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 ]


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 ]


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 ]


Absolute contraindications to cardiac stress test include:


Indications for termination:
A cardiac stress test should be terminated before completion under the following circumstances: [ 33 ] [ 34 ]


Absolute indications for termination include:


Relative indications for termination include:


Side effects from cardiac stress testing may include [ citation needed ]


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 ]


The choice of pharmacologic stress agents used in the test depends on factors such as potential drug interactions with other treatments and concomitant diseases.


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 ]


Commonly used agents include:


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 ]


Aminophylline  may be used to attenuate severe and/or persistent adverse reactions to adenosine and regadenoson. [ 39 ]


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 ]


A  cyclotron  is a type of  particle accelerator  invented by  Ernest Lawrence  in 1929–1930 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 ]


The cyclotron was the first "cyclical" accelerator. [ 8 ]  The primary accelerators before the development of the cyclotron were  electrostatic accelerators , such as the  Cockcroft–Walton 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 ]


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 ]


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 Szilárd  filed patent applications in Germany for the  linear accelerator , cyclotron, and  betatron . [ 12 ]  In these applications, Szilárd 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 Widerøe  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 ]


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 cm), and accelerated protons to an energy up to 80  keV . [ 21 ] [ 22 ]


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 in (69 cm) 4.8 MeV machine (1932), a 37 in (94 cm) 8 MeV machine (1937), and a 60 in (152 cm) 16 MeV 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 ]


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  [ ru ] . This instrument was first proposed in 1932 by  George Gamow  and  Lev Mysovskii  [ 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 ]


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 ]


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 ]


In France,  Frédéric Joliot-Curie  constructed a large 7 MeV cyclotron at the  Collège 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 ]


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 Segrè  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 ]


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 ]


Lawrence's team built one of the first synchrocyclotrons in 1946. This 184 in (4.7 m) machine eventually achieved a maximum beam energy of 350 MeV for protons. However, synchrocyclotrons suffer from low beam intensities (< 1 μA), 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 ]


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 MeV 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 ]


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 :


F

 =
 q
 [

 E

 +
 (

 v

 ×

 B

 )
 ]

 {\displaystyle \mathbf {F} =q[\mathbf {E} +(\mathbf {v} \times \mathbf {B} )]}


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 ]


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 ] : 21   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 ]


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 ]


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:


f
 =

 q
 B

 2
 π
 m

 {\displaystyle f={\frac {qB}{2\pi m}}}


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 ]


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 ]


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 :


f
 =

 v

 2
 π
 r

 {\displaystyle f={\frac {v}{2\pi r}}}


with the cyclotron frequency equation to yield:


v
 =

 q
 B
 r

 m

 {\displaystyle v={\frac {qBr}{m}}}


The kinetic energy for particles with speed  v  is therefore given by:


E
 =

 1
 2

 m

 v

 2

 =

 q

 2

 B

 2

 r

 2

 2
 m

 {\displaystyle E={\frac {1}{2}}mv^{2}={\frac {q^{2}B^{2}r^{2}}{2m}}}


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 ]


In the nonrelativistic approximation, the maximum kinetic energy per atomic mass for a given cyclotron is given by:


T
 A

 =

 (
 e
 B

 r

 max

 )

 2

 2

 m

 a

 (

 Q
 A

 )

 2

 =
 K

 (

 Q
 A

 )

 2

 {\displaystyle {\frac {T}{A}}={\frac {(eBr_{\max })^{2}}{2m_{a}}}\left({\frac {Q}{A}}\right)^{2}=K\left({\frac {Q}{A}}\right)^{2}}


where

 e

 {\displaystyle e}

  is the elementary charge,

 B

 {\displaystyle B}

  is the strength of the magnet,

 r

 max

 {\displaystyle r_{\max }}

  is the maximum radius of the beam,

 m

 a

 {\displaystyle m_{a}}

  is an  atomic mass unit ,

 Q

 {\displaystyle Q}

  is the charge of the beam particles, and

 A

 {\displaystyle A}

  is the atomic mass of the beam particles.  The value of  K


K
 =

 (
 e
 B

 r

 max

 )

 2

 2

 m

 a

 {\displaystyle K={\frac {(eBr_{\max })^{2}}{2m_{a}}}}


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 ]


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 ]


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  Δ E , the particle energy after  n  turns will be:

 E
 (
 n
 )
 =
 n
 Δ
 E

 {\displaystyle E(n)=n\Delta E}

Combining this with the non-relativistic equation for the kinetic energy of a particle in a cyclotron gives:

 r
 (
 n
 )
 =

 2
 m
 Δ
 E

 q
 B

 n

 {\displaystyle r(n)={{\sqrt {2m\Delta E}} \over qB}{\sqrt {n}}}

This is the equation of a  Fermat spiral .


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 ]


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 ]


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 ]


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° ( modulo 360°). [ 46 ] : ch.2.1.3   Poor synchronization, i.e. phase difference far from this value, leads to the particle being accelerated slowly or even decelerated (outside of the 0–180° range).


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  § Relativistic 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 ] : ch.2.1.3   Failure of the particle to be injected with phase difference within about ±20° 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 0–180° 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 ] : ch.7


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 ] : 6–9


The relativistic mass can be written as:


m
 =

 m

 0

 1
 −

 (

 v
 c

 )

 2

 =

 m

 0

 1
 −

 β

 2

 =
 γ

 m

 0

 ,

 {\displaystyle m={\frac {m_{0}}{\sqrt {1-\left({\frac {v}{c}}\right)^{2}}}}={\frac {m_{0}}{\sqrt {1-\beta ^{2}}}}=\gamma {m_{0}},}


where:


Substituting this into the equations for cyclotron frequency and angular frequency gives:


f

 =

 q
 B

 2
 π
 γ

 m

 0

 ω

 =

 q
 B

 γ

 m

 0

 {\displaystyle {\begin{aligned}f&={\frac {qB}{2\pi \gamma m_{0}}}\\[6pt]\omega &={\frac {qB}{\gamma m_{0}}}\end{aligned}}}


The  gyroradius  for a particle moving in a static magnetic field is then given by: [ 41 ] : 6–9

 r
 =

 γ
 β

 m

 0

 c

 q
 B

 =

 γ

 m

 0

 v

 q
 B

 =

 m

 0

 q
 B

 v

 −
 2

 −

 c

 −
 2

 {\displaystyle r={\frac {\gamma \beta m_{0}c}{qB}}={\frac {\gamma m_{0}v}{qB}}={\frac {m_{0}}{qB{\sqrt {v^{-2}-c^{-2}}}}}}


Expressing the speed in this equation in terms of frequency and radius

 v
 =
 2
 π
 f
 r

 {\displaystyle v=2\pi fr}

yields the connection between the magnetic field strength, frequency, and radius:

 (

 1

 2
 π
 f

 )

 2

 =

 (

 m

 0

 q
 B

 )

 2

 +

 (

 r
 c

 )

 2

 {\displaystyle \left({\frac {1}{2\pi f}}\right)^{2}=\left({\frac {m_{0}}{qB}}\right)^{2}+\left({\frac {r}{c}}\right)^{2}}


Since

 γ

 {\displaystyle \gamma }

  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 ]


In this type of cyclotron, the accelerating frequency is varied as a function of particle orbit radius such that:


f
 (
 r
 )
 =

 1

 2
 π

 (

 m

 0

 q
 B

 )

 2

 +

 (

 r
 c

 )

 2

 {\displaystyle f(r)={\frac {1}{2\pi {\sqrt {\left({\frac {m_{0}}{qB}}\right)^{2}+\left({\frac {r}{c}}\right)^{2}}}}}}


The decrease in accelerating frequency is tuned to match the increase in gamma for a constant magnetic field. [ 43 ]


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 ]


B
 (
 r
 )
 =

 m

 0

 q

 (

 1

 2
 π
 f

 )

 2

 −

 (

 r
 c

 )

 2

 {\displaystyle B(r)={\frac {m_{0}}{q{\sqrt {\left({\frac {1}{2\pi f}}\right)^{2}-\left({\frac {r}{c}}\right)^{2}}}}}}


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.


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 ]


There are a number of basic types of cyclotron: [ 53 ]


The particles for cyclotron beams are produced in  ion sources  of various types.


To make use of the cyclotron beam, it must be directed to a target. [ 57 ]


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 ]


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 ]


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 ]


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.


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 ]


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 ]


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 ]


An additional limitation of cyclotrons is due to  space charge  effects – 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 ]


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°C or 4.2 K. Some of these cyclotrons are being built for medical therapy. [ 39 ] : 6


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 ]


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 ]


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 ]


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 ]


In the 1984 film  Ghostbusters ,  a miniature cyclotron forms part of the  proton pack  used for catching ghosts. [ 87 ]


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 .


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 ]


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 ]


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 ]


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 ]


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 ]


This article related to  medical imaging  is a  stub . You can help Wikipedia by  expanding it .


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·cm 2 [ 1 ]  – sometimes the  prefixed  units dGy·cm 2 , mGy·cm 2  or cGy·cm 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 (γ) and X-rays. [ 3 ]


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.
Due 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 ∝ d 2 ), while radiation intensity (I) decreases according to the inverse square of distance (I ∝ 1/d 2 ). Consequently, the product of intensity and area, and therefore DAP, is independent of distance from the source.


DICOM  "X-Ray Acquisition Dose Module" metadata within each medical imaging study often includes various DAP and dose length product (DLP) parameters. [ 4 ]


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.

For example, a  5 cm × 5 cm  X-ray field with an entrance dose of 1 mGy will yield a 25 mGy·cm 2  DAP value. When the field is increased to  10 cm × 10 cm  with the same entrance dose, the DAP increases to 100 mGy·cm 2 , which is four times the previous value.


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

 D
 A
 P

 =

 K
 A
 P

 ×
 (
 1
 −
 g
 )

 {\displaystyle \mathrm {DAP} =\mathrm {KAP} \times (1-g)}

 , 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.


Adult  coronary angiography  and  PCI procedures  expose patients to an average DAP in the range of 20 to 106 Gy·cm 2  and 44 to 143 Gy·cm 2  respectively. [ 6 ]


Onia


Electron–positron annihilation  occurs when an  electron  ( e − ) 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 :


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:


As with any two charged objects, electrons and positrons may also interact with each other without annihilating, in general by  elastic scattering .


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  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 .


Since  neutrinos  also have a smaller mass than electrons, it is also possible – but exceedingly unlikely – for the annihilation to produce one or more neutrino– 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.


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.


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.


The heaviest particle pairs yet produced by electron–positron annihilation in  particle accelerators  are  W + – W −  pairs (mass 80.385 GeV/c 2  × 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 ]


The electron–positron 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 .
It is also used for nuclear transition.
Positron annihilation spectroscopy is also used for the study of  crystallographic defects  in metals and semiconductors;
it is considered the only direct probe for vacancy-type defects. [ 4 ]


The reverse reaction, electron–positron creation, is a form of  pair production  governed by  two-photon physics .


A  gamma camera  ( γ-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 .


Scintigraphy  ("scint") is the use of gamma cameras to capture emitted radiation from internal radioisotopes to create two-dimensional [ 1 ]  images.


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.


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 ] : 82   The construction of a gamma camera is sometimes known as a compartmental radiation construction.


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 ]


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 ] : 162


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.


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 ] : 112   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 ] : 166


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.


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 in) 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 ]


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.


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 ] : 128


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.


The best current camera system designs can differentiate two separate point sources of gamma photons located at 6 to 12 mm 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 cm and most of the left ventricle muscle is about 0.8 cm, always moving and much of it beyond 5 cm 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.


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 ] : 243


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 ]


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 ]


Internal dosimetry  is the science and art of internal  ionising radiation  dose assessment due to  radionuclides  incorporated inside the human body. [ 1 ]


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.


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.


The internal radiation dose due to injection, ingestion or inhalation radioactive substances is known as  committed dose .


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 ]


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 ]


There are a few routes of intake (of radionuclide) namely,


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 ]


In-vivo monitoring
Internal 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.


A  whole body counter [ 5 ]  has a low background arrangement with counting systems


HPGe detectors are replacing detectors for measuring the low energy and high energy photons with appropriate electronic systems.
Calibration 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 .


In-vitro monitoring
 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.


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.


The human body can be divided into three systems:


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.


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.


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 ]


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 ]


A  Jaszczak phantom  ( Polish pronunciation:   [ˈjaʂ.t͡ʂak]   ⓘ ) 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 ]


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 ]


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 ]


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.


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 mm, while the rod diameters are 4.8, 6.4, 7.9, 9.5, 11.1 and 12.7 mm. 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 ]


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.


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 ]


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  § Controversy ).


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.


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 ]


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 ]


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 Röntgen  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 ]


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 ]


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 ]


The Health Physics Society (in the United States) has published a documentary series on the origins of the LNT model. [ 16 ]


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 ]


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.


A linear model has long been used in  health physics  to set maximum acceptable radiation exposures.


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 ]


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‐induced 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 ]


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".


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 ]


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:


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.


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.


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.


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


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.


A number of organisations caution against using the Linear no-threshold model to estimate risk from radiation exposure below a certain level:


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.


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.


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.


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 ]


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 ]


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 ]


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 – for it carries a unique historical legacy". [ 41 ]


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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 ]


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 .


As of 2010, 5 billion 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   million units and  $1.1 billion . [ 3 ]


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.


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 ]


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 ]


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.


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 kHz) 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 ]


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 ]


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 ]


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 ]


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.


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.


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.


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.


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.


Tomography  is the imaging by sections or sectioning. The main such methods in medical imaging are:


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.


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 ]


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.


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 ]


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 ]


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.
In 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.
With 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.


Other proposed or developed techniques include:


Some of these techniques [ example needed ]  are still at a research stage and not yet used in clinical routines.


Neuroimaging  has also been used in experimental circumstances to allow people (especially disabled persons) to control outside devices, acting as a  brain computer interface .


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 ]


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 ]


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 ]


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.


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 ]


Medical imaging has become a major tool in clinical trials since it enables rapid diagnosis with visualization and quantitative assessment.


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.


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 ]


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.


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 ]


An imaging-based trial will usually be made up of three components:


Medical imaging can lead to patient and healthcare provider harm through exposure to  ionizing radiation ,  iodinated contrast ,  magnetic fields , and other hazards. [ 41 ]


Lead  is the main material used for  radiographic shielding  against scattered X-rays.


In  magnetic resonance imaging , there is  MRI RF shielding  as well as  magnetic shielding  to prevent external disturbance of image quality. [ 42 ]


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 ]