", "text": "There are currently three types of commercially available microsphere for SIRT. Two of these use the radionuclide  yttrium-90  ( 90 Y) and are made of either  glass  ( TheraSphere ) or  resin  ( SIR-Spheres ). The third type uses  holmium -166 ( 166 Ho) and is made of  poly(l-lactic acid) , PLLA, (QuiremSpheres). The therapeutic effect of all three types is based on local deposition of radiation dose by high-energy  beta particles . All three types of microsphere are permanent implants and stay in the tissue even after radioactivity has decayed."}
{"_id": "WikiPedia_Radiology$$$corpus_2974", "text": "90 Y, a pure beta emitter, has half-life 2.6 days, or 64.1 hours.  166 Ho emits both beta and  gamma rays  emitter, with half-life 26.8 hours. Both  90 Y and  166 Ho have mean tissue penetration of a few millimeters.  90 Y can be imaged using  bremsstrahlung   SPECT  and  positron emission tomography  (PET). Bremsstrahlung SPECT uses of the approximately 23000 Bremsstrahlung photons per  megabecquerel  that are produced by interaction of beta particles with tissue. The positrons needed for PET imaging come from a small branch of the  decay chain  ( branching ratio   32 \u00d7 10 \u22126 ) that gives positrons. [ 29 ]   90 Y's low bremsstrahlung photon and positron yield make it difficult to perform quantitative imaging. [ 30 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2975", "text": "166 Ho's additional gamma emission (81 KeV, 6.7%) makes  166 Ho microspheres quantifiable using a  gamma camera . Holmium is also  paramagnetic , enabling visibility and quantifiability in  MRI  even after the radioactivity has decayed. [ 31 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2976", "text": "1.85 (50.0%)"}
{"_id": "WikiPedia_Radiology$$$corpus_2977", "text": "Theraspheres (glass  90 Y microspheres) are  FDA  approved under a humanitarian device exemption for hepatocellular carcinoma (HCC). SIR-spheres (resin  90 Y microspheres) are FDA approved under premarket approval for colorectal metastases in combination with chemotherapy. [ 40 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2978", "text": "SIR-Spheres were  CE-marked  as a  medical device  in 2002, for treating advanced inoperable liver tumors, and Theraspheres in 2014, for treating  hepatic neoplasia . [ 37 ] \nQuiremSpheres (PLLA  166 Ho microspheres) received their CE mark in April 2015 for treating unresectable liver tumors and are currently only available for the European market. [ 37 ] [ 41 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2979", "text": "90 Y microsphere treatment requires patient-individualized planning with cross-sectional imaging and  arteriograms . [ 42 ]  Contrast  computed tomography  and/or contrast-enhanced  magnetic resonance imaging  of the liver is required to assess tumor and normal liver volumes,  portal vein  status, and extrahepatic tumor burden. Liver and kidney function tests should be performed; patients with irreversibly elevated  serum bilirubin ,  AST  and  ALT  are excluded, as these are markers of poor liver function. [ 43 ]  Use of  iodinated contrast  should be avoided or minimized in patients with  chronic kidney disease . Tumor marker levels are also evaluated. Hepatic artery  technetium (99mTc) macro aggregated albumin  (MAA) scan is performed to evaluate hepatopulmonary shunting (resulting from  hepatopulmonary syndrome ). Therapeutic radioactive particles travelling through such a shunt can result in a high  absorbed radiation dose  to the lungs, possibly resulting in  radiation pneumonitis . Lung dose >30  gray  means increased risk of such pneumonitis. [ 44 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2980", "text": "Initial  angiographic  evaluation can include an abdominal  aortogram ,  Superior mesenteric  and  Celiac  arteriograms, and selective right and left liver arteriograms. These tests can show gastrointestinal vascular anatomy and flow characteristics. Extrahepatic vessels found on angiographic evaluation can be  embolized , to prevent nontarget deposition of microspheres, that can lead to gastrointestinal  ulcers . Or the catheter tip can be moved more distally, past the extrahepatic vessels. [ 45 ]  Once the branch of the  hepatic artery  supplying the tumor is identified and the tip of the  catheter  is selectively placed within the artery, the  90 Y or  166 Ho microspheres are infused. If preferred, particle infusion can be alternated with  contrast  infusion, to check for stasis or backflow. Radiation dose absorbed, depends on microsphere distribution within the tumor vascularization. Equal distribution is necessary to ensure tumor cells are not spared due to ~2.5mm mean tissue penetration, with maximum penetration up to 11mm for  90 Y [ 46 ]  or 8.7mm for  166 Ho. [ 47 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2981", "text": "After treatment, for  90 Y microspheres, bremsstrahlung SPECT or PET scanning may be done within 24 hours after radioembolization to evaluate the distribution. For  166 Ho microspheres, quantitative SPECT or MRI can be done. Weeks after treatment,  computed tomography  or MRI can be done to evaluate anatomic changes.  166 Ho microspheres are still visible on MRI after radioactivity has decayed, because holmium is paramagnetic.  FDG  positron emission tomography may also be done to evaluate changes in metabolic activity."}
{"_id": "WikiPedia_Radiology$$$corpus_2982", "text": "Complications include postradioembolization syndrome (PRS), hepatic complications,  biliary  complications,  portal hypertension  and  lymphopenia . Complications due to extrahepatic deposition include  radiation pneumonitis , gastrointestinal  ulcers  and vascular injury. [ 48 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2983", "text": "Postradioembolization syndrome (PRS) includes fatigue, nausea, vomiting, abdominal discomfort or pain, and  cachexia , occurring in 20-70% of patients. Steroids and  antiemetic  agents may decrease the incidence of PRS. [ 49 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2984", "text": "Liver complications include  cirrhosis  leading to  portal hypertension , radioembolization-induced liver disease (REILD), transient elevations in liver enzymes, and fulminant liver failure. [ 49 ]  REILD is characterized by  jaundice ,  ascites ,  hyperbilirubinemia  and  hypoalbuminemia  developing at least 2 weeks-4 months after SIRT, absent tumor progression or biliary obstruction. It can range from minor to fatal and is related to (over)exposure of healthy liver tissue to radiation. [ 49 ] [ 50 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2985", "text": "Biliary complications include  cholecystitis  and biliary  strictures ."}
{"_id": "WikiPedia_Radiology$$$corpus_2986", "text": "Investigation of  yttrium-90  and other radioisotopes for cancer treatment began in the 1960s. Many key concepts, such as preferential blood supply and tumor vascularity, were discovered during this time. Reports of initial use of resin particles of  90 Y in humans were published in the late 1970s. In the 1980s, the safety and feasibility of resin and glass yttrium-90 microsphere therapy for liver cancer were validated in a  canine  model. Clinical trials of yttrium-90 applied to the liver continued throughout the late 1980s to the 1990s, establishing the safety of the therapy. More recently, larger trials and  RCTs  have shown safety and efficacy of  90 Y therapy for the treatment of both primary and metastatic liver malignancies. [ 40 ] [ 51 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2987", "text": "Development of holmium-166 microspheres started in the 1990s. The intention was to develop a microsphere with therapeutic radiation dose similar to  90 Y, but with better imaging properties, so that distribution of microspheres in the liver could be assessed more precisely. In the 2000s, development progressed to animal studies.  166 Ho microspheres for SIRT were first used in humans in 2009, which was first published in 2012. [ 52 ]  Since then, several trials have been performed showing safety and efficacy of  166 Ho SIRT, [ 53 ]  and more studies are ongoing. [ 54 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2988", "text": "In  medicine , a  stent  is a tube usually constructed of a metallic  alloy  or a polymer. It is inserted into the  lumen  (hollow space) of an anatomic vessel or duct to keep the passageway open."}
{"_id": "WikiPedia_Radiology$$$corpus_2989", "text": "Stenting  refers to the placement of a stent. The word \"stent\" is also used as a  verb  to describe the placement of such a device, particularly when a disease such as  atherosclerosis  has  pathologically  narrowed a structure such as an  artery ."}
{"_id": "WikiPedia_Radiology$$$corpus_2990", "text": "A stent is different from a  shunt . A shunt is a tube that connects two previously unconnected parts of the body to allow fluid to flow between them. Stents and shunts can be made of similar materials, but perform two different tasks."}
{"_id": "WikiPedia_Radiology$$$corpus_2991", "text": "There are various types of stents used for different medical purposes.  Coronary stents  are commonly used in  coronary angioplasty , with  drug-eluting stents  being the most common type. Vascular stents are used for peripheral and cerebrovascular disease, while ureteral stents ensure the patency of a ureter."}
{"_id": "WikiPedia_Radiology$$$corpus_2992", "text": "Prostatic stents can be temporary or permanent and are used to treat conditions like  benign prostatic hyperplasia . Colon and esophageal stents are palliative treatments for advanced colon and  esophageal cancer . Pancreatic and biliary stents provide drainage from the  gallbladder ,  pancreas , and bile ducts to the  duodenum  in conditions such as obstructing  gallstones . There are also different types of bare-metal, drug-eluting, and bioresorbable stents available based on their properties."}
{"_id": "WikiPedia_Radiology$$$corpus_2993", "text": "The term \"stent\" originates from  Charles Stent , an English  dentist  who made advances in denture-making techniques in the 19th century. The use of coronary stents began in 1986 by Jacques Puel and Ulrich Sigwart to prevent vessel closure during coronary surgery."}
{"_id": "WikiPedia_Radiology$$$corpus_2994", "text": "Coronary stents  are placed during a  coronary angioplasty . The most common use for coronary stents is in the  coronary arteries , into which a  bare-metal stent , a  drug-eluting stent , a bioabsorbable stent,  a  dual-therapy stent  (combination of both drug and bioengineered stent), or occasionally a covered stent is inserted.\n [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2995", "text": "The majority of coronary stents used today are drug-eluting stents, which release medication to prevent complications such as blood clot formation and restenosis (re-narrowing). Stenting is performed through a procedure called percutaneous coronary intervention (PCI), where the cardiologist uses angiography and intravascular ultrasound to assess the blockage in the artery and determine the appropriate size and type of stent. The procedure is typically done in a catheterization clinic, and patients may need to stay overnight for observation. While stenting has been shown to reduce chest pain (angina) and improve survival rates after a heart attack, its effectiveness in stable angina patients has been debated."}
{"_id": "WikiPedia_Radiology$$$corpus_2996", "text": "Studies have found that most heart attacks occur due to plaque rupture rather than an obstructed artery that would benefit from a stent. Statins, along with PCI/stenting and anticoagulant therapies, are considered part of a broader treatment strategy. Some cardiologists believe that coronary stents are overused, but there is evidence of under-use in certain patient groups like the elderly. Ongoing research continues to explore new types of stents with biocompatible coatings or absorbable materials."}
{"_id": "WikiPedia_Radiology$$$corpus_2997", "text": "Vascular stents are a common treatment for advanced  peripheral  and  cerebrovascular disease . Common sites treated with vascular stents include the  carotid ,  iliac , and  femoral  arteries. Because of the external compression and mechanical forces subjected to these locations, flexible stent materials such as  nitinol  are used in many peripheral stents. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2998", "text": "Vascular stents made of metals can lead to  thrombosis  at the site of treatment or to inflammation scarring.  Drug-eluting stents  with pharmacologic agents or as drug delivery vehicles have been developed as an alternative to decrease the chances of restenosis. [ medical citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_2999", "text": "Because vascular stents are designed to expand inside a blocked artery to keep it open, allowing blood to flow freely, the mechanical properties of vascular stents are crucial for their function: they need to be highly elastic to allow for the expansion and contraction of the stent within the blood vessel, they also need to have high strength and fatigue resistance to withstand the constant physiological load of the arteries, they should have good biocompatibility to reduce the risk of thrombosis and vascular restenosis, and to minimize the body's rejection of the implant. [ 3 ] [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3000", "text": "Vascular stents are commonly used in angioplasty, a surgical procedure that opens blocked arteries and places a stent to keep the artery open. This is a common treatment for heart attacks and is also used in the prevention and treatment of strokes. Over 2 million people receive a stent each year for coronary artery disease alone. Vascular stents can also be used to prevent the rupture of aneurysms in the brain, aorta, or other blood vessels. [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3001", "text": "Ureteral stents  are used to ensure the patency of a  ureter , which may be compromised, for example, by a  kidney stone . This method is sometimes used as a temporary measure to prevent damage to a kidney caused by a kidney stone until a procedure to remove the stone can be performed."}
{"_id": "WikiPedia_Radiology$$$corpus_3002", "text": "An ureteral stent it is typically inserted using a cystoscope, and one or both ends of the stent may be coiled to prevent movement. Ureteral stents are used for various purposes, such as temporary measures to prevent damage to a blocked kidney until a stone removal procedure can be performed, providing drainage for compressed ureters caused by tumors, and preventing spasms and collapse of the ureter after trauma during procedures like stone removal. The thread attached to some stents may cause irritation but allows for easy removal by pulling gently."}
{"_id": "WikiPedia_Radiology$$$corpus_3003", "text": "Stents without threads require cystoscopy for removal. Recent developments have introduced magnetic retrieval systems that eliminate the need for invasive procedures like cystoscopy when removing the stent. The use of magnets enables simple extraction without anesthesia and can be done by primary care physicians or nurses rather than urologists. This method has shown high success rates across different patient groups including adults, children, and kidney transplant patients while reducing costs associated with operating room procedures."}
{"_id": "WikiPedia_Radiology$$$corpus_3004", "text": "Prostatic stents  are placed from the  bladder  through the  prostatic  and  penile urethra  to allow drainage of the bladder through the  penis . This is sometimes required in  benign prostatic hyperplasia ."}
{"_id": "WikiPedia_Radiology$$$corpus_3005", "text": "A prostatic stent is used to keep the male urethra open and allow for the passage of urine in cases of prostatic obstruction and lower urinary tract symptoms (LUTS). There are two types of prostatic stents: temporary and permanent. Permanent stents, typically made of metal coils, are inserted into the urethra to apply constant gentle pressure and hold open sections that obstruct urine flow. They can be placed under anesthesia as an outpatient procedure but have disadvantages such as increased urination, limited incontinence, potential displacement or infection, and limitations on subsequent endoscopic surgical options. On the other hand, temporary stents can be easily inserted with topical anesthesia similar to a Foley catheter, and allow patients to retain volitional voiding. However, they may cause discomfort or increased urinary frequency."}
{"_id": "WikiPedia_Radiology$$$corpus_3006", "text": "In the US, there is one temporary prostatic stent that has received FDA approval called The Spanner. It maintains urine flow while allowing natural voluntary urination. [ 8 ]  Research on permanent stents often focuses on metal coil designs that expand radially to hold open obstructed areas of the urethra."}
{"_id": "WikiPedia_Radiology$$$corpus_3007", "text": "These permanent stents are used for conditions like benign prostatic hyperplasia (BPH), recurrent bulbar urethral stricture (RBUS), or detrusor external sphincter dyssynergia (DESD). The Urolume is currently the only FDA-approved permanent prostatic stent. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3008", "text": "Colon and  esophageal  stents are a  palliative  treatment for advanced  colon  and  esophageal cancer ."}
{"_id": "WikiPedia_Radiology$$$corpus_3009", "text": "A colon stent is typically made of flexible metal mesh that can expand and hold open the blocked area, allowing for the passage of stool. Colon stents are used primarily as a palliative treatment for patients with advanced colorectal cancer who are not candidates for surgery. They help relieve symptoms such as abdominal pain, constipation, and bowel obstruction caused by tumors or strictures in the colon."}
{"_id": "WikiPedia_Radiology$$$corpus_3010", "text": "The placement of a colon stent involves endoscopic techniques similar to esophageal stenting. A thin tube called an endoscope is inserted into the rectum and guided through the colon to locate the blockage. Using fluoroscopy or endoscopic guidance, a guidewire is passed through the narrowed area and then removed after positioning it properly. The stent is then delivered over the guidewire and expanded to keep open the obstructed section of the colon. Complications associated with colon stents include perforation of the intestinal wall, migration or dislodgment of the stent, bleeding, infection at insertion site, or tissue overgrowth around it. [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3011", "text": "Colon stenting provides several benefits including prompt relief from bowel obstruction symptoms without invasive surgery in many cases. It allows for faster recovery time compared to surgical interventions while providing palliative care for patients with advanced colorectal cancer by improving quality of life and enabling better nutritional intake. However, there are potential risks associated with complications such as migration or obstruction that may require additional procedures or interventions to address these issues effectively. [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3012", "text": "Pancreatic and biliary stents provide  pancreatic and bile drainage  from the  gallbladder ,  pancreas , and  bile ducts  to the  duodenum  in conditions such as  ascending cholangitis  due to obstructing  gallstones ."}
{"_id": "WikiPedia_Radiology$$$corpus_3013", "text": "Pancreatic and biliary stents can also be used to treat biliary/pancreatic leaks or to prevent post-ERCP pancreatitis. [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3014", "text": "In the case of gallstone pancreatitis, a gallstone travels from the gallbladder and blocks the opening to the first part of the small intestine (duodenum). This causes a backup of fluid that can travel up both the bile duct and the pancreatic duct. Gallbladder stones can lead to obstruction of the biliary tree via which gallbladder and pancreas enzymes are secreted into the duodenum, causing emergency events such as acute cholecystitis or acute pancreatitis. [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3015", "text": "In conditions such as ascending cholangitis due to obstructing gallstones, these stents play a crucial role. They help in maintaining the flow of bile and pancreatic juices from the gallbladder, pancreas, and bile ducts to the duodenum1. Biliary stents are often used during endoscopic retrograde cholangiopancreatography (ERCP) to treat blockages that narrow your bile or pancreatic ducts. In cases of malignant biliary obstruction, endoscopic stent placement is one of the treatment options to relieve the obstruction. Biliary drainage is considered effective, particularly in bile duct conditions that are diagnosed and treated early. [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3016", "text": "Glaucoma  drainage stents are recent developments and have been recently approved in some countries. [ 13 ]  They are used to reduce  intraocular pressure  by providing a drainage channel."}
{"_id": "WikiPedia_Radiology$$$corpus_3017", "text": "A stent graft or covered stent is type of vascular stent with a fabric coating that creates a contained tube but is expandable like a  bare metal stent . Covered stents are used in  endovascular surgical  procedures such as  endovascular aneurysm repair . Stent grafts are also used to treat  stenoses  in  vascular grafts  and  fistulas  used for  hemodialysis ."}
{"_id": "WikiPedia_Radiology$$$corpus_3018", "text": "A bioresorbable stent is a tube-like device made from a material that can release a drug to prevent scar tissue growth. It is used to open and widen clogged heart arteries and then dissolves or is absorbed by the body. Unlike traditional metal stents, bioresorbable stents can restore normal vessel function, avoid long-term complications, and enable natural reconstruction of the arterial wall."}
{"_id": "WikiPedia_Radiology$$$corpus_3019", "text": "Metal-based bioresorbable scaffolds include iron, magnesium, zinc, and their alloys. Magnesium-based scaffolds have been approved for use in several countries around the world and show promising clinical results in delivering against the drawbacks of permanent metal stents. However, attention has been given to reducing the rate of magnesium corrosion through alloying and coating techniques."}
{"_id": "WikiPedia_Radiology$$$corpus_3020", "text": "Clinical research shows that resorbable scaffolds offer comparable efficacy and safety profiles to traditional drug-eluting stents (DES). The Magmaris resorbable magnesium scaffold has reported favorable safety outcomes similar to thin-strutted DES in patient populations. The Absorb naturally dissolving stent has also shown low rates of major adverse cardiac events when compared to DES. Imaging studies demonstrate that these naturally dissolving stents begin to dissolve between six months to two years after placement in the artery."}
{"_id": "WikiPedia_Radiology$$$corpus_3021", "text": "Drug-eluting stents (DES) are specialized medical devices used to treat coronary artery disease and peripheral artery disease. They release a drug that inhibits cellular growth into the blocked or narrowed arteries, reducing the risk of blockages. DES are commonly placed using percutaneous coronary intervention (PCI), a minimally invasive procedure performed via catheter. These stents have shown clear advantages over older bare-metal stents, improving patient outcomes and quality of life for cardiac patients. With over 90% of stents used in PCI procedures being drug-eluting as of 2023, DES have become the standard choice for interventional cardiologists."}
{"_id": "WikiPedia_Radiology$$$corpus_3022", "text": "DES gradually release drugs that prevent restenosis and thrombosis within the treated arteries, addressing common complications associated with previous treatments. While risks such as clot formation and bleeding exist, studies have demonstrated superior efficacy compared to bare-metal stents in reducing major adverse cardiac events like heart attacks and repeat revascularization procedures. Long-term outcomes are still being studied due to their relatively recent introduction; however, DES have revolutionized the treatment of coronary artery disease by significantly improving patient outcomes and enhancing their quality of life."}
{"_id": "WikiPedia_Radiology$$$corpus_3023", "text": "The currently accepted origin of the word  stent  is that it derives from the name of an English  dentist ,  Charles Thomas Stent  (1807\u20131885), notable for his advances in the field of denture-making. [ 14 ] [ 15 ]  He was born in  Brighton , England, on October 17, 1807, was a dentist in London, and is most famous for improving and modifying the denture base of the  gutta-percha , creating the stent's compounding that made it practical as a material for dental impressions."}
{"_id": "WikiPedia_Radiology$$$corpus_3024", "text": "Others attribute the noun  stent  to  Jan F. Esser , a Dutch plastic surgeon who in 1916 used the word to describe a dental impression compound invented in 1856 by Charles Stent, whom Esser employed to craft a form for facial reconstruction. The full account is described in the  Journal of the History of Dentistry . [ 16 ]   According to the author, from the use of Stent's compound as a support for facial tissues evolved the use of a stent to hold open various body structures."}
{"_id": "WikiPedia_Radiology$$$corpus_3025", "text": "The verb form \"stenting\" was used for centuries to describe the process of stiffening garments (a usage long obsolete, per the  Oxford English Dictionary ), and some [ who? ]  believe this to be the origin. According to the Merriam Webster Third New International Dictionary, the noun evolved from the Middle English verb  stenten , shortened from  extenten  'to stretch', which in turn came from Latin  extentus , the past participle of  extend\u014d  'to stretch out'."}
{"_id": "WikiPedia_Radiology$$$corpus_3026", "text": "The first (self-expanding) \"stents\" used in medical practice in 1986 by  Ulrich Sigwart  in Lausanne were initially called \"Wallstents\" after their inventor, Hans Wallst\u00e9n. [ 17 ] [ 18 ] \n Julio Palmaz   et al.  created a balloon-expandable stent that is currently used. [ 19 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3027", "text": "The first use of a coronary stent is typically attributed to  Jacques Puel \u00a0[ fr ]  and  Ulrich Sigwart , who implanted a stent into a patient in Toulouse, France, in 1986. [ 14 ]  That stent was used as a scaffold to prevent a vessel from closing and to avoid  restenosis  in coronary surgery\u2014a condition where scar tissue grows within the stent and interferes with vascular flow. Shortly thereafter, in 1987,  Julio Palmaz  (known for patenting a balloon-expandable stent  [ 20 ] ) and Richard Schatz implanted their similar stent into a patient in Germany."}
{"_id": "WikiPedia_Radiology$$$corpus_3028", "text": "Though several doctors have been credited with the creation of the stent, the first  FDA -approved stent in the U.S. was created by Richard Schatz and coworkers. Named the Palmaz-Schatz ( Johnson & Johnson ), it was developed in 1987. [ 21 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3029", "text": "To further reduce the incidence of restenosis, the  drug-eluting stent  was introduced in 2003. [ 22 ]  Research has led to general stent design changes and improvements since that time. [ 23 ]  Bioresorbable scaffolds have also entered the market, though a large-scale clinical trial showed higher acute risks compared to drug-eluding stents. As a result, the FDA issued an official warning for their use in 2013, and research on the design and performance optimisation of stents is ongoing. [ 24 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3030", "text": "Surface-guided radiation therapy  (SGRT) (sometimes referred to as  Surface-image Guided Radiation Therapy ) is the process of using 3D imaging to position and track movement of  radiation therapy  patients during treatment."}
{"_id": "WikiPedia_Radiology$$$corpus_3031", "text": "SGRT can help to improve the safety, effectiveness and efficiency of radiation therapy treatments, by offering guidance across every step of the radiation therapy workflow, including simulation, planning, treatment and dose visualisation."}
{"_id": "WikiPedia_Radiology$$$corpus_3032", "text": "Developed as an advancement to  image-guided radiation therapy , SGRT relies on 3D imaging as opposed to an x-ray. [ 1 ]  SGRT uses cameras to feed data into a software program linked to the linear accelerator delivering the radiation. [ 2 ]  Each camera uses a projector and image sensors to create a 3D surface model of a patient, by projecting a red light containing a pseudo-random speckle pattern on their skin. [ 3 ]  The pattern allows the SGRT system to reference thousands of points on the skin, acting as virtual  medical tattoos . [ 4 ]  This imaging information is fed into the software to allow real-time tracking and sub-millimetric accuracy during radiotherapy treatments. Information on movements is fed back to the radiation therapist, who is alerted if the patient moves from the optimal position (as determined by their treatment plan). SGRT systems can be set to automatically stop the delivery of radiation if a patient moves outside of a certain tolerance level. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3033", "text": "SGRT can help to reduce errors in set-up and positioning, allow the margins around  target tissue  when planning to be reduced, and enable treatment to be adapted during its course, with the aim of overall improving outcomes. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3034", "text": "For breast cancer treatment, SGRT increases the patient setup information compared to laser\u2010based setup (LBS), by using the entire patient skin surface instead of only three skin marks. [ 7 ]  SGRT also enables clinicians to monitor a patient in real-time to replicate the same position during the CT scan for  sarcoma  patients. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3035", "text": "When used with  deep inspiratory breath-hold , SGRT supports initial positioning, both in free breathing (at mid-patient reference point) and in DIBH (at treatment isocenter). [ 9 ]  This process has been found to help reduce errors in set-up, positioning and improve overall outcomes for patients. It has also been used with  Stereotactic Body Radiation Therapy  to assist with the initial set-up and detect intrafraction patient motion throughout treatment. [ 3 ]  For  stereotactic surgery , SGRT allows a frameless system to be used to monitor the surface of the patient within an open-face immobilization mask. [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3036", "text": "Thoracentesis   / \u02cc \u03b8 \u0254\u02d0 r \u0259 s \u026a n \u02c8 t i\u02d0 s \u026a s / , also known as  thoracocentesis  (from  Greek     \u03b8\u03ce\u03c1\u03b1\u03be  (th\u014drax,  GEN  th\u014drakos) \u00a0'chest,  thorax ' and    \u03ba\u03ad\u03bd\u03c4\u03b7\u03c3\u03b9\u03c2  (kent\u0113sis) \u00a0'pricking, puncture'),  pleural tap ,  needle thoracostomy , or  needle decompression  (often used term), is an invasive medical procedure to remove  fluid  or  air  from the  pleural space  for diagnostic or therapeutic purposes. A  cannula , or hollow needle, is carefully introduced into the thorax, generally after administration of  local anesthesia . The procedure was first performed by  Morrill Wyman  in 1850 and then described by  Henry Ingersoll Bowditch  in 1852. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3037", "text": "The recommended location varies depending upon the source. Some sources recommend the  midaxillary line , in the eighth, ninth, or tenth  intercostal space . [ 2 ]  Whenever possible, the procedure should be performed under ultrasound guidance, which has shown to reduce complications. [ 3 ] [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3038", "text": "Tension pneumothorax  is a  medical emergency  that requires needle decompression before a  chest tube  is placed. [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3039", "text": "This procedure is indicated when unexplained fluid accumulates in the chest cavity outside the lung. In more than 90% of cases analysis of pleural fluid yields clinically useful information. If a large amount of fluid is present, then this procedure can also be used therapeutically to remove that fluid and improve patient comfort and lung function."}
{"_id": "WikiPedia_Radiology$$$corpus_3040", "text": "The most common causes of pleural  effusions  are  cancer ,  congestive heart failure ,  pneumonia , and recent  surgery . In countries where  tuberculosis  is common, this is also a common cause of pleural effusions."}
{"_id": "WikiPedia_Radiology$$$corpus_3041", "text": "When cardiopulmonary status is compromised (i.e. when the fluid or air has its repercussions on the function of heart and lungs), due to air (significant  pneumothorax ), fluid ( pleural fluid ) or  blood  ( hemothorax ) outside the lung, then this procedure is usually replaced with  tube thoracostomy , the placement of a large tube in the pleural space."}
{"_id": "WikiPedia_Radiology$$$corpus_3042", "text": "An uncooperative patient or a  coagulation  disorder that cannot be corrected are relative contraindications. [ 9 ]  Routine measurement of coagulation profiles is generally not indicated, however; when performed by an experienced operator \"hemorrhagic complications are infrequent after ultrasound-guided thoracentesis, and attempting to correct an abnormal INR or platelet level before the procedure is unlikely to confer any benefit\". [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3043", "text": "Relative contraindications include cases in which the site of insertion has known  bullous emphysema , use of  positive end-expiratory pressure  (PEEP, see  mechanical ventilation ) and only one functioning  lung  (due to diminished reserve). Traditional expert opinion suggests that the aspiration should not exceed 1\u00a0L to avoid the possible development of pulmonary edema, but this recommendation is uncertain as the volume removed does not correlate well with this complication. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3044", "text": "Major complications are  pneumothorax  (3\u201330%),  hemopneumothorax ,  hemorrhage , hypotension (low blood pressure due to a vasovagal response) and reexpansion  pulmonary edema ."}
{"_id": "WikiPedia_Radiology$$$corpus_3045", "text": "Minor complications include a dry tap (no fluid return), subcutaneous  hematoma  or  seroma , anxiety,  dyspnea  and cough (after removing large volume of fluid)."}
{"_id": "WikiPedia_Radiology$$$corpus_3046", "text": "The use of  ultrasound  for needle guidance can minimize the complication rate. [ 3 ] [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3047", "text": "While chest X-ray has traditionally been performed to assess for pneumothorax following the procedure, it may no longer be necessary to do so in asymptomatic, non-ventilated persons given the widespread use of ultrasound to guide this procedure. [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3048", "text": "Several diagnostic tools are available to determine the  etiology  of pleural fluid."}
{"_id": "WikiPedia_Radiology$$$corpus_3049", "text": "First the fluid is either  transudate  or  exudate ."}
{"_id": "WikiPedia_Radiology$$$corpus_3050", "text": "An exudate is defined as pleural fluid to serum total protein ratio of more than 0.5, pleural fluid to serum LDH ratio > 0.6, and absolute pleural fluid LDH > 200 IU or >  2 \u2044 3  of the normal."}
{"_id": "WikiPedia_Radiology$$$corpus_3051", "text": "An exudate is defined as pleural fluid that filters from the circulatory system into lesions or areas of inflammation. Its composition varies but generally includes water and the dissolved solutes of the main circulatory fluid such as blood. In the case of blood it will contain some or all plasma proteins, white blood cells, platelets and (in the case of local vascular damage) red blood cells."}
{"_id": "WikiPedia_Radiology$$$corpus_3052", "text": "Exudate"}
{"_id": "WikiPedia_Radiology$$$corpus_3053", "text": "Transudate"}
{"_id": "WikiPedia_Radiology$$$corpus_3054", "text": "A high amylase level (twice the serum level or the absolute value is greater than 160 Somogy units) in the pleural fluid is indicative of either acute or chronic  pancreatitis , pancreatic  pseudocyst  that has dissected or ruptured into the pleural space,  cancer  or esophageal rupture."}
{"_id": "WikiPedia_Radiology$$$corpus_3055", "text": "Glucose  is considered low if pleural fluid value is less than 50% of normal serum value. The  differential diagnosis  for this is:"}
{"_id": "WikiPedia_Radiology$$$corpus_3056", "text": "Normal pleural fluid pH is approximately 7.60.  A pleural fluid pH below 7.30 with normal arterial blood pH has the same differential diagnosis as low pleural fluid glucose."}
{"_id": "WikiPedia_Radiology$$$corpus_3057", "text": "Chylothorax  (fluid from  lymph vessels  leaking into the pleural cavity) may be identified by determining  triglyceride  and  cholesterol  levels, which are relatively high in  lymph . A triglyceride level over 110\u00a0mg/dl and the presence of chylomicrons indicate a  chylous effusion . The appearance is generally milky but can be  serous ."}
{"_id": "WikiPedia_Radiology$$$corpus_3058", "text": "The main cause for chylothorax is rupture of the  thoracic duct , most frequently as a result of  trauma or malignancy (such as  lymphoma )."}
{"_id": "WikiPedia_Radiology$$$corpus_3059", "text": "The number of  white blood cells  can give an indication of infection. The specific subtypes can also give clues as to the type on infection. The amount of  red blood cells  are an obvious sign of bleeding."}
{"_id": "WikiPedia_Radiology$$$corpus_3060", "text": "If the effusion is caused by  infection ,  microbiological culture  may yield the infectious organism responsible for the infection, sometimes before other cultures (e.g. blood cultures and sputum cultures) become positive. A  Gram stain  may give a rough indication of the causative organism. A  Ziehl\u2013Neelsen stain  may identify  tuberculosis  or other mycobacterial diseases."}
{"_id": "WikiPedia_Radiology$$$corpus_3061", "text": "Cytology  is an important tool in identifying effusions due to  malignancy . The most common causes for pleural fluid are  lung cancer ,  metastasis  from elsewhere and  pleural mesothelioma . The latter often presents with an effusion. Normal cytology results do not reliably rule out malignancy, but make the diagnosis more unlikely."}
{"_id": "WikiPedia_Radiology$$$corpus_3062", "text": "Transcatheter arterial chemoembolization  ( TACE ) is a  minimally invasive procedure  performed in  interventional radiology  to restrict a  tumor 's blood supply. Small  embolic  particles coated with  chemotherapeutic drugs  are injected selectively through a  catheter  into an  artery  directly supplying the tumor. These particles both block the blood supply and induce  cytotoxicity , attacking the tumor in several ways. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3063", "text": "The radiotherapeutic analogue (combining  radiotherapy  with embolization) is called radioembolization or  selective internal radiation therapy  (SIRT). [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3064", "text": "Clinical trials  determine what type of therapy is generally most successful for treating any particular type of tumor. Panels of physicians, such as the  National Comprehensive Cancer Network , determine what therapies to recommend for a given tumor type based on the outcomes of these trials. Although in theory TACE can be applied to any tumor, currently TACE is used primarily for tumors of the liver. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3065", "text": "TACE of liver tumors derives its beneficial effect by two primary mechanisms. [ 3 ]  Most tumors within the liver are supplied by the  proper hepatic artery , so arterial embolization preferentially interrupts the tumor's blood supply and stalls growth until  neovascularization . Secondly, focused administration of chemotherapy allows for delivery of a higher dose to the tissue while simultaneously reducing systemic exposure, which is typically the dose-limiting factor. This effect is potentiated by the fact that the chemotherapeutic drug is not washed out from the tumor vascular bed by blood flow after embolization. Effectively, this results in a higher concentration of drug to be in contact with the tumor for a longer period of time. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3066", "text": "Park et al. conceptualized carcinogenesis of  hepatocellular carcinoma  (HCC) as a multistep process involving parenchymal arterialization, sinusoidal capillarization, and development of unpaired arteries (a vital component of tumor  angiogenesis ). All these events lead to a gradual shift in tumor blood supply from portal to arterial circulation. This concept has been validated using dynamic imaging modalities by various investigators. Sigurdson et al. demonstrated that, when an agent was infused via the hepatic artery, intratumoral concentrations were ten times greater compared to when agents were administered through the portal vein. Hence, arterial treatment targets the tumor while normal liver is relatively spared. Embolization induces ischemic necrosis of tumor causing a failure of the  transmembrane pump , resulting in a greater absorption of cytotoxic agents by the tumor cells. Tissue concentration of agents within the tumor is greater than 40 times that of the surrounding normal liver. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3067", "text": "Transcatheter arterial chemoembolization has most widely been applied to hepatocellular carcinoma for patients who are not eligible for surgery. [ 5 ]  TACE has been shown to increase survival in patients with intermediate HCC by BCLC criteria. It has also been used as an alternative to surgery for resectable early stage HCC and in patients with regional recurrence of the tumor after previous resection. TACE may also be used to downstage HCC in patients who exceed the  Milan criteria  for  liver transplantation ."}
{"_id": "WikiPedia_Radiology$$$corpus_3068", "text": "Other treated malignancies include  neuroendocrine tumors ,  ocular melanoma ,  cholangiocarcinoma , and  sarcoma . Transcatheter arterial chemoembolization plays a  palliative  role in patients with metastatic  colon carcinoma . There is a possible benefit for liver-dominant  metastases  from other primary malignancies. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3069", "text": "TACE is an  interventional radiology  procedure performed in the  angiography  suite. The procedure involves gaining  percutaneous  transarterial access by the  Seldinger technique  to the  hepatic artery  with an arterial sheath, usually by puncturing the  common femoral artery  in the right groin and passing a  catheter  guided by a wire through the  abdominal aorta , through the  celiac trunk  and  common hepatic artery , and finally into the branch of the  proper hepatic artery  supplying the tumor."}
{"_id": "WikiPedia_Radiology$$$corpus_3070", "text": "The  interventional radiologist  then performs a selective angiogram of the  celiac trunk  and possibly the  superior mesenteric artery  to identify the branches of the hepatic artery supplying the tumor(s) and threads smaller, more selective catheters into these branches. This is done to maximize the amount of the chemotherapeutic dose that is directed to the tumor and minimize the amount of the chemotherapeutic agent that could damage the normal liver tissue. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3071", "text": "When a blood vessel supplying the tumor has been selected, alternating doses of the chemotherapy dose and of  embolic particles , or an infusion of embolic particles containing the chemotherapy agent, are injected through the catheter ."}
{"_id": "WikiPedia_Radiology$$$corpus_3072", "text": "The physician removes the catheter and access sheath, applying pressure to the entry site to prevent bleeding. The patient must lie stationary for several hours after the procedure to allow the punctured artery to heal. The clinician can apply pressure using a Femostop or close the artery using a vascular sealing device. [ 7 ]  The patient will often be kept overnight for observation and will likely be discharged the following day. The procedure is normally followed up with a  CT scan  several weeks later to check the response of the tumor to the procedure. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3073", "text": "TACE may be either conventional TACE (cTACE) or TACE with  drug-eluting beads  (DEBs) (DEB-TACE). [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3074", "text": "cTACE involves  intra-arterial injection  of  cytotoxic   chemotherapy  drugs  emulsified  in  Lipiodol , an  oily   radio-opaque  agent. [ 1 ]  Following this, an  embolic agent , for instance  gelatin sponge ,  polyvinyl alcohol particles , or  microspheres , is intra-arterially injected. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3075", "text": "DEB-TACE involves intra-arterial injection of DEBs, which are non-resorbable  embolic microspheres  that are loaded with chemotherapy drugs. [ 1 ]  DEBs allow for more sustained local chemotherapy drug release (e.g., 1 \u00a0 month) along with concomitant embolization. [ 1 ]  They are alternatively known as drug-eluting embolic (DEE) microspheres. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3076", "text": "Examples of specific types of DEBs include the following:"}
{"_id": "WikiPedia_Radiology$$$corpus_3077", "text": "EmboCept S  is an embolic agent made up of  degradable starch microspheres  (DSM). It can be mixed with low-volume chemotherapeutic agents such as  doxorubicin  and  mitomycin  and high-volume chemotherapeutic agents such as  cisplatin  and  irinotecan  to be administered into a subject. It is a short-acting, thus will be degraded 2 \u00a0 hours after procedure, limiting the risk of ischemia to other healthy liver cells. [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3078", "text": "The most commonly used chemotherapy agents in TACE for HCC are (in decreasing order of frequency):  doxorubicin ,  cisplatin ,  epirubicin ,  mitoxantrone , and  mitomycin C . [ 11 ]  Less frequently used drugs include  anthracyclines , like  pirarubicin ,  nemorubicin , and  idarubicin , and  platinum-based agents , like  miriplatin ,  carboplatin , and  lobaplatin . [ 11 ]  No evidence-based guidelines exist to guide choice of chemotherapy agents or their dosages and none of the preceding drugs are explicitly approved by regulatory authorities for loco-regional treatment of HCC. [ 11 ]  The choices of agents, doses, and procedures vary widely between centers and surgeons. [ 11 ]  There are few studies defining dose-limiting toxicity of these agents, which may explain the widely varying practices. [ 11 ]  Single-agent therapy (e.g., doxorubicin alone) is appropriate in most cases, but some centers use two- or three-drug combinations (e.g., doxorubicin plus mitomycin C, or doxurubicin plus mitomycin C plus  gemcitabine ). [ 11 ] [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3079", "text": "TACE may be used in conjunction with  systemic  chemotherapy agents. [ 13 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3080", "text": "TACE has also been used to treat people with:"}
{"_id": "WikiPedia_Radiology$$$corpus_3081", "text": "As with any interventional procedure, there is a small risk of hemorrhage and/or damage to blood vessels.  Pseudoaneurysm  can develop at the site of puncture in the  femoral artery . During this procedure  contrast media  is utilized, to which patients may develop an  allergic reaction . Symptomatic  hypothyroidism  may result from the high retained iodine load of the contrast."}
{"_id": "WikiPedia_Radiology$$$corpus_3082", "text": "Off-target delivery of embolic agents such as reflux into healthy surrounding tissue is a potential side effect that may cause complications such as ulceration of the gut or  cholecystitis . Specialized techniques and devices may decrease the risk."}
{"_id": "WikiPedia_Radiology$$$corpus_3083", "text": "TACE induces tumor necrosis in more than 50% of patients; the resulting  necrosis  releases  cytokines  and other inflammatory mediators into the bloodstream. A self-limiting postembolization syndrome of pain, fever, and malaise may occur due to  hepatocyte  and tumor necrosis. [ 16 ]   Transaminases  may elevate 100-fold, and a  leukemoid reaction  is not uncommon. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3084", "text": "Intrahepatic abscess (treated by  percutaneous drainage ) and gallbladder ischemia are extremely rare. Rising bilirubin is a warning sign of irreversible hepatic necrosis, generally occurring in the setting of cirrhosis. In an effort to reduce the likelihood of significant hepatic toxicity, chemoembolization should be restricted to a single lobe or major branch of the hepatic artery at one time. The patient may be brought back after 1 month, once toxicities and abnormal chemistries have resolved, to complete the procedure in the opposite lobe. Retreatment of new lesions may be necessary, if patients fulfill the original eligibility criteria. [ 17 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3085", "text": "In 1972, surgical ligation of the hepatic artery was first used to treat recurrent hepatic tumors followed by infusion of  5-fluorouracil  into the portal vein. Due to the liver's dual blood supply from the  hepatic artery  and  portal vein , interruption of the flow through the  hepatic artery  was demonstrated to be safe in patients. Tumor embolization eventually developed, blocking the vascular supply to a tumor by primarily endovascular approaches. The application of angiography with embolization followed, and the administration of chemotherapeutic agents with embolic particles evolved into transcatheter arterial chemoembolization. [ 18 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3086", "text": "Transjugular intrahepatic portosystemic shunt  ( TIPS  or  TIPSS ) is an artificial channel within the  liver  that establishes communication between the inflow  portal vein  and the outflow  hepatic vein . It is used to treat  portal hypertension  (which is often due to  liver cirrhosis ) which frequently leads to intestinal bleeding, life-threatening esophageal bleeding ( esophageal varices ) and the buildup of fluid within the abdomen ( ascites )."}
{"_id": "WikiPedia_Radiology$$$corpus_3087", "text": "An  interventional radiologist  creates the shunt using an image-guided  endovascular  (via the  blood vessels ) approach, with the  jugular vein  as the usual entry site."}
{"_id": "WikiPedia_Radiology$$$corpus_3088", "text": "The procedure was first described by  Josef R\u00f6sch  in 1969 at  Oregon Health and Science University . It was first used in a human patient by Dr. Ronald Colapinto, of the  University of Toronto , in 1982, but did not become reproducibly successful until the development of endovascular stents in 1985. In 1988 the first successful TIPS was realized by M. R\u00f6ssle, G.M. Richter, G. N\u00f6ldge and J. Palmaz at the  University of Freiburg . [ 1 ]  The procedure has since become widely accepted as the preferred method for treating portal hypertension that is refractory to medical therapy, replacing the surgical  portacaval shunt  in that role."}
{"_id": "WikiPedia_Radiology$$$corpus_3089", "text": "TIPS is a life-saving procedure in bleeding from esophageal or gastric varices. A randomized study showed that the survival is better if the procedure is done within 72 hours after  bleeding . [ 2 ]  TIPS has shown some promise for people with  hepatorenal syndrome . [ 3 ]  It may also help with  ascites . [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3090", "text": "Severe procedural complications during a TIPS procedure, including catastrophic bleeding or direct liver injury, are relatively uncommon. In the hands of an experienced physician, operative mortality is less than 1% [ medical citation needed ] . On the other hand, up to 25% of patients who undergo TIPS will experience transient post-operative  hepatic encephalopathy  caused by increased porto-systemic passage of nitrogen from the gut. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3091", "text": "A less common, but more serious complication, is hepatic ischemia causing acute liver failure. While healthy livers are predominantly oxygenated by portal blood supply, long-standing portal hypertension results in compensatory hypertrophy of and increased reliance on the hepatic artery for oxygenation. Thus, in people with advanced liver disease the shunting of portal blood away from hepatocytes is usually well tolerated. However, in some cases suddenly shunting portal blood flow away from the liver may result in acute liver failure secondary to hepatic ischemia. [ 6 ]  Acute hepatic dysfunction after TIPS may require emergent closure of the shunt. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3092", "text": "A rare but serious complication is persistent TIPS infection, also known as endotipsitis. [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3093", "text": "Lastly, the TIPS may become blocked by a blood clot or in-growth of endothelial cells and no longer function. This has been significantly reduced with the use of  polytetrafluoroethylene  (PTFE)\u2013covered stents. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3094", "text": "Portal hypertension, an important consequence of liver disease, results in the development of significant  collateral circulation  between the portal system and systemic venous drainage (porto-caval circulation). Portal venous congestion causes venous blood leaving the stomach and intestines to be diverted along auxiliary routes of lesser resistance in order to drain to systemic circulation. With time, the small vessels that comprise a collateral path for porto-caval circulation become engorged and dilated. These vessels are fragile and often hemorrhage into the GI tract. ( See  esophageal ,  gastric ,  rectal varices ). [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3095", "text": "A TIPS procedure decreases the effective  vascular resistance  of the liver through the creation of an alternative pathway for portal venous circulation. By creating a shunt from the portal vein to the hepatic vein, this intervention allows portal blood an alternative avenue for draining into systemic circulation. In bypassing the flow-resistant liver, the net result is a reduced  pressure drop  across the liver and a decreased portal venous pressure. Decreased portal venous pressure in turn lessens congestive pressures along veins in the intestine so that future bleeding is less likely to occur.  The reduced pressure also makes less fluid develop, although this benefit may take weeks or months to occur. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3096", "text": "Transjugular intrahepatic portosystemic shunts are typically placed by an interventional radiologist under  fluoroscopic  guidance. [ 9 ]  Access to the liver is gained, as the name 'transjugular' suggests, via the  internal jugular vein  in the  neck .  Once access to the jugular vein is confirmed, a guidewire and introducer sheath are typically placed to facilitate the  shunt 's placement.  This enables the interventional radiologist to gain access to the patient's  hepatic vein  by traveling from the  superior vena cava  into the  inferior vena cava  and finally the  hepatic vein ."}
{"_id": "WikiPedia_Radiology$$$corpus_3097", "text": "Once the catheter is in the hepatic vein, a wedge pressure is obtained to calculate the pressure gradient in the liver. Following this, carbon dioxide is injected to locate the portal vein. Then, a special needle known as a Colapinto is advanced through the liver parenchyma to connect the hepatic vein to the large  portal vein , near the center of the liver.  The channel for the shunt is next created by inflating an angioplasty balloon within the liver along the tract created by the needle.  The shunt is completed by placing a special mesh tube known as a  stent  or endograft to maintain the tract between the higher-pressure portal vein and the lower-pressure hepatic vein.  After the procedure, fluoroscopic images are made to show placement. Pressure in the portal vein and inferior vena cava are often measured. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3098", "text": "Uterine artery embolization (UAE, uterine fibroid embolization, or UFE)  is a procedure in which an  interventional radiologist  uses a  catheter  to deliver small particles that block the  blood  supply to the uterine body. The procedure is primarily done for the treatment of  uterine fibroids  and  adenomyosis . [ 1 ] [ 2 ]  Compared to surgical treatment for fibroids such as a hysterectomy, in which a woman's uterus is removed, uterine artery embolization may be beneficial in women who wish to retain their uterus. Other reasons for uterine artery embolization are postpartum hemorrhage and uterine  arteriovenous malformations . [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3099", "text": "Uterine fibroids are the most common type of benign uterine tumor and are composed of smooth muscle. [ 4 ]  They often cause bulk-related symptoms, which can be characterized by back pain, heaviness in the pelvic area, abdominal bloating. [ 5 ]  Uterine artery embolization may be done to treat bothersome bulk-related symptoms as well as abnormal or  heavy uterine bleeding  due to  uterine fibroids . Fibroid size, number, and location are three potential predictors of a successful outcome. [ 6 ] [ 7 ] [ 8 ]  Specifically, studies have demonstrated that submucosal (directly underneath the uterine lining) fibroids demonstrated the largest reduction in size while subserosal (outer layer of the uterus) had the smallest reduction. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3100", "text": "Uterine artery embolization may also be appropriate for the treatment of adenomyosis, which is when the lining of the uterus aberrantly grows into the muscle of the uterus. [ 10 ]  Symptoms of adenomyosis include heavy or prolonged menstrual bleeding and painful menstrual periods. [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3101", "text": "Uterine artery embolization can also be used to control heavy uterine bleeding for reasons other than fibroids, such as postpartum  obstetrical hemorrhage . [ 12 ]  Many women who experience postpartum hemorrhage may be successfully treated with medication or  uterine balloon tamponade . [ 13 ]  However, in cases where women continue to bleed, uterine artery embolization may be an appropriate option."}
{"_id": "WikiPedia_Radiology$$$corpus_3102", "text": "A less common indication for uterine artery embolization is for the treatment of uterine arteriovenous malformations which can be a cause of abnormal uterine bleeding or life-threatening bleeding. Roughly half of women with uterine arteriovenous malformations are born with them while the remaining form following surgical interventions or may be due to uterine tumors. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3103", "text": "Prior to undergoing UAE, the patient should be evaluated for the following absolute contra-indications to the procedure: a viable pregnancy, a current infection that is not being treated, or gynecologic malignancy (except for cases where UAE is being used as a procedure in addition to treatment for the cancer). [ 14 ]  Relative contra-indications for the procedure include a severe contrast allergy since contrast is necessary to visualize the arteries during the procedure, kidney impairment since contrast may cause damage to the kidneys, or  coagulopathy  (blood disorder that causes prolonged or excessive bleeding). [ 15 ]  However, all of the stated relative contra-indications can be managed with appropriate pre-operative planning."}
{"_id": "WikiPedia_Radiology$$$corpus_3104", "text": "The rate of serious complications is comparable to that of  myomectomy  or  hysterectomy . The advantage of somewhat faster recovery time is offset by a higher rate of minor complications and an increased likelihood of requiring surgical intervention within two to five years of the initial procedure. [ 16 ]  An analysis of 15,000 women found that those who had myomectomy required fewer additional procedures, including hysterectomies, to treat fibroids over the next five years than those who had uterine artery embolization. [ 17 ] [ 18 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3105", "text": "Complications include the following:"}
{"_id": "WikiPedia_Radiology$$$corpus_3106", "text": "Prior to a uterine artery embolization, patients should undergo a clinic visit with their  gynecologist , have a recent Pap smear, and an endometrial biopsy in cases where abnormal uterine bleeding is a presenting symptom. [ 27 ]  A clinic visit can then be made with the  interventional radiologist  performing the uterine artery embolization so that a thorough history and physical exam can be taken. Recent diagnostic imaging such as a pelvic  magnetic resonance imaging  (MRI) should also be reviewed by the interventional radiologist to rule out possible malignancy, evaluate uterine anatomy, and discuss the likelihood of fibroid passage with the patient. [ 27 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3107", "text": "The procedure is performed by an  interventional radiologist  under conscious sedation. [ 25 ]  Access is commonly through the  radial  or  femoral artery  via the wrist or groin, respectively. [ 3 ] [ 25 ]  After anesthetizing the skin over the artery of choice, the artery is accessed by a needle puncture using the  Seldinger technique . [ 25 ]  Under  fluoroscopic  guidance, a catheter is then introduced into the artery and used to select the uterine vessels for subsequent embolization. Once at the level of the uterine artery an  angiogram  with contrast is performed to confirm placement of the catheter, and the embolizing agent (spheres or beads) is released. As more embolizing agent is administered, blood flow will slow down significantly. Over time, the decreased blood flow causes the fibroid to shrink. Both the left and right uterine arteries are embolized since unilateral UAEs have a high risk of failure. [ 28 ]  The procedure can be performed in a hospital or surgical center. More recently, there has been support for UAE as an outpatient procedure, but many doctors choose an overnight admission for pain control. [ 29 ]  Follow-up for the procedure may vary based on institution, but can include a clinic appointment at 1 to 3 months following the procedure and an MRI to see if the fibroids have shrunk from the preoperative MRI. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3108", "text": "The vast majority of women who undergo UAE experience elimination of abnormal uterine bleeding and improvement in bulk symptoms. [ 15 ]  Additionally, patient satisfaction following the procedure is about 80%. [ 14 ]  One drawback of UAE is that it appears to require more repeat procedures than if surgery was done initially. [ 30 ]  However, long-term patient satisfaction outcomes of UAE are similar to that of surgery and a short-term benefit is the reduction in hospital stay with UAE. [ 30 ] [ 15 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3109", "text": "Currently the number of studies that compare pregnancy rates between UAE and myomectomy are limited. However, a 2020 systematic review assessing pregnancy outcomes after UAE for fibroids demonstrated that pregnancy rates between UAE and myomectomy are comparable. Additionally, they found that rates of pregnancy-related complications in women who underwent UAE were similar to that of the general population. [ 31 ]  Despite these findings, there is still a lack of randomized control trials that directly compare the outcomes of myomectomy and UAE for fibroids, so future studies are needed to determine which procedure yields better results."}
{"_id": "WikiPedia_Radiology$$$corpus_3110", "text": "For women with adenomyosis, the data regarding outcomes is limited. However, studies have demonstrated that about 83% of women with adenomyosis experienced an improvement in their symptoms. Additionally, the rate of improvement in symptoms increased to about 93% in women who had both adenomyosis and fibroids."}
{"_id": "WikiPedia_Radiology$$$corpus_3111", "text": "Regarding cost, the American Journal of Gynecology reports that uterine artery embolization costs 12% less than hysterectomy and 8% less than myomectomy. [ 32 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3112", "text": "UAE was used for the first time in 1979 to control bleeding in a woman with postpartum hemorrhage that did not improve after surgical treatment. [ 33 ]  Since then studies have shown that UAE is a safe and effective procedure for postpartum hemorrhage with control of bleeding in greater than 90% of women. [ 34 ]  The initial use of UAE for patients with fibroids was to limit bleeding during myomectomy. [ 35 ]  During the 1990s, doctors began expanding the indications for UAE and started using it for the treatment of the fibroids specifically. [ 36 ]  Previously, the primary treatment methods for fibroids were myomectomy or hysterectomy. Compared to surgery, UAE can be advantageous because blood loss is typically minimal, surgery and general anesthesia is avoided, recovery is shorter, and women can retain their uterus (relative to hysterectomy). [ 37 ]  UAE is thought to treat fibroids by selectively decreasing blood flow to the tumor since it is highly vascular, which causes improvement in abnormal bleeding and the bulk symptoms that are often experienced with fibroids."}
{"_id": "WikiPedia_Radiology$$$corpus_3113", "text": "For removing uterine fibroids, myomectomy and uterine artery embolisation seem to be equally effective in improving  quality of life , as measured 4-yours after surgery. [ 38 ] [ 39 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3114", "text": "Vascular closure devices  (VCDs) are medical devices used to achieve  hemostasis  of the small hole in the artery after a  cardiovascular  procedure of  endovascular surgery  requiring a  catheterization ."}
{"_id": "WikiPedia_Radiology$$$corpus_3115", "text": "Cardiovascular procedures requiring catheterization include diagnostic procedures that help diagnose diseased blood vessels and interventional procedures such as  angioplasty , the placement of a  stent  and coronary  thrombectomy ."}
{"_id": "WikiPedia_Radiology$$$corpus_3116", "text": "During such procedures, a small incision is made in the  groin  area and a hole is created in the  femoral artery  to gain access to the artery. This hole is referred to as the access site or puncture site. At the completion of the procedure, the hole needs to be closed. Metal clip-based and  suture -based VCDs may reduce time to hemostasis when compared with extrinsic (manual or mechanical) compression. However, no type of VCD has been shown to be more effective or safe than another. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3117", "text": "The main goal of a vascular closure device is to provide rapid  hemostasis  of the artery as well as reduce access site complications. [ 2 ]  VCD's also help reduce time to  ambulation  and time to hospital discharge. [ 3 ]  In addition, VCDs are more comfortable for the patient compared to manual compression."}
{"_id": "WikiPedia_Radiology$$$corpus_3118", "text": "Prior to the development of VCD's, the main method for closing the femoral artery was manual compression. Manual compression involves up to 30 minutes of manual pressure or mechanical clamps applied directly to the patient's groin, which is very painful, followed by up to 8 hours of bed rest in the hospital recovery room."}
{"_id": "WikiPedia_Radiology$$$corpus_3119", "text": "Vascular closure devices were introduced in the early 1990s in an effort to reduce the time to hemostasis, enable early ambulation and improve patient comfort. Initially, devices focused on technologies involving a  suture  or a  collagen  plug. [ 4 ]  These technologies are effective at closing the hole; however, they often leave an intravascular component in the artery, which can cause complications. In addition, these technologies failed to accurately address patient pain."}
{"_id": "WikiPedia_Radiology$$$corpus_3120", "text": "More recent methods to close the hole involve the use of novel materials that dissolve over a short period of time, such as  polyethylene glycol  found in the  Mynx vascular closure device . These technologies incorporate a more gentle deployment of the material to the outside of the artery and avoid the use of intravascular components, leaving nothing behind in the artery and consequently improving patient comfort. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3121", "text": "A  vascular snare  is an  endovascular  device that is used to remove  foreign bodies  from inside  arteries  and  veins . The snare consists of several  radiopaque  loops of wire inside a  catheter , which when extended flower out, and which collapse when withdrawn into the catheter."}
{"_id": "WikiPedia_Radiology$$$corpus_3122", "text": "Vascular snares are used to retrieve  inferior vena cava filters , lost  guide wires , or broken  central venous catheters . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3123", "text": "Vascular snaring is a component technique in  endovascular aneurysm repair  in some devices. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3124", "text": "A snare catheter is inserted using the  Seldinger technique  under  fluoroscopic  guidance. The snare wire is advanced under direct visualization and flowered open. The object being retrieved is captured within the loops of snare, and retrieved with the snare wire and catheter, being carried out of the body at the tip of the catheter."}
{"_id": "WikiPedia_Radiology$$$corpus_3125", "text": "Vertebral augmentation , including  vertebroplasty  and  kyphoplasty , refers to similar  percutaneous  spinal procedures in which  bone cement  is injected through a small hole in the skin into a fractured  vertebra  in order to relieve  back pain  caused by a vertebral  compression fracture . After decades of  medical research  into the efficacy and safety of vertebral augmentation, there is still a lack of consensus regarding certain aspects of vertebroplasty and kyphoplasty."}
{"_id": "WikiPedia_Radiology$$$corpus_3126", "text": "Vertebroplasty  and  kyphoplasty  are the two most common procedures for spinal augmentation. These  medical terms  are  classical compounds  of the suffix  -plasty  meaning \"molding or shaping surgically\" (from  Ancient Greek   plast\u00f3s  \"molded, formed\") and the prefixes  vertebro-  \"vertebra\" (from  Latin   vertebra  \"joint, joint of the spine\") and  kypho-  \"humped; stooping forward\" (from Ancient Greek  kyphos  \"crooked\"). [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3127", "text": "Vertebroplasty is typically performed by a spine surgeon or  interventional radiologist . It is a minimally invasive procedure and patients usually go home the same or next day as the procedure. Patients are given local anesthesia and light sedation for the procedure, though it can be performed using only local anesthetic for patients with medical problems who cannot tolerate sedatives well."}
{"_id": "WikiPedia_Radiology$$$corpus_3128", "text": "During the procedure, bone cement is injected with a biopsy needle into the collapsed or fractured vertebra. The needle is placed with  fluoroscopic x-ray  guidance. The cement (most commonly  poly methyl methacrylate  (PMMA), although more modern cements are used as well) quickly hardens and forms a support structure within the vertebra that provide stabilization and strength. The needle makes a small puncture in the patient's skin that is easily covered with a small bandage after the procedure. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3129", "text": "Kyphoplasty is a variation of a vertebroplasty which attempts to restore the height and angle of  kyphosis  of a fractured  vertebra  (of certain types), followed by its stabilization using injected bone cement. The procedure typically includes the use of a small balloon that is inflated in the vertebral body to create a void within the cancellous bone prior to cement delivery.  Once the void is created, the procedure continues in a similar manner as a vertebroplasty, but the bone cement is typically delivered directly into the newly created void. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3130", "text": "In a 2011 review Medicare contractor NAS determined that there is no difference between vertebroplasty and kyphoplasty, stating, \"No clear evidence demonstrates that one procedure is different from another in terms of short- or long-term efficacy, complications, mortality or any other parameter useful for differentiating coverage.\" [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3131", "text": "As of 2019, the effectiveness of vertebroplasty is not supported. [ 5 ] [ 6 ]  A 2018 Cochrane review found no role for vertebroplasty for the treatment of acute or sub-acute osteoporotic vertebral fractures. [ 7 ]  The subjects in these trials had primarily non-acute fractures and prior to the release of the results they were considered the most ideal people to receive the procedure. After trial results were released vertebroplasty advocates pointed out that people with acute  vertebral fractures  were not investigated. [ 8 ] [ 9 ]  A number of non-blinded trials suggested effectiveness, [ 10 ]  but the lack of blinding limits what can be concluded from the results and some have been criticized because of being funded by the manufacturer. [ 8 ]  One analysis has attributed the difference to  selection bias . [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3132", "text": "Some have suggested that this procedure only be done in those with fractures less than 8 weeks old; [ 12 ]  however, analysis of the two blinded trials appear not to support the procedure even in this acute subgroup. [ 13 ]  Others consider the procedure only appropriate for those with other health problems making rest possibly detrimental, those with metastatic  cancer  as the cause of the spine fracture, or those who do not improve with conservative management. [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3133", "text": "Evidence does not support a benefit of kyphoplasty over vertebroplasty with respect to pain, but the procedures may differ in restoring lost vertebral height, and in safety issues like cement  extravasation  (leakage). [ 8 ]  As with vertebroplasty, several unblinded studies have suggested a benefit from balloon kyphoplasty. [ 15 ] [ 16 ]  As of 2012 [update] , no blinded studies have been performed, and since the procedure is a derivative of vertebroplasty, the unsuccessful results of these blinded studies have cast doubt upon the benefit of kyphoplasty generally. [ 17 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3134", "text": "Some vertebroplasty practitioners and some health care professional organizations continue to advocate for the procedure. [ 18 ] [ 19 ] [ 20 ]   In 2010, the board of directors of the  American Academy of Orthopaedic Surgeons  released a statement recommending strongly against use of vertebroplasty for osteoporotic spinal compression fractures, [ 21 ]  while the Australian Medical Services Advisory Committee considers both vertebroplasty and kyphoplasty only to be appropriate in those who have failed to improve after a trial of conservative treatment, [ 22 ]  with conservative treatment (analgesics primarily) being effective in two-thirds of people. [ 23 ]  The  National Institute for Health and Care Excellence  similarly states that the procedure in those with osteoporotic fractures is only recommended as an option if there is severe ongoing pain from a recent fracture even with optimal pain management. [ 24 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3135", "text": "Vertebral body stenting , also known by the brand Kiva, is a similar procedure which also has poor evidence to support its use. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3136", "text": "Some of the associated risks are from the leak of acrylic cement to outside of the vertebral body. Although severe complications are extremely rare, infection, bleeding, numbness, tingling, headache, and paralysis may ensue because of misplacement of the needle or cement. This particular risk is decreased by the use of X-ray or other radiological imaging to ensure proper placement of the cement. [ 2 ]  In those who have fractures due to cancer, the risk of serious adverse events appears to be greater at 2%. [ 23 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3137", "text": "The risk of new fractures following these procedures does not appear to be changed; however, evidence is limited, [ 17 ]  and an increase risk as of 2012 is not ruled out. [ 25 ]  Pulmonary cement embolism is reported to occur in approximately 2-26% of procedures. [ 26 ]  It may occur with or without symptoms. [ 26 ]  Typically, if there are no symptoms, there are no long term issues. [ 26 ]  Symptoms do occur in about 1 in 2000 procedures. [ 22 ]  Other adverse effects include spinal cord injury in 0.6 per 1000. [ 22 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3138", "text": "In the United States in 2003 approximately 25,000 vertebroplasty procedures were paid for by Medicare. [ 27 ]  As of 2011/2012 this number may be as high as 70,000-100,000 per year. [ 28 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3139", "text": "Vertebroplasty had been performed as an open procedure for many decades to secure pedicle screws and fill tumorous voids. However, the results were not always worth the risk involved with an  open procedure , which was the reason for the development of  percutaneous  vertebroplasty."}
{"_id": "WikiPedia_Radiology$$$corpus_3140", "text": "The first percutaneous vertebroplasty was performed in 1984 at the University Hospital of Amiens, France to fill a vertebral void left after the removal of a benign  spinal tumor . A report of this and 6 other patients was published in 1987 and it was introduced in the United States in the early 1990s. Initially, the treatment was used primarily for tumors in Europe and vertebral compression fractures in the United States, although the distinction has largely gone away since then. [ 29 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3141", "text": "The cost of vertebroplasty in Europe as of 2010 was ~2,500 Euro. [ 23 ]  As of 2010 in the United States, when done as an outpatient, vertebroplasty costs around US$3300 while kyphoplasty costs around US$8100 and when done as an inpatient vertebroplasty cost ~US$11,000 and kyphoplasty US$16,000. [ 30 ]  The cost difference is due to kyphoplasty being an in-patient procedure while vertebroplasty is outpatient, and due to the  balloons  used in the kyphoplasty procedure. [ 31 ]  Medicare in 2011 spent about US$1 billion on the procedures. [ 28 ]  A 2013 study found that \"the average adjusted costs for vertebroplasty patients within the first quarter and the first 2 years postsurgery were $14,585 and $44,496, respectively. The corresponding average adjusted costs for kyphoplasty patients were $15,117 and $41,339. There were no significant differences in adjusted costs in the first 9 months postsurgery, but kyphoplasty patients were associated with significantly lower adjusted treatment costs by 6.8\u20137.9% in the remaining periods through two years postsurgery.\" [ 32 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3142", "text": "In response to the NEJM articles and a medical record review showing misuse of vertebroplasty and kyphoplasty,  US Medicare   contractor  Noridian Administrative Services (NAS) conducted a literature review and formed a policy regarding reimbursement of the procedures. NAS states that in order to be reimbursable, a procedure must meet certain criteria, including, 1) a detailed and extensively documented medical record showing pain caused by a fracture, 2) radiographic confirmation of a fracture, 3) that other treatment plans were attempted for a reasonable amount of time, 4) that the procedure is not performed in the emergency department, and 5) that at least one year of follow-up is planned for, among others. The policy, as referenced, applies only to the region covered by Noridian and not all of Medicare's coverage area. The reimbursement policy became effective on 20 June 2011. [ 4 ]  A 2015 comparative study of Medicare patients with vertebral compression fractures found that those who received balloon kyphoplasty and vertebroplasty therapies experienced lower mortality and overall morbidity than those who received conservative nonoperative management. [ 33 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3143", "text": "In 2015, it was reported by  The Atlantic  that a person associated with a medical device company that sells equipment related to the kyphoplasty procedure had edited the Wikipedia article on the subject to promote claims about its efficacy. [ 34 ]  Assertions about the positive effects of kyphoplasty have been found to be unsupported or disproven, according to independent researchers. [ 35 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3144", "text": "A  contrast agent  (or  contrast medium ) is a  substance  used to increase the  contrast  of structures or fluids within the body in  medical imaging . [ 1 ]  Contrast agents absorb or alter external  electromagnetism  or  ultrasound , which is different from  radiopharmaceuticals , which emit  radiation  themselves. In  X-ray  imaging, contrast agents enhance the  radiodensity  in a target tissue or structure. In  magnetic resonance imaging  (MRI), contrast agents shorten (or in some instances increase) the relaxation times of  nuclei  within body tissues in order to alter the contrast in the image."}
{"_id": "WikiPedia_Radiology$$$corpus_3145", "text": "Contrast agents are commonly used to improve the visibility of  blood vessels  and the  gastrointestinal tract ."}
{"_id": "WikiPedia_Radiology$$$corpus_3146", "text": "The types of contrast agent are classified according to their intended imaging modalities."}
{"_id": "WikiPedia_Radiology$$$corpus_3147", "text": "For  radiography , which is based on  X-rays ,  iodine  and  barium  are the most common types of contrast agent. Various sorts of iodinated contrast agents exist, with variations occurring between the  osmolarity ,  viscosity  and absolute iodine content. Non-ionic  dimers  are favored for their low osmolarity and low toxicity, but have a correspondingly higher cost attached to their use. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3148", "text": "Gadolinium  is used in  magnetic resonance imaging  as an  MRI contrast agent  or gadolinium-based contrast agent (GBCA). [ 3 ]  In the 3+ oxidation state, the metal has seven unpaired electrons. This causes water around the contrast agent to relax quickly, enhancing the quality of the MRI scan."}
{"_id": "WikiPedia_Radiology$$$corpus_3149", "text": "Microbubbles  are used as contrast agents for  sonographic  examination, specifically  echocardiograms , for the detection of a  cardiac shunt . These microbubbles are composed of agitated  saline solution , most of which are too large to pass through the  capillaries  (blood vessels) of the  lungs . Therefore, the only ones that reach the left side of the heart pass through an abnormal connection between the two sides of the heart, known as a  right-to-left shunt . In addition, pharmaceutically prepared microbubbles are composed of tiny amounts of  nitrogen  or  perfluorocarbons  strengthened and supported by a  protein ,  lipid , or  polymer  shell. [ 4 ]  These are small enough to pass through the capillaries and are used to increase the contrast in the left ventricle, improving the visualization of its walls. The drop in density on the interface between the gas in the bubble and the surrounding liquid strongly scatters and reflects the  ultrasound  back to the probe. This process of  backscattering  gives the liquid with these bubbles a high signal, which can be seen in the resulting image."}
{"_id": "WikiPedia_Radiology$$$corpus_3150", "text": "Abenacianine  for injection, also known as VGT-309, is a tumor-targeted  fluorescent  imaging agent developed by Vergent Bioscience to enhance tumor visualization during cancer surgeries. [ 1 ]  This compound binds to  cathepsins , a family of proteases that are over expressed in various solid tumors, facilitating the detection tumors. [ 2 ] [ 3 ] [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3151", "text": "Blood pool agents  (BPAs) are a class of  magnetic resonance angiography   contrast agents . [ 1 ] [ 2 ]  Blood pool agents (also known as intravascular contrast agents) are differentiated from other contrast agents due to their high molecular weight and higher  relaxivities . [ 3 ]  Their large size prevents diffusion through the  vascular   epithelium  and leakage into the  interstitial space , and because of this they stay in the vascular system for a longer time period. Most contrast agents, leave the vascular system within a few minutes, however blood pool agents remain in the circulation for up to an hour, extending the window available for imaging. Longer image acquisition times allow better  signal-to-noise ratio  and improved image resolution."}
{"_id": "WikiPedia_Radiology$$$corpus_3152", "text": "Due to their extended time in the  circulatory system , blood pool agents can be used for delayed steady-state imaging, and additionally these results can be combined with first pass arterial imaging. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3153", "text": "This class of BPAs is based on the noncovalent binding of low molecular weight Gd 3+ -based complexes to  human serum albumin . The first commercial agent to be approved in this class is  gadofosveset trisodium [ 4 ]  (also known as Vasovist [ 5 ]  or Ablavar, [ 6 ]  and previously known as MS-325 [ 7 ] ). Many clinical and case studies documenting the use of this BPA have been published, [ 8 ] [ 9 ] [ 10 ] [ 11 ] [ 12 ] [ 13 ] [ 14 ]  and its efficacy in enhancing blood vessels visibility has been demonstrated. [ 15 ]  The manufacturer ( Lantheus Medical ) discontinued production in 2017 though, due to poor sales. [ 16 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3154", "text": "Gadocoletic acid (Bracco SpA), also known as B-22956 and B22956/1, is a Gd-DTPA derivative that is currently in development, but has not yet been approved for clinical use. [ 17 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3155", "text": "Gadobenic acid  (MultiHance [ 18 ] ) is sometimes categorized as a BPA; however, as it only binds weakly to albumin and because hepatobiliary uptake of this compound occurs, this contrast agent should not be classified as a BPA."}
{"_id": "WikiPedia_Radiology$$$corpus_3156", "text": "Polymeric Gd 3+  chelates are large in size, which prevents leakage into the interstitial space, and provides long imaging windows. Several polymeric gadolinium-based BPAs are currently in development but have not yet been approved for clinical use:\nGadomelitol (Guerbet, France), also known as Vistarem and P792 [ 19 ] \nGadomer-17 (Schering AG, Berlin, Germany) also known as Gd-DTPA-17, SH L 643 A. [ 20 ]"}
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{"_id": "WikiPedia_Radiology$$$corpus_3159", "text": "Relmapirazin  ( MB-102 ) is an investigational fluorescent tracer that is exclusively excreted renally and is used to measure  glomerular filtration rate  of the kidneys. [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 5 ] [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3160", "text": "Neuroradiology  is a subspecialty of  radiology  focusing on the diagnosis and characterization of abnormalities of the  central  and  peripheral nervous system ,  spine , and head and neck using  neuroimaging  techniques. Medical issues utilizing neuroradiology include  arteriovenous malformations ,  tumors ,  aneurysms , and  strokes .  [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3161", "text": "The major professional association in the United States representing neuroradiologists is the American Society of Neuroradiology (ASNR). The ASNR publishes the  American Journal of Neuroradiology  (AJNR). The ASNR annual meeting rotates through different cities, and usually takes place between late April and early June. The specialty neuroradiology societies that are associated with the ASNR include the  American Society of Pediatric Neuroradiology  (ASPNR), the  American Society of Spine Radiology  (ASSR), the  American Society of Head and Neck Radiology  (ASHNR), and the  American Society of Functional Neuroradiology  (ASFNR). These societies contribute to the programming of the ASNR annual meeting and also hold their own annual meetings."}
{"_id": "WikiPedia_Radiology$$$corpus_3162", "text": "The major professional association in Europe is the  European Society of Neuroradiology  (ESNR). In Japan, it is the  Japanese Neuroradiological Society ; in the UK, it is the  British Society of Neuroradiologists  (BSNR); and in France, it is the  French Society of Neuroradiology  (SFNR). The ESNR and the Japanese society publish  Neuroradiology , and the SFNR publishes the  Journal of Neuroradiology ."}
{"_id": "WikiPedia_Radiology$$$corpus_3163", "text": "A  radiologic sign  is an objective indication of some medical fact (that is, a  medical sign ) that is detected by a  physician  during  radiologic examination  with  medical imaging [ 1 ]  (for example, via an  X-ray ,  CT scan ,  MRI  scan, or  sonographic scan )."}
{"_id": "WikiPedia_Radiology$$$corpus_3164", "text": "Acorn cyst sign  is a  radiologic sign  indicating the presence of a  benign  uncomplicated  cyst  in  ultrasound examinations of the breast . [ 1 ]  It consists of a deep anechoic fluid portion resembling an  acorn , and a superficial echogenic layer resembling an acorn cap. This sign is helpful for radiologists to differentiate a benign uncomplicated cyst from a complex mass. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3165", "text": "This article about a  neoplasm  is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Radiology$$$corpus_3166", "text": "In  radiology , the  air crescent sign  is a finding on  chest radiograph  and  computed tomography  that is  crescenteric  and  radiolucent , due to a  lung  cavity that is filled with  air  and has a round  radiopaque  mass. [ 1 ]   Classically, it is due to an  aspergilloma , a form of  aspergillosis , that occurs when the fungus  Aspergillus  grows in a cavity in the lung. [ 2 ] \nIt is also referred as Monad sign. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3167", "text": "This  medical sign  article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Radiology$$$corpus_3168", "text": "Aortic unfolding  is an  abnormality  visible on a  chest X-ray , that shows widening of the  mediastinum  which may mimic the appearance of a  thoracic aortic aneurysm . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3169", "text": "With aging, the ascending portion of the thoracic  aorta  increases in length by approximately 12% per decade, whereas the diameter increases by just 3% per decade. This elongation causes the ascending aorta to appear as a vertical shadow on the left  heart  border. Unfolding is often associated with aortic calcification which implies  aortic degeneration  and  hypertension .  [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3170", "text": "Bat wing appearance  is a radiologic sign referring to bilateral perihilar lung shadowing seen in frontal chest X-ray and in chest CT. [ 1 ] [ 2 ]  The most common reason for bat wing appearance is the accumulation of oedema fluid in the lungs. [ 3 ]  The batwing sign is symmetrical, usually showing  ground glass appearance  and spares the lung cortices. [ 4 ]   This sign is seen in individuals with  pneumonia , inhalation injuries,  pulmonary haemorrhage ,  sarcoidosis , bronchoalveolar carcinoma and pulmonary alveolar proteinosis. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3171", "text": "This  pulmonology  article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Radiology$$$corpus_3172", "text": "The  black pleura sign  is a radiological feature observed in  pulmonary alveolar microlithiasis  (PAM), a rare lung disorder characterized by the accumulation of tiny calcium phosphate deposits, known as microliths, within the alveoli. [ 1 ]  This sign appears as a thin, dark (lucent) line beneath the ribs on imaging studies, contrasting with the diffusely dense, calcified lung parenchyma."}
{"_id": "WikiPedia_Radiology$$$corpus_3173", "text": "In PAM, microliths predominantly accumulate in the central portions of secondary pulmonary lobules, leading to widespread calcification of the lung tissue. However, the subpleural regions often remain relatively spared from these deposits and sometimes show subpleural cystic changes. This subpleural sparing creates a peripheral zone that appears less dense (more lucent) on imaging studies, resulting in the black pleura sign. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3174", "text": "The black pleura sign is considered a characteristic indicator of pulmonary alveolar microlithiasis. Its presence on imaging studies can aid radiologists and clinicians in differentiating PAM from other interstitial lung diseases that may not exhibit subpleural sparing. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3175", "text": "Blade of grass sign  (also known as  flame sign [ 1 ] ) is a radiologic sign referring to the lytic fronts seen in the leading edge of the long bone in  Paget's disease . [ 2 ]  It is usually seen as a wedge shaped area of radiolucency in the diaphysis of long bone. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3176", "text": "The boomerang sign is a radiological finding observed on magnetic resonance imaging (MRI) of the brain, particularly in diffusion-weighted imaging (DWI) sequences. It refers to a characteristic boomerang-shaped area of restricted diffusion in the splenium of the  corpus callosum  due to  cytotoxic edema . [ 1 ]  This sign is associated with various neurological conditions and is considered a non-specific marker of splenial pathology, often reversible depending on the underlying cause. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3177", "text": "The splenium of the corpus callosum is the posterior part of the corpus callosum, a major white matter structure connecting the two cerebral hemispheres. On MRI, the boomerang sign appears as a boomerang-shaped hyperintense area on DWI. There is a corresponding low signal intensity on the apparent diffusion coefficient (ADC) map, indicating true restricted diffusion. The sign is often localized within the central or posterior splenium. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3178", "text": "The bowl of grapes sign is a descriptive radiological term used in the context of  synovial sarcoma , a malignant soft tissue tumor. [ 1 ]  This sign refers to the appearance of multiple small, rounded, fluid-containing spaces within a soft tissue mass, which resemble a cluster of grapes. [ 2 ]  These cystic spaces are typically attributed to hemorrhage, necrosis, or myxoid degeneration within the tumor, a common feature of synovial sarcoma."}
{"_id": "WikiPedia_Radiology$$$corpus_3179", "text": "The bowl of grapes sign is typically identified on magnetic resonance imaging and computed tomography, and occasionally on ultrasound. During ultrasound examination, mixed echogenicity is noted in synovial sarcoma, with hypoechoic or anechoic areas corresponding to the cystic regions."}
{"_id": "WikiPedia_Radiology$$$corpus_3180", "text": "The cystic spaces in synovial sarcoma appear hyperintense on T2-weighted images, reflecting fluid content. Solid tumor components often demonstrate heterogeneous enhancement after contrast administration. The mass may display a multilocular appearance with well-defined cystic and solid regions, contributing to the grape-like pattern. [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3181", "text": "The  bowler hat sign  is a  radiologic sign  seen on double-contrasted  barium enema  studies, indicating the presence of a  colonic polyp . [ 1 ]  A ring of barium collects at the base of the polyp and also along its dome, simulating the appearance of a bowler hat. [ 1 ]  This sign is present for growths that are an intermediate between flat and pedunculated. [ 2 ]  The  differential diagnosis  for this sign includes bubbles,  diverticula , and unusual projections of anatomic structures such as the  appendix . [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3182", "text": "The  brim sign  or the  pelvic brim sign  is a  radiologic sign  seen in cases of  Paget\u2019s disease  of bone involving the pelvis. [ 1 ]  It refers to thickened and sclerotic changes along the iliopubic line, the anteromedial portion of the pelvic brim. This sign is a key diagnostic marker for pelvic involvement in Paget\u2019s disease and is typically identified on plain radiographs. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3183", "text": "Paget\u2019s disease of bone is a chronic disorder characterized by abnormal bone remodeling. The pelvic brim sign arises due to excessive bone resorption due to increased osteoclastic activity in the early stages of the disease leads to localized bone loss, as well as excessive bone formation during the later stages of the diseases. Compensatory osteoblastic activity results in thickened, sclerotic bone along the iliopubic line."}
{"_id": "WikiPedia_Radiology$$$corpus_3184", "text": "The pelvic brim, being a weight-bearing area, shows pronounced changes, including thickening and increased density. These changes manifest radiologically as sclerosis and cortical thickening along the pelvic brim, creating the characteristic sign. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3185", "text": "A  bucket-handle tear  of the knee is a specific type of meniscal injury characterized by a longitudinal tear of the medial or lateral meniscus, where a displaced inner fragment resembles the appearance of a \"bucket handle\". [ 1 ]  This displaced meniscal fragment often remains attached at the anterior and posterior horns but dislocates into the intercondylar notch of the knee joint. Such injuries can cause mechanical symptoms, including locking and restricted movement of the knee."}
{"_id": "WikiPedia_Radiology$$$corpus_3186", "text": "The knee joint contains two crescent-shaped fibrocartilaginous structures, the menisci (medial and lateral), which serve as shock absorbers and stabilize the joint during movement. Each meniscus has an outer vascular zone (red-red zone), which has a good blood supply and healing potential as well as a central avascular zone (white-white zone), which has limited healing capability. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3187", "text": "The medial meniscus is more prone to injury due to its firm attachment to the joint capsule and limited mobility. The lateral meniscus is more mobile and less frequently injured."}
{"_id": "WikiPedia_Radiology$$$corpus_3188", "text": "A bucket-handle tear occurs when a significant longitudinal tear develops, often as a result of trauma or excessive twisting forces applied to the knee. The displaced fragment can flip into the intercondylar notch, impeding normal joint motion. The injury is most commonly seen in:"}
{"_id": "WikiPedia_Radiology$$$corpus_3189", "text": "The injury frequently occurs in conjunction with anterior cruciate ligament (ACL) tears."}
{"_id": "WikiPedia_Radiology$$$corpus_3190", "text": "Patients with a bucket-handle tear typically present with the following symptoms: [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3191", "text": "The patient may report a history of a twisting injury or sports-related trauma"}
{"_id": "WikiPedia_Radiology$$$corpus_3192", "text": "Diagnosis of a bucket-handle tear is based on a combination of clinical examination and imaging studies:"}
{"_id": "WikiPedia_Radiology$$$corpus_3193", "text": "Plain Radiographs (X-rays): While X-rays cannot visualize meniscal tears, they may rule out bony injuries. Occasionally, a joint effusion may be observed."}
{"_id": "WikiPedia_Radiology$$$corpus_3194", "text": "Management of bucket-handle tears is primarily surgical, as these tears often cause mechanical symptoms and are unlikely to heal on their own due to the displacement of the meniscal fragment. Treatment approaches include:"}
{"_id": "WikiPedia_Radiology$$$corpus_3195", "text": "Postoperative care includes: [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3196", "text": "Return to sports is usually permitted after 4\u20136 months, depending on the success of meniscus repair and concomitant injuries (e.g., ACL tear)."}
{"_id": "WikiPedia_Radiology$$$corpus_3197", "text": "Butterfly vertebra  (also known as sagittal cleft vertebra) is a rare congenital spinal anomaly characterized by the presence of a sagittal cleft within a vertebral body, giving it a butterfly-like appearance on imaging. This condition arises due to incomplete fusion of the lateral halves of a vertebra during embryonic development. While often asymptomatic, butterfly vertebrae may occasionally be associated with spinal deformities or syndromic conditions. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3198", "text": "The vertebral column develops from paired somites during embryogenesis. Normally, the right and left halves of each vertebra fuse in the midline to form a complete vertebral body. In butterfly vertebrae, this process is disrupted, leading to a persistent sagittal cleft. The defect is usually filled with fibrous or cartilaginous tissue, and the two halves of the vertebral body may remain connected by this intervening soft tissue.\nThe condition is most commonly observed in the thoracic and lumbar spine, although it can occur at any spinal level. The degree of clefting varies, resulting in a spectrum of appearances on imaging studies. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3199", "text": "Plain Radiography:  The vertebra appears divided into two symmetrical halves, separated by a vertical lucency that represents the cleft. The lateral portions of the vertebral body often appear sclerotic, and the shape resembles a butterfly when viewed in the anteroposterior projection."}
{"_id": "WikiPedia_Radiology$$$corpus_3200", "text": "CT imaging:  Provides greater detail regarding the bony anatomy, including the extent of clefting and the composition of the intervening tissue."}
{"_id": "WikiPedia_Radiology$$$corpus_3201", "text": "MRI:  Useful for evaluating associated spinal cord abnormalities or adjacent soft tissue changes. The sagittal cleft may appear as a hyperintense signal on T2-weighted images, representing cartilaginous or fibrous material. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3202", "text": "In  radiology ,  Canga's bead symptom  is the irregular appearance of  uterus  and  nodular  structures in  tuba uterina  observed in patients with genital  tuberculosis . [ 1 ] \nIt is named for  Serif Canga  (1906\u20131993), a Turkish Gynecologist, in 1971. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3203", "text": "This medical  symptom  article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Radiology$$$corpus_3204", "text": "The  cannonball sign  is a radiological term used to describe the presence of multiple, well-circumscribed, round opacities seen on X-ray or CT imaging, typically in the lungs. [ 1 ]  This finding is most commonly associated with hematogenous metastases, where malignant cells spread to the lungs via the bloodstream, forming discrete nodules that resemble cannonballs. [ 2 ]  The term \"cannonball\" reflects the large, rounded appearance of these lesions, often evident on chest radiographs or CT scans."}
{"_id": "WikiPedia_Radiology$$$corpus_3205", "text": "Cannonball metastases result from the hematogenous dissemination of malignant cells, where tumor emboli travel through the bloodstream and lodge in the pulmonary vasculature. The lungs are a frequent site of metastases due to their rich vascular supply and filtration of venous blood. The characteristic rounded nodules represent distinct tumor foci that grow in a non-infiltrative pattern. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3206", "text": "This pattern is typically associated with malignancies that produce well-demarcated metastatic deposits rather than diffuse infiltrative changes. The size and number of nodules can vary depending on the primary tumor and the extent of metastatic spread."}
{"_id": "WikiPedia_Radiology$$$corpus_3207", "text": "Chest radiograph shows multiple, rounded opacities of varying sizes, typically bilateral but may be unilateral in early stages. Lesions are well-defined, mimicking cannonballs. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3208", "text": "CT has greater sensitivity in detecting small or early nodules. Nodules are round, well-circumscribed, and randomly distributed. [ 4 ]  The nodules may reveal additional features such as  necrosis  or calcification, depending on the tumor type."}
{"_id": "WikiPedia_Radiology$$$corpus_3209", "text": "Rarely used for initial identification but can assess metastatic activity, especially in borderline or ambiguous cases."}
{"_id": "WikiPedia_Radiology$$$corpus_3210", "text": "Cannonball metastases are classically seen in  renal cell carcinoma , [ 5 ]  also seen in  choriocarcinoma ,  endometrial cancer , [ 6 ]   prostate cancer  and some gastrointestinal malignancies.\nThe presence of cannonball metastases is a hallmark of advanced systemic malignancy. Identification of these lesions often triggers search for primary tumor. Detailed history, physical examination, and further imaging studies (e.g., abdominal or pelvic CT, mammography) are needed to locate the primary malignancy. Biopsy may be performed to confirm the metastatic origin and histopathology, particularly if the primary tumor is unknown.\nCannonball metastases often indicate a poor prognosis, reflecting widespread disease."}
{"_id": "WikiPedia_Radiology$$$corpus_3211", "text": "Celery stalking  or  celery stalk metaphysis  refers to the appearance of longitudinally aligned linear sclerotic bands extending from the  epiphysis  of the long bones. [ 1 ]  This finding is seen in conditions such as  osteopathia striata ,  congenital rubella [ 2 ]  and  congenital syphilis . [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3212", "text": "Chang sign  is a radiologic sign for detecting  pulmonary embolism  in X-ray films. It refers to the dilatation and abrupt change in calibre of a previously normal descending pulmonary artery on a chest X-ray film. [ 1 ]  Chang sign usually appears within 24 hours of the onset of chest pain due to pulmonary embolism, [ 2 ]  and the maximal dilatation of the descending pulmonary artery often occurs in two to three days after the onset of pain. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3213", "text": "Chang sign is absent in case of co-existing pneumonia or other conditions causing central opacities, where the descending pulmonary artery cannot be visualised in the X-ray image. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3214", "text": "The  cheerio sign  is a  radiologic sign  that has been used to describe both pulmonary nodules and tears in the  glenoid labrum , named after its resemblance to the popular breakfast cereal \" Cheerios \"."}
{"_id": "WikiPedia_Radiology$$$corpus_3215", "text": "On  computed tomography  (CT) of the chest, the cheerio sign is seen as a ring-like structure with central  lucency  within the lung [ 1 ] . This sign most commonly indicates the presence of  pulmonary adenocarcinoma  or  Langerhans cell histiocytosis , but differential diagnosis includes  granulomatosis with polyangitis ,  rheumatoid nodules  and infections [ 1 ] ."}
{"_id": "WikiPedia_Radiology$$$corpus_3216", "text": "The cheerio sign has also been demonstrated on  CT  arthograms of the shoulder in cases of anterior and posterior tears in the superior part of the  glenoid labrum . These tears are called SLAP lesions (superior labrum; anterior, posterior). This sign is specifically seen in type 3 SLAP lesions, which involve a \"bucket-handle\" tear of predominately the anterior labrum, often with displacement into the joint. On CT, this appears as a ring of contrast material and air surrounding a core of soft tissue [ 2 ] ."}
{"_id": "WikiPedia_Radiology$$$corpus_3217", "text": "Chondrocalcinosis  or  cartilage calcification  is  calcification  (accumulation of  calcium  salts) in  hyaline cartilage  and/or  fibrocartilage . [ 1 ]  Chondrocalcinosis is an observation that can be visualized through diagnostic imaging tests such as  X-rays ,  CT ,  MRI , and  ultrasound . [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3218", "text": "Buildup of  calcium phosphate  in the  ankle joints  has been found in about 50% of the general population, and may be associated with  osteoarthritis . [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3219", "text": "Another common cause of chondrocalcinosis is  calcium pyrophosphate dihydrate crystal deposition disease  (CPPD). [ 4 ]  CPPD is estimated to affect 4\u20137% of the adult populations of Europe and the United States. [ 5 ]  Chondrocalcinosis can be seen in approximately 40% of those with CPPD. [ 6 ]  Previous studies have overestimated the prevalence by simply estimating the prevalence of chondrocalcinosis regardless of cause. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3220", "text": "A  magnesium deficiency  may cause chondrocalcinosis, and there is anecdotal evidence that magnesium supplementation may reduce or alleviate symptoms. [ 7 ]  In some cases,  arthritis  from  injury  can cause chondrocalcinosis. [ 8 ] \nOther causes of chondrocalcinosis include: [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3221", "text": "Chondrocalcinosis does not always lead to symptoms. However, chondrocalcinosis in the presence of CPPD may cause symptoms similar to Pseudogout, Pseudo-rheumatoid arthritis, and Pseudo-osteoarthritis. Chondrocalcinosis may be accompanied by joint pain, joint swelling, and decreased range of motion. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3222", "text": "Chondrocalcinosis affects common areas such as the knee, wrist, hand, and pelvis. [ 10 ]  Chondrocalcinosis can also be visualized affecting the spine. \" Crowned Dens Syndrome \" is an example of chondrocalcinosis affecting cervical vertebrae. [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3223", "text": "Chondrocalcinosis can be visualized on  projectional radiography ,  CT scan ,  MRI ,  ultrasound , and  nuclear medicine . [ 1 ]  CT scans and MRIs show calcific masses (usually within the  ligamentum flavum  or joint capsule), however radiography is more successful. [ 1 ]  At ultrasound, chondrocalcinosis may be depicted as echogenic foci with no acoustic shadow within the hyaline cartilage. [ 12 ]  As with most conditions, chondrocalcinosis can present with similarity to other diseases such as  ankylosing spondylitis  and  gout . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3224", "text": "More research is needed on the role of genetics in the development of chondrocalcinosis and CPPD, but there is some evidence that  mutations of the ANKH gene may lead to chondrocalcinosis. [ 13 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3225", "text": "The  cockade sign  is a radiological feature associated with  intraosseous lipoma , a rare benign tumor of the bone composed primarily of mature adipose tissue. [ 1 ] [ 2 ]  This sign describes the characteristic appearance of a central calcification or ossification surrounded by radiolucent fatty tissue on imaging, resembling a bullseye or  cockade . [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3226", "text": "Intraosseous lipomas are thought to arise from the proliferation of adipose tissue within the medullary cavity of bone. Over time, ischemic changes within the lesion may lead to necrosis, calcification, or cystic transformation. These secondary changes are responsible for the imaging characteristics, including the cockade sign. The cockade sign develops due to central  calcification  or  ossification . The radiolucent fatty component forms the outer ring of the lesion. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3227", "text": "Codfish vertebra  refers to the biconcave appearance of the vertebra in sagittal radiographs due to pathological changes, such as demineralisation. [ 1 ] [ 2 ] [ 3 ]  Codfish appearance of the vertebra is seen in several conditions such as osteoporosis, steroid or heparin therapy,  Cushing syndrome , idiopathic,  sickle cell disease , leukemia,  Duchenne muscular dystrophy , and homo-cystinuria. [ 4 ]  Codfish vertebra sign is usually first seen in lumbar vertebrae. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3228", "text": "The  kidney bean sign  (more commonly called the  coffee bean sign;  also  bent inner tube sign ) is a  radiologic sign  observed on  abdominal radiographs  that indicates the presence of a  sigmoid volvulus , a form of bowel obstruction. It is seen as an area of hyperlucency resembling a coffee bean. [ 1 ]  The opposed walls of adjacent bowel loops form the central cleft while the two sides of the bean represent gas\u2010filled segments of dilated bowel that form an inverted U\u2010shape. [ 2 ]  Air-fluid levels may also be seen in the segments of dilated bowel. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3229", "text": "The  colon cut-off sign  is a radiographic finding seen on abdominal radiographs and computed tomography scans. It is characterized by a marked dilatation of the transverse colon, with an abrupt transition to collapsed distal colon, particularly the splenic flexure. [ 1 ]  This sign is indicative of underlying pathology, most commonly acute pancreatitis."}
{"_id": "WikiPedia_Radiology$$$corpus_3230", "text": "The colon cut-off sign is due to local inflammation or irritation. In acute pancreatitis, the inflammatory process involving the pancreas and surrounding tissues can extend to the adjacent transverse colon through the phrenicocolic ligament. [ 2 ]  This inflammation leads to spasm and localized ileus, causing a sharp demarcation between the dilated proximal bowel and the collapsed distal segment."}
{"_id": "WikiPedia_Radiology$$$corpus_3231", "text": "The colon cut-off sign is different from  sentinel loop  sign, where the dilated segment is a part of the small intestine."}
{"_id": "WikiPedia_Radiology$$$corpus_3232", "text": "The comb sign is a radiological sign seen on computed tomography or magnetic resonance imaging scans, primarily used to identify inflammation in the mesentery. [ 1 ]  It refers to the appearance of engorged mesenteric vessels resembling the teeth of a comb, which is a key feature seen in several abdominal conditions, particularly those associated with  inflammatory bowel diseases , such as  Crohn's disease . [ 2 ]  This sign was first described by Dr. Morton Mayers. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3233", "text": "The comb sign is characterized by the appearance of dilated, prominent vessels in the  mesentery  of the abdomen, which appears similar to the teeth of a comb. These engorged vessels result from inflammation and increased blood flow in the mesenteric vessels, which is a common response to acute or chronic inflammatory conditions in the gastrointestinal tract. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3234", "text": "This sign is most often seen in patients with Crohn's disease but can also be associated with other conditions that cause mesenteric inflammation. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3235", "text": "The mesentery may appear thickened, and the mesenteric vessels (which supply blood to the intestines) become dilated and appear to resemble a comb. This sign is best seen in the small intestine or colon and can be associated with peripheral fat stranding or mesenteric fat changes indicative of active inflammation. This sign is helpful in determining the acutiy of the inflammatory process. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3236", "text": "The  comet tail sign  is a radiological finding seen in chest CT. It refers to a specific appearance resembling a comet's tail, characterised by a bright, streaky opacity due to the presence of a round atelectasis in chest CT. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3237", "text": "In case of a round atelectatic mass, the nearby bronchovascular bundle appears to be pulled into the mass, resembling the tail of a comet. The comet tail usually extends from a central point in the lung periphery towards the hilum. If intravenous contrast is injected, homogenous enhancement is seen. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3238", "text": "The  continuous diaphragm sign  is a radiological finding seen on chest X-rays that indicates the presence of gas within the thoracic cavity, specifically in the mediastinum ( pneumomediastinum ), [ 1 ]  the peritoneal cavity ( pneumoperitoneum ) or pericardium ( pneumopericardium ). [ 2 ]  This sign is characterized by the uninterrupted visualization of the diaphragm's contour across the midline, underlining both the right and left hemidiaphragms, which is normally obscured by the overlying heart and mediastinum. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3239", "text": "The diaphragm typically appears as two separate, curved outlines (hemidiaphragms) on a chest X-ray due to the heart and mediastinum obscuring its central portion. When air accumulates in the mediastinum or peritoneal cavity, it outlines the diaphragm, making its central portion visible and creating the appearance of a continuous line. [ 4 ]  The continuous diaphragm sign is most commonly caused by the presence of free air in the mediastinum where air escapes from the lungs, airways, or other mediastinal structures. The causes for pneumomediastinum include trauma, alveolar rupture, asthma exacerbations, or esophageal perforation. The sign can also be seen in pneumoperitoneum, where free air enters the abdominal cavity due to gastrointestinal perforation or surgery. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3240", "text": "The  corduroy sign  is a radiological finding observed on spinal imaging in cases of  vertebral hemangiomas . It refers to a striated or vertically oriented linear pattern seen on imaging, resembling the appearance of corduroy fabric. [ 1 ]  This sign is most commonly identified on lateral radiographs or magnetic resonance imaging (MRI) of the spine and is an important diagnostic marker for benign conditions such as vertebral hemangiomas. Patients with the typical \u2018corduroy appearance\u2019 is extremely rare clinically. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3241", "text": "Vertebral hemangiomas are benign vascular tumors of the vertebral bodies. They arise due to a proliferation of thin-walled blood vessels within the bone and are often asymptomatic. The corduroy sign reflects the characteristic trabecular changes caused by the hemangioma, namely, thinning of trabeculae as well as thickened vertical struts, resulting from compensatory hypertrophy of the remaining trabeculae to maintain structural integrity. These vertical trabecular striations give rise to the \" corduroy \" appearance on imaging. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3242", "text": "On lateral radiographs and sagittal CT of the spine, the corduroy sign appears as vertical linear striations, which are alternating bands of radiolucency (representing vascular spaces) and radiodensity (representing thickened trabeculae) within the vertebral body. The vertebral body may retain its normal shape and size unless the lesion becomes aggressive. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3243", "text": "The  cottage loaf sign  is a radiological finding associated with  diaphragmatic rupture , often observed on imaging studies such as computed tomography (CT) or Magnetic Resonance Imaging (MRI). [ 1 ]  This sign refers to the appearance of herniated liver into the thoracic cavity, with a characteristic \"stacked\" or \"two-tiered\" morphology resembling a traditional British  cottage loaf \u2014a smaller, rounded structure situated atop a larger one. It is a key indicator of diaphragmatic injury, typically resulting from blunt or penetrating trauma. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3244", "text": "C\u0153ur en sabot  (French for \"clog-shaped heart\" or \"boot-shaped heart\" [ 1 ] ) is a  radiological sign  seen most commonly in patients with  tetralogy of Fallot , [ 2 ]  a cyanotic congenital heart disease. It is a radiological term to describe the following findings in the x-ray: [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3245", "text": "Echocardiography  has been used for confirmation and differentiation of congenital heart diseases. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3246", "text": "Crazy paving  refers to a pattern seen on  computed tomography  of the chest, involving lobular  septal  thickening with variable  alveolar  filling. The finding is seen in  pulmonary alveolar proteinosis , [ 1 ]  and other diseases. [ 2 ]  Its name comes from its resemblance to irregular  paving stones , called  crazy pavings . [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3247", "text": "There are variety of causes for crazy paving patterns: infection, cancer, blood related disorders, diseases caused by inhalation of particles, and  idiopathic disease . Specific lung disorders that can cause such patterns are:  pneumocystis pneumonia ,  mucinous bronchioloalveolar carcinoma , pulmonary alveolar proteinosis,  sarcoidosis , nonspecific interstitial pneumonia,  organizing pneumonia , exogenous lipoid pneumonia, adult respiratory distress syndrome, and pulmonary hemorrhage syndromes. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3248", "text": "The  cupola sign  is seen on a supine chest or abdominal radiograph in the presence of  pneumoperitoneum ."}
{"_id": "WikiPedia_Radiology$$$corpus_3249", "text": "It refers to dependent air that rises within the  abdominal cavity  of the supine patient to accumulate underneath the central tendon of the  diaphragm  in the midline. It is seen as lucency overlying the lower thoracic vertebral bodies. The superior border is well defined, but the inferior margin is not."}
{"_id": "WikiPedia_Radiology$$$corpus_3250", "text": "\"Cupola\" is an architectural term, referring to a small dome (in particular, a small dome crowning a roof or a turret). The word derives from a Latin word for a \"little cup\"."}
{"_id": "WikiPedia_Radiology$$$corpus_3251", "text": "Many conditions of or affecting the human integumentary system have associated features that may be found by performing an x-ray or CT scan of the affected person."}
{"_id": "WikiPedia_Radiology$$$corpus_3252", "text": "Dagger sign  is a radiologic sign seen in advanced cases of  ankylosing spondylitis . [ 1 ]  The appearance of a dagger is seen in the X-ray because of ossification of the supraspinous and infraspinous ligaments. [ 2 ]  As a result, a central dense line of sclerosis, resembling a dagger can be seen in the AP radiograph of spine and pelvis. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3253", "text": "In  radiology , the  deep sulcus sign  on a supine  chest radiograph  is an indirect indicator of a  pneumothorax . [ 1 ] [ 2 ]  In a  supine  film, it appears as a deep, lucent, ipsilateral costophrenic angle [ 3 ]  within the nondependent portions of the pleural space as opposed to the  apex  (of the  lung ) when the patient is upright.  The  costophrenic angle  is abnormally deepened when the pleural air collects laterally, producing the deep sulcus sign. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3254", "text": "Patients with  chronic obstructive pulmonary disease  (COPD) may exhibit deepened lateral costophrenic angles due to hyperinflation of the lungs and cause a false deep sulcus sign. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3255", "text": "In  medicine , the  dense artery sign  or  hyperdense artery sign  is an increased  radiodensity  of an artery as seen on  computer tomography  (CT) scans, and is a  radiologic sign  of early  ischemic stroke . [ 1 ]  In earlier studies of  medical imaging  in patients with strokes, it was the earliest sign of ischemic stroke in a significant minority of cases. [ 2 ]  Its appearance portends a poor prognosis for the patient. [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3256", "text": "The sign has been observed in the  middle cerebral artery  (MCA), [ 4 ]   posterior cerebral artery  (PCA), [ 5 ]   vertebral artery , [ 2 ]  and  basilar artery ; [ 6 ]  these have been called the  dense MCA sign ,  dense PCA sign ,  dense vertebral artery sign , and  dense basilar artery sign , respectively."}
{"_id": "WikiPedia_Radiology$$$corpus_3257", "text": "Rarely, a  hypodense artery sign  can occur due to fat embolism. [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3258", "text": "Through  cerebral angiography , the sign has been demonstrated to correspond to  embolic  or  atherosclerotic  occlusion of an artery. [ 1 ]  Specifically, the hyperdensity is thought to be due to  calcification  or  hemorrhage  associated with an  atherosclerotic plaque . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3259", "text": "Identification of the dense artery sign is often based on subjective interpretation and  false positives  may occur. One study aiming to define criteria for the sign determined that measuring  Hounsfield units  on the CT scan could differentiate between the dense MCA sign associated with  ischemic stroke  and that caused by false positives. [ 8 ]  Specifically, the combination of greater than 43 Hounsfield units and an MCA density ratio of greater than 1.2 was diagnostic of a dense MCA sign associated with acute ischemic stroke. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3260", "text": "The  dense MCA sign  is a  dense artery sign  observed on non-contrast computed tomography (CT) of the brain and is an important early marker of acute ischemic stroke involving the  middle cerebral artery  territory. [ 1 ]  It refers to an abnormally increased attenuation (hyperdensity) of the MCA, reflecting an intraluminal thrombus or embolus. This sign is also referred to as the  hyperdense MCA sign ."}
{"_id": "WikiPedia_Radiology$$$corpus_3261", "text": "The dense MCA sign is caused by a fresh thrombus or embolus occluding the lumen of the middle cerebral artery. A thrombus with a high concentration of red blood cells and fibrin has increased density relative to normal flowing blood, leading to its hyperattenuating appearance on a non-contrast CT scan."}
{"_id": "WikiPedia_Radiology$$$corpus_3262", "text": "The sign typically appears within the first few hours of arterial occlusion, often before visible ischemic changes develop in brain parenchyma. Early recognition of this sign is critical as it allows prompt diagnosis and initiation of treatment to restore perfusion and minimize brain damage."}
{"_id": "WikiPedia_Radiology$$$corpus_3263", "text": "Dense MCA sign stands for a hyperdense linear structure located along the course of the middle cerebral artery (MCA), typically in the Sylvian fissure in CT images. The sign may be seen unilaterally (on the affected side) compared to the contralateral MCA, which appears of normal attenuation. The sign is most commonly observed in the M1 segment of the MCA and less commonly in distal branches (M2/M3 segments), where it is termed the hyperdense MCA dot sign. [ 2 ]  The comparison of thrombus with the unaffected side improves diagnostic accuracy. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3264", "text": "The dense MCA sign is an early indicator of acute ischemic stroke caused by MCA occlusion. Its detection has important clinical implications:"}
{"_id": "WikiPedia_Radiology$$$corpus_3265", "text": "The dense MCA sign may be the first and only sign of MCA occlusion within the first 1\u20132 hours of symptom onset, even before parenchymal hypodensity develops. Early recognition enables rapid initiation of treatment, such as intravenous thrombolysis (e.g., tissue plasminogen activator, tPA) or endovascular thrombectomy. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3266", "text": "Presence of the dense MCA sign suggests a large clot burden and is associated with more extensive infarction and worse functional outcomes if reperfusion is not achieved.Prompt recognition of the sign improves the chances of favorable recovery by allowing faster intervention."}
{"_id": "WikiPedia_Radiology$$$corpus_3267", "text": "Several conditions may mimic the dense MCA sign, leading to false positives. These include:"}
{"_id": "WikiPedia_Radiology$$$corpus_3268", "text": "The dense MCA sign may not always be present, even in cases of acute MCA occlusion. However, the sign has good sensitivity, and high specificity. [ 6 ]  Thin-section CT and appropriate windowing (narrow window settings) improve detection."}
{"_id": "WikiPedia_Radiology$$$corpus_3269", "text": "The dense MCA sign is often accompanied by other early ischemic changes on CT, including:"}
{"_id": "WikiPedia_Radiology$$$corpus_3270", "text": "The  double bronchial wall sign  is a radiological finding observed in cases of  pneumomediastinum , a condition characterized by the presence of air within the mediastinum. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3271", "text": "Pneumomediastinum occurs due to the escape of air from ruptured alveoli or airways into the mediastinal space. The rupture of alveoli due to increased intrathoracic pressure (e.g., from coughing, vomiting, or trauma) leads to air tracking along the peribronchovascular interstitium which in turn accumulates in the mediastinum. As air accumulates, it dissects along the bronchial structures, creating a visible separation of the bronchial wall from the surrounding tissue. The result is the double bronchial wall appearance on imaging, a hallmark of pneumomediastinum. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3272", "text": "The double bronchial wall sign is best visualized on CT, which provides high-resolution images of the mediastinal structures. The double bronchial wall sign is commonly seen in the central bronchi, particularly in the trachea or mainstem bronchi, where air is more likely to outline the structures. Associated findings such as air surrounding other mediastinal structures, such as the esophagus or great vessels may be present. Subcutaneous emphysema or air tracking into the neck may also be seen. This sign may also be diagnosed in X-ray images, although the sensitivity is much lower than that of CT. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3273", "text": "In  radiology , the  double bubble  sign is a feature of pediatric imaging seen on  radiographs  or  prenatal   ultrasound  in which two air filled bubbles are seen in the abdomen, representing two discontiguous loops of bowel in a proximal, or 'high,' small bowel obstruction. The finding is typically pathologic, and implies either  duodenal atresia ,  duodenal web ,  annular pancreas , or on occasion  midgut volvulus , a distinction that requires close clinical correlation and, in most cases, surgical intervention. [ 1 ] [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3274", "text": "Distal gas is more often seen with midgut volvulus, duodenal stenosis and duodenal web, though this not always present. In such cases, distinguishing the diagnoses depends on clinical presentation. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3275", "text": "A  fluoroscopic  study known as an  upper gastrointestinal series  is often the next step in management in patients that are not critically ill, though if volvulus is suspected, emergent surgical intervention is mandated. If clinical findings are equivocal, caution with non water-soluble contrast is needed, as the usage of  barium  can impede surgical revision and lead to increased post operative complications. Non ionic water-soluble contrast should be used, as the hyperosmolar agents, if aspirated, can result in life-threatening  pulmonary edema . When reflective of duodenal atresia, associations with  Down syndrome  and  VACTERL sequence  abnormalities are often seen. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3276", "text": "Certain rare anatomic anomalies, such as congenital duodenal duplication [ 6 ]  and  pyloric atresia [ 7 ]  can cause  false positives  for the sign on radiographs. Congenital pyloric atresia usually causes a single bubble on radiographs without distal gas, though an intermittent double bubble sign is occasionally seen. [ 8 ]  Duodenal atresia, while typically without distal gas, has been reported with an absent double bubble, though this variant is quite rare. [ 9 ]  On neonatal ultrasound, a double bubble can also be caused by a  choledochal  cyst,  omental  cyst, or  enteric duplication cyst ."}
{"_id": "WikiPedia_Radiology$$$corpus_3277", "text": "The  double duct sign  is a radiological finding characterized by the simultaneous dilation of the  common bile duct  and the  main pancreatic duct . This sign is significant because it often indicates an obstruction in the distal bile duct and pancreatic duct, frequently caused by serious underlying pathologies such as  pancreatic carcinoma  or  periampullary tumors . [ 1 ]  The double duct sign is most commonly visualized on imaging modalities such as computed tomography, magnetic resonance imaging, or  endoscopic retrograde cholangiopancreatography ."}
{"_id": "WikiPedia_Radiology$$$corpus_3278", "text": "The double duct sign results from the anatomical convergence of the biliary and pancreatic ducts at the  ampulla of Vater , where obstructions can disrupt the drainage of both systems simultaneously. Common causes of such obstructions include  pancreatic adenocarcinoma ,  periampullary cancer ,  cholangiocarcinoma ,  chronic pancreatitis , gallstone-related obstruction and strictures. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3279", "text": "The double duct sign is a red flag finding in radiology, with malignancies accounting for the majority of cases. Early identification is crucial for diagnosis, staging in case of malignancy, management and for performing therapeutic interventions."}
{"_id": "WikiPedia_Radiology$$$corpus_3280", "text": "The  double posterior cruciate ligament sign  (double PCL sign) is a radiological finding seen on magnetic resonance imaging of the knee, specifically in the context of a  bucket-handle tear  of the medial meniscus. It refers to the appearance of a duplicated posterior cruciate ligament, where the displaced fragment of the torn medial meniscus lies parallel and inferior to the PCL, mimicking a second ligament. [ 1 ]  The double PCL sign has high specificity for meniscal tears when noted on MRI. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3281", "text": "A bucket-handle tear is a specific type of longitudinal meniscal tear in which a fragment of the torn meniscus displaces toward the intercondylar notch of the knee. The displaced fragment often remains attached at its anterior and posterior horns but flips centrally into the notch. [ 4 ]  This displacement causes the torn meniscal fragment to align closely and parallel to the PCL, resulting in the appearance of a \"double PCL\" on sagittal MRI sequences."}
{"_id": "WikiPedia_Radiology$$$corpus_3282", "text": "The double PCL sign is best observed on sagittal T2-weighted or proton density-weighted MRI images. [ 5 ]  Key features include: [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3283", "text": "The  dripping candle wax sign  is a  radiologic sign  seen on  X-rays  of bone that indicates  melorheostosis (or Leri disease) , a rare benign bone disease characterized by bone  hypertrophy ,  dysplasia , and  sclerosis . [ 1 ]  The sclerosis typically affects one side of the  cortex  of the involved bone, appearing similar to wax melting down one side of a candle. [ 1 ]  Melorheostosis most commonly affects the  long bones  of the upper and lower extremities, but can also be seen in the hands and feet. [ 2 ]  It is usually an  incidental finding  and most patients are asymptomatic. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3284", "text": "The  drooping lily sign  is a radiological finding observed on imaging studies of the kidneys, most commonly associated with duplex collecting system and obstruction of the upper moiety. [ 1 ]  This sign is characterized by the appearance of a compressed, non-obstructed lower renal moiety, which takes on a \"drooping\" or displaced appearance due to the distension of the obstructed upper moiety. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3285", "text": "The drooping lily sign is typically seen in the context of a duplex collecting system, a congenital anomaly in which the kidney has two separate ureters draining from two distinct renal segments (upper and lower poles). When the ureter draining the upper moiety becomes obstructed, often by a  ureterocele  (a cystic dilation of the distal ureter within the bladder), the upper moiety becomes dilated while the lower moiety remains functional and compressed."}
{"_id": "WikiPedia_Radiology$$$corpus_3286", "text": "The \"drooping\" appearance arises due to the enlarged upper moiety compressing and displacing the lower moiety downward and laterally. The non-obstructed lower moiety maintains normal function but appears smaller and distorted on imaging. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3287", "text": "The  dural tail sign  (also known as \" dural thickening \", \" flare sign \", or \" meningeal sign \") is a radiological finding observed in  magnetic resonance imaging  (MRI) studies of the brain that refers to a thickening of the  dura mater  immediately adjacent to a mass lesion, such as a  brain tumor . [ 1 ]  Initially, the dural tail sign was thought to be  pathognomonic  of  meningioma , a slow-growing tumor that arises from the meninges. [ 1 ]  However, subsequent studies have shown that it can also be observed in various intra- and extra-cranial pathologies and in spinal lesions. [ 1 ]  It is not a completely  sensitive  finding, as it is seen in only 60-72% of cases. [ 2 ]  It is not completely specific either, as it has been described associated with lesions like  neuromas ,  chloromas ,  pituitary diseases ,  granulomatous disorders , cerebral  Erdheim-Chester disease ,  lymphomas ,  metastasis ,  hemangiopericytomas ,  schwannomas , and  gliomas  such as  glioblastoma multiforme  (GBM). [ 2 ] [ 3 ]  The final diagnosis should be further established through  cerebrospinal fluid analysis  or  histopathological examination  following a  biopsy . [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3288", "text": "The dural tail sign was first described in 1989 by Wilms  et al. . [ 1 ] [ 4 ]  Histopathological correlation from different studies has at times revealed tumor infiltration into the dura mater, however, in most instances, it signifies a  hypervascular , non- neoplastic  response. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3289", "text": "One study showed that including the dural tail in the  stereotactic radiosurgery  (SRS) or fractionated stereotactic radiotherapy (FSRT) volumes for meningioma treatment did not seem to impact recurrence. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3290", "text": "The  empty sella sign  is a radiological finding characterized by the partial or complete filling of the  sella turcica  with  cerebrospinal fluid  (CSF), causing the  pituitary gland  to appear flattened or compressed against the walls of the sella. [ 1 ]  This results in the sella appearing \"empty\" on imaging, despite the presence of a compressed pituitary gland. The empty sella sign is typically identified on magnetic resonance imaging (MRI) or computed tomography (CT) and can be associated with various clinical conditions or incidental findings. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3291", "text": "The empty sella sign occurs due to herniation of the subarachnoid space into the sella turcica, displacing the pituitary gland and allowing CSF to occupy the space. [ 3 ]  This phenomenon is often linked to the following mechanisms: [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3292", "text": "In both primary and secondary cases, the pituitary gland is often compressed but retains some degree of function."}
{"_id": "WikiPedia_Radiology$$$corpus_3293", "text": "MRI is the gold standard for diagnosing the empty sella sign. Key features include: [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3294", "text": "On CT, the empty sella sign may appear as hypodensity in the sella, corresponding to CSF. There may be possible sellar floor thinning or remodeling due to chronic pressure changes."}
{"_id": "WikiPedia_Radiology$$$corpus_3295", "text": "Empty vertebral body sign  is a radiological sign used for diagnosing any injury with flexion-distraction mechanism of the vertebrae, particularly  Chance fracture  of the vertebrae. [ 1 ] [ 2 ]  In Chance fracture, there is disruption and angulation superiorly or inferiorly of posterior elements of the vertebrae. As a result, the affected vertebral body is seen as radiolucent in the anterio-posterior view. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3296", "text": "Endoexoenteric  refers to a specific  radiographic  manifestation of lymphoma of the bowel."}
{"_id": "WikiPedia_Radiology$$$corpus_3297", "text": "Lymphomas  are malignant neoplasms (cancers) arising from  lymphocytes  of the immune system. When they arise in the bowel tissue, they are referred to as primary. In other instances, the tumor can arise from the lymph nodes and \"travel\" to the bowel, so-called \"extra-nodal\" disease. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3298", "text": "Marshak [ 1 ]  was the first to introduce the term \"endoexoenteric\" to refer to a specific radiographic pattern (seen on  x-rays ,  CT scans  or  PET scans ) of lymphomatous involvement of the bowel. This terminology derives from the fact that in this form of lymphomatous invasion of the bowel, the tumor extends throughout the entire width of the bowel wall, from the  luminal   or  mucosal  (endo) surface to the  serosal  (exo) surface. Enteric refers to the bowel itself. In Marshak's later textbook, published in 1980, [ 2 ]  he abandons this terminology."}
{"_id": "WikiPedia_Radiology$$$corpus_3299", "text": "Of the five patterns of bowel lymphoma described in Marshak's original work, endoexoenteric is the second most common type (the others being: infiltrative [most common], multiple nodules, polypoidal mass, and mesenteric.) [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3300", "text": "Specifically, the features of endoexoenteric lymphoma are an irregular collection of barium due to central ulceration, and displacement of adjacent bowel loops. In this form of lymphoma,  fistula  formation (an abnormal communication between the tumor and adjacent bowel loops) is common. Since the bowel is not sterile, infection can easily be introduced, leading to findings of  mesenteric  abscesses. [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3301", "text": "Imaging techniques, while very helpful in suggesting the presence of specific disease, cannot diagnose this (or any other  neoplastic  disease) with certainty. Definitive diagnosis is almost always achieved by  biopsy , followed by  microscopic ,  histologic  and  immunologic  examination of the tissues obtained. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3302", "text": "Recognition of this type of lymphoma presentation is important, in that it may predict the future course and potential complications of this disease, thereby alerting clinicians to undertake surveillance and appropriate interventions. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3303", "text": "The  eye of the tiger  sign is a  radiologic sign  observed on  T2-weighted   magnetic resonance  (MR) images of the brain. It appears as a central area of  hyperintense  signal surrounded by a ring of hypointensity in the anteromedial part of the  globus pallidus . [ 1 ]  The  eye of the tiger  sign is recognized as a diagnostic feature of  pantothenate kinase associated neurodegeneration , previously known as Hallervorden-Spatz syndrome. [ 2 ]  This is a neurodegenerative disorder associated with excess iron accumulation in the brain. The hypointense area is thought to be caused by the excess iron while the central hyperintensity is possibly a result of gliosis. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3304", "text": "The  fabella sign  is displacement of the  fabella  that is seen in cases of synovial  effusion  and  popliteal fossa  masses. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3305", "text": "The  fabella  is an accessory ossicle located inside the  gastrocnemius  lateral head  tendon  on the posterior side of the knee, in about 25% of people.  It can thus serve as a surrogate radio-opaque marker of the posterior border of the knee's  synovium .  On a lateral  radiograph  of the knee, an increase in the distance from the fabella to the  femur  or to the  tibia  can be suggestive of fluid or of a mass within the synovial fossa.  This is of particular use in radiographic detection of knee effusions, as the cause for the effusion may obscure the subcutaneous planes on x-ray that can also be used to determine presence of effusion or effusion size. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3306", "text": "The  falciform ligament sign  is a  radiological sign  observed on abdominal imaging in cases of  pneumoperitoneum , where free intraperitoneal air outlines the  falciform ligament . [ 1 ]  This sign is considered a diagnostic indicator of free air within the abdominal cavity and is most commonly identified on computed tomography (CT) scans and less frequently in abdominal radiographs. [ 2 ] [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3307", "text": "The falciform ligament is a double-layered fold of peritoneum that connects the anterior abdominal wall to the anterosuperior surface of the liver. It contains the  ligamentum teres  (a remnant of the umbilical vein) in its free edge and lies within the midline, extending from the umbilicus to the inferior surface of the diaphragm. [ 5 ] [ 6 ]  Under normal conditions, the falciform ligament is not visible on CT imaging unless surrounded by free air or fluid."}
{"_id": "WikiPedia_Radiology$$$corpus_3308", "text": "On CT, falciform ligament is seen as a linear high-attenuation structure outlined by low-attenuation free air. There may be associated findings such as the site for perforation or underlying pathology. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3309", "text": "The  fishhook ureter sign , also known as the \"hockey stick\" or \"J-shaped\"  ureter  sign, is a  radiologic sign  that has been used to describe the presence of a  retrocaval ureter , which is an anatomical anomaly where the ureter abnormally runs posterior to the  IVC . This abnormality often results in hydroureter or  hydronephrosis . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3310", "text": "The  fishook ureter sign  also describes the appearance of the ureter in patients with bladder outlet obstruction due to  benign prostatic hyperplasia  (BPH). [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3311", "text": "This  biology  article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Radiology$$$corpus_3312", "text": "Fleischner sign  is a radiological sign that aids the diagnosis of pulmonary embolism. [ 1 ]  The sign indicates the dilatation of the proximal pulmonary arteries due to pulmonary embolism. [ 2 ]  It was named after  Felix Fleischner , who first described it. [ 3 ]  The Fleishner sign is seen both on X-ray and CT scan of chest/thorax."}
{"_id": "WikiPedia_Radiology$$$corpus_3313", "text": "Fogging phenomenon  in  computerized tomography (CT) scanning  of the  head  is vanishing signs of an  infarct  on the serial  CT  imaging in a patient with a recent  stroke . [ 1 ]  It is a reversal of the  hypodensity  on the CT after an acute  ischemic stroke . This happens as a result of re-nourishment of the infarcted area in subacute phase about one to three weeks after the stroke. [ 2 ]  In fact, resolution of the edema, which was caused by the accident, leads to increased  attenuation  of infarcted area that may regain near-normal density and mask the stroke. However, in the third week,  parenchymal  volume loss commonly appears as a hypoattenuation (decreased attenuation) with a  negative mass effect  (shrinkage). [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3314", "text": "In  radiology , the  Golden S sign , also known as the  S sign of Golden , is a  radiologic sign  seen on  chest X-ray  that suggests a central  lung  mass or a  lung collapse . [ 1 ]  It was first described by, and subsequently named after, Dr Ross Golden (1889\u20131975) in 1925 in association with  bronchial carcinoma , [ 2 ]  but it is also seen in  metastatic cancer ,  enlarged lymph nodes , and collapse of the right upper lobe of the lung. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3315", "text": "The Golden S sign can be seen on  plain radiographs  as well as on  computed tomography  (CT) scans of the chest. [ 1 ] [ 3 ]  The sign is seen in the right lung as a distorted  minor fissure , whose lateral aspect is concave inferiorly and whose medial aspect is convex inferiorly. [ 1 ]  This produces a \"reverse S\" appearance, responsible for the sign being occasionally called the  reverse S sign of Golden . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3316", "text": "Ground-glass  opacity  ( GGO ) is a finding seen on  chest x-ray  (radiograph) or  computed tomography (CT)  imaging of the  lungs . It is typically defined as an area of hazy opacification (x-ray) or increased attenuation (CT) due to air displacement by fluid, airway collapse,  fibrosis , or a  neoplastic process . [ 1 ]  When a substance other than air fills an area of the lung it increases that area's density. On both x-ray and CT, this appears more grey or hazy as opposed to the normally dark-appearing lungs. Although it can sometimes be seen in normal lungs, common pathologic causes include  infections ,  interstitial lung disease , and  pulmonary edema . [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3317", "text": "In both CT and chest radiographs, normal lungs appear dark due to the relative lower  density  of air compared to the surrounding tissues. When air is replaced by another substance (e.g. fluid or fibrosis), the density of the area increases, causing the  tissue  to appear lighter or more grey. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3318", "text": "Ground-glass opacity is most often used to describe findings in  high-resolution CT  imaging of the  thorax , although it is also used when describing chest radiographs. In CT, the term refers to one or multiple areas of increased  attenuation  (density)  without  concealment of the  pulmonary vasculature . This appears more grey, as opposed to the normally dark-appearing (air-filled) lung on CT imaging. In chest radiographs, the term refers to one or multiple areas in which the normally darker-appearing (air-filled) lung appears more opaque, hazy, or cloudy. Ground-glass opacity is in contrast to  consolidation , in which the pulmonary vascular markings are obscured. [ 3 ] [ 5 ]  GGO can be used to describe both focal and diffuse areas of increased density. [ 5 ]  Subtypes of GGOs include diffuse, nodular, centrilobular, mosaic, crazy paving, halo sign, and reversed halo sign. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3319", "text": "The differential diagnosis for ground-glass opacities is broad. General etiologies include infections, interstitial lung diseases, pulmonary edema,  pulmonary hemorrhage , and neoplasm. A correlation of imaging with a patient's clinical features is useful in narrowing the diagnosis. [ 6 ] [ 7 ]  GGOs can be seen in normal lungs. Upon expiration there is less air in the lungs, leading to a relative increase in density of the tissue, and thus increased attenuation on CT. Furthermore, when a patient lays supine for a CT scan, the posterior lungs are in a dependent position, causing partial collapse of the posterior  alveoli . This leads to an increase in density of the tissue, resulting increased attenuation and a possible ground-glass appearance on CT. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3320", "text": "In the setting of  pneumonia , the presence of GGO (as opposed to consolidation) is a useful diagnostic clue. Most bacterial infections lead to lobar consolidation, while  atypical pneumonias  may cause GGOs. It is important to note that while many of the pulmonary infections listed below may lead to GGOs, this does not occur in every case. [ 2 ] [ 6 ] [ 7 ] [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3321", "text": "There are seven general patterns of ground-glass opacities. [ 6 ]  When combined with a patient's clinical signs and symptoms, the GGO pattern seen on imaging is useful in narrowing the differential diagnosis. It is important to note that while some disease processes present as only one pattern, many can present with a mixture of GGO patterns. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3322", "text": "The diffuse pattern typically refers to GGOs in multiple lobes of one or both lungs. Broadly, a diffuse pattern of GGO can be caused by displacement of air with fluid, inflammatory debris, or fibrosis.  Cardiogenic pulmonary edema  and ARDS are common causes of a fluid-filled lung.  Diffuse alveolar hemorrhage  is a rarer cause of diffuse GGO seen in some types of vasculitis, autoimmune conditions, and bleeding disorders. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3323", "text": "Inflammation  and fibrosis can also cause diffuse GGOs.  Pneumocystis  pneumonia, an infection typically seen in  immunocompromised  (e.g. patients with  AIDS ) or  immunosuppressed  individuals, is a classic cause of diffuse GGOs. Many viral pneumonias and idiopathic interstitial pneumonias can also lead to a diffuse GGO pattern. Radiation pneumonitis, a side effect of pulmonary radiation therapy, can lead to pulmonary fibrosis and diffuse GGOs. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3324", "text": "There are numerous potential causes of nodular GGOs which can be broadly separated into benign and malignant conditions. Benign conditions potentially leading to the formation of nodular GGOs include aspergillosis, acute eosinophilic pneumonia, focal interstitial fibrosis, granulomatosis with polyangiitis,  IgA vasculitis , organizing pneumonia, pulmonary contusion, pulmonary cryptococcus, and thoracic endometriosis. Focal interstitial fibrosis presents a unique challenge when differentiating from malignant nodular GGOs on CT imaging. It is typically persistent over long-term imaging follow-up and shares a similar appearance to malignant nodular GGOs. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3325", "text": "Pre-malignant or malignant causes of nodular GGOs include adenocarcinoma, adenocarcinoma in situ, and atypical adenomatous hyperplasia (AAH). One large review study found that 80% of nodular GGOs which were present on repeated CT imaging represented either pre-malignant or malignant growths. Differentiating between pre-malignancy and malignancy on the basis of CT alone can pose a challenge to radiologists; however, there are several features that are indicative of pre-malignant nodules. AAH is a pre-malignant cause of nodular GGO and is more commonly associated with lower attenuation on CT and smaller nodule size (<10\u00a0mm) compared to adenocarcinoma. [ 10 ]  In addition, AAH often lacks the solid features and spiculated appearance that are often associated with malignant growths. [ 9 ]  In contrast, as adenocarcinoma becomes invasive it will more often cause retraction of adjacent pleura and may show an increase in vascular markings. Nodules >15\u00a0mm almost always represent an invasive adenocarcinoma. [ 9 ] [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3326", "text": "Centrilobular GGOs refer to opacities occurring within one or multiple secondary lobules of the lung, which consist of a respiratory bronchiole, small pulmonary artery, and the surrounding tissue. [ 3 ]  A defining feature of these GGOs is the lack of involvement of the interlobular septum. Potential causes of centrilobular GGOs include pulmonary calcifications from  metastatic disease , some types of idiopathic interstitial pneumonias, hypersensitivity pneumonitis, aspiration pneumonitis, cholesterol granulomas, and  pulmonary capillary hemangiomastosis . [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3327", "text": "A  mosaic  pattern of GGO refers to multiple irregular areas of both increased attenuation and decreased attenuation on CT. It is often the result of occlusion of small pulmonary arteries or obstruction of small airways leading to air trapping. [ 6 ]  Sarcoidosis is an additional cause of a mosaic GGOs due to the formation of granulomas in interstitial areas. This may coexist with granulomatosis with polyangiitis, leading to diffuse areas of increased attenuation with ground-glass appearance. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3328", "text": "The crazy paving pattern may occur when there is both interlobular and intralobular widening. This sometimes resembles a road paved with irregular bricks or tiles. It is typically diffuse, involving larger areas of one or multiple lobes. There are a variety of potential causes, including Pneumocystis pneumonia, late-stage adenocarcinoma, pulmonary edema, some types of idiopathic interstitial pneumonias, diffuse alveolar hemorrhage, sarcoidosis, and pulmonary alveolar proteinosis. [ 6 ]  COVID-19 has also been shown to occasionally cause GGOs with a crazy paving pattern. [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3329", "text": "A halo sign refers to a GGO that fills the area around a consolidation or nodule. This is a most commonly seen in various types of pulmonary infections, including CMV pneumonia, tuberculosis, nocardia infection, some fungal pneumonias, and septic emboli. Schistosomiasis, a  parasitic  infection, also commonly presents with the halo sign. Important non-infectious causes include granulomatosis with polyangiitis, metastatic disease with pulmonary hemorrhage, and some types of idiopathic interstitial pneumonias. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3330", "text": "A reversed halo sign is a central ground-glass opacity surrounded by denser  consolidation . According to published criteria, the consolidation should form more than three-fourths of a circle and be at least 2\u00a0mm thick. [ 12 ]  It is often suggestive of  organizing pneumonia , [ 13 ]  but is only seen in about 20% of individuals with this condition. [ 12 ]  It can also be present in  lung infarction  where the halo consists of hemorrhage, [ 14 ]  as well as in infectious diseases such as  paracoccidioidomycosis ,  tuberculosis , and  aspergillosis , as well as in  granulomatosis with polyangiitis ,  lymphomatoid granulomatosis , and  sarcoidosis . [ 15 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3331", "text": "Ground-glass opacity is among the most common imaging findings in patients with confirmed  COVID-19 . [ 16 ] [ 17 ]  One systematic review found that among patients with COVID-19 and abnormal lung findings on CT, greater than 80% had GGOs, with greater than 50% having mixed GGOs and consolidation. [ 16 ]  GGOs with mixed consolidation has most often been found in elderly populations. [ 18 ] \nSeveral studies have described a pattern among initial, intermediate, and hospital discharge imaging findings in the disease course of COVID-19. Most commonly, initial CT imaging reveals bilateral GGOs at the periphery of the lungs. During initial stages, this is most often found in the lower lobes, although involvement of the upper lobes and right middle lobe has also been reported early in the disease course. [ 16 ] [ 18 ]  This is in contrast to the two similar coronaviruses,  SARS  and  MERS , which more commonly involve only one lung on initial imaging. [ 19 ] [ 20 ]  As the COVID-19 infection progresses, GGOs typically become more diffuse and often progress to consolidation. [ 11 ] [ 18 ]  This is sometimes accompanied by the development of a crazy paving pattern and interlobular septal thickening. [ 18 ]  In many cases the most severe pulmonary CT abnormalities occurred within 2 weeks after symptoms began. [ 17 ]  At this point, many individuals begin showing resolution of consolidation and GGOs as symptoms improve. However, some patients have worsening symptoms and imaging findings, with further increase in septal thickening, GGOs, and consolidation. These patients may develop lung \"white-out\" with progression to  acute respiratory distress syndrome (ARDS)  requiring treatment escalation. [ 17 ] [ 21 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3332", "text": "Preliminary reports have shown many patients have residual GGOs at time of discharge from the hospital. Due to the novelty of COVID-19, large studies investigating the long-term pulmonary CT changes have yet to be completed. However, long-term pulmonary changes have been seen in patients after recovery from SARS and MERS, suggesting the possibility of similar long-term complications in patients who have recovered from acute COVID-19 infection. [ 22 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3333", "text": "The first usage of \"ground-glass opacity\" by a major radiological society occurred in a 1984 publication of the  American Journal of Roentgenology.  It was published as part of a glossary of recommended nomenclature from the  Fleischner Society , a group of thoracic imaging radiologists. [ 23 ]  The original published definition read as: \"Any extended, finely granular pattern of pulmonary opacity within which normal anatomic details are partly obscured; from a fancied resemblance to etched or abraded glass.\" [ 23 ]  It was again included in an updated glossary by the Fleischner Society in 2008 with a more detailed definition. [ 24 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3334", "text": "In  radiology , the  halo sign  is a finding of a dark halo around the arterial lumen on  ultrasound  that suggests the diagnosis of  temporal arteritis . [ 1 ]   The standard diagnostic test for temporal arteritis is  biopsy ; however,  ultrasound  and  MRI  show promise for replacing it. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3335", "text": "The halo sign of temporal arteritis should not be confused with  Deuel's halo sign , which is a sign of  fetal  death. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3336", "text": "The halo sign is also understood as a region of ground-glass attenuation surrounding a pulmonary nodule on an  X-ray computed tomography  (CT scan) of the chest. It can be associated with  hemorrhagic   nodules ,  tumors , or  inflammatory  processes, but is most commonly known as an early  radiographic  sign of invasive  pulmonary  infection by the fungus species  Aspergillus ."}
{"_id": "WikiPedia_Radiology$$$corpus_3337", "text": "In  nursing , the halo sign is the result of a test to see if drainage from a head injury contains  cerebrospinal fluid . When a Dextrostix or Tes-Tape test gives a positive reading for glucose, the drainage must be further tested because glucose is also found in the blood. To perform the test, the leaking fluid is dripped onto a 4x4 gauze or towel. Positive results are indicated by blood coalescing into the center, leaving an outer ring of  cerebrospinal fluid ."}
{"_id": "WikiPedia_Radiology$$$corpus_3338", "text": "Hampton's hump , also called  Hampton hump , is a  radiologic sign  which consists of a shallow wedge-shaped opacity in the periphery of the  lung  with its base against the pleural surface. It is named after  Aubrey Otis Hampton , who first described it in 1940. [ 1 ]  Hampton's hump along with  Westermark sign  may aid in the diagnosis of  pulmonary embolism , although they are rare and their sensitivities and interoperator reliabilities are low. If the sign is present in an image, there is a high chance that the person has a pulmonary embolism, but when the sign is absent a pulmonary embolism is not ruled out."}
{"_id": "WikiPedia_Radiology$$$corpus_3339", "text": "Hampton's line  is a thin,  radiolucent  line seen across the neck of a  gastric ulcer  filled with  barium sulphate  during a  barium meal . It is a sign of  mucosal   edema . [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3340", "text": "It is named after  Aubrey Otis Hampton . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3341", "text": "High attenuation crescent sign  or  hyperdense crescent sign  is a radiologic sign indicating impending aortic rupture. [ 1 ] [ 2 ]  It is seen as a curvilinear area paralleling the vessel wall of the aorta. [ 3 ]  The hyperdense area is due to intramural or mural thrombus haemorrhage. The blood that dissects through mural thrombosis or wall of the aneurysm causes weakening of the wall. [ 4 ]  This is of relatively high density compared to the psoas muscle in contrast-enhanced CT and greater than the aorta in non-contrast CT imaging. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3342", "text": "The  hilum overlay sign  is an imaging appearance on  chest radiographs  in which the outline of the  hilum  can be seen at the level of a mass or collection in the mid chest. [ 1 ]  It implies that the mass is not in the middle  mediastinum , and  is either from anterior or posterior mediastinum(most of the masses arise from the anterior mediastinum). [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3343", "text": "The  holly leaf sign  is a  radiologic sign  observed on  chest radiographs  that has been used to describe the appearance of  pleural plaques  typically resulting from  asbestos  exposure. The irregular margins of a calcified pleural plaque are known to resemble the spikey edges of a holly leaf. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3344", "text": "The \"Honda sign\" ( H-pattern [ 1 ] ) is a radiologic sign seen in case of sacral insufficiency fracture in bilateral sacral insufficiency fractures on a radioisotope bone scan. [ 2 ]  It gets its name because the shape observed resembles the logo of the  Honda  motor company, resembling the alphabet \"H\"."}
{"_id": "WikiPedia_Radiology$$$corpus_3345", "text": "This sign is typically associated with bilateral fractures of the superior and inferior pubic rami. In simpler terms, it indicates a specific pattern of pelvic fractures where both the upper and lower parts of the pubic bones are fractured on both sides. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3346", "text": "While Honda sign is diagnostic of sacral insufficiency fracture, it is visible in only up to 40% of the cases. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3347", "text": "The  hot nose sign  refers to increased  perfusion  in the nasal region on nuclear medicine cerebral perfusion studies in the setting of  brain death . The absent or reduced flow in the  internal carotid arteries  is thought to lead to increased flow within the  external carotid arteries  and subsequent increased perfusion in the nasal region. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3348", "text": "A  hot quadrate sign  is an imaging appearance of increased enhancement in CT scans or MRI, or radiotracer accumulation in  nuclear medicine , in which there is enhancement of the  quadrate lobe  of the  liver . The appearance is an indirect reflection of the collateralized flow of  SVC syndrome , in which occlusion of the  superior vena cava  leads to preferential flow to the quadrate. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3349", "text": "The sign is similar in mechanism but distinct in significance from the  hot caudate sign , in which the  caudate lobe  of the liver shows preferential enhancement or radiotracer accumulation with  hepatic vein  occlusion in  Budd Chiari syndrome . In the latter, the caudate shows preferential flow because its direct drainage into the  inferior vena cava  remains unobstructed, as opposed to the remnant liver which drains into the hepatic vein. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3350", "text": "The  hotcross bun sign  is a  radiologic sign  observed on transverse T2-weighted  magnetic resonance  (MR) images of the brain, describing a cross-shaped (or cruciform) hyperintensity within the  pons . This sign is most commonly associated with the cerebellar subtype of  multiple system atrophy  (MSA-c). [ 1 ]  It is also associated with  spinocerebellar ataxia ,  progressive multifocal leukoencephalopathy ,  paraneoplastic cerebellar degeneration , and  Creutzfeldt-Jakob disease . [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3351", "text": "The  insular ribbon sign  (\"loss of the insular ribbon\") is a  radiologic sign  observed on  computed tomography of the brain  following acute  middle cerebral artery strokes . This sign describes the loss of definition between gray and white matter in the brain along the lateral margins of the  insular cortex . [ 1 ]  Loss of the insular ribbon occurs when  edema  forms in the cerebral tissue of the  ischemic  area following  cerebrovascular occlusion , [ 2 ]  obscuring the gray-white interface."}
{"_id": "WikiPedia_Radiology$$$corpus_3352", "text": "The  J-shaped sella sign  is a  radiologic sign  observed on lateral views of skull  radiographs  as the forward elongation of the  sella turcica , and its extension below the  anterior clinoid process . [ 1 ]  This abnormality causes the sella turcica to resemble the letter J. This sign is a normal variant in 5% of children, [ 1 ]  but it is also associated with  optic nerve glioma ,  hydrocephalus ,  mucopolysaccharidoses , and  achondroplasia . [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3353", "text": "Jackstone calculus  is a type of urinary tract stone characterized by its unique appearance with stippled and spiculated contour, resembling a  toy jack . [ 1 ] [ 2 ]  Jackstone calculi are composed of calcium oxalate dihydrate, which gives them their irregular shape. [ 3 ]  They are often detected in radiological investigations or cystoscopy. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3354", "text": "Juxtaphrenic peak sign  is a radiographic sign seen in lobar collapse or after  lobectomy  of the lung. [ 1 ] [ 2 ]  This sign was first described by Katten and colleagues in 1980, and therefore, it is also called Katten's sign. [ 3 ]  The juxtaphrenic peak is most commonly caused due to the traction from the inferior accessory fissure. [ 2 ] [ 4 ]  The prevalence of the juxtaphrenic peak sign increases gradually during the weeks after lobectomy of the lung. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3355", "text": "Kerley lines  are a  sign  seen on  chest radiographs  with interstitial  pulmonary edema . They are thin linear pulmonary opacities caused by fluid or cellular infiltration into the  interstitium of the lungs . They are named after Irish neurologist and radiologist  Peter Kerley . [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3356", "text": "They are suggestive for the diagnosis of  congestive heart failure , but are also seen in various non-cardiac conditions such as  pulmonary fibrosis , interstitial deposition of  heavy metal  particles or  carcinomatosis  of the lung.  Chronic Kerley B lines may be caused by fibrosis or  hemosiderin  deposition caused by recurrent  pulmonary edema ."}
{"_id": "WikiPedia_Radiology$$$corpus_3357", "text": "These are longer (at least 2cm and up to 6cm) unbranching lines coursing diagonally from the  hila  out to the periphery of the lungs. They are caused by distension of anastomotic channels between peripheral and central lymphatics of the lungs. Kerley A lines are less commonly seen than Kerley B lines. Kerley A lines are never seen without Kerley B or C lines."}
{"_id": "WikiPedia_Radiology$$$corpus_3358", "text": "These are short parallel lines at the lung periphery. These lines represent interlobular septa, which are usually less than 1 cm in length and parallel to one another at right angles to the  pleura . They are located peripherally in contact with the pleura, but are generally absent along fissural surfaces.  They may be seen in any zone but are most frequently observed at the lung bases at the  costophrenic angles  on the PA radiograph, and in the substernal region on lateral radiographs. [ 3 ]  Causes of Kerley B lines include pulmonary edema, lymphangitis carcinomatosa and malignant lymphoma, viral and mycoplasmal pneumonia, interstitial pulmonary fibrosis, pneumoconiosis, and sarcoidosis.  They can be an evanescent sign on the chest x-ray of a patient in and out of heart failure."}
{"_id": "WikiPedia_Radiology$$$corpus_3359", "text": "These are the least commonly seen of the Kerley lines. They are short, fine lines throughout the lungs, with a reticular appearance. They may represent thickening of anastomotic lymphatics or superimposition of many Kerley B lines."}
{"_id": "WikiPedia_Radiology$$$corpus_3360", "text": "Klemm's sign , also known as  air cushion sign , [ 1 ]  is a sign of chronic appendicitis."}
{"_id": "WikiPedia_Radiology$$$corpus_3361", "text": "Knuckle sign  is a radiologic sign used for diagnosing  pulmonary embolism . [ 1 ] [ 2 ]  The presence of a blood clot in the branch of a pulmonary artery can resemble a knuckle in CT and X-ray images, which is why it is called knuckle sign. [ 3 ]  It is frequently seen along with other signs of pulmonary embolism, such as the  Fleischner sign  and  Westermark sign . [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3362", "text": "Leadpipe colon  is a term used in radiology to describe a specific, characteristic appearance of the colon, typically seen on barium enema radiographs. The term is associated with a rigid, non-distensible colon that has lost its normal  haustral  folds, presenting a smooth, tubular, or \"pipe-like\" appearance. [ 1 ]  This condition is most commonly linked to chronic  ulcerative colitis  and other forms of  inflammatory bowel disease ."}
{"_id": "WikiPedia_Radiology$$$corpus_3363", "text": "In the leadpipe colon appearance, the colon appears straight and narrowed, with the absence of the usual haustral folds. Haustral folds are typically seen in the colon as segmental pouches or folds that help segment the large bowel. In leadpipe colon, these folds are obliterated or flattened, resulting in a smooth appearance. The colon takes on a rigid, tubular form, similar to a pipe, which is where the term \"leadpipe\" comes from, likening the colon to the appearance of a lead pipe. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3364", "text": "The classic leadpipe colon appearance is best observed on  barium enema  studies, a type of contrast X-ray imaging. During a barium enema, a contrast agent (barium sulfate) is introduced into the colon, and X-ray images are taken. In a leadpipe colon, the following features are seen: [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3365", "text": "The  licked candy stick appearance  is a  radiologic sign  observed on  bone radiographs  that refers to the tapering of the tips of the hand bones ( metacarpals  and  phalanges ), foot bones ( metatarsals ), or  clavicles  that occurs in conditions such as  psoriatic arthritis ,  rheumatoid arthritis , and  leprosy . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3366", "text": "The  light bulb sign  is a radiological finding observed on plain radiographs in the context of posterior  shoulder dislocation . [ 1 ]  It refers to the abnormal, rounded appearance of the humeral head, which resembles a \"light bulb,\" due to internal rotation of the arm following dislocation. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3367", "text": "In posterior shoulder dislocation, the humeral head is displaced posteriorly out of the glenoid cavity. This injury is frequently associated with internal rotation where the humeral head rotates internally, altering its usual elliptical contour to a more rounded shape, creating the \"light bulb\" appearance. On anteroposterior (AP) radiographs, the humeral head no longer overlaps the glenoid, further emphasizing its abnormal shape."}
{"_id": "WikiPedia_Radiology$$$corpus_3368", "text": "Posterior shoulder dislocations typically result from trauma such as seizures or electric shocks, which cause forceful contraction of the internal rotator muscles of the shoulder. [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3369", "text": "The light bulb sign is best observed on an AP radiograph of the shoulder. [ 5 ]  Key features include:"}
{"_id": "WikiPedia_Radiology$$$corpus_3370", "text": "Radiologic signs  are the signs used for diagnosing physiological and pathological conditions in radiologic images. This list includes the names of radiologic signs in alphabetical order."}
{"_id": "WikiPedia_Radiology$$$corpus_3371", "text": "The  maiden waist deformity  is a  radiologic sign  associated with  retroperitoneal fibrosis , a condition resulting from the abnormal proliferation of fibrous tissue in the  retroperitoneal space . The fibrosis can extend to adjacent anatomical structures, frequently encompassing and obstructing the  ureters . [ 1 ]  This sign refers to the alteration in the normal course of the ureters: when the fibrosis causes both ureters to be pulled medially, they may form the appearance of a \"narrow-waisted maiden\". [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3372", "text": "Mathe's sign  is an  ultrasonographic  sign that suggests the existence of an  abscess  in the proximity of a  kidney . Normally during  inspiration  when standing, the kidneys move  distally  to some extent. When one of them does not move at all or moves downwards scarcely, either in erect position or deep inspiration, the test is called positive. Along with  fever ,  urinary  symptoms, and  costovertebral angle tenderness , this will almost always indicate a  perinephric   abscess . [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 5 ] [ better\u00a0source\u00a0needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3373", "text": "Mediastinal shift  is an abnormal movement of the  mediastinal structures  toward one side of the  chest cavity . A shift indicates a severe imbalance of pressures inside the chest. [ 1 ]  Mediastinal shifts are generally caused by increased lung volume, decreased lung volume, or abnormalities in the pleural space. Additionally, masses inside the mediastinum or musculoskeletal abnormalities can also lead to abnormal mediastinal arrangement. [ 2 ]  Typically, these shifts are observed on x-ray but also on computed tomography (CT) or magnetic resonance imaging (MRI). On chest x-ray,  tracheal deviation , or movement of the trachea away from its midline position can be used as a sign of a shift. Other structures, like the heart, can also be used as reference points. [ 3 ] [ 4 ]  Below are examples of pathologies that can cause a mediastinal shift and their appearance."}
{"_id": "WikiPedia_Radiology$$$corpus_3374", "text": "Tension pneumothorax is an emergent condition in which air gets trapped in the space between the chest wall and the lung. This space is referred to as the pleural space. Because air can't escape from this space, the air pocket grows larger and larger, resulting in the lung collapse closest to the pneumothorax. Forces are transmitted to the mediastinum and effectively \"push\" the mediastinal structures to the opposite side of the chest. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3375", "text": "A pleural effusion is an accumulation of fluid inside the pleural space. If this collection of fluid gets large enough, it can also push structures in the chest away from it and cause a mediastinal shift. However, a pleural effusion can also pull the mediastinal structure towards itself. If this is the case, then there is an underlying condition causing the collapse of the lung on that side. An example is a tumor obstructing a bronchus and causing lung collapse and pleural effusion. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3376", "text": "Hemothorax, or accumulation of blood in the pleural space, can result from trauma or surgical procedures in the chest. This accumulation of blood can grow large enough to compress the lung and push away other structures in the chest, thus causing a mediastinal shift. [ 6 ]  On a chest x-ray, a hemothorax can appear similarly to a pleural effusion with blunting of the pleural recess and white out of normal lung zones. [ 7 ]  In the setting of traumatic chest injury, rib fractures are also commonly observed on x-ray. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3377", "text": "An empyema is a collection of pus inside the pleural cavity. It is a complication of pneumonia or thoracic injury or surgery and also requires urgent diagnosis and treatment. [ 9 ]  Radiographic appearance is similar to that of a pleural effusion with costophrenic angle blunting and white out of lung zones. CT imaging is necessary to evaluate the structure of the empyema and evaluate for loculation or separation of the pus into different compartments. [ 10 ]  Finally, ultrasound is becoming a more commonly used imaging technique to evaluate an empyema. Ultrasound is more readily available at the bedside, is better at detecting pleural effusion, and can be used to guide thoracentesis to remove the empyema. [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3378", "text": "Masses such as tumors can also cause compression and displacement of mediastinal structures. There are various mediastinal tumors, and they are classified by their location in the chest. Notable examples include germ cell tumors and lymphomas. [ 12 ]  Teratomas are a class of germ cell tumors that arise in the chest due to failure of germ cell migration during development. They can expand to large sizes and cause hemoptysis and pleural effusion. Radiographic features of teratomas typically include fluid and fat but also muscle, teeth, and bones inside the mass. [ 13 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3379", "text": "Atelectasis is the partial collapse of a lung that is reversible. There are numerous etiologies, including post-operative atelectasis, surfactant deficiency, mucus plugging, and foreign body aspiration. Notably, post-operative atelectasis is thought to be caused by general anesthesia administration. Collapse of the affected lung shifts mediastinal structure towards the same side and can be observed on chest x-ray or CT. Radiographic features include increased opacification of collapsed lung and/or tracheal shift. [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3380", "text": "Fetal conditions can also cause a mediastinal shift during development. For example, pulmonary hypoplasia is the underdevelopment of a lung due to various etiologies. These include agenesis due to gene mutation, fetal hydrothorax, and congenital diaphragmatic hernia. These conditions lead to incomplete development of lung tissue or hypoplasia. This can be unilateral or bilateral and is seen on x-ray as a mediastinal shift towards the side of the underdeveloped lung. [ 15 ] [ 16 ]  Additionally, mediastinal shifts can also be detected using antenatal ultrasonography. [ 17 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3381", "text": "This condition is often called \"funnel chest\" and is observed as depression of the anterior chest at the xiphisternum. Pectus excavatum is commonly unilateral and, therefore, can lead to asymmetric distribution of thoracic organs. Therefore, a mediastinal shift can be seen in severe cases.  Radiographic features include a leftward deviation of the heart and deformed third to seventh ribs. Patients often present with exercise tolerance, cardiac arrhythmias, and heart murmur. [ 18 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3382", "text": "A pneumonectomy is a surgical procedure in which an entire lung is removed. A common reason for performing this procedure is for lung cancer originating in the lung itself. [ 19 ]  This leads to a mediastinal shift towards the empty side of the thorax. Notably, patients can experience post pneumonectomy syndrome due to a severe mediastinal shift. This presents as difficulty breathing due to a shift of airways and rotation of the heart and great vessels. On x-ray, white out of the operated side and hyperinflation of the remaining lung is often observed. [ 20 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3383", "text": "Foreign body aspiration is a major cause of death in young children due to their underdeveloped swallowing coordination. Young children most commonly ingest toys, coins, or food. [ 21 ]  On chest x-ray, the most frequent sign is air trapping that can lead to a mediastinal shift. Atelectasis and pneumothorax may also occur in the setting of foreign body aspiration. The diagnosis is made in conjunction with clinical symptoms and confirmed and treated with bronchoscopy. [ 22 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3384", "text": "Bullous emphysema is a condition seen in patients with chronic obstructive pulmonary disease (COPD). The units making up the substructure of the lung (alveoli) become permanently enlarged due to the destruction of their walls. This leads to hyperinflation of the alveoli and, thus, the lungs. When this occurs asymmetrically, one lung can be larger than the other. [ 23 ]  A severe variant of this condition is called giant bullous emphysema. On chest x-ray, one lung will be significantly more inflated than the other, causing a mediastinal shift. Bullous emphysema's radiographic appearance on x-ray mimics a tension pneumothorax. This presents a medical challenge as these diseases are treated differently despite appearing similarly on x-ray. [ 24 ] [ 25 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3385", "text": "Congenital pulmonary airway malformation (CPAM) is a rare disease in which the lung airways develop abnormally in the fetus. This leads to infants having pockets of air and cystic masses in their lungs. These can expand in size and cause a mediastinal shift, especially in the higher grades of CPAM. Diagnosis is usually made on ultrasound and supplemented with x-ray, CT, or MRI to further define the malformation. On chest x-ray, CPAM has varying appearances but may look like \"bubbles\" within the lung fields. [ 26 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3386", "text": "Mercedes Benz sign  is a radiological sign seen due to the presence of  gallstones . [ 1 ]  It is a triradiate shadow, characteristic of the  Mercedes-Benz  automobile trademark. [ 2 ]  The sign occurs due to the gas fissuring within the gallstone."}
{"_id": "WikiPedia_Radiology$$$corpus_3387", "text": "Mumoli's sign  (also known as a  \" Playboy Rabbit \" sign ) is a  radiologic sign  seen in the normal  liver . It appears as a rabbit-shaped image caused by the confluence of the middle and right  hepatic veins  as they merge with the  inferior vena cava . It can be seen on  ultrasound images  of the  liver  with a transverse subcostal view during deep  inspiration ."}
{"_id": "WikiPedia_Radiology$$$corpus_3388", "text": "The image was named after Nicola Mumoli of the Department of  Internal Medicine , Livorno Hospital, Livorno, Italy. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3389", "text": "The  Napoleon hat sign  (most commonly called \" inverted Napoleon hat \") is a radiologic sign observed on frontal  radiographs  of the  spine  at the level of the fifth  lumbar vertebra  (L5) and the  sacrum  (S1) that indicates the presence of severe  spondylolisthesis  and/or severe  lumbar lordosis . When the L5 vertebra becomes severly displaced and overlaps the sacrum, the superimposed bones may appear as an inverted  Napoleon  hat (the L5 vertebral body represents the dome of the hat and the transverse processes represent the brim). [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3390", "text": "Notching of the ribs  (or  rib notching ) is a  radiologic sign  where the surface of the rib is deformed. It can be characterized as unilateral or bilateral, and should be differentiated between affecting the upper (superior) or lower (inferior) surface of the rib."}
{"_id": "WikiPedia_Radiology$$$corpus_3391", "text": "Inferior rib notching can be associated with  aortic coarctation  (as a result of dilatation of  intercostal arteries [ 1 ] ),  superior vena caval obstruction ,  arteriovenous fistula , or following a  Blalock Taussig shunt ."}
{"_id": "WikiPedia_Radiology$$$corpus_3392", "text": "Causes of inferior rib notching by etiology:"}
{"_id": "WikiPedia_Radiology$$$corpus_3393", "text": "Arterial :  aortic coarctation , aortic thrombosis, pulmonary-oligemia/arteriovenous malformation,  Blalock Taussig shunt ,  Tetralogy of fallot  (TOF), absent pulmonary artery and pulmonary stenosis."}
{"_id": "WikiPedia_Radiology$$$corpus_3394", "text": "Venous : arteriovenous malformations of chest wall, superior vena cava or other central venous obstruction."}
{"_id": "WikiPedia_Radiology$$$corpus_3395", "text": "Neurogenic : intercostal neuroma,  Neurofibromatosis type 1 ,  poliomyelitis ."}
{"_id": "WikiPedia_Radiology$$$corpus_3396", "text": "Osseous :  hyperparathyroidism ,  thalassemia ,  Melnick\u2013Needles syndrome . [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3397", "text": "Other causes of superior rib notching include:  poliomyelitis ,  osteogenesis imperfecta ,  neurofibromatosis ,  Marfan's syndrome ,  collagen vascular disease , and  hyperparathyroidism ."}
{"_id": "WikiPedia_Radiology$$$corpus_3398", "text": "Omental cake  is a  radiologic sign  indicative of an abnormally thickened  greater omentum . [ 1 ]  It refers to  infiltration  of the normal omental structure by other types of soft-tissue or chronic  inflammation  resulting in a thickened, or cake-like appearance. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3399", "text": "Typically, it is caused by infiltration of  metastatic   tumors  arising from the  stomach ,  ovary , or  colon . This dissemination of cancerous cells that do not originate from the omentum itself is called  peritoneal carcinomatosis . It can occur other regional tumors such as  lymphoma  where it is associated with regional  lymphadenopathy . [ 3 ]  It can also rarely occur as a result of infectious causes such as  tuberculous   peritonitis , peritoneal  coccidioidomycosis , and  histoplasmosis . [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3400", "text": "For the most common cause,  peritoneal carcinomatosis , omental caking is associated with a wide variety of symptoms.  Ascites  and intestinal  peristalsis  is known to have an effect on how diffusely the cancer cells are spread throughout the abdomen. This wide range of presentation makes omental caking difficult to diagnose based on symptoms alone. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3401", "text": "In patients with omental caking due to peritoneal lymphomatosis secondary to cancers such as  Non-Hodgkin's lymphoma  or  MALT lymphoma , the most frequent symptoms encountered are abdominal pain, gastric distention, and weight loss. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3402", "text": "Causes such as bacterial and fungal infections are associated with diffuse abdominal pain, intraperitoneal fluid accumulation, weight loss, fevers, and night sweats. The most common radiographic feature among patients with suspected tuberculous peritonitis was septated compartments of ascitic fluid on ultrasound and abnormal chest X-ray suggestive of previous tuberculosis. [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3403", "text": "Due to the variety of symptoms experienced by patients with omental caking, [ 5 ]  omental cakes are most frequently discovered on abdominal  computed tomography (CT)  or  ultrasound . Plain film radiography ( X-ray ) is not a suggested modality for investigating the spread of cancerous cells in the abdomen due to the poor spatial resolution amongst soft-tissue densities. Contrast resolution obtained through CT allows radiologists to investigate omental caking for morphology, intraperitoneal fluid, and regional lymphadenopathy assists in proper diagnosis so clinicians, surgeons, and oncologists can plan the appropriate course of treatment. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3404", "text": "After omental cakes have been identified on CT or ultrasound, it may be appropriate to gain more information on the characteristics of the disease by undergoing  nuclear medicine  scans that can identify tissues where the cancerous cells may have spread [ 9 ]  or  magnetic resonance imaging  (MRI) for a higher degree of spatial resolution. [ 10 ]  Suspected infectious etiologies may require another degree of medical testing including blood antigen or antibody analysis. [ 11 ]  Yet, in both malignant and infectious cases, image-guided  biopsy  with pathologic correlation is the most definitive way to confirm the diagnosis.  [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3405", "text": "The presence of omental cakes have long been seen as an indication of poor prognosis in patients with advanced-stage ovarian or gastrointestinal cancer, and medical teams usually address this through more advanced and aggressive treatments such as  cytoreductive surgery  and  hyperthermic-intraperitoneal chemotherapy  (HIPEC). [ 12 ]  During surgery, the presence of omental caking makes incomplete resection more likely. [ 13 ]  In patients where omental spread is completely removed, intestinal resections are more likely to be encountered due to the caked omentum's propensity for spreading malignancy to adjacent organs. [ 13 ] [ 14 ]  If malignant, as patients undergo treatment they are likely to undergo routine nuclear medicine imaging as surveillance for response to the treatment or recurrence of disease. [ 15 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3406", "text": "Common disease presentations that are different but may appear similar include  pseudomyxoma peritonei , peritoneal  mesothelioma ,  splenosis  in patients with a history of  splenectomy , and diffuse peritoneal  leiomyomatosis. [ 16 ]  These diagnoses should be considered in patients with suspected omental caking and a history that makes malignant or infectious causes less likely. Image-guided biopsy with pathologic correlation is the gold-standard method for distinguishing these entities. [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3407", "text": "Omental cakes have long been described during malignancy-related surgical interventions. In 1985, Drs. Stephen Rubesin and Marc Levine were the first to publish a radiographic review of omental caking and to describe the propensity for omental spread to facilitate colonic  metastases  due to the proximity of the greater omentum to bowel. [ 14 ]  Since then, many radiologists have adopted techniques to investigate omental thickening and irregularities in density using the  Hounsfield scale  and other radiographic tools to determine the extent of abdominal disease. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3408", "text": "Onion skin periosteal reaction  also known as  multilayered periosteal reaction  or  lamellated periosteal reaction  refers to the multi layered concentric layers of new bone adjacent to the bone cortex. It is called onion skin periosteal reaction because it resembles the layers of an onion. These layers are formed due to any pathological process that leads to the variable, excessive growth of the bone. [ 1 ]  Onion skin periosteal reaction is seen in  osteosarcoma , [ 2 ]   Ewing sarcoma  and  Langerhans cell histiocytosis . [ 3 ]  In radiological images, onion skin periosteal reaction is seen as radiolucent areas along the multiple layers of dense bone. [ 4 ]  The lucent areas may be occupied by tumors or inflammation."}
{"_id": "WikiPedia_Radiology$$$corpus_3409", "text": "This article related to  pathology  is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Radiology$$$corpus_3410", "text": "Osteopathia striata  is a rare entity characterized by fine linear striations about 2- to 3-mm-thick, visible by  radiographic  examination, in the metaphyses and diaphyses of long or flat bones. [ 1 ]  It is often asymptomatic, and discovered incidentally most of the time."}
{"_id": "WikiPedia_Radiology$$$corpus_3411", "text": "Palla's sign  is a  clinical sign  in which an enlarged right descending  pulmonary artery  is seen on the  chest x-ray  in patients with  pulmonary embolism . It is of low  sensitivity , and its specificity is not known. It exhibits as a \"sausage\" appearance on X-ray.  [ 1 ]  It is named after italian radiologist Antonio Palla. In 1983, he published his observations that close to 25% of patients with pulmonary embolism had a chest x-ray sign of enlarged right descending pulmonary artery. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3412", "text": "Pancake kidney  (also known as disc, shield or doughnut kidney [ 1 ] ) is a rare anomaly of the kidney with complete fusion of the superior, mild and inferior poles of both kidneys. The kidney is seen as a single, disc-shaped mass typically located in the pelvis. [ 2 ]  Each kidney has its own ureter that does not cross the midline. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3413", "text": "Pancake kidney is often associated with anomalies in other organs. Those with pancake kidneys are susceptible to urinary tract infections and renal stones due to anomalies in the collecting system of the kidneys and the short ureters. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3414", "text": "Ultrasound may initially suggest the condition, but computed tomography or magnetic resonance imaging provides a definitive diagnosis. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3415", "text": "Pencil-in-cup  is a radiologic sign indicating a deformity where fingers have the appearance of a pencil lying in a cup. [ 1 ] [ 2 ] [ 3 ]  This sign is classically seen in psoriatic arthritis, but it is also reported in systemic sclerosis and rheumatoid arthritis. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3416", "text": "Peribronchial cuffing , also referred to as  peribronchial thickening  or  bronchial wall thickening , is a  radiologic sign  which occurs when excess fluid or  mucus  buildup in the small airway passages of the  lung  causes localized patches of  atelectasis  (lung collapse). [ 1 ]  This causes the area around the  bronchus  to appear more prominent on an  X-ray . It has also been described as donut sign, considering the edge is thicker, and the center contains air."}
{"_id": "WikiPedia_Radiology$$$corpus_3417", "text": "Peribronchial cuffing is seen in a number of conditions including:"}
{"_id": "WikiPedia_Radiology$$$corpus_3418", "text": "As peribronchial cuffing is a sign rather than a symptom or condition, there is no specific treatment except to treat the underlying cause."}
{"_id": "WikiPedia_Radiology$$$corpus_3419", "text": "Pneumatosis intestinalis  (also called  intestinal pneumatosis ,  pneumatosis cystoides intestinalis ,  pneumatosis coli , or  intramural bowel gas ) is  pneumatosis  of an  intestine , that is, gas  cysts  in the bowel wall. [ 1 ] [ 2 ]  As a  radiological sign  it is highly suggestive for  necrotizing enterocolitis . This is in contrast to gas in the  intestinal lumen  (which is relieved by  flatulence ). In  newborns , pneumatosis intestinalis is considered  diagnostic  for necrotizing enterocolitis, and the gas is produced by bacteria in the bowel wall. [ 3 ]  The pathogenesis of pneumatosis intestinalis is poorly understood and is likely multifactorial.  PI itself is not a disease, but rather a clinical sign.  In some cases, PI is an incidental finding, whereas in others, it portends a life-threatening intra-abdominal condition. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3420", "text": "The  polka dot sign  is a radiological finding most commonly observed on axial computed tomography (CT) or magnetic resonance imaging (MRI) scans of the spine. [ 1 ]  It is a hallmark feature of  vertebral hemangiomas , a benign vascular tumor of the vertebral body. The sign refers to the appearance of multiple small, dot-like areas of sclerosis or hyperintensity within the vertebral body, resembling a pattern of polka dots. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3421", "text": "The polka dot sign arises due to the unique structural changes in vertebral hemangiomas. These changes include thickened vertical trabeculae, where the they apepar as small, discrete dots in axial imaging. There is also vascular proliferation and fat deposition that replaces normal bone marrow. This contributes to the mixed-density appearance of the lesion. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3422", "text": "The polka dot sign is best seen in CT imaging as multiple small, circular, sclerotic areas are seen within the vertebral body, representing cross-sections of the thickened vertical trabeculae. The background may appear lucent or hypodense due to vascular spaces and fat replacement. [ 2 ]  The sagittal view may demonstrate the  corduroy sign , which represents vertically oriented striations corresponding to the thickened trabeculae. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3423", "text": "Popcorn calcification  or  popcorn appearance  is the radiological appearance of  calcification  with irregular rings and arcs, which resembles  popcorns . The calcification patterns in chondroid lesions of the bone (such as  enchondroma  and  chondrosarcoma ), [ 1 ]   pulmonary hamartomas , [ 2 ]  degenerating fibroadenomas of the breast and calcified fibroids of the uterus have been described as 'popcorn calcification'. \nIn  osteogenesis imperfecta , popcorn calcifications are often seen around the knees and ankles in radiological imaging, and are associated with irregularity in the growth plate of the bone. [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3424", "text": "A  pulmonary consolidation  is a region of normally compressible  lung tissue  that has filled with liquid instead of air. [ 1 ]  The condition is marked by induration [ 2 ]  (swelling or hardening of normally soft tissue) of a normally aerated lung. It is considered a  radiologic sign . Consolidation occurs through accumulation of inflammatory cellular exudate in the  alveoli  and adjoining ducts. The liquid can be  pulmonary edema , inflammatory  exudate ,  pus , inhaled water, or blood (from bronchial tree or  hemorrhage  from a  pulmonary artery ). Consolidation must be present to diagnose  pneumonia : the signs of lobar pneumonia are characteristic and clinically referred to as consolidation. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3425", "text": "Signs that consolidation may have occurred include:"}
{"_id": "WikiPedia_Radiology$$$corpus_3426", "text": "Putty kidney  is a radiological term describing a calcified kidney typically seen in the end stages of chronic  renal tuberculosis . The term \"putty kidney\" derives from the radiographic appearance of extensive amorphous calcification within the kidney, resembling the consistency of putty. This finding is a hallmark of advanced genitourinary tuberculosis, which is one of the types of extrapulmonary tuberculosis. The term 'putty kidney' was first used in 1906 by Dr. F Tilden Brown, a genitourinary surgeon. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3427", "text": "Putty kidney represents the late-stage sequelae of renal tuberculosis, which results from hematogenous dissemination of  Mycobacterium tuberculosis  to the kidneys. Chronic inflammation and granuloma formation lead to: [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3428", "text": "The advanced calcified state of a putty kidney is associated with a loss of renal function and often coexists with damage to the ureters and bladder. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3429", "text": "Dense, amorphous calcifications occupying the renal region. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3430", "text": "The  pyloric tit sign  is a radiological finding observed during barium studies in cases of hypertrophic pyloric stenosis. [ 1 ]  It appears as an outpouching on the lesser curvature of the stomach, just proximal to the impression created by the hypertrophied pyloric muscle. This sign represents the transient entrapment of contrast medium between a peristaltic wave and the thickened pyloric muscle. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3431", "text": "Rice grain calcification  is a distinctive radiological finding characterized by the presence of small, elongated, or oval calcific foci resembling grains of rice. This pattern of calcification is typically observed in soft tissues and is associated with certain infectious or inflammatory conditions. It is most commonly linked to  cysticercosis , a parasitic infection caused by the larval form of  Taenia solium . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3432", "text": "In cysticercosis, the calcifications represent the remnants of degenerated larvae of  Taenia solium . When the larvae die, they become calcified over time, forming the characteristic rice grain-like appearance. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3433", "text": "Rigler's triad  is a combination of findings on an  abdominal radiograph  of people with  gallstone ileus , a condition where a large  gallstone  causes  bowel obstruction . Rigler's triad consists of: (1) small bowel obstruction, (2) a gallstone outside the  gallbladder , and (3)  air in the bile ducts . [ 1 ]  It bears the name of  Leo George Rigler  (1896\u20131979), who described it in 1941. [ 2 ] [ 3 ]  It is not the same as  Rigler's sign ."}
{"_id": "WikiPedia_Radiology$$$corpus_3434", "text": "It is most commonly seen in 6th to 7th decade of life and affects females more often. Most patients with gallstone ileus are  asymptomatic . Due to the fistula formation between the  small intestine  and gallbladder, large stones can lodge in the small bowel, leading to its obstruction.  Pneumobilia means air in the biliary tract. It is due to the transfer of air from bowel through the  fistula  into the biliary tract. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3435", "text": "A  ring-enhancing lesion  is an abnormal  radiologic sign  on  MRI  or  CT scans  obtained using  radiocontrast . On the image, there is an area of decreased density (see  radiodensity ) surrounded by a bright rim from concentration of the enhancing contrast dye. This enhancement may represent breakdown of the blood-brain barrier and the development of an inflammatory capsule. This can be a finding in numerous disease states. In the brain, it can occur with an early  brain abscess  as well as in  Nocardia  infections associated with lung cavitary lesions. In patients with HIV, the major differential is between  CNS lymphoma  and CNS  toxoplasmosis , with CT imaging being the appropriate next step to differentiate between the two conditions. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3436", "text": "In  radiology , a  Romanus lesion  is the erosion of the anterior and posterior vertebral endplates in patients with an inflammatory  spondyloarthropathy  \u2013 such as  ankylosing spondylitis  or an  enteropathic arthropathy . [ 1 ] [ 2 ]  The anterior erosion in particular causes a loss of anterior vertebral body concavity, causing the vertebra to display a squared contour or even a barrel-shape. [ 1 ]  Healing of the erosion results in a  sclerotic  increase in density causing what is known as a  shiny corner sign , [ 1 ] [ 3 ]  which can later result in  syndesmophyte  formation. [ 4 ]  It is most easily diagnosed using  MRI , compared to conventional radiography. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3437", "text": "This type of erosion was initially described by Ragnar Romanus and Sven Yd\u00e9n in a paper published in 1952. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3438", "text": "On a  chest X-ray , the  sail sign  is a  radiologic sign  that suggests  left lower lobe   collapse . [ 1 ]  In children, however, a sail sign could be normal, reflecting the shadow of the  thymus . [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3439", "text": "The  thymic sail sign  or  spinnaker-sail sign  is due to elevation of the thymic lobes in the setting of  pneumomediastinum . [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3440", "text": "Sandwich vertebral body  is a radiologic sign where the endplates of the vertebra are sclerotic, giving it the appearance of a sandwich. [ 1 ] [ 2 ]  This sign is seen in  osteopetrosis , particularly in the autosomal dominant variety. [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3441", "text": "Scottie dog sign  is a  radiological sign  which refers to the appearance of lumbar spine in oblique view X-ray. [ 1 ]  In the X-ray, the spine can be visualised as the lateral view of a  Scottie dog , [ 2 ]  with the pedicle as the eye, the transverse process as the nose, the superior articular facet as the ear and the inferior articular facet as the front leg, spinous process as the body. It was once used as a diagnostic sign for lumbar spondylolysis, but it is not commonly in use nowadays because of the advent of more sensitive diagnostic methods such as the  CT scan  and  MRI scan . [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3442", "text": "A  sentinel loop  is a  sign  seen on a radiograph that indicates localized  ileus  from nearby inflammation. [ 1 ]  Simply put, it is the dilation of a segment of  small intestine  to be differentiated from  colonic cutoff sign  which is a dilation of a segment of large bowel. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3443", "text": "An isolated distended loop of bowel is seen near the site of injured viscus or inflamed organ. This loop is called a \"sentinel loop.\" It arises from the body's efforts to localize traumatic or inflammatory lesions. The local distention of that intestinal loop is due to local paralysis and accumulation of gas in the intestinal loop. In acute  pancreatitis , the sentinel loop is usually seen in the left  hypochondrium , while in acute  cholecystitis , it is seen in the right hypochondrium. In acute  appendicitis , the sentinel loop is seen in the  right lower quadrant . [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3444", "text": "In  radiology , the  silhouette sign  refers to the loss of normal borders between  thoracic structures . [ 1 ]  It is usually caused by an  intrathoracic   radiopaque mass  that touches the border of the  heart  or  aorta . [ 2 ]  In other words, it is difficult to make out the borders of a particular structure - normal or otherwise - because it is next to another dense structure, both of which will appear white on a standard  X-ray . [ 3 ]  It may occur, for example, in  right middle lobe syndrome , where the right heart margin is obscured, and in  right lower lobe   pneumonia , where the border of the  diaphragm  on the right side is obscured, while the right heart margin remains distinct. [ 2 ] \nSilhouette sign is very useful in localizing lung lesions as all structures forming cardiac silhouette are in contact with a specific portion of the lung."}
{"_id": "WikiPedia_Radiology$$$corpus_3445", "text": "The  small bowel feces sign  is a radiological finding observed in radiological imaging studies, particularly in cases of  small bowel obstruction . [ 1 ]  It is characterized by the presence of particulate matter resembling fecal material within the lumen of dilated small bowel loops. This sign is most commonly identified on  computed tomography  (CT) scans and, less frequently, on abdominal radiographs. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3446", "text": "The small bowel feces sign results from stagnation of enteric contents within dilated segments of the small intestine. [ 1 ]  When intestinal motility is impaired due to obstruction, progressive dehydration of luminal contents occurs, leading to the formation of solid particulate matter that mimics feces. [ 3 ]  This sign often indicates a chronic or subacute obstruction where bowel function is severely compromised. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3447", "text": "The composition of the particulate matter includes partially digested food, desquamated epithelial cells and mucus, giving it the characteristic heterogeneous appearance resembling colonic feces. This radiological finding suggests that the obstruction has persisted long enough to allow for these changes to occur. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3448", "text": "On CT imaging, the small bowel feces sign appears as a mottled, mixed-density pattern within a distended small bowel loop. It is typically located proximal to the site of obstruction and is often accompanied by other features of small bowel obstruction, such as: [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3449", "text": "On plain radiographs, it may be difficult to discern this sign definitively due to its lower resolution and 2D view, compared to CT which has higher resolution and 3D orientation."}
{"_id": "WikiPedia_Radiology$$$corpus_3450", "text": "A  Sonographic Murphy sign  is a finding when performing diagnostic medical  sonography . It is different from the  Murphy sign  found on physical examination, but both signs are associated with  cholecystitis [ 1 ]  When the sonographer presses directly over the  gallbladder , and the  patient  expresses  pain , more than when the sonographer presses anywhere else, this is said to be a positive sonographic Murphy sign. [ 2 ] [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3451", "text": "A Sonographic Murphy sign is different from a Murphy sign on physical examination of the abdomen in three ways:"}
{"_id": "WikiPedia_Radiology$$$corpus_3452", "text": "In  radiology , the  steeple sign  is a  radiologic sign  found on a frontal neck  radiograph  where  subglottic   tracheal  narrowing produces the shape of a  church   steeple  within the trachea itself. [ 1 ] [ 2 ]  The presence of the steeple sign supports a  diagnosis  of  croup , usually caused by  paramyxoviruses . [ 3 ]  It can also be defined as the replacement of the usual squared-shoulder appearance of the subglottic area by cone-shaped narrowing just distal to the vocal cords. This is called the steeple or pencil-point sign."}
{"_id": "WikiPedia_Radiology$$$corpus_3453", "text": "The  stepladder sign  is a radiological finding observed in the context of small bowel obstruction on abdominal X-rays or computed tomography scans. It refers to the appearance of multiple, dilated small bowel loops arranged in a step-like configuration, typically visible in upright or lateral decubitus imaging positions. This sign is indicative of bowel obstruction and is used to identify and localize the site of obstruction, aiding in diagnosis and management. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3454", "text": "In small bowel obstruction, a mechanical or functional blockage prevents normal passage of intestinal contents leading to increased peristaltic effort in the dilated loops causing bowel loops proximal to the obstruction to dilate. Gas and fluid accumulates proximal to the obstruction. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3455", "text": "Teacup calcifications , also known as the \" teacup sign ,\" are a specific  radiologic sign  indicative of benign breast conditions, particularly milk of calcium within cysts. [ 1 ]  These calcifications exhibit a distinctive appearance on mammography, helping radiologists in distinguishing benign entities from malignant ones."}
{"_id": "WikiPedia_Radiology$$$corpus_3456", "text": "When horizontal x-ray beams, commonly used in lateral projections, are used to image the breast, the fluid inside the cysts, such as milk of calcium, is imaged tangentially. [ 2 ]  This technique often produces linear or curvilinear patterns of calcification. In some cases, a semilunar shape may appear, which is why this sign is called \"teacup sign.\""}
{"_id": "WikiPedia_Radiology$$$corpus_3457", "text": "Teacup calcifications are typically benign and do not require follow up or sampling, per the  American College of Radiology  BI-RADS recommendation. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3458", "text": "In  radiology , the  Terry-Thomas sign  is a  scapholunate ligament  dissociation on an  anteroposterior  view of the wrist. [ 1 ] [ 2 ]  Most commonly a result of a fall on the outstretched hand ( FOOSH ), the  scapholunate ligament  ruptures resulting in separation of the  lunate  and  scaphoid bones . This burst causes the  scaphoid bone  to dorsally rotate. [ 3 ]  A gap of more than 3mm is  pathognomonic  for scapholunate dissociation. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3459", "text": "The resulting separation between the scaphoid and lunate bones leaves a space on the x-ray that is similar to the gap comedian  Terry-Thomas  had between his front teeth. For newer radiology students who do not know who Terry-Thomas was, this finding might also be known as the  David Letterman  sign. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3460", "text": "In  radiology , the  thumbprint sign , or  thumbprinting , is a  radiologic sign  found on a radiograph that suggests the diagnosis of either  epiglottitis  or  intestinal ischemia ."}
{"_id": "WikiPedia_Radiology$$$corpus_3461", "text": "In a  lateral   C-spine   radiograph , the sign is caused by a thickened free edge of the  epiglottis , which causes it to appear more  radiopaque  than normal, resembling the distal  thumb ."}
{"_id": "WikiPedia_Radiology$$$corpus_3462", "text": "In an abdominal  radiography , thumbprinting has an appearance of thumbs protruding into the  intestinal lumen , and is caused by thickened  edematous   mucosal folds . [ 1 ]  Abdominal thumbprinting is a  non-specific finding , though one potential cause is  intestinal ischemia . [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3463", "text": "Tram tracks  or  tram-track signs  are  medical signs  that bear some resemblance to  tramway tracks ."}
{"_id": "WikiPedia_Radiology$$$corpus_3464", "text": "When found in the  lungs , tram tracks are  radiologic signs  that are usually accompanied by  pulmonary edema  in cases of  congestive heart failure  and  bronchiectasis . Tram tracks are caused by  bronchial wall thickening , and can be detected on a lateral  chest X-ray . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3465", "text": "The term \"tram tracks\" is also used to describe the  basement membrane  duplication found on light microscopy that is characteristic of  membranoproliferative glomerulonephritis  (MPGN) type I. (It is less commonly associated with types II and III.) [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3466", "text": "The term has also been used to describe findings associated with  optic nerve sheath meningioma . [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3467", "text": "Tram track-shaped calcifications in the  cerebral cortex  indicate  Sturge\u2013Weber syndrome . [ citation needed ]  where intracranial gyriform calcification (brain imaging) seen mostly in occipital and posterior parietal/temporal lobe ;this syndrome consists triad of port wine stain,seizure(usually focal but may become generalized),eye manifestation(e.g. glaucoma)."}
{"_id": "WikiPedia_Radiology$$$corpus_3468", "text": "Tram track appearance in mammography/USG indicates Duct Ectasia. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3469", "text": "In  radiology , the  tree-in-bud sign  is a finding on a  CT scan  that indicates some degree of  airway obstruction . [ 1 ]  The tree-in-bud sign is a nonspecific imaging finding that implies impaction within bronchioles, the smallest airway passages in the lung. The differential for this finding includes malignant and inflammatory etiologies, either infectious or sterile. This includes  fungal  infections, mycobacterial infections such as  tuberculosis  or  mycobacterium avium intracellulare ,  bronchopneumonia , chronic  aspiration pneumonia ,  cystic fibrosis  or cellular impaction from bronchovascular spread of malignancy, as can occur with breast cancer, leukemia or lymphoma. [ 2 ]  It also includes lung manifestations of autoimmune diseases such as  Sj\u00f6gren syndrome  or  rheumatoid arthritis . [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3470", "text": "Histopathologic  studies have shown that the tree-in-bud pattern is caused by demarcation of the normally invisible branching course of the peripheral airways, which usually results from bronchioles being plugged or blocked with  mucus ,  pus  or  fluid . In addition,  dilated  and  thickened  walls of the peripheral airways and  peribronchitis  can make the affected bronchioles more easily visible, as is seen in patients with  cystic fibrosis . [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3471", "text": "Water Bottle Heart  is a descriptive term used in radiology to describe the appearance of the cardiac silhouette on a chest X-ray when it resembles the shape of a water bottle. This sign is associated with  pericardial effusion , a medical condition characterized by the accumulation of fluid in the  pericardial cavity  surrounding the heart. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3472", "text": "On a chest X-ray, the normal heart silhouette should have a clear and defined outline. However, in cases of pericardial effusion, the accumulation of fluid within the pericardial sac causes the heart to appear enlarged and assumes a shape that is reminiscent of a water bottle, with relatively smooth cardiac contours. [ 2 ]  This distinct appearance is what gives rise to the term \"Water Bottle Heart.\""}
{"_id": "WikiPedia_Radiology$$$corpus_3473", "text": "Although water bottle heart is most commonly associated with pericardial effusion, it can also be seen in severe dilatation of the heart secondary to  valvular heart disease . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3474", "text": "Water lily sign  is a radiologic sign seen in  hydatid cyst  infection. [ 1 ]  It refers to floating laminated membranes of the cyst within a dense fibrous cystic wall, resembling the appearance of a water lily in radiographs. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3475", "text": "In  chest radiography , the  Westermark sign  is a  sign  that represents a focus of  oligemia  (hypovolemia) (leading to collapse of vessel) seen distal to a  pulmonary embolism  (PE). [ 1 ]  While the chest x-ray is normal in the majority of PE cases, [ 2 ]  the Westermark sign is seen in 2% of patients. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3476", "text": "Essentially, this is a plain X-ray version of a filling defect as seen on computed tomography pulmonary arteriogram."}
{"_id": "WikiPedia_Radiology$$$corpus_3477", "text": "The sign results from a combination of:"}
{"_id": "WikiPedia_Radiology$$$corpus_3478", "text": "The Westermark sign, like  Hampton's hump  (a wedge shaped, pleural based consolidation associated with  pulmonary infarction ), has a low  sensitivity  (11%) and high  specificity  (92%) for the diagnosis of pulmonary embolism. [ 4 ]   Put more simply, the Westermark sign is seldom seen in pulmonary embolism. When visible on a chest X-ray, the Positive Predictive Value is only 33%. That is, 33% of the time that Westermark sign is seen on Chest XRay does a pulmonary embolism actually exist  [1] ."}
{"_id": "WikiPedia_Radiology$$$corpus_3479", "text": "It is named after  Nils Westermark , a Swedish radiologist. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3480", "text": "The  Whirlpool sign  also known as the  Whirl sign [ 1 ]  is related to mesentery when the bowel rotates around the  mesentery  causing a swirling appearance of the mesentery around the mesenteric vessels. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3481", "text": "It can also be related to ovaries when twisting of the vascular pedicle of the ovaries takes place. [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3482", "text": "The  white cerebellum sign , also known as  reversal sign  or  dense cerebellum sign , is a radiological sign denoting the relatively white appearance of the  cerebellum  due to a generalized decrease in density of the  supratentorial  brain structures caused by extensive  edema . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3483", "text": "White cerebellum sign can be associated with raised intracranial pressure [ 2 ]  that occurs due to anoxic or ischemic changes in the brain. [ 3 ]  It can be found in:"}
{"_id": "WikiPedia_Radiology$$$corpus_3484", "text": "Diffuse brain edema is the likely cause of this radiological change observed in CT or MRI. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3485", "text": "It was considered to indicate a bad prognosis. [ 4 ]  However, evidence suggests that it could be a non-specific indicator of diffuse brain edema which might not be as ominous as previously thought. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3486", "text": "Jha, Praveen.  \"White cerebellum sign | Radiology Reference Article | Radiopaedia.org\" .  radiopaedia.org . Retrieved  2017-03-26 ."}
{"_id": "WikiPedia_Radiology$$$corpus_3487", "text": "Wilkinson's syndrome  (also known as  Sclerotic pedicle sign ) is a radiographic term which describes a unilaterally enlarged  pedicle  opposite a contralateral  pars defect . [ 1 ] [ 2 ]  The enlarged pedicle may due to stress hypertrophy, and changes may extend into the adjacent lamina and transverse processes. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3488", "text": "The characteristic radiographic feature of Wilkinson's syndrome is a missing pedicle with a thick, sclerotic contralateral pedicle at the same level. This is sometimes referred to as a \"winking owl sign\". [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3489", "text": "The  Central Brain Tumor Registry of the United States  (CBTRUS) is the primary national database of malignant and benign  tumors  of the brain, \"other  central nervous system  (CNS), tumors of the pituitary and pineal glands, olfactory tumors of the nasal cavity, and brain lymphoma and leukemia.\" [ 1 ]  A  non-profit , it was established in 1992. [ 2 ] [ 3 ] [ 4 ] [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3490", "text": "Computed tomography angiography  (also called  CT angiography  or  CTA ) is a  computed tomography  technique used for  angiography \u2014the visualization of  arteries  and  veins \u2014throughout the  human body . Using contrast injected into the blood vessels, images are created to look for blockages,  aneurysms  (dilations of walls),  dissections  (tearing of walls), and  stenosis  (narrowing of vessel). CTA can be used to visualize the vessels of the heart, the aorta and other large blood vessels, the lungs, the kidneys, the head and neck, and the arms and legs. [ citation needed ]  CTA can also be used to localise arterial or venous bleed of the gastrointestinal system. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3491", "text": "CTA can be used to examine blood vessels in many key areas of the body including the brain, kidneys, pelvis, and the lungs."}
{"_id": "WikiPedia_Radiology$$$corpus_3492", "text": "Coronary CT angiography  (CCTA) is the use of CT angiography to assess the  arteries  of the  heart . The patient receives an  intravenous injection  of  contrast  and then the heart is scanned using a high speed  CT scanner . With the advances in CT technology, patients are typically able to be scanned without needing medicines by simply holding their breath during the scan. CTA is used to assess heart or vessel irregularities, location of stents and whether they are still open, and occasionally to check for atherosclerotic disease. [ 2 ]  This method displays the anatomical detail of blood vessels more precisely than  magnetic resonance imaging  (MRI) or  ultrasound . Today, many patients can undergo CTA in place of a conventional  catheter   angiogram , a minor procedure during which a catheter is passed through the blood vessels all the way to the heart. However, CCTA has not fully replaced this procedure. CCTA is able to detect narrowing of blood vessels in time for corrective therapy to be done. CCTA is a useful way of screening for arterial disease because it is safer, much less time-consuming than catheter angiography, and is also a cost-effective procedure."}
{"_id": "WikiPedia_Radiology$$$corpus_3493", "text": "CTA can be used in the chest and abdomen to identify  aneurysms  in the aorta or other major blood vessels. These areas of weakened blood vessel walls that bulge out can life-threatening if they rupture. CTA is the test of choice when assessing aneurysm before and after endovascular stenting due to the ability to detect calcium within the wall. [ 3 ]  Another positive of CTA in abdominal aortic aneurysm assessment is that it allows for better estimation of blood vessel dilation and can better detect blood clots compared to standard  angiography . [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3494", "text": "CTA is used also to identify  arterial dissection , including  aortic dissection  in the  aorta  or its major branches. Arterial dissection is when the layers of the artery wall peel away from each other; this causes pain and can be life-threatening. CTA is a quick and non-invasive method of identifying dissections and can show the extent of the disease and if there is leakage. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3495", "text": "CT pulmonary angiogram  (CTPA) is used to examine the pulmonary arteries in the lungs, most commonly to rule out  pulmonary embolism  (PE), a serious but treatable condition. It has become the technique of choice for detection of pulmonary embolism due to its wide availability, short exam time, ability to see other diseases that may present like pulmonary embolisms, and a high degree of confidence in the validity of the test. [ 3 ] [ 4 ]  In this test, a PE will appear as a dark spot inside the blood vessel or a sudden stop of the bright contrast material. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3496", "text": "CT angiography should not be used to evaluate for  pulmonary embolism  when other tests indicate that there is a low probability of a person having this condition. [ 5 ]  A  D-dimer  assay might be a preferred alternative to test for pulmonary embolism, and that test and a low clinical prediction score on the  Wells test  or  Geneva score  can exclude pulmonary embolism as a possibility. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3497", "text": "Visualization of blood flow in the renal arteries (those supplying the kidneys) in patients with high blood pressure and those suspected of having kidney disorders can be performed using CTA. Stenosis (narrowing) of a renal artery is a cause of  hypertension  (high blood pressure) in some patients and can be corrected. A special computerized method of viewing the images makes renal CT angiography a very accurate examination. [ 6 ]  CTA is also used in the  assessment of native and transplant renal arteries. [ 3 ]  While CTA is great for imaging of the kidneys, it lacks the ability to perform procedures at the same time. Thus traditional catheter angiography is used in cases of acute renal hemorrhage or acute arterial obstruction. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3498", "text": "CTA can be used assess acute stroke patients by identifying clots in the arteries of the brain. [ 2 ]  It can also be used to identify small aneurysms or  arteriovenous malformation  inside the brain that can be life-threatening. While CTA can produce high quality images of the  carotid arteries  for grading the level of  stenosis  (narrowing of the vessel), calcium deposits (calcified plaques) in the area where the vessels split can lead to interference with accurate stenosis grading. Because of this,  magnetic resonance angiography  is used more often for this purpose. [ 3 ]  Other applications of CTA are identifying  moyamoya disease , dissections of intracranial arteries, detection of  carotid-cavernous fistula , planning for intracranial-extracranial bypass surgery, and involvement of brain tumours such as  meningioma  with surrounding intracranial vessels. [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3499", "text": "CTA can be used in the legs to detect atherosclerotic disease that has narrowed the arteries. It can also be used to image vessels in suspected blockages, trauma cases, or patients with surgical complications. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3500", "text": "CT angiography is a  contrast CT  where images are taken with a certain delay after injection of  radiocontrast  material. The contrast material is  radiodense  causing it to light up brightly within the blood vessels of interest. In order for the CT scanner to be able to scan the correct area where the contrast is, the scanner uses either automatic detectors which start scanning when enough contrast is present, or small test boluses. With the small test bolus, a small amount of contrast is injected in order to detect the speed that the contrast will move through the blood vessels. After determining this speed, the full bolus is injected and the scan is begun at the timing determined by the test bolus. After the scan is completed the images are post-processed to better visualize the vessels and can even be created in the 3D images. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3501", "text": "Harms of overuse of CT angiography include radiation exposure and the possibility of finding then seeking treatment for a clinically insignificant pulmonary embolism which ought not be treated. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3502", "text": "A reaction may occur whenever iodine contrast is injected. These reactions range in severity and it is difficult to predict if they will occur. With the current practice of using low-osmolar contrast these adverse reactions only occur in ~0.1% of cases. [ 4 ]  The severity of the reaction can be broken down into three groups:"}
{"_id": "WikiPedia_Radiology$$$corpus_3503", "text": "A patient with a history of allergy to contrast may be advised to take medications such as corticosteroids or histamine (H1) blockers before CTA to lessen the risk of allergic reaction or to undergo a different exam that does not call for contrast material injection. [ 4 ] [ 9 ]  Patients should also be well hydrated in order to minimize possible adverse effects of contrast. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3504", "text": "Contrary to popular belief there is no correlation between seafood allergies and reactions to iodine contrast, as shown by many recent studies. [ 10 ] [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3505", "text": "Historically it has been thought that contrast material can lead to  contrast-induced nephropathy  (also called CIN) in any patient. However, recent studies have shown that the risk of kidney injury caused by  contrast agent  in patients with no history of kidney problems occurs extremely infrequently. [ 12 ] [ 13 ] [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3506", "text": "The use of CTA in people with  kidney failure , kidney disease or long-standing severe diabetes should be weighed carefully as the use of IV iodine contrast material may further harm kidney function. The decision not to use contrast agents must be weighed against the possibility of misdiagnoses if contrast is not used. [ 13 ] [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3507", "text": "Compared with other imaging modalities, CTA is associated with a significant dose of ionizing radiation. Varying significantly with patient age, sex, and exam protocol, radiation risk models predict coronary CTA to increase lifetime cancer risk. [ 15 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3508", "text": "CT angiography should not be performed in patients who are pregnant as the contrast and radiation may lead to harm to the fetus. The extent of harm to the fetus has not been fully determined. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3509", "text": "By 1994 CT angiography began to replace conventional angiography in diagnosing and characterizing most cardiovascular abnormalities. [ 16 ]  Prior to this, conventional angiography had been in use for 70 years. [ 16 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3510", "text": "Computed tomography of the abdomen and pelvis  is an application of  computed tomography  (CT) and is a sensitive method for diagnosis of  abdominal  diseases. It is used frequently to determine stage of cancer and to follow progress. It is also a useful test to investigate acute abdominal pain (especially of the lower quadrants, whereas ultrasound is the preferred first line investigation for  right upper quadrant  pain).  Renal stones ,  appendicitis ,  pancreatitis ,  diverticulitis ,  abdominal aortic aneurysm , and  bowel obstruction  are conditions that are readily diagnosed and assessed with CT. CT is also the first line for detecting solid organ injury after trauma."}
{"_id": "WikiPedia_Radiology$$$corpus_3511", "text": "Multidetector CT (MDCT) can clearly delineate anatomic structures in the abdomen, which is critical in the diagnosis of internal diaphragmatic and other nonpalpable or unsuspected hernias. MDCT also offers clear detail of the abdominal wall allowing wall hernias to be identified accurately. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3512", "text": "Abdominal imaging is associated with many potential uses for the different  phases of contrast CT . The majority of abdominal and pelvic CT's can be performed using a single-phase, but the evaluation of some tumor types (hepatic/pancreatic/renal), the urinary collecting system, and trauma patients among others, may be best performed with multiple phases. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3513", "text": "In discussing the numerous phases and indications for CT, best patient care requires individualized CT protocols based upon each patient's specific symptoms, pathology, and underlying co-morbidities. Although labor intensive, this provides the highest likelihood of an accurate diagnosis with the lowest necessary radiation dose. The following discussion will provide a basic outline of current best practice, but not all clinical scenarios can be accounted for. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3514", "text": "Contrast enhanced CT examinations can be acquired at a variety of specific time points after intravenous contrast injection (timing is dependent on the phase of contrast enhancement needed and organ system being evaluated). The timing should be chosen specifically to optimize contrast distribution within the solid organ parenchyma in question. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3515", "text": "In cases of suspected bowel leak or perforation, gastrointestinal fistula, interloop abscess or other fluid collection, oncologic staging and surveillance, and CT colonography, oral positive contrast is useful in delineating the lesions. [ 3 ]  1% dilute barium solution can be administered orally for bowel preparation for CT scan of the abdomen. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3516", "text": "Non-contrast CT scans Figure 1a (left) and 1b (right) are of limited use for the differentiation of soft tissue structures. However, materials like blood, calcium (renal stones, vascular atherosclerosis), bone, and pulmonary parenchyma are highly visible and can usually be adequately assessed with non-contrast CT. For example, in the abdomen and pelvis, there are several indications for non-contrast imaging. These include: evaluation of renal calculi; assessment for gross intra-abdominal hemorrhage; and post-endostent volume measurements. In addition, non-contrast images are often obtained in conjunction with contrast enhanced images in evaluating potential renal transplant donors and in the evaluation of the pancreas (in combination with contrast phases). Of note, dual-energy CT and the development of virtual \"non-contrast\" images (VNC imaging) may ultimately obviate the combination scans. Additionally, CT angiography examinations performed for pathologies like aneurysms and dissection are frequently performed in conjunction with non-contrast imaging. The non-contrast images facilitate the differentiation of active extravasation or acute bleeding from vascular calcifications. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3517", "text": "The most common technique is to perform portal venous phase imaging in the abdomen and pelvis (approximately 60\u201390 seconds after contrast administration, figure 2). This results in near optimal contrast opacification of the majority of the solid abdominal organs and it is used for a wide variety of indications: nonspecific abdominal pain; hernia; infection; masses (with a few exceptions such as hypervascular, renal, and some hepatic tumors); and in most follow-up examinations. As a general rule, this single phase is adequate unless there is a specific clinical indication that has been shown to benefit from other phases. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3518", "text": "CT angiography (CTA) is highly effective for evaluation of the arterial system, and has largely replaced conventional angiography due to the lower risk profile and ability to survey the entire abdomen. Images are acquired after a rapid bolus of intravenous contrast material (3-7 cc/s) during the arterial phase (15\u201335 seconds after injection) when the concentration of contrast material in the arterial system is high (figures 3). Images are usually acquired using narrow collimation (<1\u00a0mm) and can be retrospectively reconstructed using dedicated 3-dimensional workstations and software. CTA is commonly used in the head and chest in the evaluation of pulmonary emboli, aneurysms, vascular malformations, dissection, bleeding and ischemia. Indications for early arterial phase imaging include: evaluation of aneurysms or dissections (cerebral, aortic, etc.), hepatic, splanchnic or renal arterial anatomy, and arterial imaging in liver or kidney transplantation. Single phase arterial imaging is often used in the evaluation of trauma patients either a complete chest/abdomen/pelvis examination with arterial phase imaging of the chest and portal venous phase imaging of the abdomen/pelvis or just a portal venous phase of abdomen and pelvis depending on the mechanism and severity of the trauma. CTA is also commonly performed in the abdomen and pelvis for evaluating vascular malformations and in the evaluation of bleeding. Mesenteric ischemia can also be evaluated using CT angiography. CTA of the abdomen and pelvis is often performed in combination with a CTA for evaluating the extremity vasculature. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3519", "text": "The late arterial phase is timed to correspond to the peak concentration of contrast material in highly vascular tumors and is performed approximately 20\u201335 seconds after the injection of intravenous contrast. Early arterial phase imaging is predominantly utilized for angiography and will be discussed separately. Late arterial phase imaging is almost always performed in conjunction with other phases (e.g. portal venous phase) to allow more complete characterization of any identified abnormalities (figure 4). The primary indication for a late arterial phase is for the evaluation of hypervascular tumors of the liver such as hepatocellular carcinoma or hypervascular metastases (figure 4). Typical hypervascular tumors for which this would be used include: hepatocellular carcinoma; renal cell carcinoma; melanoma; carcinoid/neuroendocrine tumors; some sarcomas; choriocarcinoma; and thyroid carcinoma. Although a \"hypervascular\", biphasic evaluation would generally be used for these patients, note that a single phase is often adequate for follow up imaging. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3520", "text": "CT imaging specific for the venous structures is performed uncommonly. Most venous structures are partially opacified on the routine contrast enhancing images and suffice for most examinations. However, occasionally evaluation of the inferior vena cava is desired, such as prior to IVC filter placement/removal or evaluation of IVC thrombosis. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3521", "text": "Delayed phase imaging (figure 5) encompasses scanning at a variety of different times following contrast administration, and depends on the pathology in question. Typical delayed imaging times range from a few minutes to up to 15 minutes or longer. The most common indications for delayed phase imaging are evaluation of the kidneys, collecting system (ureters and bladder) and specific kidney, liver, and adrenal tumors. Evaluation of the kidneys, ureters and bladder are discussed separately in the renal imaging section. Cholangiocarcinoma occurring within the extrahepatic biliary tree or intrahepatic cholangiocarcinomas are a common reason for delayed imaging. Cholangiocarcinomas are fibrotic tumors which enhance slowly, and are usually imaged following a 10-15 minute delay. Similarly, adrenal masses can be evaluated with multiphase imaging including an unenhanced CT, portal venous phase and a 10 minute delay CT which allows for evaluation and calculation of the enhancement and washout characteristics aiding in distinguishing benign adrenal adenomas from other adrenal masses. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3522", "text": "Outside of the evaluation of masses, delayed phase images can be used in the evaluation of active vascular extravasation in trauma patients, vascular malformations, and aneurysm disruption."}
{"_id": "WikiPedia_Radiology$$$corpus_3523", "text": "When evaluating hepatic masses, it can be advantageous to have both late arterial and portal venous phase images (biphasic imaging, figure 4) since some tumors enhance briskly during the arterial phase (hepatocellular carcinoma, hepatic adenoma, follicular nodular hyperplasia (FNH), and hypervascular metastasis), but may be occult or difficult to characterize on portal venous phase imaging alone (figure 6). However, it should be stressed that the addition of late arterial phase images is only indicated if one of these tumors is suspected, or if there is a need for further characterization of a hepatic mass, since the large majority of patients will not benefit from the addition of this phase. In addition, if there is a need to definitively characterize a hepatic mass, MRI is generally more sensitive and specific, with no associated radiation dose. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3524", "text": "Transient hepatic attenuation differences  in the arterial phase may mimic diseases of the liver. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3525", "text": "Detection and characterization of renal parenchymal masses is a frequent indication for CT. An initial noncontrast CT is important for detecting calcium or fat in a lesion, and to provide baseline attenuation of any renal masses. Following noncontrast scanning, intravenous contrast is injected and a corticomedullary phase is obtained at approximately 70 seconds (figure 7a, 7b). The corticomedullary phase is characterized by enhancement of the renal cortex as well as the renal vasculature. This phase is valuable in the evaluation of benign renal variants, lymphadenopathy and vasculature, however certain medullary renal masses may not be visible during this phase due to minimal enhancement of the medulla and collecting system. The parenchymal phase is obtained approximately 100\u2013200 seconds after the injection of contrast material (figure 7c). Parenchymal phase imaging demonstrates continued enhancement of the cortex, enhancement of the medulla, and various levels of contrast material in the collecting system. The parenchymal phase is highly important for the detection and characterization of renal masses, parenchymal abnormalities, and the renal collecting system. This method of imaging does not evaluate for abnormalities of the collecting system. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3526", "text": "Common renal masses can occasionally be differentiated from each other using this imaging technique. Renal cell carcinomas and oncocytomas typically demonstrate intense heterogeneous enhancement on the parenchymal phase images and cannot be reliably differentiated from each other but can be distinguished from other renal masses. Angiomyolipomas (AML's) also demonstrate intense contrast enhancement but characteristically contain macroscopic fat which can be detected on the noncontrast images, and can help to differentiate AML's from renal cell carcinomas and oncocytomas. Renal lymphoma on the other hand, will often have decreased enhancement when compared to the renal parenchyma on the parenchymal phase images. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3527", "text": "CT urography  (CTU) is commonly used in the evaluation of hematuria, and specifically tailored to image the renal collecting system, ureters and bladder in addition to the renal parenchyma. Initial imaging includes a noncontrast phase to detect renal calculi as a source of hematuria. Note that dual energy CT may eventually allow the noncontrast phase to be eliminated. Contrast enhancement techniques for CTU vary from institution to institution. A common technique is a double bolus, single phase imaging algorithm. Excretory phase imaging allows for not only evaluation of the ureteral lumen, but also periureteral abnormalities including external masses and lymphadenopathy. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3528", "text": "Pancreatic masses are often evaluated using both an early arterial (to evaluate for vascular involvement and thus resectability, figure 9a) and a later \"pancreatic\" phase (which optimizes pancreatic parenchymal enhancement and thus is best at differentiating pancreatic tumors from pancreatic parenchyma, figure 9b). Pancreatic adenocarcinoma typically is hypoenhancing when compared to the surrounding parenchyma. Most other common pancreatic tumors are hypervascular with avid enhancement (such as pancreatic neuroendocrine tumors) and appear brighter than the surrounding pancreatic parenchyma after the injection of intravenous contrast material. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3529", "text": "CT imaging should be performed to evaluate the specific clinical question, however incidental findings are noted in approximately 5-16\u00a0% of patients scanned for an unrelated reasons. It is not acceptable practice to anticipate the possibility of incidental lesions given their low incidence and prospectively add additional phases to routine protocols. Unfortunately, several recent surveys demonstrated that this practice is more common than might be anticipated, and contributes to unnecessary medical radiation exposure to a large population of patients. Even more egregious is the fact that many of these findings could potentially be more accurately evaluated with other non-radiation imaging modalities such as MRI or ultrasound. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3530", "text": "Although the management of incidental findings is not the focus of this chapter, some of these findings will require complete characterization with further CT phases such as arterial phase (certain liver tumors) or delayed images (adrenal lesions). Management of incidental findings has been controversial since they are relatively common, especially in the elderly, and more CT scanning may be required for further characterization of what is frequently a benign finding. In an effort to provide guidance on which incidental findings should be appropriately further evaluated and what the appropriate imaging modality should be, the ACR published a white paper on management of incidental findings detected at CT of the abdomen in 2010. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3531", "text": "Multiphase CT examinations are very important for the detection and characterization of certain clinical conditions, but should not be generalized for every patient undergoing CT of the abdomen and pelvis. A recent survey demonstrated that many physicians are routinely performing multiphase CT for the majority of patients in an attempt to prospectively characterize potential lesions detected during the scan. However, unindicated multiphase CT examinations are an important source of medical radiation that does not contribute to the care of patients. Adherence to published standards such as the ACR appropriateness criteria can both decrease medical radiation and optimize imaging for the specific clinical indication. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3532", "text": "Computed tomography of the chest  or  chest CT  is a group of  computed tomography scan   protocols  used in  medical imaging  to evaluate the  lungs  and search for  lung disorders ."}
{"_id": "WikiPedia_Radiology$$$corpus_3533", "text": "Contrast agents  are sometimes used in CT scans of the chest to accentuate or enhance the differences in  radiopacity  between  vascularized  and less vascularized structures, but a standard chest CT scan is usually non-contrasted (i.e. \"plain\") and relies on different  algorithms  to produce various series of digitalized images known as  view  or \" window \". Modern detail-oriented scans such as  high-resolution computed tomography  (HRCT) is the  gold standard  in  respiratory medicine  and  thoracic surgery  for investigating disorders of the lung  parenchyma  ( alveoli )."}
{"_id": "WikiPedia_Radiology$$$corpus_3534", "text": "Contrasted CT scans of the chest are usually used to confirm diagnosis of for  lung cancer  and  abscesses , as well as to assess  lymph node  status at the  hila  and the  mediastinum .  CT pulmonary angiogram , which uses time-matched (\"phased\") protocols to assess the lung perfusion and the patency of  great arteries  and  veins , particularly to look for  pulmonary embolism . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3535", "text": "Computed tomography of the head  uses a series of  X-rays  in a  CT scan  of the  head  taken from many different directions; the resulting data is transformed into a series of cross sections of the brain using a computer program. [ 1 ]  CT images of the head are used to investigate and diagnose  brain injuries  and other neurological conditions, as well as other conditions involving the skull or  sinuses ; it used to guide some brain surgery procedures as well. [ 2 ]   CT scans expose the person getting them to  ionizing radiation  which has a risk of eventually causing cancer; some people have allergic reactions to  contrast agents  that are used in some CT procedures. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3536", "text": "Computed tomography (CT) has become the diagnostic modality of choice for head trauma due to its accuracy, reliability, safety, and wide availability. The changes in microcirculation, impaired auto-regulation, cerebral edema, and axonal injury start as soon as head injury occurs and manifest as clinical, biochemical, and radiological changes. Proper therapeutic management of brain injury is based on correct diagnosis and appreciation of the temporal course of the disease process. CT scan detects and precisely localizes the intracranial hematomas,  cerebral contusions , edema and foreign bodies. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3537", "text": "Even in emergency situations, when a head injury is minor as determined by a physician's evaluation and based on established guidelines, CT of the head should be avoided for adults and delayed pending clinical observation in the emergency department for children. [ 3 ]  Many people visit emergency departments for minor head injuries. CT scans of the head can confirm a diagnosis of skull fracture or brain bleeding, but even in the  emergency department , such things are uncommon and not minor injuries, so CT of the head is usually not necessary. [ 3 ]  Clinical trials have shown the efficacy and safety of using CT of the head in emergency settings only when indicated, which would be at the indication of evidence-based guidelines following the physical examination and a review of the person's history. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3538", "text": "Concussion  is not a routine indication for having brain CT or brain MRI and can be diagnosed by a healthcare provider trained to manage concussions. [ 4 ]  People with concussions usually do not have relevant abnormalities about which brain imaging could give insight, so brain imaging should not routinely be ordered for people with concussions. [ 4 ]  If there is concern about a skull fracture, focal neurological symptoms present or worsening symptoms, then CT imaging may be useful. [ 4 ]  MRI may be useful for people whose symptoms worsen over time or when structural pathology is suspected. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3539", "text": "CT of the head is sometimes used for people who have sudden hearing loss. [ 5 ]  However, when there are not other neurological findings, a history of trauma, or a history of ear disease, CT scans are not useful and should not be used in response to sudden hearing loss. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3540", "text": "CT of the head is also used in CT- guided   stereotactic surgery  and  radiosurgery  for treatment of intracranial tumors, arteriovenous malformations and other surgically treatable conditions. [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3541", "text": "Special views focusing  on the  orbit  of the  eye  may be taken to investigate concerns relating to the eye. [ 8 ]   CT scans are used by  physicians  specializing in treating the eye ( ophthalmologists ) to detect  foreign bodies  (especially metallic objects),  fractures ,  abscesses ,  cellulitis ,  sinusitis , bleeding within the skull ( intracranial bleeding ),  proptosis ,  Graves disease  changes in the eye, and evaluation of the orbital apex and  cavernous sinus . [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3542", "text": "Magnetic resonance imaging  (MRI) of the head provides superior information as compared to CT scans when seeking information about headache to confirm a diagnosis of  neoplasm ,  vascular disease ,  posterior cranial fossa  lesions, cervicomedullary lesions, or  intracranial pressure  disorders. [ 9 ]  It also does not carry the risks of exposing the person to  ionizing radiation . [ 9 ]  CT scans may be used to diagnose headaches when  neuroimaging  is indicated and MRI is not available, or in emergency settings when hemorrhage,  stroke , or  traumatic brain injury  is suspected. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3543", "text": "MRI (magnetic resonance imaging)  provides more sensitivity in the evaluation of the cavernous sinus and the orbital apex. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3544", "text": "One advantage over a  brain MRI  is in the evaluation of intracerebral calcifications. [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3545", "text": "Several different views of the head are available, including  axial ,  coronal , reformatted coronal, and reformatted  sagittal  images.  However, coronal images require the person to   hyperextend  their neck, which must be avoided if any possibility of neck injury exists. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3546", "text": "CT scans of the head increase the risk of  brain cancer , especially for children. As of 2018, it appeared that there was a risk of one excess cancer per 3,000\u201310,000 head CT exams in children under the age of 10. [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3547", "text": "In  CT scan  of the  thyroid , focal and diffuse  thyroid abnormalities  are commonly encountered. These findings can often lead to a diagnostic dilemma, as the CT reflects nonspecific appearances.  Ultrasound  (US) examination has a superior  spatial resolution  and is considered the modality of choice for thyroid evaluation. Nevertheless, CT detects incidental  thyroid nodules  (ITNs) and plays an important role in the  evaluation  of  thyroid cancer . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3548", "text": "This pictorial review covers a wide spectrum of common and uncommon, incidental and non-incidental thyroid findings from  CT scans . It will also include the most common incidental thyroid findings. In addition, the role of imaging in the assessment of  thyroid carcinoma  (before and after treatment) and  preoperative  thyroid  goiter  is explored, as well as localization of  ectopic  and  congenital thyroid tissue . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3549", "text": "Thyroid ultrasonography  is the modality of choice for thyroid evaluation. [ 1 ]  Yet, focal and diffuse thyroid abnormalities [ 2 ]  are commonly encountered during the interpretation of  computed tomography  (CT) exams performed for various  clinical purposes . [ 1 ]  For example, CT often detects incidental  thyroid nodules  (ITNs). It plays an important role in the evaluation of abnormal structures including  thyroid cancer . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3550", "text": "Thyroid disorders  are common and include many entities. They can be  symptomatic ,  asymptomatic ,  diffuse , focal,  neoplastic , or non-neoplastic processes. Neck ultrasound (US), with the prospect of proceeding to  fine needle aspiration  (FNA), is the first line of investigation; however, other options are available. Thyroid Uptake Scans using  Tc-99 m  or I-123 are typically reserved for specific clinical scenarios. Cross-sectional imaging including  computed tomography (CT)  and  magnetic resonance imaging  ( MRI ) detect incidental  thyroid nodules  (ITNs) and can be used in the evaluation of  thyroid cancers  and  goiter . The aim of this article is to provide a pictorial review of a broad spectrum of incidental and non-incidental thyroid findings on CT scans. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3551", "text": "The  thyroid gland  is a  vascular , encapsulated structure made up of right and left  lobes , which are connected at the midline by the isthmus. Each lobe is about 2\u00a0cm thick, 3\u00a0cm wide, and 5\u00a0cm long. The thyroid apex is located superiorly at the level of the mid- thyroid cartilage . The inferior margin of the  gland  is at the level of the fifth or sixth  tracheal ring . The  thyroid gland  is encapsulated by the middle layer of  deep cervical fascia  and is part of the visceral space in the infrahyoid neck. It wraps around the  trachea  and is separated from the  esophagus  by the  tracheoesophageal  groove on each side, which houses the  recurrent laryngeal nerves . The thyroid has variable lymphatic drainage to the  internal jugular  chain, para-tracheal region,  mediastinum , and  retropharyngeal  area. It has homogeneous high attenuation values on a  CT scan , as compared to adjacent muscles, due to its high  iodine   concentration . It shows avid iodine contrast enhancement due to its  hypervascularity . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3552", "text": "Multi-detector volumetric acquisition from the  skull base  to the  tracheal bifurcation  is usually obtained. Multiplanar 2-mm  axial ,  coronal , and  sagittal  images are typically available. Examination can be acquired with or without administration of  intravenous (IV)  iodinated contrast. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3553", "text": "The thyroid gland can have variable CT scan findings, such as  calcifications , single or multiple nodules,  cysts , or diffuse enlargement. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3554", "text": "Thyroid calcifications on a CT scan can be seen in both benign and malignant thyroid  lesions .  Sonographic  examination of the thyroid can differentiate between micro-calcifications, which are highly associated with  papillary thyroid carcinoma , and eggshell calcifications, which favour a benign process such as  colloid cysts  (Figs. 1 and 2). In a retrospective review of preoperative CT scan, 35% (135 of 383) of the patients had detectable intrathyroidal calcifications. Among them, 48% had a  histopathologically  proven thyroid cancer. Calcified nodules had a significantly higher incidence of thyroid cancer and  lymph node  metastases. The incidence of thyroid cancer among nodules with different calcifications patterns was 79% of nodules with multiple punctate calcifications, 58% of nodules with a single punctate calcification, 21% of nodules with coarse calcification, and 22% of nodules with peripheral calcification. Most of the single calcified nodules were  malignant . However, this did not include patients with ITNs and the sample is skewed towards malignancy. Another study evaluated the presence of ITNs on CT scans and found that 12% of thyroid nodules were calcified, with no significant correlation between malignant or potentially malignant histology and punctate calcifications. As a result, some researchers believe that calcification per se is not a suspicious CT sign, and have suggested that calcified thyroid nodules on CT scans should be treated the same as non-calcified nodules. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3555", "text": "Thyroid cystic changes are variable, ranging from simple cysts with a thin wall to complex cysts with septations and solid components. An  adenoma  may undergo cystic degeneration. It is important to note that papillary carcinoma may mimic a benign-looking cyst. Simple serous cysts appear with fluid density on a CT scan, whereas a cyst with haemorrhage or high thyroglobulin content is iso-dense to muscle. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3556", "text": "Thyroid nodules that are detected by an imaging study but have not been previously detected or suspected clinically are considered to be ITNs. ITNs are one of the most common incidental findings on neck imaging. ITNs are reported in up to 25% of chest CT scans, and in 16\u201318\u00a0% of cervical region cross-sectional imaging, including CT and MRI scans. The rate of malignancy in the detected ITNs on CT and MRI scans varies from 0% to 11%. Incidentally detected thyroid carcinomas are more likely to be papillary thyroid carcinomas (PTCs) (Fig. 3). Incidentally detected cancers tend to be smaller in size and less likely to have distant metastasis, as compared to clinically suspected thyroid cancers. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3557", "text": "On CT scans, a malignant lesion is suspected when the margins are ill-defined and there is extra-thyroid extension, lymph node involvement, or invasion of the surrounding structures. The absence of these features does not exclude malignant tumours, especially papillary,  follicular , and  medullary  thyroid carcinomas (Fig. 3). Therefore, ultrasound is the modality of choice for thyroid lesion evaluation, due to its superior spatial resolution compared to CT examinations. Sonographic features of malignancy are micro-calcifications,  acoustic shadowing , anti-parallel orientation, marked hypoechogenicity, irregular or microlobulated margins, and increased vascularity. CT scans lack the ability to detect these reliable sonographic signs of malignancy. Therefore, further management of ITNs, if required, usually begins with thyroid ultrasound and FNA should be considered according to the ultrasound findings. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3558", "text": "The  American College of Radiology  (ACR) flowchart and recommendations for ITNs detected by CT or MRI offer general guidance and are not applicable to all patients. The recommendations are primarily based on the presence or absence of suspicious features, nodule size, patient's age, patient's life expectancy, and patient's comorbidities. Suspicious features that can be detected on CT scans include signs of local invasion and abnormal lymph nodes. Abnormal lymph nodes may show cystic components, calcifications, and/or increased enhancement. Mere nodal enlargement is less specific for thyroid cancer metastasis; however, further evaluation should be considered if the ITN has ipsilateral jugulodigastric lymph nodes > 1.5\u00a0cm on the short axis or > 1\u00a0cm for other groups. Cervical Level IV and VI lymphadenopathies raise a higher suspicion of thyroid carcinoma metastasis. Almost all patients with ITNs and suspicious imaging features should be evaluated with a neck ultrasound. Patients with  comorbidities  or limited life expectancy without suspicious features should not undergo further evaluation. Nevertheless, further workup might be necessary for such individuals if it is clinically warranted, or specifically requested by the referring physician or the patient. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3559", "text": "In patients with ITNs, it is important to inquire about pertinent historical factors predicting malignancy. These factors include a history of childhood or adolescent head and neck or total body radiation exposure, and familial thyroid carcinoma or thyroid cancer syndrome. Syndromes associated with thyroid cancer include  multiple endocrine neoplasia 2 , familial  adenomatous polyposis ,  Carney complex ,  Cowden's disease , and  Werner syndrome / progeria . If a patient has a first-degree relative with such a syndrome, screening based on the various components of that syndrome is advised. Nevertheless, there are no guidelines specifically addressing ITNs detected on CT scans in patients at risk of thyroid cancer. Therefore, in the absence of suspicious features on the CT scan, other criteria such as nodule size on the CT scan, patient age, and levels of  thyroid stimulating hormone  (TSH) are important in guiding management in such a patient population. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3560", "text": "Although the correlation between thyroid nodule size and malignancy risk is limited, nodule size affects prognosis in malignant nodules. Small thyroid cancers (less than 2\u00a0cm) tend to have an indolent course, with favourable prognosis even if not treated. Less than 7% of the imaging-detected ITNs are seen in younger populations. However, Shetty et al.  found a higher rate of malignancy in the ITNs detected on CT scans among patients younger than 35 years. Ito et al. found a higher tumour progression risk among young patients (<40 years) with subclinical, low-risk PTCs who undergo observation rather than surgery. Therefore, nodule size and patient age should determine the need for workup in the general population without suspicious imaging features and with normal life expectancy. Further evaluation with ultrasound is required for patients less than 35 years old with nodules measuring more than 1\u00a0cm in the  axial plane . The cutoff size for further evaluation is raised to 1.5\u00a0cm for patients more than 35 years old. This recommendation should be applied to the largest thyroid nodule in cases of multiple thyroid nodules. Incidentally discovered heterogeneous and enlarged thyroid glands should undergo dedicated ultrasound if the patient has no limited life expectancy or serious comorbidities. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3561", "text": "Primary thyroid carcinomas include papillary, follicular, medullary, and  anaplastic  carcinomas. Lymphoma and metastasis of other primary malignancies to the thyroid gland represent a minority of thyroid carcinomas. Differentiated thyroid carcinomas (DTCs) originate from follicular epithelial cells and encompass PTCs and follicular thyroid carcinomas, including the  Hurthle cell  variant of follicular carcinoma. DTCs have an excellent prognosis and fortunately represent the majority of thyroid carcinomas. PTCs and follicular thyroid carcinomas represent 88% and 8%, respectively, of all thyroid malignancies. Medullary thyroid carcinoma arises from  neuroendocrine C-cells  and has a good prognosis. Anaplastic carcinoma is an aggressive undifferentiated tumour that usually affects the elderly and tends to have a worse prognosis. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3562", "text": "Surgery is the primary mode of treatment for DTCs. Post total  thyroidectomy  radioactive iodine (RAI)  ablation  is an option, especially in patients with distant metastasis, tumours larger than 4\u00a0cm, or extra-thyroidal disease extension. Ultrasound examination is usually adequate in evaluating primary tumours and cervical lymph nodes. Preoperative cross-sectional imaging with CT or MRI is indicated if there is a concern for local invasion that may alter the patient's staging as well as surgical approach (Figs. 4, 55 and 6)6) . Some thyroid primaries may be small, diffuse, or multifocal and therefore may be occult on imaging (Fig. 4) . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3563", "text": "In patients with known thyroid malignancies, a non-enhanced exam is preferred due to the possible undesired interference of free iodide contrast medium with thyroid iodide I-131 uptake for 6\u20138 weeks or more. This would adversely affect the management of these patients by delaying diagnostic thyroid scintigraphy and radioiodine ablation in patients with DTCs for 2\u20136 months. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3564", "text": "The radiologist must evaluate the central structures draping the thyroid gland including the  trachea , oesophagus,  larynx , and  pharynx , as well as the recurrent  laryngeal nerve . Invasion is suspected if the thyroid mass abuts the airway or oesophagus for more than 180 degrees. Luminal deformity,  mucosal  thickening and mucosal focal irregularity are more specific indicators of invasion. Obliteration of the fat planes of the tracheoesophageal groove in three axial images and signs of  vocal cord paralysis  are indicative of recurrent laryngeal nerve invasion. Invasion of these central structures meets the criteria for T4a disease (Figs. 5 and and6)6). [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3565", "text": "Arterial invasion constitutes T4b disease, which may preclude curative surgery. More than 180 degrees of arterial encasement is suggestive of invasion, however, arterial deformity or narrowing is much more suspicious for invasion. The  carotid artery  is the most commonly involved artery; however, the mediastinal vessels should also be examined. Encasement of the carotid artery or mediastinal vessels for more than 270 degrees is unlikely to be resectable. On the other hand, occlusion or effacement of the internal jugular vein can occur without invasion and does not influence surgical resectability or staging. Asymmetry of the strap muscle and the tumour abutting its external surface are signs of an invasion. However, invasion of the pre-vertebral musculature is more challenging, as a large lesion can compress the muscle without invasion (Figs. 5 and and6)6). [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3566", "text": "Finally, the possibility of metastatic disease should be excluded. PTCs and medullary thyroid carcinomas tend to metastasize to regional lymph nodes. According to the AJCC/UICC TNM staging system, the nodal stage is classified by site: N1a indicates level VI nodal involvement, including paratracheal nodes; N1b indicates unilateral or bilateral lateral cervical nodal disease or superior mediastinal nodal disease (Figs. 4, 55 and and6)6). [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3567", "text": "The incidence of  hematogenous  spread of follicular carcinomas is 21\u201333\u00a0% and that of PTCs is 2\u201314\u00a0%. In medullary thyroid cancer and anaplastic thyroid cancer, distant metastasis was reported in 25% and 40% of patients, respectively. Distant metastases from DTCs tend to have a more favourable prognosis. Distant metastatic disease may appear years after the initial presentation. Therefore, imaging for distant metastases is usually done pre-operatively for anaplastic thyroid cancer and post-operatively for DTCs. DTC distant metastases sites include the lung (50%), bone (25%), lung and bone (20%), followed by other sites (5%). [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3568", "text": "The thyroid cancer recurrence rate is reported to range from 7% to 14%. Recurrence is usually detected within the first decade after the initial disease diagnosis. Large lymph node metastasis is considered the strongest predictor for thyroid cancer recurrence. Post-treatment surveillance for recurrent disease depends on the cancer type and staging. Patients with DTC are usually treated with total thyroidectomy and RAI ablation. Patients should have baseline neck US evaluation at 6\u201312 months after the RAI ablation and then periodically, depending on the patient's risk for recurrent disease and  thyroglobulin  (Tg) status. After the first post-operative RAI ablation, further RAI imaging is not necessary if the patient has normal neck US, undetectable Tg level under TSH stimulation, and negative antithyroglobulin (TgAb). Annual neck US with or without FNA, along with measurement of serum Tg and serum TgAb, is usually sufficient for post-treatment surveillance in those patients. Moreover, annual US is appropriate in patients with medullary cancer and normal calcitonin levels. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3569", "text": "The likelihood of positive anatomic imaging is greater when serum Tg is >10\u00a0ng/mL. A diagnostic CT scan adds additional value to neck US in detecting central compartment macro-metastases in the mediastinum and retro-tracheal area. According to the recent  American Thyroid Association  guidelines, an upper chest and neck CT scan with IV contrast should be obtained when: 1) neck US is inadequate in visualizing possible local nodal disease (high Tg, negative neck US, and RAI imaging); 2) US is not able to delineate the disease completely, as in the case of bulky recurrent nodal disease; or 3) evaluation of possible recurrent invasive disease is needed (Figs. 7, 88 and and9).9). CT scans are also the most sensitive diagnostic tool for the detection of pulmonary  micro-metastases . Many of the neck US features that are considered as suggestive signs of disease recurrence are also applicable to CT examination. These signs might include sizable rounded nodules in the thyroid bed, fine calcifications, or cystic change. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3570", "text": "In cases of elevated thyroglobulin with negative neck US and iodine whole body  scintigraphy  (WBS),  fluorodeoxyglucose  (FDG)  positron emission tomography  (PET) is the next modality of choice. Dedifferentiated thyroid carcinoma usually has avid FDG-PET uptake and a negative radioiodine scan typically does not respond to RAI therapy and has a poorer prognosis. There is not yet consensus in the research literature on whether cross-sectional imaging (CT or MRI) or an 18FDG-PET/CT scan should be performed as the first-line imaging modality for such patients. Enhanced CT scan was thought to be more sensitive for the detection of lymph node metastases. Nonetheless, scans using modern PET/CT equipment are as reliable as a proper routine staging CT scan. Many lesions can be found on 18FDG-PET/CT scanning despite the lack of IV contrast injection. However, differentiation between local recurrence versus lymph node metastases and detection of direct involvement of the aerodigestive axis or vascular structures are not technically possible in the absence of IV contrast administration. For these reasons, 18FDG-PET/CT utilizing contrast administration should be considered for most patients with extensive disease. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3571", "text": "Metastasis to the thyroid is rare and represents 5.5% of biopsied thyroid malignancies. It is commonly found with cancers originating from the breast, renal cell, lung, melanoma, and colon. Direct invasion from adjacent structures such as the  pharynx ,  larynx ,  trachea , or oesophagus has been reported (Fig. 10). Metastatic disease has a non-specific appearance. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3572", "text": "The presence of ITNs in patients with another known malignancy is a common clinical problem with controversial management guidelines. Wilhelm et al. followed 41 patients with a known extra-thyroid malignancy and ITNs; 35 of them met the criterion for biopsy (nodule \u2265 1\u00a0cm). Pathology revealed four papillary thyroid cancers and five micropapillary thyroid cancers. Only two metastatic cancers were detected. Clinical history (history of radiation, age, endocrine syndromes), TSH, nodule size, and sonographic features are important to determine which nodule(s) should be followed or biopsied. However, existing guidelines do not specifically address how to approach ITNs detected on CT scans in such a specific patient population. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3573", "text": "Thyroid lymphoma represents about 5% of thyroid malignancies.  Non-Hodgkin's lymphoma  is the most common type and can be secondary to generalized lymphoma or a primary tumour. Primary  thyroid lymphoma  usually pre-exists with  Hashimoto's thyroiditis . On CT scans with and without contrast, lymphomas tend to have low attenuation values. Thyroid lymphomas have a variable appearance and mostly manifest as a solitary mass (80%). They may also manifest as multiple nodules (15% to 20%) or as a bulky mass replacing the entire gland with extra-thyroid extension (Figs. 11 and and12).12). The presence of cervical lymphadenopathy supports such a diagnosis. Although it is uncommon, tumour necrosis has been reported. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3574", "text": "A goiter is an abnormal thyroid gland proliferation that manifests as multi-nodular, uni-nodular, or non-nodular diffuse glandular enlargement. A goiter is formed of solid matrix, colloid cysts, blood products, calcification, and fibrosis, and this heterogeneity may lead to variable appearances on a CT scan (Figs. 13, 1414 and and15)15). The US is more sensitive in evaluating thyroid nodules within a goiter; however, a symptomatic goiter may require surgical treatment with total thyroidectomy, and in this case CT plays an additional role in preoperative evaluation. Specific aspects for examination on a CT scan during the preoperative evaluation for goiter include extension, mass effect, and suspicious features of malignancy. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3575", "text": "Malignancy can coexist within the goiter and a CT scan may give a clue if there are abnormal cervical lymph nodes and/or signs of invasion. Retrosternal extension (Fig. 15) could affect the surgical approach, as a lower extent may require a partial or total sternotomy to facilitate complete resection. Therefore, the distance of the retrosternal extent from the sternal notch should be measured on a sagittal image. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3576", "text": "The interpreting radiologist should describe the mass effect, detailing its degree and direction of displacement of central structures, including the trachea, oesophagus, larynx, and pharynx. Attention should be directed to the upper extent of the goiter and structures immediately surrounding the thyroid gland, including the neuro-vascular structures, retropharyngeal space, and pre-vertebral space. The reporting radiologist should evaluate the vocal cords for symmetry and signs of vocal cord palsy. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3577", "text": "Inflammatory thyroid disorders include acute infectious thyroiditis,  Hashimoto's thyroiditis ,  Riedel's thyroiditis , and  granulomatous thyroiditis  (de Quervain's). Hashimoto's thyroiditis is associated with an increased risk of  lymphoma  and papillary thyroid carcinoma. The CT scan findings of thyroiditis are nonspecific and variable (Figs. 14, 1515 and and16)16). The thyroid gland has a very high iodine concentration, resulting in high CT attenuation (80\u2013100 Hounsfield Units). The presence of thyroiditis can be suggested by a diffusely enlarged and hypo-attenuating (around 45 Hounsfield Units) thyroid gland. This is probably due to follicular cell destruction and reduced thyroid iodine concentration. Marked homogeneous enhancement is typically expected. Therefore, moderate thyroid enhancement in a case of thyroiditis suggests a diffuse inflammatory process. It is essential to clinically correlate this with a thyroid function test and serum autoantibody levels. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3578", "text": "During embryogenesis, the bi-lobed thyroid migrates inferiorly from the foramen cecum of the tongue to the lower neck. Initially, the thyroid primordium passes anterior to the primordial hyoid bone, before it loops posteriorly and inferiorly to the hyoid bone. Then it continues its descent into the infra-hyoid portion of the neck, anterior to the trachea, thyroid cartilage, and thyroid membrane. Any thyroid residual along the descent course may lead to the development of ectopic thyroid glands. Thyroid carcinomas, thyroiditis, and goiter may develop within any ectopic thyroid tissue. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3579", "text": "Thyroid scanning with technetium-99 m (Tc99m) plays an important role in detecting orthotopic and ectopic thyroid tissue. Both CT scans and US can help detect ectopic tissue when a lesion demonstrates imaging and enhancement characteristics of thyroid tissue. The absence of normally sited thyroid gland in US and CT scans also supports the diagnosis. In addition, US can guide FNA for cytological confirmation of a thyroid lesion. Ectopic thyroid tissue appears as a well-circumscribed, homogeneous, highly attenuating mass relative to adjacent muscles. Normally, it enhances avidly following the administration of iodinated contrast. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3580", "text": "Ectopic thyroid tissue may be detected in the tongue near the foramen cecum (90%) and along the midline between the thyroid isthmus and posterior tongue, lateral neck, mediastinum, and oral cavity. The most frequent location is the base of the tongue (Figs. 16, 1717 and and18).18). In 70% of cases, the ectopic thyroid is the only functional thyroid tissue present in the body (Fig. 18). [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3581", "text": "Ectopic thyroid tissue lateral to the orthotopic midline location is rare. The exact anatomical definition of this rare entity is debated in the literature. To avoid confusion, some authors define a lateral neck ectopic thyroid as any thyroid tissue superficial to the strap muscles with no midline continuity. The majority of lateral thyroid ectopia cases have been reported as lesions closely related to the strap muscles. There are few reported cases of ectopic lateral thyroid tissue in the submandibular region, jugulodigastric region, or within the parotid gland substance (Fig. 17). [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3582", "text": "The origin of lateral ectopic thyroid tissue is not fully understood. Although this is controversial, some authors suggest that it might have originated from lateral thyroid anlagen ( ultimobranchial bodies ) that failed to fuse with the median anlage during caudal migration. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3583", "text": "A thyroglossal duct cyst (TDC) is a duct remnant between the foramen cecum and thyroid isthmus. Most TDCs are located below the hyoid bone and in the midline. The more caudal the cyst, the more likely it will be off midline within 2\u00a0cm (Fig. 19 and and20).20). On a CT scan, a TDC appears as a well-circumscribed area of fluid attenuation with thin walls. The cyst wall can become thick with an enhancing rim indicative of current or previous infection. These cysts maybe complicated by haemorrhage, infection, or malignancy. Therefore, their US and CT scan appearance may vary based on their content. Nodular enhancement within a TDC should initiate further workup to exclude malignancy (Fig. 21). US-guided FNA of these suspicious nodular areas is considered an appropriate next diagnostic step, taking into consideration the high rate of false negative results. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3584", "text": "Parathyroid adenoma  (PA) is the most common cause of  primary hyperparathyroidism . Ectopic parathyroid adenoma is rare. The third and fourth pharyngeal pouches represent the embryological origin of the parathyroid tissues, and ectopic parathyroid adenoma can ultimately develop anywhere along their migration course. In a large retrospective study of patients with primary hyperparathyroidism, PA was detected in the intra-thyroid location in 0.7% of cases. In another retrospective analysis of 202 patients with ectopic PA, the intra-thyroidal location was found in 18% of the cases. Intra-thyroid parathyroid adenomas mimic thyroid nodules in CT scans and may even show uptake on a thyroid iodine scan. Correlation with laboratory workup, including measurement of serum parathyroid hormone and calcium level, is required. In addition, the evaluating radiologist should search for radiological manifestations of hyperparathyroidism, such as  osteopenia ,  bone resorption , and  brown tumours  (Fig. 22). [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3585", "text": "In the case of inconclusive Tc99m Sestamibi and neck US imaging, FNA biopsy with FNA-iPTH (intact parathyroid hormone) measurement can provide simultaneous biochemical and cytological evidence. Elevated FNA-iPTH measurement, as compared to serum iPTH, is considered positive and diagnostic of parathyroid adenoma. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3586", "text": "Thyroid disorders are common and tend to have non-specific appearances on CT scans. Commonly encountered findings when evaluating a CT scan of the neck include  thyroid nodules , glandular enlargement, and  calcifications . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3587", "text": "Management of ITNs depends on several factors including nodule size, patient's age, overall health status, and the presence or absence of suspicious features such as lymphadenopathy and/or invasion of adjacent structures. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3588", "text": "A CT scan provides additional important information regarding the local extension of cancer or the presence of a mass effect, and is useful in evaluating recurrent disease. Furthermore, CT examination plays a crucial role in preoperative evaluation and preoperative surgical planning for patients with symptomatic goiter. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3589", "text": "Cone beam computed tomography  (or  CBCT , also referred to as  C-arm CT ,  cone beam  volume CT ,  flat panel CT  or  Digital Volume Tomography  (DVT)) is a  medical imaging technique  consisting of  X-ray computed tomography  where the X-rays are divergent, forming a cone. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3590", "text": "CBCT has become increasingly important in treatment planning and diagnosis in  implant dentistry , ENT, orthopedics, and  interventional radiology  (IR), among other things.  Perhaps because of the increased access to such technology, CBCT scanners are now finding many uses in dentistry, such as in the fields of  oral surgery ,  endodontics  and  orthodontics . Integrated CBCT is also an important tool for patient positioning and verification in  image-guided radiation therapy  (IGRT)."}
{"_id": "WikiPedia_Radiology$$$corpus_3591", "text": "During dental/orthodontic imaging, the CBCT scanner rotates around the patient's head, obtaining up to nearly 600 distinct images.  For interventional radiology, the patient is positioned offset to the table so that the region of interest is centered in the field of view for the cone beam.  A single 200 degree rotation over the region of interest acquires a volumetric data set.  The scanning software collects the data and reconstructs it, producing what is termed a  digital volume  composed of three-dimensional  voxels  of anatomical data that can then be manipulated and visualized with specialized software. [ 2 ] [ 3 ]  CBCT shares many similarities with  traditional (fan beam) CT  however there are important differences, particularly for  reconstruction . CBCT has been described as the gold standard for imaging the oral and maxillofacial area."}
{"_id": "WikiPedia_Radiology$$$corpus_3592", "text": "In the late 1990s, Dr Yoshinori Arai in Japan and Dr Piero Mozzo in Italy independently developed Cone Beam Computed Technology for  oral and maxillofacial radiology . [ 4 ]  The first commercial system (the NewTom 9000) was introduced in the European market in 1996 and into the US market in 2001, by Italian company Quantitative Radiology. [ 2 ] [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3593", "text": "Cone beam CT using kilovoltage  X-rays  (as used for  diagnostic , rather than  therapeutic  purposes) attached to a  linear accelerator  treatment machine was first developed in the late 1990s and early 2000s. [ 7 ]  Such systems have since become common on latest generation linacs. [ 8 ]  In the late 2010s CBCT also started to become available on-board  particle therapy  delivery systems. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3594", "text": "While CBCT with  X-ray image intensifiers  was experimented with in the late 1990s, it was not until the adoption of  flat-panel X-ray detectors , with improved contrast and spatial resolution, that CBCT became practical for clinical use in interventional radiology procedures. [ 10 ] [ 11 ]  Many fixed, and even mobile, C-arm fluoroscopy systems are now capable of CBCT acquisitions, in addition to traditional planar fluoroscopy. [ 12 ] [ 13 ]  CBCT aids image guidance during interventional radiology procedures treating various medical conditions including knee osteoarthritis, benign prostatic hyperplasia, and hepatocellular carcinoma. [ 14 ] [ 15 ] [ 16 ] [ 17 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3595", "text": "The most significant advantage of the CBCT in Endodontics is that it can show critical root canal anatomical features that conventional intraoral or panoramic images cannot. [ 18 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3596", "text": "According to the American Association of Endodontics, there are numerous specific situations in which 3D images produced by CBCT enhance diagnosis and influence treatment, and its use cannot be disputed over conventional intraoral radiology based on ALARA principles. [ 19 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3597", "text": "A dental cone beam scan offers useful information when it comes to the assessment and planning of surgical implants. The American Academy of Oral and Maxillofacial Radiology (AAOMR) suggests cone-beam CT as the preferred method for presurgical assessment of dental implant sites. [ 20 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3598", "text": "As a  3D  rendition, CBCT offers an undistorted view of the  dentition  that can be used to accurately visualize both  erupted  and non-erupted teeth, tooth root orientation and anomalous structures, that conventional  2D radiography  cannot. [ 21 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3599", "text": "Processing example using x-ray data from a tooth model:"}
{"_id": "WikiPedia_Radiology$$$corpus_3600", "text": "The CBCT scanner offers undistorted views of the extremities. One advantage of orthopedic CBCT is the ability to take weight bearing images of the  lower extremities . In the realm of the  foot  and  ankle  particularly, weight bearing CBCT is gaining momentum due to its ability to combine 3 dimensional and weight bearing information which are of the utmost importance in diagnosis and surgical planning. [ 22 ]  The preferred term used for CBCT in the lower limb is thus WBCT for Weight Bearing CT following the first scientific publications on the subject. [ 23 ] [ 24 ] [ 25 ] [ 26 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3601", "text": "Image-guided radiation therapy  is a form of  external beam radiotherapy  where the patient is positioned with the organs to be treated accurately matched in position to the treatment field, to reduce the dose to nearby organs which are not being treated. Many organs inside the body move by millimeters relative to the external skin surfaces, and a CBCT scanner mounted on the head of the radiotherapy unit is used immediately before treatment (and sometimes again during treatment) to ensure the patient's organs are in exactly the right position to match the treatment field, and to adjust the position of the treatment table if necessary. The images may also be used to check for other requirements of some types of treatment, such as full or empty bladder, empty rectum, etc. [ 8 ] [ 27 ]  The same cone beam beam source and detector can alternatively be used to take simple X-ray positioning images if the organ shows particularly well on X-ray or if  Fiducial markers  have been inserted into the organ. [ 28 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3602", "text": "The CBCT scanner is mounted on a C-arm  fluoroscopy  unit in the  interventional radiology  (IR) suite, which offers real time imaging with a stationary patient. This eliminates the time needed to transfer a patient from the  angiography  suite to a conventional  computed tomography  scanner and facilitates a broad spectrum of applications of CBCT during IR procedures. The clinical applications of CBCT in IR include treatment planning, device or implant positioning and assessment, intra-procedural localization, and assessment of procedure endpoints. CBCT is useful as a primary and supplemental form of imaging. It is an excellent adjunct to  DSA  and  fluoroscopy  for  soft tissue  and  vascular  visibility during complex procedures. The use of CBCT before fluoroscopy potentially reduces patient radiation exposure. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3603", "text": "Cone beam CT is used for material analysis,  metrology , and  nondestructive testing  in the manufacturing sector. Cone beam CT is also inspect and detect defects of tiny sizes, such as internal pitting corrosion or cracks of an object in  quality control . [ 34 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3604", "text": "Cone beam reconstruction algorithms are similar to typical  tomographic reconstruction  algorithms, and methods such as  filtered backprojection  or  iterative reconstruction  may be used. However, since the reconstruction is three-dimensional, modifications such as the FDK algorithm [ 35 ]  may be needed."}
{"_id": "WikiPedia_Radiology$$$corpus_3605", "text": "Total radiation doses from 3D dental CBCT exams are 96% lower than conventional CT exams, but deliver 5-16x more radiation than standard dental 2D x-ray (OPG). The time of exposure in CBCT is also comparatively less when compared to conventional CT.\n [ 36 ] [ 37 ] [ 38 ] [ 39 ] [ 40 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3606", "text": "CBCT use is only lightly regulated in the US. The recommended standard of care is to use the smallest possible field of view (FOV), the smallest  voxel  size, the lowest mA setting and the shortest exposure time in conjunction with a pulsed exposure mode of acquisition. [ 41 ]  International organisations such as the  World Health Organization  and  ICRP , as well as many local bodies and legislation, encourage the idea of justification for all medical exposures, where risks and benefits must be weighed up before a procedure goes ahead. [ 42 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3607", "text": "There are a number of drawbacks of CBCT technology over that of CT scans, such as increased susceptibility to movement artifacts (in first generation machines) and to the lack of appropriate bone density determination. [ 43 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3608", "text": "The  Hounsfield scale  is used to measure  radiodensity  and, in reference to  CT scans , can provide an accurate absolute density for the type of  tissue  depicted.  The radiodensity, measured in Hounsfield Units (HU, also known as CT number) is inaccurate in CBCT scans because different areas in the scan appear with different  greyscale  values depending on their relative positions in the organ being scanned, despite possessing identical densities, because the image value of a  voxel  of an organ depends on the position [ clarification needed ]  in the image volume. [ 44 ]   HU measured from the same anatomical area with both CBCT and medical-grade CT scanners are not identical [ 45 ]  and are thus unreliable for determination of site-specific, radiographically-identified bone density for purposes such as the placement of dental implants, as there is \"no good data to relate the CBCT HU values to bone quality.\" [ 46 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3609", "text": "Although some authors have supported the use of CBCT technology to evaluate bone density by measuring HU, [ 47 ] [ 48 ]  such support is provided erroneously because scanned regions of the same density in the skull can have a different grayscale value in the reconstructed CBCT dataset. [ 49 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3610", "text": "X-ray attenuation of CBCT acquisition systems currently produces different HU values for similar bony and soft tissue structures in different areas of the scanned volume (e.g. dense bone has a specific image value at the level of the menton, but the same bone has a significantly different image value at the level of the cranial base). [ 43 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3611", "text": "Dental CBCT systems do not employ a standardized system for scaling the grey levels that represent the reconstructed density values and, as such, they are arbitrary and do not allow for assessment of bone quality. [ 50 ]   In the absence of such a standardization, it is difficult to interpret the grey levels or impossible to compare the values resulting from different machines.  While there is a general acknowledgment that this deficiency exists with CBCT systems (in that they do not correctly display HU), there has been little research conducted to attempt to correct this deficiency. [ 51 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3612", "text": "With time, further advancements in CBCT reconstruction algorithms will allow for improved area detectors, [ 52 ]  and this, together with enhanced postprocessing, will likely solve or reduce this problem. [ 44 ]   A method for establishing attenuation coefficients with which actual HU values can be derived from CBCT \"HU\" values was published in 2010 and further research is currently underway to perfect this method  in vivo . [ 51 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3613", "text": "While the practicality of CBCT fosters its increasing application in IR, technical limitations hinder its integration into the field. The two most significant factors that affect successful integration are image quality and time (for set up, image acquisition, and image reconstruction). Compared to  multidetector computed tomography  (MDCT), the wider collimation in CBCT leads to increased scatter radiation and degradation of image quality as demonstrated by artifacts and decreased  contrast-to-noise ratio . The temporal resolution of  cesium iodide  detectors in CBCT slows data acquisition time to approximately 5 to 20 seconds, which increases  motion artifacts . The time required for image reconstruction takes longer for CBCT (1 minute) compared to MDCT (real time) due to the computationally demanding cone beam reconstruction algorithms. [ 3 ] [ 29 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3614", "text": "Cone-beam spiral computed tomography (CT)  is a  medical imaging  technology that has impacted healthcare since its development in the early 1990s. [ 1 ] [ 2 ]  This technology offers advancements over traditional fan-beam CT, including faster scanning speed, higher image quality, and the ability to generate true three-dimensional volumes, even with contrast-enhancement. It is estimated that the majority of the approximately 300 million CT scans performed annually worldwide use spiral  cone-beam technology."}
{"_id": "WikiPedia_Radiology$$$corpus_3615", "text": "The concept of cone-beam spiral CT was first proposed by Ge Wang in 1991, [ 3 ]  who also introduced algorithms for approximate image reconstruction. A number of researchers and companies have contributed to the development of this technology. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3616", "text": "In 2002, Alexander Katsevich formulated the first theoretically exact cone-beam spiral CT algorithm. [ 5 ] [ 6 ]  The work on cone-beam spiral CT has become a foundational aspect of modern medical imaging, allowing for accurate volumetric image reconstruction from truncated x-ray cone-beam projections. [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3617", "text": "Cone-beam spiral CT uses an X-ray source and multiple detector rows that rotate spirally around the patient. The cone-shaped X-ray beam captures a large volume of data in a single pass, enabling the reconstruction of high-resolution volumetric and dynamic images. Key steps in the cone-beam spiral CT scanning process include:"}
{"_id": "WikiPedia_Radiology$$$corpus_3618", "text": "Cone-beam spiral CT is employed in various medical imaging tasks, including:"}
{"_id": "WikiPedia_Radiology$$$corpus_3619", "text": "Coronary CT angiography  (CTA or CCTA) is the use of  computed tomography (CT) angiography  to assess the  coronary arteries  of the  heart . The patient receives an  intravenous injection  of  radiocontrast  and then the heart is scanned using a high speed  CT scanner , allowing physicians to assess the extent of occlusion in the  coronary arteries , usually in order to diagnose  coronary artery disease ."}
{"_id": "WikiPedia_Radiology$$$corpus_3620", "text": "CTA is superior to  coronary CT calcium scan  in determining the risk of Major Adverse Cardiac Events (MACE). [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3621", "text": "Faster CT machines, due to multidetector capabilities, have made imaging of the  heart  and  circulatory system  very practical in a number of clinical settings. [ 2 ]  The faster capability has allowed the imaging of the heart with minimal involuntary motion, which creates  motion blur  on the image, and has a number of practical applications. [ 2 ]  It may be useful in the diagnosis of suspected coronary heart disease, for follow-up of a  coronary artery bypass , for the evaluation of valvular heart disease and for the evaluation of cardiac masses. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3622", "text": "It is uncertain whether this modality will replace invasive  coronary catheterization . At present, it appears that the greatest utility of cardiac CT lies in ruling out coronary artery disease rather than ruling it in. This is because the test is highly sensitive (over 90% detection rate), so a negative test result largely rules out  coronary artery disease  (i.e. the test has a high  negative predictive value ). [ 3 ]  The test is somewhat less specific, however, so a positive result is less conclusive and may need to be confirmed by subsequent  invasive angiography ."}
{"_id": "WikiPedia_Radiology$$$corpus_3623", "text": "The  positive predictive value  of cardiac CTA is approximately 82% and the  negative predictive value  is around 93%. This means for every 100 patients who appear to have coronary artery disease after CT angiography, 18 of them actually won't have it, and that for every 100 patients who have a negative CT angio test result (i.e. the test says they do not have coronary artery disease), 7 will actually have the disease as defined by the reference standard of invasive coronary angiography via cardiac catheterization. [ 4 ]  Both coronary CT angiography and invasive angiography via cardiac catheterization yield similar diagnostic accuracy when both are being compared to a third reference standard such as  intravascular ultrasound  or  fractional flow reserve . [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3624", "text": "In addition to the diagnostic abilities, cardiac CTA beholds important prognostic information. Stenosis severity and extent of coronary artery disease are important prognostic indicators. [ 7 ]  However, one of the unique features of cardiac CTA is the fact that it enables the visualization of the vessel wall, in a non-invasive manner. Therefore, the technique is able to identify characteristics of coronary artery disease that are associated to the development of  acute coronary syndrome . [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3625", "text": "Because the heart is effectively imaged more than once (described above), cardiac CT angiography can result in a relatively high radiation exposure (around 12  millisievert ), although newer acquisition protocols, have recently been developed which drastically reduce this exposure to around 1\u00a0mSv (cfr. Pavone, Fioranelli,  Dowe: Computed Tomography or  Coronary Arteries, Springer 2009). By comparison, a chest X-ray carries a dose of approximately 0.02-0.2\u00a0mSv [ 10 ]  and natural  background radiation exposure  is around 2.3 mSv/year. [ 11 ]  Thus, each cardiac CT scan carried out with current protocols (dose approximately 1 mSv) is equivalent to approximately 5-50 chest X-rays or less than 1 year of background radiation. Methods are available to decrease this exposure, however, such as prospectively decreasing radiation output based on the concurrently acquired ECG (i.e. tube current modulation.)  This can result in a significant decrease in radiation exposure, at the risk of compromising image quality if there is any arrhythmia during the acquisition. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3626", "text": "The significance of the low radiation doses used in diagnostic imaging is unknown, although the possibility of increasing cancer incidence across a population is of significant concern. This potential risk must be weighed against the competing risk of not diagnosing a significant health problem in a particular individual, such as coronary artery disease."}
{"_id": "WikiPedia_Radiology$$$corpus_3627", "text": "Pregnancy is considered a relative contraindication, similarly to many forms of  medical imaging in pregnancy . The potential harms to a fetus include the application of X-rays in addition to  radiocontrast . Since an iodine-containing  contrast agent  is used, severe contrast agent allergy, uncontrolled hyperthyroidism or renal function impairment are also relative contraindications.  Cardiac arrhythmias ,  coronary artery stents  and  tachycardia  may result in a reduced image quality."}
{"_id": "WikiPedia_Radiology$$$corpus_3628", "text": "With the advent of subsecond rotation combined with multi-slice CT (up to 320 slices), high resolution and high speed can be obtained at the same time, allowing excellent imaging of the coronary arteries (cardiac CT angiography). Images with even higher temporal resolution can be obtained using multi-cycle (also called multi-segmental) image reconstruction. [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3629", "text": "In this technique, a portion of the heart is imaged during one heart cycle while an ECG trace is recorded. During the next heart cycle, the next portion of the heart is scanned for up to 5 total cycles until the entire heart is imaged. The reconstruction algorithm then combines the images from these different cycles to generate one complete image. The advantage of this method is that each image segment is acquired in less time as compared to acquiring the entire heart in one heart cycle, thus improving temporal resolution. The disadvantages are 1) the potential for image artifacts from fusing the image segments and 2) the requirement of additional X-ray radiation for image acquisition."}
{"_id": "WikiPedia_Radiology$$$corpus_3630", "text": "Dual Source CT  scanners, introduced in 2005, allow higher  temporal resolution  by acquiring a full CT slice in only half a rotation, thus reducing motion blurring at high heart rates and potentially allowing for shorter breath-hold time. This is particularly useful for ill patients having difficulty holding their breath or unable to take heart-rate lowering medication."}
{"_id": "WikiPedia_Radiology$$$corpus_3631", "text": "The speed advantages of 64-slice MSCT have rapidly established it as the minimum standard for newly installed CT scanners intended for cardiac scanning. Manufacturers have developed 320-slice and true 'volumetric' scanners, primarily for their improved cardiac scanning performance."}
{"_id": "WikiPedia_Radiology$$$corpus_3632", "text": "Introduction of a CT scanner with a 160\u00a0mm detector in 2014 allows for imaging of the whole heart in a single beat without motion of the coronary arteries, regardless of patient heart rate."}
{"_id": "WikiPedia_Radiology$$$corpus_3633", "text": "The latest MSCT scanners acquire images only at 70-80% of the R-R interval (late diastole). This prospective gating can reduce effective dose from 10 to 15\u00a0mSv to as little as 1.2\u00a0mSv in follow-up patients acquiring at 75% of the R-R interval. Effective dose using MSCT coronary imaging can average less than the dose in conventional coronary angiography."}
{"_id": "WikiPedia_Radiology$$$corpus_3634", "text": "A  CT pulmonary angiogram  ( CTPA ) is a medical diagnostic test that employs  computed tomography (CT) angiography  to obtain an image of the  pulmonary arteries . Its main use is to diagnose  pulmonary embolism  (PE). [ 1 ]  It is a preferred choice of imaging in the diagnosis of PE due to its minimally invasive nature for the patient, whose only requirement for the scan is an intravenous line."}
{"_id": "WikiPedia_Radiology$$$corpus_3635", "text": "Modern MDCT (multi-detector CT) scanners are able to deliver images of sufficient resolution within a short time period, such that CTPA has now supplanted previous methods of testing, such as direct  pulmonary angiography , as the  gold standard  for diagnosis of pulmonary embolism. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3636", "text": "The patient receives an  intravenous  injection of an iodine-containing  contrast agent  at a high rate using an injector pump. Images are acquired with the maximum intensity of radio-opaque contrast in the pulmonary arteries. This can be done using  bolus tracking ."}
{"_id": "WikiPedia_Radiology$$$corpus_3637", "text": "A normal CTPA scan will show the contrast filling the pulmonary vessels, appearing as bright white. Any mass filling defects, such as an embolus, will appear dark in place of the contrast, filling/blocking the space where blood should be flowing into the lungs."}
{"_id": "WikiPedia_Radiology$$$corpus_3638", "text": "CTPA was introduced in the 1990s as an alternative to  ventilation/perfusion scanning  (V/Q scan), which relies on  radionuclide  imaging of the blood vessels of the lung. It is regarded as a highly sensitive and specific test for pulmonary embolism. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3639", "text": "CTPA is typically only requested if pulmonary embolism is suspected clinically. If the probability of PE is considered low, a blood test called  D-dimer  may be requested. If this is negative and risk of a PE is considered negligible, then CTPA or other scans are generally not performed. Most patients will have undergone a  chest X-ray  before CTPA is requested. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3640", "text": "After initial concern that CTPA would miss smaller emboli, a 2007 study comparing CTPA directly with V/Q scanning found that CTPA identified more emboli without increasing the risk of long-term complications compared to V/Q scanning. [ 3 ]  A V/Q scan may still be recommended when a lower  radiation dose  is required. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3641", "text": "On CTPA, acute emboli have been found at  radiodensities  ranging between about 5 and 65  Hounsfield units  (HU), while chronic emboli have ranged between about 30 and 150. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3642", "text": "CTPA is less desirable in  pregnancy  due to the amount of ionizing radiation required, which may damage the breasts, which are particularly sensitive during pregnancy, and because of concerns of the effects of iodine on the fetus'  thyroid  gland. [ 6 ]  V/Q scans can offer lower radiation doses, and may be adapted to further reduce the dose by omitting the lung ventilation portion of the exam. They are therefore recommended to be preferentially applied to pregnant patients. [ 7 ] [ 8 ]  Diagnostic algorithms for pulmonary embolism in pregnancy vary; however, a common compromise is to perform ultrasound testing for  deep vein thrombosis  of the legs, and if this is positive, make the diagnosis of pulmonary embolism on the basis of symptoms and presence of the DVT. CTPA would then only be performed if exhaustive non-radiation based testing could not make a positive diagnosis."}
{"_id": "WikiPedia_Radiology$$$corpus_3643", "text": "CTPA is contraindicated in known or suspected  allergy  to  contrast media  or in  kidney failure  (where contrast agents could worsen the kidney function). [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3644", "text": "The best results are obtained using  multidetector computed tomography  (MDCT) scanners. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3645", "text": "An  intravenous cannula  is required for the administration of  iodinated contrast . The typical dose is 30-40 g of iodine (corresponding to 20\u201330 cc of 370 mg/ml iodine solution). [ 10 ]  However, for patients at high risk of  contrast-induced nephropathy , it is possible to reduce the required amount of contrast using  dual energy CT . With such a protocol, only 7\u201310 g of iodine (20\u201330 cc of 370 mg/ml iodine solution) may be needed. [ 10 ]  Many hospitals use  bolus tracking , where the scan commences when the contrast is detected at the level of the proximal  pulmonary arteries . If this is done manually, scanning commences about 10\u201312 seconds after the injection has started. Slices of 1\u20133\u00a0mm. are performed at 1\u20133\u00a0mm. intervals, depending on the nature of the scanner (single- versus multidetector). [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3646", "text": "High contrast flow rate of 4ml/sec through 18G branula at  antecubital fossa  is recommended to achieve optimal quality images. However, for those with  peripheral arterial disease  and those with  central venous catheter  with low flow rate, 2.0 to 2.5 ml/sec are still manage to produce acceptable images. [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3647", "text": "State of the art  modern CT scanners with a scan rate of up to 320\u00a0mm/s can acquire all the images within a 1-second X-ray exposure, avoiding the problems of respiratory motion, cardiac motion and contrast draining from the pulmonary circulation during the study. Even though the actual scan may be completed in 1 second or less, considerable staff and patient time is required for preparation of the contrast agent, positioning on the scanner and planning the scan. This is particularly the case, as patients undergoing CTPA are frequently seriously unwell requiring  oxygen  treatment and/or close monitoring."}
{"_id": "WikiPedia_Radiology$$$corpus_3648", "text": "On CTPA, the pulmonary vessels are filled with contrast, and appear white. Any mass filling defects ( embolus  or other matter such as  fat ) appears darker. Ideally, the scan should be complete before the contrast reaches the left side of the heart and the  aorta , as this may mean contrast has drained from the pulmonary arteries, or require a larger dose of contrast media. [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3649", "text": "Other from assessing any filing defect within the pulmonary trunk and its segmental branches, the diameter of the right heart can be compared with diameter of the left heart. The right heart diameter should not be more than the diameter of left heart. Normally, the interventricular septum should mildly bulge into the right ventricle due to high pressure within the left ventricle. Any reverse bulge or flattening of the interventricular septum indicates  pulmonary hypertension . [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3650", "text": "Pericardial effusion  may also be seen in pulmonary hypertension. Thickening of pericardium more than 4 mm or pericardial calcification indicates  constrictive pericarditis . [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3651", "text": "Digital radiography  is a form of  radiography  that uses x-ray\u2013sensitive plates to directly capture data during the patient examination, immediately transferring it to a computer system without the use of an intermediate cassette. [ 1 ]  Advantages include time efficiency through bypassing chemical processing and the ability to digitally transfer and enhance images. Also, less  radiation  can be used to produce an image of similar  contrast  to conventional radiography."}
{"_id": "WikiPedia_Radiology$$$corpus_3652", "text": "Instead of X-ray film, digital radiography uses a digital image capture device. This gives advantages of immediate image preview and availability; elimination of costly film processing steps; a wider dynamic range, which makes it more forgiving for over- and under-exposure; as well as the ability to apply special image processing techniques that enhance overall display quality of the image."}
{"_id": "WikiPedia_Radiology$$$corpus_3653", "text": "Flat panel detectors (FPDs) are the most common kind of direct digital detectors. [ 2 ]  They are classified in two main categories:"}
{"_id": "WikiPedia_Radiology$$$corpus_3654", "text": "1.  Indirect FPDs   Amorphous silicon  (a-Si) is the most common material of commercial FPDs. Combining a-Si detectors with a  scintillator  in the detector\u2019s outer layer, which is made from  caesium iodide  (CsI) or  gadolinium oxysulfide  (Gd 2 O 2 S), converts X-rays to light. Because of this conversion the a-Si detector is considered an indirect imaging device. The light is channeled through the a-Si photodiode layer where it is converted to a digital output signal. The digital signal is then read out by  thin film transistors  (TFTs) or fiber-coupled CCDs. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3655", "text": "2.  Direct FPDs . Amorphous  selenium  (a-Se) FPDs are known as \u201cdirect\u201d detectors because X-ray  photons  are converted directly into charge. The outer layer of the flat panel in this design is typically a high-voltage  bias electrode . X-ray photons create  electron-hole pairs  in a-Se, and the transit of these electrons and holes depends on the potential of the bias voltage charge. As the holes are replaced with electrons, the resultant charge pattern in the selenium layer is read out by a TFT array, active matrix array, electrometer probes or microplasma line addressing. [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3656", "text": "Detectors based on  CMOS  and  charge-coupled device  (CCD) have also been developed, but despite lower costs compared to FPDs of some systems, bulky designs and worse image quality have precluded widespread adoption. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3657", "text": "A high-density line-scan solid state detector is composed of a photostimulable barium fluorobromide doped with europium (BaFBr:Eu) or caesium bromide (CsBr) phosphor. The phosphor detector records the X-ray energy during exposure and is scanned by a laser diode to excite the stored energy which is released and read out by a digital image capture array of a CCD."}
{"_id": "WikiPedia_Radiology$$$corpus_3658", "text": "Phosphor plate radiography [ 6 ]  resembles the old analogue system of a light sensitive film sandwiched between two x-ray sensitive screens, the difference being the analogue film has been replaced by an imaging plate with photostimulable phosphor (PSP), which records the image to be read by an image reading device, which transfers the image usually to a  Picture archiving and communication system  (PACS). [ 6 ]  It is also called photostimulable phosphor (PSP) plate-based radiography or  computed radiography [ 7 ]  (not to be confused with  computed tomography  which uses computer processing to convert multiple projectional radiographies to a  3D image )."}
{"_id": "WikiPedia_Radiology$$$corpus_3659", "text": "After X-ray exposure the plate (sheet) is placed in a special scanner where the  latent image  is retrieved point by point and digitized, using  laser  light scanning. The digitized images are stored and displayed on the computer screen. [ 7 ]  Phosphor plate radiography has been described as having an advantage of fitting within any pre-existing equipment without modification because it replaces the existing film; however, it includes extra costs for the scanner and replacement of scratched plates."}
{"_id": "WikiPedia_Radiology$$$corpus_3660", "text": "Initially phosphor plate radiography was the system of choice; early DR [ clarification needed ]  systems were prohibitively expensive (each cassette costs \u00a340-\u00a350K), and as the 'technology was being taken to the patient', prone to damage. [ 8 ]  Since there is no physical printout, and after the readout process a digital image is obtained, CR [ clarification needed ]  has been known [ by whom? ]  as an indirect digital technology, bridging the gap between x-ray film and fully digital detectors. [ 9 ] [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3661", "text": "Digital radiography (DR) has existed in various forms (for example, CCD and amorphous Silicon imagers) in the security X-ray inspection field for over 20 years and is steadily replacing the use of film for inspection X-rays in the Security and  nondestructive testing  (NDT) fields. [ 11 ]  DR has opened a window of opportunity for the security NDT industry due to several key advantages including excellent image quality, high POD (probability of detection), portability, environmental friendliness and immediate imaging. [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3662", "text": "Nondestructive testing of materials is vital in fields such as  aerospace  and  electronics  where integrity of materials is vital for safety and cost reasons. [ 13 ]  Advantages of digital technologies include the ability to provide results in real time. [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3663", "text": "In  radiography ,  focal plane tomography [ 1 ]  is  tomography  (imaging a single plane, or slice, of an object) by simultaneously moving the  X-ray generator  and  X-ray detector  so as to keep a consistent exposure of only the plane of interest during image acquisition. This was the main method of obtaining tomographs in  medical imaging  until the late-1970s. It has since been largely replaced by more advanced imaging techniques such as  CT  and  MRI . It remains in use today in a few specialized applications, such as for acquiring  orthopantomographs  of the jaw in  dental radiography ."}
{"_id": "WikiPedia_Radiology$$$corpus_3664", "text": "Focal plane tomography\u2019s development began in the 1930s as a means of reducing the problem of  superimposition  of structures which is inherent to  projectional radiography . [ 2 ]  It was invented in parallel by, among others, by the French physician  Bocage , the Italian radiologist  Alessandro Vallebona  and the Dutch radiologist  Bernard George Ziedses des Plantes . [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3665", "text": "Focal plane tomography generally uses mechanical movement of an  X-ray  source and film in unison to generate a tomogram using the principles of  projective geometry . [ 4 ]  Synchronizing the movement of the radiation source and detector which are situated in the opposite direction from each other causes structures which are not in the  focal plane  being studied to blur out."}
{"_id": "WikiPedia_Radiology$$$corpus_3666", "text": "The blurring provided by focal plane tomography is only marginally effective, since it only occurs in the  X   plane . Moreover, since focal plane tomography uses plain X-rays, it is not particularly effective at resolving soft tissues."}
{"_id": "WikiPedia_Radiology$$$corpus_3667", "text": "The increased availability and power of computers in the 1960s and 70s gave rise to new imaging techniques such as CT and MRI which use computational (in addition to or in lieu of mechanical) methods to acquire and process tomographic image data, and which do not suffer from the limitations of focal plane tomography."}
{"_id": "WikiPedia_Radiology$$$corpus_3668", "text": "Initially focal plane tomography used simple linear movements. The technique advanced through the mid-twentieth century however, steadily producing sharper images, and with a greater ability to vary the thickness of the cross-section being examined. [ 4 ]  This was achieved through the introduction of more complex, pluridirectional devices that can move in more than one plane and perform more effective blurring."}
{"_id": "WikiPedia_Radiology$$$corpus_3669", "text": "This is the most basic form of conventional tomography. The  X-ray tube  moved from point \"A\" to point \"B\" above the patient, while the detector (such as cassette holder or \"bucky\") moves simultaneously under the patient from point \"B\" to point \"A\". [ 5 ]  The  fulcrum , or pivot point, is set to the area of interest. In this manner, the points above and below the focal plane are blurred out, just as the background is blurred when panning a camera during exposure. Rarely used, and has largely been replaced by  computed tomography  (CT)."}
{"_id": "WikiPedia_Radiology$$$corpus_3670", "text": "This was achieved using a more advanced X-ray apparatus that allows for more sophisticated and continuous movements of the X-ray tube and film. With this technique, a number of complex synchronous geometrical movements could be programmed, such as hypocycloidic, circular, figure 8, and  elliptical .  Philips  Medical Systems for example produced one such device called the 'Polytome'. [ 4 ]  This pluridirectional unit was still in use into the 1990s, as its resulting images for small or difficult physiology, such as the inner ear, were still difficult to image with CTs at that time. As the resolution of CT scanners got better, this procedure was taken over by CT. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3671", "text": "This is a variant of linear tomography, where a limited arc of movement is used, resulting in less blurring than linear tomography. [ 7 ]  It is still used in some centres for visualising the  kidney  during an  intravenous urogram  (IVU), [ 8 ]  though it too is being supplanted by CT. [ 9 ] [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3672", "text": "Panoramic radiography  is the only common tomographic examination still in use. This makes use of a complex movement to allow the radiographic examination of the  mandible , as if it were a flat bone. [ 11 ]  It is commonly performed in dental practices and is often referred to as a \"Panorex\", though this is a trademark of a specific company and not a generic term."}
{"_id": "WikiPedia_Radiology$$$corpus_3673", "text": "A  full-body scan  is a scan of the patient's entire body as part of the  diagnosis  or treatment of illnesses. If  computed tomography  ( CAT ) scan technology is used, it is known as a  full-body CT scan , though many medical imaging technologies can perform full-body scans."}
{"_id": "WikiPedia_Radiology$$$corpus_3674", "text": "Full-body CT scans allow a transparent view of the body. For  polytrauma  patients, aggressive use of full-body CT scanning improves early diagnosis of injury and improves survival rates,\n [ 1 ] \nwith widespread adoption of the technique seen worldwide. [ 2 ] \nFull-body CT scans are not indicated in patients with minor or single system trauma, and should be avoided in such patients. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3675", "text": "Many possible malignancies are discovered with a full-body scan, but these are almost always benign. [ 3 ] [ 4 ]  These may not be related to any disease, and may be benign growths,  scar tissue , or the remnants of previous  infections . CT scanning for other reasons sometimes identifies these \" incidentalomas \"."}
{"_id": "WikiPedia_Radiology$$$corpus_3676", "text": "However, the significance of radiation exposure as well as costs associated with these studies must be considered, especially in patients with low energy mechanisms of injury and absent physical examination findings consistent with major trauma."}
{"_id": "WikiPedia_Radiology$$$corpus_3677", "text": "A full-body scan has the potential to identify disease (e.g.  cancer ) in early stages, and early identification can improve the success of curative efforts.  Controversy arises from the use of full-body scans in the  screening  of patients who have no signs or  symptoms  suggestive of a disease. [ 5 ]  As with any test that screens for disease, the risks of full-body CT scans need to be weighed against the benefit of identifying a treatable disease at an early stage. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3678", "text": "An alternative to a full-body CT scan may be  Magnetic resonance imaging  (MRI) scans. MRI scans are generally more expensive than CT but do not expose the patient to ionizing radiation and are being evaluated for their potential value in screening. [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3679", "text": "Compared to most other diagnostic imaging procedures, CT scans result in relatively high  radiation exposure . This exposure may be associated with a very small increase in cancer risk. The question is whether that risk is outweighed by the benefits of diagnosis and therapy [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3680", "text": "The procedure has a low rate of finding disease. [ 3 ] [ 4 ]  It can cause confusion regarding  incidentalomas . It is uncertain how to treat some of them, or if treatment is even necessary. [ 9 ] \nThe test also cannot detect colors, unlike for example a  colonoscopy ."}
{"_id": "WikiPedia_Radiology$$$corpus_3681", "text": "At a cost of  US$ 600 to $3000, full-body scans are expensive, and are rarely covered by insurance. [ 10 ] [ 11 ]  However, in December 2007, the  IRS  stated that full-body scans qualify as deductible medical expenses, without a doctor's referral. This will likely lead employer-sponsored, flexible-spending plans to make the cost of the scans eligible for reimbursement. [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3682", "text": "Gynoroentgenology  is the abbreviation of  gynecological roentgenology . It is the  radiologic  imaging of the  gynecologic  parts of the  female   human body  in order to make a  radiologic   diagnosis  of a gynecologic disease.  The term  gynecologic radiology  is related to gynoroentgenology.   Gynoroentgenologic imaging  can detect and diagnose primary  neoplasms ,  metastasis , therapy-related  lesions ,  congenital  lesions,  inflammation , miscellaneous diseases, pseudolesions, normal variants, infection uterine arteriovenous  malformations  and  cystic   adenomyosis . [ 1 ]   An example procedure is  gynography ."}
{"_id": "WikiPedia_Radiology$$$corpus_3683", "text": "Lymphography  is a  medical imaging  technique in which a  radiocontrast  agent is injected, and then an  X-ray  picture is taken to visualise structures of the  lymphatic system , including  lymph nodes ,  lymph ducts ,  lymphatic tissues ,  lymph capillaries  and  lymph vessels .  Lymphangiography  is the same procedure, used only to visualize the  lymph vessels . [ 1 ]  The x-ray film or image of the  lymphatic vessels  and  lymph nodes  is called a  lymphogram  or a  lymphangiogram ."}
{"_id": "WikiPedia_Radiology$$$corpus_3684", "text": "Radiographs can be taken after injection of a  radiopaque  contrast medium into small lymphatic vessels (these are made visible by prior  subcutaneous injection  of patent blue dye). The resulting lymphogram is used to find the locations of large vessels and nodes, and to identify sites of blockage in lymphatic drainage."}
{"_id": "WikiPedia_Radiology$$$corpus_3685", "text": "Lymph nodes can also be detected via  radionuclide imaging  after injection of radioactive  colloids .  Macrophages   phagocytose  these foreign bodies and sequester in the nodes."}
{"_id": "WikiPedia_Radiology$$$corpus_3686", "text": "Lymphography is used to visualise the structures of the  lymphatic system , including  lymph nodes ,  lymph ducts ,  lymphatic tissues ,  lymph capillaries  and  lymph vessels . It can be used during thoracic duct embolisation. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3687", "text": "Lymphography is not commonly used in modern medicine since the adoption of  CT scan  and  PET scan  technologies. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3688", "text": "Lymphograhy is usually considered a very safe procedure. [ 3 ]  The most serious adverse reaction tends to be a possible  allergic reaction  to injected  contrast agent . [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3689", "text": "Lymphography is often an invasive procedure. [ 1 ]  It may be difficult to access  lymphatic vessels , as they are usually very narrow and hard to locate. The procedure also takes a very long time to perform. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3690", "text": "A needle or  catheter  is inserted into a  lymphatic vessel  in either the  foot  or the  arm . A  contrast agent  is injected into the lymphatic vessel. [ 1 ]  This may be around 2 to 4  millilitres  of  iotrolan  or  iodixanol   solution . [ 3 ]  This is performed at a very slow rate of around 0.1 millilitres per  minute . [ 3 ]  This prevents damage to the lymphatic vessel and disrupting the normal rate of lymph flow. It can take approximately 60 to 90  minutes  for all the contrast medium to be injected. Once the contrast medium is injected, the catheter is removed, and the incisions are  stitched  and  bandaged ."}
{"_id": "WikiPedia_Radiology$$$corpus_3691", "text": "A  fluoroscope  is used to follow the dye as it spreads through the lymphatic system through the  legs , into the  groin , and along the back of the  abdominal cavity .  X-rays  are taken of the legs,  pelvis ,  abdomen , and  thorax  areas. The next day, another set of X-rays may be taken."}
{"_id": "WikiPedia_Radiology$$$corpus_3692", "text": "If a site of  cancer  ( breast cancer  or  melanoma ) is being studied to evaluate spreading, a mixture of blue dye and a  radioactive  tracer is injected next to the mass. [ 3 ]  Special cameras detect the spread of tracer along lymph channels to outlying lymph nodes. A  surgeon  will then use the visible blue dye or radioactivity within nodes to guide  biopsy  within adjacent tissues (such as the arm pit for breast cancer) to determine possible routes of cancer spread. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3693", "text": "The name comes from the  Greek  words \"\u039b\u03ad\u03bc\u03c6\u03bf\u03c2\" (\"Lemphos\")(\"lymph\"), \"water lymph\", and \"graphien\" \"\u0393\u03c1\u03b1\u03c6\u03ae\"(\"Graphy\"), \"to write or record\"."}
{"_id": "WikiPedia_Radiology$$$corpus_3694", "text": "Mammography  (also called  mastography ;  DICOM  modality: MG) is the process of using low-energy  X-rays  (usually around 30  kVp ) to examine the human  breast  for diagnosis and screening. The goal of mammography is the early detection of  breast cancer , typically through detection of characteristic masses,  microcalcifications , asymmetries, and distortions."}
{"_id": "WikiPedia_Radiology$$$corpus_3695", "text": "As with all X-rays, mammograms use doses of  ionizing radiation  to create images. These images are then analyzed for abnormal findings. It is usual to employ lower-energy X-rays, typically Mo (K-shell X-ray energies of 17.5 and 19.6 keV) and Rh (20.2 and 22.7 keV) than those used for  radiography  of  bones . Mammography may be 2D or 3D ( tomosynthesis ), depending on the available equipment or purpose of the examination.  Ultrasound ,  ductography ,  positron emission mammography  (PEM), and  magnetic resonance imaging  (MRI) are adjuncts to mammography. Ultrasound is typically used for further evaluation of masses found on mammography or palpable masses that may or may not be seen on mammograms. Ductograms are still used in some institutions for evaluation of bloody nipple discharge when the mammogram is non-diagnostic. MRI can be useful for the screening of high-risk patients, for further evaluation of questionable findings or symptoms, as well as for pre-surgical evaluation of patients with known breast cancer, in order to detect additional lesions that might change the surgical approach (for example, from breast-conserving  lumpectomy  to  mastectomy )."}
{"_id": "WikiPedia_Radiology$$$corpus_3696", "text": "In 2023, the  U.S. Preventive Services Task Force  issued a draft recommendation statement that all women should receive a screening mammography every two years from age 40 to 74. [ 1 ] [ 2 ]  The American College of Radiology, Society of Breast Imaging, and American Cancer Society recommend yearly screening mammography starting at age 40. [ 3 ]  The Canadian Task Force on Preventive Health Care (2012) and the European Cancer Observatory (2011) recommend mammography every 2 to 3 years between ages 50 and 69. [ 4 ] [ 5 ]  These task force reports point out that in addition to unnecessary surgery and anxiety, the risks of more frequent mammograms include a small but significant increase in breast cancer induced by radiation. [ 6 ] [ 7 ]  Additionally, mammograms should not be performed with increased frequency in patients undergoing breast surgery, including breast enlargement, mastopexy, and breast reduction. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3697", "text": "Digital mammography is a specialized form of mammography that uses digital receptors and computers instead of  X-ray  film to help examine  breast  tissue for  breast cancer . [ 9 ]  The electrical signals can be read on computer screens, permitting more manipulation of images to allow  radiologists  to view the results more clearly. [ 9 ] [ 10 ]  The standard digital mammography is \"full field\" (FFDM), in which the entire breast is imaged in a single view. [ 9 ]  Digital mammography can also include the use of \"spot views\", in which a paddle is used to further compress areas of concern. [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3698", "text": "Digital mammography is also utilized in  stereotactic biopsy . Breast biopsy may also be performed using a different modality, such as  ultrasound  or  magnetic resonance imaging  (MRI)."}
{"_id": "WikiPedia_Radiology$$$corpus_3699", "text": "While radiologists [ 12 ]  had hoped for more marked improvement, the effectiveness of digital mammography was found comparable to traditional X-ray methods in 2004, though there may be reduced radiation with the technique and it may lead to fewer retests. [ 9 ]   Specifically, it performs no better than film for post-menopausal women, who represent more than three-quarters of women with breast cancer. [ 13 ]  The U.S. Preventive Services Task Force concluded that there was insufficient evidence to recommend for or against digital mammography over basic film mammography for breast cancer screening. [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3700", "text": "Digital mammography is a  NASA spin-off , utilizing technology developed for the  Hubble Space Telescope . [ 15 ]  As of 2022, over 99% of certified mammography centers in the United States screening centers use digital mammography. [ 16 ]  Globally, systems by  Fujifilm Corporation  are the most widely used. [ citation needed ]  In the United States, GE's digital imaging units typically cost US$300,000 to $500,000, far more than film-based imaging systems. [ 13 ]  Costs may decline as GE begins to compete with the less expensive  Fuji  systems. [ 13 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3701", "text": "Three-dimensional mammography , also known as digital breast tomosynthesis (DBT),  tomosynthesis , and 3D breast imaging, is a mammogram technology that creates a 3D view of the breast using X-rays from different angles. Supplementing standard 2D mammography with DBT has been shown to improve cancer detection. [ 17 ]  Cost effectiveness is unclear as of 2016. [ 18 ]  Another concern is that it more than doubles the radiation exposure. [ 19 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3702", "text": "Photon-counting mammography was introduced commercially in 2003 and was shown to reduce the X-ray dose to the patient by approximately 40% compared to conventional methods while maintaining image quality at an equal or higher level. [ 20 ]  The technology was subsequently developed to enable  spectral imaging  with the possibility to further improve image quality, to distinguish between different tissue types, [ 21 ]  and to measure breast density. [ 22 ] [ 23 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3703", "text": "A galactography (or breast ductography) is a now infrequently used type of mammography used to visualize the milk ducts. Prior to the mammography itself, a radiopaque substance is injected into the duct system. This test is indicated when nipple discharge exists."}
{"_id": "WikiPedia_Radiology$$$corpus_3704", "text": "Mammography can detect cancer early when it\u2019s most treatable and can be treated less invasively (thereby helping to preserve quality of life)."}
{"_id": "WikiPedia_Radiology$$$corpus_3705", "text": "According to  National Cancer Institute  data, since mammography screening became widespread in the mid-1980s, the U.S. breast cancer death rate, unchanged for the previous 50 years, has dropped well over 30 percent. [ 24 ]  In European countries like Denmark and Sweden, where mammography screening programs are more organized, the breast cancer death rate has been cut almost in half over the last 20 years. [ as of? ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3706", "text": "Mammography screening cuts the risk of dying from breast cancer nearly in half. [ 25 ]  A recent study published in  Cancer  showed that more than 70 percent of the women who died from breast cancer in their 40s at major Harvard teaching hospitals were among the 20 percent of women who were not being screened. [ 26 ] [ unreliable medical source ]  Some scientific studies [ citation needed ]  have shown that the most lives are saved by screening beginning at age 40."}
{"_id": "WikiPedia_Radiology$$$corpus_3707", "text": "A recent study in the  British Medical Journal  shows that early detection of breast cancer \u2013 as with mammography \u2013 significantly improves breast cancer survival. [ 27 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3708", "text": "The benefits of mammography screening at decreasing breast cancer mortality in randomized trials are not found in observational studies performed long after implementation of breast cancer screening programs (for instance, Bleyer et al. [ 28 ] )"}
{"_id": "WikiPedia_Radiology$$$corpus_3709", "text": "In 2014, the Surveillance, Epidemiology, and End Results Program of the National Institutes of Health reported the occurrence rates of breast cancer based on 1000 women in different age groups. [ 29 ]  In the 40\u201344 age group, the incidence was 1.5 and in the 45\u201349 age group, the incidence was 2.3. [ 29 ]  In the older age groups, the incidence was 2.7 in the 50\u201354 age group and 3.2 in the 55\u201359 age group. [ 29 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3710", "text": "While screening between ages 40 and 50 is somewhat controversial, the preponderance of the evidence indicates that there is a benefit in terms of early detection. Currently, the  American Cancer Society , the  American Congress of Obstetricians and Gynecologists (ACOG) , the  American College of Radiology , and the  Society of Breast Imaging  encourage annual mammograms beginning at age 40. [ 30 ] [ 31 ] [ 32 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3711", "text": "The  National Cancer Institute  encourages mammograms every one to two years for women ages 40 to 49. [ 33 ]   In 2023,  United States Preventive Services Task Force  (USPSTF) revised the recommendation that women and transgender men undergo biennial mammograms starting at the age of 40, rather than the previously suggested age of 50. [ 34 ]  This adjustment is prompted by the increasing incidence of breast cancer in the 40 to 49 age group over the past decade."}
{"_id": "WikiPedia_Radiology$$$corpus_3712", "text": "In contrast, the  American College of Physicians , a large internal medicine group, has recently encouraged individualized screening plans as opposed to wholesale biannual screening of women aged 40 to 49. [ 35 ]  The  American Cancer Society  recommendations for women at average risk for breast cancer is a yearly mammogram from age 45 to 54 with an optional yearly mammogram from age 40 to 44. [ 36 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3713", "text": "Women who are at high risk for early-onset breast cancer have separate recommendations for screening. These include those who:"}
{"_id": "WikiPedia_Radiology$$$corpus_3714", "text": "The  American College of Radiology  recommends these individuals to get annual mammography starting at the age of 30. Those with a history of chest radiation therapy before age 30 should start annually at age 25 of 8 years after their latest therapy (whichever is latest). [ 38 ]  The  American Cancer Society  also recommends women at high risk should get a mammogram and breast MRI every year beginning at age 30 or an age recommended by their healthcare provider. [ 36 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3715", "text": "The  National Comprehensive Cancer Network  (NCCN) advocates screening for women who possess a BRCA1 or BRCA2 mutation or have a first-degree relative with such a mutation, even in the absence of the patient being tested for BRCA1/2 mutations. For women at high risk, NCCN recommends undergoing an annual mammogram and breast MRI between the ages of 25 and 40, considering the specific gene mutation type or the youngest age of breast cancer occurrence in the family. Additionally, NCCN suggests that high-risk women undergo clinical breast exams every 6 to 12 months starting at age 25. These individuals should also engage in discussions with healthcare providers to assess the advantages and disadvantages of 3D mammography and acquire knowledge on detecting changes in their breasts. [ 39 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3716", "text": "The radiation exposure associated with mammography is a potential risk of screening, which appears to be greater in younger women. In scans where women receive 0.25\u201320 Gray (Gy) of radiation, they have more of an elevated risk of developing breast cancer. [ 40 ]  A study of radiation risk from mammography concluded that for women 40 years of age and older, the risk of radiation-induced breast cancer was minuscule, particularly compared with the potential benefit of mammographic screening, with a benefit-to-risk ratio of 48.5 lives saved for each life lost due to radiation exposure. [ 41 ]  This also correlates to a decrease in breast cancer mortality rates by 24%. [ 40 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3717", "text": "The mammography procedure can be painful. Reported pain rates range from 6\u201376%, with 23\u201395% experiencing pain or discomfort. [ 42 ]  Experiencing pain is a significant predictor in women not re-attending screening. [ 43 ]  There are few proven interventions to reduce pain in mammography, but evidence suggests that giving women information about the mammography procedure prior to it taking place may reduce the pain and discomfort experienced. [ 44 ]  Furthermore, research has found that standardised compression levels can help to reduce patients' pain while still allowing for optimal diagnostic images to be produced. [ 45 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3718", "text": "During the procedure, the breast is compressed using a dedicated mammography unit. Parallel-plate compression evens out the thickness of breast  tissue  to increase image quality by reducing the thickness of tissue that X-rays must penetrate, decreasing the amount of scattered radiation (scatter degrades image quality), reducing the required radiation dose, and holding the breast still (preventing  motion blur ). In screening mammography, both head-to-foot (craniocaudal, CC) view and angled side-view (mediolateral oblique, MLO) images of the breast are taken. Diagnostic mammography may include these and other views, including geometrically magnified and spot-compressed views of the particular area of concern. [ citation needed ]   Deodorant [ citation needed ] ,  talcum powder [ 46 ]  or  lotion  may show up on the X-ray as  calcium  spots, so women are discouraged from applying them on the day of their exam. There are two types of mammogram studies: screening mammograms and diagnostic mammograms. Screening mammograms, consisting of four standard X-ray images, are performed yearly on patients who present with no symptoms. Diagnostic mammograms are reserved for patients with breast symptoms (such as palpable lumps, breast pain, skin changes, nipple changes, or nipple discharge), as follow-up for probably benign findings (coded BI-RADS 3), or for further evaluation of abnormal findings seen on their screening mammograms. Diagnostic mammograms may also performed on patients with personal or family histories of breast cancer. Patients with breast implants and other stable benign surgical histories generally do not require diagnostic mammograms."}
{"_id": "WikiPedia_Radiology$$$corpus_3719", "text": "Until some years ago, mammography was typically performed with screen-film cassettes. Today, mammography is undergoing transition to digital detectors, known as  digital mammography  or Full Field Digital Mammography (FFDM). The first FFDM system was approved by the FDA in the U.S. in 2000. This progress is occurring some years later than in general radiology. This is due to several factors:"}
{"_id": "WikiPedia_Radiology$$$corpus_3720", "text": "As of March 1, 2010, 62% of facilities in the United States and its territories have at least one FFDM unit. [ 47 ]  (The FDA includes computed radiography units in this figure. [ 48 ] )"}
{"_id": "WikiPedia_Radiology$$$corpus_3721", "text": "Tomosynthesis, otherwise known as 3D mammography, was first introduced in clinical trials in 2008 and has been  Medicare -approved in the United States since 2015. As of 2023, 3D mammography has become widely available in the US and has been shown to have improved sensitivity and specificity over 2D mammography."}
{"_id": "WikiPedia_Radiology$$$corpus_3722", "text": "Mammograms are either looked at by one (single reading) or two (double reading) trained professionals: [ 49 ]  these film readers are generally  radiologists , but may also be  radiographers ,  radiotherapists , or breast clinicians (non-radiologist physicians specializing in breast disease). [ 49 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3723", "text": "Double reading significantly improves the  sensitivity and specificity  of the procedure, and is standard practice in the United Kingdom, but not in the United States as it is not reimbursed by Medicare or private  health insurance . This is despite multiple trials showing increased accuracy of detection and improved patient outcomes for both  morbidity  and  mortality  when double reading is employed. [ 49 ]   Clinical decision support systems  may be used with  digital mammography  (or digitized images from analogue mammography [ 50 ] ), but studies suggest these approaches do not significantly improve performance or provide only a small improvement. [ 49 ] [ 51 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3724", "text": "Stratification for breast cancer risk on a mammogram is based on a reporting system known as Breast Imaging-Reporting and Data System ( BI-RADS ), developed by the  American College of Radiology  in 1993. It has five general categories of findings: mass, asymmetry, architectural distortion, calcifications, and associated features."}
{"_id": "WikiPedia_Radiology$$$corpus_3725", "text": "The use of language with BI-RADS is extremely precise, with a limited set of permissible adjectives for lesion margins, shape and internal density, each of which carries a different prognostic significance. Margins of a lesion, for example, can only be described as  circumscribed ,  obscured ,  micropapillary ,  indistinct  or  stellate . Similarly, shape can only be  round ,  oval  or  irregular . Each of these agreed upon adjectives is referred to as a \"descriptor\" in the BI-RADS lexicon, with specific  positive  and  negative predictive values  for breast cancer with each word. Additionally, each BI-RADS category corresponds with a probability of cancer. This fastiduous attention to semantics with BI-RADS allows for standardization of cancer detection across different treatment centers and imaging modalities. [ 52 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3726", "text": "After describing the findings, the radiologist provides a final assessment ranging from 0 to 6:"}
{"_id": "WikiPedia_Radiology$$$corpus_3727", "text": "BI-RADS 3, 4 and 5 assessments on  screening mammograms  require further investigation with a second \"diagnostic\" study. The latter is a more detailed mammogram that allows dedicated attention to the abnormal finding with additional maneuvers such as magnification, rolling of breast tissue or exaggerated positioning. There may also be imaging with  ultrasound  at this time, which carries its own parallel BI-RADS lexicon. Suspicious lesions are then  biopsied  with  local anesthesia  or proceed straight to surgery depending on their  staging .  [ 55 ]  Biopsy can be done with  the help of x-rays  or  ultrasound , depending on which imaging modality shows the lesion best. [ 56 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3728", "text": "In the UK mammograms are scored on a scale from 1\u20135 (1 = normal, 2 = benign, 3 = indeterminate, 4 = suspicious of malignancy, 5 = malignant). Evidence suggests that accounting for genetic risk, factors improve breast cancer risk prediction. [ 57 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3729", "text": "As a medical procedure that induces ionizing radiation, the origin of mammography can be traced to the discovery of X-rays by  Wilhelm R\u00f6ntgen  in 1895."}
{"_id": "WikiPedia_Radiology$$$corpus_3730", "text": "In 1913, German surgeon  Albert Salomon  performed a mammography study on 3,000  mastectomies , comparing X-rays of the breasts to the actual removed tissue, observing specifically  microcalcifications . [ 58 ] [ 59 ]   By doing so, he was able to establish the difference as seen on an  X-ray  image between cancerous and non-cancerous tumors in the breast. [ 59 ]   Salomon's mammographs provided substantial information about the spread of tumors and their borders. [ 60 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3731", "text": "In 1930, American physician and radiologist  Stafford L. Warren  published \"A Roentgenologic Study of the Breast\", [ 61 ]  a study where he produced  stereoscopic  X-rays images to track changes in breast tissue as a result of  pregnancy  and  mastitis . [ 62 ] [ 63 ]  In 119 women who subsequently underwent surgery, he correctly found breast cancer in 54 out of 58 cases. [ 62 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3732", "text": "As early as 1937,  Jacob Gershon-Cohen  developed a form a mammography for a diagnostic of breast cancer at earlier stages to improve survival rates. [ 64 ]  In 1949, Raul Leborgne sparked renewed enthusiasm for mammography by emphasizing the importance of technical proficiency in patient positioning and the adoption of specific radiological parameters. He played a pioneering role in elevating imaging quality while placing particular emphasis on distinguishing between benign and malignant calcifications. [ 65 ]  In the early 1950s, Uruguayan radiologist Raul Leborgne developed the breast compression technique to produce better quality images, and described the differences between benign and malign microcalcifications. [ 66 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3733", "text": "In 1956, Gershon-Cohen conducted clinical trails on over 1,000 asymptomatic women at the  Albert Einstein Medical Center  on his screening technique, [ 64 ]  and the same year, Robert Egan at the  University of Texas M.D. Anderson Cancer Center  combined a technique of low kVp with high mA and single emulsion films developed by  Kodak  to devise a method of screening mammography. He published these results in 1959 in a paper, subsequently vulgarized in a 1964 book called  Mammography . [ 67 ]  The \"Egan technique\", as it became known, enabled physicians to detect calcification in breast tissue; [ 68 ]  of the 245 breast cancers that were confirmed by biopsy among 1,000 patients, Egan and his colleagues at M.D. Anderson were able to identify 238 cases by using his method, 19 of which were in patients whose physical examinations had revealed no breast pathology."}
{"_id": "WikiPedia_Radiology$$$corpus_3734", "text": "Use of mammography as a screening technique spread clinically after a 1966 study demonstrating the impact of mammograms on mortality and treatment led by  Philip Strax . This study, based in New York, was the first large-scale randomized controlled trial of mammography screening. [ 69 ] [ 70 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3735", "text": "In 1985,  L\u00e1szl\u00f3 Tab\u00e1r  and colleagues documented findings from mammographic screening involving 134,867 women aged 40 to 79. Using a single mediolateral oblique image, they reported a 31% reduction in mortality. [ 65 ]  Dr. Tab\u00e1r has since written many publications promoting mammography in the areas of epidemiology, screening, early diagnosis, and clinical-radiological-pathological correlation."}
{"_id": "WikiPedia_Radiology$$$corpus_3736", "text": "The use of mammography as a screening tool for the detection of early breast cancer in otherwise healthy women without symptoms is seen by some as controversial. [ 71 ] [ 72 ] [ 73 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3737", "text": "Keen and Keen indicated that repeated mammography starting at age fifty saves about 1.8 lives over 15 years for every 1,000 women screened. [ 74 ]  This result has to be weighed against the adverse effects of errors in diagnosis,  over-treatment , and radiation exposure."}
{"_id": "WikiPedia_Radiology$$$corpus_3738", "text": "The Cochrane analysis of screening indicates that it is \"not clear whether screening does more good than harm\". According to their analysis, 1 in 2,000 women will have her life prolonged by 10 years of screening, while 10 healthy women will undergo unnecessary breast cancer treatment. Additionally, 200 women will experience significant psychological stress due to false positive results. [ 75 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3739", "text": "The  Cochrane Collaboration  (2013) concluded after ten years that trials with adequate randomization did not find an effect of mammography screening on total cancer mortality, including breast cancer. The authors of this Cochrane review write: \"If we assume that screening reduces breast cancer mortality by 15% and that overdiagnosis and over-treatment is at 30%, it means that for every 2,000 women invited for screening throughout 10 years, one will avoid dying of breast cancer and 10 healthy women, who would not have been diagnosed if there had not been screening, will be treated unnecessarily. Furthermore, more than 200 women will experience important psychological distress including anxiety and uncertainty for years because of false positive findings.\" The authors conclude that the time has come to re-assess whether universal mammography screening should be recommended for any age group. [ 75 ]  They state that universal screening may not be reasonable. [ 76 ]  The Nordic Cochrane Collection updated research in 2012 and stated that advances in diagnosis and treatment make mammography screening less effective today, rendering it \"no longer effective\". They conclude that \"it therefore no longer seems reasonable to attend\" for breast cancer screening at any age, and warn of misleading information on the internet. [ 76 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3740", "text": "Newman posits that screening mammography does not reduce death overall, but causes significant harm by inflicting cancer scare and unnecessary surgical interventions. [ 77 ]  The Nordic Cochrane Collection notes that advances in diagnosis and treatment of breast cancer may make breast cancer screening no longer effective in decreasing death from breast cancer, and therefore no longer recommend routine screening for healthy women as the risks might outweigh the benefits. [ 76 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3741", "text": "Of every 1,000 U.S. women who are screened, about 7% will be called back for a diagnostic session (although some studies estimate the number to be closer to 10% to 15%). [ 78 ]   About 10% of those who are called back will be referred for a biopsy. Of the 10% referred for biopsy, about 3.5% will have cancer and 6.5% will not. Of the 3.5% who have cancer, about 2 will have an early stage cancer that will be cured after treatment."}
{"_id": "WikiPedia_Radiology$$$corpus_3742", "text": "Mammography may also produce false negatives. Estimates of the numbers of cancers missed by mammography are usually around 20%. [ 79 ]   Reasons for not seeing the cancer include observer error, but more frequently it is because the cancer is hidden by other dense tissue in the breast, and even after retrospective review of the mammogram the cancer cannot be seen. Furthermore, one form of breast cancer, lobular cancer, has a growth pattern that produces shadows on the mammogram that are indistinguishable from normal breast tissue."}
{"_id": "WikiPedia_Radiology$$$corpus_3743", "text": "The  Cochrane Collaboration  states that the best quality evidence does not demonstrate a reduction in mortality or a reduction in mortality from all types of cancer from screening mammography. [ 75 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3744", "text": "The Canadian Task Force found that for women ages 50 to 69, screening 720 women once every 2 to 3 years for 11 years would prevent one death from breast cancer. For women ages 40 to 49, 2,100 women would need to be screened at the same frequency and period to prevent a single death from breast cancer. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3745", "text": "Women whose breast cancer was detected by screening mammography before the appearance of a lump or other symptoms commonly assume that the mammogram \"saved their lives\". [ 80 ]  In practice, the vast majority of these women received no practical benefit from the mammogram. There are four categories of cancers found by mammography:"}
{"_id": "WikiPedia_Radiology$$$corpus_3746", "text": "Only 3% to 13% of breast cancers detected by screening mammography will fall into this last category. Clinical trial data suggests that 1 woman per 1,000 healthy women screened over 10 years falls into this category. [ 80 ]  Screening mammography produces no benefit to any of the remaining 87% to 97% of women. [ 80 ]  The probability of a woman falling into any of the above four categories varies with age. [ 81 ] [ 82 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3747", "text": "A 2016 review for the  United States Preventive Services Task Force  found that mammography was associated with an 8%-33% decrease in breast cancer mortality in different age groups, but that this decrease was not  statistically significant  at the age groups of 39\u201349 and 70\u201374. The same review found that mammography significantly decreased the risk of advanced cancer among women aged 50 and older by 38%, but among those aged 39 to 49 the risk reduction was a non-significant 2%. [ 83 ]  The USPSTF made their review based on data from randomized controlled trials (RCT) studying breast cancer in women between the ages of 40-49. [ 29 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3748", "text": "The goal of any screening procedure is to examine a large population of patients and find the small number most likely to have a serious condition. These patients are then referred for further, usually more invasive, testing. Thus a screening exam is not intended to be definitive; rather it is intended to have sufficient sensitivity to detect a useful proportion of cancers. The cost of higher sensitivity is a larger number of results that would be regarded as suspicious in patients without disease. This is true of mammography. The patients without disease who are called back for further testing from a screening session (about 7%) are sometimes referred to as \" false positives \". There is a trade-off between the number of patients with disease found and the much larger number of patients without disease that must be re-screened. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3749", "text": "Research shows [ 84 ]  that false-positive mammograms may affect women's well-being and behavior. Some women who receive false-positive results may be more likely to return for routine screening or perform breast self-examinations more frequently. However, some women who receive false-positive results become anxious, worried, and distressed about the possibility of having breast cancer, feelings that can last for many years. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3750", "text": "False positives also mean greater expense, both for the individual and for the screening program. Since follow-up screening is typically much more expensive than initial screening, more false positives (that must receive follow-up) means that fewer women may be screened for a given amount of money. Thus as sensitivity increases, a screening program will cost more or be confined to screening a smaller number of women. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3751", "text": "The central harm of mammographic breast cancer screening is  overdiagnosis : the detection of abnormalities that meet the pathologic definition of cancer but will never progress to cause symptoms or death. Dr.  H. Gilbert Welch , a researcher at Dartmouth College, states that \"screen-detected breast and prostate cancer survivors are more likely to have been over-diagnosed than actually helped by the test.\" [ 80 ]  Estimates of overdiagnosis associated with mammography have ranged from 1% to 54%. [ 85 ]  In 2009,  Peter C. Gotzsche  and Karsten Juhl J\u00f8rgensen reviewed the literature and found that 1 in 3 cases of breast cancer detected in a population offered mammographic screening is over-diagnosed. [ 86 ]  In contrast, a 2012 panel convened by the national cancer director for England and  Cancer Research UK  concluded that 1 in 5 cases of breast cancer diagnosed among women who have undergone breast cancer screening are over-diagnosed. This means an over-diagnosis rate of 129 women per 10,000 invited to screening. [ 87 ]  A recent systematic review of 30 studies found that screening mammography for breast cancer among women aged 40 years and older was 12.6%. [ 88 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3752", "text": "Mammograms also have a rate of missed tumors, or \"false negatives\". Accurate data regarding the number of false negatives are very difficult to obtain because  mastectomies  cannot be performed on every woman who has had a mammogram to determine the false negative rate. Estimates of the false negative rate depend on close follow-up of a large number of patients for many years. This is difficult in practice because many women do not return for regular mammography making it impossible to know if they ever developed a cancer. In his book  The Politics of Cancer , Dr. Samuel S. Epstein claims that in women ages 40 to 49, one in four cancers are missed at each mammography. Researchers have found that breast tissue is denser among younger women, making it difficult to detect tumors. For this reason, false negatives are twice as likely to occur in pre-menopausal mammograms (Prate). This is why the screening program in the UK does not start calling women for screening mammograms until age 50. [ 89 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3753", "text": "The importance of these missed cancers is not clear, particularly if the woman is getting yearly mammograms. Research on a closely related situation has shown that small cancers that are not acted upon immediately, but are observed over periods of several years, will have good outcomes. A group of 3,184 women had mammograms that were formally classified as \"probably benign\". This classification is for patients who are not clearly normal but have some area of minor concern. This results not in the patient being biopsied, but rather in having early follow up mammography every six months for three years to determine whether there has been any change in status. Of these 3,184 women, 17 (0.5%) did have cancers. Most importantly, when the diagnosis was finally made, they were all still stage 0 or 1, the earliest stages. Five years after treatment, none of these 17 women had evidence of re-occurrence. Thus, small early cancers, even though not acted on immediately, were still reliably curable. [ 90 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3754", "text": "Breast cancer imposes a significant economic strain on communities, with the expense of treating stages three and four in the United States in 2017 amounting to approximately $127,000. [ 91 ]  While early diagnosis and screening methods are important in reducing the death rates, the cost-benefit of breast cancer screening using mammography has been unclear. A recent systematic review of three studies held in Spain, Denmark, and the United States from 2000-2019 found that digital mammography is not cost-beneficial for the healthcare system when compared to other screening methods. Therefore, increasing its frequency may cause higher costs on the healthcare system. While there may be a lack of evidence, it is suggested that digital mammography be performed every two years for ages over 50. [ 92 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3755", "text": "As the  USPSTF  recommendations are so influential, changing mammography screenings from 50 to 40 years of age has significant implications to public health. The major concerns regarding this update is whether breast cancer mortality has truly been increasing and if there is new evidence that the benefits of mammography are increasing. [ 93 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3756", "text": "According to  National Vital Statistics System , mortality from breast cancer has been steadily decreasing in the United States from 2018 to 2021. There have also been no new randomized trials of screening mammography for women in their 40s since the previous USPSTF recommendation was made. In addition, the 8 most recent randomized trials for this age group revealed no significant effect. [ 94 ]  Instead, the  USPSTF  used statistical models to estimate what would happen if the starting age were lowered, assuming that screening mammography reduces breast cancer mortality by 25%. This found that screening 1,000 women from 40\u201374 years of age, instead of 50-74, would cause 1-2 fewer breast cancer deaths per 1,000 women screened over a lifetime. [ 95 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3757", "text": "Approximately 75 percent of women diagnosed with breast cancer have no family history of breast cancer or other factors that put them at high risk for developing the disease (so screening only high-risk women misses majority of cancers). An analysis by Hendrick and Helvie, [ 96 ]  published in the  American Journal of Roentgenology , showed that if USPSTF breast cancer screening guidelines were followed, approximately 6,500 additional women each year in the U.S. would die from breast cancer."}
{"_id": "WikiPedia_Radiology$$$corpus_3758", "text": "The largest (Hellquist et al) [ 97 ]  and longest running (Tabar et al) [ 98 ]  breast cancer screening studies in history re-confirmed that regular mammography screening cut breast cancer deaths by roughly a third in all women ages 40 and over (including women ages 40\u201349). This renders the USPSTF calculations off by half. They used a 15% mortality reduction to calculate how many women needed to be invited to be screened to save a life. With the now re-confirmed 29% (or up) figure, the number to be screened using the USPSTF formula is half of their estimate and well within what they considered acceptable by their formula."}
{"_id": "WikiPedia_Radiology$$$corpus_3759", "text": "Many factors affect how many people attend breast cancer screenings. For example, people from minority  ethnic communities  are also less likely to attend cancer screening. In the UK, women of  South Asian heritage  are the least likely to attend breast cancer screening. Research is still needed to identify specific barriers for the different South Asian communities. For example, a study showed that  British-Pakistani  women faced cultural and  language barriers  and were not aware that breast screening takes place in a female-only environment. [ 99 ] [ 100 ] [ 101 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3760", "text": "People with  mental illnesses  are also less likely to attend cancer screening appointments. [ 102 ] [ 103 ]  In Northern Ireland women with mental health problems were shown to be less likely to attend  screening for breast cancer , than women without. The lower attendance numbers remained the same even when marital status and  social deprivation  were taken into account. [ 104 ] [ 105 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3761", "text": "Mammography facilities in the United States and its territories (including military bases) are subject to the  Mammography Quality Standards Act  (MQSA). The act requires annual inspections and accreditation every three years through an FDA-approved body. Facilities found deficient during the inspection or accreditation process can be barred from performing mammograms until corrective action has been verified or, in extreme cases, can be required to notify past patients that their exams were sub-standard and should not be relied upon. [ 106 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3762", "text": "At this time, [ when? ]  MQSA applies only to traditional mammography and not to related scans, such as  breast ultrasound , stereotactic breast biopsy, or breast MRI."}
{"_id": "WikiPedia_Radiology$$$corpus_3763", "text": "As of September 10, 2024, the MQSA requires that all patients be notified of their breast density (\"dense\" or \"not dense\") in their mammogram reports. [ 107 ] [ 108 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3764", "text": "Recently,  artificial intelligence (AI)  programs have been developed to utilize features from screening mammography images to predict breast cancer risk. A systematic review of 16 retrospective study designs comparing median maximum  AUC  found that artificial intelligence had a comparable or better accuracy (AUC = 0.72) of predicting breast cancer than clinical risk factors alone (AUC = 0.61), suggesting a transition from clinical risk factor-based to AI image-based risk models may lead to more accurate and personalized risk-based screening approaches. [ 109 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3765", "text": "Another study of 32 published papers involving 23,804 mammograms and various machine learning methods ( CNN ,  ANN , and  SVM ) found promising results in the ability to assist clinicians in large-scale population-based breast cancer screening programs. [ 110 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3766", "text": "For patients who do not want to undergo mammography, MRI and also breast computed tomography (also called breast CT) offer a painless alternative. Whether the respective method is suitable depends on the clinical picture; it is decided by the physician. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3767", "text": "A  panoramic radiograph  is a  panoramic  scanning  dental X-ray  of the upper and lower  jaw . It shows a  two-dimensional  view of a  half-circle  from  ear  to ear. Panoramic radiography is a form of  focal plane tomography ; thus, images of multiple  planes  are taken to make up the composite panoramic image, where the  maxilla  and  mandible  are in the focal trough and the structures that are superficial and deep to the trough are blurred."}
{"_id": "WikiPedia_Radiology$$$corpus_3768", "text": "Other nonproprietary names for a panoramic radiograph are  dental panoramic radiograph  and  pantomogram ; Abbreviations include  PAN ,  DPR ,  OPT , and  OPG  (the latter, based on genericizing a trade name, are often avoided in medical editing)."}
{"_id": "WikiPedia_Radiology$$$corpus_3769", "text": "Dental  panoramic   radiography  equipment consists of a horizontal rotating arm which holds an X-ray source and a moving  film  mechanism (carrying a film) arranged at opposed extremities. The patient's  skull  sits between the X-ray generator and the film. The  X-ray  source is rectangular  collimated  beam. [ 1 ]  Also the height of that beam covers the  mandibles  and the  maxilla  regions. The arm moves and its movement may be described as a rotation around an instant center which shifts on a dedicated  trajectory ."}
{"_id": "WikiPedia_Radiology$$$corpus_3770", "text": "The manufacturers propose different solutions for moving the arm, trying to maintain constant distance between the teeth to the film and generator. Also those moving solutions try to project the teeth  arch  as  orthogonally  as possible. It is impossible to select an ideal movement as the anatomy varies very much from person to person. Finally a  compromise  is selected by each manufacturer and results in  magnification  factors which vary strongly along the film (15%-30%). The patient positioning is very critical in regard to both sharpness and distortions. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3771", "text": "There are two kinds of film moving mechanisms, one using a sliding flat  cassette  which holds the film, and another using a rotating cylinder around which the film is wound. There are two standard sizes for dental panoramic films: 30\u00a0cm \u00d7 12\u00a0cm (12\u2033 \u00d7 5\u2033) and 30\u00a0cm x 15\u00a0cm (12\u2033 \u00d7 6\u2033). The smaller size film receives 8% less X-ray  dosage  on it compared to the bigger size."}
{"_id": "WikiPedia_Radiology$$$corpus_3772", "text": "Dental X-rays' radiology is moving from film technology (involving a chemical developing process) to  digital X-ray  technology, which is based on electronic sensors and  computers . One of the principal advantages compared to film based systems is the much greater  exposure latitude . This means many fewer repeated scans, which reduces costs and also reduces patient exposure to  radiation . Lost X-rays can also be reprinted if the digital file is saved. Other significant advantages include instantly viewable images, the ability to enhance images, the ability to email images to practitioners and clients (without needing to digitize them first), easy and reliable document handling, reduced X-ray exposure, that no  darkroom  is required, and that no  chemicals  are used."}
{"_id": "WikiPedia_Radiology$$$corpus_3773", "text": "One particular type of digital system uses a  photostimulable phosphor plate  (aka PSP - Phosphor Plate) in place of the film. After X-ray exposure the plate (sheet) is placed in a special  scanner  where the  latent  formed image is retrieved point by point and  digitized , using a laser light scanning. The digitized images are stored and displayed on the computer screen. This method is in between old film based technology and the current direct digital imaging technology. It is similar to the film process because it involves the same image support handling and differs because the chemical development process is replaced by the scanning process. This is not much faster than film processing and the  resolution  and sensitivity performances are contested. However it has the clear advantage of being able to fit with any existing equipment without any modification because it replaces just the existing film."}
{"_id": "WikiPedia_Radiology$$$corpus_3774", "text": "Also sometimes the term \"digital X-rays\" is used to designate the scanned film documents which further are handled by computers."}
{"_id": "WikiPedia_Radiology$$$corpus_3775", "text": "The other types of digital imaging technologies use electronic sensors. A majority of them first convert the X-rays in light (using a GdO2S or  CsI  layer) which is further captured using a  CCD  or a  CMOS  image sensor. Few of them use a hybrid  analog-to-digital  arrangement which first converts the X-ray into  electricity  (using a  CdTe  layer) and then this electricity is rendered as an image by a reading section based on CMOS technology."}
{"_id": "WikiPedia_Radiology$$$corpus_3776", "text": "In current state-of-the-art digital systems, the image quality is vastly superior to conventional film-based systems. The latest advancements have also seen the addition on Cone Beam 3D Technology to standard digital panoramic devices."}
{"_id": "WikiPedia_Radiology$$$corpus_3777", "text": "Orthopantomograms (OPTs) are used by health care professionals to provide information on:"}
{"_id": "WikiPedia_Radiology$$$corpus_3778", "text": "Normally, the person bites on a plastic  spatula  so that all the teeth, especially the  crowns , can be viewed individually. The whole orthopantomogram process takes about one  minute . The patient's actual radiation exposure time varies between 5.5 and 22 seconds for the machine's excursion around the skull."}
{"_id": "WikiPedia_Radiology$$$corpus_3779", "text": "The  collimation  of the machine means that, while rotating, the X-rays project only a limited portion of the  anatomy  onto the film at any given instant but, as the rotation progresses around the skull, a composite picture of the maxillo-facial block is created. While the arm rotates, the film moves in a such way that the projected partial skull image (limited by the beam section) scrolls over it and exposes it entirely. Not all of the overlapping individual images projected on the film have the same magnification because the beam is  divergent  and the images have differing focus points. Also not all the element images move with the same  velocity  on the target film as some of them are more distant from and others closer to the instant rotation center. The velocity of the film is controlled in such fashion to fit exactly the velocity of projection of the anatomical elements of the dental arch side which is closest to the film. Therefore, they are recorded sharply while the elements in different places are recorded blurred as they scroll at different velocity."}
{"_id": "WikiPedia_Radiology$$$corpus_3780", "text": "The dental panoramic image suffers from important distortions because a vertical  zoom  and a horizontal zoom both vary differently along the image. The vertical and horizontal zooms are determined by the relative position of the recorded element versus film and generator. Features closer to the generator receive more vertical zoom. The horizontal zoom is also dependent on the relative position of the element to the focal path. Features inside the focal path arch receive more horizontal zoom and are blurred; features outside receive less horizontal zoom and are blurred."}
{"_id": "WikiPedia_Radiology$$$corpus_3781", "text": "The result is an image showing sharply the section along the mandible arch, and blurred elsewhere. For example, the more radio-opaque anatomical region, the cervical vertebrae (neck), shows as a wide and blurred vertical pillar overlapping the front teeth. The path where the anatomical elements are recorded sharply is called \"focal path\"."}
{"_id": "WikiPedia_Radiology$$$corpus_3782", "text": "Persons who are to undergo panoramic radiography usually are required to remove any earrings, jewellery, hair pins, glasses,  dentures  or  orthodontic appliances . [ 4 ]  If these articles are not removed, they may create artifacts on the image (especially if they contain metal) and reduce its usefulness. There is also a need for the person to stay absolutely still during the 18 or so second cycle it takes for the machine to expose the film. For this reason, radiographers often explain to the person beforehand how the machine will move. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3783", "text": "Like any medical imaging utilizing  ionizing radiation , there will be a minute degree of direct ionizing damage and indirect damage from  free radicals  created during the ionization of water molecules within cells. A rough estimate of the risk of fatal cancer from a panoramic radiograph is about 1 in 20,000,000. [ 4 ]  The age of the person being imaged also alters the risk, with younger people having a slightly higher risk. E.g. the 1 in 20,000,000 risk would be doubled for someone in the 1-10 age group (1 in 10,000,000). [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3784", "text": "1985\u20131991 \u2013 The first attempt to build a dental digital panoramic was of McDavid et al. at  UTHSCSA . [ 5 ]  Their idea was based on a linear pixel array(single pixel column) sensor which was not appropriate for such an application because: a) there is no tomographic effect; b) huge difficulties to collimate the X-rays beam and to control the X-ray dose delivered to the patient; c) poor generator efficiency."}
{"_id": "WikiPedia_Radiology$$$corpus_3785", "text": "1995 \u2013 DXIS, the first dental digital panoramic X-rays system available on the market, created by Catalin Stoichita at  Signet (France) . DXIS targeted to retrofit all the panoramic models. \n1997 \u2013 SIDEXIS, of  Siemens  (currently  Sirona Dental Systems , Germany) offered a digital option for Ortophos Plus panoramic unit, DigiPan of Trophy Radiology (France) offered a digital option  for the OP100 panoramic made by Instrumentarium (Finland). \n1998\u20132004 \u2013 many panoramic manufacturers offered their own digital systems."}
{"_id": "WikiPedia_Radiology$$$corpus_3786", "text": "Panoramic radiographs have the capability to demonstrate a portion of the neck and display atheromas (calcifications in the  carotid artery ) which are an indication of both local and generalized (systemic)  atherosclerosis . Atherosclerosis of the  coronary arteries  leading to  myocardial infarction  (heart attack), and atherosclerosis of the carotid artery leading to  stroke  are the number one and number three most common causes of death in the United States. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3787", "text": "There is interest to look at panoramic radiographs as a screening tool, however further data is needed with regards if it is able to make a meaningful difference in outcomes. [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3788", "text": "Additional research projects have further determined the prevalence rate of these atheromas in the general population (3\u20135%) [ 8 ] [ 9 ]  and among high-risk groups (over 25% in: recent stroke victims, [ 10 ]  individuals with  obstructive sleep apnea  syndrome, [ 11 ] [ 12 ] [ 13 ]   postmenopausal  women, [ 14 ] [ non-primary source needed ]   type 2 diabetics , [ 15 ] [ 13 ] [ 16 ]  individuals with  dilated cardiomyopathy , [ 17 ] [ 13 ]  and among individuals who have received  radiotherapy  directed at the neck, [ 18 ] [ non-primary source needed ] [ 19 ] [ non-primary source needed ] ). These findings have been corroborated by other several other researchers. [ 20 ] [ 21 ] [ 22 ] [ 23 ] [ 13 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3789", "text": "Atherosclerosis is attributed to risk factors that include cigarette smoking,  hyperlipidemia ,  obesity ,  diabetes mellitus , and  hypertension  (high blood pressure). These factors, however, do not fully account for the risk of disease. Atherosclerosis has been conceptualized as a chronic inflammatory response to  endothelial cell  injury [ 24 ]  and dysfunction possibly arising from chronic dental infection. In 2010, using the previously validated Mattila panoramic radiographic index to quantify the totality of dental infection (i.e., periapical and  furcal lesions ,  pericoronitis  sites,  carious  tooth roots, teeth with  pulpal  caries, and vertical bony defects), Friedlander's group determined that individuals with carotid artery atheromas on their panoramic radiographs had significantly greater amounts of dental infection/inflammation than atherogenic risk-matched controls devoid of radiographic atheromas. [ 25 ] [ non-primary source needed ] [ 26 ] [ non-primary source needed ]  While the Mattila index had been previously used to relate the extent of dental infection to  coronary artery disease , this research is the first to link the full range of dental disease that it measures to panoramic radiographs evidencing calcified carotid artery atherosclerosis."}
{"_id": "WikiPedia_Radiology$$$corpus_3790", "text": "Perfusion CT  or  CT Perfusion  is a type of  Perfusion Scanning  using  Computed Tomography . It is helpful in the evaluation of the  vascularity  of tissue in the body. In this, the temporal changes in tissue density are measured, providing information about the vascularity of the tissue.\nIn CT perfusion, a contrast media injection is given, and then the scan is taken. The acquired data are post-processed to obtain perfusion maps with different parameters, such as BV (blood volume), BF (blood flow), MTT (mean transit time), and TTP (time to peak). [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3791", "text": "CT Perfusion plays an important role in the assessment of Acute Ischemic Stroke. It is used to create maps of blood flow, blood volume, and mean transit time to assess the tissue and to differentiate between the core and penumbra in stroke. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3792", "text": "Phase-contrast X-ray imaging  or  phase-sensitive X-ray imaging  is a general term for different technical methods that use information concerning changes in the  phase  of an  X-ray  beam that passes through an object in order to create its images. Standard X-ray imaging techniques like  radiography  or  computed tomography (CT)  rely on a decrease of the X-ray beam's intensity ( attenuation ) when traversing the  sample , which can be measured directly with the assistance of an  X-ray detector . However, in phase contrast X-ray imaging, the beam's  phase shift  caused by the sample is not measured directly, but is transformed into variations in intensity, which then can be recorded by the detector. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3793", "text": "In addition to producing  projection images , phase contrast X-ray imaging, like conventional transmission, can be combined with  tomographic techniques  to obtain the 3D distribution of the real part of the  refractive index  of the sample. When applied to samples that consist of atoms with low  atomic number   Z , phase contrast X-ray imaging is more sensitive to density variations in the sample than  conventional transmission-based X-ray imaging . This leads to images with improved  soft tissue  contrast. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3794", "text": "In the last several years, a variety of phase-contrast X-ray imaging techniques have been developed, all of which are based on the observation of  interference patterns  between diffracted and undiffracted waves. [ 3 ]    The most common techniques are crystal interferometry, propagation-based imaging, analyzer-based imaging, edge-illumination and grating-based imaging (see below)."}
{"_id": "WikiPedia_Radiology$$$corpus_3795", "text": "The first to discover  X-rays  was  Wilhelm Conrad R\u00f6ntgen  in 1895, where he found that they had the ability to penetrate opaque materials. He recorded the first X-ray image, displaying the hand of his wife. [ 4 ]  He was awarded the first  Nobel Prize in Physics  in 1901 \"in recognition of the extraordinary services he has rendered by the discovery of the remarkable rays subsequently named after him\". [ 5 ]  Since then, X-rays have been used as a tool to safely determine the inner structures of different objects, although the information was for a long time obtained by measuring the transmitted intensity of the waves only, and the phase information was not accessible."}
{"_id": "WikiPedia_Radiology$$$corpus_3796", "text": "The principle of  phase-contrast imaging  was first developed by  Frits Zernike  during his work with  diffraction gratings  and visible light. [ 6 ] [ 7 ]  The application of his knowledge to microscopy won him the  Nobel Prize  in Physics in 1953. Ever since,   phase-contrast microscopy  has been an important field of  optical microscopy ."}
{"_id": "WikiPedia_Radiology$$$corpus_3797", "text": "The transfer of phase-contrast imaging from visible light to X-rays took a long time, due to slow progress in improving the quality of X-ray beams and the inaccessibility of X-ray lenses. In the 1970s, it was realized that the  synchrotron radiation , emitted from charged particles circulating in storage rings constructed for high-energy nuclear physics experiments, may have been a more intense and versatile source of X-rays than  X-ray tubes ; [ 8 ]  this, combined with progress in the development of X-rays optics, was fundamental for the further advancement of X-ray physics."}
{"_id": "WikiPedia_Radiology$$$corpus_3798", "text": "The pioneer work to the implementation of the phase-contrast method to X-ray physics was presented in 1965 by Ulrich Bonse and Michael Hart, Department of Materials Science and Engineering of Cornell University, New York. They presented a crystal  interferometer , made from a large and highly perfect  single crystal . [ 9 ]  Not less than 30 years later the Japanese scientists  Atsushi Momose , Tohoru Takeda and co-workers adopted this idea and refined it for application in biological imaging, for instance by increasing the field of view with the assistance of new setup configurations and  phase retrieval  techniques. [ 10 ] [ 11 ]  The Bonse\u2013Hart interferometer provides several orders of magnitude higher sensitivity in biological samples than other phase-contrast techniques, but it cannot use conventional X-ray tubes because the crystals only accept a very narrow energy band of X-rays (\u0394 E / E  ~ 10 \u22124 ). In 2012, Han Wen and co-workers took a step forward by replacing the crystals with nanometric phase gratings. [ 12 ]  The gratings split and direct X-rays over a broad spectrum, thus lifting the restriction on the bandwidth of the X-ray source. They detected sub nano radian  refractive bending of X-rays in biological samples with a grating Bonse\u2013Hart interferometer. [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3799", "text": "At the same time, two further approaches to phase-contrast imaging emerged with the aim to overcome the problems of crystal interferometry.\nThe propagation-based imaging technique was primarily introduced by the group of  Anatoly Snigirev \u00a0[ de ]  at the  ESRF  (European Synchrotron Radiation Facility) in Grenoble, France, [ 13 ]  and was based on the detection of \"Fresnel fringes\" that arise under certain circumstances in free-space propagation. The experimental setup consisted of an inline configuration of an X-ray source, a sample and a detector and did not require any optical elements. It was conceptually identical to the setup of Dennis Gabor's revolutionary work on  holography  in 1948. [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3800", "text": "An alternative approach called analyzer-based imaging was first explored in 1995 by Viktor Ingal and Elena Beliaevskaya at the X-ray laboratory in Saint Petersburg, Russia, [ 15 ]  and by Tim Davis and colleagues at the  CSIRO  (Commonwealth Scientific and Industrial Research Organisation) Division of Material Science and Technology in Clayton, Australia. [ 16 ]  This method uses a Bragg crystal as angular filter to reflect only a small part of the beam fulfilling the  Bragg condition  onto a detector. Important contributions to the progress of this method have been made by a US collaboration of the research teams of Dean Chapman, Zhong Zhong and William Thomlinson, for example the extracting of an additional signal caused by  ultra-small angle scattering [ 17 ]  and the first CT image made with analyzer-based imaging. [ 18 ]  An alternative to analyzer-based imaging, which provides equivalent results without requiring the use of a crystal, was developed by Alessandro Olivo and co-workers at the Elettra synchrotron in Trieste, Italy. [ 19 ]  This method, called \u201cedge-illumination\u201d, operates a fine selection on the X-ray direction by using the physical edge of the detector pixels themselves, hence the name. Later on Olivo, in collaboration with Robert Speller at University College London, adapted the method for use with conventional X-ray sources, [ 20 ]  opening the way to translation into clinical and other applications. Peter Munro (also from UCL) substantially contributed to the development of the lab-based approach, by demonstrating that it imposes practically no coherence requirements [ 21 ]  and that, this notwithstanding, it still is fully quantitative. [ 22 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3801", "text": "The latest approach discussed here is the so-called grating-based imaging, which makes use of the  Talbot effect , discovered by  Henry Fox Talbot  in 1836. [ 23 ]  This self-imaging effect creates an interference pattern downstream of a  diffraction grating . At a particular distance this pattern resembles exactly the structure of the grating and is recorded by a detector. The position of the interference pattern can be altered by bringing an object in the beam, that induces a phase shift. This displacement of the interference pattern is measured with the help of a second grating, and by certain reconstruction methods, information about the real part of the refractive index is gained. The so-called Talbot\u2013Lau interferometer was initially used in  atom interferometry , for instance by  John F. Clauser  and Shifang Li in 1994. [ 24 ]  The first X-ray grating interferometers using synchrotron sources were developed by Christian David and colleagues from the  Paul Scherrer Institute  (PSI) in Villingen, Switzerland [ 25 ]  and the group of  Atsushi Momose  from the University of Tokyo. [ 26 ]  In 2005, independently from each other, both David's and Momose's group incorporated computed tomography into grating interferometry, which can be seen as the next milestone in the development of grating-based imaging. [ 27 ] [ 28 ] \nIn 2006, another great advancement was the transfer of the grating-based technique to  conventional laboratory X-ray tubes  by  Franz Pfeiffer  and co-workers, [ 29 ]  which fairly enlarged the technique's potential for clinical use. About two years later the group of Franz Pfeiffer also accomplished to extract a supplementary signal from their experiments; the so-called \"dark-field signal\" was caused by scattering due to the porous microstructure of the sample and provided \"complementary and otherwise inaccessible structural information about the specimen at the micrometer and submicrometer length scale\". [ 30 ]  At the same time, Han Wen and co-workers at the US National Institutes of Health arrived at a much simplified grating technique to obtain the scattering (\u201cdark-field\u201d) image. They used a single projection of a grid and a new approach for signal extraction named \"single-shot Fourier analysis\". [ 31 ]  Recently, a lot of research was done to improve the grating-based technique: Han Wen and his team analyzed animal bones and found out that the intensity of the dark-field signal depends on the orientation of the grid and this is due to the anisotropy of the bone structure. [ 32 ]  They made significant progress towards biomedical applications by replacing mechanical scanning of the gratings with electronic scanning of the X-ray source. [ 33 ]  The grating-based phase-contrast CT field was extended by tomographic images of the dark-field signal [ 34 ]  and time-resolved phase-contrast CT. [ 35 ]  Furthermore, the first pre-clinical studies using grating-based phase-contrast X-ray imaging were published. Marco Stampanoni and his group examined native breast tissue with \"differential phase-contrast mammography\", [ 36 ]  and a team led by Dan Stutman investigated how to use grating-based imaging for the small joints of the hand. [ 37 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3802", "text": "Most recently, a significant advance in grating-based imaging occurred due to the discovery of a  phase moir\u00e9 effect [ 38 ] [ 39 ]  by Wen and colleagues. It led to interferometry beyond the Talbot self-imaging range, using only phase gratings and conventional sources and detectors. X-ray phase gratings can be made with very fine periods, thereby allowing imaging at low radiation doses to achieve high sensitivity."}
{"_id": "WikiPedia_Radiology$$$corpus_3803", "text": "Conventional X-ray imaging uses the drop in intensity through attenuation caused by an object in the X-ray beam and the radiation is treated as rays like in  geometrical optics . But when X-rays pass through an object, not only their amplitude but their phase is altered as well. Instead of simple  rays , X-rays can also be treated as  electromagnetic waves . An object then can be described by its  complex refractive index  (cf. [ 8 ] ):"}
{"_id": "WikiPedia_Radiology$$$corpus_3804", "text": "The term  \u03b4  is the decrement of the real part of the refractive index, and the imaginary part  \u03b2  describes the absorption index or extinction coefficient.\nNote that in contrast to optical light, the real part of the refractive index is less than but close to unity, this is \"due to the fact that the X-ray spectrum generally lies to the high-frequency side of various resonances associated with the binding of electrons\". [ 8 ]  The  phase velocity  inside of the object is larger than the  velocity of light   c . This leads to a different behavior of X-rays in a medium compared to visible light (e.g. refractive angles have negative values) but does not contradict the  law of relativity , \"which requires that only signals carrying information do not travel faster than  c . Such signals move with the  group velocity , not with the phase velocity, and it can be shown that the group velocity is in fact less than  c .\" [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3805", "text": "The impact of the index of refraction on the behavior of the wave can be demonstrated with a wave propagating in an arbitrary medium with a fixed refractive index  n . For reason of simplicity, a monochromatic  plane wave  with no  polarization  is assumed here. The wave propagates in direction normal to the surface of the medium, named  z  in this example (see figure on the right). The scalar wave function in vacuum is"}
{"_id": "WikiPedia_Radiology$$$corpus_3806", "text": "Within the medium, the  angular wavenumber  changes from  k  to  nk . Now the wave can be described as:"}
{"_id": "WikiPedia_Radiology$$$corpus_3807", "text": "where   \u03b4kz  is the phase shift and   e \u2212\u03b2 kz  is an exponential decay factor decreasing the amplitude  E 0  of the wave. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3808", "text": "In more general terms, the total phase shift of the beam propagating a distance  z  can be calculated by using the integral"}
{"_id": "WikiPedia_Radiology$$$corpus_3809", "text": "where  \u03bb  is the  wavelength  of the incident X-ray beam. This formula means that the phase shift is the projection of the decrement of the real part of the refractive index in imaging direction. This fulfills the requirement of the  tomographic principle , which states that \"the input data to the reconstruction algorithm should be a projection of a quantity  f  that conveys structural information inside a sample. Then, one can obtain a tomogram which maps the value  f .\" [ 40 ]  In other words, in phase-contrast imaging a map of the real part of the refraction index  \u03b4(x,y,z)  can be reconstructed with standard techniques like  filtered back projection  which is analog to conventional  X-ray computed tomography  where a map of the imaginary part of the refraction index can be retrieved."}
{"_id": "WikiPedia_Radiology$$$corpus_3810", "text": "To get information about the compounding of a sample, basically the density distribution of the sample, one has to relate the measured values for the refractive index to intrinsic parameters of the sample, such a relation is given by the following formulas:"}
{"_id": "WikiPedia_Radiology$$$corpus_3811", "text": "where  \u03c1 a  is the atomic number density,  \u03c3 a  the absorption  cross section ,  k  the length of the  wave vector  and"}
{"_id": "WikiPedia_Radiology$$$corpus_3812", "text": "where  p  the phase shift cross section."}
{"_id": "WikiPedia_Radiology$$$corpus_3813", "text": "Far from the absorption edges (peaks in the absorption cross-section due to the enhanced probability for the absorption of a photon that has a frequency close to the resonance frequency of the medium),  dispersion effects  can be neglected; this is the case for light elements ( atomic number   Z <40) that are the components of human tissue and X-ray energies above 20 keV, which are typically used in medical imaging.\nAssuming these conditions, the absorption cross section is approximately stated by"}
{"_id": "WikiPedia_Radiology$$$corpus_3814", "text": "where 0.02 is a constant given in  barn , the typical unit of particle interaction cross section area,  k  the length of the  wave vector ,  k 0  the length of a wave vector with wavelength of 1  Angstrom  and  Z  the  atomic number . [ 41 ]  The valid formula under these conditions for the phase shift cross section is:"}
{"_id": "WikiPedia_Radiology$$$corpus_3815", "text": "where   Z  is the  atomic number ,  k  the length of the  wave vector ,  and  r 0  the  classical electron radius ."}
{"_id": "WikiPedia_Radiology$$$corpus_3816", "text": "This results in the following expressions for the two parts of the complex index of refraction:"}
{"_id": "WikiPedia_Radiology$$$corpus_3817", "text": "Inserting typical values of human tissue in the formulas given above shows that  \u03b4  is generally three orders of magnitude larger than   \u03b2  within the diagnostic X-ray range.  This implies that the phase-shift of an X-ray beam propagating through tissue may be much larger than the loss in intensity thus making phase contrast X-ray imaging more sensitive to density variations in the tissue than absorption imaging. [ 42 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3818", "text": "Due to the proportionalities"}
{"_id": "WikiPedia_Radiology$$$corpus_3819", "text": "the advantage of phase contrast over conventional absorption contrast even grows with increasing energy. Furthermore, because the phase contrast image formation is not intrinsically linked to the absorption of X-rays in the sample, the  absorbed dose  can potentially be reduced by using higher X-ray energies. [ 29 ] [ 42 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3820", "text": "As mentioned above, concerning visible light, the real part of the refractive index n can deviate strongly from unity (n of glass in visible light ranges from 1.5 to 1.8) while the deviation from unity for X-rays in different media is generally of the order of 10 \u22125 . Thus, the refraction angles caused at the boundary between two isotropic media calculated with  Snell's formula  are also very small. The consequence of this is that refraction angles of X-rays passing through a tissue sample cannot be detected directly and are usually determined indirectly by \"observation of the interference pattern between diffracted and undiffracted waves produced by spatial variations of the real part of the refractive index.\" [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3821", "text": "Crystal interferometry , sometimes also called  X-ray interferometry , is the oldest but also the most complex method used for experimental realization. It consists of three beam splitters in  Laue geometry  aligned parallel to each other. (See figure to the right) The incident beam, which usually is collimated and filtered by a monochromator (Bragg crystal) before, is split at the first crystal (S) by  Laue diffraction  into two coherent beams, a reference beam which remains undisturbed and a beam passing through the sample. The second crystal (T) acts as a transmission mirror and causes the beams to converge one towards another. The two beams meet at the plane of the third crystal (A), which is sometimes called, the analyzer crystal, and create an interference pattern the form of which depends on the optical path difference between the two beams caused by the sample. This interference pattern is detected with an X-ray detector behind the analyzer crystal. [ 9 ] [ 43 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3822", "text": "By putting the sample on a rotation stage and recording  projections  from different angles, the 3D-distribution of the refractive index and thus  tomographic images  of the sample can be retrieved. [ 40 ] \nIn contrast to the methods below, with the crystal interferometer the phase itself is measured and not any spatial alternation of it.\nTo retrieve the phase shift out of the interference patterns; a technique called phase-stepping or fringe scanning is used: a phase shifter (with the shape of a wedge) is introduced in the reference beam. The phase shifter creates straight  interference fringes  with regular intervals; so called carrier fringes. When the sample is placed in the other beam, the carrier fringes are displaced. The phase shift caused by the sample corresponds to the displacement of the carrier fringes. Several interference patterns are recorded for different shifts of the reference beam and by analyzing them the phase information  modulo  2 \u03c0  can be extracted. [ 40 ] [ 43 ]  This ambiguity of the phase is called the  phase wrapping effect  and can be removed by so-called \"phase unwrapping techniques\". [ 44 ]  These techniques can be used when the signal-to-noise ratio of the image is sufficiently high and phase variation is not too abrupt. [ 28 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3823", "text": "As an alternative to the fringe scanning method, the Fourier-transform method can be used to extract the phase shift information with only one interferogram, thus shortening the exposure time, but this has the disadvantage of limiting the spatial resolution by the spacing of the carrier fringes. [ 45 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3824", "text": "X-ray interferometry is considered to be the most sensitive to the phase shift, of the 4 methods, consequently providing the highest density resolution in range of mg/cm 3 . [ 28 ]  But due to its high sensitivity, the fringes created by a strongly phase-shifting sample may become unresolvable; to overcome this problem a new approach called \"coherence-contrast X-ray imaging\" has been developed recently, where instead of the phase shift the change of the degree of coherence caused by the sample is relevant for the contrast of the image. [ 46 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3825", "text": "A general limitation to the spatial resolution of this method is given by the blurring in the analyzer crystal which arises from dynamical refraction, i.e. the angular deviation of the beam due to the refraction in the sample is amplified about ten thousand times in the crystal, because the beam path within the crystal depends strongly on its incident angle. This effect can be reduced by thinning down the analyzer crystal, e.g. with an analyzer thickness of 40  \u03bc m a resolution of about 6  \u03bc m was calculated. Alternatively the  Laue crystals  can be replaced by  Bragg crystals , so the beam doesn't pass through the crystal but is reflected on the surface. [ 47 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3826", "text": "Another constraint of the method is the requirement of a very high stability of the setup; the alignment of the crystals must be very precise and the path length difference between the beams should be smaller than the wavelength of the X-rays; to achieve this the interferometer is usually made out of a highly perfect single block of silicon by cutting out two grooves. By the  monolithic  production the very important spatial lattice coherence between all three crystals can be maintained relatively well but it limits the field of view to a small size,(e.g.  5\u00a0cm x 5\u00a0cm for a 6-inch ingot) and because the sample is normally placed in one of the beam paths the size of the sample itself is also constrained by the size of the silicon block. [ 9 ] [ 48 ] \nRecently developed configurations, using two crystals instead of one, enlarge the field of view considerably, but are even more sensitive to mechanical instabilities. [ 49 ] [ 50 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3827", "text": "Another additional difficulty of the crystal interferometer is that the Laue crystals filter most of the incoming radiation, thus requiring a high beam intensity or very long exposure times. [ 51 ]  That limits the use of the method to highly brilliant X-ray sources like synchrotrons."}
{"_id": "WikiPedia_Radiology$$$corpus_3828", "text": "According to the constraints on the setup the crystal interferometer works best for high-resolution imaging of small samples which cause small or smooth  phase gradients ."}
{"_id": "WikiPedia_Radiology$$$corpus_3829", "text": "To have the superior sensitivity of crystal Bonse-Hart interferometry without some of the basic limitations, the monolithic crystals have been replaced with nanometric x-ray phase-shift gratings. [ 52 ]  The first such gratings have periods of 200 to 400 nanometers. They can split x-ray beams over the broad energy spectra of common x-ray tubes. The main advantage of this technique is that it uses most of the incoming x-rays that would have been filtered by the crystals. Because only phase gratings are used, grating fabrication is less challenging than techniques that use absorption gratings. The first grating Bonse-Hart interferometer (gBH) operated at 22.5 keV photon energy and 1.5% spectral bandwidth."}
{"_id": "WikiPedia_Radiology$$$corpus_3830", "text": "The incoming beam is shaped by slits of a few tens of micrometers such that the transverse coherence length is greater than the grating period. The interferometer consists of three parallel and equally spaced phase gratings, and an x-ray camera. The incident beam is diffracted by a first grating of period 2P into two beams. These are further diffracted by a second grating of period P into four beams. Two of the four merge at a third grating of period 2P. Each is further diffracted by the third grating. The multiple diffracted beams are allowed to propagate for sufficient distance such that the different diffraction orders are separated at the camera. There exists a pair of diffracted beams that co-propagate from the third grating to the camera. They interfere with each other to produce intensity fringes if the gratings are slightly misaligned with each other. The central pair of diffraction paths are always equal in length regardless of the x-ray energy or the angle of the incident beam. The interference patterns from different photon energies and incident angles are locked in phase."}
{"_id": "WikiPedia_Radiology$$$corpus_3831", "text": "The imaged object is placed near the central grating. Absolute phase images are obtained if the object intersects one of a pair of coherent paths. If the two paths both pass through the object at two locations which are separated by a lateral distance d, then a phase difference image of \u03a6(r) - \u03a6(r-d) is detected.  Phase stepping one of the gratings is performed to retrieve the phase images. The phase difference image \u03a6(r) - \u03a6(r-d) can be integrated to obtain a phase shift image of the object."}
{"_id": "WikiPedia_Radiology$$$corpus_3832", "text": "This technique achieved substantially higher sensitivity than other techniques with the exception of the crystal interferometer. [ 12 ] [ 53 ]  A basic limitation of the technique is the chromatic dispersion of grating diffraction, which limits its spatial resolution. A tabletop system with a tungsten-target x-ray tube running at 60\u00a0kVp will have a limiting resolution of 60\u00a0\u03bcm. [ 12 ]  Another constraint is that the x-ray beam is slitted down to only tens of micrometers wide. A potential solution has been proposed in the form of parallel imaging with multiple slits. [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3833", "text": "Analyzer-based imaging (ABI)  is also known as  diffraction-enhanced imaging ,  phase-dispersion Introscopy  and  multiple-image radiography [ 54 ]  Its setup consists of a monochromator (usually a single or double crystal that also collimates the beam) in front of the sample and an analyzer crystal positioned in  Bragg geometry  between the sample and the detector. (See figure to the right)"}
{"_id": "WikiPedia_Radiology$$$corpus_3834", "text": "This analyzer crystal acts as an angular filter for the radiation coming from the sample. When these X-rays hit the analyzer crystal the condition of  Bragg diffraction  is satisfied only for a very narrow range of incident angles. When the scattered or refracted X-rays have incident angles outside this range they will not be reflected at all and don't contribute to the signal. Refracted X-rays within this range will be reflected depending on the incident angle. The dependency of the reflected intensity on the incident angle is called a rocking curve and is an intrinsic property of the imaging system, i.e. it represents the intensity measured at each pixel of the detector when the analyzer crystal is \"rocked\" (slightly rotated in angle \u03b8) with no object present and thus can be easily measured. [ 54 ]  The typical angular acceptance is from a few microradians to tens of microradians and is related to the  full width at half maximum (FWHM)  of the rocking curve of the crystal."}
{"_id": "WikiPedia_Radiology$$$corpus_3835", "text": "When the analyzer is perfectly aligned with the monochromator and thus positioned to the peak of the rocking curve, a standard X-ray radiograph with enhanced contrast is obtained because there is no blurring by scattered photons. Sometimes this is referred to as \"extinction contrast\"."}
{"_id": "WikiPedia_Radiology$$$corpus_3836", "text": "If, otherwise, the analyzer is oriented at a small angle (detuning angle) with respect to the monochromator then X-rays refracted in the sample by a smaller angle will be reflected less, and X-rays refracted by a larger angle will be reflected more. Thus the contrast of the image is based on different refraction angles in the sample.\nFor small phase gradients the refraction angle can be expressed as"}
{"_id": "WikiPedia_Radiology$$$corpus_3837", "text": "where  k  is the length of the  wave vector  of the incident radiation and the second term on the right hand side is the first  derivative  of the phase in the diffraction direction. Since not the phase itself, but the first derivative of the phase front is measured, analyzer-based imaging is less sensitive to low spatial frequencies than crystal interferometry but more sensitive than PBI."}
{"_id": "WikiPedia_Radiology$$$corpus_3838", "text": "Contrary to the former methods analyzer-based imaging usually provides phase information only in the diffraction direction, but is not sensitive to angular deviations on the plane perpendicular to the diffraction plane. This sensitivity to only one component of the phase gradient can lead to ambiguities in phase estimation. [ 55 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3839", "text": "By recording several images at different detuning angles, meaning at different positions on the rocking curve, a data set is gained which allows the retrieval of quantitative differential phase information. There are several algorithms to reconstruct information from the rocking curves, some of them provide an additional signal. This signal comes from Ultra-small-angle scattering by sub-pixel sample structures and causes angular broadening of the beam and hence a broadening of the shape of the rocking curve. Based on this scattering contrast a new kind of image called Dark-field image can be produced. [ 17 ] [ 54 ] [ 56 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3840", "text": "Tomographic imaging with analyzer-based imaging can be done by fixing the analyzer at a specific angle and rotating the sample through 360\u00b0 while the projection data are acquired. Several sets of projections are acquired from the same sample with different detuning angles and then a tomographic image can be reconstructed. Assuming that the crystals are normally aligned such that the derivative of the refractive index is measured in the direction parallel to the tomographic axis, the resulting \"refraction CT image\" shows the pure image of the out-of-plane gradient."}
{"_id": "WikiPedia_Radiology$$$corpus_3841", "text": "For analyzer-based imaging, the stability requirements of the crystals is less strict than for crystal interferometry but the setup still requires a perfect analyzer crystal that needs to be very precisely controlled in angle and the size of the analyzer crystal and the constraint that the beam needs to be parallel also limits the field of view.  Additionally as in crystal interferometry a general limitation for the spatial resolution of this method is given by the blurring in the analyzer crystal due to  dynamic diffraction effects , but can be improved by using  grazing incidence diffraction  for the crystal. [ 55 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3842", "text": "While the method in principle requires monochromatic, highly collimated radiation and hence is limited to a synchrotron radiation source, it was shown recently that the method remains feasible using a laboratory source with a polychromatic spectrum when the rocking curve is adapted to the K  \u03b1  spectral line radiation of the target material. [ 57 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3843", "text": "Due to its high sensitivity to small changes in the refraction index this method is well suited to image soft tissue samples and is already implemented to medical imaging, especially in Mammography for a better detection of microcalcifications [ 1 ]  and in bone cartilage studies. [ 58 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3844", "text": "Propagation-based imaging (PBI)  is the most common name for this technique but it is also called   in-line holography ,  refraction-enhanced imaging [ 59 ]   or  phase-contrast radiography . The latter denomination derives from the fact that the experimental setup of this method is basically the same as in conventional radiography. It consists of an in-line arrangement of an X-ray source, the sample and an X-ray detector and no other optical elements are required. The only difference is that the detector is not placed immediately behind the sample, but in some distance, so the radiation refracted by the sample can interfere with the unchanged beam. [ 13 ] \nThis simple setup and the low stability requirements provides a big advantage of this method over other methods discussed here."}
{"_id": "WikiPedia_Radiology$$$corpus_3845", "text": "Under  spatially coherent illumination  and an intermediate distance between sample and detector an interference pattern with \"Fresnel fringes\" is created; i.e. the fringes arise in the free space propagation in the  Fresnel regime , which means that for the distance between detector and sample the approximation of  Kirchhoff's diffraction formula  for the near field, the  Fresnel diffraction equation  is valid. In contrast to crystal interferometry the recorded interference fringes in PBI are not proportional to the phase itself but to the second derivative (the  Laplacian ) of the phase of the wavefront. Therefore, the method is most sensitive to abrupt changes in the decrement of the refractive index. This leads to stronger contrast outlining the surfaces and structural boundaries of the sample ( edge enhancement ) compared with a conventional radiogram. [ 60 ] [ 61 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3846", "text": "PBI can be used to enhance the contrast of an absorption image, in this case the phase information in the image plane is lost but contributes to the image intensity ( edge enhancement  of attenuation image). However it is also possible to separate the phase and the attenuation contrast, i.e.  to reconstruct the distribution of the real and imaginary part of the refractive index separately. The unambiguous determination of the phase of the wave front ( phase retrieval ) can be realized by recording several images at different detector-sample distances and using algorithms based on the  linearization  of the  Fresnel diffraction integral  to reconstruct the phase distribution, but this approach suffers from amplified noise for low spatial frequencies and thus slowly varying components may not be accurately recovered.  There are several more approaches for phase retrieval and a good overview about them is given in. [ 62 ] [ 63 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3847", "text": "Tomographic reconstructions of the 3D distribution of the refractive index or \"Holotomography\" is implemented by rotating the sample and recording for each projection angle a series of images at different distances. [ 64 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3848", "text": "A high resolution detector is required to resolve the interference fringes, which practically limits the field of view of this technique or requires larger propagation distances.  The achieved spatial resolution is relatively high in comparison to the other methods and, since there are no optical elements in the beam, is mainly limited by the degree of  spatial coherence  of the beam.\nAs mentioned before, for the formation of the Fresnel fringes, the constraint on the  spatial coherence  of the used radiation is very strict, which limits the method to small or very distant sources, but in contrast to crystal interferometry and analyzer-based imaging the constraint on the  temporal coherence , i.e. the polychromaticity is quite relaxed. [ 55 ]  Consequently, the method cannot only be used with synchrotron sources but also with polycromatic laboratory X-ray sources providing sufficient spatial coherence, such as  microfocus X-ray tubes . [ 60 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3849", "text": "Generally spoken, the image contrast provided by this method is lower than of other methods discussed here, especially if the density variations in the sample are small. Due to its strength in enhancing the contrast at boundaries, it's well suited for imaging fiber or foam samples. [ 65 ]  A very important application of PBI is the examination of  fossils  with synchrotron radiation, which reveals details about the  paleontological  specimens which would otherwise be inaccessible without destroying the sample. [ 66 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3850", "text": "Grating-based imaging (GBI)  includes  Shearing interferometry  or  X-ray Talbot interferometry (XTI) , and  polychromatic   far-field interferometry (PFI) . [ 38 ]  Since the first X-ray grating interferometer\u2014consisting of two phase gratings and an analyzer crystal [ 25 ] \u2014was built, various slightly different setups for this method have been developed; in the following the focus lies on the nowadays standard method consisting of a phase grating and an analyzer grating. [ 26 ]  (See figure to the right)."}
{"_id": "WikiPedia_Radiology$$$corpus_3851", "text": "The  XTI  technique is based on the  Talbot effect  or \"self-imaging phenomenon\", which is a  Fresnel diffraction  effect and leads to repetition of a periodic wavefront after a certain propagation distance, called the \" Talbot length \". This periodic wavefront can be generated by spatially coherent illumination of a periodic structure, like a  diffraction grating , and if so the intensity distribution of the wave field at the Talbot length resembles exactly the structure of the grating and is called a self-image. [ 23 ]  It has also been shown that intensity patterns will be created at certain fractional Talbot lengths. At half the distance the same intensity distribution appears except for a lateral shift of half the grating period while at certain smaller fractional Talbot distances the self-images have fractional periods and fractional sizes of the intensity maxima and minima, that become visible in the intensity distribution behind the grating, a so-called Talbot carpet. The Talbot length and the fractional lengths can be calculated by knowing the parameters of the illuminating radiation and the illuminated grating and thus gives the exact position of the intensity maxima, which needs to be measured in GBI. [ 67 ]  While the Talbot effect and the Talbot interferometer were discovered and extensively studied by using visible light it has been demonstrated several years ago for the hard X-ray regime as well. [ 68 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3852", "text": "In GBI a sample is placed before or behind the phase grating (lines of the grating show negligible absorption but substantial phase shift) and thus the interference pattern of the Talbot effect is modified by absorption, refraction and scattering in the sample.\nFor a phase object with a small phase gradient the X-ray beam is deflected by"}
{"_id": "WikiPedia_Radiology$$$corpus_3853", "text": "where  k  is the length of the  wave vector  of the incident radiation and the second factor on the right hand side is the first derivative of the phase in the direction perpendicular to the propagation direction and parallel to the alignment of the grating. Since the transverse shift of the interference fringes is linear proportional to the deviation angle the differential phase of the wave front is measured in GBI, similar as in ABI. In other words, the angular deviations are translated into changes of locally transmitted intensity.\nBy performing measurements with and without sample the change in position of the interference pattern caused by the sample can be retrieved. The period of the interference pattern is usually in the range of a few  micrometers , which can only be conveniently resolved by a very high resolution detector in combination with a very intense illumination ( a source providing a very high flux) and hence limits the field of view significantly . [ 69 ]  This is the reason why a second grating, typically an absorption grating, is placed at a fractional Talbot length to analyze the interference pattern. [ 26 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3854", "text": "The analyzer grating does normally have the same period as the interference fringes and thus transforms local fringe position into signal intensity variation on the detector, which is placed immediately behind the grating.\nIn order to separate the phase information from other contributions to the signal, a technique called \"phase-stepping\" is used. [ 27 ]  One of the gratings is scanned along the transverse direction term  x g ;  over one period of the grating, and for different positions of the grating an image is taken. The intensity signal in each pixel in the detector plane oscillates as a function of  x g . The recorded intensity oscillation can be represented by a  Fourier series  and by recording and comparing these intensity oscillations with or without the sample the separated differential phase shift and absorption signal relative to the reference image can be extracted. [ 27 ]  As in analyzer-based imaging, an additional signal coming from Ultra-small-angle scattering by sub-pixel microstructures of the sample, called dark-field contrast, can also be reconstructed. [ 30 ]  This method provides high spatial resolution, but also requires long exposure times."}
{"_id": "WikiPedia_Radiology$$$corpus_3855", "text": "An alternative approach is the retrieval of the differential phase by using  Moir\u00e9 fringes . These are created as a superposition of the self-image of G1 and the pattern of G2 by using gratings with the same periodicity and inclining G2 against G1 regarding to the optical axis with a very small angle(<<1). This moir\u00e9 fringes act as carrier fringes because they have a much larger spacing/period (smaller spatial frequency) than the Talbot fringes and thus the phase gradient introduced by the sample can be detected as the displacement of the Moir\u00e9 fringes. [ 26 ]   With a Fourier analysis of the Moir\u00e9 pattern the absorption and dark-field signal can also be extracted. [ 70 ] \nUsing this approach, the spatial resolution is lower than one achieved by the phase-stepping technique, but the total exposure time can be much shorter, because a differential phase image can be retrieved with only one Moir\u00e9 pattern. [ 71 ]  Single-shot Fourier analysis technique was used in early grid-based scattering imaging [ 31 ]  similar to the  shack-Hartmann wavefront sensor  in optics, which allowed first live animal studies. [ 72 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3856", "text": "A technique to eliminate mechanical scanning of the grating and still retain the maximum spatial resolution is electronic phase stepping. [ 33 ]  It scans the source spot of the x-ray tube with an electro-magnetic field. This causes the projection of the object to move in the opposite direction, and also causes a relative movement between the projection and the Moir\u00e9 fringes. The images are digitally shifted to realign the projections. The result is that the projection of the object is stationary, while the Moir\u00e9 fringes move over it. This technique effectively synthesizes the phase stepping process, but without the costs and delays associated with mechanical movements."}
{"_id": "WikiPedia_Radiology$$$corpus_3857", "text": "With both of these phase-extraction methods tomography is applicable by rotating the sample around the tomographic axis, recording a series of images with different projection angles and using back projection algorithms to reconstruct the 3-dimensional distributions of the real and imaginary part of the refractive index. [ 27 ] [ 71 ] \nQuantitative tomographic reconstruction of the dark-field signal has also been demonstrated for the phase-stepping technique [ 34 ]  and very recently for the Moir\u00e9 pattern approach as well. [ 70 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3858", "text": "It has also been demonstrated that dark-field imaging with the grating interferometer can be used to extract orientational information of structural details in the sub-micrometer regime beyond the spatial resolution of the detection system. While the scattering of X-rays in a direction perpendicular to the grating lines provides the dark-field contrast, the scattering in a direction parallel to the grating lines only lead to blurring in the image, which is not visible at the low resolution of the detector. [ 31 ]  This intrinsic physical property of the setup is utilized to extract orientational information about the angular variation of the local scattering power of the sample by rotating the sample around the optical axis of the set-up and collecting a set of several dark-field images, each measuring the component of the scattering perpendicular to the grating lines for that particular orientation. This can be used to determine the local angle and degree of orientation of bone and could yield valuable information for improving research and diagnostics of  bone diseases  like  osteoporosis  or  osteoarthritis . [ 73 ] [ 74 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3859", "text": "The standard configuration as shown in the figure to the right requires spatial coherence of the source and consequently is limited to high brilliant synchrotron radiation sources. This problem can be handled by adding a third grating close to the X-ray source, known as a  Talbot-Lau interferometer . This source grating, which is usually an absorption grating with transmission slits, creates an \"array of individually coherent but mutually incoherent sources\". As the source grating can contain a large number of individual apertures, each creating a sufficiently coherent virtual line source, standard X-ray generators with source sizes of a few square millimeters can be used efficiently and the field of view can be significantly increased. [ 29 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3860", "text": "Since the position of the interference fringes formed behind the beam-splitter grating is independent of wavelength over a wide energy range of the incident radiation the interferometer in phase-stepping configuration can still be used efficiently with polychromatic radiation. [ 27 ] \nFor the Moir\u00e9 pattern configuration the constraint on the radiation energy is a bit stricter, because a finite bandwidth of energy instead of monochromatic radiation causes a decrease in the visibility of the Moir\u00e9 fringes and thus the image quality, but a moderate polychromaticity is still allowed. [ 75 ]  A great advantage of the usage of polychromatic radiation is the shortening of the exposure times and this has recently been exploited by using white synchrotron radiation to realize the first dynamic (time-resolved) Phase contrast tomography. [ 35 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3861", "text": "A technical barrier to overcome is the fabrication of gratings with high  aspect ratio  and small periods. The production of these gratings out of a  silicon wafer  involves microfabrication techniques like  photolithography , anisotropic  wet etching ,  electroplating  and  molding . [ 76 ]  A very common fabrication process for X-ray gratings is  LIGA , which is based on deep  X-ray lithography  and electroplating. It was developed in the 1980s for the fabrication of extreme high aspect ratio microstructures by scientists from the  Karlsruhe Institute of Technology (KIT) . [ 77 ] \nAnother technical requirement is the stability and precise alignment and movement of the gratings (typically in the range of some nm), but compared to other methods, e.g. the crystal interferometer the constraint is easy to fulfill."}
{"_id": "WikiPedia_Radiology$$$corpus_3862", "text": "The grating fabrication challenge was eased by the discovery of a  phase moir\u00e9 effect [ 38 ]  which provides an all-phase-grating interferometer that works with compact sources, called the  polychromatic far-field interferometer  (see figure on the right). Phase gratings are easier to make when compared with the source and analyzer gratings mentioned above, since the grating depth required to cause phase shift is much less than what is needed to absorb x-rays. Phase gratings of 200 - 400 nanometer periods have been used to improve phase sensitivity in table-top PFI imagers. [ 39 ]  In PFI a phase grating is used to convert the fine interference fringes into a broad intensity pattern at a distal plane, based on the  phase moir\u00e9 effect . Besides higher sensitivity, another incentive for smaller grating periods is that the lateral coherence of the source needs to be at least one grating period."}
{"_id": "WikiPedia_Radiology$$$corpus_3863", "text": "A disadvantage of the standard GBI setup is the sensitivity to only one component of the phase gradient, which is the direction parallel to the 1-D gratings. This problem has been solved either by recording differential phase contrast images of the sample in both direction x and y by turning the sample (or the gratings) by 90\u00b0 [ 78 ]  or by the employment of two-dimensional gratings. [ 79 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3864", "text": "Being a differential phase technique, GBI is not as sensitive as crystal interferometry to low spatial frequencies, but because of the high resistance of the method against mechanical instabilities, the possibility of using detectors with large pixels and a large field of view and, of crucial importance, the applicability to conventional laboratory X-ray tubes, grating-based imaging is a very promising technique for medical diagnostics and soft tissue imaging.\nFirst medical applications like a pre-clinical  mammography  study, show great potential for the future of this technique. [ 36 ]  Beyond that GBI has applications in a wide field of material science, for instance it could be used to improve security screening. [ 30 ] [ 80 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3865", "text": "Edge-illumination (EI) was developed at the Italian synchrotron (Elettra) in the late \u201890s, [ 19 ]  as an alternative to ABI. It is based on the observation that, by illuminating only the edge of detector pixels, high sensitivity to phase effects is obtained (see figure)."}
{"_id": "WikiPedia_Radiology$$$corpus_3866", "text": "Also in this case, the relation between X-ray refraction angle and first derivative of the phase shift caused by the object is exploited:"}
{"_id": "WikiPedia_Radiology$$$corpus_3867", "text": "\u0394 \n \u03b1 \n = \n \n \n 1 \n k \n \n \n \n \n \n \u2202 \n \u03d5 \n ( \n x \n ) \n \n \n \u2202 \n x \n \n \n \n \n \n {\\displaystyle \\Delta \\alpha ={\\frac {1}{k}}{\\frac {\\partial \\phi (x)}{\\partial x}}}"}
{"_id": "WikiPedia_Radiology$$$corpus_3868", "text": "If the X-ray beam is vertically thin and impinges on the edge of the detector, X-ray refraction can change the status of the individual X-ray from \"detected\" to \"undetected\" and vice versa, effectively playing the same role as the crystal rocking curve in ABI. This analogy with ABI, already observed when the method was initially developed, [ 19 ]  was more recently formally demonstrated. [ 81 ]  Effectively, the same effect is obtained \u2013 a fine angular selection on the photon direction; however, while in analyzer-based imaging the beam needs to be highly collimated and monochromatic, the absence of the crystal means that edge-illumination can be implemented with divergent and polychromatic beams, like those generated by a conventional rotating-anode X-ray tube. This is done by introducing two opportunely designed masks (sometimes referred to as \u201ccoded-aperture\u201d masks [ 20 ] ), one immediately before the sample, and one in contact with the detector (see figure)."}
{"_id": "WikiPedia_Radiology$$$corpus_3869", "text": "The purpose of the latter mask is simply to create insensitive regions between adjacent pixels, and its use can be avoided if specialized detector technology is employed. In this way, the edge-illumination configuration is simultaneously realized for all pixel rows of an area detector. This plurality of individual beamlets means that, in contrast to the synchrotron implementation discussed above, no sample scanning is required \u2013 the sample is placed downstream of the sample mask and imaged in a single shot (two if phase retrieval is performed [ 22 ] ). Although the set-up perhaps superficially resembles that of a grating interferometer, the underpinning physical mechanism is different. In contrast to other phase contrast X-ray imaging techniques, edge-illumination is an incoherent technique, and was in fact proven to work with both spatially and temporally incoherent sources, without any additional source aperturing or collimation. [ 22 ] [ 82 ]  For example, 100\u00a0\u03bcm focal spots are routinely used which are compatible with, for example, diagnostic mammography systems. Quantitative phase retrieval was also demonstrated with (uncollimated) incoherent sources, showing that in some cases results analogous to the synchrotron gold standard can be obtained. [ 22 ]  The relatively simple edge-illumination set-up results in phase sensitivity at least comparable with other phase contrast X-ray imaging techniques, [ 83 ]  results in a number of advantages, which include reduced exposure time for the same source power, reduced radiation dose, robustness against environmental vibrations, and easier access to high X-ray energy. [ 83 ] [ 84 ] [ 85 ] [ 86 ]  Moreover, since their aspect ratio is not particularly demanding, masks are cheap, easy to fabricate (e.g.do not require X-ray lithography) and can already be scaled to large areas. The method is easily extended to phase sensitivity in two directions, for example, through the realization of L-shaped apertures for the simultaneous illumination of two orthogonal edges in each detector pixel. [ 87 ]  More generally, while in its simplest implementation beamlets match individual pixel rows (or pixels), the method is highly flexible, and, for example, sparse detectors and asymmetric masks can be used [ 88 ]  and compact [ 89 ]   and microscopy [ 90 ]  systems can be built. So far, the method has been successfully demonstrated in areas such as security scanning, [ 91 ]  biological imaging, [ 83 ] [ 89 ]  material science, [ 92 ]  paleontology [ 93 ] [ 94 ]  and others; adaptation to 3D (computed tomography) was also demonstrated. [ 93 ] [ 95 ]  Alongside simple translation for use with conventional x-ray sources, there are substantial benefits in the implementation of edge-illumination with coherent synchrotron radiation, among which are high performance at very high X-ray energies [ 94 ]  and high angular resolutions. [ 96 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3870", "text": "Four potential benefits of phase contrast have been identified in a medical imaging context: [ 42 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3871", "text": "A quantitative comparison of phase- and absorption-contrast mammography that took realistic constraints into account (dose, geometry, and photon economy) concluded that grating-based phase-contrast imaging (Talbot interferometry) does not exhibit a general signal-difference-to-noise improvement relative to absorption contrast, but the performance is highly task dependent. [ 97 ] [ 98 ]  Such a comparison is yet to be undertaken for all phase contrast methods, however, the following considerations are central to such a comparison:"}
{"_id": "WikiPedia_Radiology$$$corpus_3872", "text": "Some of the tradeoffs are illustrated in the right-hand figure, which shows the benefit of phase contrast over absorption contrast for detection of different targets of relevance in mammography as a function of target size. [ 97 ]  Note that these results do not include potential benefits from the dark-field signal."}
{"_id": "WikiPedia_Radiology$$$corpus_3873", "text": "Following preliminary, lab-based studies in e.g. computed tomography  [ 100 ]  and mammography, [ 101 ]  phase contrast imaging is beginning to be applied in real medical applications, such as lung imaging, [ 102 ]  imaging of extremities, [ 103 ]  intra-operative specimen imaging. [ 104 ]   In vivo  applications of phase contrast imaging have been kick-started by the pioneering mammography study with synchrotron radiation undertaken in Trieste, Italy. [ 105 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3874", "text": "Theranostics , also known as  theragnostics , [ 1 ]  is a technique commonly used in  personalised medicine . For example in  nuclear medicine , one  radioactive drug  is used to identify ( diagnose ) and a second radioactive drug is used to treat (therapy)  cancerous tumors . [ 2 ] [ 3 ] [ 4 ]  In other words, theranostics combines  radionuclide imaging  and  radiation therapy  which targets specific  biological pathways ."}
{"_id": "WikiPedia_Radiology$$$corpus_3875", "text": "Technologies used for theranostic imaging include  radiotracers ,  contrast agents ,  positron emission tomography , and  magnetic resonance imaging . [ 3 ] [ 5 ]  It has been used to treat  thyroid cancer  and  neuroblastomas . [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3876", "text": "The term \"theranostic\" is a  portmanteau  of two words,  thera peutic and diag nostic , thus referring to a combination of diagnosis and treatment that also allows for continuing medical assessment of a patient. The first known use of the term is attributed to John Funkhouser, a consultant for the company Cardiovascular Diagnostic, who used it in a press release in August 1998. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3877", "text": "Theranostics originated in the field of  nuclear medicine ;  iodine isotope  131 for the diagnostic study and treatment of  thyroid cancer  was one of its earliest applications. [ 7 ]   Nuclear medicine  encompasses various substances, either alone or in combination, that can be used for  diagnostic imaging  and targeted therapy. These substances may include ligands of  receptors  present on the target tissue or compounds, like  iodine , that are internalized by the target through metabolic processes. By using these mechanisms, theranostics enables the localization of pathological tissues with imaging and the targeted destruction of these tissues using high doses of  radiation . [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3878", "text": "Contrast agents  with therapeutic properties have been under development for several years. [ 8 ]  One example is the design of contrast agents capable of releasing a  chemotherapeutic agent  locally at the target site, triggered by a stimulus provided by the operator. This localized approach aims to increase treatment efficacy and minimize side effects. For instance,  ultrasound -based contrast media, such as  microbubbles , can accumulate in hypervascularized tissues and release the active ingredient in response to ultrasound waves, thus targeting a specific area chosen by the  sonographer . [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3879", "text": "Another approach involves linking  monoclonal antibodies  (capable of targeting different molecular targets) to  nanoparticles . This strategy enhances the drug's affinity and specificity towards the target and enables visualization of the treatment area, such as using superparamagnetic  iron oxide  particles detectable by  magnetic resonance imaging . [ 9 ]  Additionally, these particles can be designed to release  chemotherapy  agents specifically at the site of binding, producing a local  synergistic  effect with antibody action. Integrating these methods with medical-nuclear techniques, which offer greater imaging sensitivity, may aid in target identification and treatment monitoring. [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3880", "text": "Positron emission tomography  (PET) imaging in theranostics provides insight into metabolic and molecular processes within the body. The PET scanner detects   photons  and creates three-dimensional images that enable visualization and quantification of physiological and biochemical processes. [ 11 ]  PET imaging uses  radiotracers  that target specific molecules or processes. For example, [18F]  fluorodeoxyglucose  (FDG) is commonly used to assess glucose metabolism, as cancer cells exhibit increased glucose uptake. Other radiotracers target specific receptors, enzymes, or transporters, allowing the evaluation of various physiological and pathological processes. [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3881", "text": "PET imaging plays a role in both diagnosis and treatment planning. It aids in the identification and staging of diseases, such as cancer, by visualizing the extent and metabolic activity of tumors. PET scans can also guide treatment decisions by assessing treatment response and monitoring disease progression. [ citation needed ]  Additionally, PET imaging is used to determine the suitability of patients for targeted therapies based on specific molecular characteristics, enabling personalized treatment approaches.  [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3882", "text": "Single-photon emission computed tomography  (SPECT) is employed in theranostics, using  gamma rays  emitted by a  radiotracer  to generate three-dimensional images of the body. SPECT imaging involves the injection of a radiotracer that emits single photons, which are detected by a gamma camera rotating around the person undergoing imaging. [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3883", "text": "SPECT provides functional and anatomical information, allowing the assessment of organ structure, blood flow, and specific molecular targets. It is useful in evaluating diseases that involve altered blood flow or specific receptor expression. For example, SPECT imaging with  technetium-99m  (Tc-99m) radiopharmaceuticals may be able to assess myocardial perfusion and identify areas of  ischemia  or  infarction  in patients with cardiovascular diseases. [ 13 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3884", "text": "SPECT imaging helps in identifying disease localization, staging, and assessing the response to therapy. Moreover, SPECT imaging is employed in targeted  radionuclide  therapy, where the same radiotracer used for diagnostic imaging can be used to deliver therapeutic doses of radiation to the diseased tissue. [ 13 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3885", "text": "Magnetic resonance imaging  (MRI) is a non-invasive imaging technique that uses strong magnetic fields and radiofrequency pulses to generate detailed anatomical and functional images of the body. MRI provides excellent soft tissue contrast and is widely used in theranostics for its ability to visualize anatomical structures and assess physiological processes. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3886", "text": "In theranostics, MRI allows for the detection and characterization of tumors, assessment of tumor extent, and evaluation of treatment response. MRI can provide information on  tissue perfusion , diffusion, and metabolism, aiding in the selection of appropriate therapies and monitoring their effectiveness. [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3887", "text": "Advancements in MRI technology have expanded its capabilities in theranostics. Techniques such as functional MRI (fMRI) enable the assessment of brain activation and connectivity, while  diffusion-weighted imaging  (DWI) provides insights into tissue microstructure. The development of molecular imaging agents, such as superparamagnetic  iron oxide   nanoparticles , allows for targeted imaging and tracking of specific molecular entities. [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3888", "text": "Theranostics encompasses a range of therapeutic approaches that are designed to target and treat diseases with enhanced precision."}
{"_id": "WikiPedia_Radiology$$$corpus_3889", "text": "Targeted drug delivery  systems facilitate the selective delivery of therapeutic agents to specific disease sites while minimizing off-target effects. These systems employ strategies, such as  nanoparticles ,  liposomes , and  micelles , to encapsulate drugs and enhance their stability, solubility, and bioavailability. [ 15 ]  By incorporating diagnostic components, such as imaging agents or targeting  ligands , into these delivery systems, clinicians can monitor drug distribution and accumulation in real-time, ensuring effective treatment and reducing systemic toxicity. Targeted drug delivery systems hold promise in the treatment of cancer, cardiovascular diseases, and other conditions, as they allow for personalized and site-specific therapy. [ 15 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3890", "text": "Gene therapy  is a therapeutic approach that involves modifying or replacing faulty genes to treat or prevent diseases. In theranostics, gene therapy can be combined with diagnostic imaging to monitor the delivery, expression, and activity of therapeutic genes. [ 16 ]  Imaging techniques such as  MRI ,  PET , and  optical imaging  enable non-invasive assessment of gene transfer and expression, providing valuable insights into the efficacy and safety of gene-based treatments. [ 15 ]  Gene therapy has shown potential in treating  genetic disorders , cancer, and cardiovascular diseases, and its integration with diagnostic imaging offers a comprehensive approach for monitoring and optimizing treatment outcomes. [ 16 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3891", "text": "Radiotherapy  can be integrated with imaging techniques to guide treatment planning, monitor radiation dose distribution, and assess treatment response. Molecular imaging methods, such as PET and  SPECT , can be employed to visualize and quantify tumor characteristics, such as  hypoxia  or  receptor expression , aiding in personalized radiation dose optimization 10 ."}
{"_id": "WikiPedia_Radiology$$$corpus_3892", "text": "Additionally, theranostic approaches involving  radiolabeled  therapeutic agents, known as  radiotheranostics , combine the therapeutic effects of radiation with diagnostic capabilities. Radiotheranostics, including  Peptide receptor radionuclide therapy  (PRRT), hold promise for targeted radiotherapy, enabling precise tumor targeting and dose escalation, while sparing healthy tissues. [ 17 ]  For example, PRRT based on  Lutetium -177 combinations (known as  radioligands ) has emerged as a treatment option for inoperable  metastatic   neuroendocrine tumours  (NET). [ 18 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3893", "text": "Immunotherapy harnesses the body's immune system to recognize and attack cancer cells or other disease targets. In theranostics, immunotherapeutic approaches can be coupled with diagnostic imaging to assess immune cell  infiltration , tumor  immunogenicity , and treatment response. [ 7 ]  Imaging techniques, such as PET and MRI, can provide valuable information about the tumor microenvironment, immune cell dynamics, and response to immunotherapies. Furthermore, theranostic strategies involving the use of radiolabeled immunotherapeutic agents allow for simultaneous imaging and therapy, aiding in patient selection, treatment monitoring, and optimization of immunotherapeutic regimens. [ 15 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3894", "text": "Nanomedicine refers to the use of nanoscale materials for medical applications. In theranostics, nanomedicine offers opportunities for targeted drug delivery, imaging, and therapy. [ 7 ]   Nanoparticles  can be engineered to carry therapeutic payloads, imaging agents, and targeting ligands, allowing for multimodal theranostic approaches. These nanocarriers can enhance drug stability, improve drug solubility, and enable controlled release at the disease site. Additionally, nanomaterials with inherent imaging properties, such as quantum dots or gold nanoparticles, can serve as contrast agents for imaging. [ 19 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3895", "text": "Theranostics has been applied in oncology, contributing to new approaches in the diagnosis, treatment, and monitoring of cancers. By integrating diagnostic imaging and targeted therapies, theranostics offers personalized approaches that improve treatment outcomes and patient care. In oncology, theranostics encompasses a wide range of applications, including the management of various types of cancers such as breast, lung, prostate, and colorectal cancer. [ 8 ]  Molecular imaging techniques, such as  positron emission tomography  (PET) and  single-photon emission computed tomography  (SPECT), enable the visualization and characterization of cancerous lesions, aiding in early detection, staging, and assessment of treatment response. [ better\u00a0source\u00a0needed ] [ 20 ]  This allows for more accurate and tailored treatment planning, including the selection of appropriate targeted therapies or the optimization of radiation therapy."}
{"_id": "WikiPedia_Radiology$$$corpus_3896", "text": "Despite the significant progress, the translation of theranostics into routine clinical practice faces challenges, including the need for standardized imaging protocols,  biomarker  validation, and regulatory considerations. Additionally, there is a continuous need for research and development to further enhance the effectiveness and accessibility of theranostic approaches in oncology. [ 19 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3897", "text": "Theranostics extends beyond oncology and holds potential in the fields of  neurology  and  cardiology . [ 21 ] [ 22 ]  In neurology, theranostic approaches offer new avenues for the diagnosis and treatment of various neurodegenerative diseases, such as  Alzheimer's disease ,  Parkinson's disease , and   multiple sclerosis . Advanced imaging techniques, including  magnetic resonance imaging  (MRI) and positron emission tomography (PET), allow for the visualization of  neuroanatomy , functional connectivity, and molecular changes in the brain. This enables early detection, precise diagnosis, and monitoring of disease progression, facilitating the development of targeted therapeutic interventions."}
{"_id": "WikiPedia_Radiology$$$corpus_3898", "text": "Similarly, in cardiology, theranostics play a significant role in the diagnosis and treatment of cardiovascular conditions. Non-invasive imaging modalities like MRI and computed tomography (CT) provide detailed information about cardiac structure, function, and blood flow, aiding in the assessment of heart disease and the guidance of interventions. Theranostic approaches in cardiology involve targeted drug delivery systems for the treatment of conditions such as  atherosclerosis  and  restenosis , as well as image-guided interventions for precise stenting or catheter-based therapies. [ 21 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3899", "text": "Several challenges remain to be addressed for widespread adoption and integration of theranostics into routine clinical practice. Regulatory considerations will play a role in ensuring the safety, efficacy, and quality of theranostic agents and technologies. Harmonization of regulations across different countries and regions is necessary to facilitate global implementation. [ 23 ]  Cost-effectiveness is a significant challenge, as theranostic approaches can be expensive. [ 23 ]  Strategies to optimize resource utilization and reimbursement models have been discussed. Technical limitations, such as the development of more specific and sensitive imaging agents, improvement of imaging resolution and quality, and the integration of different imaging modalities, require ongoing research and technological advancements. [ better\u00a0source\u00a0needed ] [ 24 ]  Ethical considerations surrounding patient privacy, data security, and the responsible use of patient information need to be addressed. [ 24 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3900", "text": "Tomosynthesis , also  digital tomosynthesis  ( DTS ), is a method for performing high-resolution limited-angle  tomography  at  radiation dose  levels comparable with  projectional radiography . It has been studied for a variety of clinical applications, including vascular imaging, dental imaging, orthopedic imaging, mammographic imaging, musculoskeletal imaging, and chest imaging. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3901", "text": "The concept of tomosynthesis was derived from the work of Ziedses des Plantes, who developed methods of reconstructing an arbitrary number of planes from a set of projections. Though this idea was displaced by the advent of computed tomography, tomosynthesis later gained interest as a low-dose tomographic alternative to CT. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3902", "text": "Tomosynthesis reconstruction algorithms are similar to  CT  reconstructions, in that they are based on performing an inverse  Radon transform . Due to partial data sampling with very few projections, approximation algorithms have to be used. Filtered back projection and iterative, expectation-maximization algorithms have both been used to reconstruct the data. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3903", "text": "Reconstruction algorithms for tomosynthesis are different from those of conventional CT because the conventional  filtered back projection  algorithm requires a complete set of data. Iterative algorithms based upon  expectation maximization  are most commonly used, but are  computationally intensive. Some manufacturers have produced practical systems using off-the-shelf  GPUs  to perform the reconstruction in a few seconds."}
{"_id": "WikiPedia_Radiology$$$corpus_3904", "text": "Digital tomosynthesis combines digital image capture and processing with simple tube/detector motion as used in conventional computed tomography (CT). However, though there are some similarities to CT, it is a separate technique. In modern (helical) CT, the source/detector makes at least a complete 180-degree rotation about the subject obtaining a complete set of data from which images may be reconstructed. Digital tomosynthesis, on the other hand, only uses a limited rotation angle (e.g., 15-60 degrees) with a lower number of discrete exposures (e.g., 7-51) than CT. This incomplete set of projections is digitally processed to yield images similar to conventional tomography with a limited  depth of field . Because the image processing is digital, a series of slices at different depths and with different thicknesses can be reconstructed from the same acquisition. However, since fewer projections are needed than CT to perform the reconstruction, radiation exposure and cost are both reduced. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3905", "text": "Digital breast tomosynthesis  ( DBT ) [ 5 ]  is  Food and Drug Administration  (FDA) approved for use in  breast cancer screening . [ 6 ]  The benefit for screening has been debated, [ 7 ]  but consensus is being reached that the technology is improving sensitivity compared to two-view digital  mammography  at the cost of a slightly reduced specificity (increased recall rates). [ 8 ]  Because the data acquired are 85 - 160 micron typical resolution, much higher than CT, DBT is unable to offer the narrow slice widths that CT offers (typically 1-1.5\u00a0mm). However, the higher resolution detectors permit very high in-plane resolution, even if the Z-axis resolution is less. Another interesting property of breast tomosynthesis is that image quality may vary substantially through the imaging volume. [ 9 ]  DBT reading times are much higher, compared to  mammography  interpretation. [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3906", "text": "Photon-counting breast tomosynthesis has been investigated, [ 11 ]  and  spectral imaging  applications, such as  breast density  measurement and lesion characterization, [ 12 ] [ 13 ]  have been investigated on that platform."}
{"_id": "WikiPedia_Radiology$$$corpus_3907", "text": "Tomosynthesis has a much more limited depth of field than does CT. For this reason, it likely will not be able to replace CT for the evaluation of the deeper organs of the body. However, since bones are often near the skin, multiple musculoskeletal applications of tomosynthesis have been studied, most of which have mostly been used in research with limited use in everyday practice."}
{"_id": "WikiPedia_Radiology$$$corpus_3908", "text": "Tomosynthesis has been compared to both radiography and CT for the evaluation of healing fractures, especially in the presence of hardware. In a study of patients with wrist fractures, digital tomosynthesis was shown to enable detection of more fractures than radiography while simultaneously providing lower metal artifact than radiography. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3909", "text": "Tomosynthesis has been compared to  digital radiography , with CT as the standard, for the detection of erosions associated with  rheumatoid arthritis . The radiation dose of digital tomosynthesis was very close to that of digital radiography. However, tomosynthesis showed sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 80%, 75%, 78%, 76%, and 80%, compared to digital radiography were 66%, 81%, 74%, 77%, and 71%. [ 14 ]  The slight benefit digital tomosynthesis in this application may or may not justify the slightly increased cost of the modality compared to digital radiography."}
{"_id": "WikiPedia_Radiology$$$corpus_3910", "text": "Tomosynthesis is also used for x-ray inspection of electronics, [ 15 ]  particularly printed circuit board assemblies and electronic components. Tomosynthesis is usually used where a CT slice is required at high magnification, where conventional CT would not allow the sample to be located close enough to the x-ray source."}
{"_id": "WikiPedia_Radiology$$$corpus_3911", "text": "Gel dosimeters , also called  Fricke gel dosimeters , are manufactured from radiation sensitive chemicals that, upon irradiation with ionising radiation, undergo a fundamental change in their properties as a function of the absorbed radiation dose."}
{"_id": "WikiPedia_Radiology$$$corpus_3912", "text": "Over many years individuals have endeavoured to measure absorbed radiation dose distributions using gels. As long ago as 1950, the radiation-induced colour change in dyes was used to investigate radiation doses in gels. [ 1 ]  Further, in 1957 depth doses of photons and electrons in agar gels were investigated using spectrophotometry. [ 2 ]  Gel dosimetry today however, is founded mainly on the work of Gore  et al  who in 1984 [ 3 ]  demonstrated that changes due to ionising radiation in Fricke dosimetry solutions, [ 4 ]  developed in the 1920s, could be measured using  nuclear magnetic resonance  (NMR)."}
{"_id": "WikiPedia_Radiology$$$corpus_3913", "text": "Gel dosimeters generally consist of two types; Fricke and polymer gel dosimeters and are usually evaluated or 'read-out' using  magnetic resonance imaging  (MRI), optical  computer tomography  (CT),  x-ray CT  or  ultrasound ."}
{"_id": "WikiPedia_Radiology$$$corpus_3914", "text": "Since 1999 the DosGel and IC3DDose Conference Series on gel dosimetry has been held at various international venues."}
{"_id": "WikiPedia_Radiology$$$corpus_3915", "text": "Gore  et al  investigated [ 5 ]  the nuclear magnetic resonance (NMR) relaxation properties of irradiated Fricke or ferrous sulphate dosimetry solutions [ 6 ]  showing that radiation-induced changes, in which ferrous (Fe 2+ ) ions are converted to ferric (Fe 3+ ) ions, could be quantified using NMR relaxation measurements. In 1986 Appleby  et al [ 7 ]  reported that Fricke dosimetry solutions dispersed throughout a gel matrix could be used to obtain three-dimensional (3D) spatial dose information using magnetic resonance imaging (MRI). It was subsequently shown that irradiated Fricke-type gel dosimeters did not retain a spatially stable dose distribution due to ion diffusion within the irradiated dosimeters. [ 8 ]  Fricke solutions with various gelling agents such as gelatine, agarose, sephadex and polyvinyl alcohol (PVA) were investigated along with chelating agents such as  xylenol orange  (XO) to reduce diffusion. Numerous authors subsequently published results of their work to inhibit the ion diffusion with limited success and which was summarised by Baldock  et al  in 2001. [ 9 ]  By the early 1990s the diffusion problem was considered to be a significant one in the advancement of gel dosimetry."}
{"_id": "WikiPedia_Radiology$$$corpus_3916", "text": "Polymer systems for the use of radiation dosimetry were first proposed as early as 1954, where Alexander  et al [ 10 ]  discussed the effects of ionising radiation on polymethylmethacrylate. Following this, Hoecker  et al [ 11 ]  in 1958 investigated the dosimetry of radiation-induced polymerisation in liquids, and in 1961 Boni [ 12 ]  used poly acrylamide  as a gamma dosimeter. Much later in 1991, Audet  et al [ 13 ]  reported changes in NMR transverse relaxation measurements of irradiated polyethylene oxide. In 1992, Kennan  et al [ 14 ]  reported on NMR longitudinal relaxation studies performed on an irradiated aqueous solution of N,N\u2019-methylene-bis-acrylamide and agarose, which showed that the relaxation rates increased with absorbed dose."}
{"_id": "WikiPedia_Radiology$$$corpus_3917", "text": "In 1992 a new gel dosimetry formulation was proposed by Maryanski  et a l, [ 15 ]  which was based on the polymerisation of acrylamide and N,N\u2019-methylene-bis-acrylamide (bis) monomers infused in an aqueous agarose matrix. This system was given the acronym BANANA due to the use of the chemical components (bis, acrylamide,  nitrous oxide  and agarose). [ 16 ]  This type of gel dosimeter did not have the associated diffusion problem of Fricke gels and was shown to have a relatively stable post-irradiation dose distribution. The polymerisation reaction occurred by cross-linking of the monomers induced by the free radical products of water radiolysis. In 1994 the BANANA formulation was refined [ 17 ]  by replacing agarose with gelatine and given the acronym BANG (bis, acrylamide, nitrogen and aqueous gelatine), the first of a series of new polymer gel formulations. In 1994 this formulation was patented [ 18 ]  and became commercially available through MGS Research Inc. as  BANG\u00ae . Subsequently, due to the naming of the commercial product,  PAG [ 19 ]  became the polymer gel dosimeter acronym of choice for most authors. Numerous authors subsequently published results of work investigating different compositions and formulations of polymer gel dosimeters which were summarised by Lepage  et al . [ 20 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3918", "text": "Although polymer-type dosimeters did not have the diffusion limitations of Fricke-type gel dosimeters, there was another significant limitation in their use. Due to the nature of their free radical chemistry, polymer gel dosimeters were susceptible to atmospheric oxygen inhibition of the polymerisation processes. As a result, these gel dosimeters had to be manufactured in an oxygen-free environment, [ 21 ] [ 22 ]  such as in a glove box pumped with nitrogen gas. Along with the use of potentially toxic chemicals, [ 23 ]  this was a significant limitation in the introduction of gel dosimetry into the clinic."}
{"_id": "WikiPedia_Radiology$$$corpus_3919", "text": "During this period a number of studies were undertaken to investigate the clinical applications of radiological tissue-equivalent [ 24 ] [ 25 ] [ 26 ]  PAG-type polymer gel dosimeters using MRI. [ 27 ] [ 28 ] [ 29 ] [ 30 ] [ 31 ]  De Deene  et al [ 32 ]  undertook an investigation into the overall accuracy of an anthropomorphic polymer gel dosimetry phantom for the verification of conformal radiotherapy treatments. It was established that significant issues relating to the accuracy of this dosimetry technique were a result of oxygen inhibition in the polymer gel and MRI imaging artefacts."}
{"_id": "WikiPedia_Radiology$$$corpus_3920", "text": "Authors continued to investigate clinical aspects of polymer gel dosimetry using MRI including conformal therapy, IMRT and IMAT, [ 33 ] [ 34 ] [ 35 ] [ 36 ] [ 37 ] [ 38 ] [ 39 ]  stereotactic radiosurgery, [ 40 ] [ 41 ] [ 42 ] [ 43 ] [ 44 ] [ 45 ] [ 46 ] [ 47 ]  brachytherapy, [ 48 ] [ 49 ]  low energy X-rays, [ 50 ]  high-LET and proton therapy, [ 51 ] [ 52 ] [ 53 ] [ 54 ]  boron capture neutron therapy [ 55 ] [ 56 ]  and tissue inhomogeneities. [ 57 ] [ 58 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3921", "text": "A significant development in the field of gel dosimetry occurred when results of using an alternative polymer gel dosimeter formulation were published by Fong  et al  in 2001. [ 59 ]  This new type of polymer gel dosimeter, known as MAGIC gel, bound atmospheric oxygen in a metallo-organic complex thus removing the problem of oxygen inhibition and enabling polymer gels to be manufactured on the bench-top in the laboratory. This created what was to be known as a normoxic gel dosimeter, compared with the previous PAG formulation which subsequently became known as a hypoxic gel dosimeter. The MAGIC polymer gel formulation consisted of methacrylic acid, ascorbic acid, gelatine and copper. The principal behind the MAGIC gel is in the ascorbic acid oxygen scavenger. Ascorbic acid binds free oxygen contained within the aqueous gelatine matrix into metallo-organic complexes and this process is initiated by copper sulphate. It was subsequently shown by De Deene  et al  in 2002 that other antioxidants could be used in the manufacture of normoxic gels [ 60 ]  including tetrakis (hydroxymethyl) phosphonium chloride, having first been suggested to  Baldock  by Billingham in 1996. [ 61 ]  Numerous authors subsequently published results of work investigating different compositions and formulations of normoxic polymer gel dosimeters and were summarised by Senden. [ 62 ]  Other work has also included the development of less toxic polymer gels. [ 63 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3922", "text": "The fundamental science underpinning polymer gel dosimetry was reviewed along with the various 'read-out' and evaluation techniques and clinical dosimetry applications in the 2010 Topical Review publication by  Baldock   et al . [ 64 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3923", "text": "In June 1995 whilst attending the  American Association of Physicists in Medicine  (AAPM) annual meeting in Boston, US,  Clive Baldock  and L. John Schreiner discussed the appropriateness of organising some form of specialist meeting or workshop on gel dosimetry. In September 1996  Clive Baldock  and Lars Olsson, whilst attending the European Society for Radiotherapy & Oncology (ESTRO) annual meeting in Vienna, Austria initiated the organising of the international conference series on gel dosimetry which began as  DosGel 99 , the 1st International Workshop on Radiation Therapy Gel Dosimetry held in Lexington, Kentucky in 1999 and hosted by Geoff Ibbott. Since 1999, subsequent  DosGel  conferences were held in Brisbane, Australia (2001), Ghent, Belgium (2004), Sherbrooke, Canada (2006) and Crete, Greece (2008). In 2010 the conference was held in Hilton Head, South Carolina, USA and underwent a name-change to  IC3DDose . Subsequent  IC3DDose  conferences were held in Sydney, Australia (2012), Ystad, Sweden (2014), Galveston, Texas, USA (2016), Kushan, China (2018) and virtually (2021)."}
{"_id": "WikiPedia_Radiology$$$corpus_3924", "text": "The aim of the first workshop was to bring together individuals, both researchers and users, with an interest in the application of 3-dimensional radiation dosimetry techniques in the treatment of  cancer , with a mix of presentations from basic science to clinical applications. This has remained an objective for all of the conferences. One rationale of  DosGel 99  was stated as supporting the increasing clinical implementation of gel dosimetry, as the technique appeared, at that time, to be leaving the laboratories of gel dosimetry enthusiasts and entering clinical practice. Clearly by labelling the first workshop as the 1st, there was a vision of a continuing series, which has been fulfilled. On the other hand, the expectation of widespread clinical use of gel dosimetry has perhaps not been what was hoped for and anticipated. Nevertheless, the rapidly increasing demand for advanced high-precision 3D radiotherapy technology and techniques has continued apace. The need for practical and accurate 3D dosimetry methods for development and quality assurance has only increased. By the 6th meeting, held in South Carolina in 2010, the Conference Scientific Committee recognised the wider developments in 3D systems and methods and decided to widen the scope, whilst keeping the same span from basic science to applications. This was signalled by a change of name from  DosGel  to  IC3DDose , a name that has continued to the latest conference, the 11th  IC3DDose  conference, held virtually in May 2021."}
{"_id": "WikiPedia_Radiology$$$corpus_3925", "text": "Radiation therapy  or  radiotherapy  ( RT ,  RTx , or  XRT ) is a  treatment  using  ionizing radiation , generally provided as part of  cancer therapy  to either kill or control the growth of  malignant   cells . It is normally delivered by a  linear particle accelerator . Radiation therapy may be  curative  in a number of types of cancer if they are localized to one area of the body, and have not  spread to other parts . It may also be used as part of  adjuvant therapy , to prevent tumor recurrence after surgery to remove a primary malignant tumor (for example, early stages of breast cancer). Radiation therapy is synergistic with  chemotherapy , and has been used before, during, and after chemotherapy in susceptible cancers. The subspecialty of oncology concerned with radiotherapy is called radiation oncology. A physician who practices in this subspecialty is a  radiation oncologist ."}
{"_id": "WikiPedia_Radiology$$$corpus_3926", "text": "Radiation therapy is commonly applied to the cancerous tumor because of its ability to control cell growth. Ionizing radiation works by damaging the  DNA  of cancerous tissue leading to  cellular death . To spare normal tissues (such as skin or organs which radiation must pass through to treat the tumor), shaped radiation beams are aimed from several angles of exposure to intersect at the tumor, providing a much larger  absorbed dose  there than in the surrounding healthy tissue. Besides the tumor itself, the radiation fields may also include the draining lymph nodes if they are clinically or radiologically involved with the tumor, or if there is thought to be a risk of subclinical malignant spread. It is necessary to include a margin of normal tissue around the tumor to allow for uncertainties in daily set-up and internal tumor motion. These uncertainties can be caused by internal movement (for example, respiration and bladder filling) and movement of external skin marks relative to the tumor position."}
{"_id": "WikiPedia_Radiology$$$corpus_3927", "text": "Radiation oncology  is the medical specialty concerned with prescribing radiation, and is distinct from  radiology , the use of radiation in  medical imaging  and  diagnosis . Radiation may be prescribed by a radiation oncologist with intent to cure or for adjuvant therapy. It may also be used as  palliative treatment  (where cure is not possible and the aim is for local disease control or symptomatic relief) or as therapeutic treatment (where the therapy has survival benefit and can be curative). [ 1 ]  It is also common to combine radiation therapy with  surgery , chemotherapy,  hormone therapy ,  immunotherapy  or some mixture of the four. Most common cancer types can be treated with radiation therapy in some way."}
{"_id": "WikiPedia_Radiology$$$corpus_3928", "text": "The precise treatment intent (curative, adjuvant,  neoadjuvant therapeutic , or palliative) will depend on the tumor type, location, and  stage , as well as the general health of the patient.  Total body irradiation  (TBI) is a radiation therapy technique used to prepare the body to receive a  bone marrow transplant .  Brachytherapy , in which a  radioactive source  is placed inside or next to the area requiring treatment, is another form of radiation therapy that minimizes exposure to healthy tissue during procedures to treat cancers of the breast, prostate, and other organs. Radiation therapy has several applications in non-malignant conditions, such as the treatment of  trigeminal neuralgia ,  acoustic neuromas , severe  thyroid eye disease ,  pterygium ,  pigmented villonodular synovitis , and prevention of  keloid  scar growth, vascular  restenosis , and  heterotopic ossification . [ 1 ] [ 2 ] [ 3 ] [ 4 ]  The use of radiation therapy in non-malignant conditions is limited partly by worries about the risk of radiation-induced cancers."}
{"_id": "WikiPedia_Radiology$$$corpus_3929", "text": "It is estimated that half of the US' 1.2M invasive cancer cases diagnosed in 2022 received radiation therapy in their treatment program. [ 5 ]   Different cancers respond to radiation therapy in different ways. [ 6 ] [ 7 ] [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3930", "text": "The response of a cancer to radiation is described by its radiosensitivity.\nHighly radiosensitive cancer cells are rapidly killed by modest doses of radiation. These include  leukemias , most  lymphomas , and  germ cell tumors .\nThe majority of  epithelial cancers  are only moderately radiosensitive, and require a significantly higher dose of radiation (60\u201370\u00a0Gy) to achieve a radical cure.\nSome types of cancer are notably radioresistant, that is, much higher doses are required to produce a radical cure than may be safe in clinical practice.  Renal cell cancer  and  melanoma  are generally considered to be radioresistant but radiation therapy is still a palliative option for many patients with metastatic melanoma. Combining radiation therapy with  immunotherapy  is an active area of investigation and has shown some promise for melanoma and other cancers. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3931", "text": "It is important to distinguish the radiosensitivity of a particular tumor, which to some extent is a laboratory measure, from the radiation \"curability\" of a cancer in actual clinical practice. For example, leukemias are not generally curable with radiation therapy, because they are disseminated through the body. Lymphoma may be radically curable if it is localized to one area of the body. Similarly, many of the common, moderately radioresponsive tumors are routinely treated with curative doses of radiation therapy if they are at an early stage. For example,  non-melanoma skin cancer ,  head and neck cancer ,  breast cancer ,  non-small cell lung cancer ,  cervical cancer ,  anal cancer , and  prostate cancer . With the exception of oligometastatic disease,  metastatic  cancers are incurable with radiation therapy because it is not possible to treat the whole body. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3932", "text": "Modern radiation therapy relies on a CT scan to identify the tumor and surrounding normal structures and to perform dose calculations for the creation of a complex radiation treatment plan. The patient receives small skin marks to guide the placement of treatment fields. [ 10 ]  Patient positioning is crucial at this stage as the patient will have to be placed in an identical position during each treatment.  Many patient positioning devices have been developed for this purpose, including masks and cushions which can be molded to the patient.  Image-guided radiation therapy  is a method that uses imaging to correct for positional errors of each treatment session. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3933", "text": "The response of a tumor to radiation therapy is also related to its size. Due to complex  radiobiology , very large tumors are affected less by radiation compared to smaller tumors or microscopic disease. Various strategies are used to overcome this effect. The most common technique is surgical resection prior to radiation therapy. This is most commonly seen in the treatment of breast cancer with  wide local excision  or  mastectomy  followed by  adjuvant radiation therapy . Another method is to shrink the tumor with  neoadjuvant  chemotherapy prior to radical radiation therapy. A third technique is to enhance the radiosensitivity of the cancer by giving certain drugs during a course of radiation therapy. Examples of radiosensitizing drugs include  cisplatin ,  nimorazole , and  cetuximab . [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3934", "text": "The impact of radiotherapy varies between different types of cancer and different groups. [ 12 ]  For example, for breast cancer after  breast-conserving surgery , radiotherapy has been found to halve the rate at which the disease recurs. [ 13 ]  In pancreatic cancer, radiotherapy has increased survival times for inoperable tumors. [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3935", "text": "Radiation therapy (RT) is in itself painless, but has  iatrogenic side effect  risks. Many low-dose  palliative treatments  (for example, radiation therapy to bony  metastases ) cause minimal or no side effects, although short-term pain flare-up can be experienced in the days following treatment due to oedema compressing nerves in the treated area. Higher doses can cause varying side effects during treatment (acute side effects), in the months or years following treatment (long-term side effects), or after re-treatment (cumulative side effects). The nature, severity, and longevity of side effects depends on the organs that receive the radiation, the treatment itself (type of radiation, dose,  fractionation , concurrent chemotherapy), and the patient. Serious radiation complications may occur in 5% of RT cases. Acute (near immediate) or sub-acute (2 to 3 months post RT) radiation side effects may develop after 50 Gy RT dosing. Late or delayed radiation injury (6 months to decades) may develop after 65 Gy. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3936", "text": "Most side effects are predictable and expected. Side effects from radiation are usually limited to the area of the patient's body that is under treatment. Side effects are dose-dependent; for example, higher doses of head and neck radiation can be associated with  cardiovascular  complications,  thyroid  dysfunction, and  pituitary  axis dysfunction. [ 15 ]  Modern radiation therapy aims to reduce side effects to a minimum and to help the patient understand and deal with side effects that are unavoidable."}
{"_id": "WikiPedia_Radiology$$$corpus_3937", "text": "The main side effects reported are fatigue and skin irritation, like a mild to moderate sun burn. The fatigue often sets in during the middle of a course of treatment and can last for weeks after treatment ends. The irritated skin will heal, but may not be as elastic as it was before. [ 16 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3938", "text": "Late side effects occur months to years after treatment and are generally limited to the area that has been treated. They are often due to damage of blood vessels and connective tissue cells. Many late effects are reduced by fractionating treatment into smaller parts."}
{"_id": "WikiPedia_Radiology$$$corpus_3939", "text": "Cumulative effects from this process should not be confused with long-term effects \u2013 when short-term effects have disappeared and long-term effects are subclinical, reirradiation can still be problematic. [ 46 ]  These doses are calculated by the radiation oncologist and many factors are taken into account before the subsequent radiation takes place."}
{"_id": "WikiPedia_Radiology$$$corpus_3940", "text": "During the first two weeks after  fertilization , radiation therapy is lethal but not  teratogenic . [ 47 ]  High doses of radiation during pregnancy induce  anomalies ,  impaired growth  and  intellectual disability , and there may be an increased risk of  childhood leukemia  and other tumors in the offspring. [ 47 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3941", "text": "In males previously having undergone radiotherapy, there appears to be no increase in genetic defects or congenital malformations in their children conceived after therapy. [ 47 ]  However, the use of  assisted reproductive technologies  and  micromanipulation techniques  might increase this risk. [ 47 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3942", "text": "Hypopituitarism  commonly develops after radiation therapy for sellar and parasellar neoplasms, extrasellar brain tumors, head and neck tumors, and following whole body irradiation for systemic malignancies. [ 48 ]  40\u201350% of children treated for childhood cancer develop some endocrine side effect. [ 49 ]  Radiation-induced hypopituitarism mainly affects  growth hormone  and  gonadal hormones . [ 48 ]  In contrast,  adrenocorticotrophic hormone  (ACTH) and  thyroid stimulating hormone  (TSH) deficiencies are the least common among people with radiation-induced hypopituitarism. [ 48 ]  Changes in  prolactin -secretion is usually mild, and vasopressin deficiency appears to be very rare as a consequence of radiation. [ 48 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3943", "text": "Delayed tissue injury with impaired wound healing capability often develops after receiving doses in excess of 65\u00a0Gy. A diffuse injury pattern due to the  external beam radiotherapy 's  holographic isodosing  occurs. While the targeted tumor receives the majority of radiation, healthy tissue at incremental distances from the center of the tumor are also irradiated in a diffuse pattern due to beam divergence. These wounds demonstrate  progressive, proliferative endarteritis , inflamed arterial linings that disrupt the tissue's blood supply. Such tissue ends up chronically  hypoxic ,  fibrotic , and without an adequate nutrient and oxygen supply. Surgery of previously irradiated tissue has a very high failure rate, e.g. women who have received radiation for breast cancer develop late effect  chest wall  tissue fibrosis and hypovascularity, making successful reconstruction and healing difficult, if not impossible. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3944", "text": "There are rigorous procedures in place to minimise the risk of accidental overexposure of radiation therapy to patients. However, mistakes do occasionally occur; for example, the radiation therapy machine  Therac-25  was responsible for at least six accidents between 1985 and 1987, where patients were given up to one hundred times the intended dose; two people were killed directly by the radiation overdoses. From 2005 to 2010, a hospital in  Missouri  overexposed 76 patients (most with brain cancer) during a five-year period because new radiation equipment had been set up incorrectly. [ 50 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3945", "text": "Although medical errors are exceptionally rare, radiation oncologists, medical physicists and other members of the radiation therapy treatment team are working to eliminate them. In 2010 the  American Society for Radiation Oncology  (ASTRO) launched a safety initiative called   Target Safely  that, among other things, aimed to record errors nationwide so that doctors can learn from each and every mistake and prevent them from recurring. ASTRO also publishes a list of questions for patients to ask their doctors about radiation safety to ensure every treatment is as safe as possible. [ 51 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3946", "text": "Radiation therapy is used to treat early stage  Dupuytren's disease  and  Ledderhose disease . When Dupuytren's disease is at the nodules and cords stage or fingers are at a minimal deformation stage of less than 10 degrees, then radiation therapy is used to prevent further progress of the disease. Radiation therapy is also used post surgery in some cases to prevent the disease continuing to progress. Low doses of radiation are used typically three gray of radiation for five days, with a break of three months followed by another phase of three gray of radiation for five days. [ 52 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3947", "text": "Radiation therapy works by damaging the  DNA  of  cancer cells  and can cause them to undergo  mitotic catastrophe . [ 53 ]  This DNA damage is caused by one of two types of energy,  photon  or  charged particle . This damage is either direct or indirect  ionization  of the atoms which make up the DNA chain. Indirect ionization happens as a result of the ionization of water, forming  free radicals , notably  hydroxyl  radicals, which then damage the DNA."}
{"_id": "WikiPedia_Radiology$$$corpus_3948", "text": "In photon therapy, most of the radiation effect is through free radicals. Cells have mechanisms for repairing single-strand DNA damage and  double-stranded DNA  damage. However, double-stranded DNA breaks are much more difficult to repair, and can lead to dramatic chromosomal abnormalities and genetic deletions. Targeting double-stranded breaks increases the probability that cells will undergo  cell death . Cancer cells are generally less  differentiated  and more  stem cell -like; they reproduce more than most healthy differentiated cells, and have a diminished ability to repair sub-lethal damage. Single-strand DNA damage is then passed on through cell division; damage to the cancer cells' DNA accumulates, causing them to die or reproduce more slowly."}
{"_id": "WikiPedia_Radiology$$$corpus_3949", "text": "One of the major limitations of photon radiation therapy is that the cells of solid tumors become deficient in  oxygen . Solid tumors can outgrow their blood supply, causing a low-oxygen state known as  hypoxia . Oxygen is a potent  radiosensitizer , increasing the effectiveness of a given dose of radiation by forming DNA-damaging free radicals. Tumor cells in a hypoxic environment may be as much as 2 to 3 times more resistant to radiation damage than those in a normal oxygen environment. [ 54 ]  Much research has been devoted to overcoming hypoxia including the use of high pressure oxygen tanks,  hyperthermia therapy  (heat therapy which dilates blood vessels to the tumor site), blood substitutes that carry increased oxygen, hypoxic cell radiosensitizer drugs such as  misonidazole  and  metronidazole , and hypoxic  cytotoxins  (tissue poisons), such as  tirapazamine .  Newer research approaches are currently being studied, including preclinical and clinical investigations into the use of an  oxygen diffusion-enhancing compound  such as  trans sodium crocetinate  as a radiosensitizer. [ 55 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3950", "text": "Charged particles such as  protons  and  boron ,  carbon , and  neon  ions can cause direct damage to cancer cell DNA through high-LET ( linear energy transfer ) and have an antitumor effect independent of tumor oxygen supply because these particles act mostly via direct energy transfer usually causing double-stranded DNA breaks. Due to their relatively large mass, protons and other charged particles have little lateral side scatter in the tissue \u2013 the beam does not broaden much, stays focused on the tumor shape, and delivers small dose side-effects to surrounding tissue. They also more precisely target the tumor using the  Bragg peak  effect. See  proton therapy  for a good example of the different effects of intensity-modulated radiation therapy (IMRT) vs.  charged particle therapy . This procedure reduces damage to healthy tissue between the charged particle radiation source and the tumor and sets a finite range for tissue damage after the tumor has been reached. In contrast, IMRT's use of uncharged particles causes its energy to damage healthy cells when it exits the body. This exiting damage is not therapeutic, can increase treatment side effects, and increases the probability of secondary cancer induction. [ 56 ]  This difference is very important in cases where the close proximity of other organs makes any stray ionization very damaging (example:  head and neck cancers ). This X-ray exposure is especially bad for children, due to their growing bodies, and while depending on a multitude of factors, they are around 10 times more sensitive to developing secondary malignancies after radiotherapy as compared to adults. [ 57 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3951", "text": "The amount of radiation used in photon radiation therapy is measured in  grays  (Gy), and varies depending on the type and stage of cancer being treated. For curative cases, the typical dose for a solid epithelial tumor ranges from 60 to 80\u00a0Gy, while lymphomas are treated with 20 to 40\u00a0Gy."}
{"_id": "WikiPedia_Radiology$$$corpus_3952", "text": "Preventive (adjuvant) doses are typically around 45\u201360\u00a0Gy in 1.8\u20132\u00a0Gy fractions (for breast, head, and neck cancers.) Many other factors are considered by  radiation oncologists  when selecting a dose, including whether the patient is receiving chemotherapy, patient comorbidities, whether radiation therapy is being administered before or after surgery, and the degree of success of surgery."}
{"_id": "WikiPedia_Radiology$$$corpus_3953", "text": "Delivery parameters of a prescribed dose are determined during  treatment planning  (part of  dosimetry ). Treatment planning is generally performed on dedicated computers using specialized treatment planning software. Depending on the radiation delivery method, several angles or sources may be used to sum to the total necessary dose. The planner will try to design a plan that delivers a uniform prescription dose to the tumor and minimizes dose to surrounding healthy tissues."}
{"_id": "WikiPedia_Radiology$$$corpus_3954", "text": "In radiation therapy, three-dimensional dose distributions may be evaluated using the  dosimetry  technique known as  gel dosimetry . [ 58 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3955", "text": "The total dose is fractionated (spread out over time) for several important reasons. Fractionation allows normal cells time to recover, while tumor cells are generally less efficient in repair between fractions. Fractionation also allows tumor cells that were in a relatively radio-resistant phase of the cell cycle during one treatment to cycle into a sensitive phase of the cycle before the next fraction is given. Similarly, tumor cells that were chronically or acutely hypoxic (and therefore more radioresistant) may reoxygenate between fractions, improving the tumor cell kill. [ 59 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3956", "text": "Fractionation regimens are individualised between different radiation therapy centers and even between individual doctors. In North America, Australia, and Europe, the typical fractionation schedule for adults is 1.8 to 2\u00a0Gy per day, five days a week. In some cancer types, prolongation of the fraction schedule over too long can allow for the tumor to begin repopulating, and for these tumor types, including head-and-neck and cervical squamous cell cancers, radiation treatment is preferably completed within a certain amount of time. For children, a typical fraction size may be 1.5 to 1.8\u00a0Gy per day, as smaller fraction sizes are associated with reduced incidence and severity of late-onset side effects in normal tissues."}
{"_id": "WikiPedia_Radiology$$$corpus_3957", "text": "In some cases, two fractions per day are used near the end of a course of treatment. This schedule, known as a concomitant boost regimen or hyperfractionation, is used on tumors that regenerate more quickly when they are smaller. In particular, tumors in the head-and-neck demonstrate this behavior."}
{"_id": "WikiPedia_Radiology$$$corpus_3958", "text": "Patients receiving  palliative radiation  to treat uncomplicated painful bone metastasis should not receive more than a single fraction of radiation. [ 60 ]  A single treatment gives comparable pain relief and morbidity outcomes to multiple-fraction treatments, and for patients with limited life expectancy, a single treatment is best to improve patient comfort. [ 60 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3959", "text": "One fractionation schedule that is increasingly being used and continues to be studied is hypofractionation. This is a radiation treatment in which the total dose of radiation is divided into large doses. Typical doses vary significantly by cancer type, from 2.2\u00a0Gy/fraction to 20\u00a0Gy/fraction, the latter being typical of stereotactic treatments (stereotactic ablative body radiotherapy, or SABR \u2013 also known as SBRT, or stereotactic body radiotherapy) for subcranial lesions, or SRS (stereotactic radiosurgery) for intracranial lesions. The rationale of hypofractionation is to reduce the probability of local recurrence by denying clonogenic cells the time they require to reproduce and also to exploit the radiosensitivity of some tumors. [ 61 ]  In particular, stereotactic treatments are intended to destroy clonogenic cells by a process of ablation, i.e., the delivery of a dose intended to destroy clonogenic cells directly, rather than to interrupt the process of clonogenic cell division repeatedly (apoptosis), as in routine radiotherapy."}
{"_id": "WikiPedia_Radiology$$$corpus_3960", "text": "Different cancer types have different radiation sensitivity. While predicting the sensitivity based on genomic or proteomic analyses of biopsy samples has proven challenging, [ 62 ] [ 63 ]  the predictions of radiation effect on individual patients from genomic signatures of intrinsic cellular radiosensitivity have been shown to associate with clinical outcome. [ 64 ]  An alternative approach to genomics and proteomics was offered by the discovery that  radiation protection  in microbes is offered by non-enzymatic complexes of  manganese  and small organic metabolites. [ 65 ]  The content and variation of manganese (measurable by electron paramagnetic resonance) were found to be good predictors of  radiosensitivity , and this finding extends also to human cells. [ 66 ]  An association was confirmed between total cellular manganese contents and their variation, and clinically inferred radioresponsiveness in different tumor cells, a finding that may be useful for more precise radiodosages and improved treatment of cancer patients. [ 67 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3961", "text": "Historically, the three main divisions of radiation therapy are:"}
{"_id": "WikiPedia_Radiology$$$corpus_3962", "text": "The differences relate to the position of the radiation source; external is outside the body, brachytherapy uses sealed radioactive sources placed precisely in the area under treatment, and systemic radioisotopes are given by infusion or oral ingestion. Brachytherapy can use temporary or permanent placement of radioactive sources. The temporary sources are usually placed by a technique called afterloading. In afterloading a hollow tube or applicator is placed surgically in the organ to be treated, and the sources are loaded into the applicator after the applicator is implanted. This minimizes radiation exposure to health care personnel."}
{"_id": "WikiPedia_Radiology$$$corpus_3963", "text": "Particle therapy  is a special case of external beam radiation therapy where the particles are  protons  or heavier  ions ."}
{"_id": "WikiPedia_Radiology$$$corpus_3964", "text": "A review of radiation therapy randomised clinical trials from 2018 to 2021 found many practice-changing data and new concepts that emerge from RCTs, identifying techniques that improve the therapeutic ratio, techniques that lead to more tailored treatments, stressing the importance of patient satisfaction, and identifying areas that require further study. [ 68 ] [ 69 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3965", "text": "The following three sections refer to treatment using X-rays."}
{"_id": "WikiPedia_Radiology$$$corpus_3966", "text": "Historically conventional external beam radiation therapy (2DXRT) was delivered via two-dimensional beams using kilovoltage therapy X-ray units, medical linear accelerators that generate high-energy X-rays, or with machines that were similar to a linear accelerator in appearance, but used a sealed radioactive source like the one shown above. [ 70 ] [ 71 ]  2DXRT mainly consists of a single beam of radiation delivered to the patient from several directions: often front or back, and both sides."}
{"_id": "WikiPedia_Radiology$$$corpus_3967", "text": "Conventional  refers to the way the treatment is  planned  or  simulated  on a specially calibrated diagnostic X-ray machine known as a simulator because it recreates the linear accelerator actions (or sometimes by eye), and to the usually well-established arrangements of the radiation beams to achieve a desired  plan . The aim of simulation is to accurately target or localize the volume which is to be treated. This technique is well established and is generally quick and reliable. The worry is that some high-dose treatments may be limited by the radiation toxicity capacity of healthy tissues which lie close to the target tumor volume."}
{"_id": "WikiPedia_Radiology$$$corpus_3968", "text": "An example of this problem is seen in radiation of the prostate gland, where the sensitivity of the adjacent rectum limited the dose which could be safely prescribed using 2DXRT planning to such an extent that tumor control may not be easily achievable. Prior to the invention of the CT, physicians and physicists had limited knowledge about the true radiation dosage delivered to both cancerous and healthy tissue. For this reason, 3-dimensional conformal radiation therapy has become the standard treatment for almost all tumor sites. More recently other forms of imaging are used including MRI, PET, SPECT and Ultrasound. [ 72 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3969", "text": "Stereotactic radiation is a specialized type of external beam radiation therapy. It uses focused radiation beams targeting a well-defined tumor using extremely detailed imaging scans. Radiation oncologists perform stereotactic treatments, often with the help of a neurosurgeon for tumors in the brain or spine."}
{"_id": "WikiPedia_Radiology$$$corpus_3970", "text": "There are two types of stereotactic radiation.  Stereotactic radiosurgery  (SRS) is when doctors use a single or several stereotactic radiation treatments of the brain or spine.  Stereotactic body radiation therapy  (SBRT) refers to one or several stereotactic radiation treatments with the body, such as the lungs. [ 73 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3971", "text": "Some doctors say an advantage to stereotactic treatments is that they deliver the right amount of radiation to the cancer in a shorter amount of time than traditional treatments, which can often take 6 to 11 weeks. Plus treatments are given with extreme accuracy, which should limit the effect of the radiation on healthy tissues. One problem with stereotactic treatments is that they are only suitable for certain small tumors."}
{"_id": "WikiPedia_Radiology$$$corpus_3972", "text": "Stereotactic treatments can be confusing because many hospitals call the treatments by the name of the manufacturer rather than calling it SRS or SBRT. Brand names for these treatments include Axesse,  Cyberknife ,  Gamma Knife , Novalis, Primatom, Synergy,  X-Knife ,  TomoTherapy , Trilogy and  Truebeam . [ 74 ]  This list changes as equipment manufacturers continue to develop new, specialized technologies to treat cancers."}
{"_id": "WikiPedia_Radiology$$$corpus_3973", "text": "The planning of radiation therapy treatment has been revolutionized by the ability to delineate tumors and adjacent normal structures in three dimensions using specialized CT and/or MRI scanners and planning software. [ 75 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3974", "text": "Virtual simulation, the most basic form of planning, allows more accurate placement of radiation beams than is possible using conventional X-rays, where soft-tissue structures are often difficult to assess and normal tissues difficult to protect."}
{"_id": "WikiPedia_Radiology$$$corpus_3975", "text": "An enhancement of virtual simulation is  3-dimensional conformal radiation therapy (3DCRT) , in which the profile of each radiation beam is shaped to fit the profile of the target from a  beam's eye view  (BEV) using a  multileaf collimator  (MLC) and a variable number of beams. When the treatment volume conforms to the shape of the tumor, the relative toxicity of radiation to the surrounding normal tissues is reduced, allowing a higher dose of radiation to be delivered to the tumor than conventional techniques would allow. [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3976", "text": "Intensity-modulated radiation therapy (IMRT) is an advanced type of high-precision radiation that is the next generation of 3DCRT. [ 76 ]  IMRT also improves the ability to conform the treatment volume to concave tumor shapes, [ 10 ]  for example when the tumor is wrapped around a vulnerable structure such as the spinal cord or a major organ or blood vessel. [ 77 ]  Computer-controlled X-ray accelerators distribute precise radiation doses to malignant tumors or specific areas within the tumor. The pattern of radiation delivery is determined using highly tailored computing applications to perform  optimization  and treatment simulation ( Treatment Planning ). The radiation dose is consistent with the 3-D shape of the tumor by controlling, or modulating, the radiation beam's intensity. The radiation dose intensity is elevated near the gross tumor volume while radiation among the neighboring normal tissues is decreased or avoided completely. This results in better tumor targeting, lessened side effects, and improved treatment outcomes than even 3DCRT."}
{"_id": "WikiPedia_Radiology$$$corpus_3977", "text": "3DCRT is still used extensively for many body sites but the use of IMRT is growing in more complicated body sites such as CNS, head and neck, prostate, breast, and lung. Unfortunately, IMRT is limited by its need for additional time from experienced medical personnel. This is because physicians must manually delineate the tumors one CT image at a time through the entire disease site which can take much longer than 3DCRT preparation. Then, medical physicists and dosimetrists must be engaged to create a viable treatment plan. Also, the IMRT technology has only been used commercially since the late 1990s even at the most advanced cancer centers, so radiation oncologists who did not learn it as part of their residency programs must find additional sources of education before implementing IMRT."}
{"_id": "WikiPedia_Radiology$$$corpus_3978", "text": "Proof of improved survival benefit from either of these two techniques over conventional radiation therapy (2DXRT) is growing for many tumor sites, but the ability to reduce toxicity is generally accepted. This is particularly the case for head and neck cancers in a series of pivotal trials performed by Professor  Christopher Nutting  of the Royal Marsden Hospital. Both techniques enable dose escalation, potentially increasing usefulness. There has been some concern, particularly with IMRT, [ 78 ]  about increased exposure of normal tissue to radiation and the consequent potential for secondary malignancy. Overconfidence in the accuracy of imaging may increase the chance of missing lesions that are invisible on the planning scans (and therefore not included in the treatment plan) or that move between or during a treatment (for example, due to respiration or inadequate patient immobilization). New techniques are being developed to better control this uncertainty \u2013 for example, real-time imaging combined with real-time adjustment of the therapeutic beams. This new technology is called image-guided radiation therapy or four-dimensional radiation therapy."}
{"_id": "WikiPedia_Radiology$$$corpus_3979", "text": "Another technique is the real-time tracking and localization of one or more small implantable electric devices implanted inside or close to the tumor. There are various types of medical implantable devices that are used for this purpose. It can be a magnetic transponder which senses the magnetic field generated by several transmitting coils, and then transmits the measurements back to the positioning system to determine the location. [ 79 ]  The implantable device can also be a small wireless transmitter sending out an RF signal which then will be received by a sensor array and used for localization and real-time tracking of the tumor position. [ 80 ] [ 81 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3980", "text": "A well-studied issue with IMRT is the \"tongue and groove effect\" which results in unwanted underdosing, due to irradiating through extended tongues and grooves of overlapping MLC (multileaf collimator) leaves. [ 82 ]   While solutions to this issue have been developed, which either reduce the TG effect to negligible amounts or remove it completely, they depend upon the method of IMRT being used and some of them carry costs of their own. [ 82 ]   Some texts distinguish \"tongue and groove error\" from \"tongue or groove error\", according as both or one side of the aperture is occluded. [ 83 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3981", "text": "Volumetric modulated arc therapy (VMAT) is a radiation technique introduced in 2007 [ 84 ]  which can achieve highly conformal dose distributions on target volume coverage and sparing of normal tissues. The specificity of this technique is to modify three parameters during the treatment. VMAT delivers radiation by rotating gantry (usually 360\u00b0 rotating fields with one or more arcs), changing speed and shape of the beam with a  multileaf collimator  (MLC) (\"sliding window\" system of moving) and fluence output rate (dose rate) of the medical linear accelerator. VMAT has an advantage in patient treatment, compared with conventional static field intensity modulated radiotherapy (IMRT), of reduced radiation delivery times. [ 85 ] [ 86 ]  Comparisons between VMAT and conventional IMRT for their sparing of healthy tissues and Organs at Risk (OAR) depends upon the cancer type. In the treatment of  nasopharyngeal ,  oropharyngeal  and  hypopharyngeal  carcinomas VMAT provides equivalent or better protection of the organ at risk (OAR). [ 84 ] [ 85 ] [ 86 ]  In the treatment of  prostate cancer  the OAR protection result is mixed [ 84 ]  with some studies favoring VMAT, others favoring IMRT. [ 87 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3982", "text": "Temporally feathered radiation therapy (TFRT) is a radiation technique introduced in 2018 [ 88 ]  which aims to use the inherent non-linearities in normal tissue repair to allow for sparing of these tissues without affecting the dose delivered to the tumor. The application of this technique, which has yet to be automated, has been described carefully to enhance the ability of departments to perform it, and in 2021 it was reported as feasible in a small clinical trial, [ 89 ]  though its efficacy has yet to be formally studied."}
{"_id": "WikiPedia_Radiology$$$corpus_3983", "text": "Automated treatment planning has become an integrated part of radiotherapy treatment planning. There are in general two approaches of automated planning. 1) Knowledge based planning where the treatment planning system has a library of high quality plans, from which it can predict the target and dose-volume histogram of the organ at risk. [ 90 ]  2) The other approach is commonly called protocol based planning, where the treatment planning system tried to mimic an experienced treatment planner and through an iterative process evaluates the plan quality from on the basis of the protocol. [ 91 ] [ 92 ] [ 93 ] [ 94 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3984", "text": "In particle therapy ( proton therapy  being one example), energetic ionizing particles (protons or carbon ions) are directed at the target tumor. [ 95 ]  The dose increases while the particle penetrates the tissue, up to a maximum (the  Bragg peak ) that occurs near the end of the particle's  range , and it then drops to (almost) zero. The advantage of this energy deposition profile is that less energy is deposited into the healthy tissue surrounding the target tissue."}
{"_id": "WikiPedia_Radiology$$$corpus_3985", "text": "Auger therapy  (AT) makes use of a very high dose [ 96 ]  of ionizing radiation in situ that provides molecular modifications at an atomic scale. AT differs from conventional radiation therapy in several aspects; it neither relies upon radioactive nuclei to cause cellular radiation damage at a cellular dimension, nor engages multiple external pencil-beams from different directions to zero-in to deliver a dose to the targeted area with reduced dose outside the targeted tissue/organ locations. Instead, the in situ delivery of a very high dose at the molecular level using AT aims for in situ molecular modifications involving molecular breakages and molecular re-arrangements such as a change of stacking structures as well as cellular metabolic functions related to the said molecule structures."}
{"_id": "WikiPedia_Radiology$$$corpus_3986", "text": "In many types of external beam radiotherapy, motion can negatively impact the treatment delivery by moving target tissue out of, or other healthy tissue into, the intended beam path. Some form of patient immobilisation is common, to prevent the large movements of the body during treatment, however this cannot prevent all motion, for example as a result of  breathing . Several techniques have been developed to account for motion like this. [ 97 ] [ 98 ]   Deep inspiration breath-hold  (DIBH) is commonly used for breast treatments where it is important to avoid irradiating the heart. In DIBH the patient holds their breath after  breathing in  to provide a stable position for the treatment beam to be turned on. This can be done automatically using an external monitoring system such as a  spirometer  or a camera and markers. [ 99 ]  The same monitoring techniques, as well as  4DCT  imaging, can also be for respiratory gated treatment, where the patient breathes freely and the beam is only engaged at certain points in the breathing cycle. [ 100 ]  Other techniques include using 4DCT imaging to plan treatments with margins that account for motion, and active movement of the treatment couch, or beam, to follow motion. [ 101 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3987", "text": "Contact X-ray brachytherapy (also called \"CXB\", \"electronic brachytherapy\" or the \"Papillon Technique\") is a type of radiation therapy using low energy (50 kVp) kilovoltage  X-rays  applied directly to the tumor to treat  rectal cancer . The process involves endoscopic examination first to identify the tumor in the rectum and then inserting treatment applicator on the tumor through the  anus  into the rectum and placing it against the cancerous tissue. Finally, treatment tube is inserted into the applicator to deliver high doses of X-rays (30Gy) emitted directly onto the  tumor  at two weekly intervals for three times over four weeks period.  It is typically used for treating early rectal cancer in patients who may not be candidates for surgery. [ 102 ] [ 103 ] [ 104 ]  A 2015 NICE review found the main side effect to be bleeding that occurred in about 38% of cases, and radiation-induced ulcer which occurred in 27% of cases. [ 102 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3988", "text": "Brachytherapy is delivered by placing radiation source(s) inside or next to the area requiring treatment. Brachytherapy is commonly used as an effective treatment for cervical, [ 105 ]  prostate, [ 106 ]  breast, [ 107 ]  and skin cancer [ 108 ]  and can also be used to treat tumors in many other body sites. [ 109 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3989", "text": "In brachytherapy, radiation sources are precisely placed directly at the site of the cancerous tumor. This means that the irradiation only affects a very localized area \u2013 exposure to radiation of healthy tissues further away from the sources is reduced. These characteristics of brachytherapy provide advantages over external beam radiation therapy \u2013 the tumor can be treated with very high doses of localized radiation, whilst reducing the probability of unnecessary damage to surrounding healthy tissues. [ 109 ] [ 110 ]  A course of brachytherapy can often be completed in less time than other radiation therapy techniques. This can help reduce the chance of surviving cancer cells dividing and growing in the intervals between each radiation therapy dose. [ 110 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3990", "text": "As one example of the localized nature of breast brachytherapy, the SAVI device delivers the radiation dose through multiple catheters, each of which can be individually controlled. This approach decreases the exposure of healthy tissue and resulting side effects, compared both to external beam radiation therapy and older methods of breast brachytherapy. [ 111 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3991", "text": "Radionuclide therapy (also known as systemic radioisotope therapy, radiopharmaceutical therapy, or molecular radiotherapy), is a form of targeted therapy. Targeting can be due to the chemical properties of the isotope such as radioiodine which is specifically absorbed by the thyroid gland a thousandfold better than other bodily organs. Targeting can also be achieved by attaching the radioisotope to another molecule or antibody to guide it to the target tissue. The radioisotopes are delivered through  infusion  (into the bloodstream) or ingestion. Examples are the infusion of  metaiodobenzylguanidine  (MIBG) to treat  neuroblastoma , of oral  iodine-131  to treat  thyroid cancer  or  thyrotoxicosis , and of hormone-bound  lutetium-177  and  yttrium-90  to treat  neuroendocrine tumors  ( peptide receptor radionuclide therapy )."}
{"_id": "WikiPedia_Radiology$$$corpus_3992", "text": "Another example is the injection of radioactive yttrium-90 or holmium-166 microspheres into the  hepatic artery  to radioembolize liver tumors or liver metastases. These microspheres are used for the treatment approach known as  selective internal radiation therapy . The microspheres are approximately 30\u00a0 \u03bcm  in diameter (about one-third of a human hair) and are delivered directly into the artery supplying blood to the tumors. These treatments begin by guiding a  catheter  up through the femoral artery in the leg, navigating to the desired target site and administering treatment. The blood feeding the tumor will carry the microspheres directly to the tumor enabling a more selective approach than traditional systemic chemotherapy. There are currently three different kinds of microspheres:  SIR-Spheres ,  TheraSphere  and QuiremSpheres."}
{"_id": "WikiPedia_Radiology$$$corpus_3993", "text": "A major use of systemic radioisotope therapy is in the treatment of  bone metastasis  from cancer. The radioisotopes travel selectively to areas of damaged bone, and spare normal undamaged bone. Isotopes commonly used in the treatment of bone metastasis are  radium-223 , [ 112 ]   strontium-89  and  samarium ( 153 Sm) lexidronam . [ 113 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3994", "text": "In 2002, the  United States Food and Drug Administration  (FDA) approved  ibritumomab tiuxetan  (Zevalin), which is an anti- CD20   monoclonal antibody  conjugated to yttrium-90. [ 114 ] \nIn 2003, the FDA approved the  tositumomab /iodine ( 131 I) tositumomab regimen (Bexxar), which is a combination of an iodine-131 labelled and an unlabelled anti-CD20 monoclonal antibody. [ 115 ] \nThese medications were the first agents of what is known as  radioimmunotherapy , and they were approved for the treatment of refractory  non-Hodgkin's lymphoma ."}
{"_id": "WikiPedia_Radiology$$$corpus_3995", "text": "Intraoperative radiation therapy  (IORT) is applying therapeutic levels of radiation to a target area, such as a  cancer  tumor, while the area is exposed during  surgery . [ 116 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3996", "text": "The rationale for IORT is to deliver a high dose of radiation precisely to the targeted area with minimal exposure of surrounding tissues which are displaced or shielded during the IORT. Conventional radiation techniques such as external beam radiotherapy (EBRT) following surgical removal of the tumor have several drawbacks: The tumor bed where the highest dose should be applied is frequently missed due to the complex localization of the wound cavity even when modern radiotherapy planning is used. Additionally, the usual delay between the surgical removal of the tumor and EBRT may allow a repopulation of the tumor cells. These potentially harmful effects can be avoided by delivering the radiation more precisely to the targeted tissues leading to immediate sterilization of residual tumor cells. Another aspect is that wound fluid has a stimulating effect on tumor cells. IORT was found to inhibit the stimulating effects of wound fluid. [ 117 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3997", "text": "Medicine has used radiation therapy as a treatment for cancer for more than 100 years, with its earliest roots traced from the discovery of X-rays in 1895 by  Wilhelm R\u00f6ntgen . [ 118 ]   Emil Grubbe  of Chicago was possibly the first American physician to use X-rays to treat cancer, beginning in 1896. [ 119 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_3998", "text": "The field of radiation therapy began to grow in the early 1900s largely due to the groundbreaking work of  Nobel Prize \u2013winning scientist  Marie Curie  (1867\u20131934), who discovered the radioactive elements  polonium  and  radium  in 1898. This began a new era in medical treatment and research. [ 118 ]   Through the 1920s the hazards of radiation exposure were not understood, and little protection was used. Radium was believed to have wide curative powers and radiotherapy was applied to many diseases."}
{"_id": "WikiPedia_Radiology$$$corpus_3999", "text": "Prior to World War 2, the only practical sources of radiation for radiotherapy were radium, its \"emanation\",  radon  gas, and the  X-ray tube .  External beam radiotherapy  (teletherapy) began at the turn of the century with relatively low voltage (<150\u00a0kV) X-ray machines.  It was found that while superficial tumors could be treated with low voltage X-rays, more penetrating, higher energy beams were required to reach tumors inside the body, requiring higher voltages.  Orthovoltage X-rays , which used tube voltages of 200-500\u00a0kV, began to be used during the 1920s.  To reach the most deeply buried tumors without exposing intervening skin and tissue to dangerous radiation doses required rays with energies of 1\u00a0MV or above, called \"megavolt\" radiation.  Producing megavolt X-rays required  voltages  on the X-ray tube of 3 to 5 million  volts , which required huge expensive installations.  Megavoltage X-ray units were first built in the late 1930s but because of cost were limited to a few institutions. One of the first, installed at  St. Bartholomew's hospital , London in 1937 and used until 1960, used a 30 foot long X-ray tube and weighed 10 tons. Radium produced megavolt  gamma rays , but was extremely rare and expensive due to its low occurrence in ores.  In 1937 the entire world supply of radium for radiotherapy was 50 grams, valued at \u00a3800,000, or $50 million in 2005 dollars."}
{"_id": "WikiPedia_Radiology$$$corpus_4000", "text": "The invention of the  nuclear reactor  in the  Manhattan Project  during World War 2 made possible the production of artificial  radioisotopes  for radiotherapy.  Cobalt therapy ,  teletherapy  machines using megavolt gamma rays emitted by  cobalt-60 , a radioisotope produced by irradiating ordinary cobalt metal in a reactor, revolutionized the field between the 1950s and the early 1980s.  Cobalt machines were relatively cheap, robust and simple to use, although due to its 5.27 year  half-life  the cobalt had to be replaced about every 5 years."}
{"_id": "WikiPedia_Radiology$$$corpus_4001", "text": "Medical  linear particle accelerators , developed since the 1940s, began replacing X-ray and cobalt units in the 1980s and these older therapies are now declining. The first medical linear accelerator was used at the  Hammersmith Hospital  in London in 1953. [ 71 ]  Linear accelerators can produce higher energies, have more collimated beams, and do not produce radioactive waste with its attendant disposal problems like radioisotope therapies."}
{"_id": "WikiPedia_Radiology$$$corpus_4002", "text": "With  Godfrey Hounsfield 's invention of  computed tomography  (CT) in 1971, three-dimensional planning became a possibility and created a shift from 2-D to 3-D radiation delivery. CT-based planning allows physicians to more accurately determine the dose distribution using axial tomographic images of the patient's anatomy. The advent of new imaging technologies, including  magnetic resonance imaging  (MRI) in the 1970s and  positron emission tomography  (PET) in the 1980s, has moved radiation therapy from 3-D conformal to intensity-modulated radiation therapy (IMRT) and to image-guided radiation therapy  tomotherapy . These advances allowed radiation oncologists to better see and target tumors, which have resulted in better treatment outcomes, more organ preservation and fewer side effects. [ 120 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4003", "text": "While access to radiotherapy is improving globally, more than half of patients in low and  middle income countries  still do not have available access to the therapy as of 2017. [ 121 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4004", "text": "The  abscopal effect  is a hypothesis in the treatment of  metastatic cancer  whereby shrinkage of untreated tumors occurs concurrently with shrinkage of tumors within the scope of the localized treatment. R.H. Mole proposed the term \"abscopal\" ('ab' - away from, 'scopus' - target) in 1953 to refer to effects of  ionizing radiation  \"at a distance from the irradiated volume but within the same organism\". [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4005", "text": "Initially associated with single-tumor, localized radiation therapy, the term \"abscopal effect\" has also come to encompass other types of localized treatments such as electroporation and intra-tumoral injection of therapeutics. [ 2 ]  However, the term should only be used when truly local treatments result in systemic effects. For instance, chemotherapeutics commonly circulate through the blood stream and therefore exclude the possibility of any abscopal response."}
{"_id": "WikiPedia_Radiology$$$corpus_4006", "text": "The mediators of the abscopal effect of  radiotherapy  were unknown for decades. In 2004, it was postulated for the first time that the immune system might be responsible for these \"off-target\" anti-tumor effects. [ 3 ]  Various studies in animal models of melanoma, [ 4 ] [ 5 ]  mammary, [ 5 ] [ 6 ]  and colorectal tumors [ 5 ] [ 7 ]  have substantiated this hypothesis. Abscopal effects of  Targeted intraoperative radiotherapy  have been seen in clinical studies, including in randomized trials where women treated with lumpectomy for breast cancer combined with whole breast radiotherapy showed reduced mortality from non-breast-cancer causes when compared with whole breast radiotherapy. [ 8 ] [ 9 ]  Furthermore, immune-mediated abscopal effects were also described in patients with metastatic cancer. [ 10 ]  Whereas these reports were extremely rare throughout the 20th century, the clinical use of immune checkpoint blocking antibodies such as  ipilimumab  or  pembrolizumab  has greatly increased the number of abscopally responding patients in selected groups of patients such as those with metastatic melanoma  [ 11 ] [ 12 ]  or lymphoma. [ 13 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4007", "text": "Similar to immune reactions against  antigens  from bacteria or viruses, the abscopal effect requires  priming  of immune cells against tumor antigens. [ 10 ]  Local irradiation of a tumor nodule may lead to immunogenic forms of tumor cell death and liberation of tumor cell-derived antigens. These antigens can be recognized and processed by  antigen-presenting cells  within the tumor ( dendritic cells  and  macrophages ).  Cytotoxic T cells  which recognize these tumor antigens may in turn be primed by the tumor antigen-presenting cells. In contrast to the local effect of irradiation on the tumor cells, these cytotoxic T cells circulate through the blood stream and are thus able to destroy remaining tumor cells in distant parts of the body which were not irradiated. Accordingly, increases in tumor-specific cytotoxic T cells were shown to correlate with abscopal anti-tumor responses in patients. [ 11 ]  Vice versa, the abscopal effect is abolished after experimental depletion of T cells in various animal models. [ 5 ] [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4008", "text": "Abscopal effects of ionizing radiation are often blocked by the immunosuppressive  microenvironment  inside the irradiated tumor which prevents effective T cell priming. This explains why the effect is so rarely seen in patients receiving radiotherapy alone. In contrast, the combination of immunomodulatory drugs such as ipilimumab and pembrolizumab can partially reconstitute systemic anti-tumor immune reactions induced after local tumor radiotherapy. [ 4 ]  The optimal combination of radiation dose and fractionation with immunomodulatory drugs is currently under intensive investigation. In this context, it was proposed that radiation doses above 10 to 12 Gray might be ineffective in inducing immunogenic forms of cell death. [ 15 ]  However, there is so far no consensus on the optimal radiation regimen needed to increase the chance of abscopal tumor regression."}
{"_id": "WikiPedia_Radiology$$$corpus_4009", "text": "Auger therapy   is a form of  radiation therapy  for the treatment of  cancer  which relies on low-energy  electrons  (emitted by the  Auger effect ) to damage cancer cells, rather than the high-energy  radiation  used in traditional radiation therapy. [ 1 ] [ 2 ]  Similar to other forms of radiation therapy, Auger therapy relies on radiation-induced damage to cancer  cells  (particularly  DNA  damage) to arrest  cell division , stop  tumor  growth and  metastasis  and kill cancerous cells. It differs from other types of radiation therapy in that electrons emitted via the  Auger effect  (Auger electrons) are released with low  kinetic energy . In contrast to traditional \u03b1- and \u03b2-particle emitters, Auger electron emitters exhibit low cellular toxicity during transit in blood or bone marrow. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4010", "text": "Due to their low kinetic energy, emitted Auger electrons travel over a very short range: much less than the size of a single cell, on the order of less than a few-hundred  nanometers . [ 4 ]  This very short-range delivery of energy permits highly targeted therapies, since the radiation-emitting  nuclide  will be in close proximity to the delivery site (e.g., a DNA strand) to cause cytotoxicity. [ 5 ]  However, this is a technical challenge; Auger therapeutics must enter their cell-nuclear targets to be most effective. [ 4 ] [ 6 ]  Auger therapeutics are radiolabelled biomolecules, capable of entering cells of interest and binding to specific sub-cellular components. These typically carry a radioactive atom capable of emitting Auger electrons. The Auger electron emission from the atom is stimulated by  radioactive decay, or by external pst (primary system therapy, such as X-ray) excitation. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4011", "text": "The electron energy in a vacuum may be accurately measured with an electron detector in a  Faraday cage , where the  bias  placed on the cage will accurately define the particle energy reaching the detector. The range of low-energy electrons in tissue or water, particularly electrons at the nanometer scale, cannot be easily measured; it must be inferred, since low-energy electrons scatter at large angles and travel in a zigzag path whose termination distance must be considered statistically and from differential measurements of higher-energy electrons at a much higher range. A 20\u00a0 eV  electron in water, for example, could have a range of 20\u00a0nm for 103\u00a0 Gy  or 5\u00a0nm for 104.7\u00a0Gy. For a group of 9\u201312 Auger electrons with energies at 12\u201318\u00a0eV in water (including the effect of water ionization at approximately 10\u00a0eV), an estimate of 106\u00a0Gy is probably sufficiently accurate. The illustration shows the simulated dose calculation in water for an electron using a  Monte Carlo   random walk [ 7 ]  which gives up to 0.1\u00a0MGy. For a moderately-heavy atom to yield a dozen or more Auger electrons from its inner-shell ionization, the Auger dose becomes 106\u00a0Gy per event."}
{"_id": "WikiPedia_Radiology$$$corpus_4012", "text": "With a large, localized dose  in situ  for molecular modification, the most obvious target molecule is the DNA duplex (where the complementary strands are separated by several nanometers). However, DNA duplex atoms are light elements (with only a few electrons each). Even if they could be induced by a photon beam to deliver Auger electrons, at under 1\u00a0keV they would be too soft to penetrate tissue sufficiently for therapy. Mid-range or heavy atoms (from bromine to platinum, for example) which could be induced by sufficiently hard X-ray photons to generate enough electrons to provide low-energy charges in an Auger cascade, will be considered for therapy."}
{"_id": "WikiPedia_Radiology$$$corpus_4013", "text": "When a normal cell transforms, replicating uncontrollably, many unusual genes (including viral material such as herpes genes which are not normally expressed) are expressed with viral-specific functions. The molecule proposed to disrupt the herpes gene is BrdC, where Br replaces a methyl (CH3) with nearly the same ionic radius and location (at the 5th position for BrdU, which has an oxygen molecule at the top). Therefore, BrdC could be oxidized and used as BrdU. Before oxidation, BrdC was unusable as dC or dU in mammalian cells (except for the herpes gene, which could incorporate the BrdC). The bromine atom is made from  arsenic , with the addition of an  alpha particle  in a  particle accelerator  to form  77 Br . It has a half-life of 57 hours and undergoes  electron capture : the  K-electron  is captured by a proton in an unstable nucleus, creating a K hole in Br, and leading to its Auger cascade and disrupting the herpes gene without killing the cell."}
{"_id": "WikiPedia_Radiology$$$corpus_4014", "text": "This experiment was performed during the 1970s at  Memorial Sloan Kettering Cancer Center  by Lawrance Helson and C. G. Wang, using 10 neuroblastoma  cell cultures , Two cultures were successful in terminating the cell replication with  77 Br   in vitro , and the experiments were followed by a group of  nude mice  with implanted tumors."}
{"_id": "WikiPedia_Radiology$$$corpus_4015", "text": "The  in vivo  mouse experiments were complicated when the mouse livers cleaved off the sugar component of BrdC rendering the mammalian and herpes genes to incorporate the  77 Br -containing base, making no distinction between them. However, the Auger dose with 77BrdC disrupted the herpes-specific gene in several transformed cell cultures. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4016", "text": "The group of metal-based anticancer drugs originated with  cisplatin , one of the leading agents in clinical use. Cisplatin acts by binding to DNA, forming one or two intrastrand cross-links of the G-G  adduct  at 70% and the A-G adduct at ~20% of the major grooves of the  double helix . The planar  cis  compound (on the same side) is composed of a square molecule with two chloride atoms on one side and two ammonia groups on the other side, centered around the heavy  platinum  (Pt) which could initiate the Auger dose  in situ . Entering a cell with a low NaCl concentration, the aqua-chloride group would detach from the compound (allowing the missing chloride to link the G-G or A-G bases and bend the DNA helixes 45 degrees, damaging them). Although  platinum-based antineoplastics  are used in as much as 70 percent of all chemotherapy, they are not particularly effective against certain cancers (such as breast and prostate tumors)."}
{"_id": "WikiPedia_Radiology$$$corpus_4017", "text": "The aqua-Cl rationale, detaching the chloride atom from the cisplatin when it enters a cell and binding them to G-G or A-G adducts in the major grooves of the DNA helixes, could be applied to other metals\u2014such as  ruthenium  (Ru)-chemically similar to platinum. Ruthenium is used to coat the anode target of a mammography X-ray tube, enabling operation at any voltage (22\u201328\u00a0 kVp ) depending on the compressed thickness of the breast and delivering a high-contrast image. Although ruthenium is lighter than platinum, it can be induced to provide an Auger dose  in situ  to the DNA adducts and deliver localized chemotherapy. [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4018", "text": "Monochromatic X-rays may be channeled from  synchrotron radiation , obtained from filtered Coolidge  X-ray tubes  or from the preferred transmission X-ray tubes. To induce  inner-shell ionization  with resonant scattering from a moderately-heavy atom with dozens of electrons, the X-ray  photon  energy must be 30\u00a0keV or higher to penetrate tissue in therapeutic applications. Although synchrotron radiation is extremely bright and monochromatic without thermal  scattering , its brightness falls off at the fourth power of photon energy. At 15\u201320\u00a0kV or higher an X-ray tube with a  molybdenum  target, for example, could deliver as much X-ray  fluence  as a typical synchrotron. A Coolidge X-ray tube brightens by 1.7\u00a0kVp and synchrotron brightness decreases by 4\u00a0kV, implying that it is not useful for Auger therapy. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4019", "text": "In  radiation therapy ,  bolus  is a material which has properties equivalent to  tissue  when irradiated. It is widely used in practice to reduce or alter dosing for targeted radiation therapy."}
{"_id": "WikiPedia_Radiology$$$corpus_4020", "text": "It must be possible to mould the bolus to fill the tissue space. Lincolnshire and Spier's bolus, which is loosely packed in  polyethylene  bags, is suitable as the bolus bags take the shape of the skin surface these bags are easily smoothed to achieve a flat surface."}
{"_id": "WikiPedia_Radiology$$$corpus_4021", "text": "A specific thickness of bolus can be applied to the skin to alter the dose received at depth in the tissue and on the skin surface. A typical example of this is the application of a defined thickness of bolus to a chest wall for post-mastectomy chest wall treatment, to increase the skin dose. The thickness of bolus applied is dependent on the skin dose required and the angle of incidence of the treatment beams. For example, if oblique 6 MV beams are used for tangential pair, 1\u00a0cm of bolus effectively becomes 1.5\u00a0cm, i.e., \"full bolus\"."}
{"_id": "WikiPedia_Radiology$$$corpus_4022", "text": "When a full bolus is applied, bolus thickness equal to the depth of the build-up region removes the  skin-sparing effect  of a  megavoltage x-ray  beam. On the other hand, there are boluses that do not require the selection of specific thicknesses to treat a certain depth. These types of boluses have densities higher than water but can be calculated from CT images by the Treatment Planning System (TPS). One of these boluses is commonly known as high-density and high-adaptation bolus (e.g.,  eXaSkin  and  eXaSkin Plus )."}
{"_id": "WikiPedia_Radiology$$$corpus_4023", "text": "Suitable material must be pliable and easily moulded to the skin surface, but retain a constant thickness. One example includes  paraffin  gauze."}
{"_id": "WikiPedia_Radiology$$$corpus_4024", "text": "For smaller areas which do not require the bolus to be moulded over the skin,  Perspex  can be used. The use of Perspex bolus is advantageous for electron set-ups because it is transparent. Since the f.s.d. for most electron fields is 95\u00a0cm, so that the movements of the couch are not isocentric, inaccuracies may arise for aligning angled fields when an opaque bolus is inserted."}
{"_id": "WikiPedia_Radiology$$$corpus_4025", "text": "To ensure that the patient receives the required dose, bolus of the right thickness must be placed correctly. Therefore, bolus requirements must be clearly documented in the setup sheets of the treatment card. When using bolus to compensate for missing tissue, the whole of the bolussed area must be level with the point on the patient where the f.s.d. is set, to ensure dose homogeneity."}
{"_id": "WikiPedia_Radiology$$$corpus_4026", "text": "When the bolus is used to reduce the skin-sparing effect, the bolus does not necessarily need to touch the skin all over the bolussed area as the scatter is of sufficiently high energy to be unaffected by an air gap. However, it is important that the bolus is uniform thickness. Some bolus materials are easily squashed and must be carefully measured at regular intervals."}
{"_id": "WikiPedia_Radiology$$$corpus_4027", "text": "A  bone-seeking radioisotope  is a  radioactive  substance that is given through a  vein , and collects in  bone cells  and in  tumor cells  that have spread to the  bone . It kills  cancer cells  by giving off low-level  radiation ."}
{"_id": "WikiPedia_Radiology$$$corpus_4028", "text": "This article incorporates  public domain material  from  Dictionary of Cancer Terms .  U.S. National Cancer Institute ."}
{"_id": "WikiPedia_Radiology$$$corpus_4029", "text": "The  Bragg peak  is a pronounced peak on the Bragg curve which plots the energy loss of  ionizing radiation  during its travel through matter. For  protons ,  \u03b1-rays , and other  ion rays , the peak occurs immediately before the particles come to rest. It is named after  William Henry Bragg , who discovered it in 1903 using alpha particles from radium, [ 1 ] [ 2 ]  and wrote the first empirical formula for ionization energy loss per distance with Richard Kleeman. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4030", "text": "When a fast  charged particle  moves through matter, it  ionizes  atoms of the material and deposits a  dose  along its path. A peak occurs because the interaction  cross section  increases as the charged particle's energy decreases. Energy lost by charged particles is inversely proportional to the square of their velocity, which explains the peak occurring just before the particle comes to a complete stop. [ 4 ]  In the upper figure, it is the peak for alpha particles of 5.49 MeV moving through air. In the lower figure, it is the narrow peak of the \"native\" proton beam curve which is produced by a  particle accelerator  of 250  MeV . The figure also shows the absorption of a beam of energetic  photons  ( X-rays ) which is entirely different in nature; the curve is mainly  exponential ."}
{"_id": "WikiPedia_Radiology$$$corpus_4031", "text": "This characteristic of proton beams was first recommended for use in cancer therapy by Robert R. Wilson in his 1946 article, Radiological Use of Fast Protons. [ 5 ]  Wilson studied how the depth of proton beam penetration could be controlled by the energy of the protons. This phenomenon is exploited in  particle therapy  of cancer, specifically in proton therapy, to concentrate the effect of light  ion beams  on the  tumor  being treated while minimizing the effect on the surrounding healthy tissue. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4032", "text": "The blue curve in the figure (\"modified  proton beam \") shows how the originally monoenergetic proton beam with the sharp peak is widened by increasing the range of energies, so that a larger tumor volume can be treated. The plateau created by modifying the proton beam is referred to as the spread out Bragg Peak, or SOBP, which allows the treatment to conform to not only larger tumors, but to more specific 3D shapes. [ 7 ]  This can be achieved by using variable thickness  attenuators  like spinning wedges. [ 8 ]  Momentum cooling in cyclotron-based proton therapy facilities enables a sharper distal fall-off of the Bragg peak and the attainment of high dose rates.  [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4033", "text": "Chemoradiotherapy  ( CRT ,  CRTx ,  CT-RT ) is the combination of  chemotherapy  and  radiotherapy  to treat  cancer . [ 1 ]  Synonyms include  radiochemotherapy  ( RCT ,  RCTx ,  RT-CT ) and  chemoradiation . It is a type of  multimodal cancer therapy ."}
{"_id": "WikiPedia_Radiology$$$corpus_4034", "text": "Chemoradiation can be  concurrent   [ 2 ]  (together) or  sequential  (one after the other). [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4035", "text": "The chemotherapy component can be or include a  radiosensitizing agent . [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4036", "text": "Chemoradiotherapy as  neoadjuvant therapy  before surgery has been shown to be effective in  esophageal cancer . [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4037", "text": "Cobalt therapy   is the medical use of  gamma rays  from the  radioisotope   cobalt-60  to treat conditions such as  cancer .  Beginning in the 1950s, cobalt-60 was widely used in  external beam radiotherapy  (teletherapy) machines, which produced a beam of gamma rays which was directed into the patient's body to kill tumor tissue.  Because these \"cobalt machines\" were expensive and required specialist support, they were often housed in  cobalt units .  Cobalt therapy was a revolutionary advance in radiotherapy in the post-World War II period but is now being replaced by other technologies such as  linear accelerators . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4038", "text": "Before the development of medical  linear accelerators  in the 1970s, the only artificial radiation source used for  teletherapy  was the  x-ray tube .  Researchers found ordinary x-ray tubes, which used voltages of 50-150\u00a0keV, could treat superficial tumors, but did not have the energy to reach tumors deep in the body. To have the penetrating ability to reach deep-seated tumors without subjecting healthy tissue to dangerous radiation doses required rays with energy around a million electron volts (MeV), called \"megavoltage\" radiation. To produce a significant amount of MeV x-rays required potentials on the tube of 3-5 million volts (3-5 megavolts), necessitating huge, expensive x-ray machines. By the late 1930s these were being built, but they were available at only a few hospitals."}
{"_id": "WikiPedia_Radiology$$$corpus_4039", "text": "Radioisotopes  produced  gamma rays  in the megavolt range, but prior to  World War II  virtually the only radioisotope available for radiotherapy was naturally occurring  radium  (producing 1-2\u00a0MeV gamma rays), which was extremely expensive due to its low occurrence in ores. In 1937 the price of radium  US$25,000  (equivalent to $529,861 in 2023) \u00a0 per \u00a0 gram, [ 2 ]  and the total worldwide supply of radium available for beam radiotherapy (teletherapy) was 50 \u00a0 grams."}
{"_id": "WikiPedia_Radiology$$$corpus_4040", "text": "The invention of the  nuclear reactor  in the  Manhattan Project  during World War II made possible the creation of artificial radioisotopes for radiotherapy.  Cobalt-60 , produced by neutron irradiation of ordinary  cobalt  metal in a reactor, is a high activity gamma-ray emitter, emitting 1.17 and 1.33\u00a0MeV gamma rays with an activity of 44\u00a0 TBq / g  (1,200\u00a0 Ci /g).  The main reason for its wide use in radiotherapy is that it has a longer  half-life , 5.27\u00a0years, than many other gamma emitters. However, this half-life still requires cobalt sources to be replaced about every 5 years."}
{"_id": "WikiPedia_Radiology$$$corpus_4041", "text": "In 1949, Dr.  Harold E. Johns  of the  University of Saskatchewan  sent a request to the  National Research Council  (NRC) of Canada asking it to produce cobalt-60 isotopes for use in a cobalt therapy unit prototype. Two cobalt-60 apparatuses were then built, one in  Saskatoon  in the cancer wing of the University of Saskatchewan and the other in  London, Ontario . Johns collected depth-dose data at the University of Saskatchewan which would later become the world standard. [ 3 ]  The first patient to be treated with cobalt-60 radiation was treated on October 27, 1951, at the  War Memorial Children's Hospital  in London, Ontario. [ 4 ] [ 5 ]  In 1961 cobalt therapy was expected to replace X-ray radiotherapy. [ 6 ] :\u200a14\u200a  In 1966,  Walt Disney 's lung cancer was treated with this procedure, but could not prevent his death. [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4042", "text": "Dr.  Glenn T. Seaborg , chairman of the  United States Atomic Energy Commission ,  Nobel Prize  winner and former chancellor of the  University of California , dedicated the first cobalt facility of the new Radiation Therapy and Nuclear Medicine Wing of the  Cedars of Lebanon Hospital  on January 11, 1963 supervised by Dr. Henry L. Jaffe, Director of the new department. A pioneer in the use of the nicknamed \"cobalt bomb\" the Cedars unit was licensed in 1948 by the Atomic Energy Commission. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4043", "text": "The role of the cobalt unit has partly been replaced by the  linear accelerator , which can generate higher-energy radiation, and does not produce the  radioactive waste  that  radioisotopes  do with their attendant disposal problems. Cobalt treatment still has a useful role to play in certain applications and is still in widespread use worldwide, since the machinery is relatively reliable and simple to maintain compared to the modern linear accelerator. [ 9 ] [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4044", "text": "As used in  radiotherapy , cobalt units produce stable, dichromatic beams of 1.17 \u00a0 and \u00a0 1.33 MeV, resulting in an average beam energy of 1.25 \u00a0 MeV. Cobalt-60 has a  half-life  of 5.2713 \u00a0 years. [ 10 ] :\u200a39"}
{"_id": "WikiPedia_Radiology$$$corpus_4045", "text": "Henri Coutard [ a ]  (27 August 1876 \u2013 16 March 1950) was a French  radiation therapist . He is known for his studies of  radiation therapy  for the treatment of  laryngeal cancer  and the development of the \"protracted-fractional method\" of radiation dosing."}
{"_id": "WikiPedia_Radiology$$$corpus_4046", "text": "Born in  Marolles-les-Braults  in the French department of  Sarthe , Coutard attended medical school at  University of Paris  and graduated in 1902. He served in the  French Army  and lived for several years in the  Jura Mountains  before returning to Paris to study the medical applications of  radium . During World War I, he worked in one of the radiological ambulance units overseen by the Polish-French physicist and chemist  Marie Curie . He became the chief of the  X-ray  department at the  Radium Institute  of the University of Paris in 1919, working closely with  Claudius Regaud  and other scientists. Coutard's early work demonstrating the efficacy of radiating patients with laryngeal cancer led to the adoption of radiation therapy as a primary course of cancer treatment. The protracted-fractional method consisted of long durations of radiation applied over several weeks."}
{"_id": "WikiPedia_Radiology$$$corpus_4047", "text": "In the late 1930s, Coutard moved to the United States, first working at the  California Institute of Technology  and then at the Chicago Tumor Institute. During this time, he accompanied the American entrepreneur  Spencer Penrose  to Colorado Springs to treat Penrose's  esophageal cancer . After Penrose's death in 1939, his radiotherapy equipment was donated to  Penrose Hospital  and Coutard became a radiotherapist at the newly-established Penrose Tumor Clinic. In the last decade of his life, Coutard's research became more erratic. He published a  monograph  in 1949 that was largely ignored by reputable journals and his peers. He experienced an  intracerebral hemorrhage  in December 1949 and died in  Le Mans  a few months later."}
{"_id": "WikiPedia_Radiology$$$corpus_4048", "text": "Henri Coutard was born on 27 August 1876 in  Marolles-les-Braults  in the French department of  Sarthe . His father, Louis Coutard, was a local government official, and his mother, M\u00e9lanie Marie Jos\u00e9phine Coutard ( n\u00e9e  Ragot), sold  novelty items . [ 3 ] [ 4 ]  He had an older brother, Louis, and a younger sister, Hel\u00e8ne. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4049", "text": "In 1887, Coutard enrolled at the  Lyc\u00e9e Montesquieu \u00a0[ fr ] , a state  boarding school  in  Le Mans . He received a  baccalaur\u00e9at  in literature in 1893 and another in mathematics the following year. During this time, he also received an award for excellence in his school's military and gymnastics programs. After secondary school, he entered medical school at the  University of Paris , training in Parisian hospitals and completing an internship in  Nantes . [ 3 ]  His doctoral  thesis  was titled  Lesions extrap\u00e9riton\u00e9ales de la vessie et du rectum dans les fractures du bassin  (\"Extraperitoneal lesions of the bladder and rectum observed in cases of pelvic fracture\"). [ 5 ]  It summarised eight cases from the literature and one from his previous patients. He defended his thesis on 17 July 1902. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4050", "text": "After medical school, Coutard enrolled as a medical officer and captain in the  Chasseurs Alpins , the elite  mountain infantry  force of the  French Army . [ 6 ]  After contracting  pulmonary tuberculosis  he moved to the  Jura Mountains  to recover, and during that time practiced general medicine. [ 4 ]  In 1912, he returned to Paris after becoming interested in the potential medical applications of  radioactivity . [ 3 ] [ 4 ]  Radioactivity had first been discovered in the element  uranium  by the physicist  Henri Becquerel  in 1896, and over the next several years, the French researchers  Marie  and  Pierre Curie  discovered the radioactivity of additional elements:  thorium ,  polonium , and  radium . [ 7 ]  Coutard began studying the properties of radium at an experimental laboratory co-founded by the physicist  Jacques Danne \u00a0[ fr ] . [ 3 ] [ 4 ]  His research centred on therapeutic applications of radium in animals, and he presented his work at the 1912 meeting of the  French Association for the Advancement of Science \u00a0[ fr ] . [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4051", "text": "Coutard was  drafted  during World War I and worked as a  radiation therapist  in a military hospital near  Baccarat, Meurthe-et-Moselle , on the  Eastern Front . [ 3 ] [ 8 ]  There, he met  Claudius Regaud , a  radiobiologist  with whom he later collaborated. [ 3 ]  Coutard also worked in one of the radiological ambulance units overseen by Marie Curie. He attained the rank of  major  by the end of the war. [ 6 ] [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4052", "text": "In 1919, Coutard became the chief of the  X-ray  department at the  Radium Institute  of the University of Paris, working with other scientists including Regaud and  Antoine Lacassagne . [ 4 ] [ 9 ]  Using a single X-ray unit in the basement of the institute, he conducted experiments on animals, administered  radiation therapy  to patients, and performed diagnostic imaging of the  pharynx  and  larynx . [ 9 ] [ 10 ]  In his early work during this period, he observed the recurrence of cancer when  tumours  were insufficiently irradiated and the need to avoid excessive irradiation of the eyes. He believed that the dose of radiation needed to be high enough to cause an observable reaction in the  mucous membrane , and coined the term  radioepithelitis  to describe this reaction. [ 11 ]  At the 1921 International Congress of Oto-Rhino-Laryngology in Paris, Coutard presented data from six patients with  laryngeal cancer  who he had treated with radiation. His work was well received, and physicians began adopting radiation therapy as a primary course of treatment for cancer. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4053", "text": "Scientists had differing opinions on the optimal timing of radiation doses. [ 12 ]  Coutard believed that long durations of radiation, applied over several weeks, produced the best results and theorised that this technique allowed  tissue  to recover between sessions. [ 13 ] [ 12 ]  He presented his method at the 1928  International Congress of Radiology , and it became known as \"Coutard's method\" or the \"protracted-fractional method\". [ 12 ] [ 14 ]  Using this technique, Coutard achieved the first reported cures of laryngeal cancer using radiation, and by about 1930 he had obtained data on the  five-year survival rate  of his technique. [ 15 ] [ 16 ]  Though he never published rigid standards for radiation doses, he meticulously recorded the treatments that he administered to each patient, using a  radiometer  that he constructed. [ 10 ] [ 17 ]  Over the next decade, he continued experimenting with different therapy regimens, including short, intensive doses and interrupted regimens. [ 10 ]  Radiotherapists from other countries visited the Radium Institute to meet Coutard and train with him, [ 9 ]  including Simeon T. Cantril, who later became the first president of the  American Society for Radiation Oncology . [ 18 ] [ 19 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4054", "text": "Coutard grew interested in United States radiotherapy research, where supervoltage units ( X-ray generators  with a  peak kilovoltage  of several hundred kilovolts) were being produced. [ 20 ]  The physicist  Charles Christian Lauritsen , on behalf of his mentor  Robert Andrews Millikan , invited Coutard to work at the Kellogg Research Laboratory at the  California Institute of Technology . At the same time, Max Cutler of the Chicago Tumor Institute offered Coutard a leading position there. Coutard accepted both offers in late 1937. [ 21 ]  He resigned his position at the Radium Institute and was succeeded by  Fran\u00e7ois Baclesse \u00a0[ lb ] . [ 22 ]  At Caltech, he studied  high-voltage  therapy and worked closely with Millikan and the physicist  Seeley G. Mudd . [ 13 ] [ 21 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4055", "text": "After working at Caltech for six months, Coutard moved to  Chicago  and studied the use of short, concentrated doses of radiation for treating laryngeal cancer at the Chicago Tumor Institute, while teaching  graduate  courses there. [ 13 ]  Cutler's ambitions for the institute were curtailed as a result of the  Great Depression . [ 21 ]  He was unable to secure a supervoltage unit for Coutard, and the institute did not receive many patients. [ 23 ]  During this time, Coutard treated the American  entrepreneur  and  philanthropist   Spencer Penrose  for  esophageal cancer , having previously treated Penrose for laryngopharyngeal cancer in Paris in 1932. Penrose bought a radiotherapy unit for his home in  Colorado Springs, Colorado , and Coutard accompanied him there to continue his treatment. [ 24 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4056", "text": "Penrose died in 1939, and stipulated that his radiotherapy equipment be donated to the local Glockner Hospital (now  Penrose Hospital ). His wife, Julie Penrose, used funds from their  El Pomar Foundation  to establish the Penrose Tumor Clinic at the hospital and invited Coutard to practice radiotherapy at the new clinic. [ 25 ]  He accepted, and moved to Colorado Springs in 1941. [ 13 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4057", "text": "In the last decade of his life, Coutard's research became more erratic. He began to conduct unorthodox experiments, including the use of blocks of gold as  X-ray filters  and  homeopathic  theories of  beta particles , and stopped publishing papers in scientific journals. [ 13 ]  His ideas were criticised by his peers and he became increasingly isolated. [ 25 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4058", "text": "Coutard published a  monograph  in 1949, reporting on his findings from Colorado Springs. [ 25 ]  According to the radiologist and historian E. R. N. Grigg, the monograph was a \"rambling mixture of clinical observations, working hypotheses, and fantastic assumptions\"; it was largely ignored by reputable journals as well as his peers. [ 13 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4059", "text": "Coutard married Anne-Marie Ad\u00e8le Rougier in Paris on 25 March 1919, at the end of World War I. [ 13 ] [ 26 ]  During his time at the Radium Institute, they lived on the outskirts of Paris. [ 12 ]  Anne-Marie remained in Paris when Henri worked in the United States, and she died of  leukemia  there in 1940. [ 13 ] [ 23 ]  After her death, Coutard married Suzanne Rosalie Jourgeon (n\u00e9e Mathot), the widow of one of his former patients in France. [ 13 ]  She moved to Colorado Springs and they lived within walking distance of the Penrose Tumor Clinic. When Suzanne's health deteriorated in 1949, she moved back to Paris to live with her children from her first marriage; she died there later that year. [ 25 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4060", "text": "In late 1949 Coutard traveled to the Radium Station of Copenhagen, where the director, Jens Nielsen, was one of his few remaining followers. [ 25 ]  He experienced an  intracerebral hemorrhage  on a trip to France to visit his sister's family in December 1949. [ 27 ]  After several months of illness, Coutard died at his sister's home in Le Mans on 16 March 1950. [ 28 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4061", "text": "While Coutard's experiments in final years were considered unorthodox by his peers, his earlier contributions helped radiation therapy become an established treatment for people with cancer. Grigg described Coutard's most important contribution as \"teaching a generation of radiologists to observe their patients carefully and to record painstakingly the clinical course of treatment\". [ 17 ]  Coutard's protracted-fractional method laid the groundwork for modern dose fractionation methods, [ 29 ]  and he is also remembered for being the first to present results on X-ray imaging of the larynx. During his lifetime, he published about 35 papers in addition to his 1949 monograph. [ 17 ]  His hometown, Marolles-les-Braults, later named a square near the center of the town after him. [ 28 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4062", "text": "D50  in medicine is the half-maximal  dose : the dose that produces 50% of the maximum response. [ 1 ]   It may specifically refer to the radiation dose required to achieve a 50%  tumor control probability . [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4063", "text": "Deep inspiration breath-hold  (DIBH) is a method of delivering  radiotherapy  while limiting  radiation exposure  to the heart and lungs. [ 1 ]  It is used primarily for treating left-sided  breast cancer ."}
{"_id": "WikiPedia_Radiology$$$corpus_4064", "text": "The technique involves a patient holding their breath during treatment. In DIBH techniques, treatment is only delivered at certain points in the breathing cycle, where the patient holds their breath. Since the relative positions of organs in the chest naturally changes during breathing, this allows treatment to be delivered to the target (tumour) while other organs are in the optimal position to receive least dose. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4065", "text": "In the DIBH technique, the patient is initially maintained at quiet tidal  breathing  (i.e. normal, relaxed breathing), [ 3 ]  followed by a deep inspiration, a deep expiration, a second deep inspiration, and breath-hold. At this point the patient is at approximately 100%  vital capacity , and simulation, verification, and treatment take place during this phase of breath-holding. [ 4 ]  DIBH is performed with several tangential fields for left-sided breast cancer. A patient is instructed to hold the breath while viewing the breathing pattern and the breath-hold position through a head-mounted mirror, thereby ensuring reproducibility of the breath-hold position in each delivery. [ 5 ]  A pair of video goggles may also be used for monitoring the breathing cycle. Patients who cannot maintain DIBH can still benefit from lung tracking techniques, for example  4DCT . [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4066", "text": "There are two basic methods of performing DIBH: free-breathing breath-hold, and  spirometry -monitored deep inspiration breath hold. [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4067", "text": "Free-breathing breath-hold, also known as real-time position management (RPM) DIBH utilises an infra-red camera and markers placed on the patient to track movement of their chest, and their breathing. [ 8 ]  Another device for DIBH is known as Abches that monitors the breathing pattern. [ 9 ]  With the Abches, a patient is instructed to hold the breath at a specified breathing position by viewing a breathing level indicator, thereby reproducing an identical breath-hold position. [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4068", "text": "Spirometry based designs are known as active breathing coordinator (ABC) DIBH systems. ABC utilises a mouth piece for the patient which can be used to control the flow of air to provide more reproducible results. [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4069", "text": "The DIBH technique provides an advantage to conventional free-breathing treatment by decreasing lung density, reducing normal safety margins, and enabling more accurate treatment. These improvements contribute to the effective exclusion of normal lung tissue from the high-dose region and permit the use of higher treatment doses without increased risks of  toxicity . [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4070", "text": "Treatment of patients with the DIBH technique is feasible in a clinical setting. With this technique, consistent lung inflation levels are achieved in patients, as judged by both spirometry and verification films. Breathing-induced tumor motion is significantly reduced using DIBH compared to free breathing, enabling better target coverage. [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4071", "text": "There is currently no clear selection criteria to predict which patients will benefit most from the DIBH technique, other than left  breast  laterality. There is evidence to suggest  parasagittal  cardiac contact distance is a promising metric for selection and should be assessed in all future DIBH planning studies. [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4072", "text": "Diffusing Alpha-emitters Radiation Therapy  or  DaRT  is an  alpha-particle -based  radiation therapy  for the treatment of  solid tumors . [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4073", "text": "This therapy was developed at  Tel Aviv University  in Israel, by Professors Itzhak Kelson and Yona Keisari. The treatment is delivered by the intratumoral insertion of metal tubes called \u201cseeds\u201d, which have  Radium-224  atoms fixed to their surface. When the radium decays, its short-lived daughter Radon-220 is released from the seed through recoil energy. [ 3 ]  The daughters of Radon-220, in particular Pb-212, disperse in the tumor, and emit high-energy alpha particles, which destroy the tumor. Because the alpha-emitting atoms diffuse only a few millimeters in tissue, the DaRT eradicates the tumor cells and spares the surrounding healthy tissue. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4074", "text": "Alpha radiation is a nuclear phenomenon in which a heavy radionuclide emits an energetic alpha particle (consisting of two protons and two neutrons) and transmutes to a different radionuclide. The emitted alpha particle has a range in tissue of only 40-90 microns, which minimizes collateral damage when used for treatment purposes. However, this also limits its ability to destroy tumors that are many millimeters in diameter. Alpha radiation possesses a potent cell-killing capability because it has a high  linear energy transfer  (LET) which translates into a high  Relative Biological Effectiveness  (RBE). [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4075", "text": "The invention of DaRT makes possible the use of alpha radiation for treating solid tumors, because it overcomes the range limitation of alpha particles in tissue. The daughter atoms of Radium-224 can each diffuse several millimeters in tumor tissue, while emitting alpha particles. The tumor-killing capability of DaRT comes mainly from the ability of alpha radiation to irreparably break the double stranded DNA in tumor cells. [ 5 ]  This capability does not seem to be dependent on the stage of the cell cycle or the level of oxygenation of the cancer cell. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4076", "text": "Preclinical studies have demonstrated that DaRT can effectively damage all solid tumor types. Studies of 10 different tumor types in mice demonstrated that all responded to DaRT. [ 6 ] [ 7 ] [ 8 ] [ 9 ] [ 10 ] [ 11 ] [ 12 ] [ excessive citations ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4077", "text": "In preclinical studies, DaRT effectiveness was enhanced when combined with standard chemotherapies such as 5-FU. In addition, DaRT was able to turn the tumor into its own vaccine and stimulate a systemic anti-tumor immune response. [ 13 ]  This immune response was effectively augmented by addition of immunostimulants and/or inhibitors of immunosuppressive cells. This immune effect was observed not only as enhanced local tumor destruction at the primary tumor site, but also by elimination of tumor metastases in the lungs. [ 12 ] [ 14 ]   These results suggest that DaRT combined with immunotherapy induces a tumor-specific systemic immune response. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4078", "text": "The first results of the DaRT in human patients, from a pilot study of 28 patients by Prof. Popovtzer (Israel) and Dr. Bellia (Italy), were published in 2020. [ 15 ]  From among this cohort of elderly patients (median age, 80.5 years), 61% had recurrent and previously treated tumors, including 42% who were radioresistant from prior therapy. Patients were diagnosed with histopathologically confirmed  squamous cell carcinoma  of the skin or  head and neck . One-hundred percent of tumors responded to DaRT, with complete responses occurring in greater than 78% of cases, and no major toxicity was noted.  Thirty days after treatment, there was no measurable radioactivity in the blood or urine of patients. Additional studies in larger populations are now ongoing to strengthen support regarding the safety and effectiveness of this technique of intratumoral alpha radiation-based tumor ablation. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4079", "text": "In external beam  Radiotherapy , transverse and longitudinal  dose measurements  are taken by a radiation detector in order to characterise the radiation beams from medical  linear accelerators . [ 1 ]  Typically, an  ionisation chamber  and water phantom are used to create these radiation dose profiles.  Water  is used due to its tissue equivalence."}
{"_id": "WikiPedia_Radiology$$$corpus_4080", "text": "Transverse dose measurements are performed in the x (crossplane) or y (inplane) directions perpendicular to the radiation beam, and at a given depth (z) in the phantom. These are known as  dose profiles .\nDose measurements taken along the z direction create radiation dose distribution known as a depth-dose curve."}
{"_id": "WikiPedia_Radiology$$$corpus_4081", "text": "DVS (Dose Verification System) , developed by Sicel Technologies, was an implantable telemetric, radiation sensor. [ 1 ]  The device was used to measure the amount of  radiation  that was delivered to tumor and/or healthy tissue.  The DVS sensor contained a dosimeter and wireless transmitter inside a sealed, biocompatible glass capsule measuring 0.8\u00a0inches (20mm) long and 0.08\u00a0inches (2.1mm) across. The sensor was implantable transluminally or transdermally. The device had limited adoption by the radiation  oncology  community, sales were thus inadequate for profitability."}
{"_id": "WikiPedia_Radiology$$$corpus_4082", "text": "The company (Sicel) eventually ceased to exist circa 2011. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4083", "text": "A  dose-volume histogram  (DVH) is a  histogram  relating  radiation dose  to tissue  volume  in  radiation therapy  planning. [ 1 ]  DVHs are most commonly used as a plan evaluation tool and to compare doses from different plans or to structures. [ 2 ]  DVHs were introduced by Michael Goitein (who introduced radiation therapy concepts such as the \"beam's-eye-view,\" \"digitally reconstructed radiograph,\" and uncertainty/error in planning and positioning, among others) and Verhey in 1979. [ 3 ]  DVH summarizes 3D dose distributions in a graphical 2D format. In modern radiation therapy, 3D dose distributions are typically created in a computerized  treatment planning system  (TPS) based on a 3D reconstruction of a  CT  scan. The \"volume\" referred to in DVH analysis is a target of radiation treatment, a healthy organ nearby a target, or an arbitrary structure."}
{"_id": "WikiPedia_Radiology$$$corpus_4084", "text": "DVHs can be visualized in either of two ways: differential DVHs or cumulative DVHs. A DVH is created by first determining the size of the dose bins of the histogram. Bins can be of arbitrary size, 0.005\u00a0Gy, 0.2 Gy or 1\u00a0Gy for instance. [ 4 ]  The size is often a matter of tradeoff between accuracy and computational or memory cost (if we store the DVH in a database)."}
{"_id": "WikiPedia_Radiology$$$corpus_4085", "text": "In a differential DVH, bar or column height indicates the volume of structure receiving a dose given by the bin. Bin doses are along the horizontal axis, and structure volumes (either percent or absolute volumes) are on the vertical. The differential DVH takes the appearance of a typical  histogram . The total volume of the  organ  that receives a certain dose is plotted in the appropriate dose bin. [ 5 ]  This volume is determined by the total number of  voxels  characterized by a specified range of dosage for the organ considered. The differential DVH provides information about changes in dose within the structure considered as well as visualization of minimum and maximum dose. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4086", "text": "The cumulative DVH is plotted with bin doses along the horizontal axis, as well. However, the column height of the first bin (e.g., [0, 1]\u00a0Gy) represents the volume of structure receiving a dose greater than or equal to that dose. [ 5 ]  The column height of the second bin (e.g., (1, 2]\u00a0Gy) represents the volume of structure receiving greater than or equal to that dose, etc. With very fine (small) bin sizes, the cumulative DVH takes on the appearance of a smooth line graph. The lines always slope and start from top-left to bottom-right. For a structure receiving a very homogeneous dose (100% of the volume receiving exactly 10\u00a0Gy, for example) the cumulative DVH will appear as a horizontal line at the top of the graph, at 100% volume as plotted vertically, with a vertical drop at 10 Gy on the horizontal axis."}
{"_id": "WikiPedia_Radiology$$$corpus_4087", "text": "A DVH used clinically usually includes all structures and targets of interest in the  radiotherapy  plan, each line plotted a different color, representing a different structure. The vertical axis is almost always plotted as percent volume (rather than absolute volume), as well. [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4088", "text": "Clinical studies have shown that DVH metrics correlate with patient toxicity outcomes. [ 8 ]  A drawback of the DVH methodology is that it offers no spatial information; i.e., a DVH does not show where within a structure a dose is received. [ 9 ]  Also, DVHs from initial radiotherapy plans represent the doses to structures at the start of radiation treatment. As treatment progresses and time elapses, if there are changes (i.e. if patients lose weight, if tumors shrink, if organs change shape, etc.), the original DVH loses its accuracy. [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4089", "text": "Radiation dosimetry  in the fields of  health physics  and  radiation protection  is the measurement, calculation and assessment of the  ionizing radiation  dose absorbed by an object, usually the human body. This applies both internally, due to ingested or inhaled radioactive substances, or externally due to irradiation by sources of radiation."}
{"_id": "WikiPedia_Radiology$$$corpus_4090", "text": "Internal dosimetry  assessment relies on a variety of monitoring, bio-assay or radiation imaging techniques, whilst external dosimetry is based on measurements with a  dosimeter , or inferred from measurements made by other  radiological protection instruments . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4091", "text": "Radiation dosimetry is extensively used for radiation protection; routinely applied to monitor occupational radiation workers, where irradiation is expected, or where radiation is unexpected, such as in the contained aftermath of the  Three Mile Island ,  Chernobyl  or  Fukushima  radiological release incidents. The public dose take-up is measured and calculated from a variety of indicators such as ambient measurements of gamma radiation, radioactive particulate monitoring, and the measurement of levels of  radioactive contamination ."}
{"_id": "WikiPedia_Radiology$$$corpus_4092", "text": "Other significant radiation dosimetry areas are medical, where the required treatment  absorbed dose  and any collateral absorbed dose is monitored, and environmental, such as  radon  monitoring in buildings."}
{"_id": "WikiPedia_Radiology$$$corpus_4093", "text": "There are several ways of measuring absorbed doses from ionizing radiation. People in occupational contact with radioactive substances, or who may be exposed to radiation, routinely carry personal  dosimeters . These are specifically designed to record and indicate the dose received. Traditionally, these were lockets fastened to the external clothing of the monitored person, which contained photographic film known as  film badge dosimeters . These have been largely replaced with other devices such as  Thermoluminescent dosimetry (TLD),  optically stimulated luminescence (OSL), or  Fluorescent Nuclear Tract Detector (FNTD) badges. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4094", "text": "The  International Committee on Radiation Protection  (ICRP) guidance states that if a personal dosimeter is worn on a position on the body representative of its exposure, assuming whole-body exposure, the value of Personal Dose Equivalent Hp(10), is sufficient to estimate an effective dose value suitable for radiological protection. Personal Dose Equivalent is a radiation quantity specifically designed to be used for radiation measurements by personal dosimeters. [ 4 ]  Dosimeters are known as \"legal dosimeters\" if they have been approved for use in recording personnel dose for regulatory purposes. In cases of non-uniform irradiation such personal dosimeters may not be representative of certain specific areas of the body, where additional dosimeters are used in the area of concern."}
{"_id": "WikiPedia_Radiology$$$corpus_4095", "text": "A number of electronic devices known as Electronic Personal Dosimeters (EPDs) have come into general use using semiconductor detection and programmable processor technology. These are worn as badges but can give an indication of instantaneous dose rate and an audible and visual alarm if a dose rate or a total integrated dose is exceeded. A good deal of information can be made immediately available to the wearer of the recorded dose and current dose rate via a local display. They can be used as the main stand-alone dosimeter, or as a supplement to other devices. EPD's are particularly useful for real-time monitoring of dose where a high dose rate is expected which will time-limit the wearer's exposure."}
{"_id": "WikiPedia_Radiology$$$corpus_4096", "text": "In certain circumstances, a dose can be inferred from readings taken by fixed instrumentation in an area in which the person concerned has been working. This would generally only be used if personal dosimetry had not been issued, or a personal dosimeter has been damaged or lost. Such calculations would take a pessimistic view of the likely received dose."}
{"_id": "WikiPedia_Radiology$$$corpus_4097", "text": "Internal dosimetry  is used to evaluate the  committed dose  due to the intake of radionuclides into the human body."}
{"_id": "WikiPedia_Radiology$$$corpus_4098", "text": "Medical dosimetry is the calculation of absorbed dose and optimization of dose delivery in  radiation therapy . It is often performed by a professional health physicist with specialized training in that field. In order to plan the delivery of radiation therapy, the radiation produced by the sources is usually characterized with  percentage depth dose curves  and  dose profiles  measured by a  medical physicist . [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4099", "text": "In radiation therapy, three-dimensional dose distributions are often evaluated using a technique known as  gel dosimetry . [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4100", "text": "Environmental dosimetry is used where it is likely that the environment will generate a significant radiation dose. An example of this is  radon  monitoring. The largest single source of radiation exposure to the general public is naturally occurring radon gas, which comprises approximately 55% of the annual background dose. It is estimated that radon is responsible for 10% of lung cancers in the United States. Radon is a radioactive gas generated by the decay of uranium, which is present in varying amounts in the Earth's crust. Certain geographic areas, due to the underlying geology, continually generate radon which permeates its way to the Earth's surface. In some cases the dose can be significant in buildings where the gas can accumulate. A number of specialised dosimetry techniques are used to evaluate the dose that a building's occupants may receive."}
{"_id": "WikiPedia_Radiology$$$corpus_4101", "text": "Records of legal dosimetry results are usually kept for a set period of time, depending upon the legal requirements of the nation in which they are used."}
{"_id": "WikiPedia_Radiology$$$corpus_4102", "text": "Medical radiation exposure monitoring  is the practice of collecting dose information from radiology equipment and using the data to help identify opportunities to reduce unnecessary dose in medical situations. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4103", "text": "To enable consideration of stochastic health risk, calculations are performed to convert the physical quantity absorbed dose into equivalent and effective doses, the details of which depend on the radiation type and biological context. [ 7 ]  For applications in  radiation protection  and dosimetry assessment the (ICRP) and the  International Commission on Radiation Units and Measurements  (ICRU) have published recommendations and data which are used to calculate these."}
{"_id": "WikiPedia_Radiology$$$corpus_4104", "text": "There are a number of different measures of radiation dose, including  absorbed dose  ( D ) measured in:"}
{"_id": "WikiPedia_Radiology$$$corpus_4105", "text": "Each measure is often simply described as \u2018dose\u2019, which can lead to confusion. Non- SI  units are still used, particularly in the USA, where dose is often reported in rads and dose equivalent in  rems . By definition, 1 Gy = 100 rad and 1 Sv = 100 rem."}
{"_id": "WikiPedia_Radiology$$$corpus_4106", "text": "The fundamental quantity is the absorbed dose ( D ), which is defined as the mean energy imparted [by ionising radiation] (dE) per unit mass (dm) of material (D = dE/dm) [ 8 ]  The SI unit of absorbed dose is the gray (Gy) defined as one joule per kilogram. Absorbed dose, as a point measurement, is suitable for describing localised (i.e. partial organ) exposures such as tumour dose in radiotherapy. It may be used to estimate stochastic risk provided the amount and type of tissue involved is stated. Localised diagnostic dose levels are typically in the 0\u201350 mGy range. At a dose of 1 milligray (mGy) of photon radiation, each cell nucleus is crossed by an average of 1 liberated electron track. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4107", "text": "The absorbed dose required to produce a certain biological effect varies between different types of radiation, such as  photons ,  neutrons  or  alpha particles . This is taken into account by the equivalent dose (H), which is defined as the mean dose to organ T by radiation type R ( D T,R ), multiplied by a weighting factor  W R  . This designed to take into account the  biological effectiveness  (RBE) of the radiation type, [ 8 ]  For instance, for the same absorbed dose in Gy, alpha particles are 20 times as biologically potent as X or gamma rays. The measure of \u2018dose equivalent\u2019 is not organ averaged and now only used for \"operational quantities\". Equivalent dose is designed for estimation of stochastic risks from radiation exposures. Stochastic effect is defined for radiation dose assessment as the  probability  of cancer induction and genetic damage. [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4108", "text": "As dose is averaged over the whole organ; equivalent dose is rarely suitable for evaluation of acute radiation effects or tumour dose in radiotherapy. In the case of estimation of stochastic effects, assuming a  linear dose response , this averaging out should make no difference as the total energy imparted remains the same."}
{"_id": "WikiPedia_Radiology$$$corpus_4109", "text": "Effective dose is the central dose quantity for radiological protection used to specify exposure limits to ensure that the occurrence of stochastic health effects is kept below unacceptable levels and that tissue reactions are avoided. [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4110", "text": "It is difficult to compare the stochastic risk from localised exposures of different parts of the body (e.g. a chest x-ray compared to a CT scan of the head), or to compare exposures of the same body part but with different exposure patterns (e.g. a cardiac CT scan with a cardiac nuclear medicine scan). One way to avoid this problem is to simply average out a localised dose over the whole body. The problem of this approach is that the stochastic risk of cancer induction varies from one tissue to another."}
{"_id": "WikiPedia_Radiology$$$corpus_4111", "text": "The effective dose  E  is designed to account for this variation by the application of specific weighting factors for each tissue ( W T ). Effective dose provides the equivalent whole body dose that gives the same risk as the localised exposure. It is defined as the sum of equivalent doses to each organ ( H T ), each multiplied by its respective tissue weighting factor ( W T )."}
{"_id": "WikiPedia_Radiology$$$corpus_4112", "text": "Weighting factors are calculated by the International Commission for Radiological Protection (ICRP), based on the risk of cancer induction for each organ and adjusted for associated lethality, quality of life and years of life lost. Organs that are remote from the site of irradiation will only receive a small equivalent dose (mainly due to scattering) and therefore contribute little to the effective dose, even if the weighting factor for that organ is high."}
{"_id": "WikiPedia_Radiology$$$corpus_4113", "text": "Effective dose is used to estimate stochastic risks for a \u2018reference\u2019 person, which is an average of the population. It is not suitable for estimating stochastic risk for individual medical exposures, and is not used to assess acute radiation effects."}
{"_id": "WikiPedia_Radiology$$$corpus_4114", "text": "Radiation dose refers to the amount of energy deposited in matter and/or biological effects of radiation, and should not be confused with the unit of radioactive activity ( becquerel , Bq) of the source of radiation, or the strength of the radiation field (fluence). The article on the  sievert  gives an overview of dose types and how they are calculated. Exposure to a source of radiation will give a dose which is dependent on many factors, such as the activity, duration of exposure, energy of the radiation emitted, distance from the source and amount of shielding."}
{"_id": "WikiPedia_Radiology$$$corpus_4115", "text": "The worldwide average background dose for a human being is about 3.5 mSv per year  [1] , mostly from  cosmic radiation  and natural  isotopes  in the earth. The largest single source of radiation exposure to the general public is naturally occurring radon gas, which comprises approximately 55% of the annual background dose. It is estimated that radon is responsible for 10% of lung cancers in the United States."}
{"_id": "WikiPedia_Radiology$$$corpus_4116", "text": "Because the human body is approximately 70% water and has an overall density close to 1 g/cm 3 , dose measurement is usually calculated and calibrated as dose to water."}
{"_id": "WikiPedia_Radiology$$$corpus_4117", "text": "National standards laboratories such as the  National Physical Laboratory, UK  (NPL) provide calibration factors for ionization chambers and other measurement devices to convert from the instrument's readout to absorbed dose. The standards laboratories operates as a  primary standard , which is normally calibrated by absolute  calorimetry  (the warming of substances when they absorb energy). A user sends their secondary standard to the laboratory, where it is exposed to a known amount of radiation (derived from the primary standard) and a factor is issued to convert the instrument's reading to that dose. The user may then use their secondary standard to derive calibration factors for other instruments they use, which then become tertiary standards, or field instruments."}
{"_id": "WikiPedia_Radiology$$$corpus_4118", "text": "The NPL operates a graphite-calorimeter for absolute photon dosimetry. Graphite is used instead of water as its  specific heat capacity  is one-sixth that of water and therefore the temperature increase in graphite is 6 times higher than the equivalent in water and measurements are more accurate. Significant problems exist in insulating the graphite from the surrounding environment in order to measure the tiny temperature changes. A lethal dose of radiation to a human is approximately 10\u201320 Gy. This is 10\u201320 joules per kilogram. A 1\u00a0cm 3  piece of graphite weighing 2\u00a0grams would therefore absorb around 20\u201340 mJ. With a specific heat capacity of around 700 J\u00b7kg \u22121 \u00b7K \u22121 , this equates to a temperature rise of just 20 mK."}
{"_id": "WikiPedia_Radiology$$$corpus_4119", "text": "Dosimeters in radiotherapy ( linear particle accelerator  in external beam therapy) are routinely calibrated using  ionization chambers [ 14 ]  or diode technology or gel dosimeters. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4120", "text": "Although the United States Nuclear Regulatory Commission permits the use of the units  curie , rad, and  rem  alongside SI units, [ 15 ]  the  European Union   European units of measurement directives  required that their use for \"public health ... purposes\" be phased out by 31 December 1985. [ 16 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4121", "text": "The  EGS  ( Electron Gamma Shower ) computer code system is a general purpose package for the  Monte Carlo  simulation of the coupled transport of  electrons  and  photons  in an arbitrary geometry for particles with energies from a few keV up to several hundreds of GeV. [ 1 ]  It originated at  SLAC  but  National Research Council of Canada  and  KEK  have been involved in its development since the early 80s."}
{"_id": "WikiPedia_Radiology$$$corpus_4122", "text": "Development of the original EGS code ended with version EGS4. Since then two groups have re-written the code with new physics:"}
{"_id": "WikiPedia_Radiology$$$corpus_4123", "text": "EGSnrc is a general-purpose software toolkit that can be applied to build Monte Carlo simulations of coupled electron-photon transport, for particle energies ranging from 1 keV to 10 GeV. It is widely used internationally in a variety of radiation-related fields. The EGSnrc implementation improves the accuracy and precision of the charged particle transport mechanics and the atomic scattering cross-section data. [ 4 ] [ 5 ] [ 6 ]  The charged particle multiple scattering algorithm allows for large step sizes without sacrificing accuracy - a key feature of the toolkit that leads to fast simulation speeds. [ 7 ] [ 8 ]  EGSnrc also includes a C++ class library called egs++ that can be used to model elaborate geometries and particle sources."}
{"_id": "WikiPedia_Radiology$$$corpus_4124", "text": "EGSnrc is open source and distributed on  GitHub  under the  GNU Affero General Public License . Download EGSnrc for free, submit bug reports, and contribute pull requests on a group GitHub page. [ 9 ]  The documentation for EGSnrc is also available online. [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4125", "text": "EGSnrc is distributed with a wide range of applications that utilize the radiation transport physics to calculate specific quantities. These codes have been developed by numerous authors over the lifetime of EGSnrc to support the large user community. It is possible to calculate quantities such as  absorbed dose ,  kerma , particle fluence, and much more, with complex geometrical conditions. One of the most well-known EGSnrc applications is BEAMnrc, which was developed as part of the OMEGA project. This was a collaboration between the  National Research Council of Canada  and a research group at the  University of Wisconsin\u2013Madison . All types of medical  linear accelerators  can be modelled using the BEAMnrc's component module system. [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4126", "text": "This  scientific software  article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Radiology$$$corpus_4127", "text": "Electron therapy  or  electron beam therapy  ( EBT ) is a kind of  external beam radiotherapy  where  electrons  are directed to a  tumor  site for medical treatment of cancer."}
{"_id": "WikiPedia_Radiology$$$corpus_4128", "text": "Electron beam therapy is performed using a medical  linear accelerator . The same device can also be used to produce high energy photon beams. When electrons are required, the X-ray target is retracted out of the beam and the electron beam is  collimated  with a piece of apparatus known as an applicator or an additional collimating insert, constructed from a low melting point alloy."}
{"_id": "WikiPedia_Radiology$$$corpus_4129", "text": "Electron beams have a finite range, after which dose falls off rapidly. Therefore, they spare deeper healthy tissue. The depth of the treatment is selected by the appropriate energy.  Unlike photon beams there is no surface sparing effect, so electron therapy is used when the target extends to the patient's  skin ."}
{"_id": "WikiPedia_Radiology$$$corpus_4130", "text": "Electron beam therapy is used in the treatment of superficial tumors like cancer of skin regions, or total skin (e.g.  mycosis fungoides ), diseases of the limbs (e.g.  melanoma  and  lymphoma ), nodal irradiation, and it may also be used to boost the radiation dose to the surgical bed after  mastectomy  or  lumpectomy . For deeper regions  intraoperative electron radiation therapy  might be applied."}
{"_id": "WikiPedia_Radiology$$$corpus_4131", "text": "ESTRO  (The European Society for Radiotherapy and Oncology) [ 1 ]  is a  scientific society  established in 1980 in  Milan ,  Italy , [ 2 ] [ 3 ] [ 4 ]  founded by  Maurice Tubiana ,  Jerzy Einhorn , [ 5 ]   Klaas Breur , [ 6 ]   Michael Peckham , [ 7 ]  and  Emmanuel van der Schueren . It aims to advance  radiation oncology  to improve  cancer treatment  outcomes through education, research, and quality assurance. ESTRO is based in  Brussels ,  Belgium . It is governed by an elected Board and has several committees focused on areas such as education, science, and clinical practice. The society collaborates with other oncology organizations and works to promote radiation oncology at the European level. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4132", "text": "ESTRO supports its members through various initiatives:"}
{"_id": "WikiPedia_Radiology$$$corpus_4133", "text": "A  gallium scan  is a type of  nuclear medicine  test that uses either a  gallium-67  ( 67 Ga) or  gallium-68  ( 68 Ga)  radiopharmaceutical  to obtain images of a specific type of tissue, or disease state of tissue.  Gallium   salts  like gallium  citrate  and gallium  nitrate  may be used. The form of salt is not important, since it is the freely dissolved gallium ion Ga 3+  which is active. [ 1 ]  Both  67 Ga and  68 Ga salts have similar uptake mechanisms. [ 2 ]  Gallium can also be used in other forms, for example  68 Ga-PSMA is used for  cancer  imaging. The  gamma emission  of gallium-67 is imaged by a  gamma camera , while the  positron emission  of gallium-68 is imaged by  positron emission tomography  (PET)."}
{"_id": "WikiPedia_Radiology$$$corpus_4134", "text": "Gallium salts are taken up by tumors, inflammation, and both acute and chronic infection, [ 3 ] [ 4 ]  allowing these pathological processes to be imaged. Gallium is particularly useful in imaging  osteomyelitis  that involves the spine, and in imaging older and chronic infections that may be the cause of a  fever of unknown origin . [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4135", "text": "Gallium-68 DOTA scans are increasingly replacing octreotide scans (a type of  indium-111  scan using octreotide as a somatostatin receptor ligand). The gallium-68 is bound to an octreotide derivative chemical such as  DOTATOC  and the positrons it emits are imaged by  PET-CT  scan. Such scans are useful in locating  neuroendocrine tumors  and  pancreatic cancer . [ 7 ] [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4136", "text": "In the past, the gallium scan was the  gold standard  for  lymphoma  staging, until it was replaced by  positron emission tomography  (PET) using  fludeoxyglucose  (FDG). [ 9 ] [ 10 ]  Gallium imaging is still used to image inflammation and  chronic  infections, and it still sometimes locates unsuspected tumors as it is taken up by many kinds of cancer cells in amounts that exceed those of normal tissues. Thus, an increased uptake of gallium-67 may indicate a new or old infection, an inflammatory focus from any cause, or a cancerous tumor."}
{"_id": "WikiPedia_Radiology$$$corpus_4137", "text": "It has been suggested that gallium imaging may become an obsolete technique, with  indium leukocyte imaging  and  technetium antigranulocyte  antibodies replacing it as a detection mechanism for infections. For detection of  tumors , especially lymphomas, gallium imaging is still in use, but may be replaced by  fludeoxyglucose  PET imaging in the future. [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4138", "text": "In infections, the gallium scan has an advantage over indium leukocyte imaging in imaging  osteomyelitis  (bone infection) of the spine, lung infections and inflammation, and for chronic infections. In part this is because gallium binds to  neutrophil  membranes, even after neutrophil death. Indium leukocyte imaging is better for acute infections (where neutrophils are still rapidly and actively localizing to the infection), and also for osteomyelitis that does not involve the spine, and for  abdominal  and  pelvic  infections. Both the gallium scan and indium leukocyte imaging may be used to image  fever of unknown origin  (elevated temperature without an explanation). However, the indium leukocyte scan will image only the 25% of such cases which are caused by acute infections, while gallium will also localize to other sources of fever, such as chronic infections and tumors. [ 12 ] [ 13 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4139", "text": "The body generally handles Ga 3+  as though it were  ferric  iron (Fe-III), and thus the free isotope ion is bound (and concentrates) in areas of inflammation, such as an infection site, and also areas of rapid cell division. [ 14 ]  Gallium (III) (Ga 3+ ) binds to  transferrin ,  leukocyte   lactoferrin ,  bacterial   siderophores ,  inflammatory proteins , and cell-membranes in neutrophils, both living and dead. [ 15 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4140", "text": "Lactoferrin is contained within leukocytes. Gallium may bind to lactoferrin and be transported to sites of inflammation, or binds to lactoferrin released during bacterial  phagocytosis  at infection sites (and remains due to binding with  macrophage  receptors). [ 16 ]  Gallium-67 also attaches to the siderophore molecules of bacteria themselves, and for this reason can be used in  leukopenic  patients with bacterial infection (here it attaches directly to bacterial proteins, and leukocytes are not needed). [ 17 ]  Uptake is thought to be associated with a range of tumour properties including transferring receptors, anaerobic tumor metabolism and tumor perfusion and  vascular permeability . [ 18 ] [ 19 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4141", "text": "Note that all of these conditions are also seen in PET scans using the gallium-68."}
{"_id": "WikiPedia_Radiology$$$corpus_4142", "text": "The main ( 67 Ga) technique uses  scintigraphy  to produce two-dimensional images. After the tracer has been injected, images are typically taken by a  gamma camera  at 24, 48, and in some cases, 72, and 96 hours later. [ 23 ] [ 24 ]  Each set of images takes 30\u201360 minutes, depending on the size of the area being imaged. The resulting image will have bright areas that collected large amounts of tracer, because inflammation is present or rapid cell division is occurring.  Single-photon emission computed tomography  (SPECT) images may also be acquired. In some imaging centers, SPECT images may be combined with  computed tomography  (CT) scan using either fusion software or SPECT/CT hybrid cameras to superimpose both physiological image-information from the gallium scan, and anatomical information from the CT scan."}
{"_id": "WikiPedia_Radiology$$$corpus_4143", "text": "A common injection dose is around 150  megabecquerels . [ 25 ]  Imaging should not usually be sooner than 24 hours as high background at this time produces false negatives. Forty-eight-hour whole body images are appropriate. Delayed imaging can be obtained even 1 week or longer after injection if bowel is confounding. SPECT can be performed as needed. Oral laxatives or enemas can be given before imaging to reduce bowel activity and reduce dose to large bowel; however, the usefulness of bowel preparation is controversial. [ 24 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4144", "text": "10% to 25% of the dose of gallium-67 is excreted within 24 hours after injection (the majority of which is excreted through the kidneys). After 24 hours the principal excretory pathway is colon. [ 24 ]  The \"target organ\" (organ that receives the largest radiation dose in the average scan) is the colon (large bowel). [ 23 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4145", "text": "In a normal scan, uptake of gallium is seen in wide range of locations which do not indicate a positive finding. These typically include soft tissues,  liver , and bone. Other sites of localisation can be  nasopharyngeal  and  lacrimal  glands, breasts (particularly in  lactation  or  pregnancy ), normally healing wounds, kidneys, bladder and colon. [ 26 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4146", "text": "The positron emitting isotope,  68 Ga, can be used to target  prostate-specific membrane antigen  (PSMA), a  protein  which is present in  prostate cancer  cells. The technique has been shown to improve detection of  metastatic  disease compared to  MRI  or  CT scans . [ 27 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4147", "text": "In December 2020, the U.S.  Food and Drug Administration  (FDA) approved  68 Ga PSMA-11  for medical use in the United States. [ 28 ] [ 29 ]  It is  indicated  for positron emission tomography (PET) of prostate specific membrane antigen (PSMA) positive lesions in men with prostate cancer. [ 30 ] [ 29 ]  It is manufactured by the UCLA Biomedical Cyclotron Facility. [ 29 ]  The FDA approved  68 Ga PSMA-11 based on evidence from two clinical trials (Trial 1/NCT0336847 identical to NCT02919111 and Trial 2/NCT02940262 identical to NCT02918357) of male participants with prostate cancer. [ 29 ]  Some participants were recently diagnosed with the prostate cancer. [ 29 ]  Other participants were treated before, but there was suspicion that the cancer was spreading because of rising prostate specific antigen or PSA. [ 29 ]  The trials were conducted at two sites in the United States. [ 29 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4148", "text": "The FDA considers  68 Ga PSMA-11 to be a  first-in-class medication . [ 31 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4149", "text": "Gallium PSMA scanning is recommended primarily in cases of  biochemical recurrence  of prostate cancer, particularly for patients with low  PSA  values, and in patients with high risk disease where metastases are considered likely. [ 32 ] [ 33 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4150", "text": "An  intravenous  administration of 1.8\u20132.2  megabecquerels  of  68 Ga PSMA-11 per  kilogram  of bodyweight is recommended. Imaging should commence approximately 60 minutes after administration with an acquisition from mid-thigh to the base of the skull. [ 32 ] [ 34 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4151", "text": "68 Ga  DOTA  conjugated  peptides  (including  68 Ga  DOTA-TATE ,  DOTA-TOC  and  DOTA-NOC ) are used in  positron emission tomography  (PET) imaging of  neuroendocrine tumours  (NETs). The scan is similar to the SPECT  octreotide scan  in that an octreotide-based  somatostatin  analogue (such as  edotreotide ) is used as the  radioligand , and there are similar  indications  and uses as ocreotide scans, however image quality is significantly improved. [ 35 ]  Somatostatin receptors are overexpressed in many NETs, so that the  68 Ga DOTA conjugated peptide is preferentially taken up in these locations, and visualised on the scan. [ 36 ]  As well as diagnosis and staging of NETs,  68 Ga DOTA conjugated peptide imaging may be used for planning and  dosimetry  in preparation for  lutetium -177 or  yttrium-90  DOTA  therapy . [ 37 ] [ 38 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4152", "text": "In June 2016, Netspot (kit for the preparation of gallium Ga-68 dotatate injection) was approved for medical use in the United States. [ 39 ] [ 40 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4153", "text": "In August 2019,  68 Ga  edotreotide  injection ( 68 Ga DOTATOC) was approved for medical use in the United States for use with PET imaging for the localization of somatostatin receptor positive neuroendocrine tumors (NETs) in adults and children. [ 41 ] [ 42 ] [ 43 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4154", "text": "The U.S.  Food and Drug Administration  (FDA) approved  68 Ga  edotreotide  (DOTATOC) based on evidence from three clinical trials (Trial 1/NCT#1619865, Trial 2/NCT#1869725, Trial 3/NCT#2441062) of 334 known or suspected neuro-endocrine tumors. [ 42 ]  The trials were conducted in the United States. [ 42 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4155", "text": "Gallium ( 68 Ga) oxodotreotide was approved for medical use in Canada as Netspot in July 2019, [ 44 ]  and as Netvision in May 2022. [ 45 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4156", "text": "The combination germanium (68Ge) chloride / gallium (68Ga) chloride was approved for medical use in the European Union in August 2024. [ 46 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4157", "text": "Other gallium-68 based PET scanning agents may also be based on the principle of attaching peptides to chelators, such as the in-development drug  Ga-68-Trivehexin ."}
{"_id": "WikiPedia_Radiology$$$corpus_4158", "text": "Gallium-67 citrate is produced by a cyclotron. Charged particle bombardment of enriched Zn-68 is used to produce gallium-67. The gallium-67 is then complexed with citric acid to form gallium citrate. The half-life of gallium-67 is 78 hours. [ 47 ]  It decays by  electron capture , then emits de-excitation  gamma rays  that are detected by a gamma camera. Primary emission is at 93  keV  (39% abundance), followed by 185 keV (21%) and 300 keV (17%). [ 48 ] :\u200a64\u200a  For imaging, multiple gamma camera energy windows are used, typically centred around 93 and 184 keV or 93, 184, and 296 keV. [ 24 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4159", "text": "Gallium-68 , which has a 68 minutes half-life, is produced in a  gallium-68 generator  by decay of  germanium-68  with a 271 day half-life or by the irradiation of  zinc-68  through a low energy cyclotron. Use of a generator means a supply of  68 Ga can be produced easily with minimal infrastructure, for example at sites without a  cyclotron , commonly used to produce other PET isotopes.\nIt decays by  positron emission  and  electron capture  into zinc-68. [ 49 ]  Maximum energy of positron emission is at 1.9 MeV. [ 48 ] :\u200a65"}
{"_id": "WikiPedia_Radiology$$$corpus_4160", "text": "The  history of radiation therapy  or  radiotherapy  can be traced back to experiments made soon after the discovery of  X-rays  (1895), when it was shown that exposure to  radiation  produced cutaneous  burns . Influenced by  electrotherapy  and  escharotics \u2014the medical application of caustic substances\u2014doctors began using radiation to treat growths and lesions produced by diseases such as  lupus ,  basal cell carcinoma , and  epithelioma . [ 1 ]  Radiation was generally believed to have bactericidal properties, so when  radium  was discovered, in addition to treatments similar to those used with x-rays, it was also used as an additive to medical treatments for diseases such as  tuberculosis  where there were resistant  bacilli . [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4161", "text": "Additionally, because radiation was found to exist in hot spring waters which were reputed for their curative powers, it was marketed as a  wonder cure  for all sorts of ailments in  patent medicine  and  quack  cures. It was believed by medical science that small doses of radiation would cause no harm and the harmful effects of large doses were temporary. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4162", "text": "The widespread use of radium in medicine ended when it was discovered that physical tolerance was lower than expected and exposure caused long term cell damage that could appear in  carcinoma  up to 40 years after treatment. [ 5 ]  The use of radiation continues today as a treatment for cancer in  radiation therapy ."}
{"_id": "WikiPedia_Radiology$$$corpus_4163", "text": "The  imaging  properties of x-rays were discovered, their practical uses for research and diagnostics were immediately apparent, and soon their use spread in the medical field. X-rays were used to diagnose bone fractures, heart disease, and phthisis. Inventive procedures for different diagnostic purposes were created, such as filling digestive cavities with  bismuth , which allowed them to be seen through tissue and bone. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4164", "text": "During early practical work and scientific investigation, experimenters noticed that prolonged exposure to x-rays created inflammation and, more rarely, tissue damage on the skin. The biological effect attracted the interest of  L\u00e9opold Freund  and  Eduard Schiff , who, only a month or two after R\u00f6ntgen's announcement, suggested they be used in the treatment of disease. [ 7 ]  At approximately the same time,  Emil Grubbe , of Chicago was possibly the first American physician to use x-rays to treat cancer, beginning in 1896, began experimenting in Chicago with medical uses of x-rays. [ 8 ]   Escharotics  by this time had already been used to treat skin malignancies through caustic burns, and  electrotherapy  had also been experimented with, in the aim to stimulate the skin tissue. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4165", "text": "The first attempted x-ray treatment was by  Victor Despeignes , a French physician who used them on a patient with stomach cancer. In 1896, he published a paper with the results: a week-long treatment was followed by a diminution of pain and reduction in the size of the tumor, though the case was ultimately fatal. The results were inconclusive, because the patient was concurrently being given other treatments. [ 9 ]  Freund's first experiment was a tragic failure; he applied x-rays to a  naevus  in order to induce  epilation  and a deep ulcer resulted, which resisted further treatment by radiation. The first successful treatment was by Schiff, working with Freund, in a case of  lupus vulgaris .  A year later, in 1897, the two published a report of their success and this provoked further experimentation in x-ray therapies. [ 10 ]  Thereafter they did a successful treatment of  lupus erythematosus  in 1898. The lesion took a common form of a 'butterfly-patch' which appeared on both sides of the face, and Schiff applied the irradiation to one side only, in order to compare the effects. [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4166", "text": "Within a few months, scientific journals were swamped with accounts of the successful treatment of different types of skin tissue malignancies with x-rays. In Sweden,  Thor Stenbeck  published results of the first successful treatments of  rodent ulcer  and  epithelioma  in 1899, later that year confirmed by  Tage Sj\u00f6gren . [ 12 ]  Soon afterwards, their findings were confirmed by a number of other physicians. [ 13 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4167", "text": "The nature of the active agent in therapeutic treatment was still unknown, and subject to wide dispute. Freund and Schiff believed it to because of electrical discharge,  Nikola Tesla  argued they were because of the  ozone  generated by the x-rays, while others argued that it was the x-rays themselves. Tesla's position was soon refuted, and only the other two theories remained. In 1900,  Robert Kienb\u00f6ck  produced a study based on a series of experiments that demonstrated that it was the x-rays themselves. Studies published in 1899 and 1900 suggested that the rays varied in penetration according to the degree of vacuum in the tube. [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4168", "text": "Niels Finsen , a Faroese-Danish physician, had by that time already pursued interest in the biological effects of light. He published a paper,  Om Lysets Indvirkninger paa Huden  (\"On the effects of light on the skin\") in 1893. Inspired by the discovery that x-rays could have therapeutic effects, he extended his research to examine directed light rays. In 1896, he published a paper on his findings,  Om Anvendelse i Medicinen af koncentrerede kemiske Lysstraaler  (\"The use of concentrated chemical light rays in medicine\"). Finsen discovered that lupus was amenable to treatment by  ultraviolet  rays when separated out by a system of  quartz  crystals, and thereafter created a lamp to sift out the rays. The so-called  Finsen lamp  became widely used in for  phototherapy , and derivatives of it became used when experimenting with other types of radiotherapy. [ 15 ]  Modifications were made to Finsen's original design, and it found its most common forms in the  Finsen-Reyn lamp  and  Finsen-Lomholt lamp  ."}
{"_id": "WikiPedia_Radiology$$$corpus_4169", "text": "By 1905, it was estimated that fully 50 percent of the cases of lupus were successfully healed by Finsen's methods. [ 15 ]  Finsen was soon awarded a  Nobel Prize  for his research."}
{"_id": "WikiPedia_Radiology$$$corpus_4170", "text": "From initial therapeutic experiments, a new field of x-ray therapy was born, referred to as  r\u00f6ntgenotherapy  after  Wilhelm R\u00f6ntgen , the discoverer of x-rays. It was still unclear how the x-rays acted on the skin; however, it was generally agreed upon that the area affected was killed and either discharged or absorbed. [ 17 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4171", "text": "By 1900, there were four well established classes of problems that were treated by x-ray, based on a set of five classes initially outlined by Freund:  1.  in hypertrichosis, for the removal of unwanted hair;  2.  in the treatment of disease of hair and hair follicles in which it was necessary to remove hair;  3.  in the treatment of inflammatory affections on the skin like eczema and acne;  4.  and in the treatment of malignant affections on the skin in cases like lupus and epithelioma. [ 18 ] [ 19 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4172", "text": "Additionally, x-rays were successfully applied to other appearances of  carcinoma , trials were done in treating  leukemia , and because of the supposed bactericidal properties, there were suggestions it could be used in diseases such as tuberculosis. Experiments were also done using x-rays to treat  epilepsy , which had previously also experimentally been treated with electrical currents. [ 20 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4173", "text": "Because of the excitement over the new treatment, literature about the therapeutic effects of x-rays often exaggerated the propensity to cure different diseases. Reports of the fact that in some cases treatment worsened some of the patients' conditions were ignored in favor of hopeful optimism.  Henry G. Piffard  referred to these practitioners as \"radiomaniacs\" and \"radiografters\". It was found that x-rays were only capable of producing a cure in certain cases of the basal cell type of epithelioma and exceedingly unreliable in malignant cancer, not making it a suitable replacement for surgery. In many cases of treatment, the cancer recurred after a period of time. X-ray experiments in pulmonary tuberculosis proved useless. Aside from the medical profession losing faith in the ability of x-ray therapy, the public increasingly viewed it as a dangerous type of treatment. This resulted in a period of pessimism about the use of x-rays, which lasted from about 1905 to 1910 or 1912. [ 21 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4174", "text": "Soon after the discovery of  radium  in 1898 by Pierre and  Marie Curie , there was speculation in whether the radiation could be used for therapy in the same way as that from x-rays. The physiological effect of radium was first observed in 1900 by  Otto Walkhoff , [ 23 ]  and later confirmed by what famously known as the \"Becquerel burn\". In 1901,  Henri Becquerel  had placed a tube of radium in a waistcoat pocket where it had remained for several hours; a week or two after which there was severe inflammation of his skin underneath where the radium had been kept.  Ernest Besnier , a dermatologist, examined the skin and expressed the opinion that it was due to the radium, leading to experiments by Curie which confirmed it. Besnier suggested the use of radium for therapy along the same purposes as x-rays and ultraviolet rays."}
{"_id": "WikiPedia_Radiology$$$corpus_4175", "text": "Becquerel for this purpose loaned some radium to  Henri-Alexandre Danlos  of the  h\u00f4pital St. Louis  in Paris in 1901. [ 24 ]  Danlos successfully treated a few cases of lupus with an admixture of  radium  and  barium chloride . Further trials of radium therapy began, though at a much slower pace than did those using x-rays because radium was expensive and difficult to obtain."}
{"_id": "WikiPedia_Radiology$$$corpus_4176", "text": "Radium was soon seen as a way to treat disorders that were not affected enough by x-ray treatment because it could be applied in a multitude of ways in which x-rays could not. [ 15 ]  Different methods of applying radium had been tested, which fell into two categories: the use of radium emanation (now referred to as  radon ), and the use of radium salts."}
{"_id": "WikiPedia_Radiology$$$corpus_4177", "text": "One method using emanation was through inhalation, where it was mixed with air. Radium inhalation had been most studied in Germany, where regular inhalation institutes were established, and the goal was to target the lungs. That was done either to treat lung diseases, like tuberculosis, or to be absorbed through the surface of the lung to the blood, where it could circulate through the body. It was claimed that the beneficial effects produced by radium water baths were the result of inhalation of the vapors. [ 27 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4178", "text": "Another method of treatment was to condense the emanation at liquid air temperature on substances such as vasoline, glycerine, and lanoline, to apply externally to the part affected; or on quinine, bismuth, subnitrate, and arsenic, to be consumed or applied internally. [ 28 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4179", "text": "Radium emanation was also passed into glass or metal tubes or flat glass-tight applicators and applied in the same way as radium tubes. In other cases was also deposited on metal points or flat surfaces of metal using electrical devices, which had the same level of radioactivity as the parent radium, but lasted a shorter duration. One way of treatment was to then drive the deposits of radioactive material into tissue using galvanic current. It was also a method of applying radium emanation to a specially designed applicator constructed to suit the needs of the patient, who could later take it home. [ 29 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4180", "text": "Dilute solutions of radium salts were also made, meant to be used internally. Patients would be prescribed regular dosages. More rarely, the salts were also suspended in liquids to be injected in subcutaneous treatments, which could be applied locally to affected tissues. That was considered the most expensive method, because the radium used was irreparably lost. [ 28 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4181", "text": "As with radium emanation, solutions of free radium salts were also placed in tubes; in this case, the tubes were made from platinum. In metal tubes, the radium could be employed in a number of ways: externally; to the interior of the body in places like the mouth, nose, esophagus, rectum and vagina; and into the substance of a tumor through incisions. [ 29 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4182", "text": "In 1903, the discoverer of the electron,  J. J. Thomson , wrote a letter to the journal  Nature  in which he detailed his discovery of the presence of radioactivity in well water. Soon after, others found that the waters in many of the world's most famous health springs were also radioactive. This radioactivity is due to the presence of radium emanation produced by the radium that is present in the ground through which the waters flow. In 1904,  Nature  published a study on the natural radioactivity of different mineral waters. [ 30 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4183", "text": "Inspired by this, using preparations of radium salts in bath water was suggested as a way for patients to be treated at home, as the radio-activity in the bathwater was permanent. [ 31 ]  Radium baths became used experimentally to treat  arthritis ,  gout , and  neuralgias ."}
{"_id": "WikiPedia_Radiology$$$corpus_4184", "text": "X-rays and radium were noted by physicians to have different advantages in different cases. The most marked effects produced with radium therapy were with lupus, ulcerous growths, and  keloid , particularly because they could be applied more specifically to tissues than with x-rays. [ 32 ]  Radium was generally to be preferred when a localized reaction was desired, while for x-rays when a large area needed to be treated. [ 33 ]  Radium was also believed to be bactericidal, while x-rays were not. Because they could not be applied locally, x-rays were also found to have worse cosmetic effects than radium when treating malignancies. In certain cases, a combination of x-ray and radium therapy was suggested. In many skin diseases, the ulcers would be treated with radium and the surrounding areas with x-rays so it would positively affect the lymphatic systems. [ 34 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4185", "text": "After using radium in the surgical treatment of tuberculosis, researchers including  B\u00e9la Augustin  and  A. de Szendeffy  soon developed a treatment using radioactive methyholated iodine, which was patented under the name  dioradin  (formed from \"iodine and radium\") in 1911. Application of this treatment was referred to as  iodo-radium therapy , and involved injecting dioradin intramuscularly. It seemed promising to the developers, because in several cases, fever and  hemoptysis  had disappeared. [ 3 ]  Inhalation of iodine alone had been an experimental treatment for tuberculosis in France between 1830 and 1870. [ 35 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4186", "text": "Widespread commercial exploitation of radium only began in 1913, by which time more efficient methods of extracting radium from  pitchblende  had been discovered [ 37 ] [ 38 ]  and the mining of radium had taken off. [ 39 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4187", "text": "The radium commonly used in bath salts, waters, and muds was in low-grade preparations, due to the expense, and their usefulness in curative solutions was questioned, since it had been agreed upon by physicians that radium could only be used successfully in high doses. [ 40 ]  It was believed that even radiation emanation at higher doses than were useful would cause no harm, because the radioactive deposits were found to have been absorbed and released in urine and waste within a period of three hours. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4188", "text": "Radium emanation activators , apparatuses that would apply radium emanation to water, started being produced and marketed. Scientifically constructed emanators were sold to hospitals, universities, and independent researchers. Certain companies advertised that they would only give them out to others on a medical prescription [ 4 ]  and would guarantee the strength of radium in each dose."}
{"_id": "WikiPedia_Radiology$$$corpus_4189", "text": "Many products which imitated emanation activators were more broadly marketed to the public. One such product was the  Revigator , a \"radioactive water crock.\"  A dispensing jar made of radium-containing ore, the idea was that radon produced by the ore would dissolve in the water overnight. It was advertised:  \"Fill jar every night. Drink freely ... when thirsty and upon arising and retiring, average six or more glasses daily.\"  The  American Medical Association  (AMA) was concerned that the public was being fleeced by charlatans. In response, the AMA established guidelines (in effect from 1916 to 1929) that emanators seeking AMA approval had to generate more than 2\u00a0 \u03bc Ci  (74\u00a0 k Bq ) of radon per liter of water in a 24-hour period. Most devices on the market, including the  Revigator , did not meet that standard. [ 41 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4190", "text": "Many other  quack  cures and  patent medicines  were sold on the market.  Radithor , a solution of radium salts, was claimed by its developer  William J. A. Bailey  to have curative properties. Many brands of toothpaste were laced with radium that was claimed to make teeth shine whiter, such as  Doramad Radioactive Toothpaste . Ostensibly, this would be because the radium would kill the bacteria in a person's mouth. One item, called \"Degnen's Radio-Active Eye Applicator\" manufactured by the Radium Appliance Company of Los Angeles, California, was sold as a treatment for  myopia ,  hypermetropia , and  presbyopia . Face creams and powders were sold, with names like 'Revigorette' and 'Tho-radia'. It was also sold as a supplement to smoking cigarettes. Companies also marked radioactive pads and compresses for the treatment of illnesses. [ 42 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4191", "text": "In light of the supposed curative properties of radioactivity, a spa was opened up in  Joachimsthal , the place at which Madame Curie gathered some of her original samples of radium from spring waters. Radon inhalation rooms were set up, where air tubes carried the gas up from a processing tank in the basement; the visitor would then use it through an inhalation apparatus. Baths were set up which were also irradiated, and irradiated air was also filtered through a trumpet-like pipe for inhalation. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4192", "text": "Concerns about radium were brought up before the  United States Senate  by California Senator  John D. Works  as early as 1915. In a floor speech he quoted letters from doctors asking about the efficacy of the products that were marketed. He stressed that radiation had the effect of making many cancers worse, many doctors thought the belief that radium could be used to cure cancers at that stage of the development of therapy was a \"delusion\"\u2014one doctor quoted cited a failure-to-success rate of 100 to 1\u2014and the effects of radium water were undemonstrated. [ 43 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4193", "text": "Around the start of the 1920s, new public health concerns were sparked by the deaths of factory workers at a  radioluminescent  watch factory. In 1932, a well-known industrialist,  Eben Byers  died of radiation poisoning from the use of  Radithor , a radium water guaranteed by the manufacturer to contain 2\u00a0\u03bc Ci  of radium. [ 41 ]  Cases sprung up of the development of carcinoma in patients who had used conventional radium therapy up to 40 years after the original treatments. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4194", "text": "Robley D. Evans made the first measurements of exhaled radon and radium excretion from a former dial painter in 1933. At  MIT  he gathered dependable body content measurements from 27 dial painters. This information was used in 1941 by the  National Bureau of Standards  to establish the  tolerance level  for radium of 0.1\u00a0 \u03bc Ci (3.7\u00a0 k Bq ). [ 44 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4195", "text": "At the International Congress of Oncology in Paris in 1922,  Henri Coutard , a French radiologist working with the  Institut Curie , presented evidence that laryngeal cancer could be treated without disastrous side-effects. Coutard was inspired by the observations of  Claudius Regaud , who found that a single dose of x-rays enough to produce severe skin damage and tissue destruction in a rabbit, if administered in fractions, over a course of days, would sterilize the rabbit but have no effect on subcutaneous tissues. [ 45 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4196", "text": "By 1934, Coutard had developed a protracted, fractionated process that remains the basis for current radiation therapy. [ 46 ]  Coutard's dosage and fractionation were designed to create a severe but recoverable acute mucosal reaction. Unlike previous physicians, who believed that cancerous cells were more affected by radiation, he assumed that the population of cancerous cells had the same sensitivity for regeneration as normal cells. [ 47 ]  Coutard reported a 23% cure rate in the treatment of head and neck cancer. [ 48 ]  In 1935, hospitals everywhere began following his treatment plan. [ 47 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4197", "text": "\"Radiation therapy\" defined as the utilization of electromagnetic or particle radiation in medical therapy has 3 main branches, including  external beam radiation therapy  (teletherapy), locoregional ablative therapy (such as brachytherapy (sealed source radiation therapy), selective internal radiotherapy (SIRT), radiofrequency ablation, microwave ablation, and optical therapy), and systemic therapy (i.e. radiopharmaceutical therapy, such as radioligand therapy and unsealed source therapy)). There are three branches of radiology dealing with these three therapeutic domains: Radiation Oncology (teletherapy and brachytherapy), Interventional Radiology / Interventional Oncology (selective internal radiation therapy (SIRT), locoregional ablative therapy using RF ablation and microwave ablation), and Nuclear Radiology / Nuclear Medicine (using radiopharmaceutical therapy (RPT) and systemic unsealed sources)."}
{"_id": "WikiPedia_Radiology$$$corpus_4198", "text": "Particle therapy  is a special case of \"radiation therapy\" in which \"emitted atomic particles\" (such as electrons, protons, or neutrons) are used for energy delivery in therapy. Particle therapy is heavily used in Nuclear Radiology / Nuclear Medicine (radiopharmaceutical therapeutic agents are based on alpha particles, beta particles, or auger electrons), and to some extent in Radiation Oncology (external electron therapy and recent emerging modalities for external proton therapy). Nuclear Radiology / Nuclear Medicine specializes in the internal delivery of particle therapy whereas Radiation Oncology specializes in the external and locoregional delivery of particle therapy."}
{"_id": "WikiPedia_Radiology$$$corpus_4199", "text": "Intraoperative radiation therapy or  IORT  is a special type of radiation therapy that is delivered immediately after surgical removal of cancer. This method has been employed in breast cancer (TARGeted Intra-operative radiation Therapy or  TARGIT ), brain tumors, and rectal cancers."}
{"_id": "WikiPedia_Radiology$$$corpus_4200", "text": "Radioactive iodine, which has been used to treat thyroid diseases since 1941, survives today primarily in the treatment of  thyrotoxicosis  (hyperthyroidism) and some types of thyroid cancer that absorb iodine. Treatment involves the important iodine isotope  iodine-131  ( 131 I), often simply called \"radioiodine\" (though technically all  radioisotopes  of iodine are radioiodines; see  isotopes of iodine )."}
{"_id": "WikiPedia_Radiology$$$corpus_4201", "text": "The  Imaging and  Radiation Oncology Core (IROC)  is a center for the evaluation of data produced by  clinical trials  funded by the  National Cancer Institute , as part of the  National Clinical Trials Network  \"to provide integrated radiation oncology and diagnostic imaging quality control programs... thereby assuring high quality data for clinical trials designed to improve the clinical outcomes for cancer patients worldwide.\" [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4202", "text": "There are currently six centers: [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4203", "text": "IROC Houston QA Center, at the  MD Anderson Cancer Center"}
{"_id": "WikiPedia_Radiology$$$corpus_4204", "text": "IROC Ohio QA Center, at  Ohio State University Wexner Medical Center   and James Comprehensive Cancer Center."}
{"_id": "WikiPedia_Radiology$$$corpus_4205", "text": "IROC Rhode Island QA Center in Lincoln, Rhode Island, administered by the  University of Massachusetts Medical School"}
{"_id": "WikiPedia_Radiology$$$corpus_4206", "text": "IROC Philadelphia (RT) QA Center, at the ACR Research center in Philadelphia,"}
{"_id": "WikiPedia_Radiology$$$corpus_4207", "text": "IROC Philadelphia (Imaging) QA Center, at the ACR Research center in Philadelphia,"}
{"_id": "WikiPedia_Radiology$$$corpus_4208", "text": "IROC St Louis QA Center at  Washington University School of Medicine"}
{"_id": "WikiPedia_Radiology$$$corpus_4209", "text": "The history of the Rhode Island Center (previously known as QARC) goes back to the late 1970s when  Rhode Island Hospital  was conducting RT QA reviews of  leukemia -based protocols for the  CALGB , which is one of the major NCI-sponsored cooperative groups. Other cooperative groups like the  Pediatric Oncology Group  and the  Children's Cancer Study Group  decided to use the center's quality control. QARC began to seek funding from the NCI in order to manage the large influx of data, and received its first grant in  1980. [ 4 ]  Sixteen years later, in 1996, QARC switched its affiliation from  Brown Medical School  to the  University of Massachusetts Medical School  (UMMS). By late 2003, it moved from the  Roger Williams Medical Center   to offices in  Federal Hill, Providence, Rhode Island ; in August 2010, it relocated to its current site in  Lincoln, Rhode Island ."}
{"_id": "WikiPedia_Radiology$$$corpus_4210", "text": "The  indium white blood cell scan  is a  nuclear medicine  procedure in which  white blood cells  (mostly  neutrophils ) are removed from the patient, tagged with the radioisotope  Indium -111, and then injected intravenously into the patient. The tagged leukocytes subsequently localize to areas of relatively new infection. The study is particularly helpful in differentiating conditions such as  osteomyelitis  from  decubitus ulcers  for assessment of route and duration of  antibiotic  therapy. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4211", "text": "In imaging of infections, the  gallium scan  has a sensitivity advantage over the indium white blood cell scan in imaging  osteomyelitis  (bone infection [ 3 ] ) of the spine, lung infections and inflammation, and in detecting chronic infections. In part, this is because gallium binds to neutrophil membranes, even after neutrophil death, whereas localization of neutrophils labeled with indium requires them to be in relatively good functional order. However, indium leukocyte imaging is better at localizing acute (i.e., new) infections, where live neutrophils are still rapidly and actively localizing to the infection, for imaging for osteomyelitis that does not involve the spine, and for locating abdominal and pelvic infections."}
{"_id": "WikiPedia_Radiology$$$corpus_4212", "text": "Both the gallium scan and indium-111 white blood cell imaging may be used to image  fever of unknown origin  (elevated temperature without an explanation). However, the indium leukocyte scan will localize only to the approximately 25% of such cases which are caused by acute infections, while gallium is more broadly sensitive, localizing to other sources of fever, such as chronic infections and tumors. Gallium may be a better choice for spleen study because gallium does not normally accumulate in the spleen."}
{"_id": "WikiPedia_Radiology$$$corpus_4213", "text": "Intraoperative radiation therapy  (IORT) is  radiation therapy  that is administered during surgery directly in the operating room (hence  intraoperative )."}
{"_id": "WikiPedia_Radiology$$$corpus_4214", "text": "Usually  therapeutic  levels of radiation are delivered to the  tumor bed  while the area is exposed during  surgery . IORT is typically a component in the multidisciplinary treatment of locally advanced and recurrent  cancer , in combination with external beam radiation, surgery, and  chemotherapy . As a growing trend in recent years, IORT can also be used in earlier stage cancers such as prostate and  breast cancer ."}
{"_id": "WikiPedia_Radiology$$$corpus_4215", "text": "IORT was found to be useful and feasible in the multidisciplinary management of many solid tumors but further studies are needed to determine the benefit more precisely. [ 1 ]  Single-institution experiences have suggested a role of IORT e.g. in brain tumors and cerebral metastases, locally advanced and recurrent rectal cancer, skin cancer, retroperitoneal sarcoma, pancreatic cancer, and selected gynaecologic and genitourinary malignancies.  For local recurrences, irradiation with IORT is, besides brachytherapy, the only radiotherapeutic option if repeated EBRT is no longer possible. Generally, the normal tissue tolerance does not allow a second full-dose course of EBRT, even after years. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4216", "text": "On 25 July 2014, the UK National Institute for Health and Care Excellence (NICE) gave provisional recommendation for the use of TARGIT IORT with Intrabeam in the UK National Health Service. [ 4 ]  The 2015 update of guidelines of the Association of Gynecological Oncology (AGO), an autonomous community of the German Society of Gynecology and Obstetrics (DGGG) and the German Cancer Society includes TARGIT IORT during lumpectomy as a recommended option for women with a T1, Grade 1 or 2, ER positive breast cancer. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4217", "text": "The rationale for IORT is to deliver a high dose of radiation precisely to the targeted area with minimal exposure of surrounding tissues which are displaced or shielded during the IORT. Conventional radiation techniques such as external beam radiotherapy (EBRT) following surgical removal of the tumor have several drawbacks: The tumor bed where the highest dose should be applied is frequently missed due to the complex localization of the wound cavity even when modern radiotherapy planning is used. Additionally, the usual delay between the surgical removal of the tumor and EBRT may allow a repopulation of the tumor cells. These potentially harmful effects can be avoided by delivering the radiation more precisely to the targeted tissues leading to immediate sterilization of residual tumor cells. Another aspect is that wound fluid has a stimulating effect on tumor cells. IORT was found to inhibit the stimulating effects of wound fluid. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4218", "text": "Several methods are used to deliver IORT. IORT can be delivered using electron beams  (electron IORT) , orthovoltage (250\u2013300 kV) X-rays (X-ray IORT), high-dose-rate brachytherapy (HDR-IORT), or low-energy (50 kV) x-rays (low-energy IORT)."}
{"_id": "WikiPedia_Radiology$$$corpus_4219", "text": "While IORT was first used in clinical practice in 1905, [ 7 ] [ 8 ]  the modern era of IORT began with the introduction of electron IORT in the mid-1960s by transporting patients from the OR after the tumor was removed to the radiation department to receive their electron IORT. [ 9 ] [ 10 ]   Electron IORT has the advantages of being able to carefully control the depth of radiation penetration while providing a very uniform dose to the tumor bed.  Applied with energies in the range of 3 MeV to 12 MeV, electron IORT can treat to depths of up to 4\u00a0cm over areas as large as 300\u00a0cm\u00b2 (i.e. a 10\u00a0cm diameter circle) and takes only 1\u20133 minutes to deliver the prescribed radiation dose.  A few hospitals built shielded operation rooms in which a conventional linear accelerator was installed to deliver the IORT radiation.  This eliminated the complex logistics involved with patient transportation, but was so costly that only a few hospitals were able to use this approach.  The breakthrough came in 1997, with the introduction of a miniaturized, self-shielded, mobile linear accelerator (Mobetron, IntraOp Corporation, US) [ 11 ]  and a mobile but unshielded linear accelerator (Novac, Liac\u2013SIT, Italy). More than 75,000 patients have been treated with electron IORT, almost half of them since the introduction of mobile electron IORT technology."}
{"_id": "WikiPedia_Radiology$$$corpus_4220", "text": "Early practitioners of IORT treated primarily abdominal malignancies using superficial X-rays (75\u2013125 kV) and later orthovoltage x-rays (up to 300 kV in energy) prior to the advent of technology that enabled high-energy electrons. For the first 75 years, X-ray IORT was used mostly for palliation, but there were a few anecdotal reports of long-term survivors.  In the early 1980s, when the use of electron IORT was increasing and showed promising results for certain indications, a handful of hospitals installed othovoltage units in lightly shielded ORs to see if this lower cost approach could achieve comparable results to that of electron IORT.  This approach was less costly than building a shielded OR for an electron IORT unit and eliminated the logistics involved with patient transportation.  However, it had a number of problems that limited its appeal.  X-ray IORT has a poor uniformity of dose as a function of depth of penetration, the radiation does not stop at a pre-defined depth but continues to deposit radiation to underlying structures, and can do damage to boney structures if too high a dose is delivered.  Despite its long use (since the 1930s), fewer than 1000 patients have been treated with this approach, and it is no longer offered at most centers. [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4221", "text": "This technique was developed in the late 1980s in an attempt to combine the dosimetric advantages of high-dose rate brachytherapy with the challenges of treating some complex anatomic surfaces with IORT. It has the advantage of being lower cost than dedicated electron IORT systems, since many radiation centers already have an HDR system that can be transported to the OR when HDR-IORT is needed.  HDR-IORT can also treat very large and convoluted surfaces. However, it does require a shielded OR or a shielded room in the OR complex to deliver the HDR-IORT. [ 13 ]  The depth of penetration is very limited, typically either \u00bd cm to 1\u00a0cm depth, sometimes requiring extensive surgery due to the limited penetration of the radiation. Treatments tend to be 40 minutes or longer, resulting in greater OR time, more anesthesia and greater blood loss when compared to electron IORT.  There are about 10 to 20 active centers using HDR-IORT for locally advanced and recurrent disease, and approximately 2000 patients have received this treatment, mostly for colorectal cancer, head and neck cancer, and gynecologic cancer."}
{"_id": "WikiPedia_Radiology$$$corpus_4222", "text": "Intrabeam, [ 14 ]  ( Carl Zeiss AG , Germany) received FDA and CE approval in 1999 and is a miniature mobile X-ray source which emits low-energy X-ray radiation (max. 50 kV) in isotropic distribution. Due to the higher ionization density caused by soft X-ray radiation in the tissue, the  relative biological effectiveness  (RBE) of low-energy X-rays on tumor cells is higher when compared to high-energy X-rays or gamma rays which are delivered by linear accelerators. [ 15 ]  The radiation which is produced by low-energy mobile radiation systems has a limited range. For this reason, conventional walls are regarded sufficient to stop the radiation scatter produced in the operating room and no extra measures for radiation protection are necessary. This makes IORT accessible for more hospitals.  Targeted intra-operative radiotherapy  is a low-energy IORT technique. Evaluation of the long-term outcomes in patients who were treated with TARGIT-IORT for breast cancer confirmed that it is as effective as whole breast  external beam radiotherapy  in controlling cancer, and also reduces deaths from other causes [ 16 ]  as shown in a large international randomised clinical trial published in the  British Medical Journal . [ 17 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4223", "text": "Iodine-125  ( 125 I) is a  radioisotope  of  iodine  which has uses in  biological assays ,  nuclear medicine  imaging and in  radiation therapy  as brachytherapy to treat a number of conditions, including  prostate cancer ,  uveal melanomas , and  brain tumors . It is the second longest-lived radioisotope of iodine, after  iodine-129 ."}
{"_id": "WikiPedia_Radiology$$$corpus_4224", "text": "Its  half-life  is 59.392 days and it decays by  electron capture  to an excited state of  tellurium-125 . This state is not the metastable  125m Te, but rather a lower energy state that decays immediately by  gamma decay  with a maximum energy of 35  keV . Some of the excess energy of the excited  125 Te may be  internally converted  ejected electrons (also at 35 keV), or to  x-rays  (from electron  bremsstrahlung ), and also a total of 21  Auger electrons , which are produced at the low energies of 50 to 500 electron volts. [ 3 ]  Eventually, stable ground state  125 Te is produced as the final decay product."}
{"_id": "WikiPedia_Radiology$$$corpus_4225", "text": "In medical applications, the internal conversion and Auger electrons cause little damage outside the cell which contains the isotope atom. The X-rays and gamma rays are of low enough energy to deliver a higher radiation dose selectively to nearby tissues, in \"permanent\" brachytherapy where the isotope capsules are left in place ( 125 I competes with  palladium-103  in such uses). [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4226", "text": "Because of its relatively long half-life and emission of low-energy photons which can be detected by  gamma-counter   crystal detectors ,  125 I is a preferred isotope for  tagging   antibodies  in  radioimmunoassay  and other gamma-counting procedures involving  proteins  outside the body. The same properties of the isotope make it useful for brachytherapy, and for certain nuclear medicine scanning procedures, in which it is attached to proteins ( albumin  or  fibrinogen ), and where a half-life longer than that provided by  123 I is required for diagnostic or lab tests lasting several days."}
{"_id": "WikiPedia_Radiology$$$corpus_4227", "text": "Iodine-125 can be used in  scanning/imaging  the  thyroid , but iodine-123 is preferred for this purpose, due to better  radiation penetration  and shorter half-life (13 hours).  125 I is useful for  glomerular filtration rate  (GFR) testing in the diagnosis or monitoring of patients with  kidney disease . Iodine-125 is used  therapeutically  in  brachytherapy  treatments of  tumors . For  radiotherapy   ablation  of tissues that absorb iodine (such as the thyroid), or that absorb an iodine-containing  radiopharmaceutical , the  beta-emitter   iodine-131  is the preferred isotope."}
{"_id": "WikiPedia_Radiology$$$corpus_4228", "text": "When studying  plant immunity ,  125 I is used as the  radiolabel  in tracking  ligands  to determine which  plant pattern recognition receptors  (PRRs) they bind to. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4229", "text": "125 I is produced by the  electron capture  decay of  125 Xe , which is an artificial isotope of  xenon , itself created by  neutron capture  of near-stable  124 Xe  (it undergoes  double electron capture  with a half life orders of magnitude larger than the age of the universe), which makes up around 0.1% of naturally occurring xenon. Because of the artificial production route of  125 I and its short half-life, its  natural abundance  on Earth is effectively zero."}
{"_id": "WikiPedia_Radiology$$$corpus_4230", "text": "125 I is a reactor-produced radionuclide and is available in large quantities. Its production involves the two following  nuclear reactions :"}
{"_id": "WikiPedia_Radiology$$$corpus_4231", "text": "The irradiation target is the  primordial nuclide   124 Xe, which is the target isotope for making  125 I by  neutron capture . It is loaded into irradiation capsules of the zirconium alloy  zircaloy-2  (a  corrosion  resisting  alloy  transparent to  neutrons ) to a pressure of about  100  bar   (~ 100  atm ) . Upon irradiation with  slow neutrons  in a  nuclear reactor , several  radioisotopes of xenon  are produced. However, only the decay of  125 Xe leads to a radioiodine:  125 I. The other xenon radioisotopes decay either to stable  xenon , or to various  caesium isotopes , some of them radioactive (a.o., the long-lived  135 Cs  ( t \u00bd  = 1.33 Ma) and  137 Cs  ( t \u00bd  = 30 a))."}
{"_id": "WikiPedia_Radiology$$$corpus_4232", "text": "Long  irradiation  times are disadvantageous. Iodine-125 itself has a  neutron capture   cross section  of 900  barns , and consequently during a long irradiation, part of the  125 I formed will be converted to  126 I, a  beta-emitter  and  positron-emitter  with a  half-life  of 12.93\u00a0days, [ 1 ]  which is not medically useful. In practice, the most useful irradiation time in the reactor amounts to a few days. Thereafter, the irradiated gas is allowed to decay for three or four days to eliminate short-lived unwanted radioisotopes, and to allow the newly produced xenon-125 ( t \u00bd  = 17 hours) to decay to iodine-125."}
{"_id": "WikiPedia_Radiology$$$corpus_4233", "text": "To isolate radio-iodine, the irradiated capsule is first cooled at low temperature (to  condense  the free iodine gas onto the capsule inner wall) and the remaining Xe gas is vented in a controlled way and recovered for further use. The inner walls of the capsule are then rinsed with a dilute  NaOH  solution to collect iodine as  soluble   iodide  (I \u2212 ) and  hypoiodite  (IO \u2212 ), according to the standard  disproportionation  reaction of  halogens  in  alkaline  solution. Any  caesium  atom present immediately  oxidizes  and passes into the water as Cs + . In order to eliminate any long-lived  135 Cs and  137 Cs which may be present in small amounts, the solution is passed through a  cation-exchange  column, which exchanges Cs +  for another non-radioactive  cation  (e.g., Na + ). The radioiodine (as  anion  I \u2212  or IO \u2212 ) remains in solution as a mixture iodide/hypoiodite."}
{"_id": "WikiPedia_Radiology$$$corpus_4234", "text": "Iodine-125 is commercially available in dilute  NaOH  solution as  125 I-iodide (or the  hypohalite  sodium  hypoiodite , NaIO). The radioactive concentration lies at 4 to  11 GBq/mL  and the specific radioactivity is  > 75 GBq/\u03bcmol   (7.5 \u00d7 10 16  Bq/mol) . The chemical and radiochemical purity is high. The radionuclidic purity is also high; some  126 I  ( t 1/2  = 12.93 d) [ 1 ]  is unavoidable due to the  neutron capture  noted above. The  126 I tolerable content (which is set by the unwanted isotope interfering with  dose calculations  in  brachytherapy ) lies at about  0.2 atom\u00a0%  ( atom fraction ) of the total iodine (the rest being  125 I)."}
{"_id": "WikiPedia_Radiology$$$corpus_4235", "text": "As of October 2019, there were two producers of iodine-125, the  McMaster Nuclear Reactor  in  Hamilton ,  Ontario , Canada; and a VVR-SM research reactor in Uzbekistan. [ 6 ]  The McMaster reactor is presently the largest producer of iodine-125, producing approximately 60 per cent of the global supply in 2018; [ 7 ]  with the remaining global supply produced at the reactor based in Uzbekistan. Annually, the McMaster reactor produces enough iodine-125 to treat approximately 70,000 patients. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4236", "text": "In November 2019, the research reactor in Uzbekistan shut down temporarily in order to facilitate repairs. The temporary shutdown threatened the global supply of the radioisotope by leaving the McMaster reactor as the sole producer of iodine-125 during the period. [ 6 ] [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4237", "text": "Prior to 2018, the  National Research Universal  (NRU) reactor at  Chalk River Laboratories  in  Deep River , Ontario, was one of three reactors to produce iodine-125. [ 9 ]  However, on March 31, 2018, the NRU reactor was permanently shut down ahead of its scheduled decommissioning in 2028, as a result of a government order. [ 10 ] [ 11 ]  The Russian nuclear reactor equipped to produce iodine-125, was offline as of December 2019. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4238", "text": "The detailed decay mechanism to form the stable daughter nuclide tellurium-125 is a multi-step process that begins with  electron capture . This is followed by a cascade of  electron relaxation  as the core electron hole moves toward the  valence orbitals . The cascade involves many  Auger transitions , each of which cause the atom to become increasingly  ionized . The electron capture produces a tellurium-125 nucleus in an excited state with a half-life of 1.6 ns, which undergoes  gamma decay  emitting a gamma  photon  or an  internal conversion   electron  at 35.5 keV. A second electron relaxation cascade follows the gamma decay before the nuclide comes to rest.  Throughout the entire process an average of 13.3 electrons are emitted (10.3 of which are  Auger electrons ), most with energies less than 400\u00a0eV (79% of yield). [ 12 ]  The internal conversion and Auger electrons from the radioisotope have been found in one study to do little cellular damage, unless the radionuclide is directly incorporated chemically into cellular  DNA , which is not the case for present radiopharmaceuticals which use  125 I as the radioactive label nuclide. [ 13 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4239", "text": "As with other radioisotopes of iodine, accidental iodine-125 uptake in the body (mostly by the  thyroid  gland) can be blocked by the prompt administration of stable  iodine-127  in the form of an iodide salt. [ 14 ] [ 15 ]   Potassium iodide  (KI) is typically used for this purpose. [ 16 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4240", "text": "However, unjustified  self-medicated  preventive administration of stable KI is not recommended in order to avoid disturbing the normal  thyroid function . Such a treatment must be carefully dosed and requires an appropriate KI amount  prescribed  by a specialised physician."}
{"_id": "WikiPedia_Radiology$$$corpus_4241", "text": "Isocenter  in  aerial photography : it is a  point where a line cuts an angle of 90 degree of tier/2. [ clarification needed ] \nIt is the point on the aerial photo platform that directly falls on a line half-way between the Principal point and the Nadir point.\nIn  imaging physics  and  radiation oncology , the  isocenter  is termed as the point in space through which the central rays of the radiation beams pass."}
{"_id": "WikiPedia_Radiology$$$corpus_4242", "text": "In  radiation oncology  there is typically talk of two isocenters:"}
{"_id": "WikiPedia_Radiology$$$corpus_4243", "text": "Radiation isocenter is the point in space through which the central beam of radiation passes whereas the mechanical isocenter is the point where optical beams intersect. The two are closely related but differ in terms of their functionality and working in Space."}
{"_id": "WikiPedia_Radiology$$$corpus_4244", "text": "Isocenter definition in  Radiotherapy :"}
{"_id": "WikiPedia_Radiology$$$corpus_4245", "text": "The point in space relative to the treatment machine about which various components of the linac rotate. The  gantry  rotation defines\na horizontal axis which cuts a vertical axis defined by the rotation of the treatment couch. The treatment collimators also\nrotate about an axis pointing through the isocentre."}
{"_id": "WikiPedia_Radiology$$$corpus_4246", "text": "The  source to isocenter distance  (SIsoD) can be an important parameter to control in determining patient exposure and image quality in diagnostic  computed tomography  and  fluoroscopy ."}
{"_id": "WikiPedia_Radiology$$$corpus_4247", "text": "Jennifer Clare Jones  is an American  radiation oncologist  and biologist. She is an investigator and head of the translational nanobiology section at the  National Cancer Institute ."}
{"_id": "WikiPedia_Radiology$$$corpus_4248", "text": "Jones completed a M.D. and Ph.D. from  Stanford University . She is a board-certified radiation oncologist specialized training in radiosurgery, with graduate and postdoctoral training in both cancer biology and general immunology. [ 1 ]  Her doctoral advisor was  Dale Umetsu \u00a0[ Wikidata ] . Jones' dissertation in 2001 was titled,  Identification of Tapr, a T cell and airway phenotype regulatory locus, and positional cloning of the Tim gene family . [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4249", "text": "Jones is a NIH Stadtman Investigator and head of the translational  nanobiology  section at the  National Cancer Institute . [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4250", "text": "From 2001 to 2003, Jones positionally cloned the T-cell immunoglobulin mucin (TIM) gene family and demonstrated the genetic association between TIMs and immune response profiles. As a  radiation oncologist , her research is focused on developing immune-based therapies that synergize with radiation to produce optimal  anti-tumor  immune responses. Jones develops improved methods to characterize, sort, and perform functional studies of nanoparticles, and has established a translational EV analysis pipeline, with instrumentation for preparation, analysis, counting, and  cytometric  study of  extracellular vesicles . [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4251", "text": "Megavoltage X-rays  are produced by  linear accelerators  (\"linacs\") operating at  voltages  in excess of 1000\u00a0 kV  (1\u00a0MV) range, and therefore have an  energy  in the  MeV  range. The voltage in this case refers to the voltage used to accelerate electrons in the linear accelerator and indicates the maximum possible energy of the photons which are subsequently produced. [ 1 ]   They are used in medicine in  external beam radiotherapy  to treat  neoplasms ,  cancer  and  tumors .   Beams with a voltage range of 4-25 MV are used to treat deeply buried cancers because  radiation oncologists  find that they penetrate well to deep sites within the body. [ 2 ]   Lower energy x-rays, called  orthovoltage X-rays , are used to treat cancers closer to the surface. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4252", "text": "Megavoltage x-rays are preferred for the treatment of deep lying tumours as they are attenuated less than lower energy photons, and will penetrate further, with a lower skin dose. [ 4 ] [ 5 ] [ 6 ]  Megavoltage X-rays also have lower  relative biological effectiveness  than orthovoltage x-rays. [ 7 ]  These properties help to make megavoltage x-rays the most common beam energies typically used for radiotherapy in modern techniques such as  IMRT . [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4253", "text": "The use of megavoltage x-rays for treatment first became widespread with the use of  Cobalt-60 machines  in the 1950s. [ 9 ]  However prior to this other devices had been capable of producing megavoltage radiation, including the 1930s  Van de Graaff generator  and  betatron . [ 10 ] [ 11 ] [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4254", "text": "Microwave thermotherapy  is a type of treatment in which  body tissue  is heated by  microwave  irradiation to damage and kill  cancer cells  or to make cancer cells more sensitive to the effects of  radiation  and certain anticancer drugs."}
{"_id": "WikiPedia_Radiology$$$corpus_4255", "text": "A  monitor unit  ( MU ) is a measure of machine output from a clinical accelerator for  radiation therapy  such as a  linear accelerator  or an  orthovoltage  unit. Monitor units are measured by monitor chambers, which are  ionization chambers  that measure the  dose  delivered by a beam and are built into the treatment head of radiotherapy linear accelerators. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4256", "text": "Linear accelerators are calibrated to give a particular  absorbed dose  under particular conditions, although the definition and measurement configuration may vary among medical clinics. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4257", "text": "The most common definitions are: [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4258", "text": "Some linear accelerators are calibrated using source-to-axis distance (SAD) instead of source-to-surface distance (SSD), and calibration (monitor unit definition) may vary depending on hospital custom."}
{"_id": "WikiPedia_Radiology$$$corpus_4259", "text": "Early radiotherapy was performed using \"constant SSD\" treatments, and so the definition of monitor unit was adopted to reflect this calibration geometry."}
{"_id": "WikiPedia_Radiology$$$corpus_4260", "text": "Modern radiotherapy is performed using  isocentric  treatment  plans , so newer definitions of the monitor unit are based on geometry at the  isocenter  based on the source-to-axis distance (SAD)."}
{"_id": "WikiPedia_Radiology$$$corpus_4261", "text": "Nearly 60% of the reported errors involved a lack of an appropriate independent secondary check of the treatment plan or dose calculation  [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4262", "text": "With the development and technological advances, radiotherapy requires that high doses of radiation are delivered to the tumor with increasing precision. According to the recommendations of the International Commission on Radiation Units and Measurements (ICRU) in Publication 24 \n, [ 6 ]  the delivered dose should not deviate by more than \u00b1 5% of the prescribed dose. More recently, the new ICRU recommendations in Publication 62 [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4263", "text": "Commercially available computerized treatment planning systems are often used in radiotherapy services to perform monitoring unit (MU) calculations to deliver the prescribed dose to the patient. As only a part of the total dose uncertainty originates from the calculation process in treatment planning, the tolerance for accuracy of planning systems has to be smaller. [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4264", "text": "Publications on quality assurance in radiotherapy have recommended routine checks of MU calculations through independent manual calculation. This type of verification can also increase confidence in the accuracy of the algorithm and in the  data integrity  of the beams used, in addition to providing an indication of the limitations of the application of conventional dose calculation algorithms used by planning systems. [ 10 ]  Table 1 lists MU calculation software manufacturers."}
{"_id": "WikiPedia_Radiology$$$corpus_4265", "text": "VMAT"}
{"_id": "WikiPedia_Radiology$$$corpus_4266", "text": "TomoTherapy"}
{"_id": "WikiPedia_Radiology$$$corpus_4267", "text": "CyberKnife"}
{"_id": "WikiPedia_Radiology$$$corpus_4268", "text": "Halcyon"}
{"_id": "WikiPedia_Radiology$$$corpus_4269", "text": "IMRT"}
{"_id": "WikiPedia_Radiology$$$corpus_4270", "text": "A  multileaf collimator  ( MLC ) is a  Collimator  or beam-limiting device that is made of individual \"leaves\" of a high  atomic numbered  material, usually  tungsten , that can move independently in and out of the path of a  radiotherapy beam  in order to shape it and vary its intensity."}
{"_id": "WikiPedia_Radiology$$$corpus_4271", "text": "MLCs are used in external beam radiotherapy to provide conformal shaping of beams. Specifically,  conformal radiotherapy  and  Intensity Modulated Radiation Therapy  (IMRT) can be delivered using MLCs."}
{"_id": "WikiPedia_Radiology$$$corpus_4272", "text": "The MLC has improved rapidly since its inception and the first use of leaves to shape structures in 1965  [ 1 ]  to modern day operation and use. MLCs are now widely used and have become an integral part of any radiotherapy department. MLCs were primarily used for conformal radiotherapy, and have allowed the cost-effective implementation of conformal treatment with significant time saving, [ 2 ]  and also have been adapted for use for IMRT treatments. For conformal radiotherapy the MLC allows conformal shaping of the beam to match the borders of the target tumour. For intensity modulated treatments the leaves of a MLC can be moved across the field to create IMRT distributions (MLCs really provide a  fluence  modulation rather than intensity modulation)."}
{"_id": "WikiPedia_Radiology$$$corpus_4273", "text": "The MLC is an important tool for radiation therapy dose delivery. It was originally used as a surrogate for alloy block field shaping and is now widely used for IMRT. As with any tool used in radiotherapy the MLC must undergo commissioning and quality assurance. Additional commissioning measurements are completed to model a MLC for  treatment planning . Various MLCs are provided by different vendors and they all have unique design features as determined by specifications of design, [ 3 ]  and these differences are quite significant."}
{"_id": "WikiPedia_Radiology$$$corpus_4274", "text": "This article related to  medical equipment  is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Radiology$$$corpus_4275", "text": "Nanoimpellers  are an experimental technology developed to eliminate some of the harmful effects of  chemotherapy  by facilitating treatment of only specific areas of the body. Nanoimpellers are  nanoscale , light-activated containers filled with  cancer -fighting drugs that only release their contents when hit by a specific type of  laser . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4276", "text": "Nanoimpellers for cancer drug delivery were first demonstrated in 2008. [ 2 ] [ 3 ]  Initial work used  ultraviolet light , however the low penetration in tissue and potential for  toxicity  mean this is not well suited for delivery in patients. [ 1 ]  Later work has shifted to using  near infrared  light and two photon excitation (TPE) to trigger release. [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4277", "text": "Neutron generators  are  neutron source  devices which contain compact  linear particle accelerators  and that produce  neutrons  by fusing  isotopes of hydrogen  together. The  fusion  reactions take place in these devices by accelerating either  deuterium ,  tritium , or a mixture of these two isotopes into a metal  hydride  target which also contains deuterium, tritium or a mixture of these  isotopes . Fusion of deuterium atoms (D + D) results in the formation of a  helium-3  ion and a neutron with a kinetic energy of approximately 2.5\u00a0 MeV . Fusion of a deuterium and a tritium atom (D + T) results in the formation of a  helium-4  ion and a neutron with a kinetic energy of approximately 14.1\u00a0MeV. Neutron generators have applications in medicine, security, and materials analysis. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4278", "text": "The basic concept was first developed by  Ernest Rutherford 's team in the  Cavendish Laboratory  in the early 1930s. Using a linear accelerator driven by a  Cockcroft\u2013Walton generator ,  Mark Oliphant  led an experiment that fired deuterium ions into a deuterium-infused metal foil and noticed that a small number of these particles gave off  alpha particles . This was the first demonstration of nuclear fusion, as well as the first discovery of Helium-3 and tritium, created in these reactions. The introduction of new power sources has continually shrunk the size of these machines, from Oliphant's that filled the corner of the lab, to modern machines that are highly portable. Thousands of such small, relatively inexpensive systems have been built over the past five decades."}
{"_id": "WikiPedia_Radiology$$$corpus_4279", "text": "While neutron generators do produce fusion reactions, the number of accelerated ions that cause these reactions is very low. It can be easily demonstrated that the energy released by these reactions is many times lower than the energy needed to accelerate the ions, so there is no possibility of these machines being used to produce net  fusion power . A related concept,  colliding beam fusion , attempts to address this issue using two accelerators firing at each other."}
{"_id": "WikiPedia_Radiology$$$corpus_4280", "text": "Small neutron generators using the deuterium (D, hydrogen-2,  2 H) tritium (T, hydrogen-3,  3 H) fusion reactions are the most common accelerator based (as opposed to radioactive isotopes) neutron sources.  In these systems, neutrons are produced by creating ions of deuterium, tritium, or deuterium and tritium and accelerating these into a hydride target loaded with deuterium, or deuterium and tritium.  The DT reaction is used more than the DD reaction because the yield of the DT reaction is 50\u2013100 times higher than that of the DD reaction."}
{"_id": "WikiPedia_Radiology$$$corpus_4281", "text": "2 P + 2 N = 17.7 MeV  [19,34 MeV - 1,626 MeV]"}
{"_id": "WikiPedia_Radiology$$$corpus_4282", "text": "D + T \u2192 n +  4 He  \u00a0  E n  = 14.1\u00a0MeV"}
{"_id": "WikiPedia_Radiology$$$corpus_4283", "text": "D + D -> p + Positron + 3 x Gamma = 2.5 MeV"}
{"_id": "WikiPedia_Radiology$$$corpus_4284", "text": "high beginning energy: 11,4 MeV\u00a0: D + D \u2192 p + Positron + 2 Gamma +  3 He"}
{"_id": "WikiPedia_Radiology$$$corpus_4285", "text": "E n  =  13.91 MeV is right. -> sum: ca. 2.5 MeV"}
{"_id": "WikiPedia_Radiology$$$corpus_4286", "text": "Calculation:\n6,8 MeV [Proton-> Hypoproton]+   1,26*1,45 +1,26*0,42 [2,11] MeV   [Hyperneutron  -> Neutron]   +  ~ 2x 2.5 [5] MeV   [Hyperneutron-> Hyperproton]  \n2x HN Deuterium + high energie => 3 He + Proton + Positron + 2 x Gamma"}
{"_id": "WikiPedia_Radiology$$$corpus_4287", "text": "Neutrons produced by DD and DT reactions are emitted somewhat  anisotropically  from the target, slightly biased in the forward (in the axis of the ion beam) direction. The anisotropy of the neutron emission from DD and DT reactions arises from the fact the reactions are  isotropic  in the  center of momentum coordinate system (COM)  but this isotropy is lost in the transformation from the COM coordinate system to the  laboratory frame of reference . In both frames of reference, the He nuclei recoil in the opposite direction to the emitted neutron consistent with the law of  conservation of momentum ."}
{"_id": "WikiPedia_Radiology$$$corpus_4288", "text": "The gas pressure in the ion source region of the neutron tubes generally ranges between 0.1 and 0.01\u00a0 mm\u00a0Hg . The  mean free path  of electrons must be shorter than the discharge space to achieve ionization (lower limit for pressure) while the pressure must be kept low enough to avoid formation of discharges at the high extraction voltages applied between the electrodes. The pressure in the accelerating region, however, has to be much lower, as the mean free path of electrons must be longer to prevent formation of a discharge between the high voltage electrodes. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4289", "text": "The ion accelerator usually consists of several electrodes with cylindrical symmetry, acting as an  einzel lens . The ion beam can thus be focused to a small point at the target. The accelerators typically require power supplies of 100\u2013500 kV. They usually have several stages, with voltage between the stages not exceeding 200\u00a0kV to prevent  field emission . [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4290", "text": "In comparison with radionuclide neutron sources, neutron tubes can produce much higher  neutron fluxes  and consistent (monochromatic) neutron energy spectra can be obtained. The neutron production rate can also be controlled. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4291", "text": "The central part of a neutron generator is the particle accelerator itself, sometimes called a neutron tube. Neutron tubes have several components including an ion source, ion optic elements, and a beam target; all of these are enclosed within a vacuum-tight enclosure. High voltage insulation between the ion optical elements of the tube is provided by glass and/or ceramic insulators. The neutron tube is, in turn, enclosed in a metal housing, the accelerator head, which is filled with a dielectric medium to insulate the high voltage elements of the tube from the operating area. The accelerator and ion source high voltages are provided by external power supplies. The control console allows the operator to adjust the operating parameters of the neutron tube. The power supplies and control equipment are normally located within 3\u201310 metres (10\u201330\u00a0ft) of the accelerator head in laboratory instruments, but may be several  kilometers  away in  well logging  instruments."}
{"_id": "WikiPedia_Radiology$$$corpus_4292", "text": "In comparison with their predecessors, sealed neutron tubes do not require  vacuum pumps  and gas sources for operation. They are therefore more mobile and compact, while also durable and reliable. For example, sealed neutron tubes have replaced radioactive  modulated neutron initiators , in supplying a pulse of neutrons to the imploding core of modern  nuclear weapons ."}
{"_id": "WikiPedia_Radiology$$$corpus_4293", "text": "Examples of neutron tube ideas date as far back as the 1930s, pre-nuclear weapons era, by German scientists filing a 1938 German patent (March 1938, patent #261,156) and obtaining a United States Patent (July 1941, USP #2,251,190); examples of present state of the art are given by developments such as the  Neutristor , [ 3 ]  a mostly solid state device, resembling a computer chip, invented at  Sandia National Laboratories  in Albuquerque NM. [ citation needed ]  Typical sealed designs are used in a pulsed mode [ 4 ]  and can be operated at different output levels, depending on the life from the ion source and loaded targets. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4294", "text": "A good ion source should provide a strong  ion beam  without consuming much of the gas. For hydrogen isotopes, production of atomic ions is favored over molecular ions, as atomic ions have higher neutron yield on collision. The ions generated in the ion source are then extracted by an electric field into the accelerator region, and accelerated towards the target. The gas consumption is chiefly caused by the pressure difference between the ion generating and ion accelerating spaces that has to be maintained. Ion currents of 10\u00a0mA at gas consumptions of 40\u00a0cm 3 /hour are achievable. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4295", "text": "For a sealed neutron tube, the ideal ion source should use low gas pressure, give high ion current with large proportion of atomic ions, have low gas clean-up, use low power, have high reliability and high lifetime, its construction has to be simple and robust and its maintenance requirements have to be low. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4296", "text": "Gas can be efficiently stored in a replenisher, an electrically heated coil of zirconium wire. Its temperature determines the rate of absorption/desorption of hydrogen by the metal, which regulates the pressure in the enclosure."}
{"_id": "WikiPedia_Radiology$$$corpus_4297", "text": "The  Penning  source is a low gas pressure,  cold cathode  ion source which utilizes crossed electric and magnetic fields. The ion source anode is at a positive potential, either dc or pulsed, with respect to the source cathode. The ion source voltage is normally between 2 and 7 kilovolts. A magnetic field, oriented parallel to the source axis, is produced by a  permanent magnet . A  plasma  is formed along the axis of the anode which traps electrons which, in turn, ionize gas in the source. The ions are extracted through the exit cathode. Under normal operation, the ion species produced by the Penning source are over 90% molecular ions. This disadvantage is however compensated for by the other advantages of the system."}
{"_id": "WikiPedia_Radiology$$$corpus_4298", "text": "One of the cathodes is a cup made of  soft iron , enclosing most of the discharge space. The bottom of the cup has a hole through which most of the generated ions are ejected by the magnetic field into the acceleration space. The soft iron shields the acceleration space from the magnetic field, to prevent a breakdown. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4299", "text": "Ions emerging from the exit cathode are accelerated through the potential difference between the exit cathode and the accelerator electrode. The schematic indicates that the exit cathode is at ground potential and the target is at high (negative) potential. This is the case in many sealed tube neutron generators. However, in cases when it is desired to deliver the maximum flux to a sample, it is desirable to operate the neutron tube with the target grounded and the source floating at high (positive) potential. The accelerator voltage is normally between 80 and 180 kilovolts."}
{"_id": "WikiPedia_Radiology$$$corpus_4300", "text": "The accelerating electrode has the shape of a long hollow cylinder. The ion beam has a slightly diverging angle (about 0.1  radian ). The electrode shape and distance from target can be chosen so the entire target surface is bombarded with ions. Acceleration voltages of up to 200\u00a0kV are achievable."}
{"_id": "WikiPedia_Radiology$$$corpus_4301", "text": "The ions pass through the accelerating electrode and strike the target. When ions strike the target, 2\u20133 electrons per ion are produced by secondary emission. In order to prevent these secondary electrons from being accelerated back into the ion source, the accelerator electrode is biased negative with respect to the target. This voltage, called the suppressor voltage, must be at least 500 volts and may be as high as a few kilovolts. Loss of suppressor voltage will result in damage, possibly catastrophic, to the neutron tube."}
{"_id": "WikiPedia_Radiology$$$corpus_4302", "text": "Some neutron tubes incorporate an intermediate electrode, called the focus or extractor electrode, to control the size of the beam spot on the target.  The gas pressure in the source is regulated by heating or cooling the gas reservoir element."}
{"_id": "WikiPedia_Radiology$$$corpus_4303", "text": "Ions can be created by electrons formed in high-frequency electromagnetic field. The discharge is formed in a tube located between electrodes, or inside a  coil . Over 90% proportion of atomic ions is achievable. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4304", "text": "Input - target for hyperneutron decay detector: e.g. could be tungsten cones in nested pre-cylinder pre-diodes out of wolfrum\nThe targets used in neutron detector itself are  thin films  of metal such as  titanium ,  scandium , or  zirconium  which are deposited onto a  silver ,  copper  or  molybdenum  substrate. Titanium, scandium, and zirconium form stable chemical compounds called  metal hydrides  when combined with hydrogen or its isotopes. These metal hydrides are made up of two  hydrogen  ( deuterium  or  tritium ) atoms per metal atom and allow the target to have extremely high densities of hydrogen. This is important to maximize the neutron yield of the neutron tube. The gas reservoir element also uses metal hydrides, e.g.  uranium hydride , as the active material."}
{"_id": "WikiPedia_Radiology$$$corpus_4305", "text": "Titanium is preferred to zirconium as it can withstand higher temperatures (200\u00a0\u00b0C), and gives higher neutron yield as it captures  deuterons  better than zirconium. The maximum temperature allowed for the target, above which hydrogen isotopes undergo desorption and escape the material, limits the ion current per surface unit of the target; slightly divergent beams are therefore used. A 1\u00a0microampere ion beam accelerated at 200\u00a0kV to a titanium-tritium target can generate up to 10 8  neutrons per second. The neutron yield is mostly determined by the accelerating voltage and the ion current level. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4306", "text": "An example of a tritium target in use is a 0.2\u00a0mm thick silver disc with a 1\u00a0micrometer layer of titanium deposited on its surface; the titanium is then saturated with tritium. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4307", "text": "Metals with sufficiently low hydrogen diffusion can be turned into deuterium targets by bombardment of deuterons until the metal is saturated. Gold targets under such condition show four times higher efficiency than titanium. Even better results can be achieved with targets made of a thin film of a high-absorption high-diffusivity metal (e.g. titanium) on a substrate with low hydrogen diffusivity (e.g. silver), as the hydrogen is then concentrated on the top layer and can not diffuse away into the bulk of the material. Using a deuterium-tritium gas mixture, self-replenishing D-T targets can be made. The neutron yield of such targets is lower than of tritium-saturated targets in deuteron beams, but their advantage is much longer lifetime and constant level of neutron production. Self-replenishing targets are also tolerant to high-temperature  bake-out  of the tubes, as their saturation with hydrogen isotopes is performed after the bakeout and tube sealing. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4308", "text": "One approach for generating the high voltage fields needed to accelerate ions in a neutron tube is to use a  pyroelectric crystal .  In April 2005 researchers at  UCLA  demonstrated the use of a thermally cycled  pyroelectric  crystal to generate high electric fields in a neutron generator application.  In February 2006 researchers at  Rensselaer Polytechnic Institute  demonstrated the use of two oppositely poled crystals for this application.  Using these low-tech power supplies it is possible to generate a sufficiently high  electric field  gradient across an accelerating gap to accelerate deuterium ions into a deuterated target to produce the D\u00a0+\u00a0D fusion reaction.  These devices are similar in their operating principle to conventional sealed-tube neutron generators which typically use  Cockcroft\u2013Walton  type high voltage power supplies.  The novelty of this approach is in the simplicity of the high voltage source.  Unfortunately, the relatively low accelerating current that pyroelectric crystals can generate, together with the modest pulsing frequencies that can be achieved (a few cycles per minute) limits their near-term application in comparison with today's commercial products (see below).  Also see  pyroelectric fusion . [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4309", "text": "In addition to the conventional neutron generator design described above several other approaches exist to use electrical systems for producing neutrons."}
{"_id": "WikiPedia_Radiology$$$corpus_4310", "text": "Another type of innovative neutron generator is the  inertial electrostatic confinement  fusion device.  This neutron generator avoids using a solid target which will be sputter eroded causing metalization of insulating surfaces. Depletion of the reactant gas within the solid target is also avoided. Far greater operational lifetime is achieved. Originally called a fusor, it was invented by  Philo Farnsworth , the inventor of electronic  television ."}
{"_id": "WikiPedia_Radiology$$$corpus_4311", "text": "Neutron generators find application in semiconductor production industry. They also have use cases in the enrichment of depleted uranium, acceleration of breeder reactors, and activation and excitement of experimental thorium reactors."}
{"_id": "WikiPedia_Radiology$$$corpus_4312", "text": "In material analysis  neutron activation analysis  is used to determine concentration of different elements in mixed materials such as minerals or ores.\nApproximate model of a balancing hyperneutron decay detector with two decay options in normal neutrons and hyperprotons.\nThese follow-up detectors could be developed to be even more precise."}
{"_id": "WikiPedia_Radiology$$$corpus_4313", "text": "Oncology Information System  ( OIS ) is a software solution that manages departmental, administrative and clinical activities in  cancer  care. It aggregates information into a complete  oncology -specific  electronic health record  to support medical information management. The OIS allows the capture of patient history information, the documentation of the treatment response,  medical prescription  of the treatment, the storage of patient documentation and the capture of activities for billing purposes. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4314", "text": "Unlike a  hospital information system  (HIS), which is intended to manage patient records more generally, or  radiological information system  (RIS), intended to track and manage  radiology  requests and workflow, the OIS supports the delivery of integrated care and long-term treatment for cancer patients by collecting data during various phases of treatment, maintaining a history of  treatment fractions ,  screening , prevention, diagnosis, image reviews,  palliative care  and  end-of-life care . An OIS will be designed around the specific requirements of  chemotherapy ,  radiotherapy  and other supportive activities. [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4315", "text": "OIS generally support the following features: [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4316", "text": "Orthovoltage X-rays  are produced by  X-ray tubes  operating at  voltages  in the 100\u2013500  kV  range, and therefore the X-rays have a peak  energy  in the 100\u2013500  keV  range. [ 1 ]  Orthovoltage X-rays are sometimes termed  \"deep\" X-rays  (DXR). [ 2 ]  They cover the upper limit of energies used for diagnostic  radiography , and are used in  external beam radiotherapy  to treat  cancer  and  tumors .  They penetrate tissue to a useful depth of about 4\u20136\u00a0cm. [ 3 ]  This makes them useful for treating  skin , superficial tissues, and ribs, but not for deeper structures such as  lungs  or pelvic organs. [ 4 ]  The relatively low energy of orthovoltage X-rays causes them to interact with matter via different physical mechanisms compared to higher energy  megavoltage X-rays  or radionuclide  \u03b3-rays , increasing their  relative biological effectiveness .  [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4317", "text": "The energy and penetrating ability of the X-rays produced by an X-ray tube increases with the  voltage  on the tube.  External beam radiotherapy began around the turn of the 20th century with ordinary diagnostic X-ray tubes, which used voltages below 150\u00a0kV. [ 6 ]  Physicians found that these were adequate for treating superficial tumors, but not tumors inside the body. Since these low energy X-rays were mostly absorbed in the first few centimeters of tissue, to deliver a large enough radiation dose to buried tumors would cause severe skin burns. [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4318", "text": "Therefore beginning in the 1920s \"orthovoltage\" 200\u2013500 kV X-ray machines were built. [ 8 ]  These were found to be able to reach shallow tumors, but to treat tumors deep in the body more voltage was needed.   By the 1930s and 1940s  megavoltage X-rays  produced by huge machines with 3\u20135 million volts on the tube, began to be employed.  With the introduction of  linear accelerators  in the 1970s, which could produce 4\u201330\u00a0MV beams, orthovoltage X-rays are now considered quite shallow. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4319", "text": "In  biochemistry , the  oxygen effect  refers to a tendency for increased  radiosensitivity  of free  living cells  and organisms in the presence of  oxygen  than in  anoxic or hypoxic  conditions, where the  oxygen tension  is less than 1% of  atmospheric pressure  (i.e., <1% of 101.3 kPa, 760 mmHg or 760 torr)."}
{"_id": "WikiPedia_Radiology$$$corpus_4320", "text": "The oxygen effect has particular importance in external beam  radiation therapy  where the killing of  tumour cells  with  photon  and  electron  beams in well oxygenated regions can be up to three times greater than in a poorly vasculated portion of the tumour."}
{"_id": "WikiPedia_Radiology$$$corpus_4321", "text": "Besides  tumour hypoxia , the oxygen effect is also relevant to  hypoxia  conditions present in the normal physiology of  stem cell  niches such as the  endosteum  adjacent to bone in  bone marrow [ 1 ]  and the  epithelium layer  of the  intestine . [ 2 ]  In addition, there are non-malignant diseases where oxygenated tissues can become hypoxic such as in stenosed  coronary arteries  associated with  cardiovascular disease . [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4322", "text": "Holthusen (1921) [ 4 ]  first quantified the oxygen effect finding 2.5 to 3.0-fold less hatching eggs of the  nematode   Ascaris  in oxygenated compared to anoxic conditions, which was incorrectly assigned to changes in  cell division . However, two years later, Petry (1923) [ 5 ]  first attributed oxygen tension as affecting  ionizing radiation  effects on vegetable seeds. Later, the implications of the effects of oxygen on  radiotherapy  were discussed by Mottram (1936). [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4323", "text": "A key observation limiting hypotheses to explain the biological mechanisms of the oxygen effect is that the gas  nitric oxide  is a  radiosensitizer  with similar effects to oxygen observed in tumour cells. [ 7 ]  Another important observation is that oxygen must be present at irradiation or within milliseconds afterward for the oxygen effect to take place. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4324", "text": "The best known explanation of the oxygen effect is the oxygen fixation hypothesis developed by Alexander in 1962, [ 9 ]  which posited that radiation-induced non-restorable or \"fixed\" nuclear  DNA lesions  are lethal to cells in the presence of  diatomic oxygen . [ 10 ] [ 11 ]  Recent hypotheses include one based on oxygen-enhanced damage from first principles. [ 12 ]  Another hypothesis posits that ionizing radiation provokes  mitochondria  to produce reactive oxygen (and nitrogen species), which are leakage during  oxidative phosphorylation  that varies with a hyperbolic saturation relationship observed with both the oxygen and nitric oxide effects. [ 13 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4325", "text": "The oxygen effect is quantified by measuring the radiation sensitivity or  Oxygen Enhancement Ratio  (OER) of a particular biological effect (e.g.,  cell death  or  DNA damage ), [ 14 ]  which is the ratio of doses under pure oxygen and anoxic conditions. Consequently, OER varies from unity in anoxia to a maximum value for 100% oxygen of typically up to three for low ionizing-density-radiation ( beta -,  gamma -, or  x-rays ), or so-called low  linear energy transfer  (LET) radiations."}
{"_id": "WikiPedia_Radiology$$$corpus_4326", "text": "Radiosensitivity varies most rapidly for oxygen partial pressures below ~1% atmospheric (Fig. 1). Howard-Flanders and Alper (1957) [ 15 ]  developed a formula for the  hyperbolic  function of OER and its variation with oxygen concentration, or oxygen pressure in air."}
{"_id": "WikiPedia_Radiology$$$corpus_4327", "text": "Radiobiologists  identified additional characteristics of the oxygen effect that influence radiotherapy practices. They found that the maximum OER value diminishes as the  ionizing -density of the radiation increases (Fig. 2), from low-LET to high-LET radiations. [ 16 ]  The OER is unity irrespective of the  oxygen tension  for alpha-particles of high-LET around 200 keV/\u03bcm. The OER is reduced for low doses as evaluated for cultured mammalian cells exposed to  x-rays  under aerobic (21% O2, 159 mmHg) and anoxic (nitrogen) conditions. [ 17 ]  Typical  fractionation  treatments are daily 2 Gy exposures, as below this dose the so-called 'shoulder' or repair region of the  cell survival curve  is encroached upon reducing the OER (Fig. 3)."}
{"_id": "WikiPedia_Radiology$$$corpus_4328", "text": "In  optics , a  pencil  or  pencil of rays , also known as a  pencil beam  or  narrow beam , is a geometric construct ( pencil of half-lines ) used to describe a  beam  or portion of a beam of  electromagnetic radiation  or charged  particles , typically in the form of a  cone  or  cylinder ."}
{"_id": "WikiPedia_Radiology$$$corpus_4329", "text": "Antennas which strongly bundle in  azimuth  and  elevation  are often described as \"pencil-beam\" antennas. For example, a  phased array antenna  can send out a beam that is extremely thin. Such antennas are used for tracking radar, and the process is known as  beamforming ."}
{"_id": "WikiPedia_Radiology$$$corpus_4330", "text": "In  optics , the  focusing  action of a  lens  is often described in terms of pencils of  rays .  In addition to conical and cylindrical pencils, optics deals with  astigmatic  pencils as well. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4331", "text": "In  electron optics ,  scanning electron microscopes  use narrow pencil beams to achieve a deep  depth of field . [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4332", "text": "Ionizing radiation  used in  radiation therapy , whether  photons  or  charged particles , such as  proton therapy  and  electron therapy  machines, is sometimes delivered through the use of pencil beam scanning. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4333", "text": "In  backscatter X-ray  imaging a pencil beam of x-ray radiation is used to scan over an object to create an intensity image of the Compton-scattered radiation."}
{"_id": "WikiPedia_Radiology$$$corpus_4334", "text": "A 1675 work describes a pencil as \"a double cone of rays, joined together at the base.\" [ 4 ]  In his 1829  A System of Optics ,  Henry Coddington  defines a pencil as being \"a parcel of light proceeding from some one point\", whose form is \"generally understood to be that of a right cone\" and which \"becomes cylindrical when the origin is very remote\". [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4335", "text": "This  optics -related article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Radiology$$$corpus_4336", "text": "Pencil beam scanning  is the practice of steering a beam of radiation or charged particles across an object. It is often used in  proton therapy , to reduce unnecessary radiation exposure to surrounding non-cancerous cells."}
{"_id": "WikiPedia_Radiology$$$corpus_4337", "text": "Ionizing radiation   photons  or  x-rays  ( IMRT ) use pencil beam scanning to precisely target a tumor. [ 1 ]  Photon pencil beam scans are defined as crossing of two beams to a fine point."}
{"_id": "WikiPedia_Radiology$$$corpus_4338", "text": "Several  charged particles  devices used with  Proton therapy  cancer centers use pencil beam scanning. [ 2 ]  The newer proton therapy machines use a pencil beam scanning technology. [ 3 ] \nThis technique is also called spot scanning. [ 4 ]  The  Paul Scherrer Institute  was the developer of spot beam. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4339", "text": "Varian's IMPT system uses all pencil-beam controlled protons where the beam intensity can also be controlled at this small level. This can be done by going back and forth over a previously radiated area during the same radiation session."}
{"_id": "WikiPedia_Radiology$$$corpus_4340", "text": "In  radiotherapy , a  percentage depth dose curve  (PDD) (sometimes  percent  depth dose curve) relates the  absorbed dose  deposited by a radiation beam into a medium as it varies with depth along the axis of the beam. The dose values are divided by the maximum dose, referred to as d max , yielding a plot in terms of percentage of the maximum dose. Dose measurements are generally made in water or \"water equivalent\" plastic with an  ionization chamber , since water is very similar to human tissue with regard to radiation scattering and absorption."}
{"_id": "WikiPedia_Radiology$$$corpus_4341", "text": "Percent depth dose (PDD), which reflects the overall percentage of dose deposited as compared to the depth of maximum dose, depends on the depth of interest, beam energy, field size, and SSD (source to surface distance) as follows. Of note, PDD generally refers to depths  greater than  the depth of maximum dose"}
{"_id": "WikiPedia_Radiology$$$corpus_4342", "text": "Positron emission tomography for bone imaging,  as an  in vivo  tracer technique, allows the measurement of the regional concentration of  radioactivity  proportional to the image  pixel  values averaged over a region of interest (ROI) in bones. Positron emission tomography is a  functional imaging  technique that uses [ 18 F]NaF  radiotracer  to visualise and quantify regional  bone metabolism  and blood flow. [ 18 F]NaF has been used for imaging bones for the last 60 years. This article focuses on the  pharmacokinetics  of [ 18 F]NaF in bones, and various semi-quantitative and quantitative methods for quantifying regional bone metabolism using [ 18 F]NaF PET images."}
{"_id": "WikiPedia_Radiology$$$corpus_4343", "text": "The measurement of regional bone metabolism is critical to understand the  pathophysiology  of metabolic bone diseases."}
{"_id": "WikiPedia_Radiology$$$corpus_4344", "text": "The chemically stable  anion  of  Fluorine-18-Fluoride  is a  bone -seeking radiotracer in skeletal imaging. [ 18 F]NaF has an affinity to deposit at areas where the bone is newly mineralizing. [ 5 ] [ 7 ] [ 8 ] [ 9 ] [ 10 ]  Many studies have [ 18 F]NaF PET to measure  bone metabolism  at the  hip , [ 3 ]   lumbar spine , and  humerus . [ 11 ]  [ 18 F]NaF is taken-up in an exponential manner representing the equilibration of tracer with the extracellular and cellular fluid spaces with a  half-life  of 0.4 hours, and with kidneys with a half-life of 2.4 hours. [ 12 ]  The single passage extraction of [ 18 F]NaF in bone is 100%. [ 13 ]  After an hour, only 10% of the injected activity remains in the  blood . [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4345", "text": "18 F- ions are considered to occupy  extracellular fluid  spaces because, firstly, they equilibrate with  transcellular fluid  spaces and secondly, they are not entirely extracellular ions. [ 15 ] [ 16 ] [ 17 ]  Fluoride undergoes equilibrium with  hydrogen fluoride , which has a high permeability allowing fluoride to cross the plasma blood  membrane . [ 18 ]  The fluoride circulation in  red blood cells  accounts for 30%. [ 19 ]  However, it is freely available to the bone surface for uptake because the equilibrium between erythrocytes and plasma is much faster than the capillary transit time. This is supported by studies reporting 100% single-passage extraction of whole-blood  18 F- ion by bone [ 13 ]  and the rapid release of  18 F- ions from erythrocytes with a rate constant of 0.3 per second. [ 20 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4346", "text": "[ 18 F]NaF is also taken-up by immature erythrocytes in the  bone marrow , [ 21 ]  which plays a role in fluoride kinetics. [ 22 ]  The plasma protein binding of [ 18 F]NaF is negligible. [ 23 ]  [ 18 F]NaF renal clearance is affected by diet [ 24 ]  and  pH  level, [ 25 ]  due to its re-absorption in the nephron, which is mediated by hydrogen fluoride. [ 26 ]  However, large differences in  urine flow rate [ 19 ]  are avoided for controlled experiments by keeping patents well hydrated. [ 21 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4347", "text": "The exchangeable pool and the size of the metabolically active surfaces in bones determines the amount of tracer accumulated or exchanged [ 27 ]  with bone  extracellular fluid , [ 28 ]   chemisorption  onto hydroxyapatite crystals to form fluorapatite, [ 14 ] [ 29 ] [ 9 ]  as shown in Equation-1: [ 30 ] [ 31 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4348", "text": "C \n \n a \n \n 10 \n \n \n ( \n P \n \n O \n \n 4 \n \n \n \n ) \n \n 6 \n \n \n ( \n O \n H \n \n ) \n \n 2 \n \n \n + \n 2 \n F \n \u2212 \n => \n C \n \n a \n \n 10 \n \n \n ( \n P \n \n O \n \n 4 \n \n \n \n ) \n \n 6 \n \n \n \n F \n \n 2 \n \n \n + \n 2. \n O \n H \n \u2212 \n \n \n {\\displaystyle Ca_{10}(PO_{4})_{6}(OH)_{2}+2F-=>Ca_{10}(PO_{4})_{6}F_{2}+2.OH-} \n \n                                                                            Equation-1"}
{"_id": "WikiPedia_Radiology$$$corpus_4349", "text": "Fluoride ions from the crystalline matrix of bone are released when the bone is remodelled, thus providing a measure of the rate of bone metabolism. [ 32 ] [ 33 ] [ 34 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4350", "text": "The  standardized uptake value  (SUV) is defined as tissue concentration (KBq/ml) divided by activity injected normalized for  body weight . [ 35 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4351", "text": "The SUV measured from the large ROI smooths out the noise and, therefore, more appropriate in [ 18 F]NaF bone studies as the radiotracer is fairly uniformly taken up throughout the bone. The measurement of SUV is easy, [ 36 ]  cheap, and quicker to perform, making it more attractive for clinical use. It has been used in diagnosing and assessing the efficacy of therapy. [ 37 ] [ 38 ]  SUV can be measured at a single site, or the whole skeleton using a series of static scans and restricted by the small field-of-view of the PET scanner. [ 32 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4352", "text": "The SUV has emerged as a clinically useful, albeit controversial, semi-quantitative tool in PET analysis. [ 39 ]  Standardizing imaging protocols and measuring the SUV at the same time post-injection of the radiotracer, is necessary to obtain a correct SUV [ 40 ]  because imaging before the uptake plateau introduces unpredictable errors of up to 50% with SUVs. [ 41 ]  Noise, image resolution, and reconstruction do affect the accuracy of SUVs, but correction with phantom can minimize these differences when comparing SUVs for multi-centre clinical trials. [ 42 ] [ 43 ]  SUV may lack sensitivity in measuring response to treatment as it is a simple measure of tracer uptake in bone, which is affected by the tracer uptake in other competing tissues and organs in addition to the target ROI. [ 44 ] [ 45 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4353", "text": "The quantification of dynamic PET studies to measure Ki requires the measurement of the skeletal  time-activity curves  (TAC) from the region of interest (ROI) and the  arterial input function  (AIF), which can be measured in various different ways. However, the most common is to correct the image-based blood time-activity curves using several venous blood samples taken at discrete time points while the patient is scanned. The calculation of rate constants or K i  requires three steps: [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4354", "text": "The method was first described by Cunningham & Jones [ 46 ]  in 1993 for the analysis of dynamic PET data obtained in the brain. It assumes that the tissue impulse response function (IRF) can be described as a combination of many exponentials. Since A tissue TAC can be expressed as a convolution of measured arterial input function with IRF, C bone (t) can be expressed as:"}
{"_id": "WikiPedia_Radiology$$$corpus_4355", "text": "C \n \n b \n o \n n \n e \n \n \n ( \n t \n ) \n = \n \n \u2211 \n \n k \n = \n 1 \n \n \n n \n \n \n \n \u03b1 \n \n i \n \n \n . \n \n \n ( \n \n \n \n C \n \n p \n l \n a \n s \n m \n a \n \n \n ( \n t \n ) \n \u2297 \n e \n x \n p \n ( \n \u2212 \n \n \u03b2 \n \n i \n \n \n . \n t \n ) \n \n \n ) \n \n \n \n \n {\\displaystyle C_{bone}(t)=\\sum _{k=1}^{n}\\alpha _{i}.{\\bigl (}C_{plasma}(t)\\otimes exp(-\\beta _{i}.t){\\bigr )}}"}
{"_id": "WikiPedia_Radiology$$$corpus_4356", "text": "where,  \n \n \n \n \u2297 \n \n \n {\\displaystyle \\otimes } \n \n  is a convolution operator, C bone (t) is the bone tissue activity concentration of tracer (in units: MBq/ml) over a period of time t, C plasma (t) is the plasma concentration of tracer (in units: MBq/ml) over a period of time t, IRF(t) is equal to the sum of exponentials, \u03b2 values are fixed between 0.0001 sec \u22121  and 0.1 sec \u22121  in intervals of 0.0001, n is the number of \u03b1 components that resulted from the analysis and \u03b2 1 , \u03b2 2 ,..., \u03b2 n  corresponds to the respective \u03b1 1 , \u03b1 2 ,..., \u03b1 n  components from the resulted spectrum. The values of \u03b1 are then estimated from the analysis by fitting multi-exponential to the IRF. The intercept of the linear fit to the slow component of this exponential curve is considered the plasma clearance (K i ) to the bone mineral."}
{"_id": "WikiPedia_Radiology$$$corpus_4357", "text": "The method was first described by Williams et al. in the clinical context. [ 47 ]  The method was used by numerous other studies. [ 48 ] [ 49 ] [ 50 ]  This is perhaps the simplest of all the mathematical methods for the calculation of  K i  but the one most sensitive to noise present in the data. A tissue TAC is modelled as a convolution of measured arterial input function with IRF, the estimates for IRF are obtained iteratively to minimise the differences between the left- and right-hand side of the following Equation:"}
{"_id": "WikiPedia_Radiology$$$corpus_4358", "text": "C \n \n b \n o \n n \n e \n \n \n ( \n t \n ) \n = \n \n C \n \n p \n l \n a \n s \n m \n a \n \n \n ( \n t \n ) \n \u2297 \n I \n R \n F \n ( \n t \n ) \n \n \n {\\displaystyle C_{bone}(t)=C_{plasma}(t)\\otimes IRF(t)}"}
{"_id": "WikiPedia_Radiology$$$corpus_4359", "text": "where,  \n \n \n \n \u2297 \n \n \n {\\displaystyle \\otimes } \n \n  is a convolution operator, C bone (t) is the bone tissue activity concentration of tracer (in units: MBq/ml) over a period of time t, C plasma (t) is the plasma concentration of tracer (in units: MBq/ml) over a period of time t, and IRF(t) is the impulse response of the system (i.e., a tissue in this case). The  K i  is obtained from the IRF in a similar fashion to that obtained for the spectral analysis, as shown in the figure."}
{"_id": "WikiPedia_Radiology$$$corpus_4360", "text": "The measurement of Ki from dynamic PET scans require tracer kinetic modelling to obtain the model parameters describing the  biological processes  in  bone , as described by Hawkins et al. [ 22 ]  Since this model has two tissue compartments, it is sometimes called a two-tissue compartmental model. Various different versions of this model exist; however, the most fundamental approach is considered here with two tissue compartments and four tracer-exchange parameters. The whole kinetic modelling process using Hawkins model can be summed up in a single image as seen on the right-hand-side. The following differential equations are solved to obtain the rate constants:"}
{"_id": "WikiPedia_Radiology$$$corpus_4361", "text": "d \n \n \n C \n \n e \n \n \n ( \n t \n ) \n \n \n d \n \n t \n \n \n \n = \n \n K \n \n 1 \n \n \n \u2217 \n \n C \n \n p \n \n \n ( \n t \n ) \n \u2212 \n ( \n \n k \n \n 2 \n \n \n + \n \n k \n \n 3 \n \n \n ) \n \u2217 \n \n C \n \n e \n \n \n ( \n t \n ) \n + \n \n k \n \n 4 \n \n \n \u2217 \n \n C \n \n b \n \n \n ( \n t \n ) \n \n \n {\\displaystyle {\\operatorname {d} \\!C_{e}(t) \\over \\operatorname {d} \\!t}=K_{1}*C_{p}(t)-(k_{2}+k_{3})*C_{e}(t)+k_{4}*C_{b}(t)}"}
{"_id": "WikiPedia_Radiology$$$corpus_4362", "text": "d \n \n \n C \n \n b \n \n \n ( \n t \n ) \n \n \n d \n \n t \n \n \n \n = \n \n k \n \n 3 \n \n \n \u2217 \n \n C \n \n e \n \n \n ( \n t \n ) \n \u2212 \n \n k \n \n 4 \n \n \n \u2217 \n \n C \n \n b \n \n \n ( \n t \n ) \n \n \n {\\displaystyle {\\operatorname {d} \\!C_{b}(t) \\over \\operatorname {d} \\!t}=k_{3}*C_{e}(t)-k_{4}*C_{b}(t)}"}
{"_id": "WikiPedia_Radiology$$$corpus_4363", "text": "The rate constant  K 1  (in units: ml/min/ml) describes the unidirectional clearance of fluoride from plasma to the whole of the bone tissue,  k 2  (in units: min \u22121 ) describes the reverse transport of fluoride from the ECF compartment to plasma,  k 3  and  k 4  (in units min \u22121 ) describe the forward and backward transportation of fluoride from the bone mineral compartment."}
{"_id": "WikiPedia_Radiology$$$corpus_4364", "text": "K i  represents the net plasma clearance to bone mineral only.  K i  is a function of both  K 1 , reflecting bone blood flow, and the fraction of the tracer that undergoes specific binding to the bone mineral  k 3  / ( k 2  +  k 3 ). Therefore,   \n \n \n \n \n K \n \n i \n \n \n = \n \n ( \n \n \n \n \n K \n \n 1 \n \n \n \u2217 \n \n k \n \n 3 \n \n \n \n \n \n k \n \n 2 \n \n \n + \n \n k \n \n 3 \n \n \n \n \n \n ) \n \n \n \n {\\displaystyle K_{i}=\\left({\\frac {K_{1}*k_{3}}{k_{2}+k_{3}}}\\right)}"}
{"_id": "WikiPedia_Radiology$$$corpus_4365", "text": "Hawkins et al. found that the inclusion of an additional parameter called fractional  blood volume  (BV), representing the vascular tissue spaces within the ROI, improved the data fitting problem, although this improvement was not statistically significant. [ 51 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4366", "text": "Patlak method [ 52 ]  is based on the assumption that the backflow of tracer from bone mineral to bone ECF is zero (i.e., k 4 =0). The calculation of K i  using Patlak method is simpler than using  non-linear regression  (NLR) fitting the  arterial input function  and the tissue  time-activity curve  data to the Hawkins model. The Patlak method can only measure bone plasma clearance ( K i ), and cannot measure the individual kinetic parameters, K 1 , k 2 , k 3 , or k 4 ."}
{"_id": "WikiPedia_Radiology$$$corpus_4367", "text": "The concentration of tracer in tissue region-of-interest can be represented as a sum of concentration in bone ECF and the bone mineral. It can be mathematically represented as"}
{"_id": "WikiPedia_Radiology$$$corpus_4368", "text": "C \n \n b \n o \n n \n e \n \n \n ( \n T \n ) \n \n \n \n C \n \n p \n l \n a \n s \n m \n a \n \n \n ( \n T \n ) \n \n \n \n = \n \n K \n \n i \n \n \n \u2217 \n \n \n \n \n \u222b \n \n 0 \n \n \n T \n \n \n \n C \n \n p \n l \n a \n s \n m \n a \n \n \n ( \n t \n ) \n d \n t \n \n \n \n C \n \n p \n l \n a \n s \n m \n a \n \n \n ( \n T \n ) \n \n \n \n + \n \n V \n \n o \n \n \n \n \n {\\displaystyle {\\frac {C_{bone}(T)}{C_{plasma}(T)}}=K_{i}*{\\frac {\\int \\limits _{0}^{T}C_{plasma}(t)dt}{C_{plasma}(T)}}+V_{o}}"}
{"_id": "WikiPedia_Radiology$$$corpus_4369", "text": "where, within the tissue region-of-interest from the PET image, C bone (T) is the bone tissue activity concentration of tracer (in units: MBq/ml) at any time T, C plasma (T) is the plasma concentration of tracer (in units: MBq/ml) at time T, V o  is the fraction of the ROI occupied by the ECF compartment, and  \n \n \n \n \n \u222b \n \n 0 \n \n \n T \n \n \n \n C \n \n p \n l \n a \n s \n m \n a \n \n \n ( \n t \n ) \n d \n t \n \n \n {\\displaystyle \\int \\limits _{0}^{T}C_{plasma}(t)dt} \n \n  is the area under the plasma curve is the net tracer delivery to the tissue region of interest (in units: MBq.Sec/ml) over time T. The Patlak equation is a linear equation of the form  \n \n \n \n Y \n = \n m \n \u2217 \n X \n + \n c \n \n \n {\\displaystyle Y=m*X+c}"}
{"_id": "WikiPedia_Radiology$$$corpus_4370", "text": "Therefore, linear regression is fitted to the data plotted on Y- and X-axis between 4\u201360 minutes to obtain  m  and  c  values, where  m  is the slope of the regression line representing K i  and  c  is the Y-intercept of the regression line representing V o . [ 52 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4371", "text": "The calculation of Ki using arterial input function, time-activity curve, and Hawkins model was limited to a small skeletal region covered by the narrow field-of-view of the PET scanner while acquiring a dynamic scan. However, Siddique et al. [ 53 ]  showed in 2012 that it is possible to measure K i  values in bones using static [ 18 F]NaF PET scans. Blake et al. [ 32 ]  later showed in 2019 that the K i  obtained using the Siddique\u2013Blake method has precision errors of less than 10%. The Siddique\u2013Blake approach is based on the combination of the Patlak method, [ 52 ]  the semi-population based arterial input function, [ 54 ]  and the information that V o  does not significantly change post-treatment. This method uses the information that a linear regression line can be plotted using the data from a minimum of two time-points, to obtain  m  and  c  as explained in the Patlak method. However, if V o  is known or fixed, only one single static PET image is required to obtain the second time-point to measure  m , representing the K i  value. This method should be applied with great caution to other clinical areas where these assumptions may not hold true."}
{"_id": "WikiPedia_Radiology$$$corpus_4372", "text": "The most fundamental difference between SUV and K i  values is that SUV is a simple measure of uptake, which is normalized to body weight and injected activity. The SUV does not take into consideration the tracer delivery to the local region of interest from where the measurements are obtained, therefore, affected by the physiological process consuming [ 18 F]NaF elsewhere in the body. On the other hand, K i  measures the plasma clearance to bone mineral, taking into account the tracer uptake elsewhere in the body affecting the delivery of tracer to the region of interest from where the measurements are obtained. The difference in the measurement of K i  and SUV in bone tissue using [ 18 F]NaF are explained in more detail by Blake et al. [ 34 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4373", "text": "It is critical to note that most of the methods for calculating K i  require dynamic PET scanning over an hour, except, the Siddique\u2013Blake methods. Dynamic scanning is complicated and costly. However, the calculation of SUV requires a single static PET scan performed approximately 45\u201360 minutes post-tracer injection at any region imaged within the skeleton."}
{"_id": "WikiPedia_Radiology$$$corpus_4374", "text": "Many researchers have shown a high correlation between SUV and  K i  values at various skeletal sites. [ 55 ] [ 56 ] [ 57 ]  However, SUV and K i  methods can contradict for measuring response to treatment. [ 45 ]  Since SUV has not been validated against the histomorphometry, its usefulness in bone studies measuring response to treatment and disease progression is uncertain."}
{"_id": "WikiPedia_Radiology$$$corpus_4375", "text": "Plaque radiotherapy  is a type of  radiation therapy  used to treat  eye  tumors. A thin piece of metal (usually gold) with  radioactive seeds  placed on one side is  sewn  onto the outside wall of the eye with the seeds aimed at the  tumor . It is removed at the end of treatment, which usually lasts for several days."}
{"_id": "WikiPedia_Radiology$$$corpus_4376", "text": "Iodine-125  is among the isotopes used. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4377", "text": "Positron emission tomography  ( PET ) [ 1 ]  is a  functional imaging  technique that uses radioactive substances known as  radiotracers  to visualize and measure changes in  metabolic processes , and in other  physiological  activities including  blood flow , regional chemical composition, and absorption. Different tracers are used for various imaging purposes, depending on the target process within the body."}
{"_id": "WikiPedia_Radiology$$$corpus_4378", "text": "For example:"}
{"_id": "WikiPedia_Radiology$$$corpus_4379", "text": "PET is a common  imaging technique , a  medical scintillography  technique used in  nuclear medicine . A  radiopharmaceutical  \u2013 a  radioisotope  attached to a drug \u2013 is injected into the body as a  tracer . When the radiopharmaceutical undergoes  beta plus decay , a  positron  is emitted, and when the positron interacts with an ordinary electron, the two particles annihilate and two  gamma rays  are emitted in opposite directions. [ 2 ]  These gamma rays are detected by two  gamma cameras  to form a three-dimensional image."}
{"_id": "WikiPedia_Radiology$$$corpus_4380", "text": "PET scanners can incorporate a  computed tomography scanner  (CT) and are known as  PET-CT scanners . PET scan images can be reconstructed using a CT scan performed using one scanner during the same session."}
{"_id": "WikiPedia_Radiology$$$corpus_4381", "text": "One of the disadvantages of a PET scanner is its high initial cost and ongoing operating costs. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4382", "text": "PET is both a medical and research tool used in pre-clinical and clinical settings. It is used heavily in the imaging of  tumors  and the search for  metastases  within the field of  clinical oncology , and for the clinical diagnosis of certain diffuse brain diseases such as those causing various types of  dementias . PET is a valuable research tool to learn and enhance our knowledge of the normal human brain, heart function, and support drug development. PET is also used in pre-clinical studies using animals. It allows repeated investigations into the same subjects over time, where subjects can act as their own control and substantially reduces the numbers of animals required for a given study. This approach allows research studies to reduce the sample size needed while increasing the statistical quality of its results. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4383", "text": "Physiological processes lead to  anatomical  changes in the body. Since PET is capable of detecting biochemical processes as well as expression of some proteins, PET can provide molecular-level information much before any anatomic changes are visible. PET scanning does this by using radiolabelled molecular probes that have different rates of uptake depending on the type and function of tissue involved. Regional tracer uptake in various anatomic structures can be visualized and relatively quantified in terms of injected positron emitter within a PET scan. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4384", "text": "PET imaging is best performed using a dedicated PET scanner. It is also possible to acquire PET images using a conventional dual-head  gamma camera  fitted with a coincidence detector. The quality of gamma-camera PET imaging is lower, and the scans take longer to acquire. However, this method allows a low-cost on-site solution to institutions with low PET scanning demand. An alternative would be to refer these patients to another center or relying on a visit by a mobile scanner."}
{"_id": "WikiPedia_Radiology$$$corpus_4385", "text": "Alternative methods of  medical imaging  include  single-photon emission computed tomography  (SPECT), computed tomography (CT),  magnetic resonance imaging  (MRI) and  functional magnetic resonance imaging  (fMRI), and  ultrasound . SPECT is an imaging technique similar to PET that uses  radioligands  to detect molecules in the body. SPECT is less expensive and provides inferior image quality than PET."}
{"_id": "WikiPedia_Radiology$$$corpus_4386", "text": "PET scanning with the radiotracer  [ 18 F]fluorodeoxyglucose  (FDG) is widely used in clinical oncology. FDG is a  glucose   analog  that is taken up by glucose-using cells and phosphorylated by  hexokinase  (whose  mitochondrial  form is significantly elevated in rapidly growing  malignant  tumors). [ 4 ]   Metabolic trapping  of the radioactive glucose molecule allows the PET scan to be utilized. The concentrations of imaged FDG tracer indicate tissue metabolic activity as it corresponds to the regional glucose uptake. FDG is used to explore the possibility of cancer spreading to other body sites ( cancer   metastasis ). These FDG PET scans for detecting cancer metastasis are the most common in standard medical care (representing 90% of current scans). The same tracer may also be used for the diagnosis of types of  dementia . Less often, other  radioactive tracers , usually but not always labelled with  fluorine-18  ( 18 F), are used to image the tissue concentration of different kinds of molecules of interest inside the body. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4387", "text": "A typical dose of FDG used in an oncological scan has an effective radiation dose of 7.6\u00a0 mSv . [ 5 ]  Because the hydroxy group that is replaced by fluorine-18 to generate FDG is required for the next step in  glucose metabolism  in all cells, no further reactions occur in FDG. Furthermore, most tissues (with the notable exception of liver and kidneys) cannot remove the  phosphate  added by hexokinase. This means that FDG is trapped in any cell that takes it up until it decays, since  phosphorylated  sugars, due to their ionic charge, cannot exit from the cell. This results in intense radiolabeling of tissues with high glucose uptake, such as the normal brain, liver, kidneys, and most cancers, which have a higher glucose uptake than most normal tissue due to the  Warburg effect . As a result, FDG-PET can be used for diagnosis, staging, and monitoring treatment of cancers, particularly in  Hodgkin lymphoma , [ 6 ]   non-Hodgkin lymphoma , [ 7 ]  and  lung cancer . [ 8 ] [ 9 ] [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4388", "text": "A 2020 review of research on the use of PET for Hodgkin lymphoma found evidence that negative findings in interim PET scans are linked to higher  overall survival  and  progression-free survival ; however, the certainty of the available evidence was moderate for survival, and very low for progression-free survival. [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4389", "text": "A few other isotopes and radiotracers are slowly being introduced into oncology for specific purposes. For example,  11 C -labelled  metomidate  (11C-metomidate) has been used to detect tumors of  adrenocortical  origin. [ 12 ] [ 13 ]  Also,  fluorodopa  (FDOPA) PET/CT (also called F-18-DOPA PET/CT) has proven to be a more sensitive alternative to finding and also localizing  pheochromocytoma  than the  Iobenguane  (MIBG)  scan . [ 14 ] [ 15 ] [ 16 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4390", "text": "PET imaging with oxygen-15 indirectly measures blood flow to the brain. In this method, increased radioactivity signal indicates increased blood flow which is assumed to correlate with increased brain activity. Because of its 2-minute  half-life , oxygen-15 must be piped directly from a medical  cyclotron  for such uses, which is difficult. [ 17 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4391", "text": "PET imaging with FDG takes advantage of the fact that the brain is normally a rapid user of glucose. Standard FDG PET of the brain measures regional glucose use and can be used in neuropathological diagnosis."}
{"_id": "WikiPedia_Radiology$$$corpus_4392", "text": "Brain pathologies such as  Alzheimer's disease  (AD) greatly decrease brain metabolism of both glucose and oxygen in tandem.  Therefore FDG PET of the brain may also be used to successfully differentiate Alzheimer's disease from other dementing processes, and also to make early diagnoses of Alzheimer's disease. The advantage of FDG PET for these uses is its much wider availability. Some fluorine-18 based radioactive tracers used for Alzheimer's include  florbetapir ,  flutemetamol ,  Pittsburgh compound B  (PiB) and  florbetaben , which are all used to detect  amyloid-beta  plaques, a potential  biomarker  for Alzheimer's in the brain. [ 18 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4393", "text": "PET imaging with FDG can also be used for localization of \"seizure focus\". A seizure focus will appear as hypometabolic during an interictal scan. [ 19 ]  Several radiotracers (i.e. radioligands) have been developed for PET that are  ligands  for specific  neuroreceptor  subtypes such as [ 11 C] raclopride , [ 18 F] fallypride  and [ 18 F] desmethoxyfallypride  for  dopamine   D 2 / D 3  receptors; [ 11 C] McN5652  and [ 11 C] DASB  for  serotonin transporters ; [ 18 F] mefway  for serotonin  5HT 1A  receptors ; and [ 18 F] nifene  for  nicotinic acetylcholine receptors  or  enzyme substrates  (e.g. 6- FDOPA  for the  AADC enzyme ). These agents permit the visualization of neuroreceptor pools in the context of a plurality of neuropsychiatric and neurologic illnesses."}
{"_id": "WikiPedia_Radiology$$$corpus_4394", "text": "PET may also be used for the diagnosis of  hippocampal sclerosis , which causes epilepsy. FDG, and the less common tracers  flumazenil  and  MPPF  have been explored for this purpose. [ 20 ] [ 21 ]  If the sclerosis is unilateral (right hippocampus or left hippocampus), FDG uptake can be compared with the healthy side. Even if the diagnosis is difficult with MRI, it may be diagnosed with PET. [ 22 ] [ 23 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4395", "text": "The development of a number of novel probes for  non-invasive ,  in-vivo  PET imaging of neuroaggregate in human brain has brought amyloid imaging close to clinical use. The earliest  amyloid  imaging probes included [ 18 F]FDDNP [ 24 ]  developed at the  University of California, Los Angeles  and  Pittsburgh compound B  (PiB) [ 25 ]  developed at the  University of Pittsburgh . These probes permit the visualization of amyloid plaques in the brains of Alzheimer's patients and could assist clinicians in making a positive clinical diagnosis of AD pre-mortem and aid in the development of novel anti-amyloid therapies. [ 11 C] polymethylpentene  (PMP) is a novel radiopharmaceutical used in PET imaging to determine the activity of the acetylcholinergic neurotransmitter system by acting as a substrate for  acetylcholinesterase . Post-mortem examination of AD patients have shown decreased levels of acetylcholinesterase. [ 11 C]PMP is used to map the acetylcholinesterase activity in the brain, which could allow for  premortem  diagnoses of AD and help to monitor AD treatments. [ 26 ]   Avid Radiopharmaceuticals  has developed and commercialized a compound called florbetapir that uses the longer-lasting  radionuclide  fluorine-18 to detect amyloid plaques using PET scans. [ 27 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4396", "text": "To examine links between specific psychological processes or disorders and brain activity."}
{"_id": "WikiPedia_Radiology$$$corpus_4397", "text": "Numerous compounds that bind selectively to neuroreceptors of interest in biological psychiatry have been radiolabeled with C-11 or F-18. Radioligands that bind to  dopamine receptors  ( D 1 , [ 28 ]  D 2 , [ 29 ] [ 30 ]  reuptake transporter),  serotonin receptors  ( 5HT 1A ,  5HT 2A , reuptake transporter),  opioid receptors  ( mu  and  kappa ),  cholinergic receptors  (nicotinic and  muscarinic ) and other sites have been used successfully in studies with human subjects. Studies have been performed examining the state of these receptors in patients compared to healthy controls in  schizophrenia ,  substance abuse ,  mood disorders  and other psychiatric conditions. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4398", "text": "PET can also be used in  image guided surgery  for the treatment of intracranial tumors, arteriovenous malformations and other surgically treatable conditions. [ 31 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4399", "text": "Cardiology ,  atherosclerosis  and vascular disease study: FDG PET can help in identifying  hibernating myocardium . However, the  cost-effectiveness  of PET for this role versus  SPECT  is unclear. FDG PET imaging of  atherosclerosis  to detect patients at risk of  stroke  is also feasible. Also, it can help test the efficacy of novel anti-atherosclerosis therapies. [ 32 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4400", "text": "Imaging infections with  molecular imaging  technologies can improve diagnosis and treatment follow-up. Clinically, PET has been widely used to image bacterial infections using FDG to identify the infection-associated inflammatory response. Three different PET  contrast agents  have been developed to image bacterial infections in vivo are [ 18 F] maltose , [ 33 ]  [ 18 F]maltohexaose, and [ 18 F]2-fluorodeoxy sorbitol  (FDS). [ 34 ]  FDS has the added benefit of being able to target only  Enterobacteriaceae ."}
{"_id": "WikiPedia_Radiology$$$corpus_4401", "text": "In pre-clinical trials, a new drug can be radiolabeled and injected into animals. Such scans are referred to as biodistribution studies. The information regarding drug uptake, retention and elimination over time can be obtained quickly and cost-effectively compare to the older technique of killing and dissecting the animals. Commonly, drug occupancy at a purported site of action can be inferred indirectly by competition studies between unlabeled drug and radiolabeled compounds to bind with specificity to the site. A single radioligand can be used this way to test many potential drug candidates for the same target. A related technique involves scanning with radioligands that compete with an  endogenous  (naturally occurring) substance at a given receptor to demonstrate that a drug causes the release of the natural substance. [ 35 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4402", "text": "A miniature animal PET has been constructed that is small enough for a fully conscious  rat  to be scanned. [ 36 ]  This RatCAP (rat conscious animal PET) allows animals to be scanned without the confounding effects of  anesthesia . PET scanners designed specifically for imaging  rodents , often referred to as microPET, as well as scanners for small  primates , are marketed for academic and pharmaceutical research. The scanners are based on microminiature scintillators and amplified  avalanche photodiodes  (APDs) through a system that uses single-chip silicon  photomultipliers . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4403", "text": "In 2018 the  UC Davis School of Veterinary Medicine  became the first veterinary center to employ a small clinical PET scanner as a scanner for clinical (rather than research) animal diagnosis. Because of cost as well as the marginal utility of detecting cancer metastases in companion animals (the primary use of this modality), veterinary PET scanning is expected to be rarely available in the immediate future. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4404", "text": "PET imaging has been used for imaging muscles and bones. FDG is the most commonly used tracer for imaging muscles, and  NaF-F18  is the most widely used tracer for imaging bones."}
{"_id": "WikiPedia_Radiology$$$corpus_4405", "text": "PET is a feasible technique for studying  skeletal muscles  during exercise. [ 37 ]  Also, PET can provide muscle activation data about deep-lying muscles (such as the  vastus intermedialis  and the  gluteus minimus ) compared to techniques like  electromyography , which can be used only on superficial muscles directly under the skin. However, a disadvantage is that PET provides no timing information about muscle activation because it has to be measured after the exercise is completed. This is due to the time it takes for FDG to accumulate in the activated muscles. [ 38 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4406", "text": "Together with [ 18 F]sodium floride,  PET for bone imaging  has been in use for 60 years for measuring regional bone metabolism and blood flow using static and dynamic scans. Researchers have recently started using [ 18 F]sodium fluoride to study bone metastasis as well. [ 39 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4407", "text": "PET scanning is non-invasive, but it does involve exposure to  ionizing radiation . [ 3 ]  FDG, which is now the standard radiotracer used for PET neuroimaging and cancer patient management, [ 40 ]  has an effective radiation dose of 14\u00a0 mSv . [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4408", "text": "The amount of radiation in FDG is similar to the effective dose of spending one year in the American city of  Denver, Colorado  (12.4\u00a0mSv/year). [ 41 ]  For comparison, radiation dosage for other medical procedures range from 0.02\u00a0mSv for a  chest X-ray  and 6.5\u20138\u00a0mSv for a CT scan of the chest. [ 42 ] [ 43 ]  Average civil aircrews are exposed to 3\u00a0mSv/year, [ 44 ]  and the whole body occupational dose limit for nuclear energy workers in the US is 50\u00a0mSv/year. [ 45 ]  For scale, see  Orders of magnitude (radiation) ."}
{"_id": "WikiPedia_Radiology$$$corpus_4409", "text": "For PET-CT scanning, the radiation exposure may be substantial\u2014around 23\u201326\u00a0mSv (for a 70\u00a0kg person\u2014dose is likely to be higher for higher body weights). [ 46 ] [ 47 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4410", "text": "Radionuclides are incorporated either into compounds normally used by the body such as  glucose  (or glucose analogues),  water , or  ammonia , or into molecules that bind to receptors or other sites of drug action. Such labelled compounds are known as  radiotracers . PET technology can be used to trace the biologic pathway of any compound in living humans (and many other species as well), provided it can be radiolabeled with a PET isotope. Thus, the specific processes that can be probed with PET are virtually limitless, and radiotracers for new target molecules and processes are continuing to be synthesized. As of this writing there are already dozens in clinical use and hundreds applied in research. In 2020 by far the most commonly used radiotracer in clinical PET scanning is the carbohydrate derivative FDG. This radiotracer is used in essentially all scans for oncology and most scans in neurology, thus makes up the large majority of radiotracer (>95%) used in PET and PET-CT scanning."}
{"_id": "WikiPedia_Radiology$$$corpus_4411", "text": "Due to the short half-lives of most positron-emitting radioisotopes, the radiotracers have traditionally been produced using a cyclotron in close proximity to the PET imaging facility. The half-life of fluorine-18 is long enough that radiotracers labeled with fluorine-18 can be manufactured commercially at offsite locations and shipped to imaging centers. Recently  rubidium-82  generators have become commercially available. [ 49 ]  These contain strontium-82, which decays by  electron capture  to produce positron-emitting rubidium-82."}
{"_id": "WikiPedia_Radiology$$$corpus_4412", "text": "The use of positron-emitting isotopes of metals in PET scans has been reviewed, including elements not listed above, such as lanthanides. [ 50 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4413", "text": "The isotope  89 Zr has been applied to the tracking and quantification of molecular antibodies with PET cameras (a method called \"immuno-PET\"). [ 51 ] [ 52 ] [ 53 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4414", "text": "The biological half-life of antibodies is typically on the order of days, see  daclizumab  and  erenumab  by way of example. To visualize and quantify the distribution of such antibodies in the body, the PET isotope  89 Zr is well suited because its physical half-life matches the typical biological half-life of antibodies, see table above."}
{"_id": "WikiPedia_Radiology$$$corpus_4415", "text": "To conduct the scan, a short-lived radioactive tracer  isotope  is injected into the living subject (usually into blood circulation). Each tracer atom has been chemically incorporated into a biologically active molecule. There is a waiting period while the active molecule becomes concentrated in tissues of interest. Then the subject is placed in the imaging scanner. The molecule most commonly used for this purpose is FDG, a sugar, for which the waiting period is typically an hour. During the scan, a record of tissue concentration is made as the tracer decays."}
{"_id": "WikiPedia_Radiology$$$corpus_4416", "text": "As the radioisotope undergoes  positron emission  decay (also known as positive  beta decay ), it emits a positron, an  antiparticle  of the  electron  with opposite charge. The emitted positron travels in tissue for a short distance (typically less than 1\u00a0mm, but dependent on the isotope [ 54 ] ), during which time it loses kinetic energy, until it decelerates to a point where it can interact with an electron. [ 55 ]  The encounter annihilates both electron and positron, producing a pair of  annihilation  ( gamma )  photons  moving in approximately opposite directions. These are detected when they reach a  scintillator  in the scanning device, creating a burst of light which is detected by photomultiplier tubes or silicon avalanche photodiodes (Si APD). The technique depends on simultaneous or coincident detection of the pair of photons moving in approximately opposite directions (they would be exactly opposite in their  center of mass frame , but the scanner has no way to know this, and so has a built-in slight direction-error tolerance). Photons that do not arrive in temporal \"pairs\" (i.e. within a timing-window of a few nanoseconds) are ignored."}
{"_id": "WikiPedia_Radiology$$$corpus_4417", "text": "The most significant fraction of electron\u2013positron annihilations results in two 511\u00a0keV gamma photons being emitted at almost 180 degrees to each other. Hence, it is possible to localize their source along a straight line of coincidence (also called the  line of response , or  LOR ). In practice, the LOR has a non-zero width as the emitted photons are not exactly 180 degrees apart. If the resolving time of the detectors is less than 500  picoseconds  rather than about 10  nanoseconds , it is possible to localize the event to a segment of a  chord , whose length is determined by the detector timing resolution. As the timing resolution improves, the  signal-to-noise ratio  (SNR) of the image will improve, requiring fewer events to achieve the same image quality. This technology is not yet common, but it is available on some new systems. [ 56 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4418", "text": "The raw data collected by a PET scanner are a list of 'coincidence events' representing near-simultaneous detection (typically, within a window of 6 to 12 nanoseconds of each other) of annihilation photons by a pair of detectors. Each coincidence event represents a line in space connecting the two detectors along which the positron emission occurred (i.e., the line of response (LOR))."}
{"_id": "WikiPedia_Radiology$$$corpus_4419", "text": "Analytical techniques, much like the reconstruction of  computed tomography  (CT) and  single-photon emission computed tomography  (SPECT) data, are commonly used, although the  data set  collected in PET is much poorer than CT, so reconstruction techniques are more difficult. Coincidence events can be grouped into projection images, called  sinograms . The sinograms are sorted by the angle of each view and tilt (for 3D images). The sinogram images are analogous to the projections captured by CT scanners, and can be reconstructed in a similar way. The statistics of data thereby obtained are much worse than those obtained through transmission tomography. A normal PET data set has millions of counts for the whole acquisition, while the CT can reach a few billion counts. This contributes to PET images appearing \"noisier\" than CT. Two major sources of noise in PET are scatter (a detected pair of photons, at least one of which was deflected from its original path by interaction with matter in the field of view, leading to the pair being assigned to an incorrect LOR) and random events (photons originating from two different annihilation events but incorrectly recorded as a coincidence pair because their arrival at their respective detectors occurred within a coincidence timing window)."}
{"_id": "WikiPedia_Radiology$$$corpus_4420", "text": "In practice, considerable pre-processing of the data is required \u2013 correction for random coincidences, estimation and subtraction of  scattered  photons, detector  dead-time  correction (after the detection of a photon, the detector must \"cool down\" again) and detector-sensitivity correction (for both inherent detector sensitivity and changes in sensitivity due to angle of incidence)."}
{"_id": "WikiPedia_Radiology$$$corpus_4421", "text": "Filtered back projection  (FBP) has been frequently used to reconstruct images from the projections. This algorithm has the advantage of being simple while having a low requirement for computing resources. Disadvantages are that  shot noise  in the raw data is prominent in the reconstructed images, and areas of high tracer uptake tend to form streaks across the image. Also, FBP treats the data deterministically \u2013 it does not account for the inherent randomness associated with PET data, thus requiring all the pre-reconstruction corrections described above."}
{"_id": "WikiPedia_Radiology$$$corpus_4422", "text": "Statistical, likelihood-based approaches : Statistical, likelihood-based  [ 57 ] [ 58 ]  iterative  expectation-maximization algorithms  such as the Shepp\u2013Vardi algorithm [ 59 ]  are now the preferred method of reconstruction. These algorithms compute an estimate of the likely distribution of annihilation events that led to the measured data, based on statistical principles. The advantage is a better noise profile and resistance to the streak artifacts common with FBP, but the disadvantage is greater computer resource requirements. A further advantage of statistical image reconstruction techniques is that the physical effects that would need to be pre-corrected for when using an analytical reconstruction algorithm, such as scattered photons, random coincidences, attenuation and detector dead-time, can be incorporated into the likelihood model being used in the reconstruction, allowing for additional noise reduction. Iterative reconstruction has also been shown to result in improvements in the resolution of the reconstructed images, since more sophisticated models of the scanner physics can be incorporated into the likelihood model than those used by analytical reconstruction methods, allowing for improved quantification of the radioactivity distribution. [ 60 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4423", "text": "Research has shown that  Bayesian  methods that involve a Poisson likelihood function and an appropriate  prior probability  (e.g., a smoothing prior leading to  total variation regularization  or a  Laplacian distribution  leading to  \n \n \n \n \n \u2113 \n \n 1 \n \n \n \n \n {\\displaystyle \\ell _{1}} \n \n -based regularization in a  wavelet  or other domain), such as via  Ulf Grenander 's  Sieve estimator [ 61 ] [ 62 ]  or via Bayes penalty methods [ 63 ] [ 64 ]  or via  I.J. Good 's roughness method [ 65 ] [ 66 ]  may yield superior performance to expectation-maximization-based methods which involve a Poisson likelihood function but do not involve such a prior. [ 67 ] [ 68 ] [ 69 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4424", "text": "Attenuation correction : Quantitative PET Imaging requires attenuation correction. [ 70 ]  In these systems attenuation correction is based on a transmission scan using  68 Ge rotating rod source. [ 71 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4425", "text": "Transmission scans directly measure attenuation values at 511\u00a0keV. [ 72 ]  Attenuation occurs when  photons  emitted by the radiotracer inside the body are absorbed by intervening tissue between the detector and the emission of the photon. As different LORs must traverse different thicknesses of tissue, the photons are attenuated differentially. The result is that structures deep in the body are reconstructed as having falsely low tracer uptake. Contemporary scanners can estimate attenuation using integrated x-ray CT equipment, in place of earlier equipment that offered a crude form of CT using a  gamma ray  ( positron  emitting) source and the PET detectors."}
{"_id": "WikiPedia_Radiology$$$corpus_4426", "text": "While attenuation-corrected images are generally more faithful representations, the correction process is itself susceptible to significant artifacts. As a result, both corrected and uncorrected images are always reconstructed and read together."}
{"_id": "WikiPedia_Radiology$$$corpus_4427", "text": "2D/3D reconstruction : Early PET scanners had only a single ring of detectors, hence the acquisition of data and subsequent reconstruction was restricted to a single transverse plane. More modern scanners now include multiple rings, essentially forming a cylinder of detectors."}
{"_id": "WikiPedia_Radiology$$$corpus_4428", "text": "There are two approaches to reconstructing data from such a scanner:"}
{"_id": "WikiPedia_Radiology$$$corpus_4429", "text": "3D techniques have better sensitivity (because more coincidences are detected and used) hence less noise, but are more sensitive to the effects of scatter and random coincidences, as well as requiring greater computer resources. The advent of sub-nanosecond timing resolution detectors affords better random coincidence rejection, thus favoring 3D image reconstruction."}
{"_id": "WikiPedia_Radiology$$$corpus_4430", "text": "Time-of-flight (TOF) PET : For modern systems with a higher time resolution (roughly 3 nanoseconds) a technique called \"time-of-flight\" is used to improve the overall performance. Time-of-flight PET makes use of very fast gamma-ray detectors and data processing system which can more precisely decide the difference in time between the detection of the two photons. It is impossible to localize the point of origin of the annihilation event exactly (currently within 10\u00a0cm). Therefore, image reconstruction is still needed. TOF technique gives a remarkable improvement in image quality, especially signal-to-noise ratio."}
{"_id": "WikiPedia_Radiology$$$corpus_4431", "text": "PET scans are increasingly read alongside CT or MRI scans, with the combination ( co-registration ) giving both anatomic and metabolic information (i.e., what the structure is, and what it is doing biochemically). Because PET imaging is most useful in combination with anatomical imaging, such as CT, modern PET scanners are now available with integrated high-end multi-detector-row CT scanners (PET-CT). Because the two scans can be performed in immediate sequence during the same session, with the patient not changing position between the two types of scans, the two sets of images are more precisely  registered , so that areas of abnormality on the PET imaging can be more perfectly correlated with anatomy on the CT images. This is very useful in showing detailed views of moving organs or structures with higher anatomical variation, which is more common outside the brain."}
{"_id": "WikiPedia_Radiology$$$corpus_4432", "text": "At the  J\u00fclich  Institute of Neurosciences and Biophysics, the world's largest PET-MRI device began operation in April 2009. A\u00a09.4- tesla  magnetic resonance tomograph (MRT) combined with a PET. Presently, only the head and brain can be imaged at these high magnetic field strengths. [ 73 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4433", "text": "For brain imaging, registration of CT, MRI and PET scans may be accomplished without the need for an integrated PET-CT or PET-MRI scanner by using a device known as the  N-localizer . [ 31 ] [ 74 ] [ 75 ] [ 76 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4434", "text": "The minimization of radiation dose to the subject is an attractive feature of the use of short-lived radionuclides. Besides its established role as a diagnostic technique, PET has an expanding role as a method to assess the response to therapy, in particular, cancer therapy, [ 77 ]  where the risk to the patient from lack of knowledge about disease progress is much greater than the risk from the test radiation. Since the tracers are radioactive, the elderly [ dubious  \u2013  discuss ]  and pregnant are unable to use it due to risks posed by radiation."}
{"_id": "WikiPedia_Radiology$$$corpus_4435", "text": "Limitations to the widespread use of PET arise from the high costs of cyclotrons needed to produce the short-lived radionuclides for PET scanning and the need for specially adapted on-site chemical synthesis apparatus to produce the radiopharmaceuticals after radioisotope preparation. Organic radiotracer molecules that will contain a positron-emitting radioisotope cannot be synthesized first and then the radioisotope prepared within them, because bombardment with a cyclotron to prepare the radioisotope destroys any organic carrier for it. Instead, the isotope must be prepared first, then the chemistry to prepare any organic radiotracer (such as FDG) accomplished very quickly, in the short time before the isotope decays. Few hospitals and universities are capable of maintaining such systems, and most clinical PET is supported by third-party suppliers of radiotracers that can supply many sites simultaneously. This limitation restricts clinical PET primarily to the use of tracers labelled with fluorine-18, which has a half-life of 110 minutes and can be transported a reasonable distance before use, or to rubidium-82 (used as  rubidium-82 chloride ) with a half-life of 1.27 minutes, which is created in a portable generator and is used for  myocardial   perfusion  studies. In recent years a few on-site cyclotrons with integrated shielding and \"hot labs\" (automated chemistry labs that are able to work with radioisotopes) have begun to accompany PET units to remote hospitals. The presence of the small on-site cyclotron promises to expand in the future as the cyclotrons shrink in response to the high cost of isotope transportation to remote PET machines. [ 78 ]  In recent years the shortage of PET scans has been alleviated in the US, as rollout of  radiopharmacies  to supply radioisotopes has grown 30%/year. [ 79 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4436", "text": "Because the half-life of fluorine-18 is about two hours, the prepared dose of a radiopharmaceutical bearing this radionuclide will undergo multiple half-lives of decay during the working day. This necessitates frequent recalibration of the remaining dose (determination of activity per unit volume) and careful planning with respect to patient scheduling."}
{"_id": "WikiPedia_Radiology$$$corpus_4437", "text": "The concept of emission and transmission  tomography  was introduced by  David E. Kuhl , Luke Chapman and Roy Edwards in the late 1950s. Their work would lead to the design and construction of several tomographic instruments at  Washington University School of Medicine  and later at the  University of Pennsylvania . [ 80 ]  In the 1960s and 70s tomographic imaging instruments and techniques were further developed by  Michel Ter-Pogossian ,  Michael E. Phelps ,  Edward J. Hoffman  and others at  Washington University School of Medicine . [ 81 ] [ 82 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4438", "text": "Work by Gordon Brownell, Charles Burnham and their associates at the  Massachusetts General Hospital  beginning in the 1950s contributed significantly to the development of PET technology and included the first demonstration of annihilation radiation for medical imaging. [ 83 ]  Their innovations, including the use of light pipes and volumetric analysis, have been important in the deployment of PET imaging. In 1961, James Robertson and his associates at Brookhaven National Laboratory built the first single-plane PET scan, nicknamed the \"head-shrinker.\" [ 84 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4439", "text": "One of the factors most responsible for the acceptance of positron imaging was the development of radiopharmaceuticals. In particular, the development of labeled 2-fluorodeoxy-D-glucose (FDG-firstly synthethized and described by two Czech scientists from  Charles University  in Prague in 1968) [ 85 ]  by the Brookhaven group under the direction of Al Wolf and Joanna Fowler was a major factor in expanding the scope of PET imaging. [ 86 ]  The compound was first administered to two normal human volunteers by  Abass Alavi  in August 1976 at the University of Pennsylvania. Brain images obtained with an ordinary (non-PET) nuclear scanner demonstrated the concentration of FDG in that organ. Later, the substance was used in dedicated positron tomographic scanners, to yield the modern procedure."}
{"_id": "WikiPedia_Radiology$$$corpus_4440", "text": "The logical extension of positron instrumentation was a design using two 2-dimensional arrays. PC-I was the first instrument using this concept and was designed in 1968, completed in 1969 and reported in 1972. The first applications of PC-I in tomographic mode as distinguished from the computed tomographic mode were reported in 1970. [ 87 ]  It soon became clear to many of those involved in PET development that a circular or cylindrical array of detectors was the logical next step in PET instrumentation. Although many investigators took this approach, James Robertson [ 88 ]  and  Zang-Hee Cho [ 89 ]  were the first to propose a ring system that has become the prototype of the current shape of PET. The first multislice cylindrical array PET scanner was completed in 1974 at the  Mallinckrodt Institute of Radiology  by the group led by Ter-Pogossian. [ 90 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4441", "text": "The PET-CT scanner, attributed to David Townsend and Ronald Nutt, was named by  Time  as the medical invention of the year in 2000. [ 91 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4442", "text": "As of August 2008,  Cancer Care Ontario  reports that the current average incremental cost to perform a PET scan in the province is CA$1,000\u20131,200 per scan. This includes the cost of the radiopharmaceutical and a stipend for the physician reading the scan. [ 92 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4443", "text": "In the United States, a PET scan is estimated to be US$1500-$5000."}
{"_id": "WikiPedia_Radiology$$$corpus_4444", "text": "In England, the  National Health Service  reference cost (2015\u20132016) for an adult outpatient PET scan is \u00a3798. [ 93 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4445", "text": "In Australia, as of July 2018, the  Medicare Benefits Schedule Fee  for whole body FDG PET ranges from A$953 to A$999, depending on the indication for the scan. [ 94 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4446", "text": "The overall performance of PET systems can be evaluated by quality control tools such as the  Jaszczak phantom . [ 95 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4447", "text": "Prophylactic cranial irradiation  ( PCI ) is a technique used to combat the occurrence of  metastasis  to the brain in highly aggressive  cancers  that commonly metastasize to brain, most notably  small-cell lung cancer . [ 1 ]   Radiation therapy is commonly used to treat known tumor occurrence in the brain, either with highly precise  stereotactic radiation  or therapeutic cranial irradiation.  By contrast, PCI is intended as preemptive treatment in patients with no known current intracranial tumor, but with high likelihood for harboring occult microscopic disease and eventual occurrence. [ 2 ]   For small-cell lung cancer with limited [ 3 ] [ 4 ]  and select cases of extensive disease, [ 5 ]  PCI has shown to reduce recurrence of brain metastases and improve overall survival in complete remission."}
{"_id": "WikiPedia_Radiology$$$corpus_4448", "text": "During the fervor to develop treatments for pediatric leukemia in the 1960s, there was initial experimentation with PCI for children with  ALL.   Although advances in  chemotherapy  had been able to successfully treat tumor throughout the body, there remained an alarming incidence of brain metastasis following systemic chemotherapy. A theory was developed that the brain was likely a pharmacologic sanctuary where sub-clinical metastases were protected from  cytotoxic drugs  by the  blood\u2013brain barrier .  Oncologists hypothesized that treatment of this sub-clinical disease with radiation therapy may stamp out the malignant process before it could advance to cause symptoms.  Indeed, subsequent studies showed that an increased rate of disease-free survival and overall survival in those children treated with PCI.  Due to successes with pediatric blood cancers, the concept of PCI was enlisted for the treatment of other types of cancers."}
{"_id": "WikiPedia_Radiology$$$corpus_4449", "text": "Over time, there has slowly been a shift away from PCI due to incidence of long-term side effects and secondary cancers, as well as evidence of equivalent control with alternate forms of treatment such as long-term  intrathecal chemotherapy . [ 6 ]   For ALL, PCI had been reserved only for high-risk cases; however, a 2009 study by Ching-Hon et al. reporting on the results of clinical trial NCT00137111 suggesting that PCI is unwarranted even in high-risk cases. [ 7 ]    Despite changing recommendations for ALL, PCI continues to play an important role in treatment of small-cell lung cancer."}
{"_id": "WikiPedia_Radiology$$$corpus_4450", "text": "Early trials for PCI in ALL utilized high-dose treatments, up to 24 Gy cumulative dose, that resulted in significant toxicity.  Further experiments showed that lower-dose treatments (12\u201318 Gy) [ 8 ] [ 9 ]  administered in smaller fractions provide equivalent benefit with lower neuro-toxicity."}
{"_id": "WikiPedia_Radiology$$$corpus_4451", "text": "Proton computed tomography (pCT) , or  proton CT , is an imaging modality first proposed by  Cormack  in 1963  [ 1 ]  and initial experiment explorations identified several advantages over conventional  X-ray CT  (xCT).  However, particle interactions such as multiple  Coulomb scattering  (MCS) and (in)elastic nuclear scattering events deflect the  proton  trajectory, resulting in nonlinear paths which can only be approximated via  statistical assumptions , leading to lower  spatial resolution  than  X-ray tomography .  Further experiments were largely abandoned until the advent of proton  radiation therapy  in the 1990s which renewed interest in the topic due to the potential benefits of imaging and treating patients with the same particle."}
{"_id": "WikiPedia_Radiology$$$corpus_4452", "text": "Proton computed tomography (pCT) uses measurements of a proton's position/ trajectory  and  energy  before and after traversing an object to reconstruct an image of the object where each  voxel  represents the  relative stopping power  (RSP) of the material composition of the corresponding region of the object.  The deviations of a proton's path inside the object are primarily due to interactions between the  Coulomb fields  of the  proton  and the  nuclei  in the absorbing material, resulting in many small-angle deflections as it passes through the object.   Statistical models  of the effect of MCS on the trajectory of a proton were developed to calculate the most likely path (MLP) of a proton given its entry and exit position/ trajectory  and corresponding uncertainty at intermediate depths within the object. [ 2 ] [ 3 ]   Additional (in)elastic nuclear scattering events can also occur which cause larger angle deviations, which cannot easily be modeled, but these are fairly easy to identify and remove from consideration in the image reconstruction process."}
{"_id": "WikiPedia_Radiology$$$corpus_4453", "text": "With an approximate path of a proton through the object, one can then identify the voxels through which the proton passed, and the difference between entry and exit energy indicates the energy collectively deposited in these voxels.  Assuming there are  \n \n \n \n J \n \n \n {\\displaystyle J} \n \n  voxels in the image, the distance,  \n \n \n \n \u0394 \n \n l \n \n j \n \n \n \n \n {\\displaystyle \\Delta l_{j}} \n \n , the proton travels through each voxel  \n \n \n \n j \n \u2208 \n J \n \n \n {\\displaystyle j\\in J} \n \n  varies along the path and the amount of energy deposited in each voxel,  \n \n \n \n \u0394 \n \n E \n \n h \n \n \n \n \n {\\displaystyle \\Delta E_{h}} \n \n , depends on this and the voxel's RSP,  \n \n \n \n \n x \n \n j \n \n \n \n \n {\\displaystyle x_{j}} \n \n .  The total energy loss  \n \n \n \n E \n \n \n {\\displaystyle E} \n \n  is the  line integral  of RSP scaled by the intersection length, or"}
{"_id": "WikiPedia_Radiology$$$corpus_4454", "text": "E \n = \n \u222b \n \n x \n \n j \n \n \n \u0394 \n \n l \n \n j \n \n \n \n \n {\\displaystyle E=\\int x_{j}\\Delta l_{j}}"}
{"_id": "WikiPedia_Radiology$$$corpus_4455", "text": "A  PSMA scan  is a  nuclear medicine  imaging technique used in the  diagnosis  and  staging  of prostate cancer. It is carried out by injection of a  radiopharmaceutical  with a  positron  or  gamma  emitting  radionuclide  and a  prostate-specific membrane antigen  (PSMA) targeting  ligand . After injection, imaging of positron emitters such as  gallium-68  ( 68 Ga),  copper-64  ( 64 Cu), and  fluorine-18  ( 18 F) is carried out with a  positron emission tomography  (PET) scanner. For gamma emitters such as  technetium-99m  ( 99m Tc) and  indium-111  ( 111 In)  single-photon emission computed tomography  (SPECT) imaging is performed with a  gamma camera ."}
{"_id": "WikiPedia_Radiology$$$corpus_4456", "text": "As well as the diagnosis and staging of prostate cancer, PSMA imaging can also be used to assess suitability for and plan treatment with  external beam radiotherapy  and PSMA-targeted  radionuclide therapy . [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4457", "text": "Attempts have been made to target the overexpression of PSMA in prostate cancer cells for several decades, although PSMA is also found in other tissue. PSMA targeting molecules have included antibodies, aptamers, peptides, and small-molecule inhibitors. [ 3 ] [ 4 ]  Initially, development focussed on the antibody capromab. Later research has focussed on small molecule  ligands  that bind to the extracellular active centre of PSMA, such as PSMA-11. [ 5 ]  These ligands for PSMA-scanning target the large extracellular region of the PSMA  glycoprotein . [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4458", "text": "PSMA however is also over-expressed in non prostate cancer cells, including kidney, salivary gland, lacrimal gland and duodenal mucosa, where physiological uptake may be seen on imaging. [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4459", "text": "European Association of Urology  (EAU) guidelines recognise that PSMA can provide accurate staging, however there is a lack of outcome data to inform further management. [ 8 ]  The  American Society of Clinical Oncology  (ASCO) guidelines for imaging of advanced prostate cancer also recommend PSMA imaging (among other PET radiopharmaceuticals), while acknowledging that these are not FDA approved and therefore limited to a clinical trial or other controlled research setting. [ 9 ]  A 2024 overview of reviews published in Seminars of Nuclear Medicine concluded that while evidence gaps remain for some outcomes and most systematic reviews are at high or unclear risk of bias, the evidence base is broadly supportive of 18-F PSMA PET/CT in patients with high-risk prostate cancer or biochemical recurrence  [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4460", "text": "In part thanks to the wide range of similar PSMA radiopharmaceuticals, [ 4 ] [ 16 ]  approval by regulatory authorities is at varying stages. Even so, use has been widespread in some areas, particularly as part of  clinical trials . For example,   European Association of Urology  (EAU) guidelines have included recommendations to perform PSMA PET scans in certain circumstances since 2018, and there has been widespread agreement of the utility of PSMA scanning for several years. [ 17 ] [ 18 ] [ 19 ] [ 20 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4461", "text": "A kit for manufacture of a  68 Ga-PSMA-11 product, branded Illucix, was approved by Australia's  Therapeutic Goods Administration  (TGA) in 2021. [ 21 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4462", "text": "A  marketing authorisation  application for  68 Ga-PSMA-11  ( INN  Gallium (68Ga) gozetotide), under the brand name Illucix, was made to the  Danish Medicines Agency , on behalf of several EU countries and the UK. Approval is expected in 2022. [ 22 ] [ 23 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4463", "text": "In 2022 a marketing authorisation application was made by the manufacturer of  18 F-DCFPyL  (branded Pylclari) to the  European Medicines Agency . [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4464", "text": "Polish manufacturer and distributor of radiopharmaceutical procuts, Polatom, has been granted a US patent for a  99m Tc-PSMA-T4 kit. [ 24 ] [ 25 ]  In the UK, Tc-99m labelled PSMA has product authorisation but lacks funding. [ 26 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4465", "text": "A new drug submission was made to  Canada's regulator  in 2021, for  68 Ga-PSMA-11. [ 27 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4466", "text": "The first approved PSMA imaging agent was  indium-111  ( 111 In) capromab pendetide (branded Prostascint). It received  Food and Drug Administration  (FDA) approval in 1996. [ 15 ]  However, the agent had poor sensitivity and saw little widespread use. [ 19 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4467", "text": "The first PET PSMA imaging agent,  68 Ga-PSMA-11, was approved by the FDA in 2020. [ 28 ]  Listed indications include suspected metastasis prior to initial treatment, and recurrence of prostate cancer (based on elevated serum  prostate-specific antigen  (PSA) level). [ 29 ]  This was followed by two further  68 Ga-PSMA-11 agents in 2021 and 2022 (branded Illucix and Locametz). [ 30 ] [ 31 ]  Listed indications for Lucametz additionally includes selection of patients prior to  177 Lu-PSMA  radionuclide therapy. [ 32 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4468", "text": "An  18 F-PSMA agent ( 18 F-DCFPyL) (branded Pylarify) was approved by the FDA in 2021. [ 33 ]  Indications are as for  68 Ga-PSMA-11. [ 34 ] [ 35 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4469", "text": "Another  18 F-PSMA agent ( 18 F-rhPSMA-7.3) (branded Posluma) was approved by the FDA in 2023. [ 36 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4470", "text": "68 Ga-PSMA-11 (Illucixwas) was granted initial authorisation in 2021, with full approval expected in 2022. [ 37 ] [ 38 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4471", "text": "A  radiation burn  is a damage to the  skin  or other  biological tissue  and organs as an  effect of radiation . The radiation types of greatest concern are  thermal radiation , radio frequency energy,  ultraviolet light  and  ionizing radiation ."}
{"_id": "WikiPedia_Radiology$$$corpus_4472", "text": "The most common type of radiation  burn  is a  sunburn  caused by UV radiation. High exposure to  X-rays  during diagnostic  medical imaging  or  radiotherapy  can also result in radiation burns. As the ionizing radiation interacts with  cells  within the body\u2014damaging them\u2014the body responds to this damage, typically resulting in  erythema \u2014that is, redness around the damaged area. Radiation burns are often discussed in the same context as  radiation-induced cancer  due to the ability of ionizing radiation to interact with and damage  DNA , occasionally inducing a cell to become cancerous.  Cavity magnetrons  can be improperly used to create surface and internal burning. Depending on the  photon   energy ,  gamma radiation  can cause deep  gamma burns , with  60 Co  internal burns common.  Beta burns  tend to be shallow as  beta particles  are not able to penetrate deeply into a body; these burns can be similar to sunburn.  Alpha particles  can cause internal  alpha burns  if inhaled, with external damage (if any) being limited to minor erythema."}
{"_id": "WikiPedia_Radiology$$$corpus_4473", "text": "Radiation burns can also occur with high power  radio transmitters  at any frequency where the body absorbs radio frequency energy and converts it to heat. [ 1 ]  The U.S.  Federal Communications Commission  (FCC) considers 50 watts to be the lowest power above which radio stations must evaluate emission safety. Frequencies considered especially dangerous occur where the human body can become  resonant , at 35\u00a0MHz, 70\u00a0MHz, 80-100\u00a0MHz, 400\u00a0MHz, and 1\u00a0GHz. [ 2 ]  Exposure to  microwaves  of too high intensity can cause  microwave burns ."}
{"_id": "WikiPedia_Radiology$$$corpus_4474", "text": "Radiation dermatitis  (also known as  radiodermatitis ) is a  skin disease  associated with prolonged exposure to ionizing radiation. [ 3 ] :\u200a131\u20132\u200a  Radiation dermatitis occurs to some degree in most patients receiving radiation therapy, with or without chemotherapy. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4475", "text": "There are three specific types of radiodermatitis: acute radiodermatitis, chronic radiodermatitis, and eosinophilic, polymorphic, and pruritic eruption associated with radiotherapy. [ 3 ] :\u200a39\u201340\u200a  Radiation therapy can also cause radiation cancer. [ 3 ] :\u200a40"}
{"_id": "WikiPedia_Radiology$$$corpus_4476", "text": "With interventional fluoroscopy, because of the high skin  doses  that can be generated in the course of the intervention, some procedures have resulted in early (less than two months after exposure) and/or late (two months or more after exposure) skin reactions, including necrosis in some cases. [ 5 ] :\u200a773"}
{"_id": "WikiPedia_Radiology$$$corpus_4477", "text": "Radiation dermatitis, in the form of intense erythema and  vesiculation  of the skin, may be observed in radiation ports. [ 3 ] :\u200a131"}
{"_id": "WikiPedia_Radiology$$$corpus_4478", "text": "As many as 95% of patients treated with radiation therapy for cancer will experience a skin reaction. Some reactions are immediate, while others may be later (e.g., months after treatment). [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4479", "text": "Acute radiodermatitis  occurs when an \"erythema dose\" of ionizing radiation is given to the skin, after which visible erythema appears up to 24 hours after. [ 3 ] :\u200a39\u200a   Radiation dermatitis generally manifests within a few weeks after the start of radiotherapy. [ 4 ] :\u200a143\u200a   Acute radiodermatitis, while presenting as red patches, may sometimes also present with  desquamation  or blistering. [ 7 ]   Erythema may occur at a dose of 2\u00a0 Gy  radiation or greater. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4480", "text": "Chronic radiodermatitis  occurs with chronic exposure to \"sub-erythema\" doses of ionizing radiation over a prolonged period, producing varying degrees of damage to the skin and its underlying parts after a variable latent period of several months to several decades. [ 3 ] :\u200a40\u200a   In the past this type of radiation reaction occurred most frequently in  radiologists  and  radiographers  who were constantly exposed to ionizing radiation, especially before the use of  X-ray filters . [ 3 ] :\u200a40\u200a   Chronic radiodermatitis, squamous and\nbasal cell carcinomas may develop months to years after radiation exposure. [ 7 ] :\u200a130\u200a [ 9 ]   Chronic radiodermatitis presents as atrophic indurated plaques, often whitish or yellowish, with telangiectasia, sometimes with  hyperkeratosis . [ 7 ] :\u200a130"}
{"_id": "WikiPedia_Radiology$$$corpus_4481", "text": "Eosinophilic, polymorphic, and pruritic eruption associated with radiotherapy  is a skin condition that occurs most often in women receiving cobalt radiotherapy for internal cancer. [ 3 ] :\u200a39\u201340"}
{"_id": "WikiPedia_Radiology$$$corpus_4482", "text": "Radiation-induced  erythema multiforme  may occur when  phenytoin  is given prophylactically to neurosurgical patients who are receiving whole-brain therapy and systemic steroids. [ 3 ] :\u200a130"}
{"_id": "WikiPedia_Radiology$$$corpus_4483", "text": "Radiation acne  is a cutaneous condition characterized by comedo-like  papules  occurring at sites of previous exposure to therapeutic ionizing radiation, skin lesions that begin to appear as the acute phase of radiation dermatitis begins to resolve. [ 10 ] :\u200a501"}
{"_id": "WikiPedia_Radiology$$$corpus_4484", "text": "Radiation recall reactions  occur months to years after radiation treatment, a reaction that follows recent administration of a chemotherapeutic agent and occurs with the prior radiation port, characterized by features of radiation dermatitis. [ 3 ] [ 11 ]   Restated, radiation recall dermatitis is an inflammatory skin reaction that occurs in a previously irradiated body part following drug administration. [ 12 ]   There does not appear to be a minimum dose, nor an established radiotherapy dose relationship. [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4485", "text": "\"Alpha burns\"  are caused by  alpha particles , which can cause extensive tissue damage if inhaled. [ 13 ]  Due to the keratin in the  epidermal layer  of the skin, external alpha burns are limited to only mild reddening of the outermost layer of skin. [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4486", "text": "\"Beta burns\" \u2014caused by  beta particles \u2014are shallow surface burns, usually of skin and less often of  lungs  or  gastrointestinal tract , caused by beta particles, typically from  hot particles  or dissolved  radionuclides  that came to direct contact with or close proximity to the body. They can appear similar to sunburn. Unlike gamma rays, beta emissions are stopped much more effectively by materials and therefore deposit all their energy in only a shallow layer of tissue, causing more intense but more localized damage. On cellular level, the changes in skin are similar to radiodermatitis."}
{"_id": "WikiPedia_Radiology$$$corpus_4487", "text": "The dose is influenced by relatively low penetration of beta emissions through materials. The  cornified   keratine  layer of  epidermis  has enough stopping power to absorb beta radiation with energies lower than 70\u00a0keV. Further protection is provided by clothing, especially shoes. The dose is further reduced by limited retention of radioactive particles on skin; a 1 millimeter particle is typically released in 2 hours, while a 50 micrometer particle usually does not adhere for more than 7 hours. Beta emissions are also severely attenuated by air; their range generally does not exceed 6 feet (1.8\u00a0m) and intensity rapidly diminishes with distance. [ 15 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4488", "text": "The  eye lens  seems to be the most sensitive organ to beta radiation, [ 16 ]  even in doses far below maximum permissible dose.  Safety goggles  are recommended to attenuate strong beta. [ 17 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4489", "text": "Careful washing of exposed body surface, removing the radioactive particles, may provide significant dose reduction. Exchanging or at least brushing off clothes also provides a degree of protection."}
{"_id": "WikiPedia_Radiology$$$corpus_4490", "text": "If the exposure to beta radiation is intense, the beta burns may first manifest in 24\u201348 hours by itching and/or burning sensation that last for one or two days, sometimes accompanied by  hyperaemia . After 1\u20133 weeks burn symptoms appear; erythema, increased  skin pigmentation  (dark colored patches and raised areas), followed by  epilation  and  skin lesions . Erythema occurs after 5\u201315\u00a0 Gy , dry desquamation after 17\u00a0Gy, and  bullous   epidermitis  after 72\u00a0Gy. [ 15 ]   Chronic radiation keratosis  may develop after higher doses. Primary erythema lasting more than 72 hours is an indication of injury severe enough to cause chronic radiation dermatitis. Edema of  dermal papillae , if present within 48 hours since the exposition, is followed by transepidermal  necrosis . After higher doses, the  malpighian layer  cells die within 24 hours; lower doses may take 10\u201314 days to show dead cells. [ 18 ]  Inhalation of beta radioactive isotopes may cause beta burns of lungs and  nasopharyngeal  region, ingestion may lead to burns of gastrointestinal tract; the latter being a risk especially for  grazing  animals."}
{"_id": "WikiPedia_Radiology$$$corpus_4491", "text": "Lost hair begins regrowing in nine weeks and is completely restored in about half a year. [ 19 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4492", "text": "The acute dose-dependent effects of beta radiation on skin are as follows: [ 20 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4493", "text": "According to other source: [ 21 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4494", "text": "As shown, the dose thresholds for symptoms vary by source and even individually. In practice, determining the exact dose tends to be difficult."}
{"_id": "WikiPedia_Radiology$$$corpus_4495", "text": "Similar effects apply to animals, with fur acting as additional factor for both increased particle retention and partial skin shielding. Unshorn thickly wooled sheep are well protected; while the epilation threshold for sheared sheep is between 23 and 47\u00a0Gy (2500\u20135000  rep ) and the threshold for normally wooled face is 47\u201393\u00a0Gy (5000\u201310000 rep), for thickly wooled (33\u00a0mm hair length) sheep it is 93\u2013140\u00a0Gy (10000\u201315000 rep). To produce skin lesions comparable with  contagious pustular dermatitis , the estimated dose is between 465 and 1395\u00a0Gy. [ 22 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4496", "text": "The effects depend on both the intensity and the energy of the radiation. Low-energy beta (sulfur-35, 170\u00a0keV) produces shallow ulcers with little damage to dermis, while  cobalt-60  (310\u00a0keV),  caesium-137  (550\u00a0keV),  phosphorus-32  (1.71\u00a0MeV),  strontium-90  (650\u00a0keV) and its daughter product  yttrium-90  (2.3\u00a0MeV) damage deeper levels of the  dermis  and can result in  chronic  radiation dermatitis. Very high energies from  electron beams  from  particle accelerators , reaching tens of megaelectronvolts, can be deeply penetrating. Conversely, megavolt-scale beams can deposit their energy deeper with less damage to the dermis; modern radiotherapy electron beam accelerators take advantage of this. At yet higher energies, above 16\u00a0MeV, the effect does not show significantly anymore, limiting the usefulness of higher energies for radiotherapy. As a convention, surface is defined as the topmost 0.5\u00a0mm of skin. [ 23 ]  High-energy beta emissions should be shielded with plastic instead of lead, as  high-Z  elements generate deeply penetrating gamma  bremsstrahlung ."}
{"_id": "WikiPedia_Radiology$$$corpus_4497", "text": "The electron energies from  beta decay  are not discrete but form a continuous spectrum with a cutoff at maximum energy. The rest of the energy of each decay is carried off by an  antineutrino  which does not significantly interact and therefore does not contribute to the dose. Most energies of beta emissions are at about a third of the maximum energy. [ 17 ]  Beta emissions have much lower energies than what is achievable from particle accelerators, no more than few megaelectronvolts."}
{"_id": "WikiPedia_Radiology$$$corpus_4498", "text": "The energy-depth-dose profile is a curve starting with a surface dose, ascending to the maximum dose in a certain depth d m  (usually normalized as 100% dose), then descends slowly through depths of 90% dose (d 90 ) and 80% dose (d 80 ), then falls off linearly and relatively sharply though depth of 50% dose (d 50 ). The extrapolation of this linear part of the curve to zero defines the maximum electron range, R p . In practice, there is a long tail of weaker but deep dose, called \"bremsstrahlung tail\", attributable to  bremsstrahlung . The penetration depth depends also on beam shape, narrower beam tend to have less penetration. In water, broad electron beams, as is the case in homogeneous surface contamination of skin, have d 80  about E/3\u00a0cm and R p  about E/2\u00a0cm, where E is the beta particle energy in MeV. [ 24 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4499", "text": "The penetration depth of lower-energy beta in water (and soft tissues) is about 2\u00a0mm/MeV. For a 2.3\u00a0MeV beta the maximum depth in water is 11\u00a0mm, for 1.1\u00a0MeV it is 4.6\u00a0mm. The depth where maximum of the energy is deposited is significantly lower. [ 25 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4500", "text": "The energy and penetration depth of several isotopes is as follows: [ 26 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4501", "text": "For a wide beam, the depth-energy relation for dose ranges is as follows, for energies in  megaelectronvolts  and depths in millimeters. The dependence of surface dose and penetration depth on beam energy is clearly visible. [ 24 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4502", "text": "Radiation burns are caused by exposure to high levels of radiation. Levels high enough to cause burn are generally lethal if received as a whole-body dose, whereas they may be treatable if received as a shallow or local dose."}
{"_id": "WikiPedia_Radiology$$$corpus_4503", "text": "Fluoroscopy  may cause burns if performed repeatedly or for too long. [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4504", "text": "Similarly, X-ray  computed tomography  and traditional  projectional radiography  have the potential to cause radiation burns if the exposure factors and exposure time are not appropriately controlled by the operator."}
{"_id": "WikiPedia_Radiology$$$corpus_4505", "text": "A study of radiation-induced skin injuries [ 27 ] [ 28 ]  has been performed by the  Food and Drug Administration  (FDA) based on results from 1994, [ 29 ]  followed by an advisory to minimize further fluoroscopy-induced injuries. [ 30 ]  The problem of radiation injuries due to fluoroscopy has been further investigated in review articles in 2000, [ 31 ]  2001, [ 32 ] [ 33 ]  2009 [ 34 ]  and 2010. [ 35 ] [ 36 ] [ 37 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4506", "text": "Beta burns are frequently the result of exposure to  radioactive fallout  after  nuclear explosions  or  nuclear accidents . Shortly after the explosion, the  fission products  have very high beta activity, with about two beta emissions per each gamma photon."}
{"_id": "WikiPedia_Radiology$$$corpus_4507", "text": "After the  Trinity test , the fallout caused localized burns on the backs of  cattle  in the area downwind. [ 38 ]  The fallout had the appearance of small flaky dust particles. The cattle showed temporary burns, bleeding, and loss of hair. Dogs were also affected; in addition to localized burns on their backs, they also had burned paws, likely from the particles lodged between their toes as hoofed animals did not show problems with feet. About 350\u2013600 cattle were affected by superficial burns and localized temporary loss of dorsal hair; the army later bought 75 most affected cows as the discolored regrown hair lowered their market value. [ 39 ]  The cows were shipped to Los Alamos and Oak Ridge, where they were observed. They healed, now sporting large patches of white fur; some looked as if they had been scalded. [ 40 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4508", "text": "The fallout produced by the  Castle Bravo  test was unexpectedly strong. A white snow-like dust, nicknamed by the scientists \"Bikini snow\" and consisting of contaminated crushed  calcined   coral , fell for about 12 hours upon the  Rongelap Atoll , depositing a layer of up to 2\u00a0cm. Residents developed beta burns, mostly on the backs of their necks and on their feet, [ 38 ]  and were resettled after three days. After 24\u201348 hours their skin was itching and burning; in a day or two the sensations subsided, to be followed after 2\u20133 weeks by epilation and ulcers. Darker-colored patches and raised areas appeared on their skin, blistering was uncommon. Ulcers formed dry scabs and healed. Deeper lesions, painful, weeping and ulcerated, formed on more contaminated residents; the majority healed with simple treatment. In general, the beta burns healed with some cutaneous  scarring  and depigmentation. Individuals who bathed and washed the fallout particles from their skin did not develop skin lesions. [ 20 ]  The fishing ship  Daigo Fukuryu Maru  was affected by the fallout as well; the crew suffered skin doses between 1.7 and 6.0\u00a0Gy, with beta burns manifesting as severe skin lesions, erythema,  erosions , sometimes necrosis, and skin  atrophy . Twenty-three U.S. radar servicemen of the 28-member weather station on  Rongerik [ 41 ]  were affected, experiencing discrete 1\u20134\u00a0mm skin lesions which healed quickly, and ridging of  fingernails  several months later. Sixteen crew members of the aircraft carrier  USS\u00a0 Bairoko  received beta burns, and there was an increased cancer rate. [ 15 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4509", "text": "During the Zebra test of the  Operation Sandstone  in 1948, three men had beta burns on their hands when removing sample collection filters from  drones  flying through the  mushroom cloud ; their estimated skin surface dose was 28 to 149\u00a0Gy, and their disfigured hands required  skin grafts . A fourth man showed weaker burns after the earlier Yoke test. [ 42 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4510", "text": "The  Upshot\u2013Knothole Harry  test at the  Frenchman Flat  site released a large amount of fallout. A significant number of sheep died after grazing on contaminated areas. The  AEC  however had a policy to compensate farmers only for animals showing external beta burns, so many claims were denied. Other tests on the Nevada Test Site also caused fallout and corresponding beta burns to sheep, horses and cattle. [ 43 ]  During the  Operation Upshot\u2013Knothole , sheep as far as 50 miles (80\u00a0km) from the test site developed beta burns to their backs and nostrils. [ 42 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4511", "text": "During  underground nuclear testing  in Nevada, several workers developed burns and skin ulcers, in part attributed to exposure to  tritium . [ 44 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4512", "text": "Beta burns were a serious medical issue for some victims of the  Chernobyl disaster ; from 115 patients treated in Moscow, 30% had burns covering 10\u201350% of body surface, 11% were affected on 50\u2013100% of skin; the massive exposure was often caused by clothes drenched with radioactive water. Some firefighters developed beta burns of lungs and nasopharyngeal region after inhalation of massive amounts of radioactive  smoke . Out of 28 deaths, 16 had skin injuries listed among the causes. The beta activity was extremely high, with beta/gamma ratio reaching 10\u201330  [ clarification needed ]  and beta energy high enough to damage  basal layer  of the skin, resulting in large area portals for  infections , exacerbated by damage to  bone marrow  and weakened  immune system . Some patients received skin dose of 400\u2013500\u00a0Gy. The infections caused more than half of the acute deaths. Several died of fourth degree beta burns between 9\u201328 days after dose of 6\u201316\u00a0Gy. Seven died after dose of 4\u20136\u00a0Gy and third degree beta burns in 4\u20136 weeks. One died later from second degree beta burns and dose 1-4\u00a0Gy. [ 44 ]  The survivors have atrophied skin which is  spider veined  and with underlying  fibrosis . [ 15 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4513", "text": "The burns may manifest at different times at different body areas. The  Chernobyl liquidators ' burns first appeared on wrists, face, neck and feet, followed by chest and back, then by knees, hips and buttocks. [ 45 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4514", "text": "Industrial radiography  sources are a common source of beta burns in workers."}
{"_id": "WikiPedia_Radiology$$$corpus_4515", "text": "Radiation therapy sources can cause beta burns during exposure of the patients. The sources can be also lost and mishandled, as in the  Goi\u00e2nia accident , during which several people had external beta burns and more serious gamma burns, and several died. Numerous accidents also occur during radiotherapy due to equipment failures, operator errors, or wrong dosage."}
{"_id": "WikiPedia_Radiology$$$corpus_4516", "text": "Electron beam sources and particle accelerators can be also sources of beta burns. [ 46 ]  The burns may be fairly deep and require skin grafts, tissue  resection  or even  amputation  of fingers or limbs. [ 47 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4517", "text": "Radiation burns should be covered by a clean, dry dressing as soon as possible to prevent infection.  Wet dressings are not recommended. [ 48 ]  The presence of combined injury (exposure to radiation plus trauma or radiation burn) increases the likelihood of generalized sepsis. [ 49 ]  This requires  administration of systemic antimicrobial  therapy. [ 50 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4518", "text": "Radiation colitis  is injury to the  colon  caused by  radiation therapy .   It is usually associated with treatment for  prostate cancer  or  cervical cancer . [ 1 ]   Common symptoms are  diarrhea , a  feeling of being unable to empty the bowel , [ 2 ]  gastrointestinal bleeding, and abdominal pain. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4519", "text": "If symptoms of radiation colitis onset within 60 days of exposure to radiation, it is referred to as acute; otherwise, it is classified as chronic.  Acute radiation colitis may onset within a few hours of radiation exposure, and may clear up within two or three months after radiation ends. Between 5 and 15% of individuals who receive radiation to the pelvis may have chronic radiation colitis. [ 1 ]  Radiation therapy can also affect the  bowel  at the  small intestine  ( radiation enteritis ) or the  rectum  ( radiation proctitis ). [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4520", "text": "Tenesmus  or  diarrhea  appear to be the most common symptoms in patients with radiation colitis. Patients may also exhibit perforation or obstruction. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4521", "text": "Radiation colitis is typically brought on by  radiation therapy  administered to the pelvis for prostate, cervix, uterus, anus, rectum, or bladder cancers. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4522", "text": "Radiation primarily harms rapidly dividing cells by causing  DNA  strand loss that results in irreversible DNA changes. Consequently, the G2/M phase of the cell cycle, when the  DNA strands  are arranged into well-defined  chromatin  pairs and prepared for division into two  daughter cells , is when radiation damage is greatest. [ 4 ]   Colocytes , the cells that divide quickly that make up the  epithelium  lining the colon, undergo regeneration every five to six days. Its quick regeneration also makes it more vulnerable to radiation-related damage. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4523", "text": "Genetic and  cytokine  interactions are necessary for the active process of  programmed cell death  known as  apoptosis . Research on animals has demonstrated a significant increase in intestinal crypt apoptosis following low-dose radiation exposure. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4524", "text": "Through its strong fibrogenic and proinflammatory effects,  TGF-\u03b2  also plays a significant role in the pathogenesis of chronic radiation colitis.  TGF-\u03b2  levels in irradiated tissues are significantly higher and stay elevated in smooth muscle cells, vascular endothelial cells, and  fibrocytes  for up to 26 weeks. [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4525", "text": "Radiation colitis is characterized histologically by stromal injury followed by progressive  fibrosis  that results in epithelial  atrophy  and persistent mucosal  ischemia . [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4526", "text": "Radiation enteropathy  is a  syndrome  that may develop following abdominal or pelvic  radiation therapy  for  cancer . [ 1 ] [ 2 ]  Many affected people are  cancer survivors  who had treatment for  cervical cancer  or  prostate cancer .  It has also been termed  pelvic radiation disease  with  radiation proctitis  being one of its principal features [ 3 ]  and  radiation-induced lumbar plexopathy (RILP)  being a rare consequence. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4527", "text": "People who have been treated with  radiotherapy  for pelvic and other abdominal cancers frequently develop gastrointestinal symptoms. [ 3 ] [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4528", "text": "These include:"}
{"_id": "WikiPedia_Radiology$$$corpus_4529", "text": "Gastrointestinal symptoms are often found together with those in other systems including  genitourinary disorders  and  sexual dysfunction . The burden of symptoms substantially impairs the patients'  quality of life . [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4530", "text": "Nausea, vomiting, fatigue, and diarrhea may happen early during the course of radiotherapy.  Radiation enteropathy represents the longer-term, chronic effects that may be found after a latent period most commonly of 6 months to 3 years after the end of treatment.  In some cases, it does not become a problem for 20\u201330 years after successful curative therapy. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4531", "text": "A large number of people receive abdominal and or pelvic  radiotherapy  as part of their cancer treatment with 60\u201380% experiencing gastrointestinal symptoms. [ 1 ]   This is used in standard therapeutic regimens for  cervical cancer ,  prostate cancer ,  rectal cancer ,  anal cancer ,  lymphoma  and other abdominal malignancies.  Symptoms can be made worse by the effects of surgery, chemotherapy or other drugs given to treat the cancer. [ 5 ]   Improved methods of radiotherapy have reduced the exposure of non-involved tissues to radiation, concentrating the effects on the cancer.  However, as the parts of the intestine such as the  ileum  and the  rectum  are immediately adjacent to the cancers, it is impossible to avoid some radiation effects. [ 1 ]   Previous intestinal surgery, obesity, diabetes, tobacco smoking and vascular disorders increase the chances of developing enteropathy. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4532", "text": "Early radiation enteropathy is very common during or immediately after the course of radiotherapy.  This involves cell death, mucosal  inflammation  and epithelial barrier dysfunction. This injury is termed  mucositis  and results in symptoms of nausea, vomiting, fatigue, diarrhea and abdominal pain. [ 1 ] [ 6 ]   It recovers within a few weeks or months."}
{"_id": "WikiPedia_Radiology$$$corpus_4533", "text": "The delayed effects, found 3 months or more after radiation therapy, produce pathology which includes  intestinal   epithelial  mucosal  atrophy , vascular  sclerosis , and progressive  fibrosis  of the  intestinal wall , among other changes in intestinal  neuroendocrine  and immune cells and in the  gut microbiota . [ 1 ] [ 6 ]  These changes may produce  dysmotility , strictures,  malabsorption  and bleeding.  Problems in the terminal ileum and rectum predominate. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4534", "text": "Multiple disorders are found in patients with radiation enteropathy, so guidance including an algorithmic approach to their investigation has been developed. [ 5 ] [ 7 ]   This includes a holistic assessment with investigations including  upper endoscopy ,  colonoscopy , breath tests and other nutritional and gastrointestinal tests.  Full investigation is important as many cancer survivors of radiation therapy develop other causes for their symptoms such as  colonic polyps ,  diverticular disease  or  hemorrhoids . [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4535", "text": "Prevention of radiation injury to the small bowel is a key aim of techniques such as  brachytherapy , field size, multiple field arrangements, conformal radiotherapy techniques and intensity-modulated radiotherapy.  Medications including  ACE inhibitors ,  statins  and  probiotics  have also been studied and reviewed. [ 2 ] [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4536", "text": "In people presenting with symptoms compatible with radiation enteropathy, the initial step is to identify what is responsible for causing the symptoms. Management is best with a multidisciplinary team including gastroenterologists, nurses, dietitians, surgeons and others. [ 1 ]  Medical treatments include the use of  hyperbaric oxygen  which has beneficial effects in  radiation proctitis  or anal damage. [ 10 ]  Nutritional therapies include treatments directed at specific malabsorptive disorders such as low fat diets and  vitamin B12  or  vitamin D  supplements, together with  bile acid sequestrants  for  bile acid diarrhea  and possibly antibiotics for  small intestinal bacterial overgrowth . [ 2 ]  Probiotics have all been suggested as another therapeutic avenue. [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4537", "text": "Endoscopic therapies including  argon plasma coagulation  have been used for bleeding  telangiectasia  in radiation proctitis and at other intestinal sites, although there is a rick of perforation. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4538", "text": "Surgical treatment may be needed for  intestinal obstruction ,  fistulae , or perforation, which can happen in more severe cases. [ 12 ]   These can be fatal if patients present as an emergency, but with improved radiotherapy techniques are now less common. [ citation needed ] \nA systematic review has found there is some promising evidence for non-surgical interventions for late rectal damage, however due to low quality evidence no conclusions could be drawn. [ 13 ]  Optimal treatment usually produces significant improvements in quality of life. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4539", "text": "An increasing number of people are now surviving cancer, with improved treatments producing cure of the malignancy ( cancer survivors ).  There are now over 14 million such people in the US, and this figure is expected to increase to 18 million by 2022. [ 14 ]   More than half are survivors of abdominal or pelvic cancers, with about 300,000 people receiving abdominal and pelvic radiation each year.  It has been estimated there are 1.6 million people in the US with post-radiation intestinal dysfunction, a greater number than those with  inflammatory bowel disease  such as  Crohn's disease  or  ulcerative colitis . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4540", "text": "New agents have been identified in animal studies that may have effects on intestinal radiation injury. [ 1 ]   The research approach in humans has been reviewed. [ 15 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4541", "text": "A  radiation oncologist  is a specialist physician who uses  ionizing radiation  (such as  megavoltage X-rays  or  radionuclides ) in the treatment of  cancer .  Radiation oncology is one of the three primary specialties, the other two being surgical and medical oncology, involved in the treatment of cancer.  Radiation can be given as a curative modality, either alone or in combination with surgery and/or chemotherapy. It may also be used palliatively, to relieve symptoms in patients with incurable cancers. A radiation oncologist may also use radiation to treat some  benign  diseases, including benign tumors.  In some countries (not the United States), radiotherapy and chemotherapy are controlled by a single  oncologist  who is a \"clinical oncologist\". Radiation oncologists work closely with other physicians such as  surgical oncologists ,  interventional radiologists ,   internal medicine  subspecialists, and medical oncologists, as well as  medical physicists  and technicians as part of the multi-disciplinary cancer team. [ 1 ]  Radiation oncologists undergo four years of oncology-specific training whereas oncologists who deliver chemotherapy have two years of additional training in cancer care during fellowship after internal medicine residency in the United States."}
{"_id": "WikiPedia_Radiology$$$corpus_4542", "text": "In the United States, radiation oncologists undergo four years of residency (in addition to an internship), which is more dedicated to oncology training than any other medical specialty. During the four years of post-graduate training, residents learn about clinical oncology, the physics and biology of ionizing radiation, and the treatment of cancer patients with radiation.  After completion of this training, a radiation oncologist may undergo certification by the  American Board of Radiology  (ABR). Board certification includes three written tests and an oral examination which is given only once per year. The written tests include separate exams in radiation physics, and radiobiology, clinical oncology, which is followed by an eight-part oral examination given in the late spring one year into practice. Successfully passing these tests leads to the granting of a time-limited board certification. Recertification is obtained via a series of continuing medical education and practice qualifications including a written exam, clinical practice parameter evaluation, continuing medical education credits, and meeting community practice standards. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4543", "text": "Radiotherapy training in India encompasses the treatment of solid tumors in terms of  Chemotherapy ,  radiation therapy , and  palliative care  in most states. Postgraduate MD degree is awarded after 3 years of post-MBBS in-service comprehensive training and a final university level exam. MD Radiation oncology practitioners are the most proficient oncologists in India delivering radiotherapy and chemotherapy. The first Radiotherapy department of Asia was set up in 1910 at  Calcutta Medical College  in the state of West Bengal and is still a leading oncology training center of India. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4544", "text": "Radiation Oncology training in Canada is very similar to the United States. Radiation oncologists directly enter radiation oncology residencies of 5 years duration, with the first year as an internship year. During the next four years, residents complete intensive training in clinical oncology, in radiophysics and radiobiology, and in the treatment planning and delivery of radiotherapy. [ 2 ]  Most radiation oncologists also pursue a fellowship after their residency, examples of which include  brachytherapy ,  intensity modulated radiation therapy  (IMRT), gynecologic radiation oncology, and many others.  Radiation oncologists in Canada commonly treat two or three different anatomic sites, such as head and neck, breast, genitourinary, hematologic, gynecologic, central nervous system, or lung cancer."}
{"_id": "WikiPedia_Radiology$$$corpus_4545", "text": "In the United Kingdom, clinical oncologists, who practise radiotherapy are also fully qualified to administer chemotherapy. After completion of their basic medical degree, all oncologists must train fully in general internal medicine and pass the  MRCP  exam, normally 3\u20134 years after qualification. Following this, 5 years of Specialist Registrar (SpR) training is required in all non-surgical aspects of oncology in a recognised training program. During this time, the trainee must pass the  FRCR  examination in order to qualify for specialist registration as a clinical oncologist. A significant proportion of trainees will extend their time to undertake an academic fellowship, MD, or PhD. Almost all consultant clinical oncologists in the UK are Fellows of the  Royal College of Radiologists , the governing body of the specialty. Whilst most oncologists will treat a selection of common general oncology cases, there is increasing specialisation, with the expectation that consultants will specialise in one or two subsites."}
{"_id": "WikiPedia_Radiology$$$corpus_4546", "text": "In Australia and New Zealand,  The Royal Australian and New Zealand College of Radiologists  (RANZCR  Home | RANZCR ) awards a Fellowship (FRANZCR) to trainees after a 5-year program and several sets of exams and modules. As in other countries, radiation oncologists tend to subspecialize although generalists will always exist in smaller centres. Although trained in the delivery of chemotherapy, radiation oncologists in Australia and New Zealand rarely prescribe it."}
{"_id": "WikiPedia_Radiology$$$corpus_4547", "text": "In Iran, radiation oncologists, who are trained in non-surgical aspects of oncology (including radiation therapy) directly enter a 5-year residency program after completion of 7 years of training in general medicine and acceptance in national comprehensive residency exam."}
{"_id": "WikiPedia_Radiology$$$corpus_4548", "text": "In  Nepal , only  Bir Hospital  runs residency program on Radiation Oncology, under NAMS. It's a 3 years residency program, and the main domains are Chemotherapy, Radiotherapy and Palliative Care."}
{"_id": "WikiPedia_Radiology$$$corpus_4549", "text": "In Spain Radiation Oncology Specialists undertake a 4 year specialization program and are recognized to apply both ionizing radiation therapies and chemotherapy. Most fellows follow the policies emerged from leading national society SEOR (Sociedad Espa\u00f1ola de Oncolog\u00eda Radioter\u00e1pica)."}
{"_id": "WikiPedia_Radiology$$$corpus_4550", "text": "The Radiation oncologist is responsible for preparing the treatment plan where the radiation is required.  Some of the treatment methods are radioactive implantations, external beam radiotherapy, hyperthermia, and combined modality therapy such as radiotherapy with surgery, chemotherapy, or immunotherapy. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4551", "text": "To provide the treatment correctly, a series of equipment is needed which will help to complement it. First, a simulator and treatment preparation must be carried out. This consists of locating the area where the tumor is located to know where exactly the patient will be exposed at the time of treatment. The equipment used to perform this work is a computed tomography (CT) scan, a Magnetic resonance imaging (MRI), and W x-ray. Subsequently, the site targeted for treatment is marked and an immobilizer is created which helps to limit exposure another body area to the radiation. To complement this immobilizer staff will employ tape, foam sponges, headrests, molds and plaster casts. When treatment is in the head and neck area a thermoplastic mask is employed. This mask is precisely molded to the patient's shape and secured it to fasteners on the treatment table. This improves patient stability. When the treatment plan is complete, the patient will be assigned (depending upon the type of cancer and its stage) appointments to perform the therapy and monitoring. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4552", "text": "Radiation proctitis  or  radiation proctopathy  is a condition characterized by damage to the rectum after exposure to  x-rays  or other  ionizing radiation  as a part of  radiation therapy . [ 1 ]  Radiation proctopathy may occur as acute inflammation called  \"acute radiation proctitis\"  (and the related  radiation colitis ) or with chronic changes characterized by  radiation associated vascular ectasiae (RAVE) and chronic radiation proctopathy . [ 2 ] [ 1 ]   Radiation proctitis most commonly occurs after pelvic radiation treatment for  cancers  such as  cervical cancer ,  prostate cancer ,  bladder cancer , and  rectal cancer . RAVE and chronic radiation proctopathy involves the lower  intestine , primarily the  sigmoid colon  and the rectum, and was previously called chronic radiation proctitis,  pelvic radiation disease  and  radiation enteropathy . [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4553", "text": "Acute radiation proctopathy often causes pelvic pain, diarrhea, urgency, and the urge to defecate despite having an empty colon (tenesmus). [ 4 ]  Hematochezia and fecal incontinence may occur, but are less common. [ 4 ]  Chronic radiation damage to the rectum (>3 months) may cause rectal bleeding, incontinence, or a change in bowel habits secondary. Severe cases may lead to with strictures or fistulae formation. [ 5 ] [ 4 ]  Chronic radiation proctopathy can present at a median time of 8-12 months following radiation therapy. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4554", "text": "Acute radiation proctopathy occurs due to direct damage of the lining ( epithelium ) of the colon. [ 1 ]  Rectal biopsies of acute radiation proctopathy show superficial depletion of epithelial cells and acute inflammatory cells located in the lamina propria. [ 4 ]  By contrast, rectal biopsies of RAVE and chronic radiation proctopathy demonstrates ischemic endarteritis of the submucosal arterioles, submucosal fibrosis, and neovascularization. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4555", "text": "Where chronic radiation proctopathy or RAVE is suspected, a thorough evaluation of symptoms is essential. Evaluation should include an assessment of risk factors for alternate causes of proctitis, such as  C. difficile colitis ,  NSAID use , and travel history. [ 6 ]  Symptoms such as diarrhea and painful defecation need to be systematically investigated and the underlying causes each carefully treated. [ 7 ]  Testing for parasitic infections ( amebiasis ,  giardiasis ) and sexually transmitted infections ( Neisseria gonorrhoeae  and  herpes simplex virus ) should be considered. [ 6 ]  The location of radiation treatment is important, as radiation directed at regions of the body other than the pelvis (eg brain, chest, etc) should  not  prompt consideration of radiation proctopathy. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4556", "text": "Endoscopy is the mainstay of diagnosis for radiation damage to the rectum, with either  colonoscopy  or  flexible sigmoidoscopy . RAVE is usually recognized by the macroscopic appearances on endoscopy characterized by vascular ectasias. [ 8 ]  Mucosal biopsy may aid in ruling out alternate causes of proctitis, but is not routinely necessary and may increase the risk of fistulae development. [ 6 ]   Telangiectasias  are characteristic and prone to bleeding. [ 3 ]  Additional endoscopic findings may include pallor (pale appearance), edema, and friability of the mucosa."}
{"_id": "WikiPedia_Radiology$$$corpus_4557", "text": "Radiation proctitis can occur a few weeks after treatment, or after several months or years:"}
{"_id": "WikiPedia_Radiology$$$corpus_4558", "text": "Several methods have been studied in attempts to lessen the effects of radiation proctitis. Acute radiation proctitis usually resolves without treatment after several months. When treatment is necessary, symptoms often improve with hydration, anti-diarrheal agents, and discontinuation of radiation. [ 4 ]   Butyrate   enemas  may also be effective. [ 9 ] [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4559", "text": "In contrast, RAVE and chronic radiation proctopathy usually is not self-limited and often requires additional therapies. [ 4 ]  These include  sucralfate ,  hyperbaric oxygen therapy ,  corticosteroids ,  metronidazole ,  argon plasma coagulation ,  radiofrequency ablation  and  formalin  irrigation. [ 1 ] [ 3 ] [ 11 ]  The average number of treatment sessions with argon plasma coagulation to achieve control of bleeding ranges from 1 to 2.7 sessions. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4560", "text": "In rare cases that do not respond to medical therapy and endoscopic treatment, surgery may be required.  Overall, less than 10 percent of individuals with radiation proctopathy require surgery. [ 4 ]  In addition, complications such as obstruction and fistulae may require  surgery ."}
{"_id": "WikiPedia_Radiology$$$corpus_4561", "text": "Up to 30 percent of individuals who receive pelvic radiation therapy for cancer may develop radiation proctopathy. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4562", "text": "In  radiotherapy ,  radiation treatment planning  ( RTP ) is the process in which a team consisting of  radiation oncologists ,  radiation therapist ,  medical physicists  and  medical dosimetrists  plan the appropriate external beam radiotherapy or internal  brachytherapy  treatment technique for a patient with  cancer ."}
{"_id": "WikiPedia_Radiology$$$corpus_4563", "text": "In the early days of radiotherapy planning was performed on 2D  x-ray  images, often by hand and with manual calculations. Computerised treatment planning systems began to be used in the 1970s to improve the accuracy and speed of dose calculations. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4564", "text": "By the 1990s  CT scans , more powerful computers, improved dose calculation algorithms and  Multileaf collimators  (MLCs) lead to 3D conformal planning (3DCRT), categorised as a Level 2 technique by the European Dynarad consortium. [ 2 ] [ 3 ]  3DCRT uses MLCs to shape the radiotherapy beam to closely match the shape of a target tumour, reducing the dose to healthy surrounding tissue. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4565", "text": "Level 3 techniques such as  IMRT  and  VMAT  utilise inverse planning to provide further improved dose distributions (i.e. better coverage of target tumours and sparing of healthy tissue). [ 5 ] [ 6 ]  These methods are growing in use, particularly for cancers in certain locations which have been shown to derive the greatest benefits. [ 7 ] [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4566", "text": "Typically,  medical imaging  is used to form a  virtual patient  for a computer-aided design procedure. A  CT scan  is often the primary image set for treatment planning while  magnetic resonance imaging  provides excellent secondary image set for soft tissue contouring.  Positron emission tomography  is less commonly used and reserved for cases where specific uptake studies can enhance planning target volume delineation. [ 9 ]  Modern treatment planning systems provide tools for multimodality image matching, also known as image coregistration or fusion. Treatment simulations are used to plan the geometric, radiological, and dosimetric aspects of the therapy using radiation transport simulations and  optimization . For  intensity modulated radiation therapy  ( IMRT ), this process involves selecting the appropriate beam type (which may include photons, electrons and protons), energy (e.g. 6, 18  megaelectronvolt  (MeV) photons) and physical arrangements. In  brachytherapy  planning involves selecting the appropriate catheter positions and source dwell times\n [ 10 ] [ 11 ] \n(in HDR brachytherapy) or seed positions (in LDR brachytherapy)."}
{"_id": "WikiPedia_Radiology$$$corpus_4567", "text": "The more formal optimization process is typically referred to as  forward planning  and  inverse planning . [ 12 ] [ 13 ] \nPlans are often assessed with the aid of  dose-volume histograms , allowing the clinician to evaluate the uniformity of the dose to the diseased tissue (tumor) and sparing of healthy structures."}
{"_id": "WikiPedia_Radiology$$$corpus_4568", "text": "In forward planning, the planner places beams into a radiotherapy treatment planning system that can deliver sufficient radiation to a  tumour  while both sparing critical  organs  and minimising the dose to healthy tissue. The required decisions include how many radiation beams to use, which angles each will be delivered from, whether attenuating  wedges  be used, and which MLC configuration will be used to shape the radiation from each beam."}
{"_id": "WikiPedia_Radiology$$$corpus_4569", "text": "Once the treatment planner has made an initial plan, the treatment planning system calculates the required monitor units to deliver a prescribed dose to a specific area, and the distribution of dose in the body this will create. The dose distribution in the patient is dependent on the anatomy and beam modifiers such as wedges, specialized collimation, field sizes, tumor depth, etc. The information from a prior  CT scan  of the patient allows more accurate modelling of the behaviour of the radiation as it travels through the patient's tissues. Different dose calculation models are available, including  pencil beam ,  convolution-superposition  and  monte carlo simulation , with precision versus computation time being the relevant trade-off."}
{"_id": "WikiPedia_Radiology$$$corpus_4570", "text": "This type of planning is only sufficiently adept to handle relatively simple cases in which the tumour has a simple shape and is not near any critical organs."}
{"_id": "WikiPedia_Radiology$$$corpus_4571", "text": "In inverse planning a radiation oncologist defines a patient's critical organs and tumour, after which a planner gives target doses and importance factors for each. Then, an optimisation program is run to find the treatment plan which best matches all the input criteria. [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4572", "text": "In contrast to the manual trial-and-error process of forward planning, inverse planning uses the optimiser to solve the  Inverse Problem  as set up by the planner. [ 15 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4573", "text": "Radiation-induced lumbar plexopathy (RILP)  or  radiation-induced lumbosacral plexopathy (RILSP)  is nerve damage in the pelvis and lower spine area caused by therapeutic radiation treatments.  RILP is a rare side effect of  external beam radiation therapy [ 1 ] [ 2 ] [ 3 ]  and both  interstitial and intracavity brachytherapy  radiation implants. [ 4 ] [ 5 ]   RILP is a  Pelvic Radiation Disease  symptom. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4574", "text": "In general terms, such nerve damage may present in stages, earlier as  demyelination  and later as complications of  chronic radiation fibrosis . RILP occurs as a result of  radiation therapy  administered to treat  lymphoma  or cancers within the abdomen or pelvic area such as cervical, ovarian, bladder, kidney, pancreatic, prostate, testicular, colorectal, colon, rectal or anal  cancer . [ 7 ] [ 8 ]  The  lumbosacral plexus  area is  radiosensitive  and  radiation plexopathy  can occur after exposure to mean or maximum radiation levels of 50-60  Gray [ 7 ]  with a significant rate difference noted within that range. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4575", "text": "Lumbosacral plexopathy is characterized by any of the following symptoms; usually bi-lateral and symmetrical, though unilateral is known. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4576", "text": "Symptoms are typically a step-wise progression with periods of stability in between, [ 1 ] [ 3 ]  weakness often appearing years later. [ 8 ]   Weakness frequently presents in the lower leg muscle groups. [ 8 ]   Symptoms are usually irreversible. [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4577", "text": "Initial onset of symptoms may occur as early as 2 [ 8 ]  to 3 [ 11 ] [ 1 ]  months after radiotherapy.  The median onset is approximately 5 years, [ 8 ]  but can be highly variable, 2-3 decades after radiation therapy. [ 8 ]  One case study recorded the initial onset occurring 36 years post treatment. [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4578", "text": "The treatment's ionizing radiation is an activation mechanism for  apoptosis (cell death)  within the targeted cancer, [ 13 ]  but it can also impact nearby healthy radiosensitive tissues, like the  lumbosacral plexus . The occurrence and severity of RILP is related to the magnitude of  ionizing radiation [ 10 ]  and the  radiosensitivity  of peripheral nerves may be further aggravated when combined with chemotherapy, like taxanes and platinum drugs, during treatment. [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4579", "text": "The  pathophysiological process  behind radiation's RILP nerve damage has been discussed since the 1960s [ 10 ]  and is still without a precise definition. [ 1 ] [ 13 ]   Consensus does exist on a progression of RILP symptoms, with a stepping (a time delay) between two periods of plexopathy onset, the first from radiation injury and the later from fibrosis. Proposed mechanisms of the early nerve damage include microvascular damage ( ischemia ) supplying the myelin, [ 1 ]  radiation damage of the myelin, [ 15 ]  and oxygen free radical cell damage. [ 1 ] [ 15 ]  The delayed nerve damage is attributed to  compression neuropathy [ 1 ]  and a late fibro-atrophic ischemia from retractile fibrosis. [ 1 ] [ 15 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4580", "text": "The more common source of lumbar  plexopathy  is a direct or secondary [ 2 ]  tumor involvement of the plexus with  MRI  being the typical confirmation tool. [ 15 ]  Tumors typically present with enhancement of nerve roots and T2-weighted hyperintensity. [ 2 ]  The differential consideration of RILP requires taking a  medical history  and neurologic examination. [ 15 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4581", "text": "RILP's neurological symptoms can mimic other nerve disorders. People may present with pure lower motor neuron syndrome, a symptom of  amyotrophic lateral sclerosis (ALS) . [ 4 ] [ 16 ]  RILP may also be misdiagnosed as   leptomeningeal metastasis  often showing nodular  MRI  enhancement of the  cauda equina nerve roots  or having increased  CSF protein content . [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4582", "text": "Other differential diagnoses to consider are  Chronic Inflammatory Demyelinating Polyradiculoneuropathy ,  neoplastic lumbosacral   plexopathy,  paraneoplastic neuronopathy ,  diabetic lumbosacral plexopathy ,  degenerative disk disease  ( osteoporosis of the spine ),  Osteoarthritis of the spine ,  Lumbar Spinal Stenosis , post-infectious plexopathy,  carcinomatous meningitis (CM) ,  mononeuritis multiplex , and  chemotherapy-induced plexopathy . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4583", "text": "The testing to resolve a RILP diagnosis involves  blood serum  analysis,  X-rays ,  EMG , MRI and  cerebrospinal fluid   analysis . [ 2 ] [ 1 ] [ 15 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4584", "text": "Since RILP's neurological changes are typically irreversible and a curative strategy has yet to be defined, prevention is the best approach. [ 1 ]  Treating the primary cancer remains an obvious requirement, but lower levels of lumbar plexus radiation dosing will minimize or eliminate RILP. [ 1 ] [ 15 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4585", "text": "One method to reduce the lumbosacral plexus' dosing is to include it with other at-risk organs that get spared from radiation. [ 17 ] [ 18 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4586", "text": "Key to prevention is resolving the lack of clinical evidence between radiation treatments and the onset of neurological problems. That relationship is hidden by RILP's low toxicity rate, the lack of a large monitored population size and the lack of data pooling across multiple institutions. [ 1 ] [ 19 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4587", "text": "Treatment of RILP is primarily supportive [ 15 ]  with mental, [ 2 ] [ 10 ]  physiological [ 2 ] [ 1 ] [ 10 ] [ 15 ]  and social aspects [ 10 ]  and consideration of any aggravating (synergistic) neurological factors. [ 1 ] [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4588", "text": "To prevent compounding existing RILP symptoms and to minimize further progression"}
{"_id": "WikiPedia_Radiology$$$corpus_4589", "text": "The effect on the person with the condition, depends upon the type of impairment. Handicaps may include physical challenges, bowel and/or bladder dysfunction and may occur in multiple settings of work and home. [ 10 ]   Physical  and  occupational therapy  are important elements in maintaining mobility and use of the lower extremities, along with assistive aides such as  Ankle-Foot-Orthotics (AFOs) , cane, walkers, etc. [ 2 ] [ 10 ] [ 15 ]  Sensory reeducation techniques may be necessary for balance [ 2 ]  and  lymphedema  management may be required. [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4590", "text": "Pharmaceuticals that may be effective for RILP's  neuropathic pain  are"}
{"_id": "WikiPedia_Radiology$$$corpus_4591", "text": "Non-pharmaceutical RILP considerations are"}
{"_id": "WikiPedia_Radiology$$$corpus_4592", "text": "Functional impairment and residual pain can lead to social isolation. [ 10 ]  Cancer support groups are valuable resources to learn about the syndrome and therapeutic options, and are a means to voice emotions related to having cancer and surviving it. [ 10 ] [ 1 ] [ 15 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4593", "text": "With increasing cancer treatment survival rates, the quality of life for its survivors has become a public health priority. [ 1 ]   The effects of RILP can be debilitating.  With no effective treatment to control radiation damage's progressive nature, limb dysfunction is the likely result. [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4594", "text": "Radiation damage's outcome is related to its initial onset time."}
{"_id": "WikiPedia_Radiology$$$corpus_4595", "text": "An exact occurrence rate has  not  been established.  Literature  on  the topic  is  sparse. [ 21 ]  Clinical occurrences of RILP are rare, affecting between 0.3 and 1.3% of those treated with abdominal or pelvic radiation. [ 2 ]  The incidence rate is  variable, dependent upon the irradiated zone, dosage level and method of delivery. For example, when alternate dosing levels were compared, higher rates were observed, from 12 to 23%, the higher RILP rates occurring with higher dosages. [ 21 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4596", "text": "As of 1977 lumbosacral neuropathy arising from  radiation therapy  had been rarely reported.  One of the earliest cases was in 1948. [ 7 ] [ 11 ] [ 22 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4597", "text": "The incidence rate of peripheral neuropathy has been demonstrated to decrease when lower therapeutic radiation dosing levels are used. [ 21 ] [ 1 ]   A similar nerve injury,  Radiation-induced Brachial Plexopathy (RIBP) , may occur secondary to breast radiation therapy. [ 23 ]   Studies on RIBP have observed the  brachial plexus'  radiosensitivity.  Injury was observed after dosages of 40 Gy in 20 fractions and RIBP significantly increased with doses greater than 2 Gy per fraction. [ 21 ]   RIBP is more common than lumbosacral radiculoplexopathy [ 4 ]  and has a clinical history with reduced dosing levels.  RIBP occurrence rates were in the 60% range in the 1960s when 60 Gray treatments were applied in 5 Gray  fractions ; RIBP occurrences in the 2010s approach 1% with 50 Gray treatments applied in 3 Gy fractions. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4598", "text": "RILP occurrence rates are estimated at 0.3% to 1.3%, though the actual rate is likely higher. The soft tissue damage leading to RILP is more commonly seen with exposure levels over 50 Gy, though has occurred with as little as 30 Gy. [ 24 ]   A major step toward reducing RILP occurrences is by limiting the lumbosacral plexus' dosing level when treating pelvic malignancies, limiting the mean dose to < 45 Gy.  One approach to reduced levels, the plexus' mapping  with other  organs at risk , was clinically evaluated during the 2010s. [ 17 ] [ 18 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4599", "text": "Clinical evidence of the cause-and-effect for prevention and the management of radiation induced polyneuropathy is limited. [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4600", "text": "In 2011 the Radiation Oncology Institute (ROI) announced the National Radiation Oncology Registry (NROR). ROI and  Massachusetts General Hospital  would initially focus the NROR on prostate cancer, collecting efficacy and side effect information (like radiation induced neuropathy, RILP) from people treated with radiotherapy. [ 25 ]  In 2013 the  American Society for Radiation Oncology (ASTRO)  joined the effort [ 26 ]  and the number of data collection sites increased to 30 for a 1-year pilot project.  Pitfalls of medical data collection arose with only 14 sites being able to provide data and all those requiring significant manual entry efforts. [ 27 ]   The first NROR project conclusion was that future registries would need to cope with  Big data analytics . In 2015 ASTRO, the  National Cancer Institute  and the  American Association of Physicists in Medicine  sponsored a Big Data Workshop at the National Institutes of Health."}
{"_id": "WikiPedia_Radiology$$$corpus_4601", "text": "Experimental approaches for RILP treatment and management include:"}
{"_id": "WikiPedia_Radiology$$$corpus_4602", "text": "This article incorporates text in the  public domain  from the 20th edition of   Gray's Anatomy   (1918)"}
{"_id": "WikiPedia_Radiology$$$corpus_4603", "text": "Radiation-induced lung injury  ( RILI ) is a general term for damage to the  lungs  as a result of exposure to  ionizing radiation . [ 1 ]  In general terms, such damage is divided into early  inflammatory  damage ( radiation pneumonitis ) and later complications of chronic  scarring  ( radiation fibrosis ). Pulmonary radiation injury is an  unavoidable risk  of  radiation therapy  administered to treat thoracic or  lung cancer . [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4604", "text": "The  lungs  are a  radiosensitive  organ, and radiation  pneumonitis  can occur leading to  pulmonary insufficiency  and death (100% after exposure to 50 gray of radiation) in a few months. Radiation  pneumonitis  is characterized by:"}
{"_id": "WikiPedia_Radiology$$$corpus_4605", "text": "Symptoms of radiation pneumonitis include:  fever ,  cough , chest congestion,  shortness of breath , chest pain"}
{"_id": "WikiPedia_Radiology$$$corpus_4606", "text": "High resolution CT thorax"}
{"_id": "WikiPedia_Radiology$$$corpus_4607", "text": "\u201cThe Canadian Cancer society mentions these things that help to manage radiation,"}
{"_id": "WikiPedia_Radiology$$$corpus_4608", "text": "Your healthcare team may recommend medicines to treat radiation pneumonitis, such as:"}
{"_id": "WikiPedia_Radiology$$$corpus_4609", "text": "decongestants\ncough suppressants\nbronchodilators\ncorticosteroids to reduce inflammation\noxygen therapy\nYou can also try the following to help manage symptoms:"}
{"_id": "WikiPedia_Radiology$$$corpus_4610", "text": "Rest if you feel short of breath.\nDrink more fluids and use a cool-air vaporizer or humidifier to keep the air moist.\nUse an extra pillow to raise your head and upper body while resting or sleeping.\nAvoid the outdoors on hot, humid days or very cold days (which can irritate the lungs).\nWear light, loose-fitting tops and avoid anything tight around the neck, such as ties or shirt collars.\u201c [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4611", "text": "For more information go to their website, as they have accurate information. \u201cMore Info\u201d"}
{"_id": "WikiPedia_Radiology$$$corpus_4612", "text": "Radioimmunotherapy  (RIT) uses an  antibody  labeled with a  radionuclide  to deliver  cytotoxic  radiation to a target cell. [ 1 ]  It is a form of  unsealed source radiotherapy . In  cancer therapy , an antibody with  specificity  for a tumor-associated  antigen  is used to deliver a lethal dose of  radiation  to the tumor cells.  The ability for the antibody to specifically bind to a tumor-associated antigen increases the dose delivered to the tumor cells while decreasing the dose to normal tissues.  By its nature, RIT requires a tumor cell to express an antigen that is unique to the  neoplasm  or is not accessible in normal cells."}
{"_id": "WikiPedia_Radiology$$$corpus_4613", "text": "131 I tositumomab and  90 Y ibritumomab tiuxetan were the first agents of radioimmunotherapy, and they were approved for the treatment of refractory  non-Hodgkin's lymphoma .  This means they are used in patients whose lymphoma is refractory to conventional  chemotherapy  and the monoclonal antibody  rituximab ."}
{"_id": "WikiPedia_Radiology$$$corpus_4614", "text": "A set of radioimmunotherapy drugs that rely upon an  alpha-emitting  isotope (e.g.,  bismuth-213  or, preferably,  actinium-225 ), rather than a  beta emitter , as the killing source of radiation is being developed. Several  phase II clinical trials  for the treatment of  acute myeloid leukemia  have been carried out using alpha-emitting RITs. [ 10 ] [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4615", "text": "90 Y-FF-21101 is a monoclonal antibody against  P-cadherin   radiolabeled  with  yttrium-90 . [ 12 ]  It is one of several RIT treatments under investigation intending to treat  solid tumors . [ 13 ]  A  phase I clinical trial  began in 2015. [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4616", "text": "Other types of cancer for which RIT has therapeutic potential include  prostate cancer , [ 15 ]  metastatic  melanoma , [ 16 ]   ovarian cancer , [ 17 ]   neoplastic meningitis , [ 17 ]   leukemia , [ 18 ]  high-grade brain  glioma , [ 19 ]  and metastatic  colorectal cancer . [ 20 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4617", "text": "Components of the extracellular matrix and the tumor microenvironment can also be targeted by radioimmunotherapy, such as Netrin-1  [ 21 ]  (an axon guidance protein) and FAP (a marker for cancer associated fibroblasts). [ 22 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4618", "text": "Radiopharmacology  is  radiochemistry  applied to  medicine  and thus the  pharmacology  of radiopharmaceuticals ( medicinal radiocompounds , that is,  pharmaceutical drugs  that are  radioactive ). Radiopharmaceuticals are used in the field of  nuclear medicine  as  radioactive tracers  in  medical imaging  and in  therapy  for many  diseases  (for example,  brachytherapy ). Many radiopharmaceuticals use  technetium-99m  (Tc-99m) which has many useful properties as a  gamma-emitting   tracer   nuclide . In the book  Technetium  a total of 31 different radiopharmaceuticals based on Tc-99m are listed for imaging and functional studies of the  brain ,  myocardium ,  thyroid ,  lungs ,  liver ,  gallbladder ,  kidneys ,  skeleton ,  blood  and  tumors . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4619", "text": "The term  radioisotope , which in its general  sense  refers to any radioactive  isotope  ( radionuclide ), has historically been used to refer to all radiopharmaceuticals, and this usage remains common. Technically, however, many radiopharmaceuticals incorporate a  radioactive tracer  atom into a larger pharmaceutically-active molecule, which is localized in the body, after which the radionuclide tracer atom allows it to be easily detected with a  gamma camera  or similar gamma imaging device. An example is  fludeoxyglucose  in which  fluorine-18  is incorporated into  deoxyglucose . Some radioisotopes (for example  gallium-67 ,  gallium-68 , and  radioiodine ) are used directly as soluble ionic salts, without further modification. This use relies on the chemical and biological properties of the radioisotope itself, to localize it within the body."}
{"_id": "WikiPedia_Radiology$$$corpus_4620", "text": "See  nuclear medicine ."}
{"_id": "WikiPedia_Radiology$$$corpus_4621", "text": "Production of a radiopharmaceutical involves two processes:"}
{"_id": "WikiPedia_Radiology$$$corpus_4622", "text": "Radionuclides used in radiopharmaceuticals are mostly radioactive  isotopes  of elements with atomic numbers less than that of  bismuth , that is, they are radioactive isotopes of elements that also have one or more stable isotopes. These may be roughly divided into two classes:"}
{"_id": "WikiPedia_Radiology$$$corpus_4623", "text": "Because radiopharmeuticals require special licenses and handling techniques, they are often kept in local centers for medical radioisotope storage, often known as  radiopharmacies . A  radiopharmacist  may dispense them from there, to local centers where they are handled at the  practical medicine  facility."}
{"_id": "WikiPedia_Radiology$$$corpus_4624", "text": "As with other pharmaceutical drugs, there is  standardization  of the  drug nomenclature  for radiopharmaceuticals, although various standards coexist. The  International Nonproprietary Name  (INN) gives the base drug name, followed by the radioisotope (as mass number, no space, element symbol) in parentheses with no superscript, followed by the ligand (if any). It is common to see square brackets and superscript superimposed onto the INN name, because  chemical nomenclature  (such as IUPAC nomenclature) uses those. The  United States Pharmacopeia  (USP) name gives the base drug name, followed by the radioisotope (as element symbol, space, mass number) with no parentheses, no hyphen, and no superscript, followed by the ligand (if any). The USP style is not the INN style, despite their being described as one and the same in some publications (e.g.,  AMA , [ 4 ]  whose style for radiopharmaceuticals matches the USP style). The  United States Pharmacopeial Convention  is a sponsor organization of the  USAN Council , and the  USAN  for a given drug is often the same as the USP name."}
{"_id": "WikiPedia_Radiology$$$corpus_4625", "text": "Radium-223   ( 223 Ra, Ra-223) is an  isotope  of  radium  with an 11.4-day  half-life . It was discovered in 1905 by T. Godlewski, [ 2 ] [ 3 ] [ 4 ]  a Polish chemist from  Krak\u00f3w , and was historically known as  actinium X  (AcX). [ 5 ] [ 6 ]  Radium-223 dichloride is an alpha particle-emitting radiotherapy drug that mimics calcium and forms complexes with hydroxyapatite at areas of increased bone turnover. [ 7 ]  The principal use of radium-223, as a  radiopharmaceutical  to treat  metastatic  cancers in  bone , takes advantage of its chemical similarity to  calcium , and the short range of the  alpha radiation  it emits. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4626", "text": "Although radium-223 is naturally formed in trace amounts by the  decay of uranium-235 , it is generally made artificially, [ 9 ]  by exposing natural radium-226 to  neutrons  to produce radium-227, which decays with a 42-minute half-life to  actinium-227 .  Actinium-227 (half-life 21.8\u00a0years) in turn decays via  thorium-227  (half-life 18.7\u00a0days) to radium-223. This decay path makes it convenient to prepare radium-223 by \"milking\" it from an actinium-227 containing generator or \"cow\", similar to the  moly cows  widely used to prepare the medically important isotope  technetium-99m . [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4627", "text": "223 Ra itself  decays  to  219 Rn  (half-life 3.96\u00a0s), a short-lived gaseous  radon  isotope, by emitting an  alpha particle  of 5.979  MeV . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4628", "text": "The pharmaceutical product and medical use of radium-223 against skeletal metastases was invented by Roy H. Larsen, Gjermund Henriksen and \u00d8yvind S. Bruland [ 13 ]  and has been developed by the former Norwegian company  Algeta  ASA, in a partnership with  Bayer , under the trade name  Xofigo  (formerly  Alpharadin ), and is distributed as a solution containing radium-223 chloride (1100 kBq/ml), sodium chloride, and other ingredients for intravenous injection. Algeta ASA was later acquired by Bayer who is the sole owner of Xofigo. [ 12 ] [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4629", "text": "The use of radium-223 to treat metastatic bone cancer relies on the ability of  alpha radiation  from radium-223 and its short-lived decay products to kill cancer cells.  Radium is preferentially absorbed by bone by virtue of its chemical similarity to calcium, with most radium-223 that is not taken up by the bone being cleared, primarily via the gut, and excreted. [ 15 ]  Although radium-223 and its decay products also emit  beta  and  gamma radiation , over 95% of the decay energy is in the form of alpha radiation. [ 16 ]  Alpha radiation has a very short range in tissues compared to beta or gamma radiation: around 2\u201310 cells. This reduces damage to surrounding healthy tissues, producing an even more localized effect than the beta-emitter  strontium-89 , also used to treat bone cancer. [ 17 ]  Taking account of its preferential uptake by bone and the alpha particles' short range, radium-223 is estimated to give targeted  osteogenic cells  a radiation dose at least eight times higher than other non-targeted tissues. [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4630", "text": "The phase II study of radium-223 in  castration-resistant prostate cancer  (CRPC) patients with  bone metastases  showed minimum  myelotoxicity  and good tolerance for the treatment. [ 18 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4631", "text": "223 Ra successfully met the primary endpoint of  overall survival  in the  phase III  ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer patients) study for bone metastases resulting from CRPC in 922 patients. [ 19 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4632", "text": "The ALSYMPCA study was stopped early after a pre-planned efficacy interim analysis, following a recommendation from an Independent Data Monitoring Committee, on the basis of achieving a statistically significant improvement in overall survival (two-sided p-value = 0.0022, HR = 0.699, the median overall survival was 14.0\u00a0months for  223 Ra and 11.2\u00a0months for placebo). [ 19 ]  Earlier phase II of the trial showed a median increased survival of 18.9 weeks (around 4.4 months). [ 18 ]  The lower figure of 2.8 months increased survival in interim phase III results is a probable result of stopping the trial; median survival time for patients still alive could not be calculated. A 2014 update indicates a median increased survival of 3.6 months. [ 20 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4633", "text": "In May 2013,  223 Ra received marketing approval from the US  Food and Drug Administration  (FDA) [ 21 ] [ 22 ]  as a treatment for CRPC with bone metastases in people with symptomatic bone metastases and without known visceral disease.  223 Ra received priority review as a treatment for an unmet medical need, based on its ability to extend overall survival as shown its Phase III trial. [ 21 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4634", "text": "This study also led to approval in the  European Union  in November 2013, [ 12 ] [ 23 ]  The  European Medicines Agency  subsequently recommended restricting its use to patients who have had two previous treatments for metastatic prostate cancer or who cannot receive other treatments. The medicine must also not be used with  abiraterone acetate , prednisone or prednisolone and its use is not recommended in patients with a low number of osteoblastic bone metastases. [ 24 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4635", "text": "223 Ra also showed promising preliminary results in a phase IIa trial enrolling 23 women with bone metastases resulting from  breast cancer  that no longer responds to  endocrine therapy . [ 25 ]   223 Ra treatment reduced the levels of bone  alkaline phosphatase  (bALP) and urine  N-telopeptide  (uNTX), key markers of bone turnover associated with bone metastases in breast cancer, diminished bone pain slightly though consistently, and was well tolerated. Another single-arm, open-label Phase II trial reported possible efficacy of  223 Ra combined with  endocrine therapy  in hormone-receptor-positive, bone-dominant breast cancer metastasis. [ 26 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4636", "text": "The most common side effects reported during clinical trials in men receiving  223 Ra were nausea, diarrhea, vomiting and swelling of the leg, ankle or foot. The most common abnormalities detected during blood testing were  anemia ,  lymphocytopenia ,  leukopenia ,  thrombocytopenia  and  neutropenia . [ 21 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4637", "text": "Although radium does not easily form stable molecular complexes, [ 27 ]  data has been presented on methods to increase and customize its specificity for particular cancers by linking it to  monoclonal antibodies , by enclosing the  223 Ra in  liposomes  bearing the antibodies on their surface. [ 28 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4638", "text": "The side effects of radiotherapy on fertility  are a growing concern to patients undergoing radiotherapy as cancer treatments.  Radiotherapy  is essential for certain  cancer treatments  and often is the first point of call for patients. [ 1 ]   Radiation  can be divided into two categories:  ionising radiation (IR)  and  non-ionising radiation (NIR) . IR is more dangerous than NIR and a source of this radiation is X-rays used in medical procedures, for example in radiotherapy. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4639", "text": "IR can have varying impacts which depend on many factors including age,  irradiation field  and treatment dose and duration. Where the radiotherapy is directed is important as IR to the pelvis will affect the ovary and uterus or testis. Whereas cranial irradiation will disrupt the  hypothalamic-pituitary-gonadal axis  (HPG-A), causing subsequent disruption of hormone secretion. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4640", "text": "In females, IR can have long-term effects on  fertility , specifically on  ovarian insufficiency , pubertal arrest and subsequent  infertility . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4641", "text": "In males, the use of radiotherapy can disrupt the  endocrine system  leading to altered  spermatogenesis  and consequently a decrease in sperm count, sperm motility, sperm morphology and sperm viability. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4642", "text": "The rapid evolution of radiotherapy technologies has had the benefit of more effective and accurate treatments with less side effects. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4643", "text": "Radiation therapy can have a significant impact on female fertility. The damage induced varies greatly and is determined by factors such as the age of the patient along with the dose and duration of treatment given. [ 1 ]  Estimates suggest that less than 2Gy of radiation could destroy half of a female\u2019s immature  oocytes . Female ovaries are estimated to store over 1,000,000  primordial follicles  at birth which decrease in number and quality with increasing age via processes such as  apoptosis . [ 1 ]  Radiation therapy greatly accelerates this decline. Permanent damage occurs with  follicular atrophy  and reduced follicle numbers. [ 1 ]  Consequently these changes lead to uterine dysfunction due to changes in ovarian hormone production which can result in  early menopause  and risk of infertility. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4644", "text": "Hormonal disruption includes female patients experiencing decrease  LH (luteinising hormone)  secretion and attenuated LH surges leading to increased risk of ovarian failure. LH plays an important role in proper sexual development. Further potential  endocrinopathies  include  hypogonadism  and  hyperprolactinemia . [ 4 ]  Studies now suggest that the stage of follicular development may determine how much damage is induced. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4645", "text": "Radiation therapy has been seen to also have a direct impact on the uterus, leading to changes to its vascular supply, volume and elasticity.  Necrosis , atrophy and fibrosis have also all been observed in the  endometrium  and  myometrium . Changes such as these have significant consequences in regard to pregnancy outcomes; studies suggest cancer patients receiving radiation have a higher chance of experiencing  miscarriages  or having low birth weight, premature children. [ 1 ]  The likelihood of  perinatal infant mortality  and low birth weight are significantly related to radiation dose. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4646", "text": "Male fertility can be greatly impacted by radiotherapy of the reproductive system. Spermatogenesis is a process by which male sperm cells are produced. [ 6 ]  This process can take up to 70 days to complete. Some of the cells involved in this process can be damaged by the use of radiotherapy. Cells called  spermatogonia  are the most heavily impacted by radiotherapy. [ 2 ]  These are the cells that go on to divide to produce  spermatozoa , or what are commonly known as sperm cells. Spermatogonia are the most impacted by radiotherapy because they are more radiosensitive than other types of cells such as spermatozoa. [ 2 ]  This means that the whole spermatogenic process is impacted by radiotherapy."}
{"_id": "WikiPedia_Radiology$$$corpus_4647", "text": "In addition to the damage of spermatogonia, the cells which produce a hormone called testosterone are also impaired by radiotherapy. [ 2 ]   Testosterone  is the main male hormone in the body. [ 7 ]  These cells are called  Leydig cells  and they are found in the  testes . However, Leydig cells are far more resistant to radiation than other cells in the testes and only become damaged by high levels of radiotherapy. [ 2 ]  These cells are more sensitive when the radiotherapy takes place in childhood. Damaged Leydig cells reduce the levels of testosterone in the body, which in turn increases the levels of another hormone called LH. [ 2 ]  Clinically, the monitoring of these two hormones can be indicative of Leydig cell function and health. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4648", "text": "In combination, these two processes can lead to male fertility being compromised and can sometimes result in infertility."}
{"_id": "WikiPedia_Radiology$$$corpus_4649", "text": "The number of childhood cancer survivors is increasing due to technological and diagnostic advancements. [ 8 ]  However as a result, there is increasing concern of the long-term effects of cancer treatments, such as radiotherapy treatment. A significant issue associated with childhood radiotherapy includes infertility. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4650", "text": "Prepubescent  males who experience radiotherapy to their testes, can result in reduced  spermatogenesis . [ 9 ]  This can be through damage to the  germ cells , the  sertoli cells  and/or  Leydig cells . [ 9 ]  Both the dosage and the timing of the treatment can determine the extent of disruption to spermatogenesis. In prepubescent males, low doses (>1-3Gy) can cause short-term  oligospermia  or  azoospermia , while higher doses (>2-3 Gy) can cause permanent azoospermia. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4651", "text": "Moreover, testicular radiation or  central nervous system  (CNS) radiation in prepubertal males can affect  testosterone  levels and cause hypoandrogenism. Testicular radiation damages the androgen-producing Leydig cells while CNS radiation impairs the hypothalamic-pituitary-gonadal (HPG) axis, reducing  gonadotropin  production. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4652", "text": "In prepubescent females, high radiation dose to the pelvic region can also have adverse side effects on fertility. Long-term effects include early onset  menopause , ovarian failure and inability to complete puberty. [ 10 ]  Where pregnancy occurs in these individuals, there are high risks associated with the health of the offspring due to pregnancy complications. These include low birth weight, miscarriage and premature labour. [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4653", "text": "In modern medicine there are multiple options to limit the effect of cancer treatment on fertility.\u00a0 One of the preventative measures in females is transposition of gonadal organs further from local therapeutic agents with a success rate over 90%. [ 11 ]  Another less invasive method used for many years is  lead shielding  of gonadal region in both males and females as a protective measure against radiotherapy. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4654", "text": "In prepubescent males novel techniques such as  testicular tissue extraction  and  cryopreservation  as well as  in vitro  maturation of spermatogonia which can then be transferred to native tissue after the treatment are being heavily researched. [ 5 ]  The most common solution is cryopreservation of sperms in post pubertal males and cryopreservation of oocytes or embryos for females with smaller age constrain compared to males who can then utilise multiple  assisted reproductive techniques  (ART) methods such as intrauterine insemination,  IVF  or ICSI as an alternative resource for preservation of fertility. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4655", "text": "Future approach to this problem focuses on cytoprotective strategies using hormonal treatment to alter HPG-A to guard reproductive organs from radiotherapy. By disrupting the  gametogenesis  or decreasing the sensitivity of germ cells scientists could acquire quiescent state less susceptible to side effects of cancer treatment. [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4656", "text": "Sirtex Medical Limited  is a medical device firm that offers radioactive treatment for inoperable  liver cancer  called  SIR-Spheres   microspheres . [ 1 ]  Sirtex was founded in 1997 in Australia and today has offices and production facilities in the  U.S. ,  Australia ,  Germany , and  Singapore . Following its acquisition by  China Grand Pharmaceutical  and CDH Genetech, Sirtex delisted from the  Australian Securities Exchange  (ASX:SRX) on Monday, September 24, 2018."}
{"_id": "WikiPedia_Radiology$$$corpus_4657", "text": "The company is currently headed by Kevin R. Smith, who was appointed as CEO on October 16, 2019. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4658", "text": "When SIR-Sphere microspheres are used to treat liver cancer, the treatment is called  selective internal radiation therapy  (called SIRT). This is a relatively new treatment option for people suffering from  inoperable   liver cancer . [ 3 ]  SIR-Spheres are very small radioactive beads about one-third the size of a human hair that are injected into tumours within the liver."}
{"_id": "WikiPedia_Radiology$$$corpus_4659", "text": "The  radioactive  microspheres have a  half-life  of about 64 hours. They are administered by a trained interventional  radiologist  who specialises in minimally invasive, targeted treatments. The procedure is usually performed under local sedation. A small incision is made in the patient's groin, and a flexible  catheter  is guided into the  liver  through the  femoral artery  in the leg up to the tumour sites. The catheter is moved through the hepatic artery and positioned by the  interventional radiologist  to allow for targeted infusion of the SIR-Spheres microspheres to the site of the tumors. The microspheres take approximately 15 minutes to be infused, with the whole procedure taking about an hour. Most patients are discharged within 24 hours. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4660", "text": "Primary  liver cancer , also known as  hepatocellular carcinoma  (HCC), is the most frequent type of liver cancer, accounting for approximately 90% of the primary  malignant  liver tumours in adults. Liver cancer is the sixth most prevalent malignancy and the third greatest cause of cancer-related deaths worldwide. [ 5 ]  Every year, around 600,000 instances of liver cancer are diagnosed around the world. This includes around 19,000 in the US, 54,000 in Europe, and 390,000 in China, Korea, and Japan. The incidence of HCC is rising in Asia as chronic infection with Hepatitis B and C becomes more common. Additional risk factors include iron overload,  alcoholic cirrhosis  and some congenital disorders. Patients with liver cancer had a lower fiver-year survival rate than those with other cancer types. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4661", "text": "Colorectal cancer  (CRC), often known as  colon cancer  or large bowel cancer, is the third highest cause of cancer-related deaths in the western world. [ 7 ]  Each year, an estimated 1.6 million people are diagnosed with the condition around the world. An estimated 50% of CRC patients will develop liver  metastases . Sirtex targets metastatic colorectal cancer (mCRC) via SIR-Sphere microspheres. It has been thought that in 30-40% of individuals with severe illness, the liver is the only site of dissemination."}
{"_id": "WikiPedia_Radiology$$$corpus_4662", "text": "At presentation, 20-25% of patients will have clinically identifiable liver  metastases , and up to 50% of all patients develop liver metastases develop liver metastases within three years of primary tumor removal. [ 8 ]  On average, 25% of patients with metastatic liver disease are eligible for liver resection surgery, which is the only possible cure available to them. [ 9 ]  The remaining patients are eligible for alternative treatments such as  chemotherapy  and SIR-Sphere microspheres."}
{"_id": "WikiPedia_Radiology$$$corpus_4663", "text": "Sirtex is currently looking at new ways to treat other forms of cancer using the SIR-Spheres technology. This research is taking place at the  Australian National University  (ANU) and several institutions in the US and Europe. Sirtex is also working to develop a new technology that will help improve the treatment and survival of cancer patients. [ 10 ]  At present, this is focused on the three areas listed below."}
{"_id": "WikiPedia_Radiology$$$corpus_4664", "text": "Results from the largest, most comprehensive study to date evaluating SIRT in liver metastases from colorectal cancer were presented at ASCO in 2012, ASCO-GI 2013, and ASCO in 2014. The various subsets of the MORE study, led by Andrew S. Kennedy, M.D., Physician in Chief, Radiation Oncology, Sarah Cannon Research Institute, Nashville, Tenn., have demonstrated safety and efficacy as well as the same in treating the elderly. The most recent set of data presented at ASCO in 2014 documented the ability to predict the success of SIRT using standard laboratory tests prior to treatment. [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4665", "text": "In addition, the global SIRFLOX study, which completed  patient recruitment  in 2013, will evaluate SIR-Sphere microspheres as a first-line treatment for colorectal liver metastases. [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4666", "text": "SIR-Sphere microspheres [ 13 ]  are regulated as a medical device. The product was approved for sale in the US in March 2002. The US  Centers for Medicare and Medicaid Services  (CMS) currently reimburse SIR-Spheres microspheres under  Medicare  Code C2616. [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4667", "text": "SIR-Spheres are covered in Australia by private insurers and reimbursed under  Medicare . [ 15 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4668", "text": "In Europe, SIR-Sphere microspheres are regulated under the Active Implantable Medical Device Directive. The product received CE Mark approval in October 2002. [ 16 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4669", "text": "In the UK, patients treated with SIR-Spheres were either self-funded, had private medical insurance, or had the microspheres donated by Sirtex. A small number have been approved by the  National Health Service  (NHS). [ citation needed ]  This is partly due to formal guidance documentation provided by the  National Institute for Clinical Excellence  (NICE), which questioned the clinical benefits of SIR-Sphere microspheres requiring patient consent. Since 2013, it has been mandatory for NHS organisations in the UK to provide funding for medicines and treatment as recommended by NICE. [ 17 ] [ 18 ]  A favourable review will see the  National Health Service  pay for treatment across the UK and help reimbursement in other EU countries."}
{"_id": "WikiPedia_Radiology$$$corpus_4670", "text": "On 3 September 2013, Sirtex announced that dose sales of SIR-Spheres microspheres grew a solid 21 percent, with more than 4,750 doses being supplied in the Americas for the year ending June 30, 2013. Globally, revenue was $100 million Australian dollars, up 16 percent from 2012, with a net profit after tax of AU$18 million. Dose sales of SIR-Spheres microspheres grew 19 percent in fiscal year 2013, with Asia Pacific reporting growth of 29 percent and Europe, the Middle East, and Africa increasing nine percent. Sirtex plans to triple manufacturing capacity in 2014 with new facilities in Germany and the U.S. [ 19 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4671", "text": "Superficial X-rays  are low-energy  X-rays  that do not penetrate very far before they are absorbed. They are produced by  X-ray tubes  operating at  voltages  in the 10\u2013100\u00a0 kV  range, and therefore have peak energies in the 10\u2013100\u00a0 keV  range. [ 1 ]  The  Maximar-100  was a widely-adopted superficial radiation therapy unit."}
{"_id": "WikiPedia_Radiology$$$corpus_4672", "text": "Precise naming and definitions of energy ranges may vary, and X-rays at the lower end of this range may also be known as  Grenz rays . [ 2 ]  They are useful in  radiation therapy  for the treatment of various benign or malignant  skin  problems, including  skin cancer  and severe  eczema . [ 3 ] [ 4 ]  They have a useful depth of up to 5\u00a0mm. [ 2 ] [ 5 ]  In some locations, orthovoltage treatment is being replaced by  electron therapy  or  brachytherapy . [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4673", "text": "As well as  teletherapy , X-rays in this energy range (and the low  orthovoltage  range) are used for  imaging  patients, to analyse materials and objects in  industrial radiography  and for  crystallography ."}
{"_id": "WikiPedia_Radiology$$$corpus_4674", "text": "This  dermatology  article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Radiology$$$corpus_4675", "text": "Tissue-to-air ratio  (TAR) is a term used in  radiotherapy   treatment planning  to help calculate  absorbed dose  to water in conditions other than those directly measured."}
{"_id": "WikiPedia_Radiology$$$corpus_4676", "text": "The TAR at a point in a water phantom irradiated by a photon beam is taken to be the ratio of the total absorbed dose at that point to the absorbed dose at the same point in a minimal-scatter phantom with just-sufficient build-up. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4677", "text": "Tissue-air ratio is defined as the ratio of the dose to water at a given depth to the dose in air measured with a buildup cap:"}
{"_id": "WikiPedia_Radiology$$$corpus_4678", "text": "T \n A \n R \n = \n \n \n \n D \n ( \n f \n , \n z \n ) \n \n \n D \n ( \n f \n , \n 0 \n ) \n \n \n \n \n \n {\\displaystyle TAR={{D(f,z)} \\over {D(f,0)}}}"}
{"_id": "WikiPedia_Radiology$$$corpus_4679", "text": "where D(f,z) is the dose at a given depth z and distance focus-detector f; and D(f,0) is the dose in air (z=0)."}
{"_id": "WikiPedia_Radiology$$$corpus_4680", "text": "Measurements for each are taken using an  ion chamber  for identical source to detector distances and field sizes. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4681", "text": "Lynn D. Wilson  is an American radiation oncologist.  He is a professor of Therapeutic Radiology and of Dermatology, Executive Vice Chairman, Therapeutic Radiology, and Deputy Chief Medical Officer for Radiation Oncology Services at  Yale Cancer Center  and  Yale School of Medicine  in New Haven, Connecticut. [ 1 ] [ 2 ]  In 2011, Wilson was named a Fellow of the  American Society for Radiation Oncology  (FASTRO). [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4682", "text": "Wilson earned his medical degree at  George Washington University School of Medicine  in Washington, D.C., before completing a residency in radiation oncology at  Yale New Haven Hospital ; he served as a chief resident before joining the Yale School of Medicine faculty in 1994. [ 4 ]  Prior to his medical degree, Wilson received a master in public health degree, focusing on health services administration, at Yale School of Medicine. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4683", "text": "Wilson worked in the laboratory of James B. Mitchell, within the Radiation Biology Branch of the  National Cancer Institute / National Institutes of Health  (NIH) [ 6 ]  where he also collaborated with former Commissioner of  Food and Drugs   Stephen Hahn  on journal articles. [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4684", "text": "Wilson cares for patients with cutaneous lymphoma and breast cancer. His research focus is on outcomes and treatment-related factors for patients receiving radiation for cutaneous lymphoma and has published on radiation therapy for lung cancer as well as on breast cancer. [ 8 ]  Wilson has served as the director for clinical affairs in the Department of Therapeutic Radiology at Yale since in 2005 [ 9 ]  and was the residency training program director between 2004 and 2013. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4685", "text": "From 2011 to 2018, Wilson served on the board of trustees for the  American Board of Radiology [ 10 ]  and was a member of the American Society for Radiation Oncology board of directors from 2016 to 2020. [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4686", "text": "Wilson and his wife Nancy were married in 1997 and have two children. [ 13 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4687", "text": "Wilson is a former race car driver, having raced in the Rolex 24 at Daytona three times (2001, 2002, 2004). In 2001, as part of team Autometrics, Wilson and three other drivers took 23rd place overall and 13th in class after starting 75th overall. The 2001 race was the last time an air-cooled Porsche 911 ever raced in the famed Rolex 24 hours at Daytona. The Autometrics car (#14), was the only air-cooled Porsche 911 in the GT class in the 2001 race. [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4688", "text": "In 2020 Wilson received the Anthony Edward Kupka \u201964 Distinguished Alumnus Award from the  Landon School . [ 15 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4689", "text": "In 2008, Wilson received the inaugural  David J. Leffell , MD Prize for Clinical Excellence [ 16 ]  and in the same year was the recipient of the  Francis Gilman Blake  Award for teaching at Yale School of Medicine. [ 17 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4690", "text": "Radiography  is an  imaging technique  using  X-rays ,  gamma rays , or similar ionizing radiation and non-ionizing radiation to view the internal form of an object. Applications of radiography include medical  (\"diagnostic\" radiography and \"therapeutic radiography\") and  industrial radiography . Similar techniques are used in  airport security , (where \"body scanners\" generally use  backscatter X-ray ). To create an image in  conventional radiography , a beam of X-rays is produced by an  X-ray generator  and it is projected towards the object. A certain amount of the X-rays or other radiation are absorbed by the object, dependent on the object's density and structural composition. The X-rays that pass through the object are captured behind the object by a  detector  (either  photographic film  or a digital detector). The generation of flat  two-dimensional  images by this technique is called  projectional radiography . In  computed tomography  (CT scanning), an X-ray source and its associated detectors rotate around the subject, which itself moves through the conical X-ray beam produced. Any given point within the subject is crossed from many directions by many different beams at different times. Information regarding the attenuation of these beams is collated and subjected to computation to generate two-dimensional images on three planes (axial, coronal, and sagittal) which can be further processed to produce a three-dimensional image."}
{"_id": "WikiPedia_Radiology$$$corpus_4691", "text": "Radiography's origins and  fluoroscopy's origins  can both be traced to 8 November 1895, when German physics professor  Wilhelm Conrad R\u00f6ntgen  discovered the X-ray and noted that, while it could pass through human tissue, it could not pass through bone or metal. [ 1 ]  R\u00f6ntgen referred to the radiation as \"X\", to indicate that it was an unknown type of radiation. He received the first  Nobel Prize in Physics  for his discovery. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4692", "text": "There are conflicting accounts of his discovery because R\u00f6ntgen had his lab notes burned after his death, but this is a likely reconstruction by his biographers: [ 3 ] [ 4 ]  R\u00f6ntgen was investigating  cathode rays  using a  fluorescent  screen painted with barium  platinocyanide  and a  Crookes tube  which he had wrapped in black cardboard to shield its fluorescent glow. He noticed a faint green glow from the screen, about 1 metre away. R\u00f6ntgen realized some invisible rays coming from the tube were passing through the cardboard to make the screen glow: they were passing through an opaque object to affect the film behind it. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4693", "text": "R\u00f6ntgen discovered X-rays' medical use when he made a picture of his wife's hand on a photographic plate formed due to X-rays. The photograph of his wife's hand was the first ever photograph of a human body part using X-rays. When she saw the picture, she said, \"I have seen my death.\" [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4694", "text": "The first use of X-rays under clinical conditions was by  John Hall-Edwards  in  Birmingham, England , on 11 January 1896, when he radiographed a needle stuck in the hand of an associate. On 14 February 1896, Hall-Edwards also became the first to use X-rays in a  surgical operation . [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4695", "text": "The United States saw its first medical X-ray obtained using a  discharge tube  of  Ivan Pulyui 's design. In January 1896, on reading of R\u00f6ntgen's discovery, Frank Austin of  Dartmouth College  tested all of the discharge tubes in the physics laboratory and found that only the Pulyui tube produced X-rays. This was a result of Pulyui's inclusion of an oblique \"target\" of  mica , used for holding samples of  fluorescent  material, within the tube. On 3 February 1896 Gilman Frost, professor of medicine at the college, and his brother Edwin Frost, professor of physics, exposed the wrist of Eddie McCarthy, whom Gilman had treated some weeks earlier for a fracture, to the X-rays and collected the resulting image of the broken bone on  gelatin photographic plates  obtained from Howard Langill, a local photographer also interested in R\u00f6ntgen's work. [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4696", "text": "X-rays were put to diagnostic use very early; for example,  Alan Archibald Campbell-Swinton  opened a radiographic laboratory in the United Kingdom in 1896, before the dangers of ionizing radiation were discovered. Indeed,  Marie Curie  pushed for radiography to be used to treat wounded soldiers in World War I. Initially, many kinds of staff conducted radiography in hospitals, including physicists, photographers, physicians, nurses, and engineers. The medical speciality of radiology grew up over many years around the new technology. When new diagnostic tests were developed, it was natural for the  radiographers  to be trained in and to adopt this new technology. Radiographers now perform  fluoroscopy ,  computed tomography ,  mammography ,  ultrasound ,  nuclear medicine  and  magnetic resonance imaging  as well. Although a nonspecialist dictionary might define radiography quite narrowly as \"taking X-ray images\", this has long been only part of the work of \"X-ray departments\", radiographers, and radiologists. Initially, radiographs were known as roentgenograms, [ 8 ]  while  skiagrapher  (from the  Ancient Greek  words for \"shadow\" and \"writer\") was used until about 1918 to mean  radiographer .  The Japanese term for the radiograph,  rentogen  ( \u30ec\u30f3\u30c8\u30b2\u30f3 ) , shares its etymology with the original English term."}
{"_id": "WikiPedia_Radiology$$$corpus_4697", "text": "Since the body is made up of various substances with differing densities, ionising and non-ionising radiation can be used to reveal the internal structure of the body on an image receptor by highlighting these differences using  attenuation , or in the case of ionising radiation, the absorption of X-ray  photons  by the denser substances (like  calcium -rich bones). The discipline involving the study of anatomy through the use of radiographic images is known as  radiographic anatomy . Medical radiography acquisition is generally carried out by  radiographers , while image analysis is generally done by  radiologists . Some radiographers also specialise in image interpretation. Medical radiography includes a range of modalities producing many different types of image, each of which has a different clinical application."}
{"_id": "WikiPedia_Radiology$$$corpus_4698", "text": "The creation of images by exposing an object to  X-rays  or other high-energy forms of  electromagnetic radiation  and capturing the resulting remnant beam (or \"shadow\") as a latent image is known as \"projection radiography\".  The \"shadow\" may be converted to light using a fluorescent screen, which is then captured on  photographic film , it may be captured by a phosphor screen to be \"read\" later by a laser (CR), or it may directly activate a matrix of  solid-state  detectors (DR\u2014similar to a very large version of a  CCD  in a digital camera).  Bone  and some organs (such as  lungs ) especially lend themselves to projection radiography. It is a relatively low-cost investigation with a high  diagnostic  yield. The difference between  soft  and  hard  body parts stems mostly from the fact that carbon has a very low X-ray cross section compared to calcium."}
{"_id": "WikiPedia_Radiology$$$corpus_4699", "text": "Computed tomography  or CT scan (previously known as CAT scan, the \"A\" standing for \"axial\") uses ionizing radiation (x-ray radiation) in conjunction with a computer to create images of both soft and hard tissues. These images look as though the patient was sliced like bread (thus, \"tomography\" \u2013 \"tomo\" means \"slice\"). Though CT uses a higher amount of ionizing x-radiation than diagnostic x-rays (both utilising X-ray radiation), with advances in technology, levels of CT radiation dose and scan times have reduced. [ 9 ]  CT exams are generally short, most lasting only as long as a breath-hold,  Contrast agents  are also often used, depending on the tissues needing to be seen. Radiographers perform these examinations, sometimes in conjunction with a radiologist (for instance, when a radiologist performs a CT-guided  biopsy )."}
{"_id": "WikiPedia_Radiology$$$corpus_4700", "text": "DEXA , or bone densitometry, is used primarily for  osteoporosis  tests. It is not projection radiography, as the X-rays are emitted in two narrow beams that are scanned across the patient, 90 degrees from each other. Usually the hip (head of the  femur ), lower back ( lumbar spine ), or heel ( calcaneum ) are imaged, and the bone density (amount of calcium) is determined and given a number (a T-score).  It is not used for bone imaging, as the image quality is not good enough to make an accurate diagnostic image for fractures, inflammation, etc. It can also be used to measure total body fat, though this is not common. The radiation dose received from  DEXA scans  is very low, much lower than projection radiography examinations. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4701", "text": "Fluoroscopy  is a term invented by  Thomas Edison  during his early X-ray studies.  The name refers to the fluorescence he saw while looking at a glowing plate bombarded with X-rays. [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4702", "text": "The technique provides moving projection radiographs. Fluoroscopy is mainly performed to view movement (of tissue or a contrast agent), or to guide a medical intervention, such as angioplasty, pacemaker insertion, or joint repair/replacement. The last can often be carried out in the operating theatre, using a portable fluoroscopy machine called a C-arm. [ 11 ]   It can move around the surgery table and make digital images for the surgeon. Biplanar Fluoroscopy works the same as single plane fluoroscopy except displaying two planes at the same time. The ability to work in two planes is important for orthopedic and spinal surgery and can reduce operating times by eliminating re-positioning. [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4703", "text": "Angiography  is the use of fluoroscopy to view the cardiovascular system. An iodine-based contrast is injected into the bloodstream and watched as it travels around.  Since liquid blood and the vessels are not very dense, a contrast with high density (like the large iodine atoms) is used to view the vessels under X-ray. Angiography is used to find  aneurysms , leaks, blockages ( thromboses ), new vessel growth, and placement of catheters and stents.  Balloon angioplasty  is often done with angiography."}
{"_id": "WikiPedia_Radiology$$$corpus_4704", "text": "Contrast radiography uses a radiocontrast agent, a type of  contrast medium , to make the structures of interest stand out visually from their background. Contrast agents are required in conventional  angiography , and can be used in both  projectional radiography  and  computed tomography  (called  contrast CT ). [ 13 ] [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4705", "text": "Although not technically radiographic techniques due to not using X-rays, imaging modalities such as  PET  and  MRI  are sometimes grouped in radiography because the  radiology  department of hospitals handle all forms of  imaging . Treatment using radiation is known as  radiotherapy ."}
{"_id": "WikiPedia_Radiology$$$corpus_4706", "text": "Industrial radiography  is a method of  non-destructive testing  where many types of manufactured components can be examined to verify the internal structure and integrity of the specimen.  Industrial Radiography can be performed utilizing either  X-rays  or  gamma rays .  Both are forms of  electromagnetic radiation .  The difference between various forms of electromagnetic energy is related to the  wavelength .  X and gamma rays have the shortest wavelength and this property leads to the ability to penetrate, travel through, and exit various materials such as  carbon steel  and other metals. Specific methods include  industrial computed tomography ."}
{"_id": "WikiPedia_Radiology$$$corpus_4707", "text": "Image quality will depend on resolution and density.\nResolution is the ability an image to show closely spaced structure in the object as separate entities in the  image while density is the blackening power of the image.\nSharpness of a radiographic image is strongly determined by the size of the X-ray source. This is determined by the area of the electron beam hitting the anode.\nA large photon source results in more blurring in the final image and is worsened by an increase in image formation distance. This blurring can be measured as a contribution to the  modulation transfer function  of the imaging system."}
{"_id": "WikiPedia_Radiology$$$corpus_4708", "text": "The dosage of radiation applied in radiography varies by procedure. For example, the effective dosage of a chest x-ray is 0.1\u00a0mSv, while an abdominal CT is 10\u00a0mSv. [ 15 ]  The  American Association of Physicists in Medicine  (AAPM) have stated that the \"risks of medical imaging at patient doses below 50\u00a0mSv for single procedures or 100\u00a0mSv for multiple procedures over short time periods are too low to be detectable and may be nonexistent.\" Other scientific bodies sharing this conclusion include the  International Organization of Medical Physicists , the  UN Scientific Committee on the Effects of Atomic Radiation , and the  International Commission on Radiological Protection . Nonetheless, radiological organizations, including the  Radiological Society of North America  (RSNA) and the  American College of Radiology  (ACR), as well as multiple government agencies, indicate safety standards to ensure that radiation dosage is as low as possible. [ 16 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4709", "text": "Lead  is the most common shield against X-rays because of its high density (11,340\u00a0kg/m 3 ), stopping power, ease of installation and low cost. The maximum range of a high-energy photon such as an X-ray in matter is infinite; at every point in the matter traversed by the photon, there is a probability of interaction. Thus there is a very small probability of no interaction over very large distances. The shielding of photon beam is therefore exponential (with an  attenuation length  being close to the  radiation length  of the material); doubling the thickness of shielding will square the shielding effect."}
{"_id": "WikiPedia_Radiology$$$corpus_4710", "text": "Table in this section shows the recommended thickness of lead shielding in function of X-ray energy, from the Recommendations by the Second International Congress of Radiology. [ 17 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4711", "text": "In response to increased concern by the public over radiation doses and the ongoing progress of best practices, The Alliance for Radiation Safety in Pediatric Imaging was formed within the  Society for Pediatric Radiology . In concert with the  American Society of Radiologic Technologists , the  American College of Radiology , and the  American Association of Physicists in Medicine , the Society for Pediatric Radiology developed and launched the Image Gently campaign which is designed to maintain high quality imaging studies while using the lowest doses and best radiation safety practices available on pediatric patients. [ 18 ]  This initiative has been endorsed and applied by a growing list of various professional medical organizations around the world and has received support and assistance from companies that manufacture equipment used in radiology."}
{"_id": "WikiPedia_Radiology$$$corpus_4712", "text": "Following upon the success of the Image Gently campaign, the American College of Radiology, the Radiological Society of North America, the American Association of Physicists in Medicine, and the American Society of Radiologic Technologists have launched a similar campaign to address this issue in the adult population called Image Wisely. [ 19 ]  The  World Health Organization  and  International Atomic Energy Agency  (IAEA) of the United Nations have also been working in this area and have ongoing projects designed to broaden best practices and lower patient radiation dose. [ 20 ] [ 21 ] [ 22 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4713", "text": "Contrary to advice that emphasises only conducting radiographs when in the patient's interest, recent evidence suggests that they are used more frequently when dentists are paid under fee-for-service. [ 23 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4714", "text": "In medicine and dentistry,  projectional radiography  and  computed tomography images  generally use X-rays created by  X-ray generators , which generate X-rays from  X-ray tubes .  The resultant images from the radiograph (X-ray generator/machine) or CT scanner are correctly referred to as \"radiograms\"/\"roentgenograms\" and \"tomograms\" respectively."}
{"_id": "WikiPedia_Radiology$$$corpus_4715", "text": "A number of other sources of  X-ray   photons  are possible, and may be used in industrial radiography or research; these include  betatrons ,  linear accelerators  (linacs), and  synchrotrons . For  gamma rays ,  radioactive  sources such as  192 Ir ,  60 Co , or  137 Cs  are used."}
{"_id": "WikiPedia_Radiology$$$corpus_4716", "text": "An  anti-scatter grid  may be placed between the patient and the detector to reduce the quantity of scattered x-rays that reach the detector. This improves the contrast resolution of the image, but also increases radiation exposure for the patient. [ 24 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4717", "text": "Detectors can be divided into two major categories: imaging detectors (such as  photographic plates  and X-ray film ( photographic film ), now mostly replaced by various  digitizing  devices like  image plates  or  flat panel detectors ) and dose measurement devices (such as  ionization chambers ,  Geiger counters , and  dosimeters  used to measure the local  radiation exposure ,  dose , and/or dose rate, for example, for verifying that  radiation protection  equipment and procedures are effective on an ongoing basis). [ 25 ] [ 26 ] [ 27 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4718", "text": "A radiopaque anatomical side marker is added to each image. For example, if the patient has their right hand x-rayed, the radiographer includes a radiopaque \"R\" marker within the field of the x-ray beam as an indicator of which hand has been imaged. If a physical marker is not included, the radiographer may add the correct side marker later as part of digital post-processing. [ 28 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4719", "text": "As an alternative to X-ray detectors,  image intensifiers  are analog devices that readily convert the acquired X-ray image into one visible on a video screen. This device is made of a vacuum tube with a wide input surface coated on the inside with  caesium iodide  (CsI). When hit by X-rays, phosphor material causes the  photocathode  adjacent to it to emit electrons. These electrons are then focused using electron lenses inside the intensifier to an output screen coated with phosphorescent materials. The image from the output can then be recorded via a camera and displayed. [ 29 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4720", "text": "Digital devices known as array detectors are becoming more common in fluoroscopy. These devices are made of discrete pixelated detectors known as  thin-film transistors  (TFT) which can either work  indirectly  by using photo detectors that detect light emitted from a scintillator material such as CsI, or  directly  by capturing the electrons produced when the X-rays hit the detector. Direct detectors do not tend to experience the blurring or spreading effect caused by phosphorescent scintillators or by film screens since the detectors are activated directly by X-ray photons. [ 30 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4721", "text": "Dual-energy  radiography  is where images are acquired using two separate  tube voltages . This is the standard method for  bone densitometry . It is also used in  CT pulmonary angiography  to decrease the required dose of  iodinated contrast . [ 31 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4722", "text": "The  algebraic reconstruction technique  ( ART ) is an  iterative reconstruction  technique used in  computed tomography . It reconstructs an image from a series of angular projections (a  sinogram ).  Gordon , Bender and  Herman  first showed its use in image reconstruction; [ 1 ]  whereas the method is known as  Kaczmarz method  in numerical linear algebra. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4723", "text": "An advantage of ART over other reconstruction methods (such as  filtered backprojection ) is that it is relatively easy to incorporate prior knowledge into the reconstruction process."}
{"_id": "WikiPedia_Radiology$$$corpus_4724", "text": "ART can be considered as an iterative solver of a system of linear equations  \n \n \n \n A \n x \n = \n b \n \n \n {\\displaystyle Ax=b} \n \n , where:"}
{"_id": "WikiPedia_Radiology$$$corpus_4725", "text": "Given a real or complex matrix  \n \n \n \n A \n \n \n {\\displaystyle A} \n \n  and a real or complex vector  \n \n \n \n b \n \n \n {\\displaystyle b} \n \n , respectively, the method computes an approximation of the solution of the linear systems of equations as in the following formula,"}
{"_id": "WikiPedia_Radiology$$$corpus_4726", "text": "where  \n \n \n \n i \n = \n k \n \n mod \n \n m \n \n \n + \n 1 \n \n \n {\\displaystyle i=k{\\bmod {m}}+1} \n \n ,  \n \n \n \n \n a \n \n i \n \n \n \n \n {\\displaystyle a_{i}} \n \n  is the  i -th row of the matrix  \n \n \n \n A \n \n \n {\\displaystyle A} \n \n ,  \n \n \n \n \n b \n \n i \n \n \n \n \n {\\displaystyle b_{i}} \n \n  is the  i -th component of the vector  \n \n \n \n b \n \n \n {\\displaystyle b} \n \n ."}
{"_id": "WikiPedia_Radiology$$$corpus_4727", "text": "\u03bb \n \n k \n \n \n \n \n {\\displaystyle \\lambda _{k}} \n \n  is an optional relaxation parameter, of the range  \n \n \n \n 0 \n < \n \n \u03bb \n \n k \n \n \n \u2264 \n 1 \n \n \n {\\displaystyle 0<\\lambda _{k}\\leq 1} \n \n . The relaxation parameter is used to slow the convergence of the system. This increases computation time, but can improve the  signal-to-noise ratio  of the output. In some implementations, the value of  \n \n \n \n \n \u03bb \n \n k \n \n \n \n \n {\\displaystyle \\lambda _{k}} \n \n  is reduced with each successive iteration. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4728", "text": "A further development of the ART algorithm is the  simultaneous algebraic reconstruction technique  (SART) algorithm."}
{"_id": "WikiPedia_Radiology$$$corpus_4729", "text": "This  computer science  article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Radiology$$$corpus_4730", "text": "Automatic Exposure Control  (AEC) is an  X-ray  exposure termination device.  A  medical radiographic  exposure is always initiated by a human operator but an AEC detector system may be used to terminate the exposure when a predetermined amount of radiation has been received. [ 1 ]  The intention of AEC is to provide consistent x-ray image exposure, whether to film, a digital  detector  or a  CT scanner . AEC systems may also automatically set exposure factors such as the  X-ray tube  current and voltage in a CT. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4731", "text": "In  projectional radiography  an AEC system uses one or more physically thin radiation  ionization chambers  (the \"AEC detector\") which is positioned between the X-ray source and the x-ray receptor. Where low energy x-rays are used such as in  mammography  the AEC detector is placed behind the image receptor to avoid creating a shadow. [ 3 ] :\u200a106"}
{"_id": "WikiPedia_Radiology$$$corpus_4732", "text": "In early radiographic AEC systems, a large paddle (17\" x 17\") of transparent lucite was sandwiched between rare earth screens, [ 4 ]  which emitted photons when excited by X-rays. The individual lucite sections were open on one end, and a solenoid was used to select one of three, or a combination of shutters that allowed the generated light into a  Photomultiplier tube . The output of the PMT was then converted to a signal, which ramped in the positive direction until a preprogrammed threshold was reached. At this point, the X-ray generator terminated the exposure. This method is no longer used, and has been replaced by the iontomat.\nIn an iontomat, a weak ionization signal resulting from the radiographic X-rays passing through it are  integrated  as a ramp shaped  voltage   waveform .  This ramp signal rises until it matches a pre-set threshold. At this point the x-ray exposure is terminated by the X-ray generator. [ 5 ] \nAEC devices are calibrated to ensure that similar exams have linearity in  optical density . [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4733", "text": "Modern computed tomography (CT) scanners have AEC systems which aim to maintain image quality for patients of varying sizes, whilst keeping doses  as low as reasonably practicable . The systems are also designed to maintain quality with the varying size and  attenuation  of an individual patient over their length. Implementations vary between manufacturers, some systems are based on a desired  noise  level in the image, while others are based on a specified reference output (milliampere second,  mAs ). [ 7 ] [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4734", "text": "CT AEC systems use the initial \"scanogram\", a fixed angle planning view, to determine the relative size of the patient, and variation over their length. The  tube  output is then adjusted for overall size. The output is also typically modulated for each rotation in response to changes in attenuation over patient length. Some systems adjust output during each rotation, which is known as rotational modulation, based on measured attenuation in the previous rotation. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4735", "text": "Because patients vary in size and shape, an AEC device is very useful in achieving consistent x-ray film densities, which can be difficult when manually setting exposure factors without AEC. [ 3 ] :\u200a130"}
{"_id": "WikiPedia_Radiology$$$corpus_4736", "text": "AEC devices are susceptible to operator error (usually due to mispositioned  anatomy  or having the incorrect AEC chamber selected). [ 10 ]   Prosthetic  devices such as total hip hardware can also cause the selected ionization chamber to overexpose the image receptor. This is due to the absorption of the X-ray beam into the metal of the hardware as opposed to exposing the ionization chamber. [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4737", "text": "An  autoradiograph  is an image on an  X-ray  film or  nuclear emulsion  produced by the pattern of decay emissions (e.g.,  beta particles  or  gamma rays ) from a distribution of a  radioactive  substance. Alternatively, the autoradiograph is also available as a digital image (digital autoradiography), due to the recent development of  scintillation  gas detectors [ 1 ]  or rare-earth phosphorimaging systems. [ 2 ]  The film or emulsion is apposed to the labeled tissue section to obtain the autoradiograph (also called an autoradiogram).  The  auto-  prefix indicates that the radioactive substance is within the sample, as distinguished from the case of  historadiography  or microradiography, in which the sample is marked using an external source. Some autoradiographs can be examined microscopically for localization of silver grains (such as on the interiors or exteriors of cells or organelles) in which the process is termed micro-autoradiography. For example, micro-autoradiography was used to examine whether  atrazine  was being metabolized by the  hornwort  plant or by  epiphytic   microorganisms  in the  biofilm  layer surrounding the plant. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4738", "text": "In  biology , this technique may be used to determine the tissue (or cell) localization of a radioactive substance, either introduced into a metabolic pathway, bound to a receptor [ 4 ] [ 5 ]  or enzyme, or hybridized to a nucleic acid. [ 6 ]  Applications for autoradiography are broad, ranging from biomedical to environmental sciences to industry."}
{"_id": "WikiPedia_Radiology$$$corpus_4739", "text": "The use of  radiolabeled ligands  to determine the tissue distributions of receptors is termed either  in vivo  or  in vitro   receptor autoradiography  if the ligand is administered into the circulation (with subsequent tissue removal and sectioning) or applied to the tissue sections, respectively. [ 7 ]  Once the receptor density is known,  in vitro  autoradiography can also be used to determine the anatomical distribution and affinity of a radiolabeled drug towards the receptor. For  in vitro  autoradiography, radioligand was directly applying on frozen tissue sections without administration to the subject. Thus it cannot follow the distribution, metabolism and degradation situation completely in the living body. But because target in the cryosections is widely exposed and can direct contact with radioligand,  in vitro  autoradiography is still a quick and easy method to screen drug candidates,  PET  and  SPECT  ligands. The ligands are generally labeled with  3 H ( tritium ),  18 F ( fluorine ),  11 C ( carbon ) or  125 I  ( radioiodine ). Compare to  in vitro ,  ex vivo  autoradiography were performed after administration of radioligand in the body, which can decrease the artifacts and are closer to the inner environment."}
{"_id": "WikiPedia_Radiology$$$corpus_4740", "text": "The distribution of RNA transcripts in tissue sections by the use of radiolabeled, complementary oligonucleotides or ribonucleic acids (\"riboprobes\") is called  in situ hybridization histochemistry . Radioactive precursors of DNA and RNA, [ 3 H]- thymidine  and [ 3 H]- uridine  respectively, may be introduced to living cells to determine the timing of several phases of the cell cycle. RNA or DNA viral sequences can also be located in this fashion. These probes are usually labeled with  32 P,  33 P, or  35 S.  In the realm of behavioral endocrinology, autoradiography can be used to determine hormonal uptake and indicate receptor location; an animal can be injected with a radiolabeled hormone, or the study can be conducted  in vitro ."}
{"_id": "WikiPedia_Radiology$$$corpus_4741", "text": "The rate of DNA replication in a mouse cell growing  in vitro  was measured by autoradiography as 33 nucleotides per second. [ 8 ]   The rate of  phage T4  DNA elongation in phage-infected  E. coli  was also measured by autoradiography as 749 nucleotides per second during the period of exponential DNA increase at 37\u00a0\u00b0C (99\u00a0\u00b0F). [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4742", "text": "Phosphorylation  means the posttranslational addition of a  phosphate group  to specific amino acids of proteins, and such modification can lead to a drastic change in the stability or the function of a protein in the cell. Protein phosphorylation can be detected on an autoradiograph, after incubating the protein in vitro with the appropriate  kinase  and \u03b3-32P-ATP. The radiolabeled phosphate of latter is incorporated into the protein which is isolated via  SDS-PAGE  and visualized on an autoradiograph of the gel. (See figure 3. of a recent study showing that  CREB-binding protein  is phosphorylated by  HIPK2 . [ 10 ] )"}
{"_id": "WikiPedia_Radiology$$$corpus_4743", "text": "In  plant physiology , autoradiography can be used to determine sugar accumulation in leaf tissue. [ 11 ]  Sugar accumulation, as it relates to autoradiography, can described the  phloem-loading strategy  used in a plant. [ 12 ]  For example, if sugars accumulate in the  minor veins  of a leaf, it is expected that the leaves have few  plasmodesmatal  connections which is indicative of  apoplastic  movement, or an active phloem-loading strategy. Sugars, such as  sucrose ,  fructose , or  mannitol , are  radiolabeled  with [ 14-C ], and then absorbed into leaf tissue by simple  diffusion . [ 13 ]  The leaf tissue is then exposed to autoradiographic film (or emulsion) to produce an image. Images will show distinct vein patterns if sugar accumulation is concentrated in leaf veins (apoplastic movement), or images will show a static-like pattern if sugar accumulation is uniform throughout the leaf ( symplastic  movement)."}
{"_id": "WikiPedia_Radiology$$$corpus_4744", "text": "This autoradiographic approach contrasts to techniques such as  PET  and  SPECT  where the exact 3-dimensional localization of the radiation source is provided by careful use of coincidence counting, gamma counters and other devices."}
{"_id": "WikiPedia_Radiology$$$corpus_4745", "text": "Krypton-85  is used to inspect aircraft components for small defects. Krypton-85 is allowed to penetrate small cracks, and then its \npresence is detected by autoradiography. The method is called \"krypton gas penetrant imaging\". The gas penetrates smaller openings than the liquids used in  dye penetrant inspection  and  fluorescent penetrant inspection . [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4746", "text": "The task of radioactive decontamination following the  Baker  nuclear test at  Bikini Atoll  during  Operation Crossroads  in 1946 was far more difficult than the U.S. Navy had prepared for. Though the task's futility became apparent and the danger to cleanup crews mounted, Colonel  Stafford Warren , in charge of radiation safety, had difficulty persuading Vice Admiral  William H. P. Blandy  to abandon the cleanup and with it the surviving target ships. On August 10, Warren showed Blandy an autoradiograph made by a  surgeonfish  from the lagoon that was left on a photographic plate overnight. The film was exposed by alpha radiation produced from the fish's scales, evidence that plutonium, mimicking calcium, had been distributed throughout the fish. Blandy promptly ordered that all further decontamination work be discontinued. Warren wrote home, \"A self X ray of a fish\u00a0... did the trick.\" [ 15 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4747", "text": "Original publication by sole inventor\n Askins, Barbara S.  (1 November 1976). \"Photographic image intensification by autoradiography\". Applied Optics. 15 (11): 2860\u20132865. Bibcode:1976ApOpt..15.2860A. doi:10.1364/ao.15.002860."}
{"_id": "WikiPedia_Radiology$$$corpus_4748", "text": "Backscatter X-ray  is an advanced  X-ray imaging  technology. Traditional  X-ray machines  detect hard and soft materials by the variation in  x-ray  intensity transmitted through the target. In contrast, backscatter X-ray detects the radiation that  reflects  from the target. It has potential applications where less-destructive examination is required, and can operate even if only one side of the target is available for examination."}
{"_id": "WikiPedia_Radiology$$$corpus_4749", "text": "The technology is one of two types of whole-body imaging technologies that have been used to perform  full-body scans  of airline passengers to detect hidden weapons, tools, liquids, narcotics, currency, and other contraband. A competing technology is  millimeter wave scanner . One can refer to an  airport security  machine of this type as a \"body scanner\", \"whole body imager (WBI)\", \"security scanner\" or \"naked scanner\". [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4750", "text": "In the United States, the FAA Modernization and Reform Act of 2012 required that all full-body scanners operated in airports by the  Transportation Security Administration  use \"Automated Target Recognition\" software, which replaces the picture of a nude body with the cartoon-like representation. [ 3 ]   As a result of this law, all backscatter X-ray machines formerly in use by the Transportation Security Administration were removed from airports by May 2013, since the agency said the vendor ( Rapiscan ) did not meet their contractual deadline to implement the software. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4751", "text": "In the European Union, backscatter X-ray screening of airline passengers was banned in 2012 to protect passenger safety. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4752", "text": "Backscatter technology is based on the  Compton scattering  effect of  X-rays , a form of  ionizing radiation . Unlike a traditional X-ray machine, which relies on the transmission of X-rays through the object, backscatter X-ray detects the radiation that reflects from the object and forms an image. The backscatter pattern is dependent on the material property and is good for imaging organic material."}
{"_id": "WikiPedia_Radiology$$$corpus_4753", "text": "In contrast to  millimeter wave scanners , which create a 3D image, backscatter X-ray scanners will typically only create a 2D image. For airport screening, images are taken from both sides of the human body. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4754", "text": "Backscatter X-ray was first applied in a commercial low-dose personnel scanning system by Dr. Steven W. Smith. [ 7 ] [ 8 ] [ 9 ]  Smith developed the Secure 1000 whole-body scanner in 1992 and then sold the device and associated patents to Rapiscan Systems, who now manufactures and distributes the device."}
{"_id": "WikiPedia_Radiology$$$corpus_4755", "text": "Some backscatter X-ray scanners can scan much larger objects, such as trucks and containers. This scan is much faster than a physical search and could potentially allow a larger percentage of shipping to be checked for smuggled items, weapons, drugs, or people."}
{"_id": "WikiPedia_Radiology$$$corpus_4756", "text": "There are also  gamma-ray -based systems coming to market. [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4757", "text": "In May 2011, the  Electronic Privacy Information Center  filed suit against the  United States Department of Homeland Security  (DHS) under the  Freedom of Information Act , claiming that DHS had withheld nearly 1000 pages of documents related to the Z backscatter vans and other mobile backscatter devices. [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4758", "text": "Since in addition to weapons, these machines are designed to be capable of detecting drugs, currency and contraband, which have no direct effect on airport security and passenger safety, some have argued that the use of these full body scanners is a violation of the  Fourth Amendment to the United States Constitution  and can be construed as an illegal search and seizure. [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4759", "text": "Backscatter x-ray technology has been proposed as an alternative to personal searches at airport and other security checkpoints easily penetrating clothing to reveal concealed weapons. It raises privacy concerns about what is seen by the person viewing the scan. Some [ who? ]  worry that viewing the image violates confidential medical information, such as the fact a passenger uses a  colostomy bag , has a missing limb or wears a prosthesis, or is transgender."}
{"_id": "WikiPedia_Radiology$$$corpus_4760", "text": "The  ACLU  and the  Electronic Privacy Information Center  are opposed to this use of the technology. The ACLU refers to backscatter x-rays as a \"virtual strip search\". [ 13 ]  According to the  Transportation Security Administration  (TSA), in one trial 79 percent of the public opted to try backscatter over the traditional pat-down in secondary screening. [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4761", "text": "It is \"possible for backscatter X-raying to produce photo-quality images of what's going on beneath our clothes\", thus, many software implementations of the scan have been designed to distort private areas. [ 15 ]  According to the TSA, further distortion is used in the Phoenix airport's trial system where photo-quality images are replaced by chalk outlines. [ 16 ] [ 17 ]  In light of this, some journalists have expressed concern that this blurring may allow people to carry weapons or certain explosives aboard by attaching the object or substance to their genitals. [ 15 ] [ 18 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4762", "text": "The British newspaper  The Guardian  has revealed concern among British officials that the use of such scanners to scan children may be illegal under the  Protection of Children Act 1978 , which prohibits the creation and distribution of indecent images of children. This concern may delay the introduction of routine backscatter scanning in UK airports, which had been planned in response to the attempted Christmas Day 2009 attack on  Northwest Airlines Flight 253 . [ 19 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4763", "text": "The  Fiqh Council of North America  have also issued the following  fatwa  in relation to full-body scanners:"}
{"_id": "WikiPedia_Radiology$$$corpus_4764", "text": "It is a violation of clear Islamic teachings that men or women be seen naked by other men and women. Islam highly emphasizes haya (modesty) and considers it part of faith. The Quran has commanded the believers, both men and women, to cover their private parts. [ 20 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4765", "text": "In August 2010, it was reported [ 21 ] [ who? ]  that U.S. Marshals (part of the Department of Justice), [ 22 ]  saved thousands of images from a low resolution  mm wave scanner : This machine does not show details of human anatomy, and is a different kind of machine from the one used in airports. TSA, part of the Department of Homeland Security, said that its scanners do not save images and that the scanners do not have the capability to save images when they are installed in airports, [ 23 ]  but later admitted that the scanners are required to be capable of saving images for the purpose of evaluation, training and testing. [ 24 ] [ 25 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4766", "text": "Unlike cell phone signals, or millimeter-wave scanners, the energy being emitted by a backscatter X-ray is a type of  ionizing radiation  that breaks chemical bonds. Ionizing radiation is considered carcinogenic  even in very small doses  but at the doses used in airport scanners this effect is believed to be negligible for an individual. [ 26 ] [ 27 ] [ 28 ] [ 29 ]  If 1 million people were exposed to 520 scans in one year, one study estimated that roughly four additional cancers would occur due to the scanner, in contrast to the 600 additional cancers that would occur from the higher levels of radiation during flight. [ 30 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4767", "text": "Since the scanners do not have a medical purpose, the United States  Food and Drug Administration  (FDA) does not need to subject them to the same safety evaluations as medical X-rays. [ 31 ]   However, the FDA has created a webpage comparing known estimates of the radiation from backscatter X-ray body scanners to that of other known sources, which cites various reasons they deem the technology to be safe. [ 32 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4768", "text": "Four professors at the  University of California, San Francisco , among them members of NAS and an expert in cancer and imaging, in an April 2010 letter [ 33 ]  to the  presidential science and technology advisor  raised several concerns about the validity of the indirect comparisons the  Food and Drug Administration  used in evaluating the safety of backscatter x-ray machines. [ 34 ]  They argued that the effective dose is higher than claimed by the TSA and the body scanner manufacturers because the dose was calculated as if distributed throughout the whole body, whereas most of the radiation is absorbed in the skin and tissues immediately underneath. Other professors from the radiology department at UCSF disagree with the claims of the signing four professors. [ 35 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4769", "text": "The UCSF professors requested that additional data be made public detailing the specific data regarding sensitive areas, such as the skin and certain organs, as well as data on the special (high-risk) population. In October 2010, the FDA and TSA responded to these concerns. [ 36 ] [ 37 ]  The letter cites reports which show that the specific dose to the skin is some 89,000 times lower than the annual limit to the skin established by the  NCRP . Regarding the UCSF concerns over the high-risk population to sensitive organs, the letter states that such an individual \"would have to receive more than 1,000 screenings to begin to approach the annual limit\". [ 38 ] [ 39 ] [ 40 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4770", "text": "John Sedat, the principal author of the UCSF letter, responded in November 2010 that the White House's claim that full-body scanners pose no health risks to air travelers is in error, adding that the White House statement has \"many misconceptions, and we will write a careful answer pointing out their errors\". [ 41 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4771", "text": "In a December 2, 2010 letter to the House of Representatives, Dr. Steven Smith, inventor of the body scanner in 1991, stated that the concerns of Brenner and UCSF regarding the skin dose of backscatter scanners is incorrect and the result of a confusion between dose and imaging penetration. Smith demonstrated this difference with two experiments using plastic (with a similar  rate of absorption  as body tissue), copper (the image subject), and an x-ray scanner. The dose-penetration experiment shows that 5 and 50\u00a0mm (0.20 and 1.97\u00a0in) plastic samples absorb 5% and 50% of the beam intensity respectively, whereas the imaging penetration experiment shows that 4.8 and 10\u00a0mm (0.19 and 0.39\u00a0in) plastic samples reduce the image darkness by 23% and 50% respectively. Dr. Smith states that those who calculate high skin dosage have incorrectly used the shallow imaging penetration value of a few millimeters (c. 0.16\u00a0in), whereas the actual dosage is calculated by the deeper dose penetration. [ 42 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4772", "text": "The TSA has also made public various independent safety assessments of the Secure 1000 Backscatter X-ray Scanner. [ 43 ] [ 44 ] [ 45 ] [ 46 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4773", "text": "Radiation safety authorities including the  National Council on Radiation Protection and Measurements , The Health Physics Society and the  American College of Radiology , have stated that there is no specific evidence that full-body scans are unsafe. [ 47 ]  The Secure 1000 Backscatter X-ray scanner was developed in 1992 by Dr. Steve Smith. [ 9 ]  The scanner has been studied extensively for almost 20 years by the leading independent radiation safety authorities in the United States. [ 47 ] [ 48 ]  Experimental and epidemiological data do not support the proposition, however, that there is a threshold dose of radiation below which there is no increased risk of cancer. [ 49 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4774", "text": "The UK Health Protection Agency has completed an analysis of the X-ray dose from backscatter scanners and has written that the dose is extremely low and \"about the same as people receive from  background radiation  in an hour\". [ 50 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4775", "text": "The  Health Physics Society  (HPS) reports that a person undergoing a backscatter scan receives approximately 0.05\u00a0 \u03bcSv  (0.005\u00a0 mrem ) of radiation; American Science and Engineering Inc. reports 0.09\u00a0\u03bcSv (0.009\u00a0mrem). At the high altitudes typical of commercial flights, naturally occurring cosmic radiation is considerably higher than at ground level.  The radiation dose for a six-hour flight is 20\u00a0\u03bcSv (2\u00a0mrem) \u2013 200 to 400 times larger than a backscatter scan.  The  Nuclear Regulatory Commission  limits radiation exposure to the public to less than 1\u00a0mSv (100\u00a0mrem) per year from  nuclear power plants . [ 51 ]  While this is not specifically for airline-associated radiation, the limit is an effective proxy for understanding what level is deemed safe by a regulatory agency."}
{"_id": "WikiPedia_Radiology$$$corpus_4776", "text": "According to a draft [ needs update ]  standard on the United States FDA website, the allowable dose from a scan would be 0.1\u00a0\u03bcSv, and that report uses a model whereby a 0.01\u00a0\u03bcSv dose increases an individual's risk of death by cancer during his or her lifetime by  5 \u00d7 10 \u221210 . [ 52 ]  Since the dose limit is ten times higher than 0.01\u00a0\u03bcSv, their model would predict one additional cancer death per 200 million scans. Since the airports in the UK handled 218 million passengers in 2009, [ 53 ]  if all passengers in the UK were scanned at the maximum dosage, then each year this would produce on average one additional cancer death (since there would be 200 million scans per year that the scanners were in operation), though usually each death would not occur in the same year as the particular scan that caused it, since the cancer may take years to grow. In addition, additional people would be given cancer but would die from other causes."}
{"_id": "WikiPedia_Radiology$$$corpus_4777", "text": "There may not yet be evidence of hereditary effects of x-rays administered by backscatter scanners, but backscatter scanners use the same kind of x-ray photons as are produced in medical x-ray machines but expose the subject at a considerably lower dose, so it is possible that the results from medical radiology may be relevant, at least until a study is done of any effects specific to backscatter x-ray machines. Fathers exposed to medical diagnostic x-rays are more likely to have infants who contract leukemia, especially if exposure is closer to conception or includes two or more X-rays of the lower gastrointestinal (GI) tract or lower abdomen. [ 54 ]  In medical radiography the x-ray beam is adjusted to expose only the area of which an image is required, so that generally shielding is applied to the patient to avoid exposing the gonads, [ 55 ]  whereas in an airport backscatter scan, the testicles of men and boys will be deliberately subjected to the direct beam in order to check for weapons in the underpants, and some radiation will also reach the ovaries of female subjects. A linear dose-response relationship has been observed between x-ray dose and double-strand breaks in DNA in human sperm. [ 56 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4778", "text": "Extrapolations of cancer risk from minuscule exposures to radiation across large populations, however, are not supported by analysis by the  National Council on Radiation Protection  (NCRP). On May 26, 2010, NCRP issued a press release to address such comments about full body scanners that are compliant with ANSI N43.17. In Commentary No. 16 issued on May 26, 2010, it reads as follows:"}
{"_id": "WikiPedia_Radiology$$$corpus_4779", "text": "As stated in NCRP Report No. 121 (1995), Principles and Application of Collective Dose in Radiation Protection, the summation of trivial average risks over very large populations or time periods into a single value produces a distorted image of risk, completely out of perspective with risks accepted every day, both voluntarily and involuntarily. [ 57 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4780", "text": "According to NCRP, the use of statistical extrapolations that predict 1 death for every 200 million persons scanned for example (as above) is an unrealistic over-estimation. [ 57 ] [ 58 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4781", "text": "Other scientists at  Columbia University  have made the following statements in support of the safety of body scanners: [ 59 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4782", "text": "\"A passenger would need to be scanned using a backscatter scanner, from both the front and the back, about 200,000 times to receive the amount of radiation equal to one typical CT scan,\" said Dr. Andrew J. Einstein, director of cardiac CT research at Columbia University Medical Center in New York City."}
{"_id": "WikiPedia_Radiology$$$corpus_4783", "text": "\"Another way to look at this is that if you were scanned with a backscatter scanner every day of your life, you would still only receive a tenth of the dose of a typical CT scan,\" he said."}
{"_id": "WikiPedia_Radiology$$$corpus_4784", "text": "By comparison, the amount of radiation from a backscatter scanner is equivalent to about 10 minutes of natural background radiation in the United States, Einstein said. \"I believe that the general public has nothing to worry about in terms of the radiation from airline scanning,\" he added."}
{"_id": "WikiPedia_Radiology$$$corpus_4785", "text": "For moms-to-be, no evidence supports an increased risk of miscarriage or fetal abnormalities from these scanners, Einstein added."}
{"_id": "WikiPedia_Radiology$$$corpus_4786", "text": "\"A pregnant woman will receive much more radiation from cosmic rays she is exposed to while flying than from passing through a scanner in the airport,\" he said."}
{"_id": "WikiPedia_Radiology$$$corpus_4787", "text": "Furthermore, other scientists claim the health effects of backscatter are well understood whereas those from  millimeter wave scanners  are not:"}
{"_id": "WikiPedia_Radiology$$$corpus_4788", "text": "\"From a radiation standpoint there has been no evidence that there is really any untoward effect from the use of this device [backscatter scanner], so I would not be concerned about it from a radiation dose standpoint \u2013 the issues of personal privacy are a different thing,\" he said."}
{"_id": "WikiPedia_Radiology$$$corpus_4789", "text": "The health effects of the more common  millimeter wave scanner  are largely unknown, and at least one expert believes a safety study is warranted."}
{"_id": "WikiPedia_Radiology$$$corpus_4790", "text": "\"I am very interested in performing a National Council on Radiation Protection and Measurements study on the use of millimeter-wave security screening systems,\" said Thomas S. Tenforde, council president."}
{"_id": "WikiPedia_Radiology$$$corpus_4791", "text": "However, no long-term studies have been done on the health effects of millimeter wave scanners. [ 59 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4792", "text": "Experts evaluating backscatter x-ray machine technology have also argued that defects in the machines, damage from normal wear-and-tear, or software errors could focus an intense dose of radiation on just one spot of the body. [ 33 ]  For example, Dr. Peter Rez, a professor of physics at Arizona State University, has said, \"The thing that worries me the most, is not what happens if the machine works as advertised, but what happens if it doesn't\", adding that a potential malfunction of the machine could increase the radiation dose. [ 60 ] [ 61 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4793", "text": "The designers and manufacturers of backscatter X-ray scanners claim that the scanners are designed to prevent the occurrence of these kinds of errors. The scanners' safety requirements include fail-safe controls and multiple overlapping interlocks. These features, combined with fault analysis, ensure that failure of any subsystem results in non-operation of the x-ray generator to prevent accidental exposures. In the United States, the TSA requires that certification to the ANSI N43.17 safety standard is performed by a third party and not by the manufacturer themselves. [ 62 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4794", "text": "The  European Commission  issued a report stating that backscatter x-ray scanners pose no known health risk, and that \"assuming all other conditions equal\", that backscatter x-ray scanners, which expose people to ionizing radiation, should not be used when millimeter-wave scanners that \"have less effects on the human body\" are available. [ 63 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4795", "text": "However, the European Commission report provides no data substantiating its claim that \"all other conditions are equal\". One area where backscatter X-ray scanners can provide better performance than MM wave scanners, for example, is in the inspection of the shoes, groin and armpit regions of the body. [ 64 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4796", "text": "In a study published in the  Archives of Internal Medicine  on March 28, 2011, researchers at the University of California \"calculated that fully implementing backscatter scanners would not significantly increase the lifetime risk of cancer for travelers\". [ 65 ] [ 66 ]  The researchers calculated that for every 100 million passengers who flew seven one-way flights, there would be one additional cancer. [ 67 ] [ 68 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4797", "text": "In March 2012, scientist and blogger Jonathan Corbett demonstrated the ineffectiveness of the technology by publishing a viral video showing how he was able to get a metal box through backscatter x-ray and millimeter wave scanners (including the currently-used \"Automated Target Recognition\" scanners) in two US airports. [ 69 ] [ 70 ]  In April 2012, Corbett released a second video interviewing a TSA screener, who described firearms and simulated explosives passing through the scanners during internal testing and training. [ 71 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4798", "text": "Backscatter scanners installed by the TSA until 2013 were unable to screen adequately for security threats inside hats and head coverings, casts, prosthetics and loose clothing. [ 72 ] [ 73 ]   This technology limitation of current scanners often requires these persons to undergo additional screening by hand or other methods and can cause additional delay or feelings of harassment. [ 74 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4799", "text": "The next generation of backscatter scanners are able to screen these types of clothing, according to manufacturers; however, these machines are not currently in use in public airports. [ 75 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4800", "text": "In Germany, field tests on more than 800,000 passengers over a 10-month trial period concluded that scanners were effective, but not ready to be deployed in German airports due to a high rate of false alarms. [ 76 ]  The Italian Civil Aviation Authority removed scanners from airports after conducting a study that revealed them to be inaccurate and inconvenient. [ 77 ]  The European Commission decided to effectively ban backscatter machines. [ 78 ]  In a 2011 staff report by Republican Members of Congress about the TSA, airport body scanners were described as \"ineffective\" and \"easily thwarted\". [ 79 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4801", "text": "In the US, manufacturers of security related equipment can apply for protection under the SAFETY act, which limits their financial liability in product liability cases to the amount of their insurance coverage.  The Rapiscan Secure 1000 was listed in 2006. [ 80 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4802", "text": "In the US, an X-ray system can be considered to comply with requirements for general purpose security screening of humans if the device complies with American National Standards Institute (ANSI) Standard #N43.17. [ 81 ] [ 82 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4803", "text": "In the most general sense, N43.17 states that a device can be used for general purpose security screening of humans if the dose to the subject is less than 0.25\u00a0\u03bcSv (25\u00a0\u03bcrem) per examination and complies with other requirements of the standard.  This is comparable to the average dose due to background radiation (i.e. radioactivity within the surrounding environment) at sea level in 1.5 hours; it is also comparable to the dose from  cosmic rays  when traveling in an airplane at cruising altitude for two minutes. [ 83 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4804", "text": "Many types of X-ray systems can be designed to comply with ANSI N43.17 including transmission X-ray, [ 84 ]  backscatter X-ray and gamma ray systems. Not all backscatter X-ray devices necessarily comply with ANSI N43.17; only the manufacturer or end user can confirm compliance of a particular product to the standard."}
{"_id": "WikiPedia_Radiology$$$corpus_4805", "text": "ANSI standards use a standard of measurement algorithm called \"effective dose\" that considers the different exposure of all parts of the body and then weights them differently. The interior of the human body is given more weight in this survey, and the exterior, including the skin organ, are given less weight."}
{"_id": "WikiPedia_Radiology$$$corpus_4806", "text": "Some people wish to prevent either the loss of privacy or the possibility of health problems or genetic damage that might be associated with being subjected to a backscatter X-ray scan.  One company sells X-ray absorbing underwear which is said to have X-ray absorption equivalent to 0.5\u00a0mm (0.020\u00a0in) of lead. [ 85 ]   Another product, Flying Pasties, \"are designed to obscure the most private parts of the human body when entering full body airport scanners\", but their description does not seem to claim any protection from the X-ray beam penetrating the body of the person being scanned. [ 86 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4807", "text": "Carbon dioxide angiography  is a diagnostic  radiographic  technique in which a  carbon dioxide  (CO 2 ) based contrast medium is used - unlike traditional  angiography  where the contrast medium normally used is iodine based \u2013 to see and study the  body vessels . [ 1 ]  Since CO 2  is a non-radio-opaque contrast medium, angiographic procedures need to be performed in  digital subtraction angiography  (DSA)."}
{"_id": "WikiPedia_Radiology$$$corpus_4808", "text": "The use of carbon dioxide as a  contrast agent  goes back to 1920s when the gas was used to visualize retroperitoneal structures. In the 1950s and early 1960s, CO 2  was injected intravenously to delineate the right atrium for the detection of  pericardial effusion . This imaging technique developed from animal and clinical studies which demonstrated that CO 2  was safe and well tolerated with venous injections. In the early 1970s, Dr. Hawkins and Dr. Cho started using and studying CO 2  as a contrast agent also for peripheral vascular imaging and intervention. With the advent of  digital subtraction angiography  (DSA) technique in 1980s, CO 2  has evolved into a safe and useful alternative contrast agent in both arteriography and venography. Because of its lack of renal toxicity and allergic potential, CO 2  is a preferred contrast agent in patients with renal failure or iodinated contrast medium allergy, and particularly in patients who require large volumes of contrast medium for complex endovascular procedures . [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4809", "text": "CO 2  angiography is intended only for peripheral procedures. In case of procedures in the arterious system it is allowed to inject CO 2  only below the diaphragm; while in the venous system it can also be investigated supradiaphragmatic, provided that the cerebral vessels are excluded. Taking this aspect into consideration, the practical approach follows that of the iodinated contrast procedures. The contrast injection can be carried out, similarly, both with manual devices and with automatic injectors (Automated Carbon Dioxide Angiography, ACDA). [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4810", "text": "Being naturally present in the human body, CO 2  is the only 100%  biocompatible  contrast agent, meaning no adverse reactions, such as allergy, nephrotoxicity, and hepatotoxicity."}
{"_id": "WikiPedia_Radiology$$$corpus_4811", "text": "Carbon dioxide is a negative contrast medium and it has a low  radiopacity  (while iodinated contrast media are defined as positive contrast media due to their high radiopacity). Contrast is caused by the different X-ray absorption coefficients between the tissue and the contrast agent. In the vascular imaging results produced using CO 2 , vessels look brighter rather than the surrounding tissues, because the contrast medium absorbs less X-ray radiations rather an iodine-based contrast medium, where the vessel are displayed in black."}
{"_id": "WikiPedia_Radiology$$$corpus_4812", "text": "The CO 2  does not mix with blood. At  atmospheric pressure  CO 2  is in gaseous form and, when it comes out from the catheter, it forms a train of bubbles which displaces blood, causing a transient  ischemia , in relation to the bloodstream ( systolic pressure ). When added together by DSA \u201cstacking\u201d software, [ 5 ]  the result is a composite diagnostic image of the frames."}
{"_id": "WikiPedia_Radiology$$$corpus_4813", "text": "Carbon dioxide is highly  soluble , allowing multiple injections without a maximum dosage (per procedure, while it is 100 mL per injection by the literature), but, in case of multiple injections, should be considered and adequate time interval between them, so to allow the gas to be expelled from the body. Compared with the oxygen, the most present gaseous substance in the body, CO 2  is more than 20 times more soluble, meaning the possibility of injecting high quantities in the body."}
{"_id": "WikiPedia_Radiology$$$corpus_4814", "text": "High  compressibility  and explosive delivery. More pressure is exerted to the gas, more its density increases, resulting in a decrease in gas volume and an increase in gas pressure. The effusion of the gas from the catheter orifice into a state of lower pressure, such as a blood vessel, leads to a sudden increase in the volume of the gas - the \u201cexplosive delivery\u201d or \u201cjet effect\u201d - which could lead to an excessive stress in vessels walls. To avoid this, immediately prior to the injection of CO 2 , a flush is performed, injecting small amounts of CO 2  to reduce gas compression and guarantee gas delivery at a steady  flow rate ."}
{"_id": "WikiPedia_Radiology$$$corpus_4815", "text": "CO 2  is 400 times less viscous than iodinated contrast medium, allowing its injection through devices with a very little inner lumen, as microcatheters, or, even, with other devices inserted in the catheter, as guidewires, balloons or as in atherectomy procedures. The  low viscosity  of CO 2  makes it easy to pass through small vessels, visualizing tight stenosis, collaterals, small bleedings and endoleaks in AAA procedures."}
{"_id": "WikiPedia_Radiology$$$corpus_4816", "text": "Expulsion: Once dissolved in the plasma, CO 2  is transported to the lungs and removed in a single pass by the alveoli, favoring the possibility of performing multiple injections without complications (in healthy patients, meaning no severe COPD or significant POF, especially in presence of pulmonary embolism)."}
{"_id": "WikiPedia_Radiology$$$corpus_4817", "text": "Buoyancy  is defined as the tendency of a body to float when submerged into a fluid. CO 2  is lighter than blood and, therefore, floats above the bloodstream. The main advantage is represented by the simplicity of filling the more superficial (in transverse plane) vessels of the body, conversely the main disadvantage consists in a less ease of filling the deeper ones. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4818", "text": "Pins and needles/burning sensation, nausea and temporary discomfort are possible sensations during CO 2  angiography, mainly because the transient ischemia caused by the CO 2  bubbles flowing in the bloodstream. CO 2  is also neurotoxic, so brain injections should be avoided. The most feared complication for intravascular use is air embolism, which can result in stroke, myocardial infarction, paralysis, amputation, or death, although this risk across all patients is less than 1%. A large amount of CO 2  trapped in the pulmonary artery or right side of the heart (only of concern during venography) obstructs venous return resulting in bradycardia and hypotension. The patient should be rotated into a left lateral decubitus position if this happens to attempt to separate the CO 2  into a gas layer floating \"on top of\" and no longer interfering with the flow of the liquid and solid components of blood (vapor lock). Therefore, having a delivery system, which prevents air room diffusion, is a necessary safety measure for the patients. [ 7 ] [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4819", "text": "Cargo scanning  or  non-intrusive inspection  ( NII ) refers to non-destructive methods of inspecting and identifying goods in transportation systems. It is often used for scanning of  intermodal freight   shipping containers . In the US, it is spearheaded by the  Department of Homeland Security  and its  Container Security Initiative  (CSI) trying to achieve one hundred percent cargo scanning by 2012 [ 1 ]  as required by the  US Congress  and recommended by the  9/11 Commission . In the US the main purpose of scanning is to detect  special nuclear materials  (SNMs), with the added bonus of detecting other types of suspicious cargo. In other countries the emphasis is on manifest verification, tariff collection and the identification of contraband. [ 2 ]  In February 2009, approximately 80% of US incoming containers were scanned. [ 3 ] [ 4 ]  To bring that number to 100% researchers are evaluating numerous technologies, described in the following sections. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4820", "text": "Gamma-ray   radiography  systems capable of scanning trucks usually use  cobalt-60  or  caesium-137 [ 6 ]  as a radioactive source and a vertical tower of gamma  detectors . This  gamma camera  is able to produce one column of an image. The horizontal dimension of the image is produced by moving either the truck or the scanning hardware. The cobalt-60 units use gamma  photons  with a mean energy 1.25\u00a0 MeV , which can penetrate up to 15\u201318\u00a0cm of steel. [ 6 ] [ 7 ]  The systems provide good quality images which can be used for identifying cargo and comparing it with the manifest, in an attempt to detect anomalies. It can also identify high-density regions too thick to penetrate, which would be the most likely to hide nuclear threats."}
{"_id": "WikiPedia_Radiology$$$corpus_4821", "text": "X-ray  radiography is similar to gamma-ray radiography but instead of using a radioactive source, it uses a  high-energy   bremsstrahlung  spectrum with energy in the 5\u201310\u00a0MeV range [ 8 ] [ 9 ]  created by a  linear particle accelerator  (LINAC). Such X-ray systems can penetrate up to 30\u201340\u00a0cm of steel in vehicles moving with velocities up to 13\u00a0km/h. They provide higher penetration but also cost more to buy and operate. [ 7 ]  They are more suitable for the detection of  special nuclear materials  than gamma-ray systems. They also deliver about 1000 times higher dose of radiation to potential  stowaways . [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4822", "text": "Dual-energy X-ray radiography [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4823", "text": "Backscatter X-ray  radiography"}
{"_id": "WikiPedia_Radiology$$$corpus_4824", "text": "Examples of  neutron activation  systems include: pulsed fast neutron analysis (PFNA), fast neutron analysis (FNA), and thermal neutron analysis (TNA). All three systems are based on neutron interactions with the inspected items and examining the resultant gamma rays to determine the elements being radiated. TNA uses thermal neutron capture to generate the gamma rays. FNA and PFNA use fast neutron scattering to generate the gamma rays. Additionally, PFNA uses a pulsed collimated neutron beam. With this, PFNA generates a three-dimensional elemental image of the inspected item."}
{"_id": "WikiPedia_Radiology$$$corpus_4825", "text": "Muon tomography  is a technique that uses  cosmic ray   muons  to generate three-dimensional images of volumes using information contained in the  Coulomb scattering  of the muons. Since muons are much more deeply penetrating than  X-rays , muon  tomography  can be used to image through much thicker material than x-ray based tomography such as  CT scanning . The muon  flux  at the Earth's surface is such that a single muon passes through a volume the size of a human hand per second. [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4826", "text": "Muon imaging was originally proposed and demonstrated by Alvarez. [ 13 ]  The method was re-discovered and improved upon by a research team at  Los Alamos National Laboratory , [ 14 ] [ 15 ]  muon tomography is completely passive, exploiting naturally occurring  cosmic radiation . This makes the technology ideal for high throughput scanning of volume material where operators are present, such as at a marine cargo terminal. In these cases, truck drivers and customs personnel do not have to leave the vehicle or exit an exclusion zone during scanning, expediting cargo throughput."}
{"_id": "WikiPedia_Radiology$$$corpus_4827", "text": "Multi-mode passive detection systems (MMPDS), based upon  muon tomography , are currently in use by Decision Sciences International Corporation at Freeport, Bahamas, [ 16 ]  and the  Atomic Weapons Establishment  in the United Kingdom. [ 17 ]  An MMPDS system has also been contracted by Toshiba to determine the location and the condition of the nuclear fuel in the  Fukushima Daiichi Nuclear Power Plant . [ 18 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4828", "text": "Radiological materials emit gamma photons, which  gamma   radiation detectors , also called radiation portal monitors (RPM), are good at detecting. Systems currently used in US ports (and  steel mills ) use several (usually 4) large  PVT  panels as  scintillators  and can be used on vehicles moving up to 16\u00a0km/h. [ 19 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4829", "text": "They provide very little information on energy of detected photons, and as a result, they were criticized for their inability to distinguish gammas originating from nuclear sources from gammas originating from a large variety of benign cargo types that naturally emit radioactivity, including bananas,  cat litter ,  granite ,  porcelain ,  stoneware , etc. [ 4 ]  Those  naturally occurring radioactive materials , called NORMs account for 99% of nuisance alarms. [ 20 ]  Some radiation, like in the case of large loads of bananas is due to  potassium  and its rarely occurring (0.0117%) radioactive isotope potassium-40, other is due to  radium  or  uranium  that occur naturally in earth and rock, and cargo types made out of them, like cat litter or porcelain."}
{"_id": "WikiPedia_Radiology$$$corpus_4830", "text": "Radiation originating from earth is also a major contributor to  background radiation ."}
{"_id": "WikiPedia_Radiology$$$corpus_4831", "text": "Another limitation of gamma radiation detectors is that gamma photons can be easily suppressed by high-density shields made from lead or steel, [ 4 ]  preventing detection of nuclear sources. Those types of shields do not stop fission neutrons produced by  plutonium  sources, however. As a result, radiation detectors usually combine gamma and neutron detectors, making shielding only effective for certain uranium sources."}
{"_id": "WikiPedia_Radiology$$$corpus_4832", "text": "Fissile materials emit neutrons. Some nuclear materials, such as the weapons usable  plutonium-239 , emit large quantities of neutrons, making neutron detection a useful tool to search for such contraband. Radiation Portal Monitors often use  Helium-3  based detectors to search for neutron signatures. However, a global supply shortage of He-3 [ 21 ]  has led to the search for other technologies for neutron detection."}
{"_id": "WikiPedia_Radiology$$$corpus_4833", "text": "A  cephalogram  is an  X-ray  of the  craniofacial  area. [ 1 ]  A  cephalometric analysis  could be used as means for measuring growth in children."}
{"_id": "WikiPedia_Radiology$$$corpus_4834", "text": "The lateral cephalogram is a profile x-ray of the skull and soft tissues and is used to assess the relation of the teeth in the jaws, the relation of the jaws to the skull and the relation of the soft tissues to the teeth and jaws. In children, growth predictions can be made and we can also determine the changes that have occurred with treatment. In adults, treatment can be predicted with varying degrees of accuracy and results quantified."}
{"_id": "WikiPedia_Radiology$$$corpus_4835", "text": "The  CTX  ( C omputer  T omography  X -ray) is an explosive detection device, a family of  x-ray  devices developed by  InVision Technologies  in 1990 that uses  CAT scans  and sophisticated  image processing  software to automatically screen checked baggage for explosives."}
{"_id": "WikiPedia_Radiology$$$corpus_4836", "text": "In 1994, the CTX-5000 became the first  computed tomography  explosive detection system certified by the  US Federal Aviation Administration  (FAA). The certification of the CTX-5000 followed nine years of development. During that time the FAA invested $90 million in explosives detection and nearly $8.6 million in the specific technology. From 1995 to 1997, the CTX-5000 was tested to solve the challenges involved in integrating an explosives detection system into a baggage system and to validate the estimated costs of wide-scale deployment of the systems."}
{"_id": "WikiPedia_Radiology$$$corpus_4837", "text": "The CTX-5000 SP scanning system, an improved version of the CTX-5000 for checked baggage, was delivered to the FAA in 1997 and placed at several of the US's busiest and largest airports. From 1997 to 2000, more than 100 of the systems have been purchased by the FAA to install in US airports, according to  InVision ."}
{"_id": "WikiPedia_Radiology$$$corpus_4838", "text": "The CTX-5500DS is an automated explosives detection system that uses computed tomography to characterize materials in checked bags and automatically identify objects that could be  improvised explosive devices . The CTX-5500DS is the most widely used, FAA-certified Explosives Detection System in the world. [ 1 ]  It can be used for either standalone applications or in an integrated manner with airport baggage handling systems. It can also be configured to detect other types of contraband material. The CTX-5500DS has an FAA-certified throughput of 384 bags per hour. Its Dynamic Screening (DS) capability offers flexibility by allowing manual or automatic switching between various screening modes."}
{"_id": "WikiPedia_Radiology$$$corpus_4839", "text": "The CTX-2500 is a small-sized explosives detection system that is half the length of earlier CTX models. The CTX 2500 utilizes a single rotating X-ray source to acquire positioning images and CT-slice images, thus achieving its smaller size. The CTX 2500 system is the first FAA-certified Explosives Detection System (EDS) mounted on a truck for easy mobility and access to cargo. One of the units costs approximately US$700,000. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4840", "text": "The CTX-9000 DSi system is the world's fastest FAA-certified (Certification moved to TSA Transportation Security Lab in 2002) Explosives Detection System, handling 542 bags per hour. It features alternate operational modes yielding even higher throughputs. The CTX-9000 DSi is designed for integrated airport installations. Its 1-metre wide conveyor coordinates with standard airport baggage handling systems. The system's architecture utilizes modular components, helping to ease scanner upgrading and servicing. The scanner contains 4 active radiation-shielding curtains. In addition, the gantry rotates at 120 RPM, enabling a slice image to be generated within half a second. A high-speed  RF  data link connects the rotating gantry to the stationary part of the unit. An air-conditioning unit ensures high performance and reliability in hot, dusty and humid airport environments."}
{"_id": "WikiPedia_Radiology$$$corpus_4841", "text": "In the late 1990s,  L-3 Communications  developed a competing computerized tomography system that also met FAA approval, however it was not TSA Qualified until late 2002. In November 1999, the FAA awarded a contract worth up to US$75 million to  L-3  to purchase up to 60 of its explosive detection systems. The  eXaminer   3DX 6000  explosive detection system developed by  L-3  operates similarly to the CTX system."}
{"_id": "WikiPedia_Radiology$$$corpus_4842", "text": "In 2013  Rapiscan Systems  made the first delivery of its RTT product. [ 2 ]  This machine operates with a non-rotating 360 degree multi source X-ray tube and detector array CT imaging system so the only moving part is the conveyor belt. This allows it to achieve a throughput of 1800 bags per hour. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4843", "text": "Recent research has evaluated the use of  computer vision  based algorithms that operate on the volumetric data used collected as CT-slice images by these and other manufacturers  computed tomography  (CT) baggage scanner machines for the automatic detection of other threat types (e.g. guns, knives, liquid containers) using 3D object classification. [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4844", "text": "The  radiography of cultural property  is the use of  radiography  to understand intrinsic details about objects.  Most commonly this involves  X-rays  of paintings to reveal  underdrawing ,  pentimenti  alterations in the course of painting or by later restorers, and sometimes previous paintings on the support.  Many  pigments  such as  lead white  show well in radiographs."}
{"_id": "WikiPedia_Radiology$$$corpus_4845", "text": "X-ray spectromicroscopy  has also been used to analyse the reactions of pigments in paintings. For example, in analysing colour degradation in the paintings of  Vincent van Gogh . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4846", "text": "These processes can reveal various details about objects that are not visible to the naked eye. This information, which includes structural elements, aids  conservators  as they assess object condition and consider treatment plans."}
{"_id": "WikiPedia_Radiology$$$corpus_4847", "text": "For three dimensional objects, the  computed tomography (CT)  has become a common tool, which when combined with analysis can, for example, \"digitally unroll\" or unfold and make possible the reading of fragile scrolls, books, or  sealed correspondence . [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4848", "text": "Infrared  and  ultraviolet light  are also useful tools to understand the intrinsic details of certain objects. However, X-rays tend to be more useful for denser objects. [ 3 ]  The benefit of radiography is that it is not intrusive. Radiography does expose the object to  radiation , but these levels are low. In fact, they are much lower than the radiation levels required for medical X-rays. While technicians and staff conducting the X-ray must use protective gear, the object is not damaged during the process. [ 4 ] [ 5 ]  Furthermore, the use of radiography is widely accepted by conservators, art historians, and archaeologists. [ 5 ]  Several institutions around the world conduct radiography of objects in their collections including the  Victoria & Albert Museum  in London, England and the  Smithsonian , which operates the  Museum Conservation Institute ."}
{"_id": "WikiPedia_Radiology$$$corpus_4849", "text": "Conservators and art historians have used radiography to uncover technical information about paintings. Compositions of materials, previous alterations, and painting techniques have been revealed in X-rays. [ 6 ]  This data has also been used to date works and identify forgeries. [ 7 ]  Diagnostic and therapeutic X-ray systems are generally used to produce X-rays of paintings. [ 8 ]  Infrared reflectography has also been used to see  underdrawings  and previous markings on painted canvases. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4850", "text": "Paints  are produced with a variety of  elements . Depending on how much these pigments absorb X-rays affects how clear or opaque they will appear in the radiograph, this is known as X-ray  fluorescence . [ 4 ] [ 10 ]   Lead white , for example, will absorb more rays and appear much more opaque on an X-radiograph than  carbon black , which will allow most of the X-rays to pass through resulting in a clearer result on the radiograph. [ 4 ] [ 11 ]  To produce a radiograph of a painting, the radiographic film is placed on the painted surface and the X-ray tube is placed behind the canvas. [ 12 ] [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4851", "text": "An X-ray of the  Ghent Altarpiece , painted by  Jan van Eyck , in  Saint Bavo Cathedral in Ghent ,  Belgium  revealed the structure and details of the large altarpiece's painting scheme. The complete radiography of the  altarpiece  was conducted between 2010 and 2011 as part of a project largely funded by the  Getty Institute . The X-rays and other technical information that was gathered were used to prepare conservation treatments. [ 13 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4852", "text": "The Sampling Officials of the Amsterdam Drapers' Guild, also known as the  Syndics of the Drapers' Guild  or more simply as the Syndics, was painted by  Rembrandt  in 1662. An X-ray of the painting revealed that Rembrandt fine-tuned the composition several times, alternating the glances between the figures and slightly changing their positions before he settled on that is known today. [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4853", "text": "X-ray analysis revealed alterations to the paint of a sixteenth century portrait that had been identified as a  Bronzino  portrait of  Eleanor of Toledo  at the  Carnegie Museum of Art  in  Pittsburgh ,  Pennsylvania . After a conservation treatment, which removed the added paint, the subject of the portrait was found to be  Isabella de' Medici . The painting was also attributed to Alessandro Allori. [ 15 ] [ 16 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4854", "text": "Jean-Fran\u00e7ois Millet 's The Wood Sawyers at  Victoria & Albert Museum  was X-rayed, revealing that Millet had reused a canvas to complete this oil painting. The artist not only painted over a previous work, but he had also added strips of canvas to enlarge the painting area. [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4855", "text": "According to X-rays taken of Twilight by  Jean Baptiste Camille Corot , also at the Victoria & Albert Museum, the artist painted over a previous picture that had not even dried yet. Pigments from the lower painting appear through cracks in the surface layer. [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4856", "text": "The Old Guitarist  by  Pablo Picasso  at the  Art Institute of Chicago  had been previously examined with visible and ultraviolet light, which had hinted at the possibility of an earlier composition. X-rays of the painting revealed that Picasso had originally painted two female figures behind the guitarist. The X-rays also penetrated far enough to reveal how Picasso had prepared the wooden panel for painting. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4857", "text": "X-rays can provide a better picture of  plaster casts  and other works that rely on internal supports. However, size and mobility can often affect whether or not radiography is an option for sculptural works. X-rays can also identify cracks and previous repairs to  glass  and  ceramic  materials, which is important for assessing the condition. [ 4 ]  This information can also reveal details about the manufacturing process, which may be instrumental in providing establishing place of manufacture, and possibly also reveal  inherent vices  that are not visible to the naked eye. [ 5 ]   Jewelry  and other objects with  inlaid  pieces have been X-rayed to reveal more about their structure. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4858", "text": "The plaster cast of  Michelangelo's   David  at the Victoria & Albert Museum was X-rayed revealing that the supports in David's legs were positioned similarly to that of bones in a human leg. The size of this particular piece required a portable machine to complete the X-rays. [ 17 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4859", "text": "The  Museum of Applied Arts in Vienna , the  Research Centre Seibersdorf \u00a0[ de ] , and the  New York Historical Society  have used X-rays to learn more about the manufacture of  Art Nouveau  style  glass . In particular, they are investigating differences between  Tiffany glass  of New York and Austria's Loetz glass to learn more about differences in the manufacturing process. [ 18 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4860", "text": "In the X-rays of a wooden power figure at the  Indianapolis Museum of Art , conservators discovered that there were hollowed out sections through the center of the sculpture that connected three filled cavities. Information about the network inside of these sculptures has aided curators as they research the function of these pieces. The findings have led to the use of radiography to compare power figures in other collections. [ 19 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4861", "text": "X-rays can reveal information about layers of  textiles  and stitching patterns. For  quilts , for instance, different textile types and other materials are used. [ 20 ]  These materials are often hidden in the finished quilt. Therefore, X-radiography can provide conservators with useful information. For other textiles X-rays can also provide conservators with information about  dyes  since metallic mordant has historically been used in the dye making process. Details about stitching patterns can also appear on X-rays. [ 20 ]  The Victoria & Albert Museum has used X-rays as a tool for several textile conservation projects."}
{"_id": "WikiPedia_Radiology$$$corpus_4862", "text": "X-rays of the  King George III  Golden Jubilee Quilt from 1810 revealed concealed  stitching  patterns and fabric dyes. [ 20 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4863", "text": "Conservators learned more about the complex stitching of the Sundial Coverlet, which dates to 1797, through X-rays. [ 20 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4864", "text": "X-rays were used to understand some of the stains and stitching patterns on an Egyptian tunic, dating to AD 600\u2013799, in the Victoria & Albert collection. [ 21 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4865", "text": "Hidden design and structure details were visible on X-rays of pairs of  shoes  in the V&A's collection. [ 22 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4866", "text": "Archaeological materials have also benefited from X-rays. X-rays of soil segments have revealed artifacts that have eroded away, leaving them nearly undetectable to the naked eye. [ 23 ]  Worn and damaged surfaces, which appear unmarked, have yielded  inscriptions  or other markings on X-rays. [ 24 ]  Heavily corroded metal objects have also used X-rays to learn more about their original state. [ 5 ]  Industrial and medical  CT scans  have also been used by archaeologists to study a variety of artifacts. [ 25 ] [ 26 ] [ 27 ]   Underwater archaeologists  have utilized X-rays to see what is beneath layers of  concretions ."}
{"_id": "WikiPedia_Radiology$$$corpus_4867", "text": "Radiography has been used with human dry bones to diagnose pathologies, demonstrate trauma and assist age estimation through dentition eruption status. [ 28 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4868", "text": "X-rays have been employed to analyze what is under the wrappings of  mummies . [ 26 ]  In addition to providing images of the bones within, X-rays have revealed the location of jewelry and other objects that were buried with the body without disturbing the wrappings."}
{"_id": "WikiPedia_Radiology$$$corpus_4869", "text": "The  Herculaneum papyri  that survived the  Vesuvius  disaster were excavated and researchers have used X-rays to read their contents. Previous methods involved slowly unrolling the  papyrus , which damaged much of the  scrolls , some beyond repair. [ 29 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4870", "text": "X-ray technology was used to quickly identify individual  coins  uncovered in a single container. Researchers did not have to wait for slower, traditional conservation methods to separate and decipher the coins. [ 30 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4871", "text": "X-rays were among the imaging techniques used to uncover lost text on the  Archimedes Palimpsest , which is in the collection of the Walters Museum in Baltimore, Maryland. The museum spearheaded an extensive research project on the palimpsest that employed various imaging techniques including ultraviolet, infrared, and X-radiography. [ 31 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4872", "text": "The heavily corroded  Antikythera mechanism , which was uncovered from a shipwreck at the beginning of the 20th century, has been X-rayed several times in an effort to understand how it works."}
{"_id": "WikiPedia_Radiology$$$corpus_4873", "text": "Digital variance angiography (DVA)  is a novel image processing method based on  kinetic imaging , which allows the visualization of motion on image sequences generated by penetrating radiations. DVA is a specific form of kinetic imaging: it requires angiographic image series, which are created by X-ray or fluoroscopic imaging and by the administration of contrast media during various medical procedures. The resulting single DVA image visualizes the path of  contrast agent  with relatively low background noise. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4874", "text": "Between 2017 and 2019, two clinical studies have been performed to investigate the clinical usability of DVA and these studies have found that it has the potential to be used for low-dose radiographic imaging and carbon-dioxide angiography in the future. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4875", "text": "DVA is currently under development by Kinetic Health Ltd. and  Semmelweis University  (Budapest, Hungary)."}
{"_id": "WikiPedia_Radiology$$$corpus_4876", "text": "In 2018 Gy\u00e1n\u00f3 M. et al. compared the quality of DVA and  DSA (digital subtraction angiography)  images in a prospective observational crossover study, which involved the analysis of 232 image pairs of 42 patients undergoing lower limb x-ray angiography (performed by using iodinated contrast agent) between February and June 2017. Methods included the measurement of SNR ( signal-to-noise ratio ) and visual quality comparison. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4877", "text": "Although other factors like spatial resolution, sharpness, and object size may contribute to image quality and object perceptibility, noise places a fundamental limitation on the ability to recognize structures on low-contrast images and that was the main reason why the SNR measurement method was chosen. The results showed 2-3 times higher SNR values in the case of DVA images compared to traditionally used DSA images, which has indicated that DVA has the potential to improve the ability to view blood vessels, since a higher SNR value indicates lower noise levels."}
{"_id": "WikiPedia_Radiology$$$corpus_4878", "text": "Qualitative comparison has been performed by three vascular surgeons and three interventional radiologists, with about 17 years of experience on the average. In an online visual questionnaire, which showed DVA and DSA image pairs of the same anatomical regions, raters were asked to choose the image which they found to be more useful for making the diagnosis. Overall, the raters judged the kinetic images better in 69% of all images. Regarding different anatomical regions, the raters agreed that the DVA was significantly better for talocrural and popliteal regions."}
{"_id": "WikiPedia_Radiology$$$corpus_4879", "text": "Since the SNR is proportional to radiation dose, the authors have concluded that the higher SNR values indicate that the DVA method has the ability to generate angiographic images which have the same quality as the currently used DSA, but the dose of the administered radiation and/or contrast media could be lowered to achieve the same vessel visibility."}
{"_id": "WikiPedia_Radiology$$$corpus_4880", "text": "In 2019 \u00d3ri\u00e1s V. et al. published the results of a clinical study, which investigated the feasibility of digital variance angiography (DVA) in lower extremity  carbon-dioxide angiography  and compared the quantitative and qualitative performance of the new image processing technique to that of the current reference standard digital subtraction angiography (DSA). [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4881", "text": "The study enrolled 24 patients undergoing lower limb carbon-dioxide angiography between December 2017 and April 2018 at two clinical centres in Hungary. For comparison, the signal-to-noise ratio (SNR) of DSA and DVA images were calculated and the visual quality of DSA and DVA images were also compared by independent clinical specialists using an online questionnaire."}
{"_id": "WikiPedia_Radiology$$$corpus_4882", "text": "The ratio of SNR DVA /SNR DSA was calculated and the median values for the two centres were 3.53 and 4.52. During the visual evaluation 120 DSA and DVA image pairs were compared and it was judged that the DVA provided higher quality images in both centres, in 78% and 90% of comparisons. DVA images also received consistently higher individual rating than DSA images, regardless of the research site and anatomical region."}
{"_id": "WikiPedia_Radiology$$$corpus_4883", "text": "As the authors conclude, these results have shown that in lower limb carbon-dioxide angiography DVA, regardless of the image acquisition instruments and protocols, produces higher signal-to-noise ratio and significantly better image quality than DSA, therefore this new image processing method might help the widespread use of carbon-dioxide as a safer contrast agent in clinical practice."}
{"_id": "WikiPedia_Radiology$$$corpus_4884", "text": "Several oral presentations and posters have been presented at  CIRSE  2019 conference about ongoing research projects, including the study of possible application of DVA during prostatic artery embolization and the development of new algorithms for DVA to further improve image quality, which would create a 'quality reserve' and allow the reduction of radiation and contrast media dose. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4885", "text": "A  DMSA scan  is a  radionuclide  scan that uses  dimercaptosuccinic acid  (DMSA) in assessing renal morphology, structure and function. Radioactive  technetium-99m  is combined with DMSA and injected into a patient, followed by imaging with a  gamma camera after 2-3 hours . [ 1 ]  A DMSA scan is usually static imaging, while  other radiotracers like DTPA  and MAG3 are usually used for dynamic imaging to assess renal excretion. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4886", "text": "The major clinical indications for this investigation are"}
{"_id": "WikiPedia_Radiology$$$corpus_4887", "text": "Procedure: Patient is injected with 2-5 mCi of Technetium-99m DMSA intravenously and static imaging is done using Gamma camera after 2-3 hours. Imaging time is approximately 5 - 10 minutes depending on the views taken. Usually, posterior and oblique views are a must for better interpretation of the scan. Patient is asked to maintain good hydration before and after the radiotracer injection by drinking water or intravenous fluid administration, if patient cannot drink water for any reason. Usually fasting is not required for scanning purpose and patients can have light breakfast in the morning of the scan day."}
{"_id": "WikiPedia_Radiology$$$corpus_4888", "text": "The technetium-99m DMSA binds to the proximal convoluted tubules in kidney so the excretion pattern of the kidneys cannot be assessed by this for which renal dynamic scans using radiotracers like DTPA, MAG3 are used."}
{"_id": "WikiPedia_Radiology$$$corpus_4889", "text": "Flat-panel detectors  are a class of  solid-state   x-ray   digital radiography  devices similar in principle to the  image sensors  used in digital photography and video. They are used in both  projectional radiography  and as an alternative to  x-ray image intensifiers  (IIs) in  fluoroscopy  equipment."}
{"_id": "WikiPedia_Radiology$$$corpus_4890", "text": "X-rays  pass through the subject being imaged and strike one of two types of detectors."}
{"_id": "WikiPedia_Radiology$$$corpus_4891", "text": "Indirect detectors contain a layer of  scintillator  material, typically either  gadolinium oxysulfide  or  cesium iodide , which converts the x-rays into light. Directly behind the scintillator layer is an  amorphous silicon  detector array manufactured using a process very similar to that used to make  LCD  televisions and computer monitors.  Like a  TFT-LCD  display, millions of roughly 0.2\u00a0mm  pixels  each containing a  thin-film transistor  form a grid patterned in amorphous silicon on the glass substrate. [ 1 ]  Unlike an LCD, but similar to a digital camera's image sensor chip, each pixel also contains a  photodiode  which generates an electrical signal in proportion to the light produced by the portion of scintillator layer in front of the pixel. The signals from the photodiodes are amplified and encoded by additional electronics positioned at the edges or behind the  sensor array  in order to produce an accurate and sensitive digital representation of the x-ray image. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4892", "text": "Direct conversion imagers utilize  photoconductors , such as amorphous  selenium  (a-Se), to capture and convert incident x-ray photons directly into electric charge. [ 3 ]  X-ray photons incident upon a layer of a-Se generate electron-hole pairs via the internal photoelectric effect. A  bias  voltage applied to the depth of the selenium layer draw the electrons and holes to corresponding electrodes; the generated current is thus proportional to the intensity of the irradiation. Signal is then read out using underlying readout electronics, typically by a  thin-film transistor  (TFT) array. [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4893", "text": "By eliminating the optical conversion step inherent to indirect conversion detectors, lateral spread of optical photons is eliminated, thus reducing blur in the resulting signal profile in direct conversion detectors. Coupled with the small pixel sizes achievable with TFT technology, a-Se direct conversion detectors can thus provide high spatial resolution. This high spatial resolution, coupled with a-Se's relative high quantum detection efficiency for low energy photons (< 30 keV), motivate the use of this detector configuration for  mammography , in which high resolution is desirable to identify  microcalcifications . [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4894", "text": "Flat-panel detectors are more sensitive and faster than  film . Their sensitivity allows a lower dose of radiation for a given picture quality than film. For  fluoroscopy , they are lighter, far more durable, smaller in volume, more accurate, and have much less image distortion than  x-ray image intensifiers  and can also be produced with larger areas. [ 7 ]  Disadvantages compared to IIs can include defective image elements, higher costs and lower spatial resolution. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4895", "text": "In  general radiography , there are time and cost savings to be made over  computed radiography  and (especially) film systems. [ 9 ] [ 10 ]  In the  United States ,  digital radiography  is on course to surpass use of computed radiography and film. [ 11 ] [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4896", "text": "In  mammography , direct conversion FPDs have been shown to outperform film and indirect technologies in terms of resolution [ citation needed ] , signal-to-noise ratio, and quantum efficiency. [ 13 ]  Digital mammography is commonly recommended as the minimum standard for  breast screening programmes . [ 14 ] [ 15 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4897", "text": "Wolfram Conrad Fuchs  (1865\u20131908) was a German-born  electrical engineer  who became a pioneer in  radiography . He opened the first x-ray laboratory in the United States in  Chicago , and had completed over 1400 x-ray examinations by 1896. His work was critical to the history of radiation protection. [ citation needed ]  He was the father of  Arthur Wolfram Fuchs  (1895 - 1962), the inventor of the fixed kilovoltage technique of radiography."}
{"_id": "WikiPedia_Radiology$$$corpus_4898", "text": "Fuchs was born in  Germany  in 1865 to Julius and Wilhelmina Fuchs. The family emigrated to Chicago in 1870. He returned to Germany to study electrical engineering at the  University of Berlin  and graduated in 1889. He then went on to  Paris  to study at the  Ecole des Beaux Arts . Upon returning to the United States, Fuchs completed his post-graduate work at the  Massachusetts Institute of Technology  in Boston. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4899", "text": "Shortly after  Wilhelm R\u00f6ntgen 's discovery of x-rays, Fuchs was traveling in Germany and was interested in the potential implications x-rays could have for electrical engineering.  [ citation needed ] Meanwhile, in Chicago, Dr.  Friedrich Cort Hamisch  was also becoming interested in x-ray technology and had established a correspondence with R\u00f6ntgen. He set up an x-ray laboratory but eventually handed it over to Dr. Otto L. Schmidt, who placed Fuchs in charge of what was eventually known as the Fuchs X-ray Laboratory. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4900", "text": "Fuchs' son,  Arthur Wolfram Fuchs , wrote in his personal correspondence that:"}
{"_id": "WikiPedia_Radiology$$$corpus_4901", "text": "\"[the laboratory\" was a Mecca for physicians and manufacturers who wanted information regarding the machinery to use and the technic of radiography. He was, according to the men of his time, one of the outstanding radiographers. it seemed that, for a time, no one could obtain the pictures which he was able to make routinely. He was so wrapped up in his experimental work that he would often sleep in his laboratory night after night and week-ends.\" [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4902", "text": "Fuchs was called to  Buffalo , NY to aid the dying  President William McKinley  after his assassination in 1901, even though no x-rays were ever ultimately used. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4903", "text": "Fuchs realized the radiation damage from x-ray technology before it was acknowledged by the American Medical Association.  [ citation needed ]  His own extensive experimentation with x-rays resulted in severe Roentgen-Dermatitis, requiring the eventual amputation of his fingers and thumbs on both hands. Fuchs believed that \"the damage must be seen to be insignificant compared to the good that follows from this wonderful discovery,\" and came up with ideas to reduce the damage. On December 12, 1896, Fuchs made the following reasonable recommendations in  Western Electrician : [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4904", "text": "He also added that: \"The x-ray 'burn' is no more dangerous than normal burns... when the x rays encounter the skull for a longer period, the hair falls out but it grows back without any unpleasant after-effects.\" [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4905", "text": "Also suffering from  metastatic cancer , Fuchs passed away after several operations on April 21, 1907. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4906", "text": "Industrial radiography  is a modality of  non-destructive testing  that uses  ionizing radiation  to inspect materials and components with the objective of locating and quantifying defects and degradation in material properties that would lead to the failure of engineering structures. It plays an important role in the science and technology needed to ensure product quality and reliability. In Australia, industrial radiographic non-destructive testing is colloquially referred to as \"bombing\" a component with a \"bomb\"."}
{"_id": "WikiPedia_Radiology$$$corpus_4907", "text": "Industrial Radiography uses either  X-rays , produced with  X-ray generators , or  gamma rays  generated by the natural  radioactivity  of sealed  radionuclide  sources. Neutrons can also be used. After crossing the specimen, photons are captured by a  detector , such as a silver halide film, a  phosphor plate ,  flat panel detector  or  CdTe  detector. The examination can be performed in static 2D (named  radiography ), in real time 2D ( fluoroscopy ), or in 3D after image reconstruction ( computed tomography  or CT). It is also possible to perform tomography nearly in real time ( 4-dimensional computed tomography  or 4DCT). Particular techniques such as X-ray fluorescence ( XRF ), X-ray diffractometry ( XRD ), and several other ones complete the range of tools that can be used in industrial radiography."}
{"_id": "WikiPedia_Radiology$$$corpus_4908", "text": "Inspection techniques can be portable or stationary. Industrial radiography is used in  welding ,  casting  parts or  composite  pieces inspection, in food inspection and luggage control, in sorting and recycling, in  EOD  and  IED  analysis,  aircraft maintenance ,  ballistics ,  turbine  inspection, in surface characterisation, coating thickness measurement, in  counterfeit drug  control, etc."}
{"_id": "WikiPedia_Radiology$$$corpus_4909", "text": "Radiography started in 1895 with the discovery of  X-rays  (later also called  R\u00f6ntgen  rays after the man who first described their properties in detail), a type of  electromagnetic radiation . Soon after the discovery of X-rays,  radioactivity  was discovered. By using radioactive sources such as  radium , far higher  photon  energies could be obtained than those from  normal   X-ray generators . Soon these found various applications, with one of the earliest users being  Loughborough College . [ 1 ]  X-rays and gamma rays were put to use very early, before the dangers of ionizing radiation were discovered. After  World War II  new isotopes such as  caesium-137 ,  iridium-192  and  cobalt-60  became available for industrial radiography, and the use of radium and radon decreased."}
{"_id": "WikiPedia_Radiology$$$corpus_4910", "text": "Gamma radiation  sources, [ 2 ]  most commonly iridium-192 and cobalt-60, are used to inspect a variety of materials. The vast majority of radiography concerns the testing and grading of welds on piping, pressure vessels, high-capacity storage containers, pipelines, and some structural welds. Other tested materials include concrete (locating  rebar  or conduit), welder's test  coupons , machined parts, plate metal, or pipewall (locating anomalies due to corrosion or mechanical damage). Non-metal components such as ceramics used in the aerospace industries are also regularly tested. Theoretically, industrial radiographers could radiograph any solid, flat material (walls, ceilings, floors, square or rectangular containers) or any hollow cylindrical or spherical object."}
{"_id": "WikiPedia_Radiology$$$corpus_4911", "text": "The beam of radiation must  be directed to the middle of the section under examination and must be normal to the material surface at that point, except in special techniques where known defects are best revealed by a different alignment of the beam. The length of  weld  under examination for each exposure shall be such that the thickness of the material at the diagnostic extremities, measured in the direction of the incident beam, does not exceed the actual thickness at that point by more than 6%. The specimen to be inspected is placed between the source of radiation and the detecting device, usually the film in a light tight holder or cassette, and the radiation is allowed to penetrate the part for the required length of time to be adequately recorded."}
{"_id": "WikiPedia_Radiology$$$corpus_4912", "text": "The result is a two-dimensional projection of the part onto the film, producing a latent image of varying densities according to the amount of  radiation  reaching each area. It is known as a radio graph, as distinct from a photograph produced by light. Because film is cumulative in its response (the exposure increasing as it absorbs more radiation), relatively weak radiation can be detected by prolonging the exposure until the film can record an image that will be visible after development. The radiograph is examined as a  negative , without printing as a positive as in photography. This is because, in printing, some of the detail is always lost and no useful purpose is served."}
{"_id": "WikiPedia_Radiology$$$corpus_4913", "text": "Before commencing a radiographic examination, it is always advisable to examine the component with one's own eyes, to eliminate any possible external defects. If the surface of a weld is too irregular, it may be desirable to grind it to obtain a smooth finish, but this is likely to be limited to those cases in which the surface irregularities (which will be visible on the radio graph) may make detecting internal defects difficult."}
{"_id": "WikiPedia_Radiology$$$corpus_4914", "text": "After this visual examination, the operator will have a clear idea of the possibilities of access to the two faces of the weld, which is important both for the setting up of the equipment and for the choice of the most appropriate technique."}
{"_id": "WikiPedia_Radiology$$$corpus_4915", "text": "Defects such as  delaminations  and  planar  cracks are difficult to detect using radiography, particularly to the untrained eye."}
{"_id": "WikiPedia_Radiology$$$corpus_4916", "text": "Without overlooking the negatives of radiographic inspection, radiography does hold many significant benefits over ultrasonics, particularly insomuch that as a 'picture' is produced keeping a semi permanent record for the life cycle of the film, more accurate identification of the defect can be made, and by more interpreters. Very important as most construction standards permit some level of defect acceptance, depending on the type and size of the defect."}
{"_id": "WikiPedia_Radiology$$$corpus_4917", "text": "To the trained radiographer, subtle variations in visible film density provide the technician the ability to not only accurately locate a defect, but identify its type, size and location; an interpretation that can be physically reviewed and confirmed by others, possibly eliminating the need for expensive and unnecessary repairs."}
{"_id": "WikiPedia_Radiology$$$corpus_4918", "text": "For purposes of inspection, including  weld inspection , there exist several exposure arrangements."}
{"_id": "WikiPedia_Radiology$$$corpus_4919", "text": "First, there is the panoramic, one of the four single-wall exposure/single-wall view (SWE/SWV) arrangements. This exposure is created when the radiographer places the source of radiation at the center of a sphere, cone, or cylinder (including tanks, vessels, and piping). Depending upon client requirements, the radiographer would then place film cassettes on the outside of the surface to be examined. This exposure arrangement is nearly ideal \u2013 when properly arranged and exposed, all portions of all exposed film will be of the same approximate density. It also has the advantage of taking less time than other arrangements since the source must only penetrate the total wall thickness (WT) once and must only travel the radius of the inspection item, not its full diameter. The major disadvantage of the panoramic is that it may be impractical to reach the center of the item (enclosed pipe) or the source may be too weak to perform in this arrangement (large vessels or tanks)."}
{"_id": "WikiPedia_Radiology$$$corpus_4920", "text": "The second SWE/SWV arrangement is an interior placement of the source in an enclosed inspection item without having the source centered up. The source does not come in direct contact with the item, but is placed a distance away, depending on client requirements. The third is an exterior placement with similar characteristics. The fourth is reserved for flat objects, such as plate metal, and is also radiographed without the source coming in direct contact with the item. In each case, the radiographic film is located on the opposite side of the inspection item from the source. In all four cases, only one wall is exposed, and only one wall is viewed on the radiograph."}
{"_id": "WikiPedia_Radiology$$$corpus_4921", "text": "Of the other exposure arrangements, only the contact shot has the source located on the inspection item. This type of radiograph exposes both walls, but only resolves the image on the wall nearest the film. This exposure arrangement takes more time than a panoramic, as the source must first penetrate the WT twice and travel the entire outside diameter of the pipe or vessel to reach the film on the opposite side. This is a double wall exposure/single wall view DWE/SWV arrangement. Another is the superimposure (wherein the source is placed on one side of the item, not in direct contact with it, with the film on the opposite side). This arrangement is usually reserved for very small diameter piping or parts. The last DWE/SWV exposure arrangement is the elliptical, in which the source is offset from the plane of the inspection item (usually a weld in pipe) and the elliptical image of the weld furthest from the source is cast onto the film."}
{"_id": "WikiPedia_Radiology$$$corpus_4922", "text": "Both hold luggage and carry-on hand luggage are normally examined by  X-ray machines  using X-ray radiography. See  airport security  for more details."}
{"_id": "WikiPedia_Radiology$$$corpus_4923", "text": "Gamma radiography and high-energy X-ray radiography are currently used to scan  intermodal freight  cargo containers in US and other countries. Also research is being done on adapting other types of radiography like  dual-energy X-ray radiography  or muon radiography for scanning  intermodal  cargo containers."}
{"_id": "WikiPedia_Radiology$$$corpus_4924", "text": "The American artist  Kathleen Gilje  has painted copies of  Artemisia Gentileschi 's  Susanna and the Elders  and  Gustave Courbet 's  Woman with a Parrot .\nBefore, she painted in  lead white  similar pictures with differences: Susanna fights the intrusion of the elders; [ 3 ]  there is a nude Courbet beyond the woman he paints. [ 4 ] \nThen she painted over reproducing the original.\nGilje's paintings are exhibited with radiographs that show the underpaintings, simulating the study of  pentimentos  and providing a comment on the old masters' work."}
{"_id": "WikiPedia_Radiology$$$corpus_4925", "text": "Many types of ionizing radiation sources exist for use in industrial radiography."}
{"_id": "WikiPedia_Radiology$$$corpus_4926", "text": "X-ray generators  produce  X-rays  by applying a  high voltage  between the cathode and the anode of an  X-ray tube  and in heating the tube filament to start the electron emission. The electrons are then accelerated in the resulting  electric potential  and collide with the anode, which is usually made of  Tungsten . [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4927", "text": "The X-rays that are emitted by this generator are directed towards the object to control. They cross it and are absorbed according to the object material's  attenuation coefficient . [ 6 ]  The attenuation coefficient is compiled from all the  cross sections  of the interactions that are happening in the material. The three most important inelastic interactions with X-rays at those energy levels are the  photoelectric effect ,  compton scattering  and  pair production . [ 7 ]  After having crossed the object, the photons are captured by a  detector , such as a silver halide film, a  phosphor plate  or  flat panel detector . [ 8 ]  When an object is too thick, too dense, or its  effective atomic number  is too high, a  linac  can be used. They work in a similar way to produce X-rays, by electron collisions on a metal anode, the difference is that they use a much more complex method to accelerate them. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4928", "text": "Radionuclides  are often used in industrial radiography. They have the advantage that they do not need a supply of electricity to function, but it also means that they can't be turned off. The two most common radionuclides used in industrial radiography are  Iridium-192  and  Cobalt-60 . But others are used in general industry as well. [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4929", "text": "These isotopes emit radiation in a discrete set of energies, depending on the  decay  mechanism happening in the  atomic nucleus . Each energies will have different intensities depending on the probability of a particular decay interaction. The most prominent energies in Cobalt-60 are 1.33 and 1.17 MeV, and 0.31, 0.47 and 0.60 MeV for Iridium-192. [ 11 ]  From a  radiation safety  point of view, this makes them more difficult to handle and manage. They always need to be enclosed in a shielded container and because they are still radioactive after their normal life cycle, their ownership often requires a license and they are usually tracked by a governmental body. If this is the case, their disposal must be done in accordance with the national policies. [ 12 ] [ 13 ] [ 14 ]  The radionuclides used in industrial radiography are chosen for their high  specific activity . This high activity means that only a small sample is required to obtain a good radiation flux. However, higher activity often means higher dose in the case of an accidental exposure. [ 15 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4930", "text": "A series of different designs have been developed for radiographic \"cameras\". Rather than the \"camera\" being a device that accepts photons to record a picture, the \"camera\" in industrial radiography is the radioactive photon source. Most industries are moving from film based radiography to a digital sensor based radiography much the same way that traditional photography has made this move. [ 16 ] \nSince the amount of radiation emerging from the opposite side of the material can be detected and measured, variations in this amount (or intensity) of radiation are used to determine thickness or composition of material."}
{"_id": "WikiPedia_Radiology$$$corpus_4931", "text": "One design uses a moving shutter to expose the source. The radioactive source is placed inside a shielded box; a hinge allows part of the shielding to be opened, exposing the source and allowing photons to exit the radiography camera."}
{"_id": "WikiPedia_Radiology$$$corpus_4932", "text": "Another design for a shutter is where the source is placed in a metal wheel, which can turn inside the camera to move between the expose and storage positions."}
{"_id": "WikiPedia_Radiology$$$corpus_4933", "text": "Shutter-based devices require the entire device, including the heavy shielding, to be located at the exposure site. This can be difficult or impossible, so they have largely been replaced by cable-driven projectors."}
{"_id": "WikiPedia_Radiology$$$corpus_4934", "text": "Modern projector designs use a cable drive mechanism to move the source along a hollow guide tube to the exposure location. The source is stored in a block of  shielding that has an S-shaped tube-like hole through the block. In the safe position the source is in the center of the block. The source is attached to a flexible metal cable called a pigtail. To use the source a guide tube is attached to one side of the device while a drive cable is attached to the pigtail. Using a hand-operated control the source is then pushed out of the shield and along the source guide tube to the tip of the tube to expose the film, then cranked back into its fully shielded position."}
{"_id": "WikiPedia_Radiology$$$corpus_4935", "text": "In some rare cases, radiography is done with  neutrons . This type of radiography is called  neutron radiography  (NR, Nray, N-ray) or  neutron imaging . Neutron radiography provides different images than X-rays, because neutrons can pass with ease through lead and steel but are stopped by plastics, water and oils. Neutron sources include radioactive ( 241 Am/Be and Cf) sources, electrically driven D-T reactions in vacuum tubes and conventional critical nuclear reactors. It might be possible to use a neutron amplifier to increase the neutron flux. [ 17 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4936", "text": "Radiation safety is a very important part of industrial radiography. The  International Atomic Energy Agency  has published a report describing the best practices in order to lower the amount of  radiation dose  the workers are exposed to. [ 18 ] [ 19 ]  It also provides a list of national competent authorities responsible for approvals and authorizations regarding the handling of radioactive material. [ 20 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4937", "text": "Shielding  can be used to protect the user of the  harmful  properties of ionizing radiation. The type of material used for shielding depends on the type of radiation being used. National radiation safety authorities usually regulate the design, commissioning, maintenance and inspection of Industrial Radiography installations. [ 21 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4938", "text": "Industrial radiographers are in many locations required by governing authorities to use certain types of safety equipment and to work in pairs. Depending on location industrial radiographers may have been required to obtain permits, licenses and/or undertake special training. Prior to conducting any testing the nearby area should always first be cleared of all other persons and measures should be taken to ensure that workers do not accidentally enter into an area that may expose them to dangerous levels of radiation."}
{"_id": "WikiPedia_Radiology$$$corpus_4939", "text": "The safety equipment usually includes four basic items: a radiation survey meter (such as a Geiger/Mueller counter), an alarming dosimeter or rate meter, a gas-charged dosimeter, and a film badge or thermoluminescent dosimeter (TLD). The easiest way to remember what each of these items does is to compare them to gauges on an automobile."}
{"_id": "WikiPedia_Radiology$$$corpus_4940", "text": "The survey meter could be compared to the speedometer, as it measures the speed, or rate, at which radiation is being picked up. When properly calibrated, used, and maintained, it allows the radiographer to see the current exposure to radiation at the meter. It can usually be set for different intensities, and is used to prevent the radiographer from being overexposed to the radioactive source, as well as for verifying the boundary that radiographers are required to maintain around the exposed source during radiographic operations."}
{"_id": "WikiPedia_Radiology$$$corpus_4941", "text": "The alarming dosimeter could be most closely compared with the tachometer, as it alarms when the radiographer \"redlines\" or is exposed to too much radiation. When properly calibrated, activated, and worn on the radiographer's person, it will emit an alarm when the meter measures a radiation level in excess of a preset threshold. This device is intended to prevent the radiographer from inadvertently walking up on an exposed source."}
{"_id": "WikiPedia_Radiology$$$corpus_4942", "text": "The gas-charged dosimeter is like a trip meter in that it measures the total radiation received, but can be reset. It is designed to help the radiographer measure his/her total periodic dose of radiation. When properly calibrated, recharged, and worn on the radiographer's person, it can tell the radiographer at a glance how much radiation to which the device has been exposed since it was last recharged. Radiographers in many states are required to log their radiation exposures and generate an exposure report. In many countries personal dosimeters are not required to be used by radiographers as the dose rates they show are not always correctly recorded."}
{"_id": "WikiPedia_Radiology$$$corpus_4943", "text": "The film badge or TLD is more like a car's odometer. It is actually a specialized piece of radiographic film in a rugged container. It is meant to measure the radiographer's total exposure over time (usually a month) and is used by regulating authorities to monitor the total exposure of certified radiographers in a certain jurisdiction. At the end of the month, the film badge is turned in and is processed. A report of the radiographer's total dose is generated and is kept on file."}
{"_id": "WikiPedia_Radiology$$$corpus_4944", "text": "When these safety devices are properly calibrated, maintained, and used, it is virtually impossible for a radiographer to be injured by a radioactive overexposure. The elimination of just one of these devices can jeopardize the safety of the radiographer and all those who are nearby. Without the survey meter, the radiation received may be just below the threshold of the rate alarm, and it may be several hours before the radiographer checks the dosimeter, and up to a month or more before the film badge is developed to detect a low intensity overexposure. Without the rate alarm, one radiographer may inadvertently walk up on the source exposed by the other radiographer. Without the dosimeter, the radiographer may be unaware of an overexposure, or even a radiation burn, which may take weeks to result in noticeable injury. And without the film badge, the radiographer is deprived of an important tool designed to protect him or her from the effects of a long-term overexposure to occupationally obtained radiation, and thus may suffer long-term health problems as a result."}
{"_id": "WikiPedia_Radiology$$$corpus_4945", "text": "There are three ways a radiographer will ensure they are not exposed to higher than required levels of radiation: time, distance, shielding. The less time that a person is exposed to radiation the lower their dose will be. The further a person is from a radioactive source the lower the level of radiation they receive, this is largely due to the inverse square law. Lastly the more a radioactive source is shielded by either better or greater amounts of shielding the lower the levels of radiation that will escape from the testing area. The most commonly used shielding materials in use are sand, lead (sheets or shot), steel, spent (non-radioactive uranium) tungsten and in suitable situations water."}
{"_id": "WikiPedia_Radiology$$$corpus_4946", "text": "Industrial radiography appears to have one of the worst safety profiles of the radiation professions, possibly because there are many operators using strong  gamma  sources (> 2 Ci) in remote sites with little supervision when compared with workers within the  nuclear  industry or within hospitals. [ 22 ]  Due to the levels of radiation present whilst they are working many radiographers are also required to work late at night when there are few other people present as most industrial radiography is carried out 'in the open' rather than in purpose built exposure booths or rooms. Fatigue, carelessness and lack of proper training are the three most common factors attributed to industrial radiography accidents. Many of the \"lost source\" accidents commented on by the  International Atomic Energy Agency  involve radiography equipment. Lost source accidents have the potential to cause a considerable loss of human life. One scenario is that a passerby finds the radiography source and not knowing what it is, takes it home. [ 23 ]  The person shortly afterwards becomes ill and dies as a result of the radiation dose. The source remains in their home where it continues to irradiate other members of the household. [ 24 ]  Such an event occurred in March 1984 in  Casablanca ,  Morocco . This is related to the more famous  Goi\u00e2nia accident , where a related chain of events caused members of the public to be exposed to radiation sources."}
{"_id": "WikiPedia_Radiology$$$corpus_4947", "text": "Medipix  is a family of  photon counting  and particle tracking pixel detectors developed by an international collaboration, hosted by  CERN . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4948", "text": "These are  hybrid detectors  as a  semiconductor  sensor layer is bonded to a processing electronics layer."}
{"_id": "WikiPedia_Radiology$$$corpus_4949", "text": "The sensor layer is a semiconductor, such as  silicon ,  GaAs , or  CdTe  in which the incident radiation makes an electron hole/cloud. The charge is then collected to pixel electrodes and, via bump bonds, conducted to the  CMOS  electronics layer."}
{"_id": "WikiPedia_Radiology$$$corpus_4950", "text": "The pixel electronics first amplifies the signal and then compares the signal amplitude with a pre-set discrimination level (an energy threshold). The subsequent signal processing depends on the type of device. A standard Medipix detector increases the counter in the appropriate pixel if the signal is above the discrimination level. The Medipix device also contains an upper discrimination level and hence only signals within a range of amplitude could be accepted (within an energy window)."}
{"_id": "WikiPedia_Radiology$$$corpus_4951", "text": "Timepix devices offer two more modes of operation in addition to the counting. The first one is so called \u201cTime-over-Threshold\u201d mode ( Wilkinson type analog-to-digital converter ). It is a mode where the counter in each pixel records the number of clocks for which the pulse remains above the discrimination level. This number is proportional to the energy of detected radiation. This mode is useful for particle tracking applications or for direct spectral imaging."}
{"_id": "WikiPedia_Radiology$$$corpus_4952", "text": "The second mode of the Timepix chip is \u201cTime-of-arrival\u201d, in which pixel counters record time between a trigger and detection of radiation quanta with energy above the discrimination level. This mode of operation finds use in  time of flight (ToF)  applications, for instance in neutron imaging."}
{"_id": "WikiPedia_Radiology$$$corpus_4953", "text": "Every individual hit of radiation is processed by the electronics integrated in each pixel this way, therefore the device could be considered as 65 536 individual counting detectors or even spectrometers. The energy discriminators are adjustable. Therefore, scanning with their level it is possible to measure over frequency-bands of the incoming radiation; thus enabling spectroscopic x-ray imaging."}
{"_id": "WikiPedia_Radiology$$$corpus_4954", "text": "Medipix-2, Timepix, and Medipix-3 are all 256\u00d7256 pixels, each 0.055 mm (55\u00a0\u03bcm) square, forming a total area 14.08 mm \u00d7 14.08 mm. Larger area detectors can be created by bump-bonding many chips to larger monolithic sensors. Detectors of sizes from 2x2 to 2x4 chips are commonly used. Even larger, gapless areas could be created using the edgeless sensor technology. Medipix/Timepix chips each have its own sensor. These assemblies are tiled next to each other to create nearly arbitrarily sized detector arrays (the largest build using this technology has 10x10 chips, hence 14x14 cm and 2560x2560 pixels [ 2 ] )."}
{"_id": "WikiPedia_Radiology$$$corpus_4955", "text": "Photon counting pixel detectors represent the next generation of radiation imaging detectors. The photon counting technology overcomes limitations of current imaging devices. Comparison of photon counting with existing technologies is in the following table:"}
{"_id": "WikiPedia_Radiology$$$corpus_4956", "text": "Medipix-1  was the first device of the Medipix family. It had 64x64 pixels of 170\u00a0\u03bcm pitch. Pixels contained one comparator (threshold) with 3-bit per-pixel offset adjustment. The minimum threshold was ~5.5 keV. The counter depth was 15-bit. The maximum count rate per pixel was 2\u00a0MHz per pixel."}
{"_id": "WikiPedia_Radiology$$$corpus_4957", "text": "Medipix-2  is the successor of Medipix-1. The pixel pitch was reduced to 55\u00a0\u03bcm and the pixel array is of 256x256 pixels. Each pixel has two discrimination levels (upper and lower threshold) each adjustable individually in pixels using a 3-bit offset. The maximum count rate is about 100\u00a0kHz per pixel (however in pixels with 9x smaller area compared to Medipix-1)."}
{"_id": "WikiPedia_Radiology$$$corpus_4958", "text": "Medipix-2 MXR  is an improved version of Medipix-2 device with better temperature stability, pixel counter overflow protection, increased radiation hardness and many other improvements."}
{"_id": "WikiPedia_Radiology$$$corpus_4959", "text": "Timepix  is device conceptually originating from Medipix-2. It adds two more modes to the pixels, in addition to counting of detected signals: Time-over-Threshold (TOT) and Time-of-Arrival (TOA). The detected pulse height is recorded in the pixel counter in the TOT mode. The TOA mode measures time between trigger and arrival of the radiation into each pixel."}
{"_id": "WikiPedia_Radiology$$$corpus_4960", "text": "Medipix-3  is the latest generation of photon counting devices for X-ray imaging. The pixel pitch remains the same (55\u00a0\u03bcm) as well as the pixel array size (256x256). It has better energy resolution through real time correction of charge sharing. It also has multiple counters per pixel that can be used in several different modes. This allows for continuous readout and up to eight energy thresholds."}
{"_id": "WikiPedia_Radiology$$$corpus_4961", "text": "Timepix-3  is a successor of the Timepix chip. One of the biggest distinguishing changes is the approach to the data readout. All previous chips used the frame-based readout, i.e. the whole pixel matrix was read out at once. Timepix-3 has event-based readout where values recorded in pixels are read out immediately after the hit together with coordinates of the hit pixel. The chip therefore generates a continuous stream of data rather than a sequence of frames. The next major difference compared to the previous Timepix chip is the ability to measure the hit amplitude simultaneously with the time of arrival. Other parameters such as energy and timing resolution were also improved compared to the original Timepix chip."}
{"_id": "WikiPedia_Radiology$$$corpus_4962", "text": "Timepix-4  is the successor of the Timepix-3 chip. It has general stronger specifications for instance its time-of-arrival resolution is 195 ps, 8 times faster than Timepix-3, it also has a larger pixelmatrix of 512x448 pixels and can handle 8 times higher data rates. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4963", "text": "The digital data recorded by Medipix/Timepix devices are transferred to a computer via readout electronics. The readout electronics is also responsible for setup and control of the detector parameters. Several readout systems were developed within the Medipix collaboration"}
{"_id": "WikiPedia_Radiology$$$corpus_4964", "text": "Muros was one of the first readout systems of Medipix detectors. Muros was developed at  Nikhef ,  Amsterdam ,  The Netherlands . It was relatively compact readout enabling access to all features of the detector. It allowed maximum frame rate of cca 30 frames/s with a single chip."}
{"_id": "WikiPedia_Radiology$$$corpus_4965", "text": "This electronics was developed at  IEAP - CTU ,  Czech Republic . It provides a lower frame rate compared to Muros, but the electronics was integrated into a box not larger than a pack of cigarettes. Moreover, no special PC hardware card was needed as it was in case of Muros. Therefore, the  USB  interface become quickly the most used readout within the Medipix collaboration and its partners."}
{"_id": "WikiPedia_Radiology$$$corpus_4966", "text": "Relaxd is a readout electronics developed at  Nikhef . The data is transferred to PC via 1\u00a0Gbit/s Ethernet connection. The maximum frame rate is at level of 100 frame/s."}
{"_id": "WikiPedia_Radiology$$$corpus_4967", "text": "Fitpix is the next generation of the  USB  interface developed by the group in Prague. The electronics implements the parallel Medipix/Timepix readout and therefore the maximum frame rate reaches 850 frame/s. It supports also the serial readout with frame rate of 100 frames/s."}
{"_id": "WikiPedia_Radiology$$$corpus_4968", "text": "Minipix is a miniaturized integrated chip+readout electronics device developed by  ADVACAM s.r.o.  in  Prague . The whole system has size of a  USB flash drive . Several of these devices were used on the  International Space Station  as radiation monitoring systems. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4969", "text": "Spidr3 is powerful readout electronics for the TimePix3 and MediPix3 chip. The readout rate for the MediPix3 is about 12500 frames per second and for the TimePix3 of 120 Million Hits per second. The data are transferred by a powerful 10\u00a0GB optical fiber connection. The chip and readout system is developed together with Nikhef and Amsterdam Scientific Instruments."}
{"_id": "WikiPedia_Radiology$$$corpus_4970", "text": "Both systems are developed at  Diamond Light Source , UK, for Medipix3 readout and applications at synchrotrons. Merlin is available with CdTe sensors from  Quantum Detectors  who are collaborating on further development with Diamond Light Source."}
{"_id": "WikiPedia_Radiology$$$corpus_4971", "text": "Lambda is a high-speed (2,000 fps) big area (12 chips) readout systems developed at  DESY . Lambda is available with high-Z sensor options, such as GaAs (Gallium-Arsenide) and CdTe (Cadmium-Telluride)."}
{"_id": "WikiPedia_Radiology$$$corpus_4972", "text": "MARS is a gigabit Ethernet readout accommodating up to 6 Medipix 2 or Medipix 3 detectors. The electronics was developed at  University of Otago ,  Christchurch ,  New Zealand ."}
{"_id": "WikiPedia_Radiology$$$corpus_4973", "text": "X-ray imaging  is the primary application field of Medipix detectors. Medipix offers to the X-ray imaging field in particular an advantage in higher dynamic range and energy sensitivity. [ 5 ]  Examples of X-ray images from selected X-ray imaging application fields are:"}
{"_id": "WikiPedia_Radiology$$$corpus_4974", "text": "Timepix-based detectors from the Medipix2 Collaboration have been flown on the International Space Station since 2013, and on the first flight test (EFT-1) of NASA's new  Orion Multi-Purpose Crew Vehicle  in December 2014. Current plans call for similar devices to be flown as the primary radiation area monitors on the future initial crewed Orion missions."}
{"_id": "WikiPedia_Radiology$$$corpus_4975", "text": "The detectors may also find applications in  astronomy ,  high energy physics ,  medical imaging , and  X-ray spectroscopy ."}
{"_id": "WikiPedia_Radiology$$$corpus_4976", "text": "Nuclear densitometry  is a technique used in civil construction and the  petroleum industry , as well as for mining and archaeology purposes, to measure the density and inner structure of the test material. The processes uses a  nuclear density gauge , which consists of a  radiation  source that emits particles and a  sensor  that counts the received particles that are either reflected by the test material or pass through it. By calculating the percentage of particles that return to the sensor, the gauge can be calibrated to measure the density."}
{"_id": "WikiPedia_Radiology$$$corpus_4977", "text": "In  geotechnical engineering , a  nuclear densometer  or  soil density gauge  is a field instrument used  to determine the density of a compacted material. The device uses the interaction of  gamma radiation  with matter to measure density, either through direct transmission or the \"backscatter\" method.  The device determines the density of material by counting the number of photons emitted by a radioactive source (cesium-137) that are read by the detector tubes in the gauge base.  A 60-second time interval is typically used for the counting period."}
{"_id": "WikiPedia_Radiology$$$corpus_4978", "text": "Different variants are used for different purposes. For density analysis of very shallow objects such as roads or walls, a  gamma  source emitter such as  137 Cesium  is used to produce gamma radiation. These isotopes are effective in analyzing the top 10\u00a0inches (25 centimeters) with high accuracy.  226 Radium  is used for depths of 328 yards (300 meters). Such instruments can help find caves or identify locations with lower density that would make tunnel construction hazardous."}
{"_id": "WikiPedia_Radiology$$$corpus_4979", "text": "Nuclear density gauges are typically operated in one of two modes: [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4980", "text": "Direct transmission:  The retractable rod is lowered into the mat through a pre-drilled hole.  The source emits radiation, which then interact with  electrons  in the material and lose energy and/or are redirected ( scattered ).  Radiation that loses sufficient energy or is scattered away from the detector is not counted.  The denser the material, the higher the probability of interaction and the lower the detector count.  Therefore, the detector count is inversely proportional to material density.  A calibration factor is used to relate the count to the actual density."}
{"_id": "WikiPedia_Radiology$$$corpus_4981", "text": "Backscatter:  The retractable rod is lowered so that it is even with the detector but still within the instrument.  The source emits radiation, which then interact with electrons in the material and lose energy and/or are redirected (scattered).  Radiation that is scattered towards the detector is counted.  The denser the material, the higher the probability that radiation will be redirected towards the detector.  Therefore, the detector count is proportional to the density.  A calibration factor is used to correlate the count to the actual density."}
{"_id": "WikiPedia_Radiology$$$corpus_4982", "text": "Many devices are built to measure both the density and  moisture content  of material. This is important to the  civil construction  industry specifically as both are essential to verifying suitable soil conditions to support structures, streets, highways, and airport runways."}
{"_id": "WikiPedia_Radiology$$$corpus_4983", "text": "A nuclear densometer is used on a compacted base to establish its percentage of compaction. [ 2 ] [ 3 ]  Before field tests are performed, the technician performs a calibration on the gauge which records the 'standard count' of the machine. Standard counts are the amount of radiation released by the two nuclear sources inside the machine, with no loss or leakage. This allows the machine to compare the amount of radiation released to the amount of radiation received. With the use of a 3/4\" diameter rod a hole is created in the compacted base by hammering the rod into the base to produce a hole that the densometer's probe can be inserted into. The densometer is placed on top of the hole, and then the probe is inserted into the hole by unlocking the handle at the top of the probe. One source produces radiation that interacts with the atoms in the soil, and is then compared to the standard count, to calculate the density. The other source interacts with  hydrogen  atoms to calculate the percentage of water in the soil."}
{"_id": "WikiPedia_Radiology$$$corpus_4984", "text": "In direct transmission mode, the source extends through the base of the gauge into a predrilled hole, positioning the source at the desired depth.  The testing procedure is analogous to burying a known quantity of radioactive material at a specific depth, and then using a  Geiger counter  at the ground surface to measure how effectively the soil's density  blocks the penetration of gamma radiation through the soil.  As the soil's density increases, less radiation can pass through it, owing to dispersion from collisions with electrons in the soil being tested."}
{"_id": "WikiPedia_Radiology$$$corpus_4985", "text": "Since the soil's moisture level is partly responsible for its in-place density, the gauge also contains a  neutron moisture gauge  consisting of an  americium / beryllium  high-energy  neutron source  and a  thermal neutron  detector.  The high-energy neutrons are slowed when they collide with hydrogen atoms, and the detector then counts the \"slowed\" neutrons.  This count is proportional to the soil's water content, since the hydrogen in this water ( H 2 O) is responsible for almost all the hydrogen found in most soils.  The gauge calculates the moisture content, subtracts it from the soil's in-place (wet) density, and reports the soil's dry density."}
{"_id": "WikiPedia_Radiology$$$corpus_4986", "text": "Nuclear density gauges can also be used to measure the density of a liquid in a pipe.  If a source is mounted on one side of a pipe and a detector on the other, the amount of radiation seen at the detector is dependent upon the shielding provided by the liquid in the pipe.   Tracerco  pioneered the use of radiation to measure density in the 1950s and determined that the  Beer\u2013Lambert law  also applied to radiation as well as optics.  Gauges are normally calibrated using gas and a liquid of known density to find the unknowns in the equation.  Once it has been calibrated and as long as the source detector alignment remains constant, it is possible to calculate the density of the liquid in the pipe.  One factor is the  half-life  of the radioactive source (30 years for  137 Cs), which means that the system needs to be recalibrated at regular intervals.  Modern systems incorporate correction for source decay. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4987", "text": "Another variant is to use a strong neutron source like  241 americium/beryllium to produce  neutron radiation  and then measure the energy of returning  neutron scattering . As  hydrogen  characteristically slows down neutrons,  the sensor can calculate the density of hydrogen - and find pockets of underground water, humidity up to a depth of several meters, moisture content, or asphalt content."}
{"_id": "WikiPedia_Radiology$$$corpus_4988", "text": "Neutron sources can also be used to assess the performance of a  separator (oil production)  in the same way.  Gas, oil, water and sand all have different concentrations of hydrogen atoms which reflect different amounts of slow neutrons.  Using a head which contains an  241 AmBe neutron source  and a slow  neutron detector , by scanning it up and down a separator it is possible to determine the interface levels within the separator."}
{"_id": "WikiPedia_Radiology$$$corpus_4989", "text": "The  New York City Police Department  is reported to have a number of  military-grade [ 1 ]   X-ray vans  that contain  X-ray  equipment for inspecting vehicles. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4990", "text": "They are described as being able to see into walls [ 1 ]  and other vehicles using  Z backscatter  technology. [ 3 ] [ 1 ]  They are estimated to cost between $729,000 and $825,000. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4991", "text": "The NYPD has not disclosed how this technology is used as it would reveal investigation techniques, however  Police Commissioner  William Bratton  states that they are not used to scan people for weapons. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4992", "text": "According to the  New York University School of Law  Policing Project, the manufacturer of the vans is  American Science and Engineering . [ 4 ]  The product website for the van depicts a video where the van slowly drives past empty passenger cars, and in real time generates an x-ray image. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4993", "text": "The x-ray van manufacturer found that the vans expose bystanders to a 40% larger dose of ionizing radiation than the radiation delivered by airport scanners utilizing similar technology. In airports, The European Union and United States Transportation Security Administration banned the use of this type of radiation technology citing privacy and health concerns such as cancer. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4994", "text": "On December 18, 2019, the  NYCLU  submitted testimony in support of Intro. 487, the  Public Oversight of Surveillance Technology (\u201cPOST\u201d) Act .  In it, the NYCLU cited the example of X-ray vans as a violation of privacy, and stated in general that, \"Left unchecked, police surveillance has the potential to chill the exercise of First Amendment-protected speech and religious worship, intrude on Fourth Amendment-protected privacy rights, and cast entire communities under a cloak of suspicion in contravention of the Fourteenth Amendment\u2019s guarantee of equal protection.\" [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4995", "text": "In 2015  ProPublica  issued an Article 78 proceeding in order to have the NYPD respond to  FOIL requests [ 7 ] [ 1 ]  to give further information about the usage and health risks of the x-ray technology. Although initially the lower court granted the request, the NYPD issued an appeal and the lower court ruling was overturned. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4996", "text": "The NYPD has refused to release details of the uses and operation of these vans. [ 8 ]  The  New York Civil Liberties Union  have filed an  amici curiae  brief in support of a legal action by the journalist Michael Grabell, who is attempting to obtain more information about these vehicles. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4997", "text": "The NYU Policing project asserts that exposure to the levels of  Ionizing radiation  that are used in these vans is linked to increased rates of cancer. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_4998", "text": "Orbitomeatal line  is a positioning line used in radiography of the skull. [ 1 ]  It passes through the outer  canthus  of the eye and the center of the  external auditory meatus . It is used for positioning the patient for different radiographic views including  Water's view ,  Perorbital view ,  Lateral view , and others."}
{"_id": "WikiPedia_Radiology$$$corpus_4999", "text": "Photographic plates  preceded  photographic film  as a capture medium in photography. The light-sensitive  emulsion  of  silver salts  was coated on a  glass plate , typically thinner than common window glass. They were heavily used in the late 19th century. With the spread of photographic film, the use of plates declined through the 20th. They were still used in some communities, particularly in science and  medicine , until the late 20th century."}
{"_id": "WikiPedia_Radiology$$$corpus_5000", "text": "Glass plates were far superior to film for research-quality imaging because they were stable and less likely to bend or distort, especially in large-format frames for wide-field imaging. Early plates used the wet  collodion process . The wet plate process was replaced late in the 19th century by  gelatin   dry plates ."}
{"_id": "WikiPedia_Radiology$$$corpus_5001", "text": "A  view camera  nicknamed \"The Mammoth\" weighing 1,400 pounds (640\u00a0kg) was built by  George R. Lawrence  in 1899, specifically to photograph \"The  Alton Limited \" train owned by the  Chicago & Alton Railway . It took photographs on glass plates measuring 8 feet (2.4\u00a0m) \u00d7 4.5 feet (1.4\u00a0m). [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5002", "text": "Glass plate photographic material largely faded from the consumer market in the early years of the 20th century, as more convenient and less fragile films were increasingly adopted. However, photographic plates were reportedly still being used by one photography business in London until the 1970s, [ 2 ]  and by one in Bradford called the Belle Vue Studio that closed in 1975. [ 3 ]  They were in wide use by the professional  astronomical  community as late as the 1990s. Workshops on the use of glass plate photography as an alternative medium or for artistic use are still being conducted."}
{"_id": "WikiPedia_Radiology$$$corpus_5003", "text": "Many famous  astronomical surveys  were taken using photographic plates, including the first  Palomar Observatory  Sky Survey ( POSS ) of the 1950s, the follow-up POSS-II survey of the 1990s, and the UK  Schmidt Telescope   survey  of southern  declinations . A number of  observatories , including  Harvard College  and  Sonneberg , maintain large archives of photographic plates, which are used primarily for historical research on  variable stars ."}
{"_id": "WikiPedia_Radiology$$$corpus_5004", "text": "Many solar system objects were discovered by using photographic plates, superseding earlier visual methods. Discovery of  minor planets  using photographic plates was pioneered by  Max Wolf  beginning with his discovery of  323 Brucia  in 1891.  The first  natural satellite  discovered using photographic plates was  Phoebe  in 1898.   Pluto  was discovered using photographic plates in a  blink comparator ; its moon  Charon  was discovered 48 years later in 1978 by  U.S. Naval Observatory  astronomer  James W. Christy   by carefully examining a bulge in Pluto's image on a photographic plate.\n [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5005", "text": "Glass-backed plates, rather than film, were generally used in astronomy because they do not shrink or deform noticeably in the development process or under environmental changes. Several important applications of  astrophotography , including  astronomical spectroscopy  and  astrometry , continued using plates until  digital imaging  improved to the point where it could outmatch photographic results.  Kodak  and other manufacturers discontinued production of most kinds of plates as the market for them dwindled between 1980 and 2000, terminating most remaining astronomical use, including for sky surveys. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5006", "text": "Photographic plates were also an important tool in early  high-energy physics , as they are blackened by  ionizing radiation .  Ernest Rutherford  was one of the first to study the absorption, in various materials, of the rays produced in  radioactive decay , by using photographic plates to measure the intensity of the rays.  Development of particle detection optimised  nuclear emulsions  in the 1930s and 1940s, first in physics laboratories, then by commercial manufacturers, enabled the discovery and measurement of both the  pi-meson  and  K-meson , in 1947 and 1949, initiating a flood of new particle discoveries in the second half of the 20th century. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5007", "text": "Photographic emulsions were originally coated on thin glass plates for imaging with  electron microscopes , which provided a more rigid, stable and flatter plane compared to plastic films. [ 7 ]  Beginning in the 1970s, high-contrast, fine grain emulsions coated on thicker plastic films manufactured by Kodak, Ilford and DuPont replaced glass plates. These films have largely been replaced by digital imaging technologies. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5008", "text": "The sensitivity of certain types of photographic plates to ionizing radiation (usually  X-rays ) is also useful in  medical imaging  and  material science  applications, although they have been largely replaced with reusable and computer readable  image plate  detectors and other types of  X-ray detectors ."}
{"_id": "WikiPedia_Radiology$$$corpus_5009", "text": "The earliest flexible films of the late 1880s were sold for amateur use in medium-format cameras. The plastic was not of very high optical quality and tended to curl and otherwise not provide as desirably flat a support surface as a sheet of glass. Initially, a transparent plastic base was more expensive to produce than glass. Quality was eventually improved, manufacturing costs came down, and most amateurs gladly abandoned plates for films. After large-format high quality cut films for professional photographers were introduced in the late 1910s, the use of plates for ordinary photography of any kind became increasingly rare."}
{"_id": "WikiPedia_Radiology$$$corpus_5010", "text": "The persistent use of plates in astronomical and other scientific applications started to decline in the early 1980s as they were gradually replaced by  charge-coupled devices  (CCDs), which also provide outstanding dimensional stability. CCD cameras have several advantages over glass plates, including high efficiency, linear light response, and simplified image acquisition and  processing . However, even the largest CCD formats (e.g., 8192 \u00d7 8192 pixels) still do not have the detecting area and  resolution  of most photographic plates, which has forced modern survey cameras to use large CCD arrays to obtain the same coverage."}
{"_id": "WikiPedia_Radiology$$$corpus_5011", "text": "The manufacture of photographic plates has been discontinued by Kodak, Agfa and other widely known traditional makers. Eastern European sources have subsequently catered to the minimal remaining demand, practically all of it for use in  holography , which requires a recording medium with a large surface area and a submicroscopic level of resolution that currently (2014) available electronic image sensors cannot provide. In the realm of traditional photography, a small number of historical process enthusiasts make their own wet or dry plates from raw materials and use them in vintage large-format cameras."}
{"_id": "WikiPedia_Radiology$$$corpus_5012", "text": "Several institutions have established archives to  preserve photographic plates  and prevent their valuable historical information from being lost. The emulsion on the plate can deteriorate. In addition, the glass plate medium is fragile and prone to cracking if not stored correctly. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5013", "text": "The United States  Library of Congress  has a large collection of both wet and dry plate photographic negatives, dating from 1855 through 1900, [ 10 ]  over 7,500 of which have been digitized from the period 1861 to 1865. [ 11 ] \nThe  George Eastman Museum  holds an extensive collection of photographic plates. [ 12 ] [ failed verification ]  In 1955, wet plate negatives measuring 4\u00a0feet 6\u00a0inches (1.37\u00a0m) \u00d7 3\u00a0feet 2\u00a0inches (0.97\u00a0m) were reported to have been discovered in 1951 as part of the  Holtermann Collection . These purportedly were the largest glass negatives discovered at that time. [ 13 ]  These images were taken in 1875 by  Charles Bayliss [ 14 ]  and formed the \"Shore Tower\" panorama [ 15 ]  of Sydney Harbour. [ 13 ]  Albumen contact prints made from these negatives are in the holdings of the Holtermann Collection, the negatives are listed among the current holdings of the Collection. [ 14 ] [ 16 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5014", "text": "Preservation of photographic plates is a particular need in astronomy, where changes often occur slowly and the plates represent irreplaceable records of the sky and astronomical objects that extend back over 100 years. The method of digitization of astronomical plates enables free and easy access to those unique astronomical data and it is one of the most popular approaches to preserve them. This approach was applied at the  Baldone Astrophysical Observatory  where about 22,000 glass and film plates of the  Schmidt Telescope  were scanned and cataloged. [ 17 ]  Another example of an astronomical plate archive is the Astronomical Photographic Data Archive (APDA) at the  Pisgah Astronomical Research Institute  (PARI).  APDA was created in response to recommendations of a group of international scientists who gathered in 2007 to discuss how to best preserve astronomical plates (see the Osborn and Robbins reference listed under Further reading).  The discussions revealed that some observatories no longer could maintain their plate collections and needed a place to archive them. APDA is dedicated to housing and cataloging unwanted plates, with the goal to eventually catalog the plates and create a database of images that can be accessed via the Internet by the global community of scientists, researchers, and students. APDA now has a collection of more than 404,000 photographic images from over 40 observatories that are housed in a secure building with environmental control.  The facility possesses several plate scanners, including two high-precision ones, GAMMA I and GAMMA II, built for NASA and the Space Telescope Science Institute (STScI) and used by a team under the leadership of the late Barry Lasker to develop the Guide Star Catalog and Digitized Sky Survey that are used to guide and direct the  Hubble Space Telescope .  APDA's networked storage system can store and analyze more than 100 terabytes of data. [ 18 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5015", "text": "A historical collection of photographic plates from  Mt. Wilson observatory  is available at the  Carnegie Observatories . [ 19 ]  Metadata is available via a searchable database, [ 20 ]  while a portion of the plates has been digitized."}
{"_id": "WikiPedia_Radiology$$$corpus_5016", "text": "Photostimulated luminescence  ( PSL ) is the release of stored energy within a  phosphor  by stimulation with visible light, to produce a luminescent signal.  X-rays  may induce such an energy storage. A plate based on this mechanism is called a  photostimulable phosphor (PSP) plate  (or  imaging plate ) and is one type of  X-ray detector  used in  projectional radiography . Creating an image requires illuminating the  plate  twice: the first exposure, to the  radiation  of interest, \"writes\" the image, and a later, second illumination (typically by a visible-wavelength  laser ) \"reads\" the image. The device to read such a plate is known as a  phosphorimager  (occasionally spelled  phosphoimager , perhaps reflecting its common application in  molecular biology  for detecting  radiolabeled   phosphorylated   proteins  and  nucleic acids )."}
{"_id": "WikiPedia_Radiology$$$corpus_5017", "text": "Projectional radiography  using a photostimulable phosphor plate as an  X-ray detector  can be called \" phosphor plate radiography \" [ 1 ]  or \" computed radiography \" [ 2 ]  (not to be confused with  computed tomography  which uses computer processing to convert multiple projectional radiographies to a  3D image )."}
{"_id": "WikiPedia_Radiology$$$corpus_5018", "text": "On photostimulable phosphor (PSP) plates, the phosphor layer is typically 0.1 to 0.3\u00a0mm thick. After the initial exposure by short- wavelength  (typically,  X-ray )  electromagnetic radiation , excited electrons in the  phosphor  material remain 'trapped' in 'colour centres' (\"F-centers\") in the  crystal   lattice  until stimulated by the second illumination. For example, Fuji's photostimulable phosphor is deposited on a flexible polyester film support with grain size about 5  micrometers , and is described as \" barium fluorobromide  containing a trace amount of bivalent  europium  as a luminescence center\". [ 3 ]  Europium is a  divalent  cation that replaces barium to create a  solid solution . When Eu 2+  ions are struck by ionizing radiation, they lose an additional electron to become Eu 3+  ions. These electrons enter the  conduction band  of the crystal and become trapped in the bromine ion empty lattice of the crystal, resulting in a  metastable state  that is higher in energy than the original condition."}
{"_id": "WikiPedia_Radiology$$$corpus_5019", "text": "A lower-frequency light source that is insufficient in energy to create more Eu 3+  ions can return the trapped electrons to the conduction band. As these mobilized electrons encounter Eu 3+  ions, they release a blue-violet 400\u00a0nm luminescence. [ 4 ]   This light is produced in proportion to the number of trapped electrons, and thus in proportion to the original X-ray signal.  It can be collected often by a  photomultiplier tube , which is clocked at a specific resolution or pixel capture frequency. The light is thereby converted to an electronic signal and significantly amplified. The electronic signal is then quantized via an  ADC  to discrete (digital) values for each pixel and placed into the image processor pixel map."}
{"_id": "WikiPedia_Radiology$$$corpus_5020", "text": "Afterwards, the plates can be \"erased,\" by exposing the plate to room-intensity  white light . Thereby, the plate can be used over and over again. Imaging plates can theoretically be re-used thousands of times if they are handled carefully and under certain radiation exposure conditions. PSP plate handling under industrial conditions often results in damage after a few hundred uses. Mechanical damage such as scratches and abrasions are common, as well as radiation fatigue or imprinting due to high energy applications. An image can be erased by simply exposing the plate to a room-level fluorescent light - but more efficient, complete erasure is required to avoid signal carry-over and artifacts. Most laser scanners automatically erase the plate (current technology uses red LED lighting) after laser scanning is complete. The imaging plate can then be re-used."}
{"_id": "WikiPedia_Radiology$$$corpus_5021", "text": "Reusable phosphor plates are environmentally safe but need to be disposed of according to local regulations due to the composition of the phosphor, which contains the heavy metal Barium."}
{"_id": "WikiPedia_Radiology$$$corpus_5022", "text": "Computed radiography is used for both  industrial radiography  and medical  projectional radiography . Image plate detectors have also been used in numerous  crystallography  studies. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5023", "text": "In phosphor plate radiography, the imaging plate is housed in a special cassette and placed under the body part or object to be examined and the x-ray exposure is made. The imaging plate is then run through a special laser scanner, or CR reader, that reads and converts the image to a  digital radiograph . The digital image can then be viewed and enhanced using software that has functions very similar to other conventional digital image-processing software, such as contrast, brightness, filtration and zoom. CR imaging plates (IPs) can be retrofitted to existing exam rooms and used in multiple x-ray sites since IPs are processed through a CR reader (scanner) that can be shared between multiple exam rooms. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5024", "text": "PSP plate radiography is often distinguished from  Direct Radiography  (DR). Direct radiography usually refers to image capture onto an amorphous silicon or selenium  flat panel detector  (FPD), the data being directly passed electronically to the processing computer. PSP plate radiography instead uses a cassette containing the imaging plate, which stores the image until it is read out and loaded into the computer. This additional extra step, from exposing the detector to a viewable digital image, is the main difference between the two techniques. [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5025", "text": "PSP plates and DR FPDs are typically used for  projectional radiography . This should not be confused with  fluoroscopy , where there is a continuous beam of radiation and the images appear on the screen in real time, for which PSP plates cannot be used. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5026", "text": "PSP plates are commonly used as x-ray detectors for measurements in  high energy-density physics .  Examples include self-emission imaging of  inertial confinement fusion  implosions, [ 9 ]  backlit radiographic microscopy, [ 9 ]  and spatially-resolved  emission spectroscopy  of  quantum dots . [ 10 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5027", "text": "Image plates were pioneered for commercial medical use by  Fuji  in the 1980s. [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5028", "text": "Patients  are exposed to  ionizing radiation  when they undergo  diagnostic examinations using x-rays  or  radiopharmaceuticals . Radiation emitted by radioisotopes or radiation generators is utilized in therapy for cancer or benign lesions and also in interventional procedures using  fluoroscopy . There has been a tremendous increase in the use of ionizing radiation in medicine during recent decades and health professionals and patients are concerned about the harmful effects of radiation. [ 1 ]  The  International Atomic Energy Agency  (IAEA) has established a program on  radiological protection of patients  in recognition of the increasing importance of this topic. The emphasis in the past had been on  radiation protection  of staff and this has helped to reduce radiation doses to staff at levels well below the limits prescribed by the  International Commission on Radiological Protection  (ICRP) and accepted by most countries. The recent emphasis on  radiation protection  of patients is helping in developing strategies to reduce radiation doses to patients without compromising on diagnostic or therapeutic purpose. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5029", "text": "\" ALARA \" (\"As Low As Reasonably Achievable\") should be maintained to reduce radiation doses to staff as well as patients. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5030", "text": "Radioanatomy  ( x-ray anatomy ) is an  anatomy   discipline  that involves studying anatomy through the use of  radiographic films . [ 3 ] \nThe x-ray film represents a two-dimensional image of a three-dimensional object due to the summary projection of different anatomical structures  onto a planar surface."}
{"_id": "WikiPedia_Radiology$$$corpus_5031", "text": "It requires certain skills for the correct interpretation of such images. Radiological anatomy is a necessary component of training for medical students and radiologists."}
{"_id": "WikiPedia_Radiology$$$corpus_5032", "text": "This  anatomy  article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Radiology$$$corpus_5033", "text": "Rarefying osteitis  is a general term for a  radiolucent  lesion on a  radiograph  usually diagnosed as a  periapical abscess  or a  periapical cyst . [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5034", "text": "This article about a  disease , disorder, or medical condition is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Radiology$$$corpus_5035", "text": "A  scorotron  (from  screen controlled corona [ 1 ] ), also called a  corona grid , [ 2 ]  is a device which creates  corona discharge  current, used in  xerography .  Scorotrons appear in  photocopiers , in  xeroradiography  equipment, [ 3 ]  and similar applications."}
{"_id": "WikiPedia_Radiology$$$corpus_5036", "text": "A  sensitivity speck  or  sensitivity center  is an imperfection or other specific point in a  silver halide  crystal which traps  electrons , causing  photosensitivity . This can produce a  latent image  in the crystal, having applications in  photography [ 1 ]  and  dosimetry . [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5037", "text": "A sensitivity speck is very often the site of shallow electron traps, such as crystalline defect (particularly edge  dislocation ) and  silver sulfide  specks created by sulfur sensitization process."}
{"_id": "WikiPedia_Radiology$$$corpus_5038", "text": "When a photon is absorbed by a silver halide crystal, a free-carrier (electron in the conduction band) is generated. This free-carrier can migrate through the  crystal lattice  of silver halide, until captured by the shallow electron trap, where the electron is likely to reduce an interstitial silver ion to form an atomic silver. Subsequent exposure can grow the size of silver cluster through the same mechanism. This forms the  latent image  where the silver cluster becomes large enough to render the entire crystal developable in developer solution."}
{"_id": "WikiPedia_Radiology$$$corpus_5039", "text": "This photography-related article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Radiology$$$corpus_5040", "text": "Spectral imaging  is an umbrella term for energy-resolved  X-ray imaging  in medicine. [ 1 ]  The technique makes use of the energy dependence of X-ray attenuation to either increase the  contrast-to-noise ratio , or to provide quantitative image data and reduce image artefacts by so-called material decomposition. Dual-energy imaging, i.e. imaging at two energy levels, is a special case of spectral imaging and is still the most widely used terminology, but the terms \"spectral imaging\" and \"spectral CT\" have been coined to acknowledge the fact that  photon-counting detectors  have the potential for measurements at a larger number of energy levels. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5041", "text": "The first medical application of spectral imaging appeared in 1953 when B. Jacobson at the  Karolinska University Hospital , inspired by  X-ray absorption spectroscopy , presented a method called \"dichromography\" to measure the concentration of  iodine  in X-ray images. [ 4 ]  In the 70's, spectral  computed tomography  (CT) with exposures at two different voltage levels was proposed by  G.N. Hounsfield  in his landmark CT paper. [ 5 ]  The technology evolved rapidly during the 70's and 80's, [ 6 ] [ 7 ]  but technical limitations, such as motion artifacts, [ 8 ]  for long held back widespread clinical use."}
{"_id": "WikiPedia_Radiology$$$corpus_5042", "text": "In recent years, however, two fields of technological breakthrough have spurred a renewed interest in energy-resolved imaging. Firstly, single-scan energy-resolved CT was introduced for routine clinical use in 2006 and is now available by several major manufacturers, [ 9 ]  which has resulted in a large and expanding number of clinical applications. Secondly, energy-resolving  photon-counting detectors  start to become available for clinical practice; the first commercial photon-counting system was introduced for mammography in 2003, [ 10 ]  and  CT systems  are at the verge of being feasible for routine clinical use. [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5043", "text": "An energy-resolved imaging system probes the object at two or more photon energy levels. In a generic imaging system, the projected signal in a detector element at energy level  \n \n \n \n \u03a9 \n \u2208 \n { \n \n E \n \n 1 \n \n \n , \n \n E \n \n 2 \n \n \n , \n \n E \n \n 3 \n \n \n , \n \u2026 \n } \n \n \n {\\textstyle \\Omega \\in \\{E_{1},E_{2},E_{3},\\ldots \\}} \n \n  is [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5044", "text": "where  \n \n \n \n q \n \n \n {\\textstyle q} \n \n  is the number of incident photons,  \n \n \n \n \u03a6 \n \n \n {\\textstyle \\Phi } \n \n  is the normalized incident energy spectrum, and  \n \n \n \n \u0393 \n \n \n {\\textstyle \\Gamma } \n \n  is the detector response function.  Linear attenuation coefficients  and integrated thicknesses for materials that make up the object are denoted  \n \n \n \n \u03bc \n \n \n {\\textstyle \\mu } \n \n  and  \n \n \n \n t \n \n \n {\\textstyle t} \n \n  (attenuation according to  Lambert\u2013Beers law ). Two conceivable ways of acquiring spectral information are to either vary  \n \n \n \n q \n \u00d7 \n \u03a6 \n \n \n {\\textstyle q\\times \\Phi } \n \n  with  \n \n \n \n \u03a9 \n \n \n {\\textstyle \\Omega } \n \n , or to have  \n \n \n \n \u03a9 \n \n \n {\\textstyle \\Omega } \n \n -specific  \n \n \n \n \u0393 \n \n \n {\\textstyle \\Gamma } \n \n , here denoted incidence-based and detection-based methods, respectively."}
{"_id": "WikiPedia_Radiology$$$corpus_5045", "text": "Most elements appearing naturally in human bodies are of low  atomic number  and lack  absorption edges  in the diagnostic X-ray energy range. The two dominating X-ray interaction effects are then  Compton scattering  and the  photo-electric effect , which can be assumed to be smooth and with separable and independent material and energy dependences. The linear attenuation coefficients can hence be expanded as [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5046", "text": "In contrast-enhanced imaging, high-atomic-number  contrast agents  with K absorption edges in the diagnostic energy range may be present in the body. K-edge energies are material specific, which means that the energy dependence of the photo-electric effect is no longer separable from the material properties, and an additional term can be added to Eq. ( 2 ) according to [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5047", "text": "where  \n \n \n \n \n a \n \n K \n \n \n \n \n {\\textstyle a_{K}} \n \n  and  \n \n \n \n \n f \n \n K \n \n \n \n \n {\\textstyle f_{K}} \n \n  are the material coefficient and energy dependency of contrast-agent material  \n \n \n \n K \n \n \n {\\textstyle K} \n \n ."}
{"_id": "WikiPedia_Radiology$$$corpus_5048", "text": "Summing the energy bins in Eq. ( 1 ) ( \n \n \n \n n \n = \n \u2211 \n \n n \n \n \u03a9 \n \n \n \n \n {\\textstyle n=\\sum n_{\\Omega }} \n \n ) yields a conventional non-energy-resolved image, but because X-ray contrast varies with energy, a weighted sum ( \n \n \n \n n \n = \n \u2211 \n \n w \n \n \u03a9 \n \n \n \u00d7 \n \n n \n \n \u03a9 \n \n \n \n \n {\\textstyle n=\\sum w_{\\Omega }\\times n_{\\Omega }} \n \n ) optimizes the  contrast-to-noise-ratio  (CNR) and enables a higher CNR at a constant patient  dose  or a lower dose at a constant CNR. [ 13 ]  The benefit of energy weighting is highest where the photo-electric effect dominates and lower in high-energy regions dominated by Compton scattering (with weaker energy dependence)."}
{"_id": "WikiPedia_Radiology$$$corpus_5049", "text": "Energy weighting was pioneered by Tapiovaara and Wagner [ 13 ]  and has subsequently been refined for projection imaging [ 14 ] [ 15 ]  and CT [ 16 ]  with CNR improvements ranging from a few percent up to tenth of percent for heavier elements and an ideal CT detector. [ 17 ]  An example with a realistic detector was presented by Berglund et al. who modified a photon-counting mammography system and raised the CNR of clinical images by 2.2\u20135.2%. [ 18 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5050", "text": "Equation ( 1 ) can be treated as a system of equations with material thicknesses as unknowns, a technique broadly referred to as material decomposition. System properties and linear attenuation coefficients need to be known, either explicitly (by modelling) or implicitly (by calibration). In CT, implementing material decomposition post reconstruction (image-based decomposition) does not require coinciding projection data, but the decomposed images may suffer from beam-hardening artefacts because the reconstruction algorithm is generally non-reversible. [ 19 ]  Applying material decomposition directly in projection space instead (projection-based decomposition), [ 6 ]  can in principle eliminate beam-hardening artefacts because the decomposed projections are quantitative, but the technique requires coinciding projection data such as from a detection-based method."}
{"_id": "WikiPedia_Radiology$$$corpus_5051", "text": "In the absence of K-edge contrast agents and any other information about the object (e.g. thickness), the limited number of independent energy dependences according to Eq. ( 2 ) means that the system of equations can only be solved for two unknowns, and measurements at two energies ( \n \n \n \n \n | \n \n \u03a9 \n \n | \n \n = \n 2 \n \n \n {\\textstyle |\\Omega |=2} \n \n ) are necessary and sufficient for a unique solution of  \n \n \n \n \n t \n \n 1 \n \n \n \n \n {\\textstyle t_{1}} \n \n  and  \n \n \n \n \n t \n \n 2 \n \n \n \n \n {\\textstyle t_{2}} \n \n . [ 7 ]  Materials 1 and 2 are referred to as basis materials and are assumed to make up the object; any other material present in the object will be represented by a linear combination of the two basis materials."}
{"_id": "WikiPedia_Radiology$$$corpus_5052", "text": "Material-decomposed images can be used to differentiate between healthy and malignant tissue, such as  micro calcifications in the breast , [ 20 ]  ribs and pulmonary nodules, [ 21 ]   cysts , solid  tumors  and normal breast tissue, [ 22 ]  posttraumatic  bone bruises  ( bone marrow edema ) and the bone itself, [ 23 ]  different types of  renal calculi  (stones), [ 24 ]  and  gout  in the joints. [ 25 ]  The technique can also be used to characterize healthy tissue, such as the composition of  breast tissue  (an independent risk factor for breast cancer) [ 26 ] [ 27 ] [ 28 ]  and  bone-mineral density  (an independent risk factor for fractures and all-cause mortality). [ 29 ]  Finally, virtual autopsies with spectral imaging can facilitate detection and characterization of bullets, knife tips, glass or shell fragments etc. [ 30 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5053", "text": "The basis-material representation can be readily converted to images showing the amounts of photoelectric and Compton interactions by invoking Eq. ( 2 ), and to images of  effective-atomic-number  and  electron density  distributions. [ 6 ]  As the basis-material representation is sufficient to describe the linear attenuation of the object, it is possible to calculate virtual monochromatic images, which is useful for optimizing the CNR to a certain imaging task, analogous to energy weighting. For instance, the CNR between grey and white brain matter is maximized at medium energies, whereas artefacts caused by photon starvation are minimized at higher virtual energies. [ 31 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5054", "text": "In  contrast-enhanced imaging , additional unknowns may be added to the system of equations according to Eq. ( 3 ) if one or several K absorption edges are present in the imaged energy range, a technique often referred to as K-edge imaging. With one K-edge contrast agent, measurements at three energies ( \n \n \n \n \n | \n \n \u03a9 \n \n | \n \n = \n 3 \n \n \n {\\textstyle |\\Omega |=3} \n \n ) are necessary and sufficient for a unique solution, two contrast agents can be differentiated with four energy bins ( \n \n \n \n \n | \n \n \u03a9 \n \n | \n \n = \n 4 \n \n \n {\\textstyle |\\Omega |=4} \n \n ), etc. K-edge imaging can be used to either enhance and quantify, or to suppress a contrast agent."}
{"_id": "WikiPedia_Radiology$$$corpus_5055", "text": "Enhancement of contrast agents can be used for improved detection and diagnosis of tumors, [ 32 ]  which exhibit increased retention of contrast agents. Further, differentiation between iodine and  calcium  is often challenging in conventional CT, but energy-resolved imaging can facilitate many procedures by, for instance, suppressing bone contrast [ 33 ]  and improving characterization of  atherosclerotic plaque . [ 34 ]  Suppression of contrast agents is employed in so-called virtual unenhanced or virtual non-contrast (VNC) images. VNC images are free from iodine staining (contrast-agent residuals), [ 35 ]  can save dose to the patient by reducing the need for an additional non-contrast acquisition, [ 36 ]  can improve  radiotherapy  dose calculations from CT images, [ 37 ]  and can help in distinguishing between contrast agent and foreign objects. [ 38 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5056", "text": "Most studies of contrast-enhanced spectral imaging have used iodine, which is a well-established contrast agent, but the K edge of iodine at 33.2 keV is not optimal for all applications and some patients are hypersensitive to iodine. Other contrast agents have therefore been proposed, such as  gadolinium  (K edge at 50.2 keV), [ 39 ]  nanoparticle  silver  (K edge at 25.5 keV), [ 40 ]   zirconium  (K edge at 18.0 keV), [ 41 ]  and  gold  (K edge at 80.7 keV). [ 42 ]  Some contrast agents can be targeted, [ 43 ]  which opens up possibilities for  molecular imaging , and using several contrast agents with different K-edge energies in combination with photon-counting detectors with a corresponding number of energy thresholds enable multi-agent imaging. [ 44 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5057", "text": "Incidence-based methods obtain spectral information by acquiring several images at different  tube voltage  settings, possibly in combination with different filtering. Temporal differences between the exposures (e.g. patient motion, variation in contrast-agent concentration) for long limited practical implementations, [ 6 ]  but dual-source CT [ 9 ]  and subsequently rapid kV switching [ 45 ]  have now virtually eliminated the time between exposures. Splitting the incident radiation of a scanning system into two beams with different filtration is another way to quasi-simultaneously acquire data at two energy levels. [ 46 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5058", "text": "Detection-based methods instead obtain spectral information by splitting the spectrum after interaction in the object. So-called sandwich detectors consist of two (or more) detector layers, where the top layer preferentially detects low-energy photons and the bottom layer detects a harder spectrum. [ 47 ] [ 48 ]  Detection-based methods enable projection-based material decomposition because the two energy levels measured by the detector represent identical ray paths. Further, spectral information is available from every scan, which has work-flow advantages. [ 49 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5059", "text": "The currently most advanced detection-based method is based on  photon-counting detectors . As opposed to  conventional detectors , which integrate all photon interactions over the exposure time, photon-counting detectors are fast enough to register and measure the energy of single photon events. [ 50 ]  Hence, the number of energy bins and the spectral separation are not determined by physical properties of the system (detector layers, source / filtration etc.), but by the detector electronics, which increases efficiency and the degrees of freedom, and enable elimination of  electronic noise . The first commercial photon-counting application was the MicroDose mammography system, introduced by Sectra Mamea in 2003 (later acquired by Philips), [ 10 ]  and spectral imaging was launched on this platform in 2013. [ 51 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5060", "text": "The MicroDose system was based on silicon strip detectors, [ 10 ] [ 51 ]  a technology that has subsequently been refined for CT with up to eight energy bins. [ 52 ] [ 53 ]   Silicon  as sensor material benefit from high charge-collection efficiency, ready availability of high-quality high-purity silicon crystals, and established methods for test and assembly. [ 54 ]  The relatively low photo-electric cross section can be compensated for by arranging the silicon wafers edge on, [ 55 ]  which also enables depth segments. [ 56 ]   Cadmium telluride (CdTe)  and  cadmium\u2013zinc telluride (CZT)  are also being investigated as sensor materials. [ 57 ] [ 58 ] [ 59 ]  The higher atomic number of these materials result in a higher photo-electric cross section, which is advantageous, but the higher fluorescent yield degrades spectral response and induces cross talk. [ 60 ] [ 61 ]  Manufacturing of macro-sized crystals of these materials have so far posed practical challenges and leads to charge trapping [ 62 ]  and long-term polarization effects (build-up of space charge). [ 63 ]  Other solid-state materials, such as  gallium arsenide [ 64 ]  and  mercuric iodide , [ 65 ]  as well as gas detectors, [ 66 ]  are currently quite far from clinical implementation."}
{"_id": "WikiPedia_Radiology$$$corpus_5061", "text": "The main intrinsic challenge of photon-counting detectors for medical imaging is pulse pileup, [ 62 ]  which results in lost counts and reduced energy resolution because several pulses are counted as one. Pileup will always be present in photon-counting detectors because of the  Poisson distribution  of incident photons, but detector speeds are now so high that acceptable pileup levels at CT count rates begin to come within reach. [ 67 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5062", "text": "Tudor Scan Tech  SA is a Swiss company that manufactures  aircraft  and  cargo  scanners, including  x-ray scanners  and robotic scanning systems. The company was founded in 2014 by Mircea Tudor and is currently headquartered in  Saint-Imier, Switzerland . [ 1 ]  Tudor Scan Tech incorporates  MBTelecom Ltd , a Romanian company developing high technologies for the security industry, and also heps customs and border officials to check for  illegal weapons ,  contraband , and  explosive materials . [ 2 ]  They have won The Grand Prix of the International Exhibition of Inventions thrice, 2009, 2013 and 2014. [ 3 ] [ 4 ]  The company has also won WIPO Awards in 2009, organized by  World Intellectual Property Organization . [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5063", "text": "Tudor Scan Tech SA (TST) was founded by Mircea Tudor in 2014, in  Switzerland , forming a group of companies with the Romanian company MBTelecom Ltd. (MBT) founded in 1994 by Mircea Tudor. The group of companies designs and manufactures inspection scanners, including x-ray, linear accelerators and  gamma ray  scanning system for aircraft, cargo, containers, occupied cars and vans, heavy vehicle and border control. [ 1 ] [ 7 ] [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5064", "text": "In 2009, the group started to develop the first ever non- intrusiveness  inspection technology, Roboscan Aeria. The company was awarded in 2009 with The Grand Prix of the 37th International Exhibition of Inventions of  Geneva  for the invention of the first robotic mobile scanner for trucks and containers. During the same year, the company also won World Intellectual Property Organisation Award. The company was nominated and awarded again at The Grand Prix of the 41st International Exhibition of Inventions of Geneva for the first scanner for civil and military aircraft. [ 9 ] [ 10 ] [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5065", "text": "In 2013, they launched a new plant worth 5 million euros to increase the airplane scanners production. [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5066", "text": "Tudor Scan Tech is also a strategic security partner of  International Air Transport Association  (IATA). [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5067", "text": "Roboscan Aeria is a patented design for aircraft security inspection developed inside the group MBT-TST. Roboscan Aeria is designed to scan and detect threats, illegal or undeclared goods within the aircraft. [ 13 ]  The scanning process is remotely operated without any human exposure to  ionizing radiations .  Radiography  detects any object with a resolution of 0.5\u00a0mm. [ 5 ] [ 9 ] [ 14 ]  The first scanner is installed at Bucharest's Henri Coanda Airport. [ 15 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5068", "text": "Unsharpness  is the loss of  spatial resolution  in a  radiographic  image. There are generally considered to be three types of unsharpness: geometric unsharpness, motion unsharpness and photographic or system unsharpness. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5069", "text": "Motion unsharpness  is caused by movement of the patient, the detector or the source of  X-rays , during the exposure. Movement of the patient, either voluntary or otherwise, is the most common cause and this can be minimised in a number of ways: immobilizing the patient, asking the patient to keep still or to hold the breath and keeping exposure time short, and thereby giving them less time in which to move, are the most obvious."}
{"_id": "WikiPedia_Radiology$$$corpus_5070", "text": "System unsharpness  (previously called photographic unsharpnesss) is the result of the detector system employed. Every detector type has a limiting factor which determines its maximum spatial resolution. In film systems it is the size of the grains of photographic chemical. In  computed radiography  systems it the size of the laser used to read the phosphor plate in the cassette reader. In  digital radiography  systems it is the size of the individual  thin film transistors . Since each type has a maximum capability, there is no way to minimise this system other than using a better and probably more expensive machine."}
{"_id": "WikiPedia_Radiology$$$corpus_5071", "text": "Geometric unsharpness  is caused by aspects of the geometry of the X-ray beam. Two principal factors play simultaneously: the apparent focal spot size and the ratio between object-film distance (OFD) and focus-film distance (FFD). Fine focal spot sizes will minimise geometric unsharpness, and therefore give more detailed images, but it is often impossible to employ them due to the tube loading necessary in the exposure. Keeping the ratio FFD:OFD high will minimise geometric unsharpness. This is most easily done by keeping the OFD to a minimum, i.e., keeping the part of the body being X-rayed as close to the detector as possible. If this is not possible however, then increasing FFD beyond the normal 100\u2013110\u00a0cm will be necessary to keep the unsharpness level acceptable."}
{"_id": "WikiPedia_Radiology$$$corpus_5072", "text": "In  urology ,  voiding cystourethrography  ( VCUG ) is a frequently performed technique for visualizing a person's  urethra  and  urinary bladder  while the person  urinates  (voids). It is used in the diagnosis of  vesicoureteral reflux  (kidney reflux), among other disorders. [ 1 ]   The technique consists of  catheterizing  the person in order to fill the bladder with a  radiocontrast  agent, typically  diatrizoic acid . Under  fluoroscopy  (real time x-rays) the  radiologist  watches the contrast enter the bladder and looks at the anatomy of the patient. If the contrast moves into the  ureters  and back into the  kidneys , the  radiologist  makes the diagnosis of  vesicoureteral reflux , and gives the degree of severity a score. The exam ends when the person voids while the radiologist is watching under fluoroscopy. Consumption of fluid promotes excretion of contrast media after the procedure. It is important to watch the contrast during voiding, because this is when the bladder has the most pressure, and it is most likely this is when reflux will occur.  Despite this detailed description of the procedure, at least as of 2016 [update]  the technique had not been standardized across practices. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5073", "text": "Some uses of this procedure are: to study the presence of  vesicoureteric reflux , study of urethra during micturition, presence of bladder leak post surgery or trauma, and is used in  urodynamic testing  to assess  urinary incontinence . [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5074", "text": "Indications  for performing VCUG:"}
{"_id": "WikiPedia_Radiology$$$corpus_5075", "text": "Contraindications for voiding cystourethrogram is when the subject is having:"}
{"_id": "WikiPedia_Radiology$$$corpus_5076", "text": "A high osmolar contrast agent such as  diatrizoate  or a low osmolar contrast agent such as  Iotalamic acid  with a concentration of 150 mg per ml is used for the procedure. [ 2 ] [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5077", "text": "The urinary bladder is catheterised under aseptic technique. The contrast medium is slowly injected or dripped in. The level of bladder filling is observed by taking intermittent images using  fluoroscopy . The early filling of the bladder should be monitored carefully to detect any accidental placement of the catheter in the distal  ureter  or  vagina  and to detect any reflux of contrast into the ureters. The bladder should be filled up with as much contrast as possible until the subject is unable to tolerate it or when there is no more contrast going into the bladder. If the subject is able to pee, then the catheter can be removed for the subject to do so. If there is no confidence that the subject is able to pee, then the urinary catheter should remain in place. It is more convenient for adults to pee in an erect position with a urine receiver. Meanwhile, children can pee while lying down on a table with a urine receiver. Infants and smaller children can lie down on a table and pee onto absorbent pads. For those children or infants with a neuropathic bladder, pressure on the  suprabic  region can help them to pee. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5078", "text": "Fluoroscopic spot images and videos are taken during the micturition phase to detect any reflux. The lower ureter is best seen on an anterior oblique position. In males, peeing should be done in oblique or lateral positions to visualise the whole of urethra. Finally, the whole abdomen is imaged to detect any undetected reflux in previous images. Any urine left in the bladder after peeing is also recorded in this image. Lateral views are useful to evaluate any fistulas from the bladder connecting into the rectum or vagina. Oblique views are used to evaluate any leaks from the bladder or urethra. Stress views are useful in urodynamic studies. [ 2 ]  The  verumontanum  appears elongated and the proximal bulbal urethra has a less conical appearance. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5079", "text": "Children may have painful micturition after the procedure, which can lead to  urinary retention  (children afraid to pee due to pain). Some painkillers or peeing inside a warm bath may help. Those children who receive antibiotics before the procedure for urinary tract infection will double the dose for 3 days after the procedure. Those not already on antibiotics will be prescribed with 3 days of  trimethoprim . Haematuria (blood in urine) may also occur after the procedure. [ 2 ]     With respect to post-procedural urinary tract infection, the risk has been found to be sufficiently low, except in patients with a pre-existing urologic diagnosis, that pre-operative antibiotic use is not considered a necessary adjunct. [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5080", "text": "The procedure is invasive and uncomfortable, and it carries a high potential for psychological trauma for both children and parents. [ 1 ] [ 6 ]  The long-term psychological effects of VCUGs on children have been compared to that of childhood  sexual abuse . [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5081", "text": "Another complication is perforation of the bladder due to over-distension. Accidental catherisation of vagina or unusual urethral opening and retention of urinary catheter are also possible. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5082", "text": "An increased risk of cancer, in particular genitourinary cancer, has been observed in one study arising from the radiation exposure inherent in the procedure. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5083", "text": "An  X-ray  (also known in many languages as  R\u00f6ntgen radiation ) is a form of high-energy  electromagnetic radiation  with a  wavelength  shorter than those of  ultraviolet  rays and longer than those of  gamma rays . Roughly, X-rays have a  wavelength  ranging from 10\u00a0 nanometers  to 10\u00a0 picometers , corresponding to  frequencies  in the range of 30\u00a0 petahertz  to 30\u00a0 exahertz  ( 3 \u00d7 10 16 \u00a0Hz  to  3 \u00d7 10 19 \u00a0Hz ) and photon energies in the range of 100\u00a0 eV  to 100\u00a0 keV , respectively. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5084", "text": "X-rays were discovered in  1895  by the German scientist  Wilhelm Conrad R\u00f6ntgen , [ 2 ]  who named it  X-radiation  to signify an unknown type of radiation. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5085", "text": "X-rays can penetrate many solid substances such as construction materials and living tissue, [ 4 ]  so X-ray  radiography  is widely used in  medical diagnostics   (e.g., checking for  broken bones ) and  material science  (e.g., identification of some  chemical elements  and detecting weak points in construction materials). [ 5 ]   However X-rays are  ionizing radiation  and exposure can be hazardous to health, causing  DNA  damage, cancer and, at higher intensities, burns and  radiation sickness .  Their generation and use is strictly controlled by public health authorities."}
{"_id": "WikiPedia_Radiology$$$corpus_5086", "text": "X-rays were originally noticed in science as a type of unidentified  radiation  emanating from  discharge tubes  by experimenters investigating  cathode rays  produced by such tubes, which are energetic  electron  beams that were first observed in 1869. Early researchers noticed effects that were attributable to them in many of the early  Crookes tubes  (invented around  1875 ). Crookes tubes created free electrons by  ionization  of the residual air in the tube by a high  DC   voltage  of anywhere between a few  kilovolts  and 100\u00a0kV. This voltage accelerated the electrons coming from the  cathode  to a high enough velocity that they created X-rays when they struck the  anode  or the glass wall of the tube. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5087", "text": "The earliest experimenter thought to have (unknowingly) produced X-rays was  William Morgan . In  1785 , he presented a  paper  to the  Royal Society of London  describing the effects of passing  electrical currents  through a partially evacuated glass tube, producing a glow created by X-rays. [ 7 ] [ 8 ]  This work was further explored by  Humphry Davy  and his assistant  Michael Faraday . [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5088", "text": "Starting in 1888, Philipp Lenard conducted experiments to see whether cathode rays could pass out of the Crookes tube into the air. He built a Crookes tube with a \"window\" at the end made of thin aluminium, facing the cathode so the cathode rays would strike it (later called a \"Lenard tube\"). He found that something came through, that would expose photographic plates and cause fluorescence. He measured the penetrating power of these rays through various materials. It has been suggested that at least some of these \"Lenard rays\" were actually X-rays. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5089", "text": "Helmholtz formulated mathematical equations for X-rays. He postulated a dispersion theory before R\u00f6ntgen made his discovery and announcement. He based it on the  electromagnetic theory of light . [ 10 ] [ full citation needed ]  However, he did not work with actual X-rays."}
{"_id": "WikiPedia_Radiology$$$corpus_5090", "text": "In early 1890, photographer  William Jennings  and associate professor of the  University of Pennsylvania  Arthur W. Goodspeed were making photographs of coins with electric sparks. On 22 February after the end of their experiments two coins were left on a stack of photographic plates before Goodspeed demonstrated to Jennings the operation of  Crookes tubes . While developing the plates, Jennings noticed disks of unknown origin on some of the plates, but nobody could explain them, and they moved on. Only in 1896 they realized that they accidentally made an X-ray photograph (they didn't claim a discovery). [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5091", "text": "Also in 1890, Roentgen's assistant  Ludwig Zehnder  noticed a flash of light from a fluorescent screen immediately before the covered tube he was switching on punctured. [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5092", "text": "When  Stanford University  physics professor  Fernando Sanford  conducted his \"electric photography\" experiments in 1891\u20131893 by photographing coins in the light of electric sparks, [ 13 ]  like Jennings and Goodspeed, he may have unknowingly generated and detected X-rays. His letter of  6 January 1893  to the  Physical Review  was duly published [ 13 ]  and an article entitled  Without Lens or Light, Photographs Taken With Plate and Object in Darkness  appeared in the  San Francisco Examiner . [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5093", "text": "In  1894 ,  Nikola Tesla  noticed damaged film in his lab that seemed to be associated with Crookes tube experiments and began investigating this invisible,  radiant energy . [ 15 ] [ 16 ]  After R\u00f6ntgen identified the X-ray, Tesla began making X-ray images of his own using high voltages and tubes of his own design, [ 17 ]  as well as Crookes tubes."}
{"_id": "WikiPedia_Radiology$$$corpus_5094", "text": "On  8 November 1895 , German physics professor  Wilhelm R\u00f6ntgen  stumbled on X-rays while experimenting with Lenard tubes and  Crookes tubes  and began studying them. He wrote an initial report \"On a new kind of ray: A preliminary communication\" and on 28 December 1895, submitted it to  W\u00fcrzburg 's Physical-Medical Society journal. [ 18 ]  This was the first paper written on X-rays. R\u00f6ntgen referred to the radiation as \"X\", to indicate that it was an unknown type of radiation. Some early texts refer to them as Chi-rays, having interpreted \"X\" as the uppercase  Greek letter Chi ,  \u03a7 . [ 19 ] [ 20 ] [ 21 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5095", "text": "There are conflicting accounts of his discovery because R\u00f6ntgen had his  lab notes  burned after his death, but this is a likely reconstruction by his biographers: [ 22 ] [ 23 ]  R\u00f6ntgen was investigating cathode rays from a Crookes tube which he had wrapped in black cardboard so that the visible light from the tube would not interfere, using a  fluorescent  screen painted with barium  platinocyanide . He noticed a faint green glow from the screen, about 1 meter (3.3\u00a0ft) away. R\u00f6ntgen realized some invisible rays coming from the tube were passing through the cardboard to make the screen glow. He found they could also pass through books and papers on his desk. R\u00f6ntgen threw himself into investigating these unknown rays systematically. Two months after his initial discovery, he published his paper. [ 24 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5096", "text": "R\u00f6ntgen discovered their medical use when he made a picture of his wife's hand on a photographic plate formed due to X-rays. The photograph of his wife's hand was the first photograph of a human body part using X-rays. When she saw the picture, she said \"I have seen my death.\" [ 27 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5097", "text": "The discovery of X-rays generated significant interest. R\u00f6ntgen's biographer  Otto Glasser  estimated that, in  1896  alone, as many as 49 essays and 1044 articles about the new rays were published. [ 28 ]  This was probably a conservative estimate, if one considers that nearly every paper around the world extensively reported about the new discovery, with a magazine such as  Science  dedicating as many as 23 articles to it in that year alone. [ 29 ]  Sensationalist reactions to the new discovery included publications linking the new kind of rays to occult and paranormal theories, such as telepathy. [ 30 ] [ 31 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5098", "text": "The name X-rays stuck, although (over R\u00f6ntgen's great objections) many of his colleagues suggested calling them  R\u00f6ntgen rays . They are still referred to as such in many languages, including  German ,  Hungarian ,  Ukrainian ,  Danish ,  Polish ,  Czech ,  Bulgarian ,  Swedish ,  Finnish ,  Portuguese ,  Estonian ,  Slovak ,  Slovenian ,  Turkish ,   Russian ,  Latvian ,  Lithuanian ,  Albanian ,  Japanese ,  Dutch ,  Georgian ,  Hebrew ,  Icelandic , and  Norwegian . [ original research? ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5099", "text": "R\u00f6ntgen received the first  Nobel Prize in Physics  for his discovery. [ 32 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5100", "text": "R\u00f6ntgen immediately noticed X-rays could have medical applications. Along with his 28 December Physical-Medical Society submission, he sent a letter to physicians he knew around Europe (1 January 1896). [ 33 ]  News (and the creation of \"shadowgrams\") spread rapidly with Scottish electrical engineer  Alan Archibald Campbell-Swinton  being the first after R\u00f6ntgen to create an X-ray photograph (of a hand). Through February, there were 46 experimenters taking up the technique in North America alone. [ 33 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5101", "text": "The first use of X-rays under clinical conditions was by  John Hall-Edwards  in Birmingham, England on 11 January 1896, when he radiographed a needle stuck in the hand of an associate. On 14 February 1896, Hall-Edwards was also the first to use X-rays in a surgical operation. [ 34 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5102", "text": "In early 1896, several weeks after R\u00f6ntgen's discovery,  Ivan Romanovich Tarkhanov  irradiated frogs and insects with X-rays, concluding that the rays \"not only photograph, but also affect the living function\". [ 35 ]  At around the same time, the zoological illustrator James Green began to use X-rays to examine fragile specimens.  George Albert Boulenger  first mentioned this work in a paper he delivered before the  Zoological Society of London  in May 1896. The book  Sciagraphs of British Batrachians and Reptiles  (sciagraph is an obsolete name for an X-ray photograph), by Green and James H. Gardiner, with a foreword by Boulenger, was published in 1897. [ 36 ] [ 37 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5103", "text": "The first medical X-ray made in the United States was obtained using a discharge tube of  Ivan Puluj 's design. [ 38 ]  In January 1896, on reading of R\u00f6ntgen's discovery, Frank Austin of  Dartmouth College  tested all of the discharge tubes in the physics laboratory and found that only the Puluj tube produced X-rays. This was a result of Puluj's inclusion of an oblique \"target\" of  mica , used for holding samples of  fluorescent  material, within the tube. On 3 February 1896, Gilman Frost, professor of medicine at the college, and his brother Edwin Frost, professor of physics, exposed the wrist of Eddie McCarthy, whom Gilman had treated some weeks earlier for a fracture, to the X-rays and collected the resulting image of the broken bone on  gelatin photographic plates  obtained from Howard Langill, a local photographer also interested in R\u00f6ntgen's work. [ 39 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5104", "text": "Many experimenters, including R\u00f6ntgen himself in his original experiments, came up with methods to view X-ray images \"live\" using some form of luminescent screen. [ 33 ]  R\u00f6ntgen used a screen coated with barium  platinocyanide . On 5 February 1896, live imaging devices were developed by both Italian scientist Enrico Salvioni (his \"cryptoscope\") and  William Francis Magie  of  Princeton University  (his \"Skiascope\"), both using barium platinocyanide. American inventor  Thomas Edison  started research soon after R\u00f6ntgen's discovery and investigated materials' ability to fluoresce when exposed to X-rays, finding that  calcium tungstate  was the most effective substance. In May 1896, he developed the first mass-produced live imaging device, his \"Vitascope\", later called the  fluoroscope , which became the standard for medical X-ray examinations. [ 33 ]  Edison dropped X-ray research around 1903, before the death of  Clarence Madison Dally , one of his glassblowers. Dally had a habit of testing X-ray tubes on his own hands, developing a cancer in them so tenacious that both arms were  amputated  in a futile attempt to save his life; in 1904, he became the first known death attributed to X-ray exposure. [ 33 ]  During the time the fluoroscope was being developed, Serbian American physicist  Mihajlo Pupin , using a calcium tungstate screen developed by Edison, found that using a fluorescent screen decreased the exposure time it took to create an X-ray for medical imaging from an hour to a few minutes. [ 40 ] [ 33 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5105", "text": "In 1901,  U.S. President William McKinley was shot twice  in an assassination attempt while attending the  Pan American Exposition  in  Buffalo, New York . While one bullet only grazed his  sternum , another had lodged somewhere deep inside his  abdomen  and could not be found. A worried McKinley aide sent word to inventor Thomas Edison to rush an  X-ray machine  to Buffalo to find the stray bullet. It arrived but was not used. While the shooting itself had not been lethal,  gangrene  had developed along the path of the bullet, and McKinley died of  septic shock  due to bacterial infection six days later. [ 41 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5106", "text": "With the widespread experimentation with X\u2011rays after their discovery in  1895  by scientists, physicians, and inventors came many stories of burns, hair loss, and worse in technical journals of the time. In February 1896, Professor John Daniel and  William Lofland Dudley  of  Vanderbilt University  reported hair loss after Dudley was X-rayed. A child who had been shot in the head was brought to the Vanderbilt laboratory in 1896. Before trying to find the bullet, an experiment was attempted, for which Dudley \"with his characteristic devotion to science\" [ 42 ] [ 43 ] [ 44 ]  volunteered. Daniel reported that 21 days after taking a picture of Dudley's  skull  (with an exposure time of one hour), he noticed a bald spot 5 centimeters (2\u00a0in) in diameter on the part of his head nearest the X-ray tube: \"A plate holder with the plates towards the side of the skull was fastened and a  coin  placed between the skull and the head. The tube was fastened at the other side at a distance of one-half-inch [1.3\u00a0cm] from the hair.\" [ 45 ]  Beyond burns, hair loss, and cancer, X-rays can be linked to infertility in males based on the amount of radiation used. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5107", "text": "In August 1896, H. D. Hawks, a graduate of Columbia College, suffered severe hand and chest burns from an X-ray demonstration. It was reported in  Electrical Review  and led to many other reports of problems associated with X-rays being sent in to the publication. [ 46 ]  Many experimenters including  Elihu Thomson  at Edison's lab,  William J. Morton , and  Nikola Tesla  also reported burns. Elihu Thomson deliberately exposed a finger to an X-ray tube over a period of time and suffered pain, swelling, and blistering. [ 47 ]  Other effects were sometimes blamed for the damage including ultraviolet rays and (according to Tesla) ozone. [ 15 ]  Many physicians claimed there were no effects from X-ray exposure at all. [ 47 ]  On 3 August 1905, in San Francisco, California,  Elizabeth Fleischman , an American X-ray pioneer, died from complications as a result of her work with X-rays. [ 48 ] [ 49 ] [ 50 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5108", "text": "Hall-Edwards developed a cancer (then called X-ray dermatitis) sufficiently advanced by 1904 to cause him to write papers and give public addresses on the dangers of X-rays. His left arm had to be amputated at the elbow in 1908, [ 51 ] [ 52 ]  and four fingers on his right arm soon thereafter, leaving only a thumb. He died of cancer in 1926. His left hand is kept at  Birmingham University . [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5109", "text": "The many applications of X-rays immediately generated enormous interest. Workshops began making specialized versions of Crookes tubes for generating X-rays and these first-generation  cold cathode  or Crookes X-ray tubes were used until about 1920. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5110", "text": "A typical early 20th-century medical X-ray system consisted of a  Ruhmkorff coil  connected to a  cold cathode Crookes X-ray tube . A spark gap was typically connected to the high voltage side in parallel to the tube and used for diagnostic purposes. [ 53 ]  The spark gap allowed detecting the polarity of the sparks, measuring voltage by the length of the sparks thus determining the \"hardness\" of the vacuum of the tube, and it provided a load in the event the X-ray tube was disconnected. To detect the hardness of the tube, the spark gap was initially opened to the widest setting. While the coil was operating, the operator reduced the gap until sparks began to appear. A tube in which the spark gap began to spark at around 6.4 centimeters (2.5\u00a0in) was considered soft (low vacuum) and suitable for thin body parts such as hands and arms. A 13-centimeter (5\u00a0in) spark indicated the tube was suitable for shoulders and knees. An 18-to-23-centimeter (7 to 9\u00a0in) spark would indicate a higher vacuum suitable for imaging the abdomen of larger individuals. Since the spark gap was connected in parallel to the tube, the spark gap had to be opened until the sparking ceased to operate the tube for imaging. Exposure time for photographic plates was around half a minute for a hand to a couple of minutes for a thorax. The plates may have a small addition of fluorescent salt to reduce exposure times. [ 53 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5111", "text": "Crookes tubes were unreliable. They had to contain a small quantity of gas (invariably air) as a current will not flow in such a tube if they are fully evacuated. However, as time passed, the X-rays caused the glass to absorb the gas, causing the tube to generate \"harder\" X-rays until it soon stopped operating. Larger and more frequently used tubes were provided with devices for restoring the air, known as \"softeners\". These often took the form of a small side tube that contained a small piece of  mica , a mineral that traps relatively large quantities of air within its structure. A small electrical heater heated the mica, causing it to release a small amount of air, thus restoring the tube's efficiency. However, the mica had a limited life, and the restoration process was difficult to control. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5112", "text": "In  1904 ,  John Ambrose Fleming  invented the  thermionic diode , the first kind of  vacuum tube . This used a  hot cathode  that caused an  electric current  to flow in a  vacuum . This idea was quickly applied to X-ray tubes, and hence heated-cathode X-ray tubes, called \"Coolidge tubes\", completely replaced the troublesome cold cathode tubes by about 1920. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5113", "text": "In about 1906, the physicist  Charles Barkla  discovered that X-rays could be scattered by gases, and that each element had a characteristic  X-ray spectrum . He won the  1917   Nobel Prize in Physics  for this discovery. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5114", "text": "In  1912 ,  Max von Laue , Paul Knipping, and Walter Friedrich first observed the  diffraction  of X-rays by crystals. This discovery, along with the early work of  Paul Peter Ewald ,  William Henry Bragg , and  William Lawrence Bragg , gave birth to the field of  X-ray crystallography . [ 54 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5115", "text": "In  1913 ,  Henry Moseley  performed crystallography experiments with X-rays emanating from various metals and formulated  Moseley's law  which relates the frequency of the X-rays to the atomic number of the metal. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5116", "text": "The  Coolidge X-ray tube  was invented the same year by  William D. Coolidge . It made possible the continuous emissions of X-rays. Modern X-ray tubes are based on this design, often employing the use of rotating targets which allow for significantly higher heat dissipation than static targets, further allowing higher quantity X-ray output for use in high-powered applications such as rotational CT scanners. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5117", "text": "The use of X-rays for medical purposes (which developed into the field of  radiation therapy ) was pioneered by Major  John Hall-Edwards  in  Birmingham , England. Then in 1908, he had to have his left arm amputated because of the spread of  X-ray dermatitis  on his arm. [ 55 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5118", "text": "Medical science also used the motion picture to study human physiology. In 1913, a motion picture was made in Detroit showing a hard-boiled egg inside a human stomach. This early X-ray movie was recorded at a rate of one still image every four seconds. [ 56 ]  Dr Lewis Gregory Cole of New York was a pioneer of the technique, which he called \"serial radiography\". [ 57 ] [ 58 ]  In 1918, X-rays were used in association with  motion picture cameras  to capture the human skeleton in motion. [ 59 ] [ 60 ] [ 61 ]  In 1920, it was used to record the movements of tongue and teeth in the study of languages by the Institute of Phonetics in England. [ 62 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5119", "text": "In  1914 ,  Marie Curie  developed radiological cars to support soldiers injured in  World War I . The cars would allow for rapid X-ray imaging of wounded soldiers so battlefield surgeons could quickly and more accurately operate. [ 63 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5120", "text": "From the early 1920s through to the 1950s, X-ray machines were developed to assist in the fitting of shoes [ 64 ]  and were sold to commercial shoe stores. [ 65 ] [ 66 ] [ 67 ]  Concerns regarding the impact of frequent or poorly controlled use were expressed in the 1950s, [ 68 ] [ 69 ]  leading to the practice's eventual end that decade. [ 70 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5121", "text": "The  X-ray microscope  was developed during the 1950s. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5122", "text": "The  Chandra X-ray Observatory , launched on  23 July 1999 , has been allowing the exploration of the very violent processes in the  universe  that produce X-rays. Unlike  visible light , which gives a relatively stable view of the universe, the X-ray universe is unstable. It features  stars  being torn apart by  black holes ,  galactic collisions , and  novae , and  neutron stars  that build up layers of  plasma  that then  explode  into  space . [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5123", "text": "An  X-ray laser  device was proposed as part of the  Reagan Administration 's  Strategic Defense Initiative  in the 1980s, but the only test of the device (a sort of laser \"blaster\" or  death ray , powered by a thermonuclear explosion) gave inconclusive results. For technical and political reasons, the overall project (including the X-ray laser) was defunded (though was later revived by the second  Bush Administration  as  National Missile Defense  using different technologies). [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5124", "text": "Phase-contrast X-ray imaging  refers to a variety of techniques that use phase information of an X-ray beam to form the image. Due to its good sensitivity to density differences, it is especially useful for imaging soft tissues. It has become an important method for visualizing cellular and histological structures in a wide range of biological and medical studies. There are several technologies being used for X-ray phase-contrast imaging, all using different principles to convert phase variations in the X-rays emerging from an object into intensity variations. [ 71 ] [ 72 ]  These include propagation-based phase contrast, [ 73 ]   Talbot  interferometry, [ 72 ]  refraction-enhanced imaging, [ 74 ]  and X-ray interferometry. [ 75 ]  These methods provide higher contrast compared to normal absorption-based X-ray imaging, making it possible to distinguish from each other details that have almost similar density. A disadvantage is that these methods require more sophisticated equipment, such as  synchrotron  or  microfocus  X-ray sources,  X-ray optics , and high resolution X-ray detectors. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5125", "text": "X-rays with high  photon energies  above 5\u201310\u00a0keV (below 0.2\u20130.1\u00a0nm wavelength) are called  hard X-rays , while those with lower energy (and longer wavelength) are called  soft X-rays . [ 76 ]  The intermediate range with photon energies of several keV is often referred to as  tender X-rays . Due to their penetrating ability, hard X-rays are widely used to image the inside of objects (e.g. in  medical radiography  and  airport security ). The term  X-ray  is  metonymically  used to refer to a  radiographic  image produced using this method, in addition to the method itself. Since the wavelengths of hard X-rays are similar to the size of atoms, they are also useful for determining crystal structures by  X-ray crystallography . By contrast, soft X-rays are easily absorbed in air; the  attenuation length  of 600\u00a0eV (~2\u00a0nm) X-rays in water is less than 1\u00a0micrometer. [ 77 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5126", "text": "There is no consensus for a definition distinguishing between X-rays and  gamma rays . One common practice is to distinguish between the two types of radiation based on their source: X-rays are emitted by  electrons , while gamma rays are emitted by the  atomic nucleus . [ 78 ] [ 79 ] [ 80 ] [ 81 ]  This definition has several problems: other processes can also generate these high-energy  photons , or sometimes the method of generation is not known. One common alternative is to distinguish X- and gamma radiation on the basis of wavelength (or, equivalently, frequency or photon energy), with radiation shorter than some arbitrary wavelength, such as 10 \u221211 \u00a0m (0.1\u00a0 \u00c5 ), defined as gamma radiation. [ 82 ]  This criterion assigns a photon to an unambiguous category, but is only possible if wavelength is known. (Some measurement techniques do not distinguish between detected wavelengths.) However, these two definitions often coincide since the electromagnetic radiation emitted by  X-ray tubes  generally has a longer wavelength and lower photon energy than the radiation emitted by  radioactive   nuclei . [ 78 ]  Occasionally, one term or the other is used in specific contexts due to historical precedent, based on measurement (detection) technique, or based on their intended use rather than their wavelength or source.\nThus, gamma-rays generated for medical and industrial uses, for example  radiotherapy , in the ranges of 6\u201320\u00a0 MeV , can in this context also be referred to as X-rays. [ 83 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5127", "text": "X-ray  photons  carry enough energy to  ionize  atoms and disrupt  molecular bonds . This makes it a type of  ionizing radiation , and therefore harmful to living  tissue . A very high  radiation dose  over a short period of time causes burns and  radiation sickness , while lower doses can give an increased risk of  radiation-induced cancer . In medical imaging, this increased cancer risk is generally greatly outweighed by the benefits of the examination. The ionizing capability of X-rays can be used in  cancer treatment  to kill  malignant   cells  using  radiation therapy . It is also used for material characterization using  X-ray spectroscopy . [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5128", "text": "Hard X-rays can traverse relatively thick objects without being much  absorbed  or  scattered . For this reason, X-rays are widely used to  image  the inside of visually opaque objects. The most often seen applications are in medical  radiography  and  airport security  scanners, but similar techniques are also important in industry (e.g.  industrial radiography  and  industrial CT scanning ) and research (e.g.  small animal CT ). The  penetration depth  varies with several  orders of magnitude  over the X-ray spectrum. This allows the photon energy to be adjusted for the application so as to give sufficient  transmission  through the object and at the same time provide good  contrast  in the image. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5129", "text": "X-rays have much shorter wavelengths than visible light, which makes it possible to probe structures much smaller than can be seen using a normal  microscope . This property is used in  X-ray microscopy  to acquire high-resolution images, and also in  X-ray crystallography  to determine the positions of  atoms  in  crystals . [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5130", "text": "X-rays interact with matter in three main ways, through  photoabsorption ,  Compton scattering , and  Rayleigh scattering . The strength of these interactions depends on the energy of the X-rays and the elemental composition of the material, but not much on chemical properties, since the X-ray photon energy is much higher than chemical binding energies. Photoabsorption or photoelectric absorption is the dominant interaction mechanism in the soft X-ray regime and for the lower hard X-ray energies. At higher energies, Compton scattering dominates. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5131", "text": "The probability of a photoelectric absorption per unit mass is approximately proportional to  \n \n \n \n \n Z \n \n 3 \n \n \n \n / \n \n \n E \n \n 3 \n \n \n \n \n {\\textstyle Z^{3}/E^{3}} \n \n , where  \n \n \n \n Z \n \n \n {\\textstyle Z} \n \n  is the  atomic number  and  \n \n \n \n E \n \n \n {\\textstyle E} \n \n  is the energy of the incident photon. [ 84 ]  This rule is not valid close to inner shell electron binding energies where there are abrupt changes in interaction probability, so called  absorption edges . However, the general trend of high  absorption coefficients  and thus short  penetration depths  for low photon energies and high atomic numbers is very strong. For soft tissue, photoabsorption dominates up to about 26\u00a0keV photon energy where Compton scattering takes over. For higher atomic number substances, this limit is higher. The high amount of  calcium  ( \n \n \n \n Z \n = \n 20 \n \n \n {\\textstyle Z=20} \n \n ) in bones, together with their high density, is what makes them show up so clearly on medical radiographs. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5132", "text": "A photoabsorbed photon transfers all its energy to the electron with which it interacts, thus ionizing the atom to which the electron was bound and producing a photoelectron that is likely to ionize more atoms in its path. An outer electron will fill the vacant electron position and produce either a characteristic X-ray or an  Auger electron . These effects can be used for elemental detection through  X-ray spectroscopy  or  Auger electron spectroscopy . [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5133", "text": "Compton scattering is the predominant interaction between X-rays and soft tissue in medical imaging. [ 85 ]  Compton scattering is an  inelastic scattering  of the X-ray photon by an outer shell electron. Part of the energy of the photon is transferred to the scattering electron, thereby ionizing the atom and increasing the wavelength of the X-ray. The scattered photon can go in any direction, but a direction similar to the original direction is more likely, especially for  high-energy X-rays . The probability for different scattering angles is described by the  Klein\u2013Nishina formula . The transferred energy can be directly obtained from the scattering angle from the  conservation of energy  and  momentum . [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5134", "text": "Rayleigh scattering is the dominant  elastic scattering  mechanism in the X-ray regime. [ 86 ]  Inelastic forward scattering gives rise to the refractive index, which for X-rays is only slightly below 1. [ 87 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5135", "text": "Whenever charged particles (electrons or ions) of sufficient energy hit a material, X-rays are produced."}
{"_id": "WikiPedia_Radiology$$$corpus_5136", "text": "X-rays can be generated by an  X-ray tube , a  vacuum tube  that uses a high voltage to accelerate the  electrons  released by a  hot cathode  to a high velocity. The high velocity electrons collide with a metal target, the  anode , creating the X-rays. [ 90 ]  In medical X-ray tubes the target is usually  tungsten  or a more crack-resistant alloy of  rhenium  (5%) and tungsten (95%), but sometimes  molybdenum  for more specialized applications, such as when softer X-rays are needed as in mammography. In crystallography, a copper target is most common, with  cobalt  often being used when fluorescence from iron content in the sample might otherwise present a problem. When even lower energies are needed, as in  X-ray photoelectron spectroscopy , the K \u03b1  X-rays from an aluminium or magnesium target are often used. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5137", "text": "The maximum energy of the produced X-ray  photon  is limited by the energy of the incident electron, which is equal to the voltage on the tube times the electron charge, so an 80\u00a0kV tube cannot create X-rays with an energy greater than 80\u00a0keV. When the electrons hit the target, X-rays are created by two different atomic processes: [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5138", "text": "So, the resulting output of a tube consists of a continuous  Bremsstrahlung  spectrum falling off to zero at the tube voltage, plus several spikes at the characteristic lines. The voltages used in diagnostic X-ray tubes range from roughly 20\u00a0kV to 150\u00a0kV and thus the highest energies of the X-ray photons range from roughly 20\u00a0keV to 150\u00a0keV. [ 91 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5139", "text": "Both of these X-ray production processes are inefficient, with only about one percent of the electrical energy used by the tube converted into X-rays, and thus most of the  electric power  consumed by the tube is released as waste heat. When producing a usable flux of X-rays, the X-ray tube must be designed to dissipate the excess heat."}
{"_id": "WikiPedia_Radiology$$$corpus_5140", "text": "A specialized source of X-rays which is becoming widely used in research is  synchrotron radiation , which is generated by  particle accelerators . Its unique features are X-ray outputs many orders of magnitude greater than those of X-ray tubes, wide X-ray spectra, excellent  collimation , and  linear polarization . [ 92 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5141", "text": "Short nanosecond bursts of X-rays peaking at 15\u00a0keV in energy may be reliably produced by peeling pressure-sensitive adhesive tape from its backing in a moderate vacuum. This is likely to be the result of recombination of electrical charges produced by  triboelectric charging . The intensity of X-ray  triboluminescence  is sufficient for it to be used as a source for X-ray imaging. [ 93 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5142", "text": "X-rays can also be produced by fast protons or other positive ions. The proton-induced X-ray emission or  particle-induced X-ray emission  is widely used as an analytical procedure. For high energies, the production  cross section  is proportional to  Z 1 2 Z 2 \u22124 , where  Z 1  refers to the  atomic number  of the ion,  Z 2  refers to that of the target atom. [ 94 ]  An overview of these cross sections is given in the same reference."}
{"_id": "WikiPedia_Radiology$$$corpus_5143", "text": "X-rays are also produced in lightning accompanying  terrestrial gamma-ray flashes . The underlying mechanism is the acceleration of electrons in lightning related electric fields and the subsequent production of photons through  Bremsstrahlung . [ 95 ]  This produces photons with energies of some few  keV  and several tens of MeV. [ 96 ]  In laboratory discharges with a gap size of approximately 1\u00a0meter length and a peak voltage of 1\u00a0MV, X-rays with a characteristic energy of 160\u00a0keV are observed. [ 97 ]  A possible explanation is the encounter of two  streamers  and the production of high-energy  run-away electrons ; [ 98 ]  however, microscopic simulations have shown that the duration of electric field enhancement between two streamers is too short to produce a significant number of run-away electrons. [ 99 ]  Recently, it has been proposed that air perturbations in the vicinity of streamers can facilitate the production of run-away electrons and hence of X-rays from discharges. [ 100 ] [ 101 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5144", "text": "X-ray detectors vary in shape and function depending on their purpose. Imaging detectors such as those used for  radiography  were originally based on  photographic plates  and later  photographic film , but are now mostly replaced by various  digital  detector types such as  image plates  and  flat panel detectors . For  radiation protection  direct exposure hazard is often evaluated using  ionization chambers , while  dosimeters  are used to measure the  radiation dose  the person has been exposed to. X-ray  spectra  can be measured either by energy dispersive or wavelength dispersive  spectrometers . For  X-ray diffraction  applications, such as  X-ray crystallography ,  hybrid photon counting detectors  are widely used. [ 102 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5145", "text": "Since R\u00f6ntgen's discovery that X-rays can identify bone structures, X-rays have been used for  medical imaging . [ 103 ]  The first medical use was less than a month after his paper on the subject. [ 39 ]  Up to 2010, five\u00a0billion medical imaging examinations had been conducted worldwide. [ 104 ]  Radiation exposure from medical imaging in 2006 made up about 50% of total ionizing radiation exposure in the United States. [ 105 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5146", "text": "Projectional radiography  is the practice of producing two-dimensional images using X-ray radiation. Bones contain a high concentration of  calcium , which, due to its relatively high  atomic number , absorbs X-rays efficiently. This reduces the amount of X-rays reaching the detector in the shadow of the bones, making them clearly visible on the radiograph. The lungs and trapped gas also show up clearly because of lower absorption compared to tissue, while differences between tissue types are harder to see. [ 106 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5147", "text": "Projectional radiographs are useful in the detection of  pathology  of the  skeletal system  as well as for detecting some disease processes in  soft tissue . Some notable examples are the very common  chest X-ray , which can be used to identify lung diseases such as  pneumonia , lung cancer, or  pulmonary edema , and the  abdominal x-ray , which can detect  bowel (or intestinal) obstruction , free air (from visceral perforations), and free fluid (in  ascites ). X-rays may also be used to detect pathology such as  gallstones  (which are rarely  radiopaque ) or  kidney stones  which are often (but not always) visible. Traditional plain X-rays are less useful in the imaging of soft tissues such as the brain or  muscle . One area where projectional radiographs are used extensively is in evaluating how an orthopedic  implant , such as a knee, hip or shoulder replacement, is situated in the body with respect to the surrounding bone. This can be assessed in two dimensions from plain radiographs, or it can be assessed in three dimensions if a technique called '2D to 3D registration' is used. This technique purportedly negates projection errors associated with evaluating implant position from plain radiographs. [ 107 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5148", "text": "Dental radiography  is commonly used in the diagnoses of common oral problems, such as  cavities ."}
{"_id": "WikiPedia_Radiology$$$corpus_5149", "text": "In medical diagnostic applications, the low energy (soft) X-rays are unwanted, since they are totally absorbed by the body, increasing the radiation dose without contributing to the image. Hence, a thin metal sheet, often of aluminium, called an  X-ray filter , is usually placed over the window of the X-ray tube, absorbing the low energy part in the spectrum. This is called  hardening  the beam since it shifts the center of the spectrum towards higher energy (or harder) X-rays."}
{"_id": "WikiPedia_Radiology$$$corpus_5150", "text": "To generate an image of the  cardiovascular system , including the arteries and veins ( angiography ) an initial image is taken of the anatomical region of interest. A second image is then taken of the same region after an iodinated  contrast agent  has been injected into the blood vessels within this area. These two images are then digitally subtracted, leaving an image of only the iodinated contrast outlining the blood vessels. The  radiologist  or surgeon then compares the image obtained to normal anatomical images to determine whether there is any damage or blockage of the vessel."}
{"_id": "WikiPedia_Radiology$$$corpus_5151", "text": "Computed tomography  (CT scanning) is a medical imaging modality where  tomographic images  or slices of specific areas of the body are obtained from a large series of two-dimensional X-ray images taken in different directions. [ 108 ]  These cross-sectional images can be combined into a  three-dimensional  image of the inside of the body. [ 109 ]  CT scans are a quicker and more cost effective imaging modality that can be used for diagnostic and therapeutic purposes in various medical disciplines. [ 109 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5152", "text": "Fluoroscopy  is an imaging technique commonly used by physicians or  radiation therapists  to obtain real-time moving images of the internal structures of a patient through the use of a fluoroscope. [ 110 ]  In its simplest form, a fluoroscope consists of an X-ray source and a fluorescent screen, between which a patient is placed. However, modern fluoroscopes couple the screen to an  X-ray image intensifier  and  CCD   video camera  allowing the images to be recorded and played on a monitor. This method may use a contrast material. Examples include cardiac catheterization (to examine for  coronary artery blockages ), embolization procedures (to stop bleeding during  hemorrhoidal artery embolization ), and barium swallow (to examine for  esophageal disorders  and swallowing disorders). As of recent, modern fluoroscopy utilizes short bursts of x-rays, rather than a continuous beam, to effectively lower radiation exposure for both the patient and operator. [ 110 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5153", "text": "The use of X-rays as a treatment is known as  radiation therapy  and is largely used for the management (including  palliation ) of cancer; it requires higher radiation doses than those received for imaging alone. X-rays beams are used for treating skin cancers using lower energy X-ray beams while higher energy beams are used for treating cancers within the body such as brain, lung, prostate, and breast. [ 111 ] [ 112 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5154", "text": "X-rays are a form of  ionizing radiation , and are classified as a  carcinogen  by both the World Health Organization's  International Agency for Research on Cancer  and the U.S. government. [ 104 ] [ 113 ]   Diagnostic X-rays (primarily from CT scans due to the large dose used) increase the risk of developmental problems and cancer in those exposed. [ 114 ] [ 115 ] [ 116 ]   It is estimated that 0.4% of current cancers in the United States are due to  computed tomography  (CT scans) performed in the past and that this may increase to as high as 1.5\u20132% with 2007 rates of CT usage. [ 117 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5155", "text": "Experimental and epidemiological data currently do not support the proposition that there is a  threshold dose of radiation  below which there is no increased risk of cancer. [ 118 ]  However, this is under increasing doubt. [ 119 ]  Cancer risk can start at the exposure of 1100 mGy. [ 120 ]  It is estimated that the additional radiation from diagnostic X-rays will increase the average person's cumulative risk of getting cancer by age 75 by 0.6\u20133.0%. [ 121 ]  The amount of absorbed radiation depends upon the type of X-ray test and the body part involved. [ 117 ]  CT and fluoroscopy entail higher doses of radiation than do plain X-rays."}
{"_id": "WikiPedia_Radiology$$$corpus_5156", "text": "To place the increased risk in perspective, a plain chest X-ray will expose a person to the same amount from  background radiation  that people are exposed to (depending upon location) every day over 10 days, while exposure from a dental X-ray is approximately equivalent to 1 day of environmental background radiation. [ 122 ]  Each such X-ray would add less than 1 per 1,000,000 to the lifetime cancer risk. An abdominal or chest CT would be the equivalent to 2\u20133 years of background radiation to the whole body, or 4\u20135 years to the abdomen or chest, increasing the lifetime cancer risk between 1 per 1,000 to 1 per 10,000. [ 122 ]  This is compared to the roughly 40% chance of a US citizen developing cancer during their lifetime. [ 123 ]  For instance, the effective dose to the torso from a CT scan of the chest is about 5\u00a0mSv, and the absorbed dose is about 14\u00a0mGy. [ 124 ]  A head CT scan (1.5\u00a0mSv, 64\u00a0mGy) [ 125 ]  that is performed once with and once without contrast agent, would be equivalent to 40 years of background radiation to the head. Accurate estimation of effective doses due to CT is difficult with the estimation uncertainty range of about \u00b119% to \u00b132% for adult head scans depending upon the method used. [ 126 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5157", "text": "The risk of radiation is greater to a fetus, so in pregnant patients, the benefits of the investigation (X-ray) should be balanced with the potential hazards to the fetus. [ 127 ] [ 128 ]  If there is 1 scan in 9 months, it can be harmful to the fetus. [ 129 ]  Therefore, women who are pregnant get ultrasounds as their diagnostic imaging because this does not use radiation. [ 129 ]  If there is too much radiation exposure there could be harmful effects on the fetus or the reproductive organs of the mother. [ 129 ]  In the US, there are an estimated 62\u00a0million CT scans performed annually, including more than 4\u00a0million on children. [ 117 ]  Avoiding unnecessary X-rays (especially CT scans) reduces radiation dose and any associated cancer risk. [ 130 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5158", "text": "Medical X-rays are a significant source of human-made radiation exposure. In 1987, they accounted for 58% of exposure from human-made sources in the United States. Since human-made sources accounted for only 18% of the total radiation exposure, most of which came from natural sources (82%), medical X-rays only accounted for 10% of  total  American radiation exposure; medical procedures as a whole (including  nuclear medicine ) accounted for 14% of total radiation exposure. By 2006, however, medical procedures in the United States were contributing much more ionizing radiation than was the case in the early 1980s. In 2006, medical exposure constituted nearly half of the total radiation exposure of the U.S. population from all sources. The increase is traceable to the growth in the use of medical imaging procedures, in particular  computed tomography  (CT), and to the growth in the use of nuclear medicine. [ 105 ] [ 131 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5159", "text": "Dosage due to dental X-rays varies significantly depending on the procedure and the technology (film or digital). Depending on the procedure and the technology, a single dental X-ray of a human results in an exposure of 5 to 40\u00a0\u03bcSv. A full mouth series of X-rays may result in an exposure of up to 60 (digital) to 180 (film) \u03bcSv, for a yearly average of up to 400\u00a0\u03bcSv. [ 132 ] [ 133 ] [ 134 ] [ 135 ] [ 136 ] [ 137 ] [ 138 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5160", "text": "Financial incentives have been shown to have a significant impact on X-ray use with doctors who are paid a separate fee for each X-ray providing more X-rays. [ 139 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5161", "text": "Early photon tomography or EPT [ 140 ]  (as of 2015) along with other techniques [ 141 ]  are being researched as potential alternatives to X-rays for imaging applications."}
{"_id": "WikiPedia_Radiology$$$corpus_5162", "text": "Other notable uses of X-rays include:"}
{"_id": "WikiPedia_Radiology$$$corpus_5163", "text": "While generally considered invisible to the human eye, in special circumstances X-rays can be visible. Brandes, in an experiment a short time after R\u00f6ntgen's landmark 1895 paper, reported after dark adaptation and placing his eye close to an X-ray tube, seeing a faint \"blue-gray\" glow which seemed to originate within the eye itself. [ 146 ]  Upon hearing this, R\u00f6ntgen reviewed his record books and found he too had seen the effect. When placing an X-ray tube on the opposite side of a wooden door R\u00f6ntgen had noted the same blue glow, seeming to emanate from the eye itself, but thought his observations to be spurious because he only saw the effect when he used one type of tube. Later he realized that the tube which had created the effect was the only one powerful enough to make the glow plainly visible and the experiment was thereafter readily repeatable. The knowledge that X-rays are actually faintly visible to the dark-adapted naked eye has largely been forgotten today; this is probably due to the desire not to repeat what would now be seen as a recklessly dangerous and potentially harmful experiment with  ionizing radiation . It is not known what exact mechanism in the eye produces the visibility: it could be due to conventional detection (excitation of  rhodopsin  molecules in the retina), direct excitation of retinal nerve cells, or secondary detection via, for instance, X-ray induction of  phosphorescence  in the eyeball with conventional retinal detection of the secondarily produced visible light. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5164", "text": "Though X-rays are otherwise invisible, it is possible to see the  ionization  of the air molecules if the intensity of the X-ray beam is high enough. The beamline from the  wiggler  at the   European Synchrotron Radiation Facility [ 147 ]  is one example of such high intensity. [ 148 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5165", "text": "The measure of X-rays  ionizing  ability is called the exposure: [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5166", "text": "However, the effect of ionizing radiation on matter (especially living tissue) is more closely related to the amount of energy deposited into them rather than the  charge  generated. This measure of energy absorbed is called the  absorbed dose : [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5167", "text": "The  equivalent dose  is the measure of the biological effect of radiation on human tissue. For X-rays it is equal to the  absorbed dose . [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5168", "text": "X-ray detectors  are devices used to measure the  flux ,  spatial  distribution,  spectrum , and/or other properties of  X-rays ."}
{"_id": "WikiPedia_Radiology$$$corpus_5169", "text": "Detectors can be divided into two major categories: imaging detectors (such as  photographic plates  and X-ray film ( photographic film ), now mostly replaced by various  digitizing  devices like  image plates  or  flat panel detectors ) and dose measurement devices (such as  ionization chambers ,  Geiger counters , and  dosimeters  used to measure the local  radiation exposure ,  dose , and/or dose rate, for example, for verifying that  radiation protection  equipment and procedures are effective on an ongoing basis)."}
{"_id": "WikiPedia_Radiology$$$corpus_5170", "text": "To obtain an image with any type of image detector the part of the patient to be X-rayed is placed between the X-ray source and the image receptor to produce a shadow of the internal structure of that particular part of the body. X-rays are partially blocked (\"attenuated\") by dense tissues such as bone, and pass more easily through soft tissues. Areas where the X-rays strike darken when developed, causing bones to appear lighter than the surrounding soft tissue."}
{"_id": "WikiPedia_Radiology$$$corpus_5171", "text": "Contrast compounds containing  barium  or  iodine , which are  radiopaque , can be ingested in the gastrointestinal tract (barium) or injected in the artery or veins to highlight these vessels. The contrast compounds have high atomic numbered elements in them that (like bone) essentially block the X-rays and hence the once hollow organ or vessel can be more readily seen. In the pursuit of nontoxic contrast materials, many types of high atomic number elements were evaluated. Some elements chosen proved to be harmful\u00a0\u2013 for example,  thorium  was once used as a contrast medium ( Thorotrast )\u00a0\u2013 which turned out to be toxic, causing a very high incidence of cancer decades after use. Modern contrast material has improved and, while there is no way to determine who may have a sensitivity to the contrast, the incidence of serious allergic reactions is low. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5172", "text": "Typical x-ray film contains  silver halide  crystal \"grains\", typically primarily  silver bromide . [ 2 ]  Grain size and composition can be adjusted to affect the film properties, for example to improve  resolution  in the developed image. [ 3 ]  When the film is exposed to radiation the halide is  ionised  and free  electrons  are trapped in  crystal defects  (forming a  latent image ). Silver ions are attracted to these defects and  reduced , creating clusters of  transparent  silver  atoms . [ 4 ]  In the developing process these are converted to  opaque   silver  atoms which form the viewable image, darkest where the most radiation was detected. Further developing steps stabilise the sensitised grains and remove unsensitised grains to prevent further exposure (e.g. from  visible light ). [ 5 ] :\u200a159\u200a [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5173", "text": "The first radiographs (X-ray images) were made by the action of X-rays on sensitized glass photographic plates. X-ray film (photographic film) soon replaced the glass plates, and film has been used for decades to acquire (and display) medical and industrial images. [ 7 ]  Gradually, digital  computers  gained the ability to store and display enough data to make digital imaging possible. Since the 1990s, computerized radiography and digital radiography have been replacing photographic film in medical and dental applications, though film technology remains in widespread use in industrial radiography processes (e.g. to inspect welded seams). The metal  silver  (formerly necessary to the radiographic & photographic industries) is a  non-renewable resource  although silver can easily be reclaimed from spent X-ray film. [ 8 ]  Where X-ray films required wet processing facilities, newer digital technologies do not. Digital archiving of images also saves physical storage space. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5174", "text": "Phosphor plate radiography [ 10 ]  is a method of recording X-rays using  photostimulated luminescence  (PSL), pioneered by  Fuji  in the 1980s. [ 11 ]  A photostimulable phosphor plate (PSP) is used in place of the photographic plate. After the plate is X-rayed, excited electrons in the phosphor material remain 'trapped' in ' colour centres ' in the crystal lattice until stimulated by a laser beam passed over the plate surface. [ 12 ]  The  light  given off during laser stimulation is collected by a  photomultiplier tube , and the resulting signal is converted into a digital image by computer technology. The PSP plate can be reused, and existing X-ray equipment requires no modification to use them. The technique may also be known as computed radiography (CR). [ 13 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5175", "text": "X-rays are also used in \"real-time\" procedures such as  angiography  or contrast studies of the hollow organs (e.g.  barium enema  of the small or large intestine) using  fluoroscopy .  Angioplasty , medical interventions of the arterial system, rely heavily on X-ray-sensitive contrast to identify potentially treatable lesions."}
{"_id": "WikiPedia_Radiology$$$corpus_5176", "text": "Solid state detectors use  semiconductors  to detect x-rays. Direct digital detectors are so-called because they directly convert x-ray photons to electrical charge and thus a digital image. Indirect systems may have intervening steps for example first converting x-ray photons to  visible light , and then an electronic signal. Both systems typically use  thin film transistors  to read out and convert the electronic signal to a digital image. Unlike film or CR no manual scanning or development step is required to obtain a digital image, and so in this sense both systems are \"direct\". [ 14 ]  Both types of system have considerably higher  quantum efficiency  than CR. [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5177", "text": "Since the 1970s,  silicon  or  germanium  doped with  lithium  (Si(Li) or Ge(Li))  semiconductor detectors  have been developed. [ 15 ]  X-ray photons are converted to electron-hole pairs in the semiconductor and are collected to detect the X-rays. When the temperature is low enough (the detector is cooled by  Peltier effect  or even cooler  liquid nitrogen ), it is possible to directly determine the X-ray energy spectrum; this method is called  energy-dispersive X-ray spectroscopy  (EDX or EDS); it is often used in small  X-ray fluorescence   spectrometers .  Silicon drift detectors  (SDDs), produced by conventional  semiconductor fabrication , provide a cost-effective and high resolving power radiation measurement. [ 16 ]  Unlike conventional X-ray detectors, such as Si(Li), they do not need to be cooled with liquid nitrogen. These detectors are rarely used for imaging and are only efficient at low energies. [ 17 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5178", "text": "Practical application in  medical imaging  started in the early 2000s. [ 18 ]  Amorphous  selenium  is used in commercial large area flat panel X-ray detectors for  mammography  and general  radiography  due to its high spatial resolution and x-ray absorbing properties. [ 19 ]  However Selenium's low atomic number means a thick layer is required to achieve sufficient sensitivity. [ 20 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5179", "text": "Cadmium telluride  ( Cd Te ), and its alloy with  zinc ,  cadmium zinc telluride , is considered one of the most promising semiconductor materials for x-ray detection due to its wide  band-gap  and high quantum number resulting in room temperature operation with high efficiency. [ 21 ] [ 22 ]  Current applications include  bone densitometry  and  SPECT  but flat panel detectors suitable for radiographic imaging are not yet in production. [ 23 ]  Current research and development is focused around energy resolving   pixel detectors , such as  CERN 's  Medipix  detector and  Science and Technology Facilities Council 's  HEXITEC  detector. [ 24 ] [ 25 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5180", "text": "Common  semiconductor   diodes , such as  PIN photodiodes  or a  1N4007 , will produce a small amount of current in  photovoltaic mode  when placed in an X-ray beam. [ 26 ] [ 27 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5181", "text": "Indirect detectors are made up of a  scintillator  to convert x-rays to visible light, which is read by a TFT array. This can provide sensitivity advantages over current (amorphous selenium) direct detectors, albeit with a potential trade-off in resolution. [ 20 ]  Indirect  flat panel detectors  (FPDs) are in widespread use today in medical, dental, veterinary, and industrial applications."}
{"_id": "WikiPedia_Radiology$$$corpus_5182", "text": "The TFT array consists of a sheet of glass covered with a thin layer of silicon that is in an amorphous or disordered state. At a microscopic scale, the silicon has been imprinted with millions of transistors arranged in a highly ordered array, like the grid on a sheet of graph paper. Each of these  thin-film transistors  (TFTs) is attached to a light-absorbing photodiode making up an individual  pixel  (picture element).  Photons  striking the photodiode are converted into two  carriers of electrical charge , called electron-hole pairs. Since the number of charge carriers produced will vary with the intensity of incoming light photons, an electrical pattern is created that can be swiftly converted to a voltage and then a digital signal, which is interpreted by a computer to produce a digital image. Although silicon has outstanding electronic properties, it is not a particularly good absorber of X-ray photons. For this reason, X-rays first impinge upon  scintillators  made from such materials as  gadolinium oxysulfide  or  caesium iodide . The scintillator absorbs the X-rays and converts them into visible light photons that then pass onto the photodiode array."}
{"_id": "WikiPedia_Radiology$$$corpus_5183", "text": "X-rays going through a  gas  will  ionize  it, producing positive  ions  and free  electrons . An incoming photon will create a number of such ion pairs  proportional  to its energy. If there is an  electric field  in the gas chamber ions and electrons will move in different directions and thereby cause a detectable  current . The behaviour of the gas will depend on the applied  voltage  and the geometry of the chamber. This gives rise to a few different types of gas detectors described below."}
{"_id": "WikiPedia_Radiology$$$corpus_5184", "text": "Ionization chambers  use a relatively low electric field of about 100 V/cm to extract all ions and electrons before they recombine. [ 28 ]  This gives a steady current proportional to the  dose  rate the gas is exposed to. [ 7 ]  Ion chambers are widely used as hand held radiation  survey meters  to check radiation dose levels."}
{"_id": "WikiPedia_Radiology$$$corpus_5185", "text": "Proportional counters  use a geometry with a thin positively charged  anode  wire in the center of a cylindrical chamber. Most of the gas volume will act as an ionization chamber, but in the region closest to the wire the electric field is high enough to make the electrons ionize gas molecules. This will create an  avalanche effect  greatly increasing the output signal. Since every electron cause an avalanche of approximately the same size the collected charge is proportional to the number of ion pairs created by the absorbed x-ray. This makes it possible to measure the energy of each incoming photon."}
{"_id": "WikiPedia_Radiology$$$corpus_5186", "text": "Geiger\u2013M\u00fcller counters  use an even higher electric field so that  UV-photons  are created. [ 29 ]  These start new avalanches, eventually resulting in a total ionization of the gas around the anode wire. This makes the signal very strong, but causes a dead time after each event and makes it impossible to measure the X-ray energies. [ 30 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5187", "text": "Gas detectors are usually single pixel detectors measuring only the average dose rate over the gas volume or the number of interacting photons as explained above, but they can be made spatially resolving by having many crossed wires in a  wire chamber ."}
{"_id": "WikiPedia_Radiology$$$corpus_5188", "text": "It was demonstrated in the 1960s that silicon PN  solar cells  are suitable for detection of all forms of ionizing radiation including  extreme UV , soft X-rays, and hard X-rays. This form of detection operates via  photoionization , a process where ionizing radiation strikes an atom and releases a free electron. [ 31 ]  This type of  broadband ionizing radiation sensor  requires a solar cell, an  ammeter , and a visible light filter on top of the solar cell that allows the ionizing radiation to hit the solar cell while blocking unwanted wavelengths."}
{"_id": "WikiPedia_Radiology$$$corpus_5189", "text": "Self-developing radiochromic film can provide very high resolution measurements, for dosimetry and profiling purposes, particularly in radiotherapy physics. [ 32 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5190", "text": "An  X-ray machine  is a device that uses  X-rays  for a variety of applications including  medicine ,  X-ray fluorescence , electronic assembly inspection, and measurement of material thickness in manufacturing operations. In medical applications, X-ray machines are used by  radiographers  to acquire x-ray images of the internal structures (e.g., bones) of living organisms, and also in  sterilization ."}
{"_id": "WikiPedia_Radiology$$$corpus_5191", "text": "An X-ray generator generally contains an  X-ray tube  to produce the X-rays. Possibly,  radioisotopes  can also be used to generate X-rays. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5192", "text": "An X-ray tube is a simple  vacuum tube  that contains a  cathode , which directs a stream of electrons into a vacuum, and an  anode , which collects the electrons and is made of tungsten to evacuate the heat generated by the collision. When the electrons collide with the target, about 1% of the resulting energy is emitted as  X-rays , with the remaining 99% released as heat. Due to the high energy of the electrons that reach relativistic speeds, the target is usually made of  tungsten  even if other material can be used particularly in XRF applications. [ citation needed ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5193", "text": "An X-ray generator also needs to contain a cooling system to cool the anode; many X-ray generators use water or oil recirculating systems. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5194", "text": "In medical imaging applications, an X-ray machine has a control console that is used by a radiologic technologist to select X-ray techniques suitable for the specific exam, a power supply that creates and produces the desired kVp (peak kilovoltage), mA (milliamperes, sometimes referred to as mAs which is actually mA multiplied by the desired exposure length) for the X-ray tube, and the X-ray tube itself."}
{"_id": "WikiPedia_Radiology$$$corpus_5195", "text": "The discovery of X-rays came from experimenting with  Crookes tubes , an early experimental electrical discharge tube invented by English physicist  William Crookes  around 1869\u20131875. In 1895,  Wilhelm R\u00f6ntgen  discovered X-rays emanating from Crookes tubes and the many uses for X-rays were immediately apparent. One of the first X-ray photographs was made of the hand of R\u00f6ntgen's wife. The image displayed both her wedding ring and bones. On January 18, 1896 an  X-ray machine  was formally displayed by  Henry Louis Smith . A fully functioning unit was introduced to the public at the  1904 World's Fair  by  Clarence Dally . [ 3 ]  The technology developed quickly: In 1909  M\u00f3nico S\u00e1nchez Moreno  had produced the first portable medical device and during World War I  Marie Curie  led the development of X-ray machines mounted in \"radiological cars\" to provide mobile X-ray services for military field hospitals."}
{"_id": "WikiPedia_Radiology$$$corpus_5196", "text": "In the 1940s and 1950s, X-ray machines were used in stores to help sell footwear. These were known as  Shoe-fitting fluoroscopes . However, as the harmful effects of  X-ray   radiation  were properly considered, they finally fell out of use. Shoe-fitting use of the device was first banned by the state of  Pennsylvania  in 1957. (They were more a clever marketing tool to attract customers, rather than a fitting aid.) Together with  Robert J. Van de Graaff ,  John G. Trump  developed one of the first million-volt X-ray generators."}
{"_id": "WikiPedia_Radiology$$$corpus_5197", "text": "An X-ray imaging system consists of a generator control console where the operator selects desired techniques to obtain a quality readable image(kVp, mA and exposure time), an x-ray generator which controls the x-ray tube current, x-ray tube kilovoltage and x-ray emitting exposure time, an  X-ray tube  that converts the kilovoltage and mA into actual x-rays and an image detection system which can be either a film (analog technology) or a digital capture system and a  PACS ."}
{"_id": "WikiPedia_Radiology$$$corpus_5198", "text": "X-ray machines are used in  health care  for visualising bone structures, during surgeries (especially orthopedic) to assist surgeons in reattaching broken bones with screws or structural plates, assisting cardiologists in locating blocked arteries and guiding stent placements or performing angioplasties and for other dense tissues such as  tumours . Non-medicinal applications include  security  and material analysis."}
{"_id": "WikiPedia_Radiology$$$corpus_5199", "text": "The main fields in which x-ray machines are used in medicine are  radiography , radiotherapy, and  fluoroscopic-type procedures . Radiography is generally used for fast, highly penetrating images, and is usually used in areas with a high bone content but can also be used to look for tumors such as with mammography imaging.  Some forms of radiography include:"}
{"_id": "WikiPedia_Radiology$$$corpus_5200", "text": "In fluoroscopy, imaging of the digestive tract is done with the help of a  radiocontrast agent  such as  barium sulfate , which is opaque to X-rays."}
{"_id": "WikiPedia_Radiology$$$corpus_5201", "text": "Radiotherapy  \u2014 the use of x-ray radiation to treat malignant and benign  cancer cells , a non-imaging application"}
{"_id": "WikiPedia_Radiology$$$corpus_5202", "text": "Fluoroscopy  is used in cases where real-time visualization is necessary (and is most commonly encountered in everyday life at  airport security ). Some medical applications of fluoroscopy include:"}
{"_id": "WikiPedia_Radiology$$$corpus_5203", "text": "X-rays are highly penetrating,  ionizing radiation , therefore X-ray machines are used to take pictures of dense tissues such as bones and teeth. This is because bones absorb the radiation more than the less dense  soft tissue . X-rays from a source pass through the body and onto a photographic cassette.  Areas where radiation is absorbed show up as lighter shades of grey (closer to white). This can be used to diagnose broken or fractured bones."}
{"_id": "WikiPedia_Radiology$$$corpus_5204", "text": "In 2012, European Commission of Radiation Protection set leakage radiation limit from X-ray generators such as X-ray tubes and CT machines as one mGy/hour at one metre distance from the machine. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5205", "text": "X-ray machines are used to screen objects non-invasively. Luggage at  airports  and student baggage at some  schools  are examined for possible weapons, including bombs. Prices of these Luggage X-rays vary from $50,000 to $300,000. The main parts of an X-ray Baggage Inspection System are the generator used to generate x-rays, the detector to detect radiation after passing through the baggage, signal processor unit (usually a PC) to process the incoming signal from the detector, and a conveyor system for moving baggage into the system. Portable pulsed X-ray Battery Powered X-ray Generator used in Security as shown in the figure provides EOD responders safer analysis of any possible target hazard."}
{"_id": "WikiPedia_Radiology$$$corpus_5206", "text": "When baggage is placed on the conveyor, it is moved into the machine by the operator. There is an  infrared  transmitter and receiver assembly to detect the baggage when it enters the tunnel. This assembly gives the signal to switch on the generator and signal processing system. The signal processing system processes incoming signals from the detector and reproduce an image based upon the type of material and material density inside the baggage. This image is then sent to the display unit."}
{"_id": "WikiPedia_Radiology$$$corpus_5207", "text": "The colour of the image displayed depends upon the material and material density\u00a0: organic material such as paper, clothes and most explosives are displayed in orange. Mixed materials such as aluminum are displayed in green. Inorganic materials such as copper are displayed in blue and non-penetrable items are displayed in black (some machines display this as a yellowish green or red). The darkness of the color depends upon the density or thickness of the material."}
{"_id": "WikiPedia_Radiology$$$corpus_5208", "text": "The material density determination is achieved by two-layer detector. The layers of the detector pixels are separated with a strip of metal. The metal absorbs soft rays, letting the shorter, more penetrating wavelengths through to the bottom layer of detectors, turning the detector to a crude two-band spectrometer."}
{"_id": "WikiPedia_Radiology$$$corpus_5209", "text": "A film of  carbon nanotubes  (as a cathode) that emits electrons at room temperature when exposed to an electrical field has been fashioned into an X-ray device. An array of these emitters can be placed around a target item to be scanned and the images from each emitter can be assembled by computer software to provide a 3-dimensional image of the target in a fraction of the time it takes using a conventional X-ray device. The system also allows rapid, precise control, enabling prospective physiological gated imaging. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5210", "text": "Engineers at the  University of Missouri  (MU),  Columbia , have invented a compact source of x-rays and other forms of radiation.\nThe radiation source is the size of a stick of gum and could be used to create portable x-ray scanners. A prototype handheld x-ray scanner using the source could be manufactured in as soon as three years. [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5211", "text": "An  X-ray image intensifier  (XRII) is an  image intensifier  that converts  X-rays  into visible light at higher  intensity  than the more traditional  fluorescent  screens can. Such intensifiers are used in X-ray imaging systems (such as  fluoroscopes ) to allow low-intensity X-rays to be converted to a conveniently  bright  visible light output. The device contains a low absorbency/scatter input window, typically aluminum, input fluorescent screen, photocathode, electron optics, output fluorescent screen and output window. These parts are all mounted in a high vacuum environment within glass or, more recently, metal/ceramic. By its  intensifying  effect, It allows the viewer to more easily see the structure of the object being imaged than fluorescent screens alone, whose images are dim. The XRII requires lower  absorbed doses  due to more efficient conversion of X-ray quanta to visible light. This device was originally introduced in 1948. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5212", "text": "The overall function of an image intensifier is to convert incident x-ray photons to light photons of sufficient intensity to provide a viewable image. This occurs in several stages. The input window is convex is shape, made up of aluminium to minimise the scattering of X-rays. The window is 1 mm in thickness. Once X-rays pass through the aluminium windows, it encounters input  phosphor  that converts X-rays into light photons. The thickness of input phosphor range from 300 to 450 micrometres reach a compromise between absorption efficiency of X-rays and spatial resolution. Thicker input phosphor has higher absorption efficiency but poor spatial resolution and vice versa. Sodium activated Caesium Iodide is typically used due to its higher conversion efficiency thanks to high  atomic number  and  mass attenuation coefficient , when compared to zinc-cadmium sulfide. The input phosphor are arranged into small tubes, to allow photons to pass through the tube, without scattering, this improving the spatial resolution. [ 2 ]  The light photons are then converted to  electrons  by a photocathode. The photocathode is made up of antimony caesium, which is to match the photons produced from input phosphor, thus maximise the efficiency of producing photoelectrons. The photocathode has a thickness of 20 nm with absorption efficacy of 10 to 15%. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5213", "text": "A  potential difference  (25-35 kilovolts) created between the anode and photocathode then accelerates these photoelectrons while  electron lenses  focus the beam down to the size of the output window. The output window is typically made of silver-activated zinc-cadmium sulfide and converts incident electrons back to visible light photons. [ 2 ]  At the input and output phosphors the number of photons is multiplied by several thousands, so that overall there is a large brightness gain. This gain makes image intensifiers highly sensitive to X-rays such that relatively low doses can be used for fluoroscopic procedures. [ 3 ] [ 4 ] [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5214", "text": "X-ray image intensifiers became available in the early 1950s and were viewed through a microscope. [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5215", "text": "Viewing of the output was via mirrors and optical systems until the adaption of television systems in the 1960s. [ 8 ]  Additionally, the output was able to be captured on systems with a 100mm cut film camera using pulsed outputs from an X-ray tube similar to a normal radiographic exposure; the difference being the II rather than a film screen cassette provided the image for the film to record."}
{"_id": "WikiPedia_Radiology$$$corpus_5216", "text": "The input screens range from 15\u201357\u00a0cm, with the 23\u00a0cm, 33\u00a0cm and 40\u00a0cm being among the most common. Within each image intensifier, the actual field size can be changed using the voltages applied to the internal electron optics to achieve magnification and reduced viewing size. For example, the 23\u00a0cm commonly used in cardiac applications can be set to a format of 23, 17, and 13\u00a0cm. Because the output screen remains fixed in size, the output appears to \"magnify\" the input image.  High-speed digitalisation with analogue video signal came about in the mid-1970s, with pulsed fluoroscopy developed in the mid-1980s harnessing low dose rapid switching X-ray tubes. In the late 1990s image intensifiers began being replaced with flat panel detectors (FPDs) on fluoroscopy machines giving competition to the image intensifiers. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5217", "text": "\"C-arm\" mobile fluoroscopy machines are often colloquially referred to as  image intensifiers  (or IIs), [ 10 ]  however strictly speaking the image intensifier is only one part of the machine (namely the detector)."}
{"_id": "WikiPedia_Radiology$$$corpus_5218", "text": "Fluoroscopy, using an X-ray machine with an image intensifier, has applications in many areas of medicine. Fluoroscopy allows live images to be viewed so that  image-guided surgery  is feasible. Common uses include  orthopedics ,  gastroenterology  and  cardiology . [ 11 ]  Less common applications can include  dentistry . [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5219", "text": "A system containing an  image intensifier  may be used either as a fixed piece of equipment in a dedicated screening room or as mobile equipment for use in an  operating theatre . A mobile fluoroscopy unit generally consists of two units, the  X-ray generator  and image detector (II) on a moveable C-arm, and a separate workstation unit used to store and manipulate the images. [ 13 ]  The patient is positioned between the two arms, typically on a  radiolucent  bed. Fixed systems may have a c-arm mounted to a ceiling gantry, with a separate control area. Most systems arranged as c-arms can have the image intensifier positioned above or below the patient (with the X-ray tube below or above respectively), although some static in room systems may have fixed orientations. [ 14 ]  From a  radiation protection  standpoint, under-couch (X-ray tube) operation is preferable as it reduces the amount of  scattered  radiation on operators and workers. [ 15 ] [ 16 ]  Smaller \"mini\" mobile c-arms are also available, primarily used to image extremities, for example for minor  hand surgery . [ 17 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5220", "text": "Flat Detectors are an alternative to Image Intensifiers. The advantages of this technology include: lower patient dose and increased image quality because the X-rays are always pulsed, and no deterioration of the image quality over time.  Despite FPD being at a higher cost than II/TV systems, the noteworthy changes in the physical size and accessibility for the patients is worth it, especially when dealing with paediatric patients. [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5221", "text": "X-ray Markers , also known as: anatomical side markers, [ 1 ]   Pb  markers,  lead  markers,  x-ray  lead markers, or radiographic film identification markers, are used to mark x-ray films, both in  hospitals  and in industrial workplaces (such as on  aeroplane  parts and  motors ). They are used on radiographic images to determine anatomical side of body, date of the procedure, and may include patients name."}
{"_id": "WikiPedia_Radiology$$$corpus_5222", "text": "Most X-ray markers consist of a right and a left letter with the  radiographer's  initials. There are also available markers to indicate positioning of the body e.g. supine, or as to time when performing procedures such as an  Intravenous pyelogram ."}
{"_id": "WikiPedia_Radiology$$$corpus_5223", "text": "It has been suggested that radiographic markers are a potential  fomite  for harmful bacteria such as  MRSA , and that they should be cleaned on a regular basis; this, however, is not always done. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5224", "text": "X-ray motion analysis  is a technique used to track the movement of objects using  X-rays . This is done by placing the subject to be imaged in the center of the X-ray beam and recording the motion using an  image intensifier  and a  high-speed camera , allowing for high quality videos sampled many times per second. Depending on the settings of the X-rays, this technique can visualize specific structures in an object, such as  bones  or  cartilage . X-ray motion analysis can be used to perform  gait analysis , analyze  joint  movement, or record the motion of bones obscured by  soft tissue . The ability to measure skeletal motions is a key aspect to one's understanding of vertebrate  biomechanics ,  energetics , and  motor control . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5225", "text": "Many X-ray studies are performed with a single X-ray emitter and camera. This type of imaging allows for tracking movements in the two-dimensional plane of the X-ray. Movements are performed parallel to the camera's imaging plane in order for the motion to be accurately tracked. [ 2 ]  In  gait analysis , planar X-ray studies are done in the  sagittal plane  to allow for highly accurate tracking of large movements. [ 3 ]  Methods have been developed to allow for estimating all  six degrees of freedom  of movement from a planar X-ray and a model of the tracked object. [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5226", "text": "Few movements are truly planar; [ 2 ]  planar X-ray imaging can capture the majority of movement, but not all of it. Accurately capturing and quantifying all three dimensions of movement requires a biplanar imaging system. [ 2 ]  Biplanar imaging is difficult to perform because many facilities have access to only one X-ray emitter. [ 1 ]  With the addition of a second X-ray and camera system, the 2-D plane of imaging expands to a 3-D volume of imaging at the intersection of the X-ray beams. Because the volume of imaging is at the intersection of two X-ray beams, the overall size of it is limited by the area of the X-ray emitters."}
{"_id": "WikiPedia_Radiology$$$corpus_5227", "text": "Motion capture techniques often use reflective markers for the image capturing. In X-ray imaging, markers that appear opaque in the X-ray images are utilized. [ 2 ]  This frequently involves using radio-opaque spheres attached to the subject. Markers can be implanted in the subject's bones, which would then appear visible in the X-ray images. [ 6 ]  This method requires surgical procedures for implanting and a healing period before the subject can undergo a motion analysis. For accurate 3-D tracking, at least three markers need to be implanted onto each bone to be tracked. [ 7 ]  Markers can also be placed on the subject's skin to track the motion of the underlying bones, though markers placed on the skin are sensitive to skin movement artifacts. These are errors in the measurement of the location of a skin-placed marker compared to a bone-implanted marker. This occurs at locations where soft tissue moves more freely than the overlaying skin. [ 2 ] [ 4 ] [ 6 ] [ 8 ]  The markers are then tracked relative to the X-ray camera(s) and the motions are mapped to the local anatomical bodies."}
{"_id": "WikiPedia_Radiology$$$corpus_5228", "text": "Emerging techniques and software are allowing for motion to be tracked without the need for radio-opaque markers. By using a 3-D model of the object being tracked, the object can be overlaid on the images of the X-ray video at each frame. [ 7 ]  The translations and rotations of the model, as opposed to a set of markers, are then tracked relative to the X-ray camera(s). [ 7 ]  Using a local coordinate system, these translations and rotations can then be mapped to standard anatomical movements. The 3-D model of the object is generated from any 3-D imaging technique, such as an MRI or CT scan. Markerless tracking has the benefit of being a non-invasive tracking method, avoiding any complications due to surgeries. One difficulty comes from generating the 3-D model in animal studies, as the animals are required to be sedated or sacrificed for the scan."}
{"_id": "WikiPedia_Radiology$$$corpus_5229", "text": "In planar X-ray imaging, the motions of the markers or bodies are tracked in a specialized software. An initial location guess is supplied by the user for the markers or bodies. The software, depending on its capabilities, requires the user to manually locate the markers or bodies for each frame of the video, or can automatically track the locations throughout the video. The automatic tracking has to be monitored for accuracy and may require manually relocating the markers or bodies. After the tracking data is generated for each marker or body of interest, the tracking is applied to the local anatomical bodies. For example, markers placed at the hip and knee would track the motion of the femur. Using knowledge of the local anatomy, these motions can then be translated into  anatomical terms of motion  in the plane of the X-ray. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5230", "text": "In biplanar X-ray imaging, the motions are also tracked in a specialized software. Similar to planar analysis, the user provides an initial location guess and either tracks the markers or bodies manually or the software can automatically track them. However, biplanar analysis requires that all tracking be done on both video frames at the same time, positioning the object in free space. Both X-ray cameras have to be calibrated using an object of known volume. This allows the software to locate the cameras' positions relative to each other and then allows the user to position the 3-D model of the object in line with both video frames. The tracking data is generated for each marker or body and then applied to the local anatomical bodies. The tracking data is then further defined as  anatomical terms of motion  in free space. [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5231", "text": "X-ray motion analysis can be used in  human gait analysis  to measure the  kinematics  of the lower limbs. Treadmill gait or overground gait [ 9 ]  can be measured depending on the mobility of the X-ray system. Other types of movements, such as a jump-cut maneuver, [ 10 ]  have also been recorded. By combining X-ray motion analysis with  force platforms , a  joint torque analysis  can be performed. [ 10 ] [ 11 ]   Rehabilitation  is an important application of X-ray motion analysis. X-ray imaging has been used for medical diagnostic purposes since shortly after its discovery in 1895. [ 12 ]  X-ray motion analysis can be utilized in joint imaging or analyzing joint-related diseases. It has been used to quantify  osteoarthritis  in the knee, [ 13 ]  estimate  knee cartilage  contact areas, [ 14 ]  and analyze the results of rotator cuff repair by imaging the  shoulder joint , [ 15 ]  among other applications."}
{"_id": "WikiPedia_Radiology$$$corpus_5232", "text": "Animal locomotion  can also be analyzed with X-ray imaging. As long as the animal can be placed between the X-ray emitter and the camera, the subject can be imaged. Examples of gaits that have been studied are rats, [ 8 ] [ 16 ]  guineafowl, [ 17 ]  horses, [ 6 ]  bipedal birds, [ 18 ]  and frogs, [ 11 ]  among others. Aside from locomotion, X-ray motion analysis has been utilized in the study and research of other moving morphology analyses, such as pig mastication [ 2 ]  and movement of the  temporomandibular joint  in rabbits. [ 19 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5233", "text": "X-ray optics  is the branch of  optics  dealing with  X-rays , rather than  visible light . It deals with focusing and other ways of manipulating the X-ray beams for research techniques such as  X-ray diffraction ,  X-ray crystallography ,  X-ray fluorescence ,  small-angle X-ray scattering ,  X-ray microscopy ,  X-ray phase-contrast imaging , and  X-ray astronomy ."}
{"_id": "WikiPedia_Radiology$$$corpus_5234", "text": "X-rays and visible light are both  electromagnetic waves , and propagate in space in the same way, but because of the much higher  frequency  and  photon  energy of X-rays they interact with matter very differently. Visible light is easily redirected using  lenses  and  mirrors , but because the real part of the  complex refractive index  of all materials is very close to 1 for X-rays, [ 1 ]  they instead tend to initially penetrate and eventually get absorbed in most materials without significant change of direction."}
{"_id": "WikiPedia_Radiology$$$corpus_5235", "text": "There are many different techniques used to redirect X-rays, most of them changing the directions by only minute angles. The most common principle used is  reflection  at  grazing incidence  angles, either using  total external reflection  at very small angles or  multilayer coatings . Other principles used include  diffraction  and  interference  in the form of  zone plates ,  refraction  in  compound refractive lenses  that use many small X-ray lenses in series to compensate by their number for the minute index of refraction, and  Bragg reflection  from a crystal plane in flat or bent  crystals ."}
{"_id": "WikiPedia_Radiology$$$corpus_5236", "text": "X-ray beams are often  collimated  (reduced in size) using pinholes or movable slits typically made of tungsten or some other high- Z  material. Narrow parts of an X-ray spectrum can be selected with  monochromators  based on one or multiple Bragg reflections by crystals. X-ray spectra can also be manipulated by passing the X-rays through a  filter  that typically reduces the low-energy part of the spectrum, and possibly parts above  absorption edges  of the  elements  used for the filter."}
{"_id": "WikiPedia_Radiology$$$corpus_5237", "text": "Analytical X-ray techniques such as X-ray crystallography, small-angle X-ray scattering,  wide-angle X-ray scattering , X-ray fluorescence,  X-ray spectroscopy  and  X-ray photoelectron spectroscopy  all benefit from high X-ray flux densities on the samples being investigated. This is achieved by focusing the divergent beam from the  X-ray source  onto the sample using one of several possible focusing optical components. This is also useful for  scanning probe  techniques such as  scanning transmission X-ray microscopy  and scanning X-ray fluorescence imaging."}
{"_id": "WikiPedia_Radiology$$$corpus_5238", "text": "Polycapillary lenses are arrays of small hollow glass tubes that guide the X-rays with many  total external reflections  on the inside of the tubes. [ 2 ] \nThe array is tapered so that one end of the capillaries points at the X-ray source and the other at the sample. Polycapillary optics are achromatic and thus suitable for scanning fluorescence imaging and other applications where a broad X-ray spectrum is useful. They collect X-rays efficiently for  photon energies  of 0.1 to 30\u00a0 keV  and can achieve gains of 100 to 10000 in flux over using a  pinhole  at 100\u00a0mm from the X-ray source. [ 3 ] \nSince only X-rays entering the capillaries within a very narrow angle will be totally internally reflected, only X-rays coming from a small spot will be transmitted through the optic. Polycapillary optics cannot image more than one point to another, so they are used for illumination and collection of X-rays."}
{"_id": "WikiPedia_Radiology$$$corpus_5239", "text": "Zone plates consist of a substrate with concentric zones of a phase-shifting or absorbing material with zones getting narrower the larger their radius. The zone widths are designed so that a transmitted wave gets  constructive interference  in a single point giving a focus. [ 4 ]  Zone plates can be used as  condensers  to collect light, but also for direct full-field imaging in e.g. an X-ray microscope. Zone plates are highly  chromatic  and usually designed only for a narrow energy span, making it necessary to have  monochromatic  X-rays for efficient collection and high-resolution imaging."}
{"_id": "WikiPedia_Radiology$$$corpus_5240", "text": "Since refractive indices at X-ray wavelengths are so close to 1, the  focal lengths  of normal  lenses  get impractically long. To overcome this, lenses with very small  radii of curvature  are used, and they are stacked in long rows, so that the combined  focusing power  becomes appreciable. [ 5 ]  Since the refractive index is less than 1 for X-rays, these  lenses must be concave  to achieve focusing, contrary to visible-light lenses, which are  convex  for a focusing effect. Radii of curvature are typically less than one millimeter, making the usable X-ray beam width at most about 1\u00a0mm. [ 6 ]  To reduce the  absorption  of X-rays in these stacks, materials with very low atomic number such as  beryllium  or  lithium  are often used. Lenses from other materials are also available: radiation-resistant polymer (Epoxy based) such as  SU-8 ,  nickel  and  silicon . Since the refractive index depends strongly on X-ray wavelength, these lenses are highly  chromatic , and the variation of the focal length with wavelength must be taken into account for any application."}
{"_id": "WikiPedia_Radiology$$$corpus_5241", "text": "The basic idea is to  reflect  a beam of X-rays from a surface and to measure the intensity of X-rays reflected in the specular direction (reflected angle equal to incident angle). It has been shown that a reflection off a parabolic mirror followed by a reflection off a hyperbolic mirror leads to the focusing of X-rays. [ 7 ]  Since the incoming X-rays must strike the tilted surface of the mirror, the collecting area is small. It can, however, be increased by nesting arrangements of mirrors inside each other. [ 8 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5242", "text": "The ratio of reflected intensity to incident intensity is the  X-ray reflectivity  for the surface. If the interface is not perfectly sharp and smooth, the reflected intensity will deviate from that predicted by the  Fresnel reflectivity  law; the deviations can be analyzed to obtain the density profile of the interface normal to the surface. For films with multiple layers, X-ray reflectivity may show oscillations with wavelength, analogous to the  Fabry\u2013P\u00e9rot effect . These oscillations can be used to infer layer thicknesses and other properties."}
{"_id": "WikiPedia_Radiology$$$corpus_5243", "text": "In X-ray diffraction a beam strikes a crystal and  diffracts  into many specific directions. The angles and intensities of the diffracted beams indicate a three-dimensional density of  electrons  within the crystal. X-rays produce a diffraction pattern because their  wavelength  typically has the same  order of magnitude  (0.1\u201310.0\u00a0nm) as the spacing between the atomic planes in the crystal."}
{"_id": "WikiPedia_Radiology$$$corpus_5244", "text": "Each atom re-radiates a small portion of an incoming beam's intensity as a spherical wave. If the atoms are arranged symmetrically (as is found in a crystal) with a separation  d , these spherical waves will be  in phase  (add constructively) only in directions where their path-length difference 2 d \u2009sin\u00a0 \u03b8  is equal to an integer multiple of the wavelength  \u03bb . The incoming beam therefore appears to have been deflected by an angle 2 \u03b8 , producing a  reflection  spot in the  diffraction pattern ."}
{"_id": "WikiPedia_Radiology$$$corpus_5245", "text": "X-ray diffraction is a form of  elastic scattering  in the forward direction; the outgoing X-rays have the same energy, and thus the same wavelength, as the incoming X-rays, only with altered direction. By contrast,  inelastic scattering  occurs when energy is transferred from the incoming X-ray to an inner-shell electron, exciting it to a higher  energy level . Such inelastic scattering reduces the energy (or increases the wavelength) of the outgoing beam. Inelastic scattering is useful for probing such  electron excitation , but not in determining the distribution of atoms within the crystal."}
{"_id": "WikiPedia_Radiology$$$corpus_5246", "text": "Longer-wavelength photons (such as  ultraviolet   radiation ) would not have sufficient resolution to determine the atomic positions. At the other extreme, shorter-wavelength photons such as  gamma rays  are difficult to produce in large numbers, difficult to focus, and interact too strongly with matter, producing  particle\u2013antiparticle pairs ."}
{"_id": "WikiPedia_Radiology$$$corpus_5247", "text": "Similar diffraction patterns can be produced by scattering electrons or  neutrons . X-rays are usually not diffracted from atomic nuclei, but only from the electrons surrounding them."}
{"_id": "WikiPedia_Radiology$$$corpus_5248", "text": "X-ray  interference  due to the  superposition  of two or more X-ray  waves  produces a new wave pattern. X-ray interference usually refers to the interaction of waves that are correlated or  coherent  with each other, either because they come from the same source or because they have the same or nearly the same  frequency ."}
{"_id": "WikiPedia_Radiology$$$corpus_5249", "text": "Two non- monochromatic  X-ray waves are only fully coherent with each other if they both have exactly the same range of  wavelengths  and the same  phase  differences at each of the constituent wavelengths."}
{"_id": "WikiPedia_Radiology$$$corpus_5250", "text": "The total phase difference is derived from the sum of the path difference and the initial phase difference (if the X-ray waves are generated from two or more different sources). It can then be concluded whether the X-ray waves reaching a point are  in phase  (constructive interference) or  out of phase  (destructive interference)."}
{"_id": "WikiPedia_Radiology$$$corpus_5251", "text": "There are a variety of techniques used to funnel X-ray photons to the appropriate location on an X-ray detector:"}
{"_id": "WikiPedia_Radiology$$$corpus_5252", "text": "Most X-ray optical elements (with the exception of grazing-incidence mirrors) are very small and must be designed for a particular  incident angle  and energy, thus limiting their applications in divergent  radiation . As of 2009 [update] , although the technology had advanced rapidly, its practical uses outside research were limited. Efforts were ongoing to introduce X-ray optics in medical  X-ray imaging . For instance, one of the applications showing greater promise is in enhancing both the  contrast  and  resolution  of  mammographic  images, compared to conventional  anti-scatter grids . [ 16 ]  Another application is to optimize the energy distribution of the X-ray beam to improve  contrast-to-noise ratio  over conventional energy filtering. [ 17 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5253", "text": "X-ray mirrors can be made of glass, ceramic, or metal foil, coated by a reflective layer. [ 1 ]  The most commonly used reflective materials for X-ray mirrors are  gold  and  iridium . Even with these the critical reflection angle is energy-dependent. For gold at 1\u00a0keV, the critical reflection angle is 2.4\u00b0. [ 18 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5254", "text": "The use of X-ray mirrors simultaneously requires:"}
{"_id": "WikiPedia_Radiology$$$corpus_5255", "text": "No material has substantial reflection for X-rays, except at very small grazing angles. Multilayers enhance the small reflectivity from a single boundary by adding the small reflected amplitudes from many boundaries coherently in phase. For example, if a single boundary has a reflectivity of  R  = 10 \u22124  (amplitude  r  = 10 \u22122 ), then the addition of 100 amplitudes from 100 boundaries can give reflectivity  R  close to one. The period \u039b of the multilayer that provides the in-phase addition is that of the standing wave produced by the input and output beam, \u039b =  \u03bb /2 sin\u00a0 \u03b8 , where  \u03bb  is the wavelength, and 2 \u03b8  the half angle between the two beams. For  \u03b8  = 90\u00b0, or reflection at normal incidence, the period of the multilayer is \u039b =  \u03bb /2. The shortest period that can be used in a multilayer is limited by the size of the atoms to about 2\u00a0nm, corresponding to wavelengths above 4\u00a0nm. For shorter wavelength a reduction of the incidence angle  \u03b8  toward more grazing has to be used."}
{"_id": "WikiPedia_Radiology$$$corpus_5256", "text": "The materials for multilayers are selected to give the highest possible reflection at each boundary and the smallest absorption or the propagation through the structure. This is usually achieved by light, low-density materials for the spacer layer and a heavier material that produces high contrast. The absorption in the heavier material can be reduced by positioning it close to the nodes of the standing-wave field inside the structure. Good low-absorption spacer materials are Be, C, B, B 4 C and Si. Some examples of the heavier materials with good contrast are W, Rh, Ru and Mo."}
{"_id": "WikiPedia_Radiology$$$corpus_5257", "text": "Applications include:"}
{"_id": "WikiPedia_Radiology$$$corpus_5258", "text": "Mo/Si is the material selection used for the near-normal incidence reflectors for EUV lithography."}
{"_id": "WikiPedia_Radiology$$$corpus_5259", "text": "An X-ray mirror optic for the  NuSTAR  space telescope working at 79\u00a0keV (hard, i.e. high-energy X-radiation) was made using multilayered coatings, computer-aided manufacturing, and other techniques. [ 19 ]  The mirrors use a  tungsten / silicon  (W/Si) or  platinum / silicon-carbide  (Pt/SiC) multicoating on  slumped  glass, allowing a  Wolter telescope  design. [ 19 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5260", "text": "An  X-ray telescope  ( XRT ) is a  telescope  that is designed to observe remote objects in the  X-ray  spectrum. X-rays are absorbed by the  Earth's atmosphere , so instruments to detect X-rays must be taken to high altitude by  balloons ,  sounding rockets , and  satellites ."}
{"_id": "WikiPedia_Radiology$$$corpus_5261", "text": "The basic elements of the telescope are the  optics  (focusing or  collimating ), that collects the  radiation  entering the telescope, and the  detector , on which the radiation is collected and measured. A variety of different designs and technologies have been used for these elements."}
{"_id": "WikiPedia_Radiology$$$corpus_5262", "text": "Many X-ray telescopes on satellites are compounded of multiple small detector-telescope systems whose capabilities add up or complement each other, and additional fixed or removable elements [ 1 ] [ 2 ]  (filters, spectrometers) that add functionalities to the instrument."}
{"_id": "WikiPedia_Radiology$$$corpus_5263", "text": "X-ray telescopes were first used for astronomy to observe the  Sun , which was the only source in the sky bright enough in X-rays for those early telescopes to detect. Because the Sun is so bright in X-rays, early X-ray telescopes could use a small focusing element and the X-rays would be detected with photographic film. The first X-ray picture of the Sun from a rocket-borne telescope was taken by John V. Lindsay of the NASA  Goddard Space Flight Center  and collaborators in 1963. The first orbiting X-ray telescope flew on  Skylab  in the early 1970s and recorded more than 35,000 full-disk images of the Sun over a 9-month period. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5264", "text": "First specialised X-ray satellite,  Uhuru , was launched by  NASA  in 1970. It detected 339 X-ray sources in its 2.5-year lifetime. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5265", "text": "The  Einstein Observatory , launched in 1978, was the first imaging X-ray observatory. It obtained high-resolution X-ray images in the energy range from 0.1 to 4 keV of stars of all types, supernova remnants, galaxies, and clusters of galaxies. Another large project was  ROSAT  (active from 1990 to 1999), which was a heavy X-ray space observatory with focusing X-ray optics, and European  EXOSAT . [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5266", "text": "The  Chandra X-Ray Observatory  was launched by NASA in 1999 and is operated for more than 25 years in a high elliptical orbit, returning thousands 0.5 arc-second images and high-resolution spectra of all kinds of astronomical objects in the energy range from 0.5 to 8.0 keV. Chandra's resolution is about 50 times superior to that of ROSAT. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5267", "text": "Satellites in use today include  ESA 's  XMM-Newton observatory  (low to mid energy X-rays 0.1-15 keV),  NASA 's  Swift  observatory,  Chandra  observatory and  IXPE  telescope.  JAXA  has launched the  XRISM  telescope, while  ISRO  has launched  Aditya-L1  and  XPoSat ."}
{"_id": "WikiPedia_Radiology$$$corpus_5268", "text": "The  GOES 14  spacecraft carries on board a Solar X-ray Imager to monitor the Sun's X-rays for the early detection of solar flares, coronal mass ejections, and other phenomena that impact the geospace environment. [ 5 ]  It was launched into orbit on June 27, 2009, at 22:51 GMT from  Space Launch Complex 37B  at the  Cape Canaveral Air Force Station ."}
{"_id": "WikiPedia_Radiology$$$corpus_5269", "text": "The Chinese  Hard X-ray Modulation Telescope  was launched on June 15, 2017 to observe black holes, neutron stars, active galactic nuclei and other phenomena based on their X-ray and gamma-ray emissions. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5270", "text": "The  Lobster-Eye X-ray Satellite  was launched on 25 July 2020 by  CNSA  making it is the first in-orbit telescope to utilize the  lobster-eye  imaging technology of ultra-large field of view imaging to search for dark matter signals in the x-ray energy range. [ 7 ]   Lobster Eye Imager for Astronomy  was launched on 27 July 2022 as a technology demonstrator for  Einstein Probe , launched on January 9, 2024, dedicated to time-domain  high-energy astrophysics . [ 8 ]  The  Space Variable Objects Monitor  observatory launched on 22 June 2024 is directed towards studying the explosions of massive stars and analysis of  gamma-ray bursts . [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5271", "text": "A  soft X-ray  solar imaging telescope is on board the  GOES-13  weather satellite launched using a  Delta IV  from  Cape Canaveral  LC37B on May 24, 2006. [ 10 ]  However, there have been no GOES 13 SXI images since December 2006."}
{"_id": "WikiPedia_Radiology$$$corpus_5272", "text": "The Russian-German  Spektr-RG  carries the  eROSITA  telescope array as well as the  ART-XC  telescope. It was launched by  Roscosmos  on 13 July 2019 from  Baikonur  and began collecting data in October 2019."}
{"_id": "WikiPedia_Radiology$$$corpus_5273", "text": "The most common methods used in X-ray optics are  grazing incidence mirrors  and  collimated apertures . Only three geometries that use  grazing incidence reflection  of X-rays to produce X-ray images are known:  Wolter system ,  Kirkpatrick-Baez system , and  lobster-eye optics . [ 11 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5274", "text": "A simple parabolic mirror was originally proposed in 1960 by  Riccardo Giacconi  and  Bruno Rossi , the founders of extrasolar X-ray astronomy. This type of mirror is often used as the primary reflector in an optical telescope. However, images of off-axis objects would be severely blurred. The German physicist  Hans Wolter  showed in 1952 that the reflection off a combination of two elements, a paraboloid followed by a hyperboloid, would work far better for X-ray astronomy applications. Wolter described three different imaging configurations, the  Types I, II, and III . The design most commonly used by X-ray astronomers is the Type I since it has the simplest mechanical configuration. In addition, the Type I design offers the possibility of nesting several telescopes inside one another, thereby increasing the useful reflecting area. The Wolter Type II is useful only as a narrow-field imager or as the optic for a dispersive spectrometer. The Wolter Type III has never been employed for X-ray astronomy. [ 12 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5275", "text": "With respect to collimated optics, focusing optics allow:"}
{"_id": "WikiPedia_Radiology$$$corpus_5276", "text": "The mirrors can be made of  ceramic  or  metal foil [ 13 ]  coated with a thin layer of a reflective material (typically  gold  or  iridium ). Mirrors based on this construction work on the basis of  total reflection  of light at grazing incidence."}
{"_id": "WikiPedia_Radiology$$$corpus_5277", "text": "This technology is limited in energy range by the inverse relation between critical angle for total reflection and radiation energy. The limit in the early 2000s with  Chandra  and  XMM-Newton  X-ray  observatories  was about 15 kilo- electronvolt  (keV) light. [ 14 ]  Using new multi-layered coated mirrors, the X-ray mirror for the  NuSTAR  telescope pushed this up to 79 keV light. [ 14 ]  To reflect at this level, glass layers were multi-coated with  tungsten  (W)/ silicon  (Si) or  platinum  (Pt)/ silicon carbide (SiC). [ 14 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5278", "text": "While earlier X-ray telescopes were using simple collimating techniques (e.g. rotating collimators, wire collimators), [ 15 ]  the technology most used in the present day employs coded aperture masks. This technique uses a flat aperture patterned grille in front of the detector. This design gives results that are less sensitive than focusing optics; also the imaging quality and identification of source position is much poorer. Though this design offers a larger  field of view  and can be employed at higher energies, where grazing incidence optics become ineffective. Also the imaging is not direct, but the image is rather reconstructed by post-processing of the signal."}
{"_id": "WikiPedia_Radiology$$$corpus_5279", "text": "X-rays has a huge span in wavelength (~8\u00a0nm - 8 pm), frequency (~50 PHz - 50 EHz) and energy (~0.12 - 120 keV). In terms of temperature, 1 eV = 11,604 K. Thus X-rays (0.12 to 120 keV) correspond to 1.39 \u00d7 10 6  to 1.39 \u00d7 10 9  K. From 10 to 0.1 nanometers (nm) (about 0.12 to 12  keV ) they are classified as soft X-rays, and from 0.1\u00a0nm to 0.01\u00a0nm (about 12 to 120 keV) as hard X-rays."}
{"_id": "WikiPedia_Radiology$$$corpus_5280", "text": "Closer to the visible range of the electromagnetic spectrum is the  ultraviolet . The draft ISO standard on determining solar  irradiances  (ISO-DIS-21348) [ 16 ]  describes the ultraviolet as ranging from ~10\u00a0nm to ~400\u00a0nm. That portion closest to X-rays is often referred to as the \"extreme ultraviolet\" ( EUV  or XUV). When an EUV photon is absorbed,  photoelectrons  and  secondary electrons  are generated by  ionization , much like what happens when X-rays or electron beams are absorbed by matter. [ 17 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5281", "text": "The distinction between X-rays and  gamma rays  has changed in recent decades. Originally, the electromagnetic radiation emitted by  X-ray tubes  had a longer  wavelength  than the radiation emitted by  radioactive   nuclei  (gamma rays). [ 18 ]  So older literature distinguished between X- and gamma radiation on the basis of wavelength, with radiation shorter than some arbitrary wavelength, such as 10 \u221211  m, defined as gamma rays. [ 19 ]  However, as shorter wavelength continuous spectrum \"X-ray\" sources such as  linear accelerators  and longer wavelength \"gamma ray\" emitters were discovered, the wavelength bands largely overlapped. The two types of radiation are now usually distinguished by their origin: X-rays are emitted by electrons outside the nucleus, while gamma rays are emitted by the  nucleus . [ 18 ] [ 20 ] [ 21 ] [ 22 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5282", "text": "Although the more energetic X-rays,  photons  with an energy greater than 30  keV  (4,800  a J), can penetrate the  Earth's atmosphere  at least for distances of a few meters, the Earth's atmosphere is thick enough that virtually none are able to penetrate from outer space all the way to the Earth's surface. X-rays in the 0.5 to 5 keV (80 to 800 aJ) range, where most celestial sources give off the bulk of their energy, can be stopped by a few sheets of paper; 90% of the photons in a beam of 3 keV (480 aJ) X-rays are absorbed by traveling through just 10\u00a0cm of air."}
{"_id": "WikiPedia_Radiology$$$corpus_5283", "text": "A  proportional counter  is a type of  gaseous ionization detector  that counts  particles  of  ionizing radiation  and measures their energy. It works on the same principle as the  Geiger-M\u00fcller counter , but uses a lower operating  voltage . All X-ray proportional counters consist of a windowed gas cell. [ 23 ]  Often this cell is subdivided into a number of low- and high-electric field regions by some arrangement of electrodes."}
{"_id": "WikiPedia_Radiology$$$corpus_5284", "text": "Proportional counters were used on  EXOSAT , [ 24 ]  on the US portion of the  Apollo\u2013Soyuz  mission (July 1975), and on French  TOURNESOL  instrument. [ 25 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5285", "text": "Monitoring generally means to be aware of the state of a system. A device that displays or sends a signal for displaying X-ray output from an X-ray generating source so as to be aware of the state of the source is referred to as an X-ray monitor in space applications. \nOn  Apollo 15  in orbit above the  Moon , for example, an X-ray monitor was used to follow the possible variation in solar X-ray intensity and spectral shape while mapping the lunar surface with respect to its chemical composition due to the production of  secondary X-rays . [ 26 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5286", "text": "The X-ray monitor of  Solwind , designated NRL-608 or XMON, was a collaboration between the  Naval Research Laboratory  and  Los Alamos National Laboratory . The monitor consisted of 2 collimated argon proportional counters."}
{"_id": "WikiPedia_Radiology$$$corpus_5287", "text": "A scintillator is a material which exhibits the property of  luminescence [ 27 ]  when excited by  ionizing radiation . Luminescent materials, when struck by an incoming particle, such as an X-ray photon, absorb its energy and scintillate, i.e. reemit the absorbed energy in the form of a small flash of light, typically in the visible range."}
{"_id": "WikiPedia_Radiology$$$corpus_5288", "text": "The scintillation X-ray detector were used on  Vela 5A  and its twin  Vela 5B ; [ 28 ]  the X-ray telescope onboard  OSO 4  consisted of a single thin NaI(Tl) scintillation crystal plus phototube assembly enclosed in a CsI(Tl) anti-coincidence shield.  OSO 5  carried a CsI crystal scintillator. The central crystal was 0.635\u00a0cm thick, had a sensitive area of 70\u00a0cm 2 , and was viewed from behind by a pair of photomultiplier tubes."}
{"_id": "WikiPedia_Radiology$$$corpus_5289", "text": "The  PHEBUS  had two independent detectors, each detector consisted of a bismuth germinate (BGO) crystal 78\u00a0mm in  diameter  by 120\u00a0mm thick. [ 25 ]  The  KONUS-B  instrument consisted of seven detectors distributed around the spacecraft that responded to  photons  of 10\u00a0keV to 8\u00a0MeV energy. They consisted of  NaI (Tl) scintillator crystals 200\u00a0mm in diameter by 50\u00a0mm thick behind a  Be  entrance window.  Kvant-1  carried the HEXE, or High Energy X-ray Experiment, which employed a  phoswich  of sodium iodide and caesium iodide."}
{"_id": "WikiPedia_Radiology$$$corpus_5290", "text": "In  electronics ,  modulation  is the process of varying one waveform in relation to another waveform. With a 'modulation collimator' the amplitude (intensity) of the incoming X-rays is reduced by the presence of two or more 'diffraction gratings' of parallel wires that block or greatly reduce that portion of the signal incident upon the wires."}
{"_id": "WikiPedia_Radiology$$$corpus_5291", "text": "An  X-ray collimator  is a device that filters a stream of X-rays so that only those traveling parallel to a specified direction are allowed through."}
{"_id": "WikiPedia_Radiology$$$corpus_5292", "text": "Minoru Oda , President of Tokyo University of Information Sciences, invented the modulation collimator, first used to identify the counterpart of Sco X-1 in 1966, which led to the most accurate positions for X-ray sources available, prior to the launch of X-ray imaging telescopes. [ 29 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5293", "text": "SAS 3  carried modulation collimators (2-11 keV) and Slat and Tube collimators (1 up to 60keV). [ 30 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5294", "text": "On board the  Granat  Observatory were four  WATCH  instruments that could localize bright sources in the 6 to 180 keV range to within 0.5\u00b0 using a Rotation Modulation Collimator. Taken together, the instruments' three fields of view covered approximately 75% of the sky. [ 25 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5295", "text": "The  Reuven Ramaty High Energy Solar Spectroscopic Imager  (RHESSI), Explorer 81, images solar flares from soft X-rays to gamma rays (~3 keV to ~20 MeV). Its imaging capability is based on a Fourier-transform technique using a set of 9  Rotational Modulation Collimators ."}
{"_id": "WikiPedia_Radiology$$$corpus_5296", "text": "OSO 8  had on board a Graphite Crystal X-ray Spectrometer, with energy range of 2-8 keV, FOV 3\u00b0."}
{"_id": "WikiPedia_Radiology$$$corpus_5297", "text": "The  Granat   ART-S X-ray spectrometer  covered the energy range 3 to 100\u00a0keV, FOV 2\u00b0 \u00d7 2\u00b0. The instrument consisted of four detectors based on  spectroscopic   MWPCs , making an effective area of 2,400\u00a0cm 2  at 10\u00a0keV and 800\u00a0cm 2  at 100\u00a0keV. The time resolution was 200  microseconds . [ 25 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5298", "text": "The X-ray spectrometer aboard  ISEE-3  was designed to study both solar flares and cosmic gamma-ray bursts over the energy range 5-228 keV. The experiment consisted of 2 cylindrical X-ray detectors: a Xenon filled proportional counter covering 5-14 keV, and a NaI(Tl) scintillator covering 12-1250 keV."}
{"_id": "WikiPedia_Radiology$$$corpus_5299", "text": "Most existing X-ray telescopes use  CCD  detectors, similar to those in visible-light cameras. In visible-light, a single photon can produce a single electron of charge in a pixel, and an image is built up by accumulating many such charges from many photons during the exposure time. When an X-ray photon hits a CCD, it produces enough charge (hundreds to thousands of electrons, proportional to its energy) that the individual X-rays have their energies measured on read-out."}
{"_id": "WikiPedia_Radiology$$$corpus_5300", "text": "Microcalorimeters  can only detect X-rays one photon at a time (but can measure the energy of each)."}
{"_id": "WikiPedia_Radiology$$$corpus_5301", "text": "Transition-edge sensors  are the next step in microcalorimetry. In essence they are super-conducting metals kept as close as possible to their transition temperature. This is the temperature at which these metals become super-conductors and their resistance drops to zero. These transition temperatures are usually just a few degrees above absolute zero (usually less than 10  K )."}
{"_id": "WikiPedia_Radiology$$$corpus_5302", "text": "Xeromammography  is a  photoelectric  method of recording an  x-ray  image on a coated metal plate, using low-energy  photon  beams, long  exposure time , and dry  chemical developers ."}
{"_id": "WikiPedia_Radiology$$$corpus_5303", "text": "It is a form of  xeroradiography . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5304", "text": "This process was developed in the late 1960s by  Jerry Hedstrom , and used to image  soft tissue , and later focused on using the process to detect  breast cancer ."}
{"_id": "WikiPedia_Radiology$$$corpus_5305", "text": "Xeroradiography  is a type of X-ray imaging in which a picture of the body is recorded on paper rather than on  film . In this technique, a plate of selenium, which rests on a thin layer of aluminium oxide, is charged uniformly by passing it in front of a  scorotron . [ 1 ] \nThe process was developed by engineer Dr. Robert C. McMaster in 1950. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5306", "text": "As X-ray photon impinges on this amorphous coat of selenium, charges diffuse out, in proportion to energy content of the X-ray. This occurs as a result of  photoconduction . The resulting imprint, in the form of charge distribution on the plate, attracts toner particles, which is then transferred to reusable paper plates. In contrast to conventional X-rays,  photographic developers  are not needed. Hence the term xeroradiography; 'xero' meaning dry in Greek.\nIt requires more radiation exposure. Historically used in mammography prior to the advent of digital mammography."}
{"_id": "WikiPedia_Radiology$$$corpus_5307", "text": "Xeromammography  is a form of xeroradiography. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5308", "text": "Celedonio Calatayud Costa  ( Spanish pronunciation:   [\u03b8ele\u02c8\u00f0onjo   kalata\u02c8\u029du\u00f0   \u02c8kosta] ; October 29, 1880 in  Pedreguer  \u2013 January 24, 1931 in  Madrid ) was a Spanish  scientist  and  radiologist , remembered for his achievements on  radiology ,  radiotherapy , and electrology. He pioneered the use of radiology and electrology in Europe for both diagnostics and therapeutical purposes, introducing  radiotherapy  in Spain in 1906. He founded the Spanish Medical Electrology and Radiology Society (Sociedad Espa\u00f1ola de Radiolog\u00eda y Electrolog\u00eda M\u00e9dicas), [ 1 ]  promoted the doctoral chair of Electro-radiology and was elected as the first professor to chair it [ 2 ]  at the Universidad Central (later renamed  Complutense University of Madrid ). He also was the driving force behind and creator of the  First National Medical Congress  that took place in  Madrid  in 1919, [ 3 ] [ 4 ]  precursor of the use of  diathermy  in gynecologic therapy, founder of the  Spanish Journal of Medical Electrology and Radiology  ( Revista Espa\u00f1ola de Radiolog\u00eda y Electrolog\u00eda M\u00e9dicas ) and  Tribuna M\u00e9dica , as well as author of many papers on electrodiagnosis,  electrotherapy ,  roentgenology , and  radiotherapy ."}
{"_id": "WikiPedia_Radiology$$$corpus_5309", "text": "Michael Grace Kawooya  (born 1958) is a  Ugandan   physician ,  academic ,  researcher  and  academic administrator , who serves as Director at the  Ernest Cook Ultrasound Research and Education Institute  (ECUREI). He is a Professor (emeritus) of Radiology at  Makerere University College of Health Sciences . [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5310", "text": "He was born in the  Buganda Region  of Uganda circa 1958. After attending local elementary and secondary schools, he was admitted to  Makerere University Medical School  in 1978. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5311", "text": "He graduated with a  Bachelor of Medicine and Bachelor of Surgery  degree, in 1983. He went on to obtain a  Master of Medicine  degree in  Radiology  from the same university, in 1988. [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5312", "text": "He followed that with a two-year fellowship in radiology from the  University of T\u00fcbingen  in  T\u00fcbingen , Germany. In 2001, he studied at the  Thomas Jefferson University , in  Philadelphia , Pennsylvania, United States in a fellowship in ultrasound. [ 1 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5313", "text": "He started his teaching career in the Department of Radiology at  Makerere University Medical School , as a lecturer to undergraduate and postgraduate students. Over the years he was promoted and given more responsibilities, as his experience increased and broadened. He has supervised over forty radiologists at the Master of Medicine level and above. He attained full professorship in radiology at  Makerere University . [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5314", "text": "Professor Kawooya\u2019s area of super-specialization is  ultrasound . He has in excess of fifty-five published articles in peer-reviewed journals, and five chapters in books on different topics, including imaging of tropical diseases. He has many professional awards including as an Honorary Fellow of the  American Institute of Ultrasound in Medicine , awarded in 2015, and as an Honorary Member of the  European Society of Radiology , awarded in 2019. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5315", "text": "In 2002, with the support of  Thomas Jefferson University , in  Philadelphia , Pennsylvania, United States, Professor Kawooya, with other Ugandan radiologists, founded the  Ernest Cook Ultrasound Research And Education Institute (ECUREI) , based at  Mengo Hospital , in  Kampala , Uganda's capital city. [ 2 ] [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5316", "text": "ECUREI, which also receives partial funding from the  Fontys University of Applied Sciences , in the Netherlands trains students for the  Diploma in Ultrasound  qualification. Trainees come from  Uganda ,  Kenya ,  Tanzania , the  Democratic Republic of the Congo  and  Zambia . [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5317", "text": "Robert Kienb\u00f6ck  (11 January 1871 \u2013 8 September 1953) was an Austrian  radiologist  who was a native of  Vienna ."}
{"_id": "WikiPedia_Radiology$$$corpus_5318", "text": "In 1895 he earned his medical doctorate at the  University of Vienna , and spent the next year abroad ( London  and  Paris ). He returned to Vienna as an assistant to  Leopold von Schr\u00f6tter  (1837\u20131908), a  laryngologist , and began working in the new science of  radiology . Several years later, he became head of the radiological department at  Vienna General Hospital . In 1926 he became an associate professor of radiology."}
{"_id": "WikiPedia_Radiology$$$corpus_5319", "text": "In June 1923, along with  Guido Holzknecht  (1872-1931), he was co-founder of the  Wiener Gesellschaft f\u00fcr R\u00f6ntgenkunde  (Vienna Radiology Society). He was elected president of the  \u00d6sterreichische Gesellschaft f\u00fcr R\u00f6ntgenkunde  (Austrian Radiology Society) in 1934 and honorary president of that body after the  Second World War . [ 1 ] [ 2 ]  With Holzknecht, he published the two-part  R\u00f6ntgenologie. Eine Revision ihrer technischen Einrichtungen und praktische Methoden  ( Roentgenology . A review of its technical facilities and practical methods). [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5320", "text": "Kienb\u00f6ck was a pioneer in the use of  x-ray  technology for medical diagnosis and therapy. He specialized in research of  skeletal  diseases and its treatment through radiology. In 1910 he described a disorder which consisted of breakdown of the  lunate bone  in the wrist. He called the disorder \"lunatomalacia\", which is now known as  Kienb\u00f6ck's disease . [ 4 ]  \nKienb\u00f6ck published his findings in a treatise titled  \u00dcber traumatische Malazie des Mondbeins und ihre Folgezust\u00e4nde  (Traumatic  malacia  of the lunate and its consequences). [ 5 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5321", "text": "This biographical article related to medicine in Austria is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Radiology$$$corpus_5322", "text": "Sergey Pavlovich Morozov  ( Russian :  \u0421\u0435\u0440\u0433\u0435\u0439 \u041f\u0430\u0432\u043b\u043e\u0432\u0438\u0447 \u041c\u043e\u0440\u043e\u0437\u043e\u0432 ; born 10 March 1979) is a Russian radiologist and healthcare official."}
{"_id": "WikiPedia_Radiology$$$corpus_5323", "text": "Sergey Morozov was born in Moscow on March 10, 1979. In 2002, he graduated from  I.M. Sechenov First Moscow State Medical University  with honors with a degree in Internal Medicine. In 2002\u20132004, he completed postgraduate training in Diagnostic Imaging and Radiography at Sechenov University and the  Moscow State University of Medicine and Dentistry  and fellowship programs at the University of Illinois in Chicago, Memorial Sloan-Kettering Cancer Center ( USA ), Oslo University ( Norway ), and Universita La Sapienza ( Italy )."}
{"_id": "WikiPedia_Radiology$$$corpus_5324", "text": "In 2004, Sergey Morozov completed his  candidate  thesis working on functional  magnetic resonance imaging ; his  doctoral  thesis on diagnostic imaging in  orthopedics  was accepted in 2010. [ 1 ]  Sergey Morozov received the master's degree from the Harvard School of Public Health (Boston, USA) in 2006, followed by another master's degree from the  Russian Presidential Academy of National Economy and Public Administration  in Economics and Business Administration in 2013. Sergey Morozov became a professor of Radiology and Radiotherapy in 2015 and a Certified Imaging Informatics Professional (CIIP) in 2017, completing a certification program at the Society for Imaging Informatics in Medicine (SIIM). During his early career, Morozov was a radiologist at the Radiology Department of I.M. Sechenov Moscow Medical Academy. In 2007\u20132013, he headed the Department of X-Ray and MR Diagnostics at the  Moscow Central Clinical Hospital . Since 2004, Morozov has been a lecturer at the Department of Radiology and Radiotherapy of  Sechenov University , holding the positions of a teaching assistant, associate professor, and later becoming a professor. From 2013, Morozov was the medical school rector and radiology department head at the European Medical Center. [ 2 ]  In December 2015, he was appointed CEO of the Moscow Center for Diagnostics & Telemedicine of the Moscow Healthcare Department. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5325", "text": "In 2016\u20132018, Morozov was the president of the European Society of Medical Imaging Informatics (EuSoMII). [ 4 ]  He became the Chief External Officer for Radiology of the Moscow Healthcare Department in 2015 and the Chief External Officer for Radiology and Instrumental Diagnostics in 2019 to chair the expert  certification  panel in Radiology, Diagnostic Ultrasonography, and Radiography. [ 5 ]  In 2017, he was promoted to Chief Regional Radiology and Instrumental Diagnostics Officer of the Ministry of Health of the Russian Federation for the Central Federal District. Morozov is the chair of the Moscow Regional Office of the Russian Society of Radiologists and Radiotherapists (MRO of RSRR) and the founder of Management in  Radiology  (MIR) national school and MIR international summit. He is a member of ESR committees, organizer and Chair of Artificial Intelligence in Healthcare subcommittee, and member of the Expert Council of the  Moscow International Medical Cluster  (Skolkovo). [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5326", "text": "Morozov is a co-organizer and academic director of Healthcare Management: Leaders of Change graduation program at the  Moscow School of Management SKOLKOVO . He founded Digital Diagnostics peer-reviewed  scientific journal  and is its Deputy Editor-In-Chief. [ 7 ]  Moreover, Morozov is an editorial board member at Diagnostic and Interventional Radiology, Journal of Telemedicine and E-Health, [ 8 ]  and Medical Visualization. [ 9 ] \nAfter the beginning of the special operation in February 2022, he left [ 10 ]  Russia and accepted [ 11 ]  a position of Innovations Director in a Belgian company, [ 12 ]  specializing in IT solutions for radiology."}
{"_id": "WikiPedia_Radiology$$$corpus_5327", "text": "Morozov is an author and co-author of more than 250 papers,  monographs , and books. He owns 28  patents  and certificates of invention and has supervised five PhD thesis.  Russian Science Citation Index  (SPIN) 8542-1720. [ 13 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5328", "text": "Morozov co-initiated and developed Radiography Guidelines (effective in Russia from 2021) and took part in the development of the new Ultrasound Guidelines, Occupational Standards for Radiographers, and Diagnostic Imaging Guidelines in  COVID-19 . He organized the pilot projects on Moscow LDCT  Lung Cancer  Screening and Moscow  Breast Cancer  Screening and created the National Ranking of Radiology Departments, which has been calculated annually since 2018. In 2016\u20132018, he promoted the creation of a  PET/CT  imaging system that can be accessible to general public."}
{"_id": "WikiPedia_Radiology$$$corpus_5329", "text": "Morozov is a co-author and co-editor of Artificial Intelligence in Medical Imaging published by  Springer Science+Business Media , which provides a historical overview of  artificial intelligence  use in radiology, its technical background, and discusses the impact of new and emerging technologies on medical imaging. Morozov is an initiator and co-author of the Fundamentals of Management in Radiology."}
{"_id": "WikiPedia_Radiology$$$corpus_5330", "text": "As a strong supporter of  digitalization  of healthcare,  automation  of diagnostic imaging, development of innovative technologies and methods, their incorporation into clinical practice, and  big data  use in healthcare, Morozov initiated the creation of the Unified Radiological Information Service and the launch of the Moscow Experiment on the Use of Innovative Computer Vision Technologies for Analysis of Medical Images. In 2019, he piloted a project to equip outpatient radiology departments with  speech recognition  systems. In 2020, at the Moscow Center for Diagnostics & Telemedicine, Morozov facilitated the foundation of Moscow Radiology Reference Center, the first teleradiology center in the Russian public healthcare sector."}
{"_id": "WikiPedia_Radiology$$$corpus_5331", "text": "At the Moscow Center for Diagnostics and Telemedicine, Morozov supervises a research team that managed to collect the world's largest dataset of anonymized chest CT scans of patients with confirmed  COVID-19 ."}
{"_id": "WikiPedia_Radiology$$$corpus_5332", "text": "Sydney Domville Rowland  (29 March 1872 \u2013 6 March 1917) was an English physician and the world's first editor of a  radiology  journal. He coined the term \" skiagraphy \" and wrote some of the first works on  X-rays  in the  Archives of Clinical Skiagraphy  that preceded the  British Journal of Radiology ."}
{"_id": "WikiPedia_Radiology$$$corpus_5333", "text": "Rowland worked in India and helped confirm how  plague  is spread by rats carrying fleas, and later joined the  Royal Army Medical Corps  in the  First World War  as a bacteriologist in France, where he worked on septic wounds,  typhoid  carriers and  gas gangrene , and set up No. 1 Mobile Laboratory, the  first of its kind . He died at the age of 44 years after contracting  meningitis  during his work."}
{"_id": "WikiPedia_Radiology$$$corpus_5334", "text": "Sydney Rowland was born in  Cornwall , the United Kingdom, on 29 March 1872, [ 2 ]  the eldest son of the Reverend William J. Rowland and Margaret Domville. [ 3 ]  He had one sister, Agnes, and two brothers, William and Cecil. [ 3 ]   Ernest Hart , editor of the  British Medical Journal  ( BMJ ), was his uncle. [ 3 ]  In 1873, he moved to India with his family and lived in  Jabalpur ,  Calcutta  (now Kolkata), and  Darjeeling . [ 3 ]  In 1880 he returned to England and attended  Berkhamsted School , where he held a scholarship. [ 3 ] [ 4 ]  He won a  natural sciences  scholarship to  Downing College , Cambridge, [ 5 ]  where he was president of the Natural History Society, and from where he graduated in 1892 with a 1st Class in Natural Sciences Tripos Part I, and in 1893 with a 2nd Class in Part II. [ 3 ] [ 4 ]  He passed his first and second M.B. at Cambridge and won the Shuter scholarship at  St Bartholomew's Hospital , London, from where he graduated M.R.C.S., L.R.C.P. in 1897. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5335", "text": "Rowland's career began in medical journalism while he was still a medical student when, in 1896, as Hart's intern, the year following the  discovery of X-rays , [ 6 ]  the  BMJ  appointed Rowland as \"Special Commissioner\" to produce a report on the clinical use of X-rays titled \"Report on the Application of the New Photography in Medicine and Surgery.\" [ 3 ] [ 6 ] [ a ]  It was published in 17 parts between 8 February 1896 and 12 June 1897. [ 3 ]  In May 1896, he founded the world's first X-ray journal, the  Archives of Clinical Skiagraph , a radiology journal that preceded the  British Journal of Radiology . [ 3 ] [ 6 ]  In the preface to the first issue, written in April 1896, he wrote that \"the object of this publication is to put on record in permanent form some sort of the most striking applications of the new photography to the needs of medicine and surgery\". [ 6 ]  He coined the term \" skiagraphy \" to describe the making of X-ray pictures and wrote some of the early works on  radiology . [ 3 ]  Without any radiology experts or X-ray departments at the time, his journal became an essential reading. [ 6 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5336", "text": "He stopped studying X-rays in 1897 and moved into the field of laboratory medicine. [ 4 ]  The following year, he became an assistant bacteriologist at the  Lister Hospital . [ 3 ] [ 4 ]  In 1905, the Lister sent him to India to investigate and confirm the theory that plague is spread by rats carrying fleas. [ 4 ]  He returned to England in 1908 and 1909 and was sent to the Plague Commission again. Still, this time to investigate plague prevention in the UK and later to find out how an outbreak of plague appeared in  Freston  village, East Suffolk. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5337", "text": "Later, he joined the  Royal Army Medical Corps  in the  First World War  as a bacteriologist. [ 3 ]  In 1914, he bought a large motor caravan in England and set up  No. 1 Mobile Laboratory , which he drove to the army area in France himself. [ 7 ]  The first of its kind, it formed the model for later mobile laboratories. [ 7 ]  During the war, he also worked on septic wounds, typhoid carriers, and gas gangrene. [ 4 ] [ 8 ]  In 1915 he rose to the rank of Major and worked with the 26th General Hospital Royal Army Medical Corps. [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5338", "text": "Rowland died on 6 March 1917, at age 44, after contracting  meningitis . He is buried at  \u00c9taples Military Cemetery . [ 4 ] [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5339", "text": "Jalal Jalal Shokouhi  (born 1950,  Miandoab ,  West Azerbaijan ) is an Iranian radiologist, writer and historical and cultural researcher. He is the chief of  Iranian Society of Radiology  and also the first person who made polymer samples of  Saltman . [ 1 ]  He was one of the candidates for president election of  Iranian Medical Council . [ 2 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5340", "text": "Jalal Jalal Shokouhi was born in 1950 in Miandoab a city in West Azerbaijan province of  Iran . He attended elementary school and high school there and then traveled to  Mashhad  to study as a  general practitioner . In 1977 he graduated from  Mashhad University of Medical Sciences  and then continued his studies to his doctorate degree from  Shahid Beheshti University of Medical Sciences ."}
{"_id": "WikiPedia_Radiology$$$corpus_5341", "text": "After completing his academic educations in Iran, he also attended many courses such as Advanced  Radiology ,  Ultrasound ,  MRI  and intervention in Germany. He also earned his PhD degree in \"Head and Neck\" field. [ 3 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5342", "text": "Through his working years he taught as a professor in  Shahid Chamran Hospital ,  Shahid Beheshti University of Medical Sciences ,  Islamic Azad University  of Medical Science and also he cooperated with  Loghman Hakim Hospital . [ 4 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5343", "text": "Now Jalal Shokouhi is the chief of Iranian Society of Radiology and years of activity in this field made him one of the well-known figures in radiology science."}
{"_id": "WikiPedia_Radiology$$$corpus_5344", "text": "Activities of Jalal Jalal Shokouhi contain a wide range of medical to cultural ones. Besides decades in medical science and radiology, which is his special field, he also wrote a number of books in history and culture."}
{"_id": "WikiPedia_Radiology$$$corpus_5345", "text": "One of the most well-known activities of Jalal Shokouhi is his project in partnership with the Iranian  Cultural Heritage, Handcrafts and Tourism Organization ,  National Museum of Iran \nand  Zanjan Museum  about Radiology and CT Scan of  Saltman  and also some crafts and Pottery, determining their antiquity and properties. [ 5 ]  This project started in 2005 and resulted in building  polymer  samples of Saltman's skull."}
{"_id": "WikiPedia_Radiology$$$corpus_5346", "text": "In this case he presented many articles in different conferences and made interviews in many TV programs as a science,  anthropology  and sociology expert in  Iran  and Japan, like \"Saltman Documentary\" directed by \"Hassan Dehghan\". Today, he also cooperates with Iran's Heritage Organization as an adviser in radiography."}
{"_id": "WikiPedia_Radiology$$$corpus_5347", "text": "Shokouhi also had done completed many projects as a radiologist. He is the chief of Iranian Society of Radiology and presented many papers in journals like \"Ettelaat Elmi\", \" Biomedical Engineering \" and \"Radiology Management\". He also cooperates with Iranian  Medical jurisprudence  in its commissions."}
{"_id": "WikiPedia_Radiology$$$corpus_5348", "text": "Jalal Shokouhi also wrote a number of books in Radiology and Culture. \"Radiography Made Simple\" and \" Orthopedic surgery  and  MRI \" are two of his books which are also referred to by academics. [ 7 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5349", "text": "He was the manager of Iran Radiology Conference for several years and Middle East and Europe Conference on spinal cord, in 2007 and 2009 at  Abu Dhabi  and  Kish Island . [ 8 ]  He was also selected as the premier doctor of Iranian Medical Council."}
{"_id": "WikiPedia_Radiology$$$corpus_5350", "text": "In terms of cultural activities, he published some books in history and  travel literature . Moreover, he is the chief of Shokouhi's Foundation which publishes and revives old books and  manuscripts . [ 9 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5351", "text": "Objection to Arresting Radiologists"}
{"_id": "WikiPedia_Radiology$$$corpus_5352", "text": "After that incident, Jalal Jalal Shokouhi as the chief of Iranian Society of Radiology, wrote a letter to the Iranian Ministry of Health and expressed his willingness to solve the problem using reason and conversation. [ 13 ]"}
{"_id": "WikiPedia_Radiology$$$corpus_5353", "text": "Fang-Fang Yin  is a Chinese-born radiologist."}
{"_id": "WikiPedia_Radiology$$$corpus_5354", "text": "Yin earned a Bachelor of Science degree from  Zhejiang University  in 1982. He subsequently moved to the United States, completing a Master of Science degree at  Bowling Green State University  in 1987, followed by a doctorate at the  University of Chicago  in 1992. [ 1 ] [ 2 ]  Yin teaches at  Duke University , where he is affiliated with the  Duke Cancer Institute , [ 3 ]  and was appointed the Gustavo S. Montana Professor of Radiation Oncology in 2021. [ 4 ] [ 5 ]"}
{"_id": "ultrasound$$$ba40d9af-b271-432e-8e15-74c42cb63074", "text": "As early as the 1990s, there was discussion in the literature regarding the usefulness of ultrasound in the rapid assessment of blunt trauma.[3] The natural advantage of ultrasound over pure clinical intervention is the accuracy of visualization, sensitivity (49\u201399% versus 27\u201345%), and specificity (95\u2013100%). The advantage of ultrasound over CT scanning is the rapidity of the exam and the fact that the physician may remain at the bedside to make critical decisions regarding the potential rapidly changing condition of the patient. In a patient who has received blunt trauma (often from a motor vehicle accident) or penetrating trauma (such as a gunshot wound), the presence of free blood or free air in the abdomen may be seen within a few minutes by an experienced clinician.[4]"}
{"_id": "ultrasound$$$ea3f77ee-61c4-4b93-bdc6-68136f16cb9e", "text": "The original basis of trauma ultrasound was that the blood that escaped the vascular system due to trauma (e.g., bleeding inside the abdomen) would be seen as an abnormal hypoechoic entity in the abdomen. This concept is greatly aided by the fact that there are anatomic \u201cpotential spaces\u201d where fluid, mostly extravascular blood, collects. Potential spaces had been known for centuries as locations where abnormal fluid collections could be reliably found and removed. It is with the more sophisticated radiology modalities that the fluid can be located before surgery and used diagnostically to help determine if surgery is necessary. Ultrasound imaging quickly and reliably indicates emergent surgery to stop the bleeding from a liver laceration, a splenic laceration, an ectopic pregnancy rupture, a bladder rupture, an injury to a major blood vessel, or less frequent injuries to other organs."}
{"_id": "ultrasound$$$8399d2c2-db05-43e5-b65c-9b555284b7d7", "text": "The FAST exam evaluates the right upper quadrant, the left upper quadrant, and the pelvis, as shown in Figure 11-1.[5] Most famous because of the more defined areas are Morrison\u2019s pouch (in the right upper quadrant, highlighted by the contrasting bright, hyperechoic Gerota\u2019s fascia) and the pouch of Douglas (in the low midline of the pelvis between the hyperechoic borders of the bladder in males or vagina in females superiorly and the rectum inferiorly). The splenic-renal recess in the left upper quadrants and the paracolic gutters in both the right and left lower quadrants are important to access but less easy to navigate."}
{"_id": "ultrasound$$$60158f42-1320-4af2-967f-a191fc3c3889", "text": "The rapid ultrasound exam for trauma has extended to areas above the diaphragm as ultrasound has progressed. The eFAST (the extended FAST exam) also evaluates the lungs and heart[6] in addition to the abdomen, as shown in Figure 11-1. The probe is pointed superiorly from the xiphoid area to gain views of the heart and lungs. Again, the hypoechoic reflection of free, abnormal fluid is used as an indication of emergent surgery."}
{"_id": "ultrasound$$$270c98af-5359-4807-bc97-af7da4012da7", "text": "Above the diaphragm, this fluid collection indicates emergent action in the form of a pericardial or pleural effusion. In the case of pericardial effusion, cardiac tamponade can occur and must be treated immediately. Cardiac tamponade is a medical condition that causes the restriction of ventricular filling due to pressure of fluid in the pericardium. In the case of pleural effusion, the restriction is not the initial problem. However, there may be ongoing bleeding contributing to the effusion that must be stopped. Cardiac imaging is used to evaluate pericardial effusion. There are two different cardiac views. The parasternal long-axis view is obtained by placing the transducer just left of the sternum in the fourth or fifth intercostal space oriented to the right shoulder, as shown in Figure 11-2. The parasternal sagittal ultrasound view of the heart is shown in Figure 11-3. The abbreviations LV, RV, LA, RA, and A have been used for the left ventricle, right ventricle, left atrium, right ventricle, and aorta, respectively, in some of the following ultrasound images."}
{"_id": "ultrasound$$$78c81975-a844-4172-ad96-37d4ac7b248e", "text": "The subxiphoid view can sometimes be challenging in a patient who is considered obese. First, locate the xiphoid process, place the transducer down in a transverse position with the indicator facing toward the right, and aim between the head and left shoulder, as shown in Figure 11-4. Gently apply pressure downward, and visualize the cardiac contractility during respiration to identify the best visualization. Figure 11-5 shows the four-chamber view of the heart during this evaluation. Assess for hemopericardium, or fluid around the heart."}
{"_id": "ultrasound$$$9fbd8784-efc8-4dd6-9ee8-56ec001639d6", "text": "Pulmonary imaging in trauma has evolved over the years. Most recently, with the COVID-19 pandemic, it has become a more detailed and important part of the evaluation addressed in Chapter 8."}
{"_id": "ultrasound$$$ffd3bebc-83f4-4d32-8193-06bdc7f4b345", "text": "Peritoneal imaging of the abdomen/pelvis evaluates fluid in the hepatorenal recess (also referred to as Morrison\u2019s pouch), splenorenal recess, and pelvic cavity. Figure 11-6 shows a cross-sectional diagram of the abdomen, demonstrating Morrison\u2019s pouch (hepatorenal recess) and the splenorenal recess. The most straightforward abdominal view is to place the transducer in the midaxillary line at the 8th to 11th intercostal space with cephalad orientation."}
{"_id": "ultrasound$$$e0518679-61bf-40f3-9fe7-7ca825910af2", "text": "First, start on the right abdominal region in the midaxillary line between the 8th to 11th intercostal spaces, as shown in Figure 11-7. Maneuver the transducer by sliding, fanning, angling, and rotating until you can visualize the liver and kidney well. The abbreviations L, R, K, P, and S have been labeled in some of the following ultrasound images, representing liver, recess (hepatorenal and splenorenal), kidney, pleura, and spleen, respectively. Figure 11-8 represents the hepatorenal view, showing the liver, hepatorenal recess, kidney, and pleura."}
{"_id": "ultrasound$$$8b9c69d7-5d3d-4334-8ff4-108681b628b3", "text": "Next, place the transducer in the longitudinal plane with the indicator facing the patient\u2019s head, evaluating between the fifth to ninth intercostal spaces, as shown in Figure 11-9. Again, maneuver the transducer until you can visualize the spleen and kidney well. Figure 11-10 represents the splenorenal view, showing the spleen, splenorenal recess, and kidney."}
{"_id": "ultrasound$$$b13e2beb-cea9-42f1-acf2-41dfa0693370", "text": "The pelvic cavity also has an area where peritoneal fluid can collect within the pouch. In women, it is called the rectouterine pouch or pouch of Douglas (peritoneum between the rectum and uterus). In men, it is referred to as the rectovesical pouch (peritoneum between the rectum and bladder), as shown in Figure 11-11."}
{"_id": "ultrasound$$$5fa5147c-08f5-4ff7-bf65-fa584ec2ee2b", "text": "Figure 11-12 shows an ultrasound image of the bladder (abbreviated B on the image) obtained by placing the transducer in the patient\u2019s midline, right above the pubic symphysis. This concludes the eFAST exam."}
{"_id": "ultrasound$$$ac905635-2981-4e4a-b7b6-f55b10013a80", "text": "The best time to stop bleeding is as soon as possible. When the bleeding is not apparent or external, ultrasound has made leaps of progress regarding rapid diagnosis. The first hour after trauma, known as the \u201cGolden Hour of Trauma,\u201d is a recognized time entity in which medical professionals aim to provide definitive care. In the future, it may well be a standard of care for paramedics to perform ultrasound on the scene. In this case, the image will be transmitted to an emergency department and a trauma surgeon\u2019s cell phone so that preparations for emergent surgery may be made before the patient arrives. Perhaps in the future, the patient will be taken immediately off the ambulance and directly to surgery. Trials of this technology are ongoing all over the world."}
{"_id": "ultrasound$$$b93950ed-22b5-4904-b90e-f16e9013bf8e", "text": "The primary physiologic functions of the venous system are to return the deoxygenated blood to the heart, thermoregulate, store blood (at any instance, the venous system contains up to 70% of the circulating blood), and regulate the cardiac output. It is divided into three systems: superficial, perforating, and deep veins. Figure 10-1 shows the anatomy of the venous system. Blood flows from the superficial to deep veins through branching perforating veins. The deep veins usually follow the arteries in the same areas and often have similar names. For example, the femoral vein is beside the femoral artery. The deep venous system eventually returns blood to the right side of the heart. Since the venous system is usually a low-pressure system, veins have bicuspid valves to allow flow in one direction from superficial to deep (the foot is the exception) and from distal to proximal. Muscular contraction helps with venous flow, such as in the calf muscle pump in the leg.[1]"}
{"_id": "ultrasound$$$632ce9e8-b8a4-48b9-a4af-145661e9f41a", "text": "Venous pathophysiology has many etiologies, such as trauma and genetic predisposition, and can occur when outflow is impaired by dysfunctional valves, resulting in retrograde flow and causing a condition known as chronic venous insufficiency. Vein thrombosis is another condition with many hereditary and acquired etiologies, such as trauma or prolonged immobilization. Deep vein thrombosis is especially important to evaluate and treat.[2]"}
{"_id": "ultrasound$$$9d40ab2e-c955-4112-89a5-d26d863909cc", "text": "The great saphenous vein (GSV) is the longest vein in the human body, as shown in Figure 10-2. It originates in the medial aspect of the foot as part of the dorsal arch. It continues proximally along the medial aspect of the foot and passes anterior to the medial malleolus on the tibia. It ascends along the medial aspect of the leg between the superficial and deep fascia. It typically has 10\u201320 valves and terminates at the saphenofemoral junction (SFJ). Once flow enters the femoral vein, it is in the deep venous system. Venous anatomy can vary from individual to individual. However, the GSV typically has branching superficial veins, such as the anterior and posterior accessory saphenous veins in the thigh.[3]"}
{"_id": "ultrasound$$$0ce8893b-65d3-4a6e-922b-ae4aedcb93ec", "text": "The small saphenous vein (SSV) is the second most significant superficial vein that joins the dorsal venous arch in the lateral aspect of the foot. It ascends proximally behind the lateral malleolus and terminates into the deep popliteal vein, although this is highly variable and can extend into the thigh. The SSV typically has 9\u201312 valves. Like the GSV, the SSV lies between the superficial and deep fascia and can have many branching superficial veins. Perforating veins connect superficial to deep veins. They usually contain a bicuspid valve.[4]"}
{"_id": "ultrasound$$$cdce2c10-7107-4b98-9a9f-5963cc01100b", "text": "The deep venous system includes the common femoral vein, profunda femoral vein, deep femoral vein, popliteal vein, gastrocnemius veins, soleus veins, anterior tibial veins, posterior tibial veins, and peroneal veins. The direction of venous flow is described as antegrade, retrograde, or absent. In both the deep and superficial venous systems, it is essential to check for the following characteristics: compressibility, spontaneous flow, respiratory variation, augmentation, intraluminal defects, and venous reflux."}
{"_id": "ultrasound$$$87edb9d1-080e-4869-9f1b-64ead1f3211d", "text": "Compressibility evaluates if the vein collapses by applying downward pressure with the transducer. Typically, it should compress, since it is a low-pressure vessel. A thrombus can occlude the lumen and prevent compression. Spontaneous flow is observed when the blood flow moves actively without external influences, such as an augmentation maneuver. Respiratory variation, also known as phasicity, refers to regular venous flow changes that occur secondary to intrathoracic pressure during breathing cycles. Augmentation is a maneuver that is used to evaluate possible abnormal flow patterns. For example, by squeezing a distal portion in the calf, an increase in venous flow should be observed just proximal to this area. Absent or diminished flow could suggest obstruction, such as in a thrombus formation, and reversal of flow could indicate incompetent venous valves, such as in venous reflux disease."}
{"_id": "ultrasound$$$248e1ec2-a018-40e1-902d-e3963a654a30", "text": "Intraluminal defects usually describe a thrombus formation within the lumen of the vein. It is crucial to describe the details of the thrombus formation and whether it is obstructive."}
{"_id": "ultrasound$$$07e3fe47-442c-4991-ac90-f39130a2560a", "text": "Finally, venous reflux describes blood flow going in the wrong direction, usually from incompetent valves. Maneuvers are usually done to augment blood flow to test for reflux, which is significant if it exceeds seconds in the superficial venous system, seconds in perforators, and 1 second in the deep venous system."}
{"_id": "ultrasound$$$4d557358-6ca5-4b8b-85bc-d2b3a1e36e00", "text": "A complete venous duplex ultrasound of the lower extremities starts with a proximal to distal evaluation of the deep venous system in a transverse (TRV) side-by-side image without compression and with compression (COMP). This is followed by a sagittal (SAG) view with augmentation (AUG) using the color Doppler. The veins that are evaluated in succession include the common femoral vein (CFV), profunda femoral vein (PROF V), femoral vein (FV), popliteal vein (POP V), gastrocnemius vein (GASTROC V), posterior tibial vein (PTV), peroneal vein (PERO V), anterior tibial vein (ATV), great saphenous vein (GSV), and small saphenous vein (SSV). The abbreviations given in parentheses in the last few sentences have been labeled in some of the following ultrasound images for venous system discussion. Figure 10-3 shows a side-by-side transverse ultrasound view of the right common femoral vein without compression and with compression, while Figure 10-4 represents the sagittal view of the right common femoral vein with augmentation."}
{"_id": "ultrasound$$$73ecf0b4-cd2c-40ac-a0af-43305c53777a", "text": "Figure 10-5 shows a side-by-side transverse ultrasound view of the right profunda femoral vein without compression and with compression, while Figure 10-6 represents the sagittal view of the right profunda femoral vein with augmentation."}
{"_id": "ultrasound$$$ae0a41c0-35dd-4d6a-9699-1e3d3b08c89a", "text": "Figure 10-7 shows a side-by-side transverse ultrasound view of the right femoral vein without compression and with compression, while Figure 10-8 represents the sagittal view of the right femoral vein with augmentation."}
{"_id": "ultrasound$$$18b2cb77-a6c1-4fef-8094-dfd2d69bcf68", "text": "Figure 10-9 shows a side-by-side transverse ultrasound view of the right popliteal vein without compression and with compression, while Figure 10-10 represents the sagittal view of the right popliteal vein with augmentation."}
{"_id": "ultrasound$$$8b196d0e-2c9b-486a-8a13-a47093c403a2", "text": "Figure 10-11 shows a side-by-side transverse ultrasound view of the right gastrocnemius vein without compression and with compression, while Figure 10-12 represents the sagittal view of the right gastrocnemius vein with augmentation."}
{"_id": "ultrasound$$$273ff9a6-4b2e-42f7-9cbe-2fdd18e43e13", "text": "Figure 10-13 shows a side-by-side transverse ultrasound view of the right posterior tibial vein without compression and with compression, while Figure 10-14 represents the sagittal view of the right posterior tibial vein with augmentation."}
{"_id": "ultrasound$$$004926eb-ed66-4ae4-afe3-5b5a9f521f91", "text": "Figure 10-15 shows a side-by-side transverse ultrasound view of the right peroneal vein without compression and with compression, while Figure 10-16 represents the sagittal view of the right peroneal vein with augmentation."}
{"_id": "ultrasound$$$079f0445-b767-43b9-a975-3ee5d53e3245", "text": "Figure 10-17 shows a side-by-side transverse ultrasound view of the anterior tibial vein without compression and with compression, while Figure 10-18 represents the sagittal view of the right anterior tibial vein with augmentation."}
{"_id": "ultrasound$$$833c69a2-b385-4b33-afd0-087b1e083eb4", "text": "Next, in the complete venous duplex ultrasound, we look at the superficial venous system from proximal to distal, starting with the GSV at the SFJ in the transverse plane with a side-by-side image without and with color Doppler, followed by a sagittal image with augmentation with color Doppler. Figure 10-19 shows a side-by-side transverse ultrasound view of the right GSV at the SFJ, while Figure 10-20 represents the sagittal view of the right GSV at the SFJ with augmentation."}
{"_id": "ultrasound$$$14d6c230-ba8c-43e3-91b4-134eeb29be3a", "text": "Next, we continue to follow and evaluate the GSV distally from above the knee (AK) to below the knee (BK) in the transverse plane without color, followed by the sagittal plane with augmentation with color Doppler. The abbreviations AK and BK have been used in the ultrasound images discussed here. Figure 10-21 shows a side-by-side transverse ultrasound view of the right GSV above the knee. Figure 10-22 represents the sagittal view of the right GSV above the knee with augmentation."}
{"_id": "ultrasound$$$2006bafb-e7f9-4370-868d-1d8efe73b50b", "text": "Figure 10-23 shows a transverse ultrasound view of the right GSV below the knee, while Figure 10-24 represents the sagittal view of the right GSV below the knee with augmentation."}
{"_id": "ultrasound$$$b8f859e9-52cb-4e7a-b656-915686b480ac", "text": "The next superficial vein to be evaluated is the SSV, starting in the popliteal area of the lower extremity and using the same approach as the great saphenous vein. We first start with a transverse image at the saphenopopliteal junction (SPJ) without color Doppler, followed by a sagittal image with augmentation with color Doppler. Figure 10-25 shows a side-by-side transverse ultrasound view of the right SSV at the SPJ, while Figure 10-26 represents the sagittal view of the right SSV at the SPJ with augmentation."}
{"_id": "ultrasound$$$98d923c3-87d9-4816-bc06-fb301173a6f5", "text": "Also, anterior and posterior accessory saphenous veins are often evaluated as part of the superficial venous system, and perforating veins that connect superficial to deep veins are often evaluated during the study."}
{"_id": "ultrasound$$$848a0bae-b4da-4b21-811e-109e271e68bd", "text": "The template shown in the next couple of pages can be used to perform a complete venous duplex Doppler ultrasound examination of the lower extremities."}
{"_id": "ultrasound$$$8b7c6a6e-54d6-4c37-bdc3-56bc6cd5a295", "text": "Figure 10-27 shows the anatomy of the arterial system, which will be helpful in discussing and understanding various ultrasonography images of the arteries."}
{"_id": "ultrasound$$$f21a23d7-1ed0-4d43-9af1-60e0e148f375", "text": "Norwegian physicist Rune Aaslid developed intracranial ultrasound in 1982. Transcranial imaging was subsequently developed by a German neurologist, Ulrich Bogdahn, in 1990. It was the first noninvasive way to evaluate the circle of Willis using a low-frequency transducer (2 MHz).[5],[6]"}
{"_id": "ultrasound$$$2f10db14-ef44-4f68-b9da-74c786178474", "text": "Transcranial Doppler (TCD) can detect intracranial stenosis, vasospasm secondary to subarachnoid hemorrhage, and arteriovenous malformations and assess suspected brain death. A TCD system usually has a 2 MHz pulsed Doppler with a spectrum analyzer. A typical TCD probe is shown in Figure 10-28. Blood flow in TCD is usually measured in cm/sec, and Figure 10-29 represents a TCD velocity distribution. When evaluating intracranial vessels, it is vital to know the acoustic window, depth, direction of blood flow, velocity, and angle of insonation. One important principle when evaluating pathology is the pulsatility index (PI)."}
{"_id": "ultrasound$$$de8dbeb8-e1bf-474f-bc9c-2505312a4c31", "text": "A high PI (>) can indicate increased intracranial pressure, microvascular disease, or distal vasospasm. Also, a low PI (<) can be seen with carotid stenosis or occlusion as well as arteriovenous malformations.[7],[8]"}
{"_id": "ultrasound$$$a8931776-ed59-4704-b984-e5fa3c9e2f93", "text": "The three most common acoustic windows that provide direction to evaluate the intracranial vessels are the transtemporal, transorbital, and transforaminal windows, as shown in Figure 10-30. The transcranial evaluation begins with the transtemporal approach on each side to identify the anterior, middle, and posterior cerebral arteries, and sometimes, the most distal aspect of the internal carotid artery (ICA) may also be evaluated.[9],[10]"}
{"_id": "ultrasound$$$b8e09b8c-3314-4b65-be3a-592b86544531", "text": "When evaluating the anterior cerebral artery, normal flow is away from the probe, the depth is 60\u201370 mm, and the velocity ranges from 41\u201376 cm/sec. The middle cerebral artery has normal flow toward the probe, a depth of 30\u201360 mm, and a velocity that ranges from 46\u201386 cm/sec. The posterior cerebral artery typically has flow toward the probe, a depth of 60\u201370 mm, and a velocity range of 33\u201364 cm/sec, as shown in Figure 10-31.[11],[12],[13]"}
{"_id": "ultrasound$$$9b4c0284-15fd-4a8b-b09c-a49f26bf8340", "text": "The transorbital approach is followed and used to evaluate the ophthalmic artery and carotid siphon on each side, as shown in Figure 10-32. The location for of obtaining flow patterns is essential in this window, since it is difficult to determine the anatomic structure, as in the transtemporal approach demonstrating the circle of Willis. Comparisons can be made between different flow patterns."}
{"_id": "ultrasound$$$504c2b01-6a86-4ccd-9eb3-73d048d5a69b", "text": "The transforaminal approach is then used to evaluate the intracranial vertebral arteries and the basilar arteries, as shown in Figure 10-33."}
{"_id": "ultrasound$$$417ca75c-1e42-4c39-9bbc-986a4bb357cf", "text": "In the vertebral arteries, normal blood flow is away from the probe, the depth is 60\u201370 mm, and the velocity ranges from 27\u201355 cm/sec. In the basilar arteries, normal blood flow is away from the probe, the depth is 80\u2013120 mm, and the velocity is 30\u201357 cm/sec."}
{"_id": "ultrasound$$$8ebf445d-b3df-4c01-99cd-3db6494256ca", "text": "Figure 10-34 shows the positioning of the ultrasound probe for carotid artery evaluations. A high-frequency linear transducer (\u201310 MHz) is most appropriate for carotid sonography. Transverse and longitudinal views are both imaged in B-mode, color, and spectral Doppler. In the sagittal plane, the ICA, external carotid artery (ECA), and right common carotid artery (CCA) are followed from the clavicle to the mandible with anterior, oblique, lateral, and posterior projections to identify plaque formation. Comparison flow characteristics are made from one side to the other as well as from proximal to distal segments of the ICA, ECA, and CCA.[14] In the transverse plane, the ICA and CCA are followed to evaluate plaque formations. The percentage of stenosis can then be evaluated by looking at the diameter reduction. Plaque characteristics can be evaluated for calcification, thrombosis, and fibrosis."}
{"_id": "ultrasound$$$ce1340e3-b56c-4112-bbce-201c0030fb81", "text": "Figure 10-35 shows the CCA in the proximal transverse plane with the jugular vein on top, demonstrating blood flow in the opposite direction following the BART principle. Prox is the abbreviation used for proximal in the image for Figure 10-35 and some of the other following ones. Pulsed Doppler with spectral analysis is the primary tool for evaluating blood flow in the vascular study."}
{"_id": "ultrasound$$$32e398b1-097a-4150-b31b-4d8abdf29c31", "text": "Figure 10-36 shows the pulsed wave (PW) Doppler with spectral analysis of the right CCA in the distal sagittal plane. Spectral analysis is a method of displaying the variety of frequencies of blood flow during systole and diastole. The scanner technology automatically analyzes and displays the individual frequencies of the returned signals, creating a velocity profile consisting of time on the horizontal axis, frequency shifts on the vertical axis, and amplitude as brightness. This combination of blood flow analysis and anatomic information is the basis of duplex ultrasonography,[15] as discussed in Chapter 2."}
{"_id": "ultrasound$$$f2a96a7d-486c-4569-8f45-78a1a7cdd901", "text": "The Doppler characteristics of the carotid artery system are different. The ICA and CCA usually have low flow resistance, as shown in Figures 10-37 and 10-38, respectively. Flow occurs throughout the cardiac cycle. The diastolic segment does not touch the baseline. The ECA has high flow resistance with little or no diastolic or reversed diastolic flow. Reproducible and consistent velocity measurements require an angle of 60 degrees or less. Although a zero-degree angle of insonation provides the most remarkable Doppler shift because this depends on the angle\u2019s cosine, this would be difficult with most vessels. The criteria used for the interpretation of velocity measurements were established using a 60-degree angle.[16],[17]"}
{"_id": "ultrasound$$$b3467db5-ffd6-44f2-8cd5-c306a8ac0e52", "text": "Since the brain is a low-resistance vascular bed, the ICA is less pulsatile with increased flow during diastole. The typical waveform of the ICA has a rapid upstroke during systole and a high diastolic component with a possible dicrotic notch and gradual downslope."}
{"_id": "ultrasound$$$f074685e-b117-45de-a014-504a95073394", "text": "With the common carotid artery in the longitudinal plane, the transducer is angled more posterolaterally to identify the vertebral artery. Vertical shadows will appear running through the vertebral arteries, which are the transverse processes of the vertebrae, as shown in Figure 10-39. Vert in the image represents the vertebral artery. Flow direction is documented."}
{"_id": "ultrasound$$$4a722eaa-e710-4357-aec1-b8f9b6b40190", "text": "The ECA supplies blood to vascular areas with higher resistance, such as the scalp. It has a rapid upstroke in systole and rapid downstroke in diastole with a dicrotic notch, as shown in Figure 10-40."}
{"_id": "ultrasound$$$70753ce5-5b81-4532-bf03-9257d002fba7", "text": "Both the CCA and vertebral arteries have low flow resistance. The flow characteristics are similar to the ICA. Multiple guidelines and trials are used to determine the percentage of diameter stenosis and clinically relevant stenosis. The ICA is of the most importance for surgical intervention. The Society of Radiologists in Ultrasound Consensus, one of the most widely used guidelines to assess ICA stenosis, is presented in Table 10-1 the table below.[18]"}
{"_id": "ultrasound$$$aa0fe0b5-4efd-40ed-a847-1e1afe947808", "text": "The North American Symptomatic Endarterectomy Trial was published in the journal Stroke in 1991.[19] The results concluded that patients with 70\u201399% stenosis of the ICA benefit from surgical intervention in the appropriate clinical setting."}
{"_id": "ultrasound$$$f9e32249-c52e-433d-9c02-4e2c22855481", "text": "The aorta is the largest artery in humans. It branches off the heart\u2019s left ventricle into the thoracic and abdominal cavities, as shown in Figure 10-41. The abdominal aorta branches into the right and left iliac arteries at the level of the umbilicus, where it carries oxygenated blood to each lower extremity. When the wall of the aorta weakens and expands, an aneurysm develops (with an increased risk of rupture under this high-pressure system)."}
{"_id": "ultrasound$$$3b0dc5bf-a6f0-4e9b-912a-14409d9e8d1b", "text": "Each year, 200,000 people in the United States are diagnosed with an abdominal aortic aneurysm (AAA). Of these, nearly % have a life-threatening risk of rupture. The majority of patients with AAA are asymptomatic. The aorta\u2019s diameter must be greater less than 3 cm to be diagnosed as an aneurysm. When it reaches 5 cm or greater, very close monitoring and surgical options are entertained. Risk factors for an AAA include hypertension, smoking, and genetic factors, especially involving immediate relatives with AAA. Men over the age of 60 are also at greater risk.[20]"}
{"_id": "ultrasound$$$c2ffb4cf-6483-4409-b8c1-e2dd95678652", "text": "The ultrasound evaluation of the abdominal aorta (A or AA) should include the proximal, mid, and distal aorta to the bifurcation in the transverse and longitudinal planes, as shown in Figure 10-42. Evaluation of the branches of the aorta should include the celiac artery (C), superior mesenteric artery (SMA), and renal artery branches, as shown in Figures 10-43 and 10-44, without and with color Doppler, respectively.[21] The abbreviations given in parentheses in this paragraph have been labeled in some of the ultrasound images discussed below."}
{"_id": "ultrasound$$$7875d3f8-b4eb-4b87-aa2b-1f6ac49e503f", "text": "Figure 10-45 shows the normal anatomical branches of the arterial system in the lower extremity. Peripheral artery disease (PAD) is a condition in which the arteries of the lower extremities are narrowed primarily from atherosclerosis. Approximately 8 million people in the United States have PAD. Men and women are affected equally. Risk factors include smoking, diabetes, hypertension, high cholesterol, and being over 60 years of age. A classic symptom of PAD is claudication, or pain when walking. Lower-extremity arterial duplex scanning is a noninvasive way to identify the presence and severity of arterial occlusive disease."}
{"_id": "ultrasound$$$3b8c1cb7-15bc-47a6-b95f-bd41798bf7f8", "text": "It can also be used to follow the progression of the disease. The patient must rest for at least 20 minutes before testing, since this can affect the results, especially if the patient has PAD. The patient is then positioned supine with the lower extremities at the heart level so the hydrostatic pressure cannot falsely elevate the measurements."}
{"_id": "ultrasound$$$bdb38034-e378-4f1b-bb82-0453154a23af", "text": "During an arterial Doppler exam, various cuffs are placed on the patient\u2019s legs and arms. This exam uses color wave (CW) Doppler. CW Doppler employs two crystals contained in the same probe: one that transmits the signal and one that receives the reflected sound wave of the blood cells. The reflected frequency is either higher or lower than the transmitted frequency, depending on the flow direction. This change in frequency is called the Doppler shift. The ankle brachial index (ABI) is recorded, and the waveforms are analyzed. The ABI is a simple test that compares the blood pressure in the upper and lower limbs. The ABI is calculated by dividing the blood pressure in an ankle artery by the blood pressure in an arm artery. An ABI value of less than indicates PAD."}
{"_id": "ultrasound$$$619edc60-d14a-4b53-987f-4a81e9cda247", "text": "An arterial duplex is another type of evaluation that uses ultrasound. It starts proximally at the common femoral artery with a side-by-side transverse image without and with color Doppler, followed by a sagittal image of the artery in red and sometimes the corresponding vein(s) in blue, and finally, a sagittal image of the artery with waveform analysis, which includes peak systolic velocity (PSV) and end-diastolic velocity (EDV). As the arterial study is performed from proximal to distal, the same approach is obtained with each artery, including, in succession, the common femoral artery (CFA), profunda femoral artery (Prof A), superficial femoral artery (SFA), popliteal artery (Pop A), posterior tibial artery (PTA), peroneal artery (Pero A), anterior tibial artery (ATA), and dorsalis pedis artery (DPA). The abbreviations given in parentheses in the previous sentence have been labeled in some of the ultrasound images discussed below. The abbreviation Trans used in some of these images is for transverse. Figures 10-46 and 10-47 show the transverse and sagittal views, respectively, of the side-by-side images of the right common femoral artery without and with color Doppler. Figure 10-48 shows the sagittal view of the right common femoral artery with color Doppler and waveform analysis."}
{"_id": "ultrasound$$$2581c6ab-0aac-4157-a843-2c1496881d43", "text": "Figures 10-49 and 10-50 show the transverse and sagittal views, respectively, of the right profunda femoral artery without and with color Doppler. Figure 10-51 shows the sagittal view of the right profunda femoral artery with color Doppler and waveform analysis."}
{"_id": "ultrasound$$$43d08458-5c86-4a25-aff3-98d30a37c21a", "text": "Figures 10-52 and 10-53 show the transverse and sagittal views, respectively, of the right proximal superficial femoral artery without and with color Doppler. Figure 10-54 shows the sagittal view of the right proximal superficial femoral artery with color Doppler and waveform analysis."}
{"_id": "ultrasound$$$bb438e72-e30f-4886-831e-ed5dd480fec6", "text": "Figures 10-55 and 10-56 show the transverse and sagittal views, respectively, of the right middle superficial femoral artery without and with color Doppler. Figure 10-57 shows the sagittal view of the right middle superficial femoral artery with color Doppler and waveform analysis."}
{"_id": "ultrasound$$$9a922b13-37ac-40e7-ab87-f0abf8bafe82", "text": "Figures 10-58 and 10-59 show the transverse and sagittal views of the right distal superficial femoral artery without and with color Doppler. Figure 10-60 shows the sagittal view of the right distal superficial femoral artery with color Doppler and waveform analysis."}
{"_id": "ultrasound$$$19d7d0f6-9820-4d8c-a234-46958e7de23c", "text": "Figures 10-61 and 10-62 show the transverse and sagittal views, respectively, of the right popliteal artery without and with color Doppler. Figure 10-63 shows the sagittal view of the right popliteal artery with color Doppler and waveform analysis."}
{"_id": "ultrasound$$$c6108d25-ac76-4792-b31d-d908d2ffe791", "text": "Figures 10-64 and 10-65 show the transverse and sagittal views, respectively, of the right posterior tibial artery without and with color Doppler. Figure 10-66 shows the sagittal view of the right posterior tibial artery with color Doppler and waveform analysis."}
{"_id": "ultrasound$$$50756455-bf16-4a78-971a-d9c061217434", "text": "Figures 10-67 and 10-68 show the transverse and sagittal views, respectively, of the right peroneal artery without and with color Doppler. Figure 10-69 shows the sagittal view of the right peroneal artery with color Doppler and waveform analysis."}
{"_id": "ultrasound$$$7892e433-90f3-4778-bae9-26cbfc843d85", "text": "Figure 10-70 shows the side-by-side sagittal view of the right anterior tibial artery without and with color Doppler. Figure 10-71 shows the sagittal view of the right anterior tibial artery with color Doppler and waveform analysis."}
{"_id": "ultrasound$$$eb3e2998-f1ef-40f7-8375-2b107aa016e6", "text": "Figure 10-72 shows the transverse view of the right dorsalis pedis artery without and with color Doppler. Figure 10-73 shows the sagittal view of the right dorsalis pedis artery with color Doppler and waveform analysis."}
{"_id": "ultrasound$$$8dac82d2-2320-40d3-9abe-fa0d7d5b54f3", "text": "Figure 10-73: Sagittal image of the right dorsalis pedis artery with color Doppler."}
{"_id": "ultrasound$$$4aad36ce-bbd0-4e22-b52f-27c1b9666a00", "text": "When evaluating the lower extremities for diagnostic criteria for PAD, the PSV and velocity ratio (VR) are often used. The VR is defined as the ratio of the PSV of the stenotic area to the PSV of the standard proximal segment. The degree of stenosis is determined by these values of the PSV and VR, as illustrated in Table 10-2.[22]"}
{"_id": "ultrasound$$$fa16e870-67a3-4f62-9870-23f6aaeab1d9", "text": "Kidneys are interesting because understanding renal function and disease involves several disciplines, including chemistry, biology, and physics. In clinical medicine, we often analyze renal function using standard lab tests such as urinalysis, serum creatinine, and serum blood urea nitrogen (BUN). These tests give us clues about both normal function and etiologies of pathology. Examples of how the three tests help us begin abound: too much protein in the urine in the shape of a glomerulus (called \u201ccasts\u201d) may indicate immune-mediated glomerulonephritis, too-high creatinine alone may indicate diffuse renal failure and intravascular fluid overload, and an altered creatinine-BUN ratio may indicate intravascular fluid depletion."}
{"_id": "ultrasound$$$1af6b45f-cc53-4158-a3b9-ce6da84e45a8", "text": "In a typical ultrasound fashion, we will look at the end anatomic result of renal function and formulate a theory of a patient\u2019s condition. Figure 9-1 shows an ultrasonography scan of the longitudinal view of the usual left kidney."}
{"_id": "ultrasound$$$4ee7dc40-e07a-4002-9723-16304e36c6e4", "text": "Although it might be challenging to view a nephron or its functional parts on ultrasound, we can observe the results of renal malfunction with our gross anatomic view and make some rapid observations that may help a patient. The fascia is the outer fibrous covering of many organs, and Gerota\u2019s fascia is the one that surrounds the kidneys and adrenal glands. This fascia is particularly dense and hyperechoic, most often producing a bright reflection (white) back onto the screen in the B-mode. From this distinct outline, we can determine the size, shape, location, and consistency of the surrounding structures near the kidney. The kidney measures approximately 11\u201314 cm in length, 6 cm in width, and 4 cm in thickness. You may measure these at first, but you may soon only estimate the size visually. Other hyperechoic structures typically surround the kidney. The liver is located superior to the right kidney, and the spleen is located superior to the left kidney. The kidneys are retroperitoneal, or behind the peritoneal cavity. Difficulties in visualizing a kidney are due to the presence of air-filled lungs superior to it as well as the ribs. Air, of course, disperses the ultrasound waves so that reflection is complex. Ribs cause shadowing, which may completely prohibit your initial viewing attempts. Because the liver does not fully extend to the left side, the left kidney is often partially covered by the thoracic cavity and more challenging to visualize."}
{"_id": "ultrasound$$$6fb9dba2-7f71-4324-9224-043f32d51c0c", "text": "Other than size and shape, a general clinician ultrasound exam may include lobules, evaluation of cortex thickness, evaluation of the renal pelvis, a survey to evaluate hyperechoic renal calculi (kidney stones), and observation of the vessels entering and leaving the renal pelvis (renal arteries, renal veins, and ureters). If atrophy is noted or a patient has marked hypertension, renal artery blood flow velocity is calculated via Doppler technology to determine if there is renal artery stenosis. This latter exam is usually outside the realm of general clinical ultrasound. It may be best for the general ultrasound clinician to refer this exam to those who do the exam often."}
{"_id": "ultrasound$$$9952ffed-02e2-4753-a6a9-9b590efebbf5", "text": "Large kidneys, or hydronephrosis, may be due to congenital variation, but this most often is a condition due to distal obstruction. Figure 9-2 shows an ultrasound image of end-stage hydronephrosis. Most often, there is only unilateral obstruction of the ureter. As the kidney continues to make urine in the presence of ureteral obstruction, there is backflow pressure and renal swelling. This is often seen in patient care with ureteral calculi obstructing a ureter. Hematuria (blood in the urine), unilateral pain, and unilateral hydronephrosis are diagnostic of ureteral calculi, even if a calculus is too small to be seen (usually less than 3 mm). Treatment is begun based on this clinical presumption."}
{"_id": "ultrasound$$$28bcd32e-af5d-4d70-b78d-c0d899dc808c", "text": "Choices to diagnose kidney and ureteral stones include intravenous pyelogram (IVP), plain radiographs, CT scans (which allow the synthesis of a 3D picture from multiple radiologic views), and ultrasound. Plain radiography, or shooting an X-ray through the abdomen, is the oldest evaluation method but is still used. Often hydronephrosis and occasionally an actual stone may be visualized. This method is often used to follow a visible stone over several days. IVP production involves injecting dye into a patient\u2019s vein and taking serial plain X-rays to observe the flow of dye through the kidney and ureter. This method has lost great popularity due to the dye load on the kidney occasionally causing renal malfunction and less accuracy in diagnosis. CT technology is fast, does not require dye in this particular study, and is most accurate. The clarity of this technology is evident to the most inexperienced patient. Even a very small stone with a typical size of 1 mm may be measured more accurately. The stone may be more easily seen even if it does not contain calcium to reflect ultrasound waves. CT is used most often, but ultrasound is becoming more popular due to cost and the lack of ionizing radiation. Figure 9-3 shows an ultrasound image of a renal stone located at the pyeloureteral junction."}
{"_id": "ultrasound$$$e6681785-c04e-4f7c-bd54-0d1710fc83e1", "text": "Over 70 million CT scans are performed in the United States every year.[1] The malignant potential of CT scans was most famously brought to the forefront in 2007 by David Brenner and Eric Hall in the New England Journal of Medicine.[2] Determining the medical cost of a CT scan is also a complex issue. There is a wide range of costs for CT imaging, typically running from $900 to $3,000. It is conceded by most that clinician-generated ultrasound avoids both of these menacing issues."}
{"_id": "ultrasound$$$9a6fd7a4-f37f-48b5-b16e-7a0e07269571", "text": "Clinically, significantly small bilateral kidneys with a thin cortex may indicate chronic renal disease from a diffuse process such as glomerulonephritis or chronic urinary tract infections causing scarring. This condition is distinct from a single small kidney and indicates a localized problem, such as decreased blood flow to only one kidney, known as renal artery stenosis."}
{"_id": "ultrasound$$$2c2bf2a1-ff3a-407f-a2cd-a009445f05d4", "text": "Gallbladder ultrasounds are standard diagnostic investigations that can be done by primary care and emergency providers. The capsule of the gallbladder, with its fluid-filled contents, often makes a very clearly defined reflective surface. Figure 9-4 shows an ultrasound image of a gallbladder stone. Calculi, often called \u201cgallstones,\u201d may be seen within the gallbladder because of the high density and reflectivity of the discrete objects sitting in often clear fluid. Another feature called \u201cshadowing\u201d is helpful in diagnosis. Shadowing refers to the sharply demarcated darkness that is under the gallstone. Not all gallstones cause disease or need to be addressed. Other features that can be noted on ultrasound and can indicate pathology or a diseased state in a patient include the location of the calculi, the size of the gallbladder, inflammation of the gallbladder, and acute cholecystitis."}
{"_id": "ultrasound$$$e5a68e0e-4466-4b68-989f-ff0064fd9916", "text": "Gallstones close to the gallbladder neck are speculated to have more potential to eventually migrate through the gallbladder neck, into the cystic duct, and even into the common bile duct. Gallstones are often more challenging to visualize in the cystic duct or common bile duct due to their small size and coexisting bowel gas reflecting the ultrasound beam before it can reach the gallbladder. Other modalities are often needed to assist in diagnosis."}
{"_id": "ultrasound$$$040945be-cd35-4e05-a5e1-d765b41ecce9", "text": "The gallbladder contracts with cholecystokinin hormone, stimulating the vagus nerve in the parasympathetic nervous system. A small gallbladder may indicate chronic inflammation and scarring. A large gallbladder may also be pathological, even indicating rare gallbladder cancer. The gallbladder size is recorded by manipulating the measurement function on the machine."}
{"_id": "ultrasound$$$20785897-cb32-4494-8f4b-e3510a38c524", "text": "The wall of the gallbladder can be thickened from inflammation. Greater than cm wall thickness is often defined as being pathologically thickened."}
{"_id": "ultrasound$$$d0d1c926-85d0-48f5-9894-61bd047f5d46", "text": "Surrounding a thickened wall can also be inflammatory fluid, indicating an acute inflammatory response or \u201cacute cholecystitis.\u201d This inflammatory fluid will be seen as a dark area outside the (usually thickened) gallbladder wall, as shown in Figure 9-5."}
{"_id": "ultrasound$$$6e41a2d8-cd4c-46c4-8da0-547a50cecee8", "text": "Figure 9-6 is an abdominal ultrasound showing the right lobe of the liver and right kidney. Compared to the gallbladder, kidney, intestine, or bladder, the liver\u2019s thin covering makes it less distinctive. Distinctive features include the following:"}
{"_id": "ultrasound$$$a88c93dc-e581-4a7e-b203-eaf04b6b551f", "text": "While both systems are housed in the thorax, pulmonary and cardiac ultrasound approaches and findings can be strikingly different. As briefly discussed in the previous chapter, cardiac ultrasound has specific measures used for valves, blood velocity, and cardiac muscle contractility. The operators\u2019 abilities can adversely affect measurement accuracy on such subtle issues as the angle at which the probe is held and, subsequently, the angle at which measurements are obtained. One of the productive uses of artificial intelligence in the ultrasound field allows the operator to know when the best angle of insonation is obtained before the image is captured. Clear imaging is partially achieved by filtering raw images and removing portions of the images that are confusing to obtain the measurements. These measurements then determine important treatment routes, including choosing medication for the patient and even deciding if cardiac surgery is necessary."}
{"_id": "ultrasound$$$1e9c197f-655a-46c3-8f3d-1cba7b24cc13", "text": "In many ways, pulmonary ultrasound is the antithesis of cardiac ultrasound. The motion cycle of the lungs is less dramatic and less frequent, and the \u201csnow patterns\u201d on the screen caused by a lung consolidation or other conditions allow health care providers to make rapid, critical, and often lifesaving decisions about patients who are most ill. The total picture of the reflections of an ultrasound beam that is received from the same beam-emitting probe is often blurred. The \u201cartifacts\u201d are often distracting and even prohibitive in making the exact measurements. Figure 8-1 shows an ultrasound image of the intercostal space. Daniel Lichtenstein, known by many as the father of critical care ultrasound, was one of the first experts to recognize that the artifacts emitted in the lungs were not the problem but part of the solution in determining the pulmonary and vascular status of the patient.[3] The notion of lung ultrasound was possible and pertinent through Dr. Lichtenstein and his colleagues\u2019 recognition and hard work."}
{"_id": "ultrasound$$$35ed0473-4705-4971-8041-b2ffd57e8706", "text": "Successful respiratory cycles are controlled at many levels, from the brain to the alveoli. Clinically, we focus on what we can change to improve our patients\u2019 conditions. The brain\u2019s complex mechanisms and primary circuits, such as the autonomic nervous system and vagus nerve, are often out of our reach to meaningfully control for the long-term. We can mimic respiratory control by completely paralyzing our muscles and forcing air with oxygen concentrations into the lungs at a rate determined to be optimal by the clinician. This action is almost always temporary, such as for patients needing general anesthesia for surgery or patients in respiratory failure needing intensive care unit (ICU) attention. Lung ultrasound is most often used to help diagnose the cause of acute respiratory failure or evaluate continuing critical care efforts on patients already being actively treated for respiratory failure."}
{"_id": "ultrasound$$$25cf0360-6dcd-41b3-a883-8e2e617d6e19", "text": "Low-frequency curvilinear transducers with frequencies in the range of 3\u20136 MHz are best suited for lung ultrasound. Much of the recorded action of the lung begins and ends with the pleura. The pleura, a general term for the parietal pleura, air, and visceral pleura, is the denser outer covering of the lung that moves with the lung. From a sonographer\u2019s perspective, the pleura is the most easily visualized lung structure. Inspecting the pleura sonographically allows for observations of both pleural motion and pleural sonographic disruption."}
{"_id": "ultrasound$$$d5ed7821-bc22-424f-8a05-f8f7695a01df", "text": "As the pleura moves, it moves the rest of the lung. This \u201csliding lung sign\u201d accurately indicates lung motion and successful ventilation. If the pleura is not sliding, the lung, at least on the side of the thorax being inspected, is not ventilating thoroughly. Quick speculations about the causes of a lack of ventilation can be confirmed and treated to save lives. Below are some causes of a lack of ventilation that can be considered when there is no sliding lung sign:[4]"}
{"_id": "ultrasound$$$c4b0b8cf-8273-4965-88f4-28c2ba437e94", "text": "What have been named \u201cA-lines\u201d are the results of a reverberation artifact from the pleura or recurrent mirror images of the pleura that appear under the pleural lining at regular intervals, as shown in Figure 8-2. Disruption of the interstitium of the pleura changes the entire pleural reflection. Because the beam is prevented from uniformly penetrating the pleura, the areas that are disrupted are now seen as \u201cB-lines,\u201d as shown in Figure 8-3. There is no longer a reverberation artifact or A-lines when there are B-lines in motion."}
{"_id": "ultrasound$$$608a8e3f-e51b-4804-a7cc-6cc986c20841", "text": "B-lines representing pleural interstitial disruption often represent pulmonary edema or vascular overload, as shown in the right diagram of Figure 8-3. The edema, which collects on the pleural surface, causes \u201ccomet tail\u201d artifacts that account for the lines extending the lungs\u2019 entire length. It is often in the realm of intensivists or pulmonologists to ascertain a patient\u2019s intravascular volume. Dr. Lichtenstein was an original contributor to the direct visualization of the inferior vena cava to determine intravascular blood volume. He later discovered that B-lines might more accurately represent intravascular volume overload."}
{"_id": "ultrasound$$$3757a99d-fe22-4680-a42d-816003167221", "text": "Ultrasound principles allow us to understand that the complete reflection of the waves due to necrotic debris is represented as a bright image on the screen in the area of the lung parenchyma. Nonsonographic clues such as a fever may lead the clinician to speculate that the bright reflection is an infection of the alveolar cells or pneumonia. Since alveoli have such thin walls that allow oxygen to be exchanged, it is often accurately feared that this same thin wall would easily allow infectious organisms to also cross from the alveoli to the bloodstream. Noninfectious obstructions around the alveoli appear as a similar bright reflection of the ultrasound image. This scarring is known as atelectasis and is often considered much less dangerous to the patient."}
{"_id": "ultrasound$$$77438786-bc1e-4e74-bcab-7e34f1ec3447", "text": "Due to many factors, it is a slippery slope to write anything about COVID-19. The disease is widespread, the actual effectiveness of isolation is unknown, testing has been inaccurate for the most part, supplies to even care for patients have been limited to an unprecedented extent in most developed countries, and the treatment theories change almost daily."}
{"_id": "ultrasound$$$a89ad325-338e-4f78-a57f-3c8b40fec1f8", "text": "Far too many patients diagnosed with COVID-19 have had a rapid downhill course and go on to have a painfully long critical care course with a high mortality rate. For the first time in the world, there have been several considerations brought to the forefront. There has been a common consensus that COVID-19 has caused significant shortages of medical supplies both in the United States and worldwide, including those in testing capacity, ICU and hospital bed supply, hospital staff, personal protective equipment (PPE), and mechanical ventilators for affected regions.[5] There is greatly magnified attention on the safety of caretakers of the most critically ill patients. The mental health and well-being of health care professionals have been the focus of increased attention, with persistent evidence of high burnout, psychosocial stress, and mortality rates.[6] There has been a realization of how the increased vulnerability of our underserved population will perhaps impact how medical care is distributed in the future. The prevalence of COVID-19 has had a disproportionate impact on the poor, minorities, and a broad range of vulnerable populations due to its inequitable spread in areas of dense population and limited mitigation capacity resulting from a high prevalence of chronic conditions or poor access to high-quality public health and medical care.[7] There has been a growing need for more research on health equity in order to increase global knowledge and allow cross-national learning of what works for those most in need due to the direct and collateral effects of COVID-19. It has also been demonstrated that a pandemic can quickly destroy many characteristics of our society, affecting the economic, social, and personal habits of people in all countries. The World Health Organization has warned of a mental health burden related to the spread of COVID-19 infection through the global population: stress, worry, fear, and changes in our daily lives (working from home, temporary unemployment, homeschooling, etc.) are all challenging people\u2019s mental and physical health as well as the global health care system and economy.[8]"}
{"_id": "ultrasound$$$7bc2a51d-280e-4918-b0c6-3d16bf932d13", "text": "COVID-19 has been a very humbling condition to deal with for any health care professional. Many patients do well even with a positive COVID test. Many patients found to be COVID-positive on routine screening remain asymptomatic. On the other end of the care spectrum, too many people without major risk factors are experiencing significant acute and chronic symptoms from the virus. Many have died, and a handful of them have been health care workers. The objective predictors of who will do well, such as lab tests and plain X-rays, have been inaccurate in too many cases. Especially in developed countries, diagnosticians can usually rely on numerous pieces of data to arrive at a reasonable treatment plan. At the time of this writing, COVID-19 remains a disease where the outcome can be unpredictable in a most painful manner. Patients with comorbidities are indeed at far greater risk of doing poorly, up to the point of having a much higher mortality rate. Age, congestive heart failure, chronic obstructive pulmonary disease, and dementia significantly increase the chance of doing poorly. The realization that an extensive ICU run for patients with limited life expectancy may not be in the best interest of the patient or a society where ICU resources are limited has been a most painful reality for medical workers to consider."}
{"_id": "ultrasound$$$41aa6553-4191-4b6f-8406-207225b7981c", "text": "Lung ultrasound with handheld machines has developed into the most useful serial evaluator of the progression of COVID-19 lung disease. One of the challenges during the COVID-19 pandemic is was that several patients had to undergo ultrasound examinations within a limited amount of time, and those ultrasound tests needed to be completed on easily transportable machines. It was imperative for these machines to have the least number of knobs and small unreachable parts or spaces so that they can be sterilized quickly for immediate use with other COVID-19 patients."}
{"_id": "ultrasound$$$2fcc663c-369b-4692-b4e0-88b5ab0a18a4", "text": "Returning to the earlier chapters, we recall that degrees of brightness represent specific tissue characteristics, such as density. Pleura is one of those highly reflective densities. As the acute phase of COVID-19 disease progresses, distinctive changes may be observed first on lung ultrasound, which warns the clinician that the patient may be quickly worsening. Initially, COVID-19 may begin to change the pleura and cause the patient\u2019s condition to worsen due to pleural thickening and focal fluid collection in some areas. Pleural thickening can be relatively easily seen on lung ultrasound, as shown in Figure 8-4."}
{"_id": "ultrasound$$$3b6dfbe8-78cb-4f4e-a815-5eb562a493ef", "text": "As the thickened pleura from COVID-19 becomes even more inflamed, adhesions can develop in specific areas of the lungs. These adhesions may also be focal so that there may be focal areas of impaired ventilation even on the same side of the lung. As COVID-19 disease progresses, there can be focal infiltrates in the posterior and inferior portions of the lung, which are unique and can be identified on an ultrasound as gray areas (these regions appear anechoic on the normal lungs) commonly referred to as \u201cground glass\u201d. The nature of the infiltrates with \u201cground glass\u201d is present. The \u201cground glass\u201d is from inflammation of the bronchioles and alveoli. This type of inflammation is characteristic of COVID-19."}
{"_id": "ultrasound$$$9b2f3549-7eb8-4bb8-8472-dfac231d1569", "text": "It has been suggested that the ultrasound or CT findings of infiltrates in certain distributions can also be used as a diagnostic test suggesting the need for imploring further specific COVID-19-influenced testing. CT almost always presents a more precise view of the anatomic effects of the COVID virus on a patient. Handheld ultrasound is more accurate in evaluating the physiological effects of COVID-19 on ventilation, especially when considering the sliding lung sign. CT is more expensive and delivers more radiation. It may not be as practical to clean thoroughly to prevent droplet transmission of infection."}
{"_id": "ultrasound$$$a3572532-9bb2-4ac1-ab16-3630c27c6ab3", "text": "As opposed to other serious systemic diseases, progressive lung findings may remain focal or become more diffuse in the lungs. As the disease progresses, a more diffuse systemic condition from adhesions and inflammation may develop. This is known as acute respiratory distress syndrome (ARDS), which often leads to the need for ventilator support for several weeks. Several characteristics of COVID-19 have forced ethical discussions of patient care to very different levels from those for patients with other conditions."}
{"_id": "ultrasound$$$c04c198c-b11f-4bf8-ae64-cb3903964fff", "text": "Given the dismal results of cardiopulmonary resuscitation (CPR) in treating patients with COVID and the genuine risk to presumably healthy medical professionals, modifications to CPR have been suggested by many institutions that influence health care actions. These include the following:[9]"}
{"_id": "ultrasound$$$1175afac-cde2-4d92-9d11-94acba8877ae", "text": "Some of the humbling parts of COVID-19 can be seen in the personal experiences of clinicians who have authentic discussions with patients with COVID-19 and the statistics of their success or failure in helping the most ill:"}
{"_id": "ultrasound$$$8a1d4f4c-fa95-4247-8f40-564f7775e25e", "text": "As the pandemic progresses, chronic health outcomes associated with acute COVID are becoming more frequent and are classified under the \u201clong COVID\u201d category. While the acute phase of COVID-19, which is often mild or moderate, usually lasts one to two weeks, the symptoms of long COVID can last for several months and often appear to be nonspecific and not restricted to organ systems. Clarifying the underlying causes and developing a meaningful, effective, and focused diagnostic algorithm are critical. Lung ultrasound will almost certainly be an essential consideration in the care of these patients, and it has been shown to be useful for the diagnosis of COVID-19 in the acute stage of the disease.[18] Clofent et al. were able to show, in their study of 352 adult long-COVID patients with a long-term follow-up of 2\u20135 months, that lung ultrasound could be implemented as a first-line diagnostic procedure in the treatment course.[19] It was shown that the outcome of lung ultrasound in adults could produce good discrimination between patients with persistent abnormalities compared with high-resolution CT. However, in this population, Clofent et al. found a high rate of interstitial lung disease after acute COVID-19 infection. On the other hand, according to a study conducted on children and adolescents by Gr\u00e4ger et al.,[20] lung ultrasound is not suitable as a standard in the follow-up of long-COVID patients without initial pneumonia or pathological findings in an existing baseline examination. They concluded that better standard examination protocols need to be established for this patient group. Nevertheless, lung ultrasound is an important diagnostic tool for the lung because of its radiation-free nature, rapid availability, and increasing establishment in practice (with increasing experience of the examiners). In summary, much is yet to be discovered from a more adequate evaluation and treatment of worsening patients with COVID-19."}
{"_id": "ultrasound$$$47158f00-ca4f-45c7-b571-0f2ed470caa5", "text": "The position of the heart in the thorax is much more variable than often expected. The heart may be in a more superior or lateral placement in the thoracic cavity due to abdominal anatomical abnormalities. Lung conditions, such as emphysema, may present a heart in a vertical orientation due to chronic lung overdistension. In most healthy individuals, the heart may be best seen in a view called the parasternal long axis, where the probe is held at the second or third intercostal space immediately left of the sternum, as shown in Figure 7-1. Directly below the palpated area will be the chamber walls of the left atrium and the left ventricle."}
{"_id": "ultrasound$$$32120b99-a474-4b9c-a1d6-b170d2a95158", "text": "With optimal health, the heart contracts and expands synchronously. The circulation of the blood in the heart is shown in Figure 7-2. Blood enters the right atrium from the inferior vena cava and the superior vena cava. Blood then flows through the tricuspid valve to the right ventricle during cardiac expansion or diastole; this is mostly a passive flow. Blood is then expelled from the right ventricle during systole (or cardiac contraction) through the pulmonary artery and into the progressively smaller pulmonary arteries, pulmonary arterioles, and finally, pulmonary capillaries. Carbon dioxide and oxygen exchange occurs between the pulmonary capillaries and alveolar sacs of the lungs. Freshly oxygenated blood then returns via the pulmonary veins to the left atrium. Blood flows mostly passively from the left atrium, through the mitral valve, and into the left ventricle during diastole. Blood is finally propelled during systole through the aortic valve into the aorta and the body. The heart adapts to different behavioral and physiological stressors."}
{"_id": "ultrasound$$$b0981303-d81a-47d6-a016-500f42ca9272", "text": "A commonly performed, more sophisticated ultrasound evaluation of the heart is called echocardiography, often performed by technicians and cardiologists. Echocardiography machines are generally highly sophisticated (and expensive), with the capability and clarity of the views obtained improving over the years."}
{"_id": "ultrasound$$$b60492bb-5dbd-48f1-b049-ebab56cacdf0", "text": "Some of the most sophisticated machines that are routinely used in echocardiography can evaluate wall motion of specific areas of the heart and perform static measurements of both the opening and closing of the valves that are cycling more frequently than once. Color flow Doppler features in these machines can simultaneously differentiate blood flows going through insufficient valves. These findings help determine what procedures are best for patients with heart disease. Some patient conditions and the ultrasound principles behind the evaluations are described below."}
{"_id": "ultrasound$$$e75a39a6-4e0a-4a8e-bd3a-e2c07d32064b", "text": "Ischemia is inadequate blood flow through the coronary arteries that may lead to myocardial (cardiac muscle cell) dysfunction or myocardial death. Ischemia typically results in chest pain. Temporary chest pain from reversible ischemia is called angina. Permanent myocardial tissue death from ischemia is called myocardial infarction. It is a common task of primary care providers to determine if the chest pain symptom an individual is experiencing is related to ischemia or another medical cause. Shortness of breath (dyspnea) is also a common symptom of ischemia. The goal is to address angina or reversible ischemia before irreversible global myocardial tissue death. The next step in addressing suspected coronary artery ischemia for patients fortunate enough to access the best health care is coronary artery catheterization. Further diagnosis and treatment with coronary artery catheterization are often done during the same procedure.[1] A coronary artery blockage can be treated with a small open mesh tube called a stent. If indicated, a stent or other procedure to reduce the blockage is completed to restore adequate blood flow."}
{"_id": "ultrasound$$$54650e8d-d1da-4a7b-82dd-069de172632f", "text": "It is common in the United States to try to diagnose those patients with risk factors and typical chest pain with an evaluation called a stress echocardiogram, also known as a \u201cstress echo\u201d or cardiopulmonary exercise testing with echocardiographic examination. In this test, the patient\u2019s heart rate is increased either by having them exercise on a treadmill or bike or by pharmacological measures to increase heart rate and heart contractility.[2] Pharmacological measures are used for patients with comorbidities, such as orthopedic or neurological conditions that may prevent safe treadmill or bike use. If there is a blockage of a single vessel in a stress echo, the part of the heart that this particular vessel supplies blood to will contract less efficiently. For example, the left main coronary artery (LCA) supplies blood to the anterior part of the heart. In patients with a blockage of their LCA, the anterior portion of the heart will have noticeably less contractility. The reduction of contractility may be coupled with symptoms such as angina or dyspnea during physical movement. The contractility dysfunction that is induced by a rapid heart rate is often followed by cardiac catheterization. A coronary artery bypass grafting during an open-heart procedure may be needed in more severe cases. If so, a large incision is made in the chest to expose the heart. A vessel is removed from the patient\u2019s leg, chest, or arm and grafted around the coronary artery with blockage."}
{"_id": "ultrasound$$$e63a4120-c4d3-402c-8df7-22a501794b52", "text": "Myocardial muscle function has been assessed for over 200 years, and knowledge of congestive heart failure continues to change. Without imaging, it was hypothesized that heart contractility could be impaired and that the acceptance of incoming blood would be likewise impaired. This was realized to result in increased vascular pressure and fluid leakage in the peripheral interstitium, leading to ankle edema and edema in the lungs.[3] A stethoscope was used to hear the lung edema and probably first noted in an autopsy. Treatment at first involved trying to reduce intravascular volume by using a tourniquet or bloodletting. This was done with some success. One of the first medicines to treat it was a purification of products of the foxglove plant to produce a derivative of digitalis. To this day, medical providers continue to try to decrease intravascular volume and increase cardiac contractility. Digitalis derivatives like digoxin continue to be prescribed for abnormal heart rhythms."}
{"_id": "ultrasound$$$814cfd56-d730-4853-9920-d96c08f2c09c", "text": "Echocardiography is most important in the initial diagnosis and ongoing care of reduced myocardial contractility. Heart muscle contractility is assessed for quality and calculated as an ejection fraction (EF).[4]\u00a0This is calculated by measuring the area of the left ventricle during diastole when the left ventricle is at the endpoint of receiving all of the blood prior to the contraction and at the point where the left ventricle has reached end-systole, which is the greatest point of contraction. The blood volumes corresponding to the endpoints during diastole and systole are referred to as end-diastolic volume (EDVol) and end-systolic volume (ESVol), respectively. Stroke volume (SVol) is calculated by subtracting ESVol from EDVol. EF can then be mathematically expressed as follows:[5]"}
{"_id": "ultrasound$$$e18f96e1-d648-47ab-9b79-28e51f004796", "text": "If the left ventricle contains 100 ml of blood at the end of diastole and 40 ml when it fully contracts during systole, SVol is 60 ml, and thus, the EF is 60%. A normal EF percent is considered to be around 55\u201375%. EF percent measurements are becoming more reliable. This is largely due to software improvements allowing the area of a 3D object to be measured on a 2D screen. The description of a patient having an EF percent of significantly less than 50% gives experienced clinicians a good idea of a patient\u2019s morbidity and mortality."}
{"_id": "ultrasound$$$533c4d70-864e-4949-8a1f-6b28086e72dd", "text": "Heart valves allow blood to travel from one area of the heart to another and prevent \u201cbackflow\u201d from its new area to the old area. The four valves evaluated by echocardiography are the aortic valve (between the left ventricle and aorta), the mitral valve (between the left atrium and the left ventricle), the tricuspid valve (between the right atrium and right ventricle), and the pulmonary valve (between the right ventricle and the pulmonary artery). Clinically relevant dysfunction is much more common in the aortic and mitral valves. There are two common types of valvular dysfunction."}
{"_id": "ultrasound$$$e792164b-835d-4e19-819d-51c09454bc43", "text": "Echocardiography evaluates valvular dysfunction by direct visualizations (measuring valve diameter in systole and diastole). This is obtaining static views for those changing most often more frequently than once per second in real time. Indirect measurements are obtained by measuring blood velocity through the valve and watching the color Doppler backflow of blood through valves with regurgitation."}
{"_id": "ultrasound$$$5c221601-b7a3-4e59-b718-5266208b8ecf", "text": "In general, transverse and longitudinal planes (also called sagittal planes) should be obtained of all key anatomic structures and pathologies when performing a diagnostic evaluation. It is always important to know your orientation when visualizing the images. Transducers usually have an indicator on one side at the end of the probe, such as a light, knob, or notch corresponding to the right side of the screen\u2019s image. If you are unsure, just touch one edge of the probe with your finger, and look at the screen to see if you are on the right or left side before imaging. During the evaluation, compare static images, dynamic images, Doppler evaluation, and possible contralateral evaluation. Also, document any masses or fluid collections, such as bursal distension, by indicating the location, size, shape, echotexture, compressibility, and presence or absence of flow with Doppler.[2]"}
{"_id": "ultrasound$$$7dd1c996-580c-4581-ae03-1e6dd86d49c2", "text": "Image optimization is obtained by selecting the proper transducer with appropriate frequencies. In general, a high-frequency linear transducer (10 MHz or higher) will be the appropriate selection for the evaluation of most joints. However, sometimes a curvilinear transducer gives better imaging in larger joints and in the evaluation of most adult hips, which usually require deeper penetration for visualization. Another exception would be the evaluation of superficial detailed structures such as the pulley system of the digits in the hand. A hockey stick transducer (>10 MHz) would be more appropriate for better resolution. Figure 6-1 shows some commonly used transducers in musculoskeletal ultrasound assessment. When evaluating a joint, it is helpful to start by directing your angle of insonation to the bony cortex, which is usually the most distal and hyperechoic structure, to avoid anisotropy.[3]"}
{"_id": "ultrasound$$$cce5442f-e77e-4dcd-bfcc-5c659211fc1f", "text": "The normal sonographic appearance of MSK structures often has characteristic ultrasound images that are best visualized in the longitudinal plane. For example, tendons usually appear as a hyperechoic fibrillar echotexture. Ligaments are similar but more compact and connect two osseous structures. Muscle tissue appears more hypoechoic with septations, a pennate (featherlike) appearance in the longitudinal plane, and a starry-night appearance in the transverse plane with dynamic maneuvers. Bone is usually very hyperechoic. It creates a significant acoustic impedance mismatch and therefore is very reflective and appears bright white (hyperechoic) on the image. Adipose tissue and cartilage tend to be hypoechoic. Nerves tend to have both a hypoechoic and hyperechoic honeycomb appearance. The location and function of the structures are always helpful when determining normal anatomy and pathology."}
{"_id": "ultrasound$$$d16f348f-0e87-449d-aaf6-960a192cea29", "text": "Injuries, inflammation, or infections are divided into acute and chronic and can affect any musculoskeletal structure. Acutely, the sonographic structures tend to be hyperechoic, with possible hypertrophy, hypervascularity, fluid, and disruption of fibers in structures such as tendons. Chronic sonographic images tend to be more hypoechoic, with possible atrophy, scarring, and areas of calcification. Bone abnormalities can also be seen in acute and chronic processes. The normal bone cortex is smooth, uniform, and hyperechoic. A bone fracture can be visualized as a discontinuity of the bone cortex and disruption of the cartilage. Arthritis can have characteristic bone images such as crystal deposits on the cartilage surface in gout and synovial hypertrophy with bone erosions in rheumatoid arthritis."}
{"_id": "ultrasound$$$74bf8e0a-f055-4024-a861-9c1f86bce087", "text": "Sonographic artifacts are not uncommon with MSK ultrasound, some of which have been discussed in earlier chapters. It is vital that the sound beam is perpendicular to the anatomic structure being visualized, or anisotropy can be encountered and give false information. To correct for anisotropy, performing a heel-to-toe maneuver on the long axis and toggling the transducer on the short axis are often helpful to finely tune the ultrasound image."}
{"_id": "ultrasound$$$fb051694-bf0e-46e7-afd8-aff8ec5caa1c", "text": "Figure 6-2 shows the anterior view of the shoulder anatomy. The shoulder is one of the most accessible joints to perform a comprehensive ultrasound evaluation. An ultrasound evaluation can be as reliable as an MRI for a rotator cuff tear. A complete shoulder evaluation should include the rotator cuff\u2019s tendons and muscles, including the subscapularis, supraspinatus, infraspinatus, and teres minor. Also, examine the biceps brachii (with dynamic maneuvers, if indicated for subluxation, dislocation, or impingement), the acromioclavicular joint, the suprascapular nerve (in the suprascapular notch and the spinoglenoid notch), and the posterior glenohumeral joint.[4] Evaluating each anatomic structure in the transverse and longitudinal planes is essential."}
{"_id": "ultrasound$$$397a225b-7f03-4991-9b96-a7b1fdc47894", "text": "For examination of the patient\u2019s shoulder, developing an approach that allows for the best visualization with dynamic maneuvers is helpful. One approach would be to start by standing in front of the seated patient with their arm at their side, the elbow at 90 degrees flexion, the forearm in supination, and the ultrasound machine on one side of the patient for exam visualization."}
{"_id": "ultrasound$$$1ba3dc4c-f546-4069-9472-bfdfff5d1e55", "text": "The long-head biceps tendon is the first structure to be evaluated, and it works as a good reference point for the anterior shoulder evaluation. The origin of the long-head biceps is the supraglenoid tubercle of the scapula, and the insertion is the radial tuberosity and bicipital aponeurosis. It is innervated by the musculocutaneous nerve. Its action is flexion and supination of the forearm at the elbow joint and flexion of the arm at the shoulder joint. First, look at the transverse position within the bicipital groove of the humeral head with a linear transducer."}
{"_id": "ultrasound$$$7b04ce25-19d5-4539-8bb1-08094a8e79eb", "text": "The biceps tendon should have a bright, dense, ovoid, and bristle-like appearance. It should be assessed from proximal to distal in the transverse and longitudinal planes, as shown in Figure 6-3. It is essential to evaluate the most proximal area where the biceps tendon courses over the humeral head because this is a common site for pathology. Also, fluid distension within the bicipital tendon sheath often indicates shoulder pathology, since part of it communicates with the shoulder joint. Continue the evaluation distally until the fibrous-appearing band of the pectoralis major inserted into the proximal humerus is visualized. This is sometimes where a bicipital tendon tear can be found separated from the muscle after an injury. Dynamic maneuvers, both active and passive, can be very helpful in the evaluation."}
{"_id": "ultrasound$$$d4ad118c-a2b4-4553-aab0-33a419a2c9da", "text": "After looking at the bicipital tendon/muscle, return to the point of reference within the bicipital groove of the humerus in the transverse plane. Next, evaluate the subscapularis, which originates at the subscapular fossa and inserts into the lesser tubercle of the humerus. It is innervated by the upper superior and lower inferior subscapular nerves, and the action is for internal rotation of the humeral head. It prevents anterior displacement of the humerus. First, start by moving the transducer medially to the lesser tuberosity to evaluate the rotator interval, which is the space between the anterior margin of the supraspinatus tendon and the superior margin of the subscapularis tendon. The subscapularis tendon/muscle is evaluated by a passive range of motion with external rotation, as shown in Figure 6-4. This brings the subscapularis into the longitudinal (sagittal) plane as it rotates over the humerus. During this dynamic maneuver, also evaluate for coracoid impingement. A limited view of the anterior glenohumeral joint can also be evaluated in this position. The probe is then rotated 90 degrees clockwise in the transverse plane. In this view, the subscapularis will have a characteristic vertical hypoechoic segmented appearance secondary to the musculoskeletal junction, which is usually normal anatomy and not a tear. The evaluation should again include any evidence of effusion, synovial hypertrophy, or tearing.[5],[6]"}
{"_id": "ultrasound$$$8298e819-4749-4713-a101-0a312bb0343e", "text": "The next anatomic structure to evaluate in the anterior position of the patient is the acromioclavicular (AC) joint, shown in Figure 6-5. The most straightforward approach is to palpate the AC joint and place the linear transducer on top of it in the transverse plane. Evaluate for widening, such as in a tear or effusion, which is sometimes indicative of rotator cuff pathology."}
{"_id": "ultrasound$$$9c174bd1-5d63-476c-8fdf-5d2cb3da399f", "text": "The next rotator cuff to be evaluated is the supraspinatus, which originates in the supraspinatus fossa and is inserted on the superior facet of the greater tubercle of the humerus. Innervation is by the suprascapular nerve; its action is the abduction of the arm and stabilization of the glenohumeral joint. The best position for the patient to be in is called the modified crass position. In this position (which involves extension, adduction, and internal rotation), the patient is sitting upright with the palm of their hand on the ipsilateral hip and the elbow flexed and pointed posteriorly. This brings the supraspinatus out from under the cover of the acromion. Over 90% of rotator cuff injuries involve the supraspinatus.[7],[8] First, evaluate the supraspinatus tendon in the longitudinal plane, as shown in Figure 6-6. This image is the most essential view and should have a bird\u2019s beak appearance. Next, include the transverse plane view. Evaluate the bony cortex, hyaline cartilage, supraspinatus tendon/muscle, peribursal fat, and the subacromial bursa. Pooling of fluid within the subacromial bursa or restrictive motion of the supraspinatus tendon could indicate subacromial impingement.[9]"}
{"_id": "ultrasound$$$810d7bbd-4356-49dc-9916-c3501fd35601", "text": "It is vital to evaluate the tears of the supraspinatus with the correct description. First, determine if it is a full-thickness tear extending from the articular to the bursal surface or a partial-thickness tear. Partial-thickness tears involve the articular or bursal surface or are localized within the tendon, not extending to either surface. This is called an intrasubstance tear. When evaluating the diameter of the tear, measure along the long and short axis."}
{"_id": "ultrasound$$$88bfd4f9-b0ba-4d82-9429-7398bbf24370", "text": "Posterior cuff imaging is evaluated next by facing the posterior shoulder, palpating the scapular spine, and placing the transducer below it in an oblique axial plane angled superiorly toward the humeral head. A curvilinear probe is sometimes needed for better penetration, since the posterior shoulder is a deeper structure. The infraspinatus and teres minor tendons are first evaluated in the longitudinal plane from the scapular fossa\u2019s origin to the humerus\u2019s greater tuberosity, as shown in Figure 6-7. The origin of the infraspinatus is the infraspinatus fossa of the scapula, and the insertion is on the middle facet of the greater tuberosity of the humerus. The suprascapular nerve innervates it, and its action is for external rotation and abduction of the arm at the shoulder joint with stabilization of the shoulder joint. The teres minor originates on the lateral border of the scapula and inserts onto the inferior facet of the greater tuberosity of the humerus. It is innervated by the axillary nerve and functions similarly to the infraspinatus."}
{"_id": "ultrasound$$$6ea029f0-bcd2-44fb-a0ad-57d5b21e21a1", "text": "Next, evaluate the suprascapular nerve in the suprascapular notch and the spinoglenoid notch. Sometimes, turning on the Doppler to better visualize the suprascapular artery is helpful, and right next to it is the suprascapular nerve."}
{"_id": "ultrasound$$$b30a3821-b75a-4627-99ec-2e3f9bdd1bb7", "text": "Finally, evaluate the posterior glenohumeral joint, as shown in Figure 6-8. Look for joint effusion, cortical irregularities, and osteophytes, and evaluate the posterior labrum for cysts or tears. Also, this is a good approach for intra-articular glenohumeral joint injections using a posterior approach. This completes the shoulder evaluation."}
{"_id": "ultrasound$$$437ee1cb-dd32-486c-9a28-c7568c7b1a1e", "text": "The entire elbow examination is usually accomplished with a linear transducer. Like all the other joints, the elbow is best evaluated in a quadrant approach: anterior, medial, lateral, and posterior. Figures 6-9 and 6-10 show the anatomical structures of the elbow."}
{"_id": "ultrasound$$$cc785d45-d3a5-4eaa-9e8a-ecad96c7601c", "text": "Anteriorly, look at the joint space for narrowing, cortical and cartilage irregularities, synovial hypertrophy, and effusion. Also evaluate the brachialis, biceps, median and radial nerves, and the brachial artery, as shown in Figure 6-11."}
{"_id": "ultrasound$$$5a3f3656-284d-4854-a00f-846b35ab211c", "text": "Next, the medial elbow evaluation is performed with the elbow in partial extension and the probe in a longitudinal axis, as shown in Figure 6-12. Evaluate the anterior band of the ulnar collateral ligament (UCL). It will have a characteristic triangular homogenous appearance as it spans from its attachment proximally to the humeral trochlea and distally to the olecranon. The common flexor tendon is superficial to the UCL and evaluated carefully at the insertion point of the medial epicondyle, since this is the site of medial epicondylitis. The pronator teres should also be examined for any evidence of tears, effusion, or synovial hypertrophy.[10],[11]"}
{"_id": "ultrasound$$$b6c7d8fd-5af9-4382-b818-8018dfcc11c6", "text": "The lateral elbow is next approached with the elbow flexed at 90 degrees and the ipsilateral hand resting in pronation, as shown in Figure 6-13. A longitudinal probe placement is performed to evaluate the bony margins of the capitulum of the humerus and the radial head. Evaluate the radial collateral ligament complex and the common extensor tendon (CET). Closely evaluate the attachment of the CET to the lateral epicondyle, the site of lateral epicondylitis."}
{"_id": "ultrasound$$$f89fcac1-24df-49f8-9c52-e4d65001c6c2", "text": "Finally, the posterior evaluation is performed with the elbow at approximately 90 degrees of flexion, as shown in Figure 6-14. Evaluate the triceps muscle and tendon, olecranon bursa, and the ulnar nerve within the groove between the medial epicondyle and the olecranon of the ulna. This can be a site for entrapment of the ulnar nerve, which should have an area of 7 mm or less.[12],[13]"}
{"_id": "ultrasound$$$3f8f509f-f991-4857-857d-3520d9fe56e9", "text": "The wrist and hand anatomy involve superficial structures; therefore, the best approach is to use a high-frequency hockey stick transducer for better resolution. Figure 6-15 shows the anatomical structure of the wrist and hand."}
{"_id": "ultrasound$$$a628bb34-f0b1-4427-9f29-70ab1bd78309", "text": "Start with the palm of the hand facing down. Identify Lister\u2019s tubercle (see Figure 6-17) on the dorsum of the distal radius by digital palpation, and place the transducer on top of it in a transverse plane, as shown in Figure 6-16. This bony prominence separates the second and third extensor tendon compartments of the six in the wrist and helps with identification and orientation. Just radial to Lister\u2019s tubercle is the second compartment containing the extensor carpi radialis brevis and the extensor carpi radialis longus."}
{"_id": "ultrasound$$$584de14e-d711-4c77-9a9f-6956272be08e", "text": "With further radial movement, the first compartment on the side of the wrist is identified, which contains extensor pollicis brevis and abductor pollicis longus tendons. The first compartment is the site of de Quervain\u2019s tenosynovitis. Evaluate each compartment from proximal to distal in both planes with active and passive dynamic maneuvers depending on the clinical concerns. Superficial to the compartments is the extensor retinaculum."}
{"_id": "ultrasound$$$370de007-9a12-47c6-80ca-af329ecff6a1", "text": "The third compartment is on the ulnar aspect of Lister\u2019s tubercle and contains the extensor pollicis longus, as shown in Figure 6-17. Moving further toward the ulna, next to the third compartment, is the fourth compartment, which contains multiple extensor digitorum tendons and extensor indicis. Compartment five contains the extensor digiti minimi, and the sixth compartment contains the extensor carpi ulnaris, as shown in Figure 6-17. Evaluate each for any pathology."}
{"_id": "ultrasound$$$bc0c05fb-ff3a-4ae9-87f2-48922564f601", "text": "After evaluating each compartment, return to Lister\u2019s tubercle in the transverse plane, and move the probe distally to the radiocarpal joint. The bone just distal to the radius is the scaphoid, and the lunate bone is next to the scaphoid in the ulnar direction. Between the dorsal aspects of both bones is a triangular area that represents the scapholunate ligament, which has a compact hyperechoic fibrillar echotexture, as shown in Figure 6-18. This is a common site for injuries from falls involving extended wrists that could result in a tear of the scapholunate ligament. It is also a common site for ganglion cysts."}
{"_id": "ultrasound$$$713b8385-c361-453d-ae19-664116b78afc", "text": "Now rotate the hand to evaluate the volar aspect, as shown in Figure 6-19. Evaluate the median nerve, flexor tendons, volar joint recesses, flexor carpi radialis, palmaris longus, and radial artery and the flexor tendons, pulleys, volar plates, collateral ligaments, and joint recesses of the fingers as clinically indicated. The median nerve is found between the flexor carpi radialis and palmaris longus. Place the transducer between these two tendons in the distal wrist crease in the transverse plane, and move the probe proximally as the honeycomb appearance of the median nerve courses radial to the flexor tendons and then moves ulnar and deep between the flexor digitorum superficialis and profundus. If the median nerve has a cross-sectional area of 12 mm2 or greater, this suggests carpal tunnel syndrome. Also, a 2 mm2 or greater difference in the cross-sectional area of the median nerve measured proximally at the level of the pronator quadratus and distally at the level of carpal tunnel has a 99% accuracy for carpal tunnel syndrome.[14]"}
{"_id": "ultrasound$$$f2567925-2688-4770-b776-a7a35919fef4", "text": "Finally, individual digits should be evaluated in the transverse and longitudinal planes using dynamic maneuvers as clinically indicated for the evaluation of pathology. There are five flexor tendon pulleys in the fingers, which are named A1\u2013A5 and consist of annular ligament pulleys and cruciate pulleys\u2014that is, the flexor tendon pulley system. The thumb only has two pulleys, which are labeled A1 and A2. When evaluating the pulley system in the digits, the A2 and A4 pulleys are most important in the sagittal plane, as shown in Figure 6-20. If pathology is present, this may demonstrate bowstringing and hypoechoic edema.[15]"}
{"_id": "ultrasound$$$22aca1c1-1504-4acb-84e5-3e9979c51c2e", "text": "Figure 6-21 shows a schematic of the skeletal structure and tendons of the hip. The low-frequency curvilinear transducer is most appropriate for hip evaluation. Start with the anterior evaluation by having the patient supine with the ipsilateral leg in full extension and with slight external rotation, as shown in Figure 6-22."}
{"_id": "ultrasound$$$cdb9e49a-d342-40d9-acc6-b55c5a42d0cf", "text": "Superficial to the capsule is the potential space between the capsule and the iliopsoas muscle, which is the iliopsoas bursa. This is the largest bursa in the human body, and an iliopsoas bursitis would be considered an extracapsular effusion. Like hip capsulitis, iliopsoas bursitis can be approached with an injection\u2014but more superficial. The iliopsoas tendon is then evaluated by placing the transducer in the longitudinal plane in line with the femoral shaft and medial. The iliopsoas is a conjoined muscle composed of the iliacus and the psoas major muscles, which attach to the intertrochanteric line of the femur. This is evaluated from proximal to distal in the longitudinal and transverse planes. Also, consider evaluating the femoral vessels and nerve, sartorius muscle, tensor fascia lata tendons and muscles, lateral femoral cutaneous nerve, and rectus femoris tendon and muscles. Dynamic hip maneuvers may also help evaluate for tears, subluxation, or dislocation.[16]"}
{"_id": "ultrasound$$$c77d6dd7-4d5f-44b4-b714-beae6b996bd9", "text": "Now have the patient in the lateral decubitus position with the hip to be evaluated up in a flexed 20\u201330 degree position to examine the gluteus muscles and tendons, as shown in Figures 6-23 through 6-25. The gluteus minimus, which is deep to the gluteus medius, originates from the ilium between the inferior and anterior gluteal lines. It inserts onto both the anterior aspect of the capsule and via its long head onto the anterior surface of the greater trochanter. The gluteus minimus and gluteus medius work together to abduct and internally rotate the hip. Finally, the gluteus maximus starts in the posterior iliac crest and sacrum/coccyx, crosses over the posterior facet, and inserts into the proximal femur, as Figure 6-25 shows. It extends and laterally rotates the hip."}
{"_id": "ultrasound$$$0c0d884d-e832-424b-ada8-a45a7074335b", "text": "To visualize the tendons in the sagittal plane, rotate the probe 90 degrees and angle the beam anterior to posterior to visualize the gluteus minimus and posterior to anterior to visualize the gluteus medius, as shown in Figure 6-24, and the gluteus maximus, as shown in Figure 6-25."}
{"_id": "ultrasound$$$799095d3-ea8c-42e1-8e69-ac0488656125", "text": "To evaluate the hamstrings, first identify the ischial tuberosity to locate the origins of the semimembranosus, biceps femoris, and semitendinosus tendons. Locate the conjoined tendons of the biceps femoris and semitendinosus, as shown in Figure 6-26. The semimembranosus lies deep and usually slightly inferior to the conjoined tendons."}
{"_id": "ultrasound$$$3d24aaee-cd0a-4cd4-85dc-0620ac5282a6", "text": "Start the evaluation by using a high-frequency linear transducer and having the patient in the supine position. The anterior evaluation starts in the suprapatellar area with the probe in line with the femur, as shown in Figure 6-28."}
{"_id": "ultrasound$$$da240aa9-8e4f-4c96-8b89-37d8277a0932", "text": "Evaluate the following structures from deep to superficial, starting with the bony cortex of the femur, the quadriceps muscles and fascial planes, the femoral trochlea, the prefemoral fat pad, the suprapatellar bursa, and the suprapatellar fat pad. Evaluate proximally from the quadriceps muscle to the distal area over the patella in the longitudinal and transverse planes, looking for any pathology such as effusion or tears, as shown in Figures 6-29 and 6-30. It is sometimes helpful to perform toggling and heel-to-toe maneuvers to fine-tune the anatomy and avoid anisotropy."}
{"_id": "ultrasound$$$1ed09168-b376-4337-9334-24ba2090fabf", "text": "Next, slide the transducer medially, and evaluate the medial aspect of the knee joint from the femoral to the tibial condyles in the sagittal and transverse planes, as shown in Figures 6-31 and 6-32. Also, evaluate the medial collateral ligament and the medial meniscus in the joint space. As you move the transducer distally, evaluate the pes anserine complex for any evidence of injury or inflammation, such as pes anserine bursitis."}
{"_id": "ultrasound$$$b3a13ade-c40e-4f20-a4cb-b8b6db876029", "text": "Next, slide the probe to the lateral aspect of the knee joint, and evaluate the joint space of the distal femur and fibular head, as shown in Figure 6-33. In the longitudinal and transverse planes, evaluate the peripheral margin of the lateral meniscus and the lateral collateral ligament from proximal to distal."}
{"_id": "ultrasound$$$e08d1f5a-66a6-4ea0-82d9-c34dbbf988b2", "text": "Next, scan the infrapatellar area in the longitudinal plane with the bony landmarks proximally of the femur and tibia joint space and distally of the proximal tibia, as shown in Figure 6-34. Keep light pressure on the probe to avoid compressing any possible fluid within the bursa. There are two bursae superficial to the patellar tendon near the patella and one deep to the patellar ligament in the area of the proximal tibia. Evaluate the patellar ligament, sometimes called the patellar tendon, which is the portion of the quadriceps femoris tendon that continues from the patella to the tibial tuberosity."}
{"_id": "ultrasound$$$16a00555-ca8f-47d5-8314-ffece92b88ab", "text": "Finally, the posterior view of the knee is evaluated with the knee slightly flexed at 10\u201320 degrees, as shown in Figure 6-35. Many structures can be seen in the popliteal fossa, including the popliteal artery and vein. One important area to evaluate is the area between the medial head of the gastrocnemius muscle and the semimembranosus tendon, which is the usual site of a Baker\u2019s cyst. This completes the knee evaluation."}
{"_id": "ultrasound$$$741724c3-e1d1-4bb8-9d0c-128300453a67", "text": "Figure 6-36 shows the anatomical view of the foot and ankle. The ankle and foot can be challenging to evaluate, since many structures require anatomic familiarity and detailed imaging. However, in general, a systematic approach is helpful. As with the other joint evaluations, a quadrant approach works best. Start with the anterior/dorsal evaluation by flattening the foot with an anterior longitudinal plane of the probe across the joint space of the tibia and talus, as shown in Figure 6-37. This provides an excellent focal point to sweep across the ankle joint to evaluate the muscles from medial to lateral: tibialis anterior, extensor hallucis longus, and extensor digitorum longus, as shown in Figure 6-38."}
{"_id": "ultrasound$$$1c297f72-5a65-4f1d-a53c-aec2a8b9c3f6", "text": "The subtalar joint is often of interest for evaluation and injection purposes. It is found in the longitudinal plane just medial to the lateral malleolus in the talus and calcaneus joint space."}
{"_id": "ultrasound$$$5da60c3e-f921-4f75-8a00-218b4487096e", "text": "Evaluate from the proximal muscle to the tendon insertion points in the transverse and longitudinal planes as clinically indicated.[17] Dynamic imaging is helpful to evaluate the integrity of the ligament. Now place the probe behind the lateral malleolus in the longitudinal plane with a posterior to anterior angle of insonation to evaluate the peroneus longus, which is superficial to the peroneus brevis. Evaluate both the longitudinal and transverse planes proximally and distally to their insertion points, as shown in Figures 6-39 and 6-40."}
{"_id": "ultrasound$$$f5488363-d170-479f-86dd-3dacb517ae48", "text": "Place the probe in the transverse plane behind the medial malleolus to evaluate the medial side of the ankle and foot, as shown in Figure 6-41. Now we can evaluate the cross-sectional area of the structures in the tarsal tunnel. From medial to lateral, we have the Tibialis posterior tendon, flexor Digitorum longus tendon, posterior tibial Artery/Vein/Nerve, and flexor Hallucis longus tendon. Tom, Dick, And Very Nervous Harry is a commonly used mnemonic to recall these anatomical structures. This is important to evaluate for tarsal tunnel syndrome if clinically indicated.[18]"}
{"_id": "ultrasound$$$97cfe372-c879-4c4a-98f3-863e5bd5b459", "text": "To complete the evaluation, look at the Achilles tendon in the transverse and sagittal planes from the proximal gastrocnemius and soleus muscles to the insertion into the calcaneus, as shown in Figures 6-42 and 6-43."}
{"_id": "ultrasound$$$21c1bdb5-b568-47d2-9745-e8afd7657f1f", "text": "Finally, evaluate the foot\u2019s plantar fascia in the longitudinal plane, as shown in Figure 6-44. The thickness at the insertion to the calcaneus should not be more than 4 mm, which would be suggestive of plantar fasciitis."}
{"_id": "ultrasound$$$ef8d2761-fe84-429b-bba9-729594d98f48", "text": "Obstetrics encompasses some of the same considerations as adult diagnostic ultrasound with a critical addition: rapid growth. There is no other time in life when various organs\u2019 functionality is time dependent. The developmental changes in early organ growth are part of the most fascinating differentiation process. What is being observed within a specific imaging procedure in utero, although completely normal, actually changes over time. Broken down further, findings at specific gestational times depend on the level of differentiation an organ has undergone at a specific time in gestational development."}
{"_id": "ultrasound$$$45dfc132-ba4e-4716-8b64-b9fe0cd99b04", "text": "The accuracy of ultrasound is variable, and the issue of diagnostic accuracy is essential to understand for any medical professional. Sensitivity and specificity are commonly used quantitative measures to report such accuracy. For a given test and disease/condition, sensitivity is the ability of the test to correctly identify something being positive. Its specificity for a given test and disease/condition is how well it can distinguish those with disease from those without.[1] Expressed as equations, the calculations may be done as follows:"}
{"_id": "ultrasound$$$53e1e0f3-11b7-4125-aa51-07189d900996", "text": "In recent years more than ever, another consideration is the cost of medical interventions. Clinicians should have a good idea of the impact of the tests that they order:"}
{"_id": "ultrasound$$$ceeac4fd-9d26-4959-b56a-6e70ce4173a9", "text": "An example of a standard test is the complete blood count (CBC). The CBC is relatively inexpensive, reproducible among different labs, and often clinically helpful. The sensitivity of the CBC is regarded as relatively high. The specificity is often not very high. On this latter point, an elevated CBC can often be one of the first and most important clues to an impending worsening of an infectious process such as appendicitis. An elevated CBC can also be considered a \u201cfalse positive\u201d caused by medicines such as steroids or endogenous epinephrine secretion (for example, if the patient recently experienced a traumatic event). In the early stages of pregnancy, a CBC test can help determine various health abnormalities, including anemia and infections."}
{"_id": "ultrasound$$$56ad4755-3966-49fd-8597-6ec4afbc4ec7", "text": "Maternal-fetal medicine specialists and their specialized technicians understand fetal development and testing rationales to make truly unique diagnoses. It is not unusual for heart development to be assessed weekly or even more frequently when difficulties are suspected, as cardiac problems can develop as gestation progresses. The following basic assessments are commonly performed in obstetrics ultrasound."}
{"_id": "ultrasound$$$de30f12f-eaeb-4caf-ae51-cc29e74c4811", "text": "The volume of amniotic fluid is calculated by what is called the amniotic fluid index. Even debris (represented by diffuse abnormal reflections in the amniotic fluid) is a harbinger of difficulties. At first glance, the ease of clarity and measurement is heavily influenced by the amount of amniotic fluid. As discussed in the earlier chapters, media, especially fluid, influences the quality of ultrasound wave transmission and reflection. Figure 5-2 shows an ultrasound image at 23 weeks of the fetus, amniotic fluid, and normal fetal morphology. A clear initial view is not necessarily a good sign, since excess amniotic fluid (a condition referred to as polyhydramnios) may make the images easy to obtain but may, more importantly, indicate problems. It has been noted that polyhydramnios represents a high-risk obstetric condition as much as 20% of the time.[2],[3]"}
{"_id": "ultrasound$$$4f266643-0c87-453e-8714-f22a30c49faa", "text": "Fetal cardiac development (the development of the four chambers) is fascinating. The normal opening between the two upper chambers of the fetus\u2019s heart, the right and left atria, is called the foramen ovale (FO). The FO permits blood flow to bypass the lungs before the infant is born (a fetus gets its oxygen from the placenta, not the lungs). As a result, the heart does not have to work as hard to pump blood where it is not needed. The FO typically closes six months to a year after the infant is born. A patent foramen ovale (PFO) occurs when the FO remains open after birth. A PFO often does not cause any issues.[4] When an infant is born with congenital heart abnormalities, the FO is more likely to remain open."}
{"_id": "ultrasound$$$2854845e-0e28-4025-bb1d-e67db181292e", "text": "There is a division of a single atrium and a single ventricle by the growth of a septal wall from the wall of the single cavity in all directions toward the middle. This is a gradual and persistent hole in the septum that grows abnormally, leading to the septum closing, which results in a septal defect. Fortunately, one can detect both an atrial septal defect and/or a ventricular septal defect using ultrasound, as shown in Figure 5-3. Color flow ultrasound Doppler is often helpful, as one can view the flow from one side of the dividing atrial atrium or ventricle to the other side."}
{"_id": "ultrasound$$$390776e8-d04c-4842-9937-2f454c111ef5", "text": "Different gestational sizes of different organs in the same fetus can indicate genetic and fetal nutritional problems. Intrauterine Growth Retardation (IUGR) can be either symmetric or asymmetric:"}
{"_id": "ultrasound$$$8adac8d0-f30f-42fc-8e17-66a6ea7d7f28", "text": "(A) Symmetric indicates a genetic or chromosomal difficulty. The term symmetric refers to the abnormal influence (mostly delayed growth) that affects all organs equally. It is essential to correctly postulate why a symmetric IUGR is often more reversible. Ultrasound-guided intrauterine blood transfusion is often used to improve IUGR in earlier fetal life."}
{"_id": "ultrasound$$$e66a3e2b-3031-48b7-8cb0-575c35421bb4", "text": "(B) Asymmetric indicates that the head/brain is of the expected size but the baby\u2019s body size and other measures, such as the abdominal circumference, are relatively small. This often indicates poor growth due to inadequate umbilical cord perfusion or anemia."}
{"_id": "ultrasound$$$8ec4b9ff-e74d-4c03-8af3-fdf69ea11e3f", "text": "Spinal vertebra development, or lack thereof, can be the first diagnostic clue to spina bifida. Without normal closure, the thecal sac enveloping the spinal cord in the vertebra may be seen to be bulging outside of the vertebrae. Limb development can be noted to have an abnormally small size or an abnormal shape."}
{"_id": "ultrasound$$$46f4493d-1a97-4b93-825c-6bade520dc6c", "text": "Genital development, more than ever before, may be evaluated before delivery. This is made possible by the higher resolution of high-end obstetric ultrasound machines."}
{"_id": "ultrasound$$$c2f4c7e0-3dce-444c-b51b-61254c86f13f", "text": "The fetus\u2019s activity can indicate variable states ranging from fetal distress to the infant sleeping. The biophysical profile (BPP) calculates different aspects of fetal motion that indicate fetal well-being. If the fetus has an abnormally low BPP, and especially if the fetus is mature enough to do well outside of the uterus, delivery is often induced or a cesarean is performed."}
{"_id": "ultrasound$$$3551a164-e08a-456f-98cf-6d4c52defe5f", "text": "Prenatal ultrasound has a continuing rapid pace of development with the advent of 3D and 4D technology. The debate regarding both the usefulness of prenatal ultrasound in terms of the wise expenditure of health care dollars and diagnostic accuracy has lagged behind the explosion of technology. We are charmed by babies, and rightfully so. The development of prenatal ultrasound will no doubt continue and will hopefully benefit humanity."}
{"_id": "ultrasound$$$082a6e3c-6d35-4653-b030-aff28e31395d", "text": "The subject of prenatal ultrasound allows some discussion about the considerations of technological development. With the development of the prenatal ultrasound technique come widespread expectations and assumptions that may not be true. First, with the demonstrable development of a new technology, it is assumed to work for the intended purpose. It is easy for a layperson to believe that such sophisticated modalities would be 100% accurate and, therefore, worth it. For prenatal ultrasound, it would be predicted that a clear picture would allow for not only accurate prenatal diagnosis but meaningful intrauterine treatment of most conditions. The truth of this assumption is variable, depending, of course, on the condition being evaluated. The greatest accuracy of diagnosis has to do with conditions related to abnormality of amniotic fluid volume. The most discouraging levels of accuracy have to do with the detection of heart defects and isolated congenital abnormalities such as a cleft palate. This subject quickly becomes more complex as one progresses into discussions about issues such as the sensitivity index, cumulative Gaussian distribution, and dimensionless statistics."}
{"_id": "ultrasound$$$79a5c0e5-070e-4616-a24d-9a1f064cb76a", "text": "If abnormalities are accurately discovered, the next hurdle is finding an effective treatment. Routinely in sophisticated medical centers, maternal-fetal medicine specialists and perinatologists perform procedures such as amniotic blood transfusions, fetal ureteral valve repair, and removal/replenishment of amniotic fluid volume due to abnormalities. In individual cases, there have been unbelievable advances and actual lives saved with this sophisticated technology. In our ever-cost-sensitive environment, we must balance this incredible cost against the expenditures of limited dollars for patient education."}
{"_id": "ultrasound$$$e216b56c-aa11-433a-9405-1fcc5aa371af", "text": "The first trimester of pregnancy is when there is the most danger of mishap. Due to the rapid cell division and differentiation of the embryo in unbelievable numbers, even minor \u201cerrors\u201d in cellular division may cause the very common event of spontaneous abortion. In the emergency department, it is often an unhappy task for a health professional to explain this issue to patients and their families. It is essential to be careful in doing so due to the tendency of many patients to wonder why a tragedy has occurred and to cast blame on themselves. Without careful explanation, patients who experience spontaneous abortion, or expulsion of an unsuccessful pregnancy through the vagina, may feel that they were at fault when this is not the case."}
{"_id": "ultrasound$$$a0267643-fbdb-4851-aa9e-cecbf9e3bde5", "text": "One can evaluate the earliest pregnancies with many parameters. The serial evaluation of the lab value of the \u201cpregnancy hormone,\u201d beta human chorionic gonadotropin (BHCG), over a few days gives an indication of developmental health. Early in pregnancy, the BHCG should double every 2\u20133 days. If there is a decrease or no increase in the value, this is a most worrisome sign for embryologic death. Often, early fetal demise will not be 100% certain, and the ultrasound and BHCG evaluation are done serially over a few days. Two ultrasounds without a heartbeat at the appropriate fetal age and an inappropriately declining BHCG are often considered diagnostic for intrauterine fetal death and likely spontaneous abortion."}
{"_id": "ultrasound$$$f34e29b5-1eec-4c39-bba0-c2f640f59b99", "text": "Ultrasound evaluation can most accurately begin in early pregnancy with a longer, higher-frequency transvaginal probe. Returning to the knowledge of ultrasound physics from earlier chapters, it is crucial to realize why a higher-frequency probe is placed through the vagina and near the cervix. The accuracy of the higher-frequency probe allows a marked improvement in resolution when the reflection is only a short distance. At four to five weeks gestation, we first see the fetal yolk sac, fetal pole, gestational sac, and fetal heartbeat. An irregularly shaped gestational sac or lack of a fetal heartbeat when the embryologic or crown-rump length is greater than five weeks are ominous signs of possible embryological death. It is estimated that up to 50% of pregnancies end in spontaneous abortion, often so early in development that the patient does not recognize the pregnancy."}
{"_id": "ultrasound$$$b8272123-5204-4770-b380-1dfe736ccd30", "text": "The other common peril in the first trimester of pregnancy is ectopic pregnancy, or pregnancy outside the uterus. As with intrauterine pregnancies, ectopic pregnancies grow and develop at very fast rates. Figure 5-4 shows an ectopic pregnancy adjacent to the left ovary. Most ectopic pregnancies are in the ovaries, fallopian tubes, or uterine horn. In either event, the pregnancies can \u201coutgrow their blood supply,\u201d rupturing and leading to maternal hemorrhage and potential death."}
{"_id": "ultrasound$$$73e720f9-46e9-4e5c-9498-383e5f0aab12", "text": "Sonographic signs of an intact ectopic pregnancy include enlargement in the area of implantation (even a functioning fetal heartbeat) and an \u201cempty uterus\u201d or lack of an intrauterine pregnancy when the BHCG is greater than 1500 international units. A patient with a ruptured ectopic pregnancy classically presents with sudden-onset unilateral pelvic pain and possibly signs of hemorrhagic shock. On the ultrasound, free fluid may be noted most commonly not only in the pouch of Douglas but also in the paracolic gutters or Morrison\u2019s pouch. This is often a surgical emergency; the bleeding must be stopped before maternal death occurs from hemorrhage."}
{"_id": "ultrasound$$$c17a52ba-633f-4d94-887b-2a10e94f6971", "text": "Gestational dating refers to the estimation of the gestation of the pregnancy. This is somewhat helpful when the medical provider evaluates issues such as whether to try to delay a patient in preterm labor or if induction of a patient who continues pregnancy more than 10 days after the estimated date of confinement (EDC) is indicated. Both of these issues have several determining factors. For preterm labor, infant mortality significantly decreases as delivery is delayed in many cases. For postterm situations, having a healthy term fetus more than 10 days after the EDC may pose unnecessary risks. These are complex decisions based on such data. To further complicate the issue, gestational dating may have variable accuracies. Some individuals have little or no prenatal care (i.e., some show up only to the emergency department when they are about to deliver or deliver at home without ever being evaluated by a medical provider). If one does have prenatal care and prenatal ultrasound, gestational dating accuracy remains variable. The facet that introduces the most variability is the gestational age at which the scan is performed. It has been traditionally noted that gestational dating accuracy has an 8% variability of the maturity of the pregnancy.[5] An example is that a 45-day gestation would have an accuracy of \u00b1days, and a pregnancy of approximately 250 days would have an accuracy of \u00b120 days. This variability may decrease as ultrasound machines become more sophisticated. The principle, however, continues to make sense that as pregnancies mature, the genetic and environmental issues that make us all different have a greater influence on growth."}
{"_id": "ultrasound$$$abb32e8b-6419-4415-95c3-e14eadfb025e", "text": "At approximately 14 weeks gestation, evaluation of organogenesis becomes more useful. As there is fetal growth, there is predictably more accuracy but fewer chances for potential interventions that may help as pathologic damage becomes irreversible. Organogenesis evaluation may differ according to the medical circumstances. Diagnostic capabilities vary according to the operator and machine."}
{"_id": "ultrasound$$$93a973b7-34ca-4661-8bcb-6bbf8bc7b2c7", "text": "The head, heart chambers, lungs, abdominal organs, genitals, and bones may be more successfully evaluated in the second trimester. While diagnostic accuracy improves, individual organs remain the most difficult to evaluate. Detecting some prenatal heart defects is an area of great interest and some improvement. The most common advantage of prenatal diagnosis of congenital heart defects is that if the condition is known, in more developed countries, the delivery can often be done at a tertiary medical center where there are maternal-fetal medicine specialists, pediatric cardiologists, pediatric surgeons, neonatal ventilators, and other sophisticated options for immediate treatment."}
{"_id": "ultrasound$$$96ca80e0-0e1f-4634-b727-12f4207ee7d3", "text": "Warda et al.[6] are originally credited with developing regression analysis values to use fetal growth parameters to estimate gestational age. Due to an interesting phenomenon known as \u201corgan sparing,\u201d some organs are more reflective of accurate gestational dating than others. If there is placental insufficiency, the head will continue to grow more normally, but abdominal growth will lag. This increasing discrepancy between fetal head and abdominal growth may lead to the diagnosis of IUGR and indicate induced delivery of a small or preterm infant."}
{"_id": "ultrasound$$$d68afd6d-98df-44fc-a8b5-44d094c36b60", "text": "The head measurement is first determined by the biparietal diameter and occipital-frontal circumference. There is a flow pattern of cerebrospinal fluid (CSF) through the brain\u2019s ventricular system and into the spinal cord through the foramen of Magendie and the foramen of Luschka. An obstruction of this flow causes increased back pressure, dilation of the ventricles, and pathologic pressure of the surrounding brain tissue. Many other conditions other than stenosis of the foramina cause hydrocephalus. This abnormality may be seen on prenatal ultrasound first as an increased head size and then as an increased ventricular size. Figure 5-5 shows an ultrasound image of fetal hydrocephalus. Hydrocephalus intervention is most often treated with postdelivery shunt placement, which involves placing a tube in the cerebral ventricles to bypass the obstruction and drain the excess fluid into other body cavities, such as the abdomen, where the fluid may be reabsorbed."}
{"_id": "ultrasound$$$98e1ad28-0210-4e83-b51a-42a511c01439", "text": "Other than abnormalities in CSF flow, there may be other abnormalities that are represented by an abnormal prenatal head ultrasound. These abnormalities have a wide range of etiologies, including genetic abnormalities, congenital abnormalities, and abnormal growth in an otherwise normal fetus. Genetic abnormalities have to do with abnormal chromosomes primarily due to mutation. Congenital abnormalities usually begin in the prenatal period and are evident at birth."}
{"_id": "ultrasound$$$84295ea5-b29c-460c-8de2-163ff1bf86e1", "text": "Cardiac ultrasound accurately predicts congenital abnormalities for many more subtle conditions. The most common congenital heart disease is patent ductus arteriosus, where the fetal ductus arteriosus that diverts the circulation away from the prenatal lungs and into the aorta does not close upon birth. This, of course, is never diagnosed prenatally. Rare but hazardous and sometimes fatal conditions such as transposition of the great vessels or defects of the central cardiac wall (called the septal wall) may be undetected by screening ultrasound exams. The complexity increases when there are combinations of heart defects such as tetralogy of Fallot, including pulmonary stenosis, right ventricular hypertrophy, ventricular septal defect, and an aorta that receives blood from both the right and left ventricle. In developed countries, when a fetal cardiac ultrasound is suspected from a routine prenatal ultrasound, a targeted ultrasound using more specialized machines and more specialized operators is subsequently performed. There may also be noncardiac prenatal ultrasound signs of heart disease, such as fetal hydrops (swelling) for fetal congestive heart failure."}
{"_id": "ultrasound$$$04b623ac-7617-43ca-bb39-cc9852a6fc66", "text": "Most intrauterine conditions that are treatable prior to delivery are identified in the abdominal exam. The umbilical cord is utilized as a site of intrauterine blood transfusions (by maternal-fetal specialists) to correct fetal anemia and hypovolemia. This procedure is done under real-time ultrasound and may be genuinely lifesaving as well as preventative of anomalies such as Potter\u2019s sequence."}
{"_id": "ultrasound$$$2d987574-3dfc-42ef-8393-8f846a3da3aa", "text": "The fascinating development of the normal kidneys involves the division and migration of one central organ into a right and left kidney. Abnormalities in this separation and division include the persistence of the larger central organ, called a \u201chorseshoe kidney.\u201d Difficulties in renal function, such as nonfunction, may be suspected when the kidney appears small or atrophic. If a kidney is obstructed but functioning, \u201cbackward pressure\u201d from the fetal urine may cause the kidney to enlarge, a condition known as hydronephrosis."}
{"_id": "ultrasound$$$65f42c44-a944-4b07-8051-4f5d7f993b2d", "text": "Some urinary tract obstructions may be corrected by intrauterine surgery. Posterior urethral valves in the male are the most common correction. When successful, relieving the obstruction prevents further renal damage and restores the average amniotic fluid volume to prevent complications from abnormal pressure."}
{"_id": "ultrasound$$$81af0862-8f4c-4c42-b6fd-d0d30f53cb67", "text": "Evidence of the normal flow of amniotic fluid is indicated by amniotic fluid volume. Contributions to the average amniotic fluid volume are mostly from fetal urine production, with some contributions from umbilical cord filtrate. Detraction from the amniotic fluid volume is mainly from fetal swallowing and fetal aspiration of the amniotic fluid into the lungs."}
{"_id": "ultrasound$$$47f112c9-9747-41a6-ae01-1ac06220c016", "text": "Oligohydramnios, a condition caused by reduced amniotic fluid volume from the reduced contribution of urine, creates well-known fetal anomalies called Potter\u2019s sequence. This condition is described as including particular fetal facial characteristics, fetal limb abnormalities, and pulmonary hypoplasia. The limb abnormalities are from abnormal pressure."}
{"_id": "ultrasound$$$cd0f5775-0df0-4615-b898-a3cc7884bd22", "text": "Polyhydramnios may be from inadequate fetal swallowing of amniotic fluid, inadequate fetal aspiration of amniotic fluid, or fetal gastrointestinal obstruction that prevents amniotic fluid from progressing once swallowed."}
{"_id": "ultrasound$$$84c9926d-b163-400c-bb38-30c72e0aaff8", "text": "The femur length is often considered to be the most reliable indicator of gestational age. Congenital abnormalities of the femur that make this statement not 100% true are rare and often apparent, as the femur abnormality coexists with other skeletal difficulties."}
{"_id": "ultrasound$$$aa646de5-dff3-4f80-a2e5-f63dfde9bedd", "text": "In first discussing the more common screening prenatal ultrasound exams, we have made mention of more targeted exams. Thoracic measurements, measurement of bones other than the femur, more targeted cardiac exams, more central nervous system ventricular evaluations, and fetal neck skin thickness measurements are made. For example, Figure 5-6 shows ultrasound images of a fetus\u2019s face and arms during week 20."}
{"_id": "ultrasound$$$39d5ac62-2eca-4ad0-86ba-73ea5ee2376d", "text": "More specific investigation of suspected abnormalities may indicate some conditions that can be corrected prenatally by thrilling advanced treatments such as umbilical cord blood transfusions, correction of amniotic fluid abnormalities, relief of posterior ureteral valve abnormality, or other intrauterine surgeries. As discussed earlier, almost all of these procedures are initiated by the targeted ultrasound."}
{"_id": "ultrasound$$$bc575a2b-2457-49bc-9fd9-6b04c0411a13", "text": "In 2023, as in every other year in the history of humanity, it remains true that the results of the most sophisticated events in fetal development can be influenced by some of the simplest yet sometimes neglected measures: receiving good prenatal care, ceasing maternal smoking or other substance use, and taking prenatal vitamins. We believe that it is important for future clinicians reading this to never tire of reminding patients to optimize their developing infants\u2019 likelihood of being healthy."}
{"_id": "ultrasound$$$1cea81f8-42d4-4fab-9537-f809b8fda57e", "text": "When using ultrasound, risks must be minimized to ensure patient safety. There are two basic rules of medical ethics:[1]"}
{"_id": "ultrasound$$$749dd97a-d7e8-45e7-94e8-b6d903cb6d04", "text": "In that case, a procedure is deemed ethical only when it benefits the patient."}
{"_id": "ultrasound$$$5555e979-37b2-48f4-8eb8-1dac202bd685", "text": "Ultrasound is generally considered safe if used properly. While there is no evidence it will physically affect the patient long-term, it should still be noted that it is a form of energy, and even at low levels, some studies suggest that overexposure to ultrasound can lead to potential undesirable effects such as"}
{"_id": "ultrasound$$$50c67ea3-ad36-432c-b6b7-6721a7b39efe", "text": "The damage type and extent mainly depend on the ultrasound wave characteristics such as frequency, intensity level, and exposure time, among other factors."}
{"_id": "ultrasound$$$6f66d46c-8da0-470c-a516-1f447cc17707", "text": "There are two possible biological effects of ultrasound exposure: (1) thermal (heating) effect and (2) mechanical (cavitation and streaming) effect. These effects can be quantified by reading the mechanical index (MI) and the thermal index (TI) on the ultrasound output display. The MI and TI are on-screen indicators of the potential bioeffects of ultrasound exposure. While imperfect, the TI and MI are considered good thermal and nonthermal risk assessments. These are discussed in detail in the sections below."}
{"_id": "ultrasound$$$d5b6a5cb-9e19-428c-8d19-7ab0c2d75005", "text": "As the ultrasound traverses the tissue, it absorbs some of the energy, causing the tissue temperature to increase. The rate at which the energy is absorbed depends on"}
{"_id": "ultrasound$$$cd148fb3-dd4f-4f5f-b475-b2381e55efb3", "text": "Higher thermal effects occur in tissues with higher absorption coefficients (such as bones), and lower thermal effects occur in tissues with lower absorption coefficients (such as amniotic fluids).[2] There is a concern that the embryo and fetus are particularly susceptible to heat energy."}
{"_id": "ultrasound$$$e2371fa9-eb39-4df7-90c1-c3ec62c747d4", "text": "The TI is a relative indicator of thermal risk for the likely temperature rise that might be produced after prolonged exposure. A more significant TI value represents a higher temperature and a higher risk. Three kinds of TI values can be displayed on an ultrasound machine depending on the type of application:[3]"}
{"_id": "ultrasound$$$51c035e2-b6cf-4c16-ad3e-65d1879f5d12", "text": "The thermal index (TI) is calculated as the ratio of the acoustic power produced by the transducer (Wp) to the power required by the tissue to raise its temperature by 1 degree Celsius (WDeg). In mathematical form:"}
{"_id": "ultrasound$$$ec2bb83d-ba17-403a-9ffd-f03692646f18", "text": "The index allows sonographers and clinicians to assess the relative potential heating effects associated with ultrasound imaging. A thermal index of 1 indicates the amount of acoustic power required to raise the tissue temperature by 1 degree Celsius. A higher TI value indicates a higher temperature and a higher risk."}
{"_id": "ultrasound$$$bd32c11f-3a1d-45fd-9bc6-cb83c138d8df", "text": "In general, tissue heating by ultrasound is related directly to the intensity of ultrasound waves. The rate of increase in temperature is related to the ultrasound intensity and degree of absorption. It is inversely proportional to tissue density and specific heat. The rate at which the tissue absorbs the heat depends on the protein concentration. For example, fat heats much faster than dense tissue such as muscles."}
{"_id": "ultrasound$$$f7a9e693-2328-466d-99b1-5c2ed01c120f", "text": "Nevertheless, the tissue temperature rise is also limited by the cooling effects of the blood flow, which makes it more challenging to heat vascular organs (such as the liver and kidney) than bone.[4] Another concern is that the presence of bones increases the likelihood of a temperature rise due to absorption in the bone and the conduction of heat from bone to adjacent tissues. However, TI values of greater than can occur on Doppler ultrasound. Therefore, prolonged pulsed Doppler ultrasound is not recommended for sensitive tissues such as those of the embryo (less than eight weeks), eye, head, brain, and spine.[5]"}
{"_id": "ultrasound$$$ffbb7405-88d1-43c4-95b0-cd26d0baa25f", "text": "Oscillations of gas bubbles (cavitation) occur inside tissue due to ultrasound pressure waves. The cavitation effect happens due to the excitation of a stable gas bubble by an acoustic field (noninertial cavitation\u2014the formed bubble oscillates in the acoustic field), and streaming effects result from the movement of complex fluids due to radiation force pressures (inertial, or transient, cavitation\u2014the formed bubble rapidly collapses and produces a shock wave that can be capable of causing biological damage).[6],[7] Bubbles are formed in a liquid when the local pressure falls (rarefaction part of the ultrasound wave) below the vapor pressure of the liquid. This cavitation effect is dependent on the fluid inertia, viscosity, and surface tension. Therefore, it is important to shorten the exposure time to minimize cavitation. Another critical point is that cavitation is likely to occur at lower transducer frequencies. However, cavitation-related bioeffects require the presence of cavitation nuclei (or bubbles) close to cells and physical or chemical interaction between bubbles and cells."}
{"_id": "ultrasound$$$47a30129-3979-4fcf-b0b3-e2ce3d6ad97a", "text": "The use of the MI as an indicator is based on the assumption that sound induces oscillations of microbubbles, which can cause an increase in the internal temperature of a water gas bubble."}
{"_id": "ultrasound$$$093cf76e-6ca5-409b-a371-cc1f2aa2bd0a", "text": "Nevertheless, tissue viscosity is 100 times greater than that of water such that bubble oscillations are greatly limited. A typical display of soft tissue TI and MI values for a carotid exam is shown in the top right corner of the Doppler image in Figure 4-1."}
{"_id": "ultrasound$$$2a82aad0-f946-48a1-a631-d4d5e95c41f1", "text": "The risk of cavitation increases with increasing MI values. Other studies suggest that high MI values are associated with the induction of premature ventricular contractions in echocardiography.3 The potential for nonthermal biohazards is likely to increase if the equipment is not used correctly. Such biohazards have been observed in animal tissues with gas bubbles at MI values greater than .[8]3 The bioeffects associated with MI values of or less have been reported in skeletal muscle, fat, myocardia, kidneys, livers, and intestines.[9]"}
{"_id": "ultrasound$$$794a8933-d75b-4d93-a500-5f548635fd76", "text": "Consequently, unnecessary exposure to tissues such as the neonatal lungs should be avoided. Ultrasound operators should keep the MI values as low as possible when carrying out a diagnosis."}
{"_id": "ultrasound$$$3f2465c6-1148-43be-918d-0144d6793ed0", "text": "As discussed earlier, the other indicators of thermal effects include the TIS, TIB, and TIC values. The TIS is used when the ultrasound beam passes through soft tissue only, such as in the abdomen and fetal examination during the first trimester. If bones are present, the TIC is used (e.g., in head examinations). The TIB is used if the ultrasound encounters a bone (e.g., in the fetal examination in the second and third trimesters). In addition, the TIS is commonly used for fetal scanning during the first eight weeks of gestation, and the TIB is used after eight weeks. In adults, the TIS is commonly used for eye scanning. In pediatric and adult patients, the TIC is used when examining areas close to skull bone. The TIB is used for all other purposes."}
{"_id": "ultrasound$$$b2d1cfdd-9ba3-4123-943c-0a08bc943210", "text": "Following the correct electrical safety procedures reduces the possibility of fire, muscle contracture, and tissue burns. Shocks can occur when a person touches electrical wires due to broken insulation in the circuit, which may contract muscles, alter brain function, or lead to ventricular fibrillation. Small currents can harm patients through saline catheters, which convert them to relatively large current densities. To reduce patient susceptibility to electrical hazards, equipment with any broken or uninsulated cables and damaged probes must not be used."}
{"_id": "ultrasound$$$a483a27f-8cbb-4dd6-978c-f524b5bd3487", "text": "A major concern in the safety of ultrasound has been the exposure of the embryo and fetus during pregnancy examination. Based on current knowledge, there is insufficient information to link diagnostic ultrasound and recognized adverse effects in humans."}
{"_id": "ultrasound$$$474600c4-5aa0-4e57-8da5-a8e601655eb3", "text": "The use of diagnostic ultrasound equipment is limited to medical diagnosis only. It can only be used by personnel who are fully trained in the safe and proper operation of the equipment. Other expectations are that the operator should have a complete awareness of machine settings and understand the effect of those machine settings on thermal and mechanical bioeffects. The simple rule that must be followed is that the default power setting protocols should be set at \u201cAs Low As (is) Reasonably Achievable\u201d (ALARA) to produce diagnostic quality images. In order to minimize the exposure time on a specific anatomical structure, it is recommended to move or lift the probe when stationary imaging is not necessary. When feasible, it is advisable to avoid imaging fields of view that contain sensitive tissues, including the eye, lungs, and intestines (gas-filled tissues) and fetal calcified structures, such as the skull and spine."}
{"_id": "ultrasound$$$41a6e201-21b8-4fcd-b5d9-fa74a6290649", "text": "The AIUM, the U.S. Food and Drug Administration (U.S. FDA), and other organizations have issued some guidelines on the use of medical ultrasound in the United States. These guidelines are presented in the sections below."}
{"_id": "ultrasound$$$a8c50c0f-9ccc-4623-b240-c7e71cc25fbe", "text": "The AIUM has issued minimum criteria for a complete medical examination of different parts of the body.[10] According to the AIUM guidelines, there are no independently confirmed significant biological effects in the low megahertz frequency range for ultrasound with intensities below 100 mW/cm2. In addition, for focused ultrasound, such effects have not been proven even at higher intensities for exposure times below 500 s. When adjusting controls that influence acoustic output, the AIUM stresses that it is essential to adhere to the ALARA principle and take into account both the duration of transducer dwell and the total scanning time. It is important to be knowledgeable about the MI upper limit, TI upper limit, and associated duration limits for the examination type being conducted. For example, the guidelines established by Harris et al.[11] and endorsed by the AIUM for the recommended maximum duration of ultrasound exposure at a given setting of the TI are presented in Tables 4-1 and 4-2."}
{"_id": "ultrasound$$$332b0bef-a5eb-49e7-9f2f-1c311ba5523c", "text": "Table 4-1: Recommended maximum exposure time and TI ranges for obstetric (including gynecologic when pregnancy is possible), neonatal transcranial, and neonatal spinal examinations."}
{"_id": "ultrasound$$$963f4430-f32f-4f4b-96c1-7d9063038fdc", "text": "Table 4-2: Recommended maximum exposure time and TI ranges for adult transcranial, general abdominal, peripheral vascular, neonatal (except head and spine), and other scanning examinations (except the eye)."}
{"_id": "ultrasound$$$499500f7-975b-4c5c-851f-c76ecbaf0cee", "text": "Even if it is necessary to go beyond the recommended values, an undesirable thermal effect is unlikely to occur in most scanning environments due to attenuating factors such as sensor motion and tissue perfusion. However, it is important to adhere to the ALARA principle so that the duration of the examination is limited to the amount of time needed to obtain a useful diagnostic result."}
{"_id": "ultrasound$$$0d1171a8-59dd-4afb-9bf8-4aeef6479bb6", "text": "U.S. Food and Drug Administration Guidelines"}
{"_id": "ultrasound$$$6dd28dce-0249-4685-b862-09d8ff2c9777", "text": "Because of the likelihood that ultrasound may have some potential heating and mechanical effects, the U.S. FDA states that the use of ultrasound is not entirely harmless. For this reason, it discourages the nonmedical use of ultrasound devices. The guideline established by the U.S. FDA uses the spatial peak pulse-average intensity (Isppa) and the spatial peak temporal-average intensity (Ispta) in addition to the MI as safety measures for diagnostic ultrasound.[12]\u00a0Ispta indicates the highest intensity measured at any point in the ultrasound beam averaged over the temporal (time) duration of the pulse, and Isppa represents the highest intensity measured at any point in the ultrasound beam averaged over the pulse repetition period. Table 4-3 lists the highest limit values for these acoustic indicators for diagnostic ultrasound devices."}
{"_id": "ultrasound$$$e09d3ae4-c564-43bc-9a68-5aa7b1e44231", "text": "Table 4-3: U.S. FDA-issued acoustic output exposure level limits."}
{"_id": "ultrasound$$$e7ac5f09-2a35-43a5-9082-b2b04c381f09", "text": "Other categories that could be included in Table 4-3 are abdominal, intraoperative, pediatric, and small organ (breast, thyroid, testes, etc.). The U.S. FDA also mandates the display of the likelihood of ultrasound-induced bioeffects, known as the Standard for Real-Time Display of Thermal and Mechanical Acoustic Output Indices, on diagnostic ultrasound equipment capable of producing higher thermal or mechanical effects. The U.S. FDA discourages any unapproved use of medical devices without a physician\u2019s order. Such practices may be in violation of state laws or regulations. The operator has the ultimate responsibility for the safe use of ultrasound equipment."}
{"_id": "ultrasound$$$0571d725-0f4f-4d17-9702-d2e001b00d6a", "text": "The National Collaborating Centre for Women\u2019s and Children\u2019s Health recommends fetal ultrasound screening between 18 and 20 weeks gestation.[13] The guideline was issued on the basis that there is no evidence to support the need for routine use of ultrasound screening after 24 weeks gestation. The Society of Maternal and Fetal Medicine[14] recommended only one medically indicated ultrasound per pregnancy."}
{"_id": "ultrasound$$$aeb882ec-2d79-45c6-9eba-8e7d4c09a59e", "text": "Medical equipment, including ultrasound machines and transducers, may act as both sources and vectors of microbial transmission during examination. Globally, medical equipment\u2013acquired infections are on the increase. Several studies have confirmed the transmission of bacteria and viruses through improper hygienic use of medical equipment. Common transmittable bacteria and viruses that have been identified include Staphylococcus aureus, Pseudomonas, Acinetobacter species, Candida albicans, hepatitis B, hepatitis C, human immunodeficiency virus, and herpes.[15]"}
{"_id": "ultrasound$$$dfafd78c-880f-4797-b8fa-696f0e58e014", "text": "Just as with any medical procedure, there is a potential risk for cross infection (patient-to-patient, patient-to-operator, or operator-to-patient) if proper procedures are not followed. The risk of infection is highest in procedures that utilize transducers in intracavities or where body fluids are encountered. These risks are classified into three categories:"}
{"_id": "ultrasound$$$e3335d3a-2eb8-47e8-b5a3-ba7953960ba0", "text": "The cleaning, disinfecting, and sterilizing of reusable medical and surgical equipment or devices must comply with the manufacturer\u2019s requirements and safety protocols. Routine cleaning must include removing the coupling gel and any visible residue from the probe using the recommended detergent. Disposable gloves must be worn during the cleaning process. Areas that require extensive cleaning or disinfection are the transducer probes and ultrasound machine screens. The keyboard is another critical area that can be easily forgotten during cleaning or disinfection. The choice of the keyboard matters\u2014keyboards similar to those used for computers are not ideal for medical purposes, as it is impossible to clean in between the keys after every medical examination. Most modern ultrasound keyboards now come with disinfectable polyurethane covers, which make them easier to clean."}
{"_id": "ultrasound$$$d1783b75-f03b-4213-827e-59d71b14e978", "text": "A simple rule is to regard every patient as a potential source of infection. To prevent the risk of cross infection, the following minimum precautions are recommended in every examination:"}
{"_id": "ultrasound$$$47444442-efb8-41ec-bf3e-5abd5f1ddd2a", "text": "While the use of ultrasound in medicine has gained traction over the past two decades, it still faces significant hurdles in some parts of the globe. This is partly due to differences in culture. For example, in some countries, ultrasound is now used for sex-selective abortion.[16] The purpose of this book is not to debate these ethical issues but to bring an awareness of how different societies view the use of ultrasound in medicine."}
{"_id": "ultrasound$$$73920767-8ba9-44c5-8a75-4335386b3a03", "text": "Clinicians often find themselves in difficult situations, especially when diagnosed anomalies require critical procedures. For example, some fetal abnormalities present ethical dilemmas concerning patient counseling, and abortion issues present challenges in gynecology and obstetrics."}
{"_id": "ultrasound$$$c069b630-e21e-4f19-8bbc-24b0b58df383", "text": "That means clinicians have to play a pivotal role in educating patients about the need to perform these procedures and their benefits to allay the emotional nature of the ultrasound diagnosis or obstetric scanning and the associated implications. In addition, clinicians performing the screening may face dilemmas when diagnosing life-threatening problems with no corrective solutions. In some sections of society, revealing the life span of a patient may not be well received or accepted. That leaves the burden of counseling to the clinicians."}
{"_id": "ultrasound$$$f7fa6317-d215-4aff-8142-90fcabf80e20", "text": "Two-dimensional ultrasound is considered a standard or conventional imaging technique. In 2D scanning, a series of thin slices make up an image, and only one slice can be seen at a time."}
{"_id": "ultrasound$$$d6355d00-b714-496c-b0e0-21b99b62f4dc", "text": "Three- and four-dimensional clinical ultrasounds have been around for nearly 25 years. However, their use has lagged behind that of computerized tomography (CT) and magnetic resonance imaging (MRI) due to the difficulty in rendering the data in 3D.[1] However, ultrasound equipment\u2019s increasing computing power has helped resolve complex signal processing tasks needed to render 3D ultrasound data."}
{"_id": "ultrasound$$$474f61cc-6d35-45b2-9a84-bdf103cb2750", "text": "Three-dimensional ultrasound is based on the same principles of operation as 2D ultrasound but has an added position-sensing component to produce the effect of a 3D image, as illustrated in Figure 3-1. In 3D ultrasound imaging, echoes are used to form real-like realistic volume images."}
{"_id": "ultrasound$$$6d3d705e-c3c4-47e6-ba8a-c016c343a5fb", "text": "A 4D ultrasound shows 3D ultrasound images in motion. Two-dimensional ultrasound images are commonly used because they are less expensive than 3D or 4D. However, many centers now use 3D/4D ultrasound. The most common area of use has been fetal cardiovascular scanning. The 3D/4D technology offers real-time motion-gated cardiac scanning."}
{"_id": "ultrasound$$$7f017ea0-029b-4fe5-bd1c-3e16b1283c66", "text": "A 3D/4D ultrasound offers expecting parents a memorable lifetime opportunity to see the features of their unborn babies. Figure 3-2 shows 2D grayscale and 3D colored images."}
{"_id": "ultrasound$$$edc55de3-e5e3-4467-817a-cd141591ae76", "text": "Acquiring qualitative and quantitative sonographic volume data such as multiplanar imaging, surface and volume rendering, and semiautomated volume calculation gives 3D/4D an added advantage over 2D imaging. Virtual planes provide extra information that cannot be viewed with a standard 2D technique.[2] The American Institute of Ultrasound in Medicine (AIUM) notes that the ability to take images in any plane in real time has enormous potential use in medical diagnosis.[3] Another advantage is that 3D ultrasound can provide measurements in three planes with acceptable reliability."}
{"_id": "ultrasound$$$a0e9c8b5-6faa-449b-b169-b1880310eb9d", "text": "A 3D ultrasound uses a series of 2D images covering a volume of a particular area. This allows the images to be rotated and displayed in different orientations. When displayed in real time, or live, they form a 4D ultrasound. Volume acquisition is achieved by using an array of transducers consisting of many 2D frames, one behind the other. Automated mathematical algorithms are then used to process the volume data to produce the desired image, as illustrated in Figure 3-3."}
{"_id": "ultrasound$$$ccbafe67-7027-4c66-b261-682f81e07550", "text": "The reconstruction in Figure 3-3 occurs in a matter of seconds such that the spatio-temporal imaging correlation (STIC) acquisition is completed in the presence of the patient. The STIC acquisition mode can be combined with B-mode, color, and power Doppler. From a good STIC acquisition, a sequential plane may be viewed in corresponding transverse and longitudinal planes at any time point, simultaneously."}
{"_id": "ultrasound$$$e50f981e-d828-49c6-bb2d-e9a49534d80e", "text": "The B-flow image is a live grayscale depiction of blood flow and cardiac chambers. When applied to 3D fetal echocardiography, the B-flow image shows blood flow in the heart and great vessels in real time.[4]"}
{"_id": "ultrasound$$$6b8bf4fb-faed-4d70-af8a-ff4a664ef6de", "text": "Four-dimensional imaging involves a 3D image moving in real time, created from a volume of data that allows the live reconstruction of images in different planes and renderings. Rendering is taking voxel-based data and converting it into a viewable image with added depth. Three- and four-dimensional imaging function by reconstructing an image from multiple 2D planes."}
{"_id": "ultrasound$$$8ea07ff9-12da-4a54-b4fd-cc16ff6f0c18", "text": "The 3D color and power Doppler ultrasound technology can be used in vascular abnormality assessments such as the fetal placental cord and pulmonary vessels. Three-dimensional ultrasound is not yet widely used in many routine medical procedures but has been widely used in gynecology, obstetrics, and biopsy."}
{"_id": "ultrasound$$$dcfb99e1-2177-4465-b08b-4a26b1930299", "text": "The application of 3D/4D ultrasound in biopsy allows for needle tracking in multiple planes simultaneously and imaging of the morphology and proximity of local anesthetic spread around the target nerves.[6] Other specialties in which 3D/4D ultrasound can be applied include dermatology and ophthalmology."}
{"_id": "ultrasound$$$f7b7295c-75f2-4152-90e6-b2f1e10f6bca", "text": "In 2D ultrasound imaging, a series of noncontinuous and presumably representative sections of the imaged organ is used to visualize the anatomy of the organ. Repeated examination is required in order to reconstruct cross sections visually. The absence of quantitative spatial documentation means clinicians must rely on image labels and trust the acquisition technique. Repeated examinations may not produce exact image planes, making comparing serial exams difficult.[7] In addition, every time an organ is examined, it\u2019s likely to give rise to varying measurements of a specific organ or structure, as the imaging process is highly operator-dependent. Volumetric (3D) ultrasound allows volumetric acquisition of anatomic data, which may be needed to examine internal organs such as the liver, gallbladder, gallstones, or kidneys."}
{"_id": "ultrasound$$$3239502a-8a35-4ec1-a65f-53682e148687", "text": "In 3D/4D, volume data are obtained in a single image, allowing the operator to view any plane in the volume. The multiplanar rendering mode options also allow for viewing images in real-time motion. Three-dimensional imaging is helpful in examining contours such as those in the facial area, the heart chambers, and the valves. The 4D ultrasound provides a motion video of the 3D structure in real time. Together, 3D and 4D ultrasound have been quite successful in examining the inside or outside of organs, nodules, cysts, or tumors. The 3D ultrasound also offers a more comprehensive image of anatomical structures and pathological conditions. A 3D echocardiography can provide estimates of ventricular volume and function. Comparing 2D and 4D, qualitative 4D ultrasound is considered superior to 2D in real time. However, 4D is inferior to 2D ultrasound for quantitative analysis of movements. For example, 4D evaluation of complex fetal facial activity and expression is better than that of 2D.[8]"}
{"_id": "ultrasound$$$4b48ce6a-3964-4910-9dca-182e6ce29afa", "text": "Hence 3D and 4D ultrasound imaging allow more accessible and more rapid screening than 2D ultrasound imaging. Irregularly shaped organ volumes can be more accurately visualized using 3D than 2D imaging ultrasound. In addition, 3D measurements are more reproducible than 2D ultrasound and provide the option to rotate the volume, which is often necessary to allow optimal visualization of the geometric structure of the organ under examination and determine the position of the structure in the volume.[9]"}
{"_id": "ultrasound$$$73583c23-ead2-4d40-beee-34509dd98504", "text": "The market for small, portable ultrasound machines has flourished over the past decade. They have gained popularity and significant usefulness in the medical sector, especially in the emergency medicine department. There are two specific reasons for this popularity: (1) they are smaller/lighter and portable, which makes the whole process of scanning the patients quicker, more accessible, and safer at the same time, and (2) their portability, ease of use, connectivity, and cleanability make them ideal tools for diverse care settings. Conventional large-sized ultrasound machines are demanding and come with certain limits. For instance, these larger machines are laborious and challenging to sterilize thoroughly in comparison to small handheld machines. Also, a physician performing any intervention with this machine usually requires an extra pair of hands to help set it up and obtain clinical images."}
{"_id": "ultrasound$$$c410ce0c-fa50-4fc1-bdaf-28230fb428ed", "text": "Both laptop and handheld models of portable ultrasound systems are available. There are also a few models that are intermediate between these two. Therefore, portable ultrasound machines can be broadly divided into three categories. The first category is the large, laptop-sized device weighing 12 to 15 pounds. An example of such a device is GE HealthCare\u2019s LOGIQTM e portable ultrasound. The second category involves a smaller device, almost the size of a smaller laptop and weighing about 6 to 10 pounds. An example of such a device is the Sonosite Edge machine."}
{"_id": "ultrasound$$$97c25b56-194d-4d3f-8e05-e08df558d50c", "text": "With technological innovations, even smaller and lighter ultrasound devices with better image quality are now available (such as those manufactured by GE HealthCare, Siemens, and Philips). The third category is the handheld ultrasound device that weighs under a pound. Philips\u2019s Lumify is an example of one such device; it costs around $6,000 to buy or $2,300 per year to lease. This device operates through a simple USB connection of the transducer to a compatible device such as a smartphone. GE HealthCare\u2019s Vscan is a pocket-size ultrasound device that provides real-time gray anatomic and color flow images. It is optimized for physicians to quickly inspect the heart, abdominal organs, and urinary bladder. It can provide insights into areas of obstetrics and gynecology, pleural fluid and motion detection, and pediatrics. A recently extended version of the Vscan handheld ultrasound device can be used to help confirm and monitor the progression of acute respiratory diseases like COVID-19."}
{"_id": "ultrasound$$$e184f48f-9dd7-4797-a091-6095c57049d7", "text": "While 3D/4D ultrasounds show success in some cases, they have some limitations in their clinical applications. Three-dimensional renderings have demonstrated impressive results in some areas; the interfaces are complex and difficult to interpret. Other significant issues raised by the AIUM[10] are that the protocols and manipulation techniques are not standardized across manufacturers with respect to the terminology of functions and the display, therefore requiring time and effort to perfect operator skill and accuracy. Standardization is also needed in image orientation. Another challenge is that 3D/4D does not solve poor 2D image problems for several reasons: (1) artifacts and orientation can be confusing, and (2) resolution decreases in reconstructed images such that in some cases, 3D/4D images may be inferior to 2D images. Currently, 2D fetal echocardiography with color Doppler has a success rate of up to 92% in diagnosing congenital heart diseases.[11] Research findings have shown that there are limitations to adequate visualization of fetal anatomy with 3D/4D ultrasound if there is inadequate amniotic fluid surrounding the fetus or if the fetus has its face in the posterior position. Another reported limitation with current 3D/4D Doppler ultrasound technology is that endometrial and subendometrial blood flows measured at one time point during IVF treatment were not good predictors of pregnancy.[12]"}
{"_id": "ultrasound$$$7424c46b-444e-4ee1-a012-496f34237a52", "text": "The AIUM organized a meeting of physicians and scientists to discuss the diagnostic benefits and technical limitations of 3D ultrasound in obstetrics and gynecology and its potential use in various clinical practices now and in the future. Their recommendations, together with the equipment manufacturers and other safety regulations, will be reviewed in the next section."}
{"_id": "ultrasound$$$ac6528b8-b0ab-4fa4-907b-daab138b866c", "text": "As shown in Figure 2-1, an ultrasound machine includes the following major components:"}
{"_id": "ultrasound$$$7560208e-8c9a-43b0-b384-92670a326c40", "text": "Figure 2-2 shows a generalized schematic of ultrasound machines\u2019 mode of operation."}
{"_id": "ultrasound$$$1d7e4f44-13c3-41e6-8914-b6b85de0ad71", "text": "More details about the operations of the components of the ultrasound machine are discussed in the sections below."}
{"_id": "ultrasound$$$eae5b0c6-a3cc-480e-a256-25fb867d830a", "text": "In the 19th century, Pierre and Jacques Curie discovered that some materials generate electric potentials in response to mechanical deformation (material shrinks or expands) or stress (the substance is squeezed or stretched)\u2014a phenomenon called the piezoelectric effect, which is illustrated in Figure 2-3. Conversely, the same materials change their shapes when an electric field is applied."}
{"_id": "ultrasound$$$3f5a0f7f-0dbf-4c0e-876b-374b57ccf6f2", "text": "Examples of such materials include silicon oxide, potassium sodium tartrate, barium titanate, and lithium niobate. Bones, tendons, skin, and some man-made polymeric materials can also exhibit the piezoelectric effect. These materials bend in different ways depending on the frequency and their shape, which can result in different vibration modes. The modes are the basis for developing transducers that operate at different frequencies."}
{"_id": "ultrasound$$$21ea2cce-2b35-49d2-b305-ec9206d1a049", "text": "A typical ultrasound probe with its components is shown in Figure 2-4. The vibration of crystals in an ultrasound machine\u2019s transducer generates ultrasound, and the transducer can detect the echoes and convert them to electrical signals. A transducer is composed of piezoelectric crystals, which respond to pressure to generate an electric current. The alternating current causes the piezoelectric crystals to vibrate at a desired frequency corresponding to ultrasound waves. The produced ultrasound beam is directed into the tissues by moving the transducer and changing the angle of incidence of the ultrasonic beam. Conversely, when an electric current is applied to the crystals, its shape changes with polarity, producing electrical signals from echoes that are processed to generate a display. Hence the crystals act as transmitters (for a short time) and receivers (most of the time)."}
{"_id": "ultrasound$$$94811f99-172d-4f5b-b147-104bc6827fcf", "text": "Since the air between the tissue and the transducer inhibits the propagation of the ultrasound beam, a conducting gel is usually applied between them."}
{"_id": "ultrasound$$$630d92c7-dc16-4dc5-9257-db9e15ba9009", "text": "Figure 2-5 shows a block diagram of an ultrasound imaging system. Two modes are essential in the formation of an ultrasound image. These are the transmission modes that convert an alternating current into mechanical pressure waves. The backscattered pressure waves are picked up by the receiving mode, which converts them into electrical signals. The ultrasound waves that get fully transmitted through any tissues or structures do not produce echoes and appear dark. For example, all fluids appear echo-free and black on the ultrasound image."}
{"_id": "ultrasound$$$e1884315-5857-43d0-8267-a013b09efebe", "text": "The transducer generates pulses and detects backscattered energy from the tissue boundaries, as shown in Figure 2-6. The length of delay between the transmitted and received pulses is used to determine the depth of the tissue boundary or organ under examination."}
{"_id": "ultrasound$$$e1cb142a-d659-48b4-be24-15b5df92ded4", "text": "These piezoelectric signals from the crystals are amplified and converted into a gray or white color on the ultrasound image via a computer program. The difference in tissue reflectivity allows us to see individual structures. When ultrasound hits a dense object, it is wholly reflected, forming a posterior acoustic shadow (a bright and echogenic image). This is because no ultrasound is transmitted, creating an echo void. The computer can calculate the tissue\u2019s depth by measuring the time between when the wave was sent and when an echo was detected."}
{"_id": "ultrasound$$$f85ae033-ef2c-4743-ae8e-bea40f1a01a8", "text": "There are several assumptions about sound waves in ultrasound system operation. These assumptions, when violated, result in the formation of image artifacts, which often make it difficult to distinguish between real and fictitious features in an image. These assumptions are"}
{"_id": "ultrasound$$$e1406c09-c5e7-4fc9-be2e-49c06c33addd", "text": "Artifacts are fictitious portions of images (distortions of the actual anatomy of the tissue). Improper scanning techniques may cause some artifacts, while others result from the physical limitations of the instrument. Such artifacts can be explained using the properties of the ultrasound waves, their propagation through tissue, and the assumptions used in image processing. Typical artifacts include shadowing, beam width, side lobe, reverberation, comet tail, ring down, mirror image, and refraction. They are formed primarily due to multiple echo paths or velocity errors and attenuation errors."}
{"_id": "ultrasound$$$0d70a4c7-b6cc-4419-8c2e-149cc2c06a7b", "text": "Highly reflective or attenuating tissues reduce the ultrasound beam intensity inside the tissues, leading to obscured images close to or behind them. This shadowing artifact results from refraction that causes echoes to appear darker, like a shadow, due to the ultrasound beam\u2019s decreased amplitude, intensity, and power."}
{"_id": "ultrasound$$$ee3a1fe3-d05c-4493-9e30-24eba25f7416", "text": "Shadows occur when an ultrasound beam cannot pass through an area deeply due to the presence of a strongly reflecting or attenuating tissue. Figure 2-7 shows acoustic shadowing caused by the stones in the gallbladder. The shadows occur in regions of high acoustic impedance mismatch, such as soft tissue / gas or soft tissue / bone interfaces. These shadowing artifacts prevent visualization of the accurate anatomy on a scan by covering it with an anechoic shadow. This may cause misdiagnosis of the tissue anatomy."}
{"_id": "ultrasound$$$9d5452c2-6a31-477b-b3a8-0d54d6033e57", "text": "Other causes of shadowing artifacts are improper scanning techniques, improper settings, or poor ultrasound systems."}
{"_id": "ultrasound$$$d59d7b0a-9152-49a1-936f-218e5bb1b28a", "text": "Some possible ways to reduce these artifacts include taking images from several angles, changing the lateral resolution, or decreasing the frequency to avoid missing information."}
{"_id": "ultrasound$$$3daef67e-2dd5-434e-8fbb-d719d1d0e989", "text": "Mirror Image Artifact (a.k.a. Ghost Artifact)"}
{"_id": "ultrasound$$$cfd32dde-14b6-413f-abe5-2a7983530f65", "text": "Multiple reflections (reverberation) often occur in regions with high impedance mismatches, such as air/fluid or flesh/bone interfaces. The multiple reflections duplicate a true reflector when the waves from a highly reflective surface are redirected toward a second structure. The redirected waves form a replica of the original structure, which appears on the image as a second structure."}
{"_id": "ultrasound$$$fa3de6bb-03e5-41e5-ad9d-ba85b8fb9acd", "text": "Mirror image artifacts occur in both grayscale and color Doppler imaging. The true reflector and the artifact are equidistant from the mirror plane located between the two, as shown in Figure 2-8. This violates the assumptions that (1) ultrasound waves travel in a straight line and (2) waves travel directly to a reflecting tissue and are reflected directly back to the transducer."}
{"_id": "ultrasound$$$bc9f6cb0-1004-4468-aab7-0e672923c67e", "text": "A ghost artifact can develop on a color Doppler image when multiple reflections occur beyond borders. Ghost or mirror image artifacts can be reduced by decreasing the overall gain or changing the beam angle. During diagnosis, mirror images should be clearly separated from actual anatomy, especially in guided needle biopsy, where samples must be taken from a specific location."}
{"_id": "ultrasound$$$ada9e603-3ce4-4713-994e-dfb8d56493ce", "text": "Two possible ways by which mirror image artifacts can be formed are illustrated in Figure 2-9a."}
{"_id": "ultrasound$$$cc2c1ae8-6ab7-4ecf-8051-2e78c5a3a6e3", "text": "Circular structures such as cysts can cause refraction, which produces shadows on the object\u2019s edge due to a mismatch in acoustic impedance at the boundary or interface. The change in direction (bending) results from the change in the propagation velocity of the ultrasound waves. A schematic of this process is illustrated in Figure 2-9b."}
{"_id": "ultrasound$$$4d97ebad-4bee-4604-b21f-5ddc8384d31c", "text": "Beams generated from the edges of a single-element transducer tend to spread from the primary beam, as shown in Figure 2-10. These lobe beams can be reflected into the primary beam, adding energy to the beam\u2019s main axis. These artifacts violate the assumption that all reflections occur in the path of the beam\u2019s main axis."}
{"_id": "ultrasound$$$1c900944-be4e-450f-b1a0-54daa93a46a2", "text": "This duplication of the true anatomy with false reflection results from strong reflections that return to the transducer. Since the machine assumes all echoes to be coming from a true anatomic structure, incorrect images are displayed together with the correct ones."}
{"_id": "ultrasound$$$2b379c11-63fb-4f56-b869-704a39fcbd36", "text": "A rapidly oscillating ultrasound beam produces multiple side lobe echoes that appear on the display as a curved line equidistant from the transducer. The two most important features that distinguish a side lobe artifact from an anatomical structure are that it is equidistant to the transducer along its length and it passes through anatomical structures."}
{"_id": "ultrasound$$$27f37706-d7b9-4367-b0a0-988d39cea73c", "text": "The side lobe artifact is corrected by imaging the structure in multiple directions. The artifact will not appear in all viewing directions."}
{"_id": "ultrasound$$$63766a7f-154b-4ca2-bd3e-d8382ee385ee", "text": "While the assumption is that all reflections are in the path of the beam\u2019s main axis, as the beam is projected from the transducer into the tissue, some of the ultrasound waves spread outward, as shown in Figure 2-11. The presence of a strong reflector along the path of the diffracted waves produces echoes that are misinterpreted as being along the beam\u2019s main axis. The grating lobe artifact generally appears weaker than the true reflector. This obscures the actual anatomy with a false reflection."}
{"_id": "ultrasound$$$aa308a33-07c8-4c1d-9c15-751fe342404d", "text": "The artifact is corrected by taking multiple views of the structure under examination. An artifact will not appear in all views."}
{"_id": "ultrasound$$$89a3c4a4-7ee1-4eec-a2c7-3c65998214f6", "text": "Multipath artifacts occur when the primary ultrasound beam reflects off anatomy at an angle such that a part of the echo returns to the transducer and at the same time, another echo also reaches the transducer after reflecting off a second boundary."}
{"_id": "ultrasound$$$b0893dbc-2290-4b33-9095-15bfee75e847", "text": "The echo from the secondary reflector takes a longer path and hence longer time to get back to the transducer. Since ultrasound machines measure the depth based on the time between the transmitted signal and the received echo, the machine will perceive a longer time and depth and position the image on the wrong spot, as shown in Figure 2-12."}
{"_id": "ultrasound$$$eb05a650-d111-4586-9a2f-f556bd3e67da", "text": "In this case, the assumption that the ultrasound beam travels directly to the reflector and back to the transducer is violated. This phenomenon creates what is called a propagation path error. These artifacts give rise to the incorrect axial location of an object due to longer path lengths."}
{"_id": "ultrasound$$$d70fe753-ba13-41fd-bfda-39453da25d9d", "text": "Multipath reflections may form images that appear deeper or misplaced. The problem can be reduced by taking multiple views at different angles."}
{"_id": "ultrasound$$$c3b89cb6-99a0-435c-a5b9-4ebd9973dfa5", "text": "An ultrasound beam incident on a curved or oblique boundary is reflected in various directions. Some of the reflected waves are directed away from the transducer. This reflection is similar to the scattering process. In this case, reflectors do not appear on the image due to longer path lengths and increasing attenuation."}
{"_id": "ultrasound$$$e7144c72-2e7c-4383-8ee3-f202651df621", "text": "Figure 2-13 illustrates the possible reflections from an oblique surface in various directions. This observation contradicts the assumption that an ultrasound pulse travels directly to a reflecting boundary surface and back to the transducer."}
{"_id": "ultrasound$$$5ee7cfc8-ea64-4c90-9a79-437958123325", "text": "The strength of the echo received by the transducer is less than the expected intensity, which gives false brightness, missing reflections, or an improper location of the anatomic structure. These artifacts are associated with weak, too-bright echoes or improperly located structures. This artifact can be reduced by changing the transducer angle or by using a large footprint."}
{"_id": "ultrasound$$$5766d62f-5c35-4771-a717-6d1ecdbf4667", "text": "While it may be convenient to assume that the beam width stays approximately equal to the transducer size, the ultrasound beam actually spreads out as it moves away from the transducer, as Figure 2-14 shows. Due to this divergence, the echoes generated from the edge of the beam appear to be coming from the center of the beam. The artifacts are most apparent when most of the beam travels through the fluid and part of it interacts with adjacent soft tissue, as shown in Figure 2-14."}
{"_id": "ultrasound$$$f9ece966-5d13-4881-8761-a7e58a5198a2", "text": "While the ultrasound machine is based on the assumptions that (1) sound travels in a straight line, (2) all echoes are parallel to the transducer axis, and (3) sound waves travel at 1540 m/s in soft tissue, the ultrasound echoes may be reflected repeatedly between two highly reflective surfaces that are parallel to the primary ultrasound beam. This causes reflections that oscillate between the tissue and the transducer. The artifacts appear on the image as multiple stairways that are equally spaced apart from one another and tend to increase with increasing tissue depth."}
{"_id": "ultrasound$$$dcb36d76-cd1b-4bf5-ada0-35b02c45ee00", "text": "Figure 2-15 shows an image with multiple reflections, indicated by arrows at the top. The first bright line at the top close to the transducer is the only real line image. The other bright images below the actual reflector are artifacts. Another way reverberation artifacts can occur is when the transducer behaves as another reflecting surface such that the returning echoes are rereflected back into the tissue-reflecting structure, resulting in the formation of an identical artifact located at twice the distance from the transducer."}
{"_id": "ultrasound$$$ebda50ab-c188-4a6b-9587-1ce34803f63f", "text": "Because of attenuation, each image formed due to subsequent echoes is weaker than the first, as shown in Figure 2-15. The artifact can be prevented by moving the transducer probe at various angles to see an area covered by the artifact."}
{"_id": "ultrasound$$$f4f08bee-1006-479e-8555-5bf233191066", "text": "There are various possible causes of comet tail artifacts. These are"}
{"_id": "ultrasound$$$62489a39-bb87-4cf0-b21e-1fcbd1ba1f21", "text": "The artifact typically appears as one or multiple solid bright \u201ctails\u201d parallel to the axis of the primary sound beam, as shown in Figure 2-16. The pattern may differ depending on the size, shape, and composition of the reflecting tissue structure and the scan orientation and distance from the transducer."}
{"_id": "ultrasound$$$810990c2-3e79-4255-9e23-c117c5babc64", "text": "This artifact helps diagnose or rule out pneumothorax. If the pneumothorax is present, the air within the pleural space hinders the propagation of ultrasound waves, thereby preventing the formation of comet tail artifacts."}
{"_id": "ultrasound$$$180e878e-3c2e-4353-a7d5-632009269397", "text": "The major problem is that the tails cause significant attenuation such that the beam becomes significantly weak and cannot reach deeper regions of the tissue. These tails prevent the scan from imaging the underside of the reflecting structure. The artifact can be prevented by performing multiple scans at different angles to view the area obscured by the tail."}
{"_id": "ultrasound$$$9266761e-8da4-4991-8395-e4c542105887", "text": "One of the other assumptions of ultrasound machine operation is that the speed of sound in soft tissue is exactly 1540 m/s. However, sometimes the waves may propagate through a medium at a speed other than that of a soft tissue. This produces the correct number of reflectors, which appear at incorrect depths. For speeds greater than 1540 m/s, the depths are underestimated due to the short transmission-reception time of the beam from the transducer to the reflector and back to the transducer. When the sound travels at a speed slower than 1540 m/s, the distances of the reflectors are overestimated."}
{"_id": "ultrasound$$$2603bcd9-574e-4f3e-8449-98836bf0106f", "text": "These artifacts can be reduced by changing the beam\u2019s angle, which may help minimize the difference in propagating speed. Speed error artifacts cannot be prevented entirely. It should be remembered that the artifact causes incorrect placement of the reflectors on the image display."}
{"_id": "ultrasound$$$10db5979-540d-4d0d-a4b0-f64ea9538d14", "text": "Care must be taken to identify incorrect placements to avoid misinterpreting the image. This is often achieved by taking images from different angles. If the placement of the reflectors cannot be duplicated at different angles, then the image is an artifact. These speed errors can make the image appear \u201csplit\u201d or \u201ccut.\u201d The speed error degrades the quality of an image that relies on resolution, such as the differentiation of lesions and cysts and guided biopsy."}
{"_id": "ultrasound$$$b1165f37-bdc2-4867-a9cf-9e7003b833ea", "text": "Two assumptions of the ultrasound machine are that echoes come from the main axis of the beam and that sound travels in a straight line. However, very small structures between the beamlines degrade the image detail and produce misleading echoes. The artifact can be prevented by having a higher spatial resolution or line density. Low line density per frame produces poor detail in images. Another cause is excess gain, which tends to create or obscure information and reduce lateral resolution."}
{"_id": "ultrasound$$$ca5534ab-eb82-4790-8564-aa1c94ecadf9", "text": "The resolution can be corrected by choosing the proper gain or focal zone setting to reduce erroneous echo contrast. An appropriate setting reduces the grainy pattern."}
{"_id": "ultrasound$$$3e424c93-67fe-44e5-9115-c3e1fdc4531a", "text": "Near field clutter is an artifact that arises from multiple noise sources. Any acoustic noise near the transducer may cause high-amplitude oscillations of the piezoelectric crystals in the transducer. It involves the near field and may hinder the identification of structures that are close to the transducer. These oscillations cause the artifacts to appear and disappear. In general, artifacts change their appearance and appear or disappear depending on the view."}
{"_id": "ultrasound$$$f5648420-5673-443c-b55b-f8547b795937", "text": "The artifact occurs due to acoustic noise near the transducer, resulting from high-amplitude oscillations of the piezoelectric elements. The appearance of additional echoes from high-amplitude reflections from the transducer in the near field can overshadow the weaker echoes from true anatomic structures. Nevertheless, when viewed from multiple angles, the real tissue structures will remain constant, while the artifacts will appear and disappear as the scan angle changes."}
{"_id": "ultrasound$$$288b3420-1f0c-4e7e-a4bf-9f139a10d395", "text": "This artifact is caused by small gas bubbles, which produce reflections after the transducer receives the initial reflection. The transducer sees the echoes as though they are coming from structures in the deeper part of the tissue. The pocket of fluid and air continuously resonates, reflecting ultrasound and creating a hyperechoic region. This process commonly occurs in regions with air bubbles and water."}
{"_id": "ultrasound$$$67242a67-007a-42ea-87d3-da43d11dfd10", "text": "The artifact generally appears as very bright and continuous parallel bands extending to the image\u2019s bottom. Its brightness makes it hard to view the region beneath it. The effect can be reduced by moving the scanning beam at different angles."}
{"_id": "ultrasound$$$3e64d55b-28dc-41c4-938a-8bda9c54c266", "text": "This artifact is the opposite of the shadowing effect due to low attenuation. It is common in fluid-filled structures such as the gallbladder, the urinary bladder, or cysts due to excessive brightness. The primary causes are improper ultrasound settings and scanning techniques."}
{"_id": "ultrasound$$$b3c9f9b5-5b33-46ff-9e6d-b6bc92822ea2", "text": "Focal enhancement is formed due to attenuation effects, improper ultrasound settings, and improper brightness, which cause the sound waves to weaken as they propagate in the medium. This is because the amplitude decreases."}
{"_id": "ultrasound$$$ae55a0c5-c532-4b49-9445-493555303f38", "text": "The change in the propagation speed of ultrasound due to differences in impedance causes the transmitted beam to change its direction after passing through the boundary. When the beam moves from one medium to another with a higher (or lower) impedance, the transmitted beam is refracted toward (or away from) the normal at the point of incidence."}
{"_id": "ultrasound$$$2544cbbc-a61c-43b1-8158-2ffcd859ae80", "text": "This phenomenon occurs when a beam hits the interface obliquely, creating separate beams with different propagating speeds, contrary to the assumption that sound travels in a straight path. This can create a duplication of the anatomic features. For example, refraction may cause a single feature to appear as a double feature."}
{"_id": "ultrasound$$$3664798a-6d80-425d-90b5-7bb66f04f763", "text": "A propagating artifact appears when the beam dimension is far greater than the reflector size. Another possible cause is improper elevation resolution. The artifact \u201ccreates\u201d debris that appears in cyst images, which can lead to false diagnoses. This is because the image plane is neither extremely thin nor uniform, as assumed. Using tissue harmonic imaging and thinner transducer arrays would reduce the problem."}
{"_id": "ultrasound$$$ad3c8a13-f0ef-4424-b20b-216b46bca33a", "text": "Transducers are available in various shapes and sizes depending on users\u2019 needs. As discussed earlier, a transducer consists of piezoelectric crystals\u2014not one crystal but an array of multiple crystal elements. The various arrays and transducers are discussed below, and their schematics are shown in Figure 2-17."}
{"_id": "ultrasound$$$f6cae4ba-1724-4179-b8f3-3759c91a2dee", "text": "Modern linear ultrasound transducers contain 256 to 512 elements. Their advantage is high sensitivity when directed perpendicular to the surface under examination. However, the beam cannot be steered, which limits the field of view."}
{"_id": "ultrasound$$$3479c7dd-c2c8-4fc7-80c8-84d7848336ad", "text": "The arrays are similar to those in the linear array but are curved, which gives them the advantage of scanning a wider field of view than linear arrays."}
{"_id": "ultrasound$$$5f3d9690-d9fc-4b2b-a163-ab7352dcde6e", "text": "Phased arrays have much smaller elements than those in a linear array. Typically, they contain 128 elements to transmit and receive each data line. Linear phased arrays are typically used for viewing restricted acoustic windows."}
{"_id": "ultrasound$$$c848757d-a556-4db8-8445-60d48e20fb58", "text": "Ultrasound images are generated when the transducer transforms the reflected wave or echo from the mechanical energy of vibration into an electrical signal that is converted into an image on the display. The image can be displayed in any of the following three modes: (1) amplitude (A) mode, (2) brightness (B) mode, or (3) motion (M) mode. These are discussed in detail in the sections below."}
{"_id": "ultrasound$$$73f9eee2-d67c-4ef4-8f49-3fadfa06499e", "text": "The A-mode is the first form of image display. The depth (reflector-time relationship) is represented on the horizontal axis, and amplitude is displayed on the vertical axis. The A-mode measures the reflectivity at different depths under the transducer. It is commonly used for examining the eyes, the liver, and the brain. Low frequencies of 2\u20135 MHz are used for abdominal, cardiac, and brain scanning. Organs such as the eyes and peripheral blood vessels use a 5\u201315 MHz frequency."}
{"_id": "ultrasound$$$8073b444-59b6-4428-9550-ef2281091677", "text": "In the B-mode, the echoes are represented by bright dots. A shade of gray is assigned to each echo. The brightness of the dots indicates the strength of the echoes. The position of a dot on the screen represents the reflector distance and is determined by the transducer-reflector time relationship. Many diagnoses are made in the B-mode (in black and white) with a relatively simple probe and protocol. It finds use in the study of both stationary and moving structures. The B-mode is an electronic conversion of the A-mode and A-line information into brightness-modulated dots on the display screen, as illustrated in Figure 2-18."}
{"_id": "ultrasound$$$10e60eb9-e3f7-44c5-900a-a8b33e64cc3a", "text": "The B-mode display can be used for the M-mode and 2D grayscale imaging. Modern B-mode ultrasound uses both the fundamental and the second harmonic frequencies. Harmonic imaging is most useful in patients with thick and complicated body wall structures. Figure 2-19 shows anatomical structures in the B-mode."}
{"_id": "ultrasound$$$0b113810-32c1-4c9c-9916-922056c7b34c", "text": "The B-mode is also used for early intima-media thickness analysis of the carotid arteries (located in the neck) to determine the potential for lethal cardiac events. Abnormal thickening of the arterial walls of the carotid arteries is an early indicator of vascular disease throughout the body. The thicker the arterial wall, the greater the risk of heart attack or stroke."}
{"_id": "ultrasound$$$064bc4e5-84f7-4fd9-94d8-2232a5daf1d0", "text": "In the M-mode, the motion of an object points along the transducer axis and is revealed by a bright trace moving up and down across the image. This display is commonly used to evaluate the morphology, movement, and velocity of cardiac valves and walls."}
{"_id": "ultrasound$$$30945be5-7e9f-422c-a5a3-de482ea1a956", "text": "Imaging the pattern of moving cardiac structures over time constitutes M-mode echocardiography, as Figure 2-20 shows."}
{"_id": "ultrasound$$$362d7398-42f5-449e-b00a-4c0d75a8e077", "text": "Doppler imaging is based on the Doppler effect, which shows the relationship between velocity and frequency shift. This imaging system is mainly used to measure blood flow velocity to determine any narrowing of the arteries and assess the risk of stroke occurrence."}
{"_id": "ultrasound$$$55fd43cd-276d-493d-a15c-91302ae9c8f7", "text": "In the sonographic application of the Doppler effect, a typical moving source would be flowing blood, and a typical receiver would be a stationary transducer. When the source is moving away, the detected frequency is lower. Conversely, a source moving closer to the receiver would have a higher detected frequency."}
{"_id": "ultrasound$$$0d3dcee4-dea9-44e8-b849-a498a15f6f52", "text": "For a stationary source (transducer) and a receiver (target) moving with velocity (v) at an angle (\u03b8) relative to the direction of the incident wave of frequency (fs) from the transducer, the Doppler frequency is given by"}
{"_id": "ultrasound$$$6c0ed5c0-28c1-46b3-875a-fad1aee8cd80", "text": "where c is the speed of sound in the tissue, which is 1540 m/s."}
{"_id": "ultrasound$$$0a003347-99e4-4348-8313-3006fad1bfa4", "text": "The transducer transmits and receives sound waves in the form of sinusoidal signal waves. The magnitude of the Doppler shift is related to the velocity of the blood cells or moving tissue, and the polarity of the shift reflects the direction of blood flow. The blood flowing toward the transducer is positive, and the blood flowing away from the transducer is negative."}
{"_id": "ultrasound$$$6d10fb6c-9939-4ab2-a3e2-27f26ba93666", "text": "The Doppler shift (\u0394f) is directly proportional to the velocity (v) of the blood cells, the transducer frequency (fs), and the cosine of the angle of incidence (\u03b8) and is inversely proportional to the velocity of sound in tissue (c = 1540 m/s). In cardiac applications, the angle of incidence in the Doppler equation is assumed to be 0 or 180 degrees."}
{"_id": "ultrasound$$$5773a07e-047e-4b1a-b1c2-d42d868a174c", "text": "Three modalities are currently used in Doppler echocardiography, and these are pulsed wave (PW) Doppler, continuous wave (CW) Doppler, and color flow (CF) Doppler imaging. Color flow imaging evaluates the Doppler flow information for its direction toward or away from the transducer based on the color display. A commonly used acronym for remembering the color and direction is BART\u2014blue away, red toward. The PW Doppler does not continuously transmit and receive the ultrasound pulse. Multiple crystals in the transducer are excited in a quick burst, producing ultrasound waves. This transmission burst is then followed by a \u201clistening\u201d period during which the crystals detect the reflected signals. Signals from more superficial structures are received sooner than those from deeper structures with more extended \u201clistening\u201d periods. This feature allows signals only from specific depths to be processed, thereby controlling sample size and range resolution. Therefore, two vessels located above each other can be evaluated separately, and vessels can also be followed as their courses change. The PW Doppler wave is site-specific and can only measure low-flow velocities\u2014it cannot correctly measure high velocities (above \u2013m/s). The CW Doppler uses two piezoelectric crystals, one to emit ultrasound continuously and the other to receive the reflected waves continuously. This results in a fixed sample size and no range resolution or ability to place the sample volume at a specific depth. It also cannot create anatomic images. It is used for precise settings such as very high peak systolic velocities.1 The CW Doppler measures very high blood flow velocities, and the color flow CF Doppler is a PW Doppler with multiple gates that allow it to measure the flow velocity through the heart on the two-dimensional echocardiographic image. Physicians often use Doppler imaging to detect blockages to the blood flow (due to clots), constriction of vessels or tumors, and congenital vascular malformations. Figure 2-21 shows an ultrasound image of the right common carotid artery and the corresponding Doppler waveform."}
{"_id": "ultrasound$$$23f187ae-5ac9-4a60-8f06-0fdaf128cca5", "text": "Duplex ultrasonography combines physiologic information based on Doppler shift frequencies with anatomic information from real-time, high-resolution B-mode imaging."}
{"_id": "ultrasound$$$0e394c39-0d2b-4b29-abef-8056d4cb667d", "text": "Understanding blood flow dynamics is important in the study of vascular disease development, such as atherosclerosis, thrombosis, or aneurysms. The circulation system transports nutrients and waste around the body (delivering oxygen and nutrients to the cells and removing cellular wastes and carbon dioxide). Its other function is to maintain a constant temperature and potential or power of hydrogen (pH) in all organs of the body. The circulation system comprises the heart (the pump that drives the blood to all body tissues), blood vessels (delivery routes), and blood (the medium that transports the food and the waste materials). The blood flows continuously through two separate loops that originate and terminate at the heart: the pulmonary circulation and systemic circulation loops, as shown in Figure 2-22. Pulmonary circulation carries blood between the heart and lungs, and systemic circulation carries blood between the heart and the body\u2019s organs and tissues. At any time, about 84% of the entire blood volume is in systemic circulation, 7% is in the heart, and 9% is in the pulmonary vessels."}
{"_id": "ultrasound$$$51405623-d214-4853-b606-938a4cb827bb", "text": "Under normal conditions, the average resting heart rate of an adult between the ages of 18 and 80 is about 75 beats/min, with a stroke volume of 70 mL/beat (cardiac output of L/min). For vigorous-intensity physical activity, the heart rate can increase to as high as 200 beats/min, with a stroke volume of up to 150 mL/beat (cardiac output of about 25 L/min).[1] The arteries respond to varying pressure conditions by dilating or shrinking to accommodate the hemodynamic demands."}
{"_id": "ultrasound$$$d5568f5d-f20f-4b4a-8909-4d37b92f15e5", "text": "The presence of a pressure gradient between the aorta and the veins ensures the blood keeps moving to the peripherals. In mathematical form, the volume per unit time (Q) can be expressed using Dacy\u2019s law: Q = \u0394P/R, where \u0394P is the pressure differential and R is the resistance. Figure 2-23 shows the systemic blood pressure throughout different paths of the body."}
{"_id": "ultrasound$$$10a4dfdd-37b2-41c3-aa17-e7916d895767", "text": "As the heart pumps the blood, the pressure varies between systolic pressure (pressure peak after ventricular systole) and diastolic pressure (pressure drop during ventricular diastole). In the aorta, the systolic average pressure is about 120 mm of Hg, while the diastolic average pressure is about 80 mm of Hg."}
{"_id": "ultrasound$$$d1131fa2-7f21-4a8e-9b7c-e1f99a7c26a9", "text": "The velocity of the flow is mainly determined by three critical variables: radius (r), vessel length (\u03bb), and viscosity (\u03b7), which are related to one another by Poiseuille\u2019s equation:"}
{"_id": "ultrasound$$$2a516815-4417-42e8-9523-0256cccb3fb4", "text": "where \u0394P is the pressure differential and resistance is given by"}
{"_id": "ultrasound$$$b34dbb50-c5fb-403b-8248-86303d6eec8e", "text": "This shows that since the radius changes with vasoconstriction and vasodilation, the effect will be a dramatic change in the resistance and flow of blood."}
{"_id": "ultrasound$$$9e6e0d61-2435-4834-ac88-e507ef8ab58a", "text": "The blood flow through straight, long, and smooth vessels is almost linear, with each layer of blood remaining the same distance from the walls of the vessels. These different layers flow at different velocities. Speed is dependent on both the axial distance and pressure. At high pressure, the velocity is high, whereas at low pressure, the velocity is low. This leads to a decrease in pressure and velocity from the heart to peripheral circulation."}
{"_id": "ultrasound$$$77aeca56-7f5b-4342-9d53-744e268d9004", "text": "Due to the difference in systolic and diastolic pressures, pulse pressure is generated during systole. A pulsatile blood flow is created down the pressure gradient into systemic circulation. The pulse pressure is ~ 40 mm of Hg, the difference between systolic and diastolic pressures."}
{"_id": "ultrasound$$$ce337dc4-0ce0-4e1c-a177-337ef22b27e3", "text": "In a laminar flow, the motion of the fluid is very orderly, with all particles moving in straight lines parallel to the walls of the tube, as shown on the left of Figure 2-24. The velocity profile across the tube is parabolic, with the fluid\u2019s highest velocity at the tube\u2019s center, as shown in Figure 2-25. The parabolic profile arises because the fluid molecules touching the walls experience more resistance than those at the center."}
{"_id": "ultrasound$$$2a03ea6b-4511-428a-ba83-a3f23b8f2229", "text": "When the velocity of the blood becomes too high as it passes through a constricted vessel or a rough surface, the flow may become irregular, resulting in random fluctuations in position and time, leading to turbulent flow."}
{"_id": "ultrasound$$$9c30835e-8403-4c0f-bf3d-eaabd9de8074", "text": "The tendency for turbulent flow is measured using the Reynolds number, which depends on the velocity of the flow, the diameter of the vessel, and the density of the blood:"}
{"_id": "ultrasound$$$a91336d1-9659-4b2a-bd81-b43c69d5f781", "text": "where \u03bd is the average blood flow velocity (in cm/s), d is the vessel diameter (in cm), \u03c1 is density, and \u03b7 is the viscosity of the blood. In these units, turbulence occurs when Re > 200, resulting in the formation of eddies. Turbulence can occur in regions of stenosis with increased flow velocity. This type of flow is not common in healthy vessels."}
{"_id": "ultrasound$$$8ba496d8-c40f-452b-af5b-9bf1cfa3d324", "text": "where PSV and EDV represent the peak systolic velocity and end-diastolic velocity, respectively."}
{"_id": "ultrasound$$$56ff5788-0ced-4279-95e6-4a01b431a134", "text": "The RI index is used as an indicator for detecting and managing renal artery stenosis, evaluating risk in chronic kidney disease, compiling differential diagnoses in acute and chronic obstructive renal disease, and predicting renal and global outcomes in critically ill patients."}
{"_id": "ultrasound$$$9e711dda-673c-4c04-a36a-04b38b0ad986", "text": "Recent studies have shown that an increased RI reflects changes in intrarenal perfusion and systemic hemodynamics and the presence of subclinical atherosclerosis and, therefore, may provide valuable prognostic information for patients with primary hypertension.[2]"}
{"_id": "ultrasound$$$4742c532-7521-41a0-8079-4ddd21917bf4", "text": "Ultrasound has a wide range of medical applications. These include its use in obstetrics (monitoring the progress of pregnancy), oncology (monitoring the growth of tumors), cardiology (visualizing heart function and physiology), and biopsy (guiding needles in various procedures) and as a rehabilitation modality. For example, today, an estimated 60\u201370% of pregnant women in the United States undergo ultrasound examinations during pregnancy. An estimated 250 million fetal ultrasound examinations are performed annually in the United States.[1] The examination aims to assess fetal abnormalities, confirm the site of pregnancy within the uterus, and determine gestational age."}
{"_id": "ultrasound$$$c6c42a7e-dcb5-485d-81e6-f9bda2f046aa", "text": "Due to the increasing use of ultrasound in health care, most medical schools are transforming curricula to include medical ultrasound applications. In addition, most medical professions require successful completion of a Sonography Principles and Instrumentation (SPI) examination and some specialty examinations administered by the American Registry for Diagnostic Medical Sonography (ARDMS). The SPI examination requires a sound knowledge of the physical principles of ultrasound and imaging, which includes an understanding of the physics of ultrasound and imaging techniques. This requirement is appalling to most clinicians with no physics background. On the other hand, depending on the individual\u2019s interest, a specialty examination will be given in one or more of the following areas: abdomen, breast, echocardiography, obstetrics, gynecology, pediatric, vascular technology, or musculoskeletal ultrasound. Most hospitals recognize ARDMS credentials as requirements for clinical sonographers and physicians."}
{"_id": "ultrasound$$$724379cb-6bd6-4289-8a22-bd1e3f993cde", "text": "Ultrasound images in medical imaging are generated from sound waves reflected from different tissues and organs and converted into electrical signals, which a computer processes to create an image displayed on a screen. This technology helps health care professionals visualize internal structures and diagnose medical conditions. To make it easier to understand the operation of a medical ultrasound machine, we will first discuss some basic physics principles."}
{"_id": "ultrasound$$$ff14df7c-f49d-4cfa-ad03-37f14f428a6b", "text": "A mechanical vibration is a back-and-forth motion. When vibrations affect the media around them, waves are generated. These waves transport energy from one point to another. If a single vibratory disturbance moves from one point to the other, it is called a pulse. A back-and-forth motion that occurs repeatedly is called a periodic motion."}
{"_id": "ultrasound$$$06708e13-5f36-4588-ba5c-826e48f9dde8", "text": "A mechanical wave requires a material medium (such as a solid, liquid, or gas) to propagate through; its speed depends on the properties of that medium. Mechanical waves fall into two classes: longitudinal and transverse waves. For a transverse wave, the displacement of the medium is perpendicular to the direction of the motion of the wave. In a longitudinal wave, the displacement of the medium is in the same direction as wave motion. One example of a longitudinal wave is sound. These waves are similar to the motion of a pulse on a slinky, as illustrated in Figure 1-1."}
{"_id": "ultrasound$$$b613c9ab-3917-44dd-8e75-231d25383637", "text": "A sound wave comprises alternating regions of low and high pressures. The waveform is a sinusoidal wave function in which the crests and troughs represent high- and low-pressure regions, respectively, as shown in Figure 1-2."}
{"_id": "ultrasound$$$41928900-1660-4888-9c70-5f340af2a1a9", "text": "The maximum displacement or height from the horizontal axis, the equilibrium position, is the amplitude (A) of the wave. The distance between two successive points in the same phase is the wavelength (\u03bb). For example, the wavelength is the distance between neighboring peaks, neighboring troughs, or any two points where the wave returns to the same shape, as shown in Figure 1-3."}
{"_id": "ultrasound$$$b60bc043-0901-44f8-9e27-bbedcd62df64", "text": "The time for one complete cycle is the period (T); it is related to the number of oscillations (complete cycles) per unit time, called the frequency (f), as follows: T = 1/f. The unit of frequency is the cycle/second = 1/s or s-1. One cycle per second = 1 hertz (Hz)."}
{"_id": "ultrasound$$$de6c17d2-0769-4a8a-888a-b39342b5d553", "text": "The rate at which the waveform changes position with respect to time is called the velocity (v) of the wave. In mathematical form, v = f \u03bb. The wave velocity depends on the characteristics of the medium in which it travels. The velocity has a unit of meters per second if the frequency (f) is in hertz and the wavelength (\u03bb) is in meters. The speed of sound is fastest in solids, slower in liquids, and slowest in air. Sound does not travel through free space or vacuums due to the lack of a medium."}
{"_id": "ultrasound$$$883ecdb4-dcd4-46b2-9a57-81c750b3a750", "text": "Sound waves are classified into three categories based on their frequency: infrasonic, audible, and ultrasonic waves."}
{"_id": "ultrasound$$$5aa80107-5b98-4240-9895-4504f80b014f", "text": "Infrasonic waves: These are waves with frequencies of less than 20 Hz; they are not audible to the human ear. Various natural and man-made sources produce them, including earthquakes, volcanoes, thunderstorms, and industrial machinery. Animals such as elephants, whales, and alligators also produce these waves to communicate over long distances."}
{"_id": "ultrasound$$$81eccbb1-efb9-4d11-8f65-7ccecae57223", "text": "Audible waves: These are sound waves with frequencies that the human ear can hear. The audible frequencies fall in the range of about 20 Hz to 20 kHz. The audible range of sound can vary between individuals due to various factors. Age is one factor that can affect a person\u2019s ability to hear some frequencies, as the ear\u2019s sensitivity decreases with age. For example, younger people are likely to hear sounds of up to 20 kHz, while older people mostly hear frequencies of far less than 20 kHz. Certain diseases and medical conditions, such as otitis media, otosclerosis, or Meniere\u2019s disease, can also affect a person\u2019s hearing ability. Additionally, individuals with hearing impairments or disabilities may have a reduced hearing range due to damage to the ear or nerve pathways involved in hearing."}
{"_id": "ultrasound$$$c4dcef15-ce54-4914-9ca9-234297201f0c", "text": "Ultrasonic waves (also called ultrasound): These are waves with a frequency of more than 20 kHz. Humans cannot hear ultrasound, but bats use these waves for navigation. However, medical professionals use these waves to examine or image the different parts of the human body, a practice also known as sonography. Medical ultrasound imaging typically uses the to 20 MHz frequency range."}
{"_id": "ultrasound$$$c7719661-e564-4a35-878b-acf0773a12ad", "text": "The amount of sound energy flux per unit of time is called the sound intensity (I). For a point source generating sound with acoustic power (P), the intensity (I) at distance (r) from the source obeys the inverse square law:"}
{"_id": "ultrasound$$$1df58a7b-8cfc-4918-9045-c2748bffb08b", "text": "The acoustic power of an ultrasound wave is the quantity of energy generated per unit of time. The standard unit of acoustic power is the watt (W), and 1 watt = 1 joule per second. Therefore, the unit of sound intensity is W/m2. The intensity equation shows that sound intensity decreases as the square of the distance from the point source. We all know that sound loudness (ear perception of sound intensity level) decreases as we move away from the source, as illustrated in Figure 1-4."}
{"_id": "ultrasound$$$d1bdb2eb-eb39-4dfe-ba83-ad28757e16b1", "text": "The sound intensity level (also called the sound acoustic level) is commonly measured relative to the standard threshold of hearing intensity (Io) in decibels. A decibel is a dimensionless quantity (no units) represented as dB, which is based on the logarithmic scale. In mathematical form, the sound intensity level (\u00df) is expressed as"}
{"_id": "ultrasound$$$25adb5cb-cf9c-4894-b816-311292508c5b", "text": "where Io = 10-12 W/m2, which is the faintest audible sound intensity."}
{"_id": "ultrasound$$$bc391069-f9e7-415f-a981-cb6979dab963", "text": "Clinicians examine body tissue structures using ultrasound waves with 2 to 20 MHz frequencies. Inside the tissue structures, the waves propagate through the medium by vibrating molecules of the medium. In soft tissues, the propagation velocity is relatively constant at 1540 m/s. This velocity value is used by ultrasound machines for all human tissue. Ultrasound waves propagating through tissue undergo reflection, refraction, attenuation, scattering, and diffraction."}
{"_id": "ultrasound$$$507c54b7-ef71-413e-8958-ce867bb566d4", "text": "Like any wave, ultrasound waves are reflected at tissue boundaries and interfaces. The transducer detects these reflected waves, and piezoelectric signals are generated and processed into an image form via a computerized processing unit. These signals form the basis of all ultrasound imaging. The number of reflected waves detected by the transducer depends on the angle of incidence at the band boundary and the difference in acoustic impedance between the two tissues traversed by the beam. More details about the acoustic impedance will be discussed later. However, it represents the resistance of a tissue to the passage of ultrasound. Typically, a propagating ultrasound wave is split into two components, as Figure 1-5 illustrates."}
{"_id": "ultrasound$$$30ab11aa-78ca-47bd-85f2-45b1f8ec6bb1", "text": "If the wave traverses from medium 1 (with acoustic impedance Z1) to medium 2 (with acoustic impedance Z2), the reflection coefficient is"}
{"_id": "ultrasound$$$ca26653d-2041-42e6-b877-bfdea1dd4355", "text": "where \u03b8i is the angle of incidence, \u03b8r is the reflected angle, and \u03b8t is the angle of transmission. Pr and Pi represent the reflection and incident probability amplitudes, respectively."}
{"_id": "ultrasound$$$0392caf1-c857-45ac-8e02-b4474259e8e5", "text": "Reflections can also be classified into two categories: specular and diffuse, as illustrated in Figure 1-6."}
{"_id": "ultrasound$$$f13ec0d4-918a-44d2-b9f3-597ce06a9387", "text": "The ultrasound beam that succeeds in penetrating the boundary layers or interface is called the transmitted wave. The transmission coefficient is mathematically expressed in the following form (refer to Figures 1-5 and 1-7):[2]"}
{"_id": "ultrasound$$$d286f5ba-57f3-498e-a7f6-78df26c4f4f1", "text": "The ratio of the speed of the transmitted wave (v2) to that of the incident wave (v1) is related to the ratio of the sines of the angles of transmission and incidence, a relationship called Snell\u2019s law:"}
{"_id": "ultrasound$$$37d19691-6b2d-4a46-a792-cf49522e0d3e", "text": "When the waves are reflected from a perfectly flat surface or boundary, the reflected waves tend to be uniformly parallel to each other. In contrast, they tend to be diffuse for rough surfaces. This phenomenon is commonly observed as a \u201cmirage\u201d when driving on a hot summer day, and the road appears to have a wet surface that disappears as one gets closer. This leads to two different kinds of reflections, specular and diffuse, which are illustrated in Figure 1-6."}
{"_id": "ultrasound$$$36a37054-51f5-43fb-8012-6d2db5dfd122", "text": "The transducer picks up the reflected waves and converts the echoes into images. The strength of the echoes depends on the acoustic impedance between the two tissues through which the waves pass. Typically, boundary reflections occur on blood vessel walls and organ boundaries."}
{"_id": "ultrasound$$$c8108331-7bdd-41ac-b939-e7c33b58961a", "text": "When an ultrasound beam strikes a tissue boundary obliquely, the transmitted component of the beam undergoes a change in direction. This change is due to the differences in the velocities of the incident and transmitted beams. This bending process, called refraction, is illustrated in Figure 1-8 and is often related to the formation of artifacts during ultrasound image acquisition."}
{"_id": "ultrasound$$$555c47cc-52c6-40bf-9753-e9bacd216566", "text": "In ultrasound imaging, refraction can result in the formation of artifacts such as double image artifacts, as shown in Figure 1-9. This artifact is caused by the differential refraction of the ultrasound beam while passing through the relatively different echogenic tissues, such as muscle and fat tissues, and the difference in velocities in those tissues."}
{"_id": "ultrasound$$$0e7d06d6-8940-4d41-96cd-bf0224c73b6d", "text": "Inside the human body, scattering is mostly a result of small changes in the density, compressibility, and absorption properties of the tissues. Ultrasound scanners detect these scattered waves to show the backscattered signal in the form of images. Scattered waves are primarily caused by red blood cells, or erythrocytes, due to their relatively small diameter of 6\u20138 \u00b5m, compared to the commonly used ultrasound wavelength of about mm. For ultrasound frequencies below 20 MHz, the backscattering signal from blood is about 10 to 27 dB lower than from the surrounding tissue.[3] This difference makes it possible to image the blood flow inside the tissue."}
{"_id": "ultrasound$$$220a6dc7-80dc-40f1-bcab-e3b6ce89724d", "text": "As the ultrasound beam traverses the tissue structures, it also loses energy through absorption. The lost energy varies depending on the tissue\u2019s characteristics and the ultrasound wave\u2019s frequency. For example, bones absorb more ultrasound energy than soft tissue does. Absorption of ultrasound in tissue is frequency dependent\u2014it increases with increasing frequency."}
{"_id": "ultrasound$$$e48d8b65-e273-4ca6-8293-358568497be2", "text": "As the ultrasound moves through tissues, some of the ultrasound energy is lost due to absorption through heat, reflection, refraction, and scattering. The beam weakens with increased depth into the tissue, increasing acoustic impedance mismatch. Another factor is the presence of air bubbles inside the tissue, which tend to form virtually impenetrable barriers to ultrasound. Attenuation becomes higher not only with increasing distance from the transducer but also because of the heterogeneity caused by acoustic impedance mismatch as well as the higher frequency of the transducer, as illustrated in Figure 1-10. This is because air has a higher resistance to ultrasound propagation than fluids."}
{"_id": "ultrasound$$$3551265a-ac1d-4650-9080-3f5abe8b263d", "text": "The intensity (Ix) of an ultrasound beam at tissue depth x can be estimated using Beer\u2019s law:"}
{"_id": "ultrasound$$$0c1c38e1-0b08-434e-ad2d-139905d2b955", "text": "where Io is the incident intensity at the tissue surface and \u03bc is the intensity attenuation coefficient. Of this attenuation, absorption contributes about 60\u201380%.[4]"}
{"_id": "ultrasound$$$5ddc7f54-7db6-49ee-8dad-28b20ea4c22e", "text": "Attenuation increases with increasing gas and fat. The higher the tissue density (or impedance), the lower the reflection. For example, blood has an attenuation coefficient value closer to dB/MHz.cm, while the typical value for bone is around dB/MHz.cm.2"}
{"_id": "ultrasound$$$8500b2fc-db8e-48ed-b345-fc0ec1eba0c0", "text": "Attenuation generally increases linearly with increasing frequency among different body tissues. Fluid-filled structures have much lower attenuation than solid structures. Hence the transmitted pulse from a fluid-filled structure is usually more substantial than that from passing through an equivalent amount of solid tissue."}
{"_id": "ultrasound$$$99d34e43-ff9b-4b27-8e61-1f7df5832e24", "text": "The ultrasound beam spreads out with distance from the transducer as it passes through the tissue, causing diffraction, as shown in Figure 1-11. This results in the reduction of beam intensity."}
{"_id": "ultrasound$$$0877934c-afb8-4fd9-a5e9-bfcdbb2ed4a6", "text": "This diffraction pattern is highly dependent on the shape and size of the transducer relative to the wavelength of ultrasound. This phenomenon causes a decrease in the intensity of the ultrasound beam. To achieve a parallel beam, the diameter of the crystal face is designed to be approximately 10 to 20 times the wavelength of ultrasound."}
{"_id": "ultrasound$$$2a3def90-3d80-4d18-8525-19fea8981d9a", "text": "Acoustic impedance (Z) is the resistance of a tissue to the passage of ultrasound. It depends on the density of the tissue (\u03c1) and the velocity of propagation (v) of the ultrasound through the tissue: Z = \u03c1v. If the density is in kg/m3 and the velocity is in m/s, then the specific acoustic impedance is expressed in the unit of rayl (Ry), which is equivalent to 1 kg/(m2s). A typical value of acoustic impedance is rayls for air, rayls for the liver and blood, and around 5 rayls for the bone.[5]"}
{"_id": "ultrasound$$$8225d787-2b1f-4d5b-8fd2-c149122583ef", "text": "The greater the difference between two tissues (media), the more the ultrasound is reflected and the lesser the transmission through the tissue. For example, more ultrasound beams will be reflected at soft tissue / bone and soft tissue / air interfaces than at soft tissue / blood interfaces. The difference in acoustic impedance is called acoustic impedance mismatch. A greater acoustic mismatch results in a greater reflection and a lower transmission.[6]"}