Daily Papers

Autonomous computational pathology (ACP) converts high-level pathology analysis goals into executable, traceable and clinically bounded workflows. Realizing this capability requires adapting general agentic harness systems to pathology-specific tasks, tools, evidence standards and clinical claim boundaries. We contribute ACP-Bench, a framework that adapts existing harness systems from computational pathology support toward ACP workflow capability. ACP-Bench evaluates 41 pathology workflow tasks, including 24 biomarker, 7 morphology and 10 prognosis tasks spanning 6 body-system groups and 9 endpoint families. The benchmark evaluates 9 models and 3 harness groups (Claude Code, Codex and Open Code), yielding 369 complete trajectories. ACP-Bench evaluates each trajectory across workflow execution, diagnostic performance and clinical-boundary alignment, combining expert-adjudicated process audits, diagnostic assessment and pathologist-validated safety review. Across evaluated systems, workflow initiation, task interpretation and diagnostic reporting were more mature than tool-bound execution, result binding and reflective workflow revision, and formal end-to-end completion remained rare. ACP-Bench provides a reusable standard for auditing whether agentic systems can operationalize pathology workflows before claims of reliable clinical autonomy.

Large language models (LLMs) are increasingly used for medical and health-related questions, yet their safety in high-risk medical scenarios remains poorly understood. We introduce MedHarmCode and data will be released upon acceptance. Due to the sensitive nature of high-risk medical queries, data access will be available to qualified researchers upon request., a high-risk medical safety benchmark with 1,100 medically grounded queries across 10 safety-critical categories, including toxicology, pharmacology, covert poisoning, anesthesia, and fetal harm. Unlike broad medical QA benchmarks, MedHarm targets realistic clinical, educational, and technical prompts that require refusal, caution, or safe redirection rather than direct helpfulness. We evaluate 15 LLMs spanning general-purpose, medical-purpose, closed-source, and downstream SFT models, together with 4 representative guardrail models. Results reveal a substantial gap between apparent alignment and medical safety: aligned models can still produce unsafe or actionable responses, medical fine-tuning can amplify harmful specificity, and external guardrails reduce some failures while introducing brittle blocking and weak safe helpfulness. These findings show that medical safety cannot be inferred from general alignment or medical capability alone, highlighting the need for domain-specific stress testing before deploying LLMs in safety-critical medical applications.

Although large language models (LLMs) demonstrate expert-level medical knowledge, aligning their open-ended outputs with fine-grained clinician preferences remains challenging. Existing methods often rely on coarse objectives or unreliable automated judges that are weakly grounded in professional guidelines. We propose a two-stage framework to address this gap. First, we introduce HealthRubrics, a dataset of 7,034 physician-verified preference examples in which clinicians refine LLM-drafted rubrics to meet rigorous medical standards. Second, we distill these rubrics into HealthPrinciples: 119 broadly reusable, clinically grounded principles organized by clinical dimensions, enabling scalable supervision beyond manual annotation. We use HealthPrinciples for (1) offline alignment by synthesizing rubrics for unlabeled queries and (2) an inference-time tool for guided self-revision. A 30B parameter model that activates only 3B parameters at inference trained with our framework achieves 33.4% on HealthBench-Hard, outperforming much larger models including Deepseek-R1 and o3, establishing a resource-efficient baseline for clinical alignment.

Vision-Language Models (VLM) can support clinicians by analyzing medical images and engaging in natural language interactions to assist in diagnostic and treatment tasks. However, VLMs often exhibit "hallucinogenic" behavior, generating textual outputs not grounded in contextual multimodal information. This challenge is particularly pronounced in the medical domain, where we do not only require VLM outputs to be accurate in single interactions but also to be consistent with clinical reasoning and diagnostic pathways throughout multi-turn conversations. For this purpose, we propose a new alignment algorithm that uses symbolic representations of clinical reasoning to ground VLMs in medical knowledge. These representations are utilized to (i) generate GPT-4-guided visual instruction tuning data at scale, simulating clinician-VLM conversations with demonstrations of clinical reasoning, and (ii) create an automatic reward function that evaluates the clinical validity of VLM generations throughout clinician-VLM interactions. Our algorithm eliminates the need for human involvement in training data generation or reward model construction, reducing costs compared to standard reinforcement learning with human feedback (RLHF). We apply our alignment algorithm to develop Dr-LLaVA, a conversational VLM finetuned for analyzing bone marrow pathology slides, demonstrating strong performance in multi-turn medical conversations.

The integration of large language models (LLMs) into medical practice holds transformative potential, yet their real-world clinical utility remains limited by critical alignment challenges: (1) a disconnect between static evaluation benchmarks and dynamic clinical cognitive needs, (2) difficulties in adapting to evolving, multi-source medical standards, and (3) the inability of conventional reward models to capture nuanced, multi-dimensional medical quality criteria. To address these gaps, we propose MR-RML (Multidimensional Rubric-oriented Reward Model Learning) via GPRC (Geometric Projection Reference Constraints), a novel alignment framework that integrates medical standards into a structured "Dimensions-Scenarios-Disciplines" matrix to guide data generation and model optimization. MR-RML introduces three core innovations: (1) a "Dimensions-Scenarios-Disciplines" medical standard system that embeds domain standards into the full training pipeline; (2) an independent multi-dimensional reward model that decomposes evaluation criteria, shifting from real-time rubric-based scoring to internalized reward modeling for improved consistency and cost-efficiency; (3) geometric projection reference constraints that transform medical cognitive logic into mathematical regularization, aligning scoring gradients with clinical reasoning and enabling synthetic data-driven training. Through extensive evaluations on the authoritative medical benchmark Healthbench, our method yields substantial performance gains over the base LLM Qwen-32B (45% on the full subset and 85% on Hard subset, respectively). It achieves a SOTA among open-source LLMs with scores of 62.7 (full subset) and 44.7 (hard subset), while also outperforming the majority of closed-source models.

Medical image segmentation exhibits intra- and inter-annotator variability due to ambiguous object boundaries, annotator preferences, expertise, and tools, among other factors. Lesions with ambiguous boundaries, e.g., spiculated or infiltrative nodules, or irregular borders per the ABCD rule, are particularly prone to disagreement and are often associated with malignancy. In this work, we curate IMA++, the largest multi-annotator skin lesion segmentation dataset, on which we conduct an in-depth study of variability due to annotator, malignancy, tool, and skill factors. We find a statistically significant (p<0.001) association between inter-annotator agreement (IAA), measured using Dice, and the malignancy of skin lesions. We further show that IAA can be accurately predicted directly from dermoscopic images, achieving a mean absolute error of 0.108. Finally, we leverage this association by utilizing IAA as a "soft" clinical feature within a multi-task learning objective, yielding a 4.2% improvement in balanced accuracy averaged across multiple model architectures and across IMA++ and four public dermoscopic datasets. The code is available at https://github.com/sfu-mial/skin-IAV.

While reinforcement learning for large language model alignment has progressed rapidly in recent years, transferring these paradigms to high-stakes medical question answering reveals a fundamental paradigm mismatch. Reinforcement Learning from Human Feedback relies on preference annotations that are prohibitively expensive and often fail to reflect the absolute correctness of medical facts. Reinforcement Learning from Verifiable Rewards lacks effective automatic verifiers and struggles to handle complex clinical contexts. Meanwhile, medical alignment requires the simultaneous optimization of correctness, safety, and compliance, yet multi-objective heterogeneous reward signals are prone to scale mismatch and optimization conflicts.To address these challenges, we propose a robust medical alignment paradigm. We first construct a holistic multi-dimensional medical alignment matrix that decomposes alignment objectives into four categories: fundamental capabilities, expert knowledge, online feedback, and format specifications. Within each category, we establish a closed loop of where observable metrics inform attributable diagnosis, which in turn drives optimizable rewards, thereby providing fine-grained, high-resolution supervision signals for subsequent iterative optimization. To resolve gradient domination and optimization instability problem caused by heterogeneous signals, we further propose a unified optimization mechanism. This mechanism employs Reference-Frozen Normalization to align reward scales and implements a Tri-Factor Adaptive Dynamic Weighting strategy to achieve collaborative optimization that is weakness-oriented, risk-prioritized, and redundancy-reducing. Experimental results demonstrate the effectiveness of our proposed paradigm in real-world medical scenario evaluations, establishing a new paradigm for complex alignment in vertical domains.

Skin carcinoma is the most prevalent form of cancer globally, accounting for over $8 billion in annual healthcare expenditures. In clinical settings, physicians document patient visits using detailed SOAP (Subjective, Objective, Assessment, and Plan) notes. However, manually generating these notes is labor-intensive and contributes to clinician burnout. In this work, we propose a weakly supervised multimodal framework to generate clinically structured SOAP notes from limited inputs, including lesion images and sparse clinical text. Our approach reduces reliance on manual annotations, enabling scalable, clinically grounded documentation while alleviating clinician burden and reducing the need for large annotated data. Our method achieves performance comparable to GPT-4o, Claude, and DeepSeek Janus Pro across key clinical relevance metrics. To evaluate clinical quality, we introduce two novel metrics MedConceptEval and Clinical Coherence Score (CCS) which assess semantic alignment with expert medical concepts and input features, respectively.

Medical image segmentation plays a crucial role in clinical diagnosis and treatment planning, where accurate boundary delineation is essential for precise lesion localization, organ identification, and quantitative assessment. In recent years, deep learning-based methods have significantly advanced segmentation accuracy. However, two major challenges remain. First, the performance of these methods heavily relies on large-scale annotated datasets, which are often difficult to obtain in medical scenarios due to privacy concerns and high annotation costs. Second, clinically challenging scenarios, such as low contrast in certain imaging modalities and blurry lesion boundaries caused by malignancy, still pose obstacles to precise segmentation. To address these challenges, we propose MedSAM-CA, an architecture-level fine-tuning approach that mitigates reliance on extensive manual annotations by adapting the pretrained foundation model, Medical Segment Anything (MedSAM). MedSAM-CA introduces two key components: the Convolutional Attention-Enhanced Boundary Refinement Network (CBR-Net) and the Attention-Enhanced Feature Fusion Block (Atte-FFB). CBR-Net operates in parallel with the MedSAM encoder to recover boundary information potentially overlooked by long-range attention mechanisms, leveraging hierarchical convolutional processing. Atte-FFB, embedded in the MedSAM decoder, fuses multi-level fine-grained features from skip connections in CBR-Net with global representations upsampled within the decoder to enhance boundary delineation accuracy. Experiments on publicly available datasets covering dermoscopy, CT, and MRI imaging modalities validate the effectiveness of MedSAM-CA. On dermoscopy dataset, MedSAM-CA achieves 94.43% Dice with only 2% of full training data, reaching 97.25% of full-data training performance, demonstrating strong effectiveness in low-resource clinical settings.

Skin carcinoma is the most prevalent form of cancer globally, accounting for over $8 billion in annual healthcare expenditures. Early diagnosis, accurate and timely treatment are critical to improving patient survival rates. In clinical settings, physicians document patient visits using detailed SOAP (Subjective, Objective, Assessment, and Plan) notes. However, manually generating these notes is labor-intensive and contributes to clinician burnout. In this work, we propose skin-SOAP, a weakly supervised multimodal framework to generate clinically structured SOAP notes from limited inputs, including lesion images and sparse clinical text. Our approach reduces reliance on manual annotations, enabling scalable, clinically grounded documentation while alleviating clinician burden and reducing the need for large annotated data. Our method achieves performance comparable to GPT-4o, Claude, and DeepSeek Janus Pro across key clinical relevance metrics. To evaluate this clinical relevance, we introduce two novel metrics MedConceptEval and Clinical Coherence Score (CCS) which assess semantic alignment with expert medical concepts and input features, respectively.

Vision-language pre-training (VLP) models have shown significant advancements in the medical domain. Yet, most VLP models align raw reports to images at a very coarse level, without modeling fine-grained relationships between anatomical and pathological concepts outlined in reports and the corresponding semantic counterparts in images. To address this problem, we propose a Medical Dual-Stream Language-Image Pre-training (MeDSLIP) framework. Specifically, MeDSLIP establishes vision-language fine-grained alignments via disentangling visual and textual representations into anatomy-relevant and pathology-relevant streams. Moreover, a novel vision-language Prototypical Contr-astive Learning (ProtoCL) method is adopted in MeDSLIP to enhance the alignment within the anatomical and pathological streams. MeDSLIP further employs cross-stream Intra-image Contrastive Learning (ICL) to ensure the consistent coexistence of paired anatomical and pathological concepts within the same image. Such a cross-stream regularization encourages the model to exploit the synchrony between two streams for a more comprehensive representation learning. MeDSLIP is evaluated under zero-shot and supervised fine-tuning settings on three public datasets: NIH CXR14, RSNA Pneumonia, and SIIM-ACR Pneumothorax. Under these settings, MeDSLIP outperforms six leading CNN-based models on classification, grounding, and segmentation tasks.

Supervised synthetic CT generation from CBCT requires registered training pairs, yet perfect registration between separately acquired scans remains unattainable. This registration bias propagates into trained models and corrupts standard evaluation metrics. This may suggest that superior benchmark performance indicates better reproduction of registration artifacts rather than anatomical fidelity. We propose physics-based CBCT simulation to provide geometrically aligned training pairs by construction, combined with evaluation using geometric alignment metrics against input CBCT rather than biased ground truth. On two independent pelvic datasets, models trained on synthetic data achieved superior geometric alignment (Normalized Mutual Information: 0.31 vs 0.22) despite lower conventional intensity scores. Intensity metrics showed inverted correlations with clinical assessment for deformably registered data, while Normalized Mutual Information consistently predicted observer preference across registration methodologies (rho = 0.31, p < 0.001). Clinical observers preferred synthetic-trained outputs in 87% of cases, demonstrating that geometric fidelity, not intensity agreement with biased ground truth, aligns with clinical requirements.

Clinical AI development has traditionally followed a collaborative paradigm that depends on close interaction between clinicians and specialized AI teams. This paradigm imposes a practical challenge: clinicians must repeatedly communicate and refine their requirements with AI developers before those requirements can be translated into executable model development. This iterative process is time-consuming, and even after repeated discussion, misalignment may still exist because the two sides do not fully share each other's expertise. However, autonomous coding agents may change this paradigm, raising the possibility that clinicians could develop clinical AI models independently through natural-language interaction alone. In this study, we present such an autonomous prototype for clinician-driven clinical AI development. We evaluated the system on five clinical tasks spanning dermoscopic lesion classification, melanoma-versus-nevus triage, wrist-fracture detection (including a weakly supervised variant with only 5% bounding-box annotations), and debiased pneumothorax classification on chest radiographs. Across these settings, the system consistently developed models from clinician requests and achieved promising performance. Notably, in a debiased pneumothorax classification task on chest radiographs, where chest drains can act as a major confounder, the system successfully mitigated shortcut learning and nearly halved the model's reliance on chest drains. These findings provide proof of concept that autonomous coding agents may help shift clinical AI development toward a more clinician-driven paradigm, reducing the communication overhead and dependence on specialized AI developers. Although further validation and robustness assessment are needed, this study suggests a promising path toward making clinical AI development more accessible.

Image registration is fundamental in medical imaging, enabling precise alignment of anatomical structures for diagnosis, treatment planning, image-guided treatment or longitudinal monitoring. This work introduces IMPACT (Image Metric with Pretrained model-Agnostic Comparison for Transmodality registration), a generic semantic similarity metric designed for seamless integration into diverse image registration frameworks (such as Elastix and Voxelmorph). It compares deep learning-based features extracted from medical images without requiring task-specific training, ensuring broad applicability across various modalities. By leveraging the features of the large-scale pretrained TotalSegmentator models and the ability to integrate Segment Anything Model (SAM) and other large-scale segmentation networks, this approach offers significant advantages. It provides robust, scalable, and efficient solutions for multimodal image registration. The IMPACT loss was evaluated on five challenging registration tasks involving thoracic CT/CBCT, and pelvic MR/CT datasets. Quantitative metrics, such as Target Registration Error and Dice Similarity Coefficient, demonstrated significant improvements in anatomical alignment compared to baseline methods. Qualitative analyses further confirmed the increased robustness of the proposed metric in the face of noise, artifacts, and modality variations. IMPACT's versatility and efficiency make it a valuable tool for advancing registration performance in clinical and research applications, addressing critical challenges in multimodal medical imaging.

Trustworthiness is essential for the precise and interpretable application of artificial intelligence (AI) in medical imaging. Traditionally, precision and interpretability have been addressed as separate tasks, namely medical image analysis and explainable AI, each developing its own models independently. In this study, for the first time, we investigate the development of a unified medical vision-language pre-training model that can achieve both accurate analysis and interpretable understanding of medical images across various modalities. To build the model, we construct MedConcept-23M, a large-scale dataset comprising 23 million medical image-text pairs extracted from 6.2 million scientific articles, enriched with concepts from the Unified Medical Language System (UMLS). Based on MedConcept-23M, we introduce ConceptCLIP, a medical AI model utilizing concept-enhanced contrastive language-image pre-training. The pre-training of ConceptCLIP involves two primary components: image-text alignment learning (IT-Align) and patch-concept alignment learning (PC-Align). This dual alignment strategy enhances the model's capability to associate specific image regions with relevant concepts, thereby improving both the precision of analysis and the interpretability of the AI system. We conducted extensive experiments on 5 diverse types of medical image analysis tasks, spanning 51 subtasks across 10 image modalities, with the broadest range of downstream tasks. The results demonstrate the effectiveness of the proposed vision-language pre-training model. Further explainability analysis across 6 modalities reveals that ConceptCLIP achieves superior performance, underscoring its robust ability to advance explainable AI in medical imaging. These findings highlight ConceptCLIP's capability in promoting trustworthy AI in the field of medicine.

Medical report generation from X-ray images is a challenging task, particularly in an unpaired setting where paired image-report data is unavailable for training. To address this challenge, we propose a novel model that leverages the available information in two distinct datasets, one comprising reports and the other consisting of images. The core idea of our model revolves around the notion that combining auto-encoding report generation with multi-modal (report-image) alignment can offer a solution. However, the challenge persists regarding how to achieve this alignment when pair correspondence is absent. Our proposed solution involves the use of auxiliary tasks, particularly contrastive learning and classification, to position related images and reports in close proximity to each other. This approach differs from previous methods that rely on pre-processing steps, such as using external information stored in a knowledge graph. Our model, named MedRAT, surpasses previous state-of-the-art methods, demonstrating the feasibility of generating comprehensive medical reports without the need for paired data or external tools.

Anatomical structure labels for chest radiographs are essential for medical image segmentation and a broad range of downstream diagnostic tasks. However, annotating anatomy directly on 2D chest radiographs is labor-intensive and intrinsically ambiguous, as 3D anatomical structures are projected onto a single 2D plane where boundaries may overlap, be occluded, or appear only partially visible. Consequently, existing anatomy-labeled chest radiograph datasets remain limited in scale, anatomy coverage, and label reliability. To address these limitations, we introduce RadGenome-Anatomy, the largest anatomy-labeled chest radiograph dataset, containing over 10 million segmentation masks across 210 anatomical structures in 25,692 studies. It is constructed by projecting large-scale 3D anatomical masks from CT volumes into 2D radiographic space through canonical radiographic geometry. This shifts annotation from directly tracing uncertain 2D boundaries to defining anatomy in volumetric space, where structures that overlap or become partially invisible in radiographs remain spatially separable. As a result, each 2D mask represents the physically grounded projected footprint of a volumetrically defined structure. The scale and broad anatomical coverage of RadGenome-Anatomy, including structures that are overlapping, partially visible, or difficult to delineate directly, enable research on geometric measurements as explicit evidence for chest radiograph interpretation. We demonstrate this by training XAnatomy to predict structure-specific masks and derive clinically relevant measurements, achieving diagnostic accuracies of 96.4%, 95.6%, and 89.2% for cardiomegaly, kyphosis, and scoliosis, respectively.

Recent advances in large language models have enabled their application to a range of healthcare tasks. However, aligning LLMs with the nuanced demands of medical ethics, especially under complex real world scenarios, remains underexplored. In this work, we present MedES, a dynamic, scenario-centric benchmark specifically constructed from 260 authoritative Chinese medical, ethical, and legal sources to reflect the challenges in clinical decision-making. To facilitate model alignment, we introduce a guardian-in-the-loop framework that leverages a dedicated automated evaluator (trained on expert-labeled data and achieving over 97% accuracy within our domain) to generate targeted prompts and provide structured ethical feedback. Using this pipeline, we align a 7B-parameter LLM through supervised fine-tuning and domain-specific preference optimization. Experimental results, conducted entirely within the Chinese medical ethics context, demonstrate that our aligned model outperforms notably larger baselines on core ethical tasks, with observed improvements in both quality and composite evaluation metrics. Our work offers a practical and adaptable framework for aligning LLMs with medical ethics in the Chinese healthcare domain, and suggests that similar alignment pipelines may be instantiated in other legal and cultural environments through modular replacement of the underlying normative corpus.

Safety alignment in Large Language Models is critical for healthcare; however, reliance on binary refusal boundaries often results in over-refusal of benign queries or unsafe compliance with harmful ones. While existing benchmarks measure these extremes, they fail to evaluate Safe Completion: the model's ability to maximise helpfulness on dual-use or borderline queries by providing safe, high-level guidance without crossing into actionable harm. We introduce Health-ORSC-Bench, the first large-scale benchmark designed to systematically measure Over-Refusal and Safe Completion quality in healthcare. Comprising 31,920 benign boundary prompts across seven health categories (e.g., self-harm, medical misinformation), our framework uses an automated pipeline with human validation to test models at varying levels of intent ambiguity. We evaluate 30 state-of-the-art LLMs, including GPT-5 and Claude-4, revealing a significant tension: safety-optimised models frequently refuse up to 80\% of "Hard" benign prompts, while domain-specific models often sacrifice safety for utility. Our findings demonstrate that model family and size significantly influence calibration: larger frontier models (e.g., GPT-5, Llama-4) exhibit "safety-pessimism" and higher over-refusal than smaller or MoE-based counterparts (e.g., Qwen-3-Next), highlighting that current LLMs struggle to balance refusal and compliance. Health-ORSC-Bench provides a rigorous standard for calibrating the next generation of medical AI assistants toward nuanced, safe, and helpful completions. The code and data will be released upon acceptance. red{Warning: Some contents may include toxic or undesired contents.}

The development of large-scale image-text pair datasets has significantly advanced self-supervised learning in Vision-Language Processing (VLP). However, directly applying general-domain architectures such as CLIP to medical data presents challenges, particularly in handling negations and addressing the inherent data imbalance of medical datasets. To address these issues, we propose a novel approach that integrates clinically-enhanced dynamic soft labels and medical graphical alignment, thereby improving clinical comprehension and the applicability of contrastive loss in medical contexts. Furthermore, we introduce negation-based hard negatives to deepen the model's understanding of the complexities of clinical language. Our approach is easily integrated into the medical CLIP training pipeline and achieves state-of-the-art performance across multiple tasks, including zero-shot, fine-tuned classification, and report retrieval. To comprehensively evaluate our model's capacity for understanding clinical language, we introduce CXR-Align, a benchmark uniquely designed to evaluate the understanding of negation and clinical information within chest X-ray (CXR) datasets. Experimental results demonstrate that our proposed methods are straightforward to implement and generalize effectively across contrastive learning frameworks, enhancing medical VLP capabilities and advancing clinical language understanding in medical imaging.

Geometric alignment appears in a variety of applications, ranging from domain adaptation, optimal transport, and normalizing flows in machine learning; optical flow and learned augmentation in computer vision and deformable registration within biomedical imaging. A recurring challenge is the alignment of domains whose topology is not the same; a problem that is routinely ignored, potentially introducing bias in downstream analysis. As a first step towards solving such alignment problems, we propose an unsupervised algorithm for the detection of changes in image topology. The model is based on a conditional variational auto-encoder and detects topological changes between two images during the registration step. We account for both topological changes in the image under spatial variation and unexpected transformations. Our approach is validated on two tasks and datasets: detection of topological changes in microscopy images of cells, and unsupervised anomaly detection brain imaging.

Medical image encoders from different groups are increasingly treated as interchangeable, on the assumption that scale and clinical supervision concentrate their representations onto a shared structure. Whether this convergence is real, what produces it, and whether it is clinically usable are untested, and the similarity measures behind such claims are fragile. We present a controlled dissection across 18 image and 7 text encoders, all open-weight and run locally, spanning 7M to 27B parameters and five imaging modalities, including 650,982 chest radiographs from six datasets. To isolate cause, we train encoders that vary only the objective under fixed data, architecture, and scale, and reproduce the effect in a synthetic model. Convergence is modest but above a random floor, driven by the self-supervised objective, not clinical supervision: matched self-supervised encoders aligned most (40.4% on chest radiography), with label-supervised (21.1%) and image-text (3.3%) far lower, and did not grow with size (Spearman 0.302, p=0.223) or capability. It is within-modality, does not reach clinical language, and does not reproduce how radiologists judge case similarity. Yet a linear classifier transfers across encoders and to five held-out hospitals, retaining about 85% of within-encoder performance. Convergence in medical imaging is therefore set by the pretraining objective, not inherited from scale or clinical supervision. Interoperability is accordingly something to design for through that objective, and to validate where the shared geometry is weakest, across patient subgroups and against clinical judgment.

The integration of Large Language Models (LLMs) into healthcare demands a safety paradigm rooted in primum non nocere. However, current alignment techniques rely on generic definitions of harm that fail to capture context-dependent violations, such as administrative fraud and clinical discrimination. To address this, we introduce Medical Malice: a dataset of 214,219 adversarial prompts calibrated to the regulatory and ethical complexities of the Brazilian Unified Health System (SUS). Crucially, the dataset includes the reasoning behind each violation, enabling models to internalize ethical boundaries rather than merely memorizing a fixed set of refusals. Using an unaligned agent (Grok-4) within a persona-driven pipeline, we synthesized high-fidelity threats across seven taxonomies, ranging from procurement manipulation and queue-jumping to obstetric violence. We discuss the ethical design of releasing these "vulnerability signatures" to correct the information asymmetry between malicious actors and AI developers. Ultimately, this work advocates for a shift from universal to context-aware safety, providing the necessary resources to immunize healthcare AI against the nuanced, systemic threats inherent to high-stakes medical environments -- vulnerabilities that represent the paramount risk to patient safety and the successful integration of AI in healthcare systems.

Vision-grounded medical report generation aims to produce clinically accurate descriptions of medical images, anchored in explicit visual evidence to improve interpretability and facilitate integration into clinical workflows. However, existing methods often rely on separately trained detection modules that require extensive expert annotations, introducing high labeling costs and limiting generalizability due to pathology distribution bias across datasets. To address these challenges, we propose Self-Supervised Anatomical Consistency Learning (SS-ACL) -- a novel and annotation-free framework that aligns generated reports with corresponding anatomical regions using simple textual prompts. SS-ACL constructs a hierarchical anatomical graph inspired by the invariant top-down inclusion structure of human anatomy, organizing entities by spatial location. It recursively reconstructs fine-grained anatomical regions to enforce intra-sample spatial alignment, inherently guiding attention maps toward visually relevant areas prompted by text. To further enhance inter-sample semantic alignment for abnormality recognition, SS-ACL introduces a region-level contrastive learning based on anatomical consistency. These aligned embeddings serve as priors for report generation, enabling attention maps to provide interpretable visual evidence. Extensive experiments demonstrate that SS-ACL, without relying on expert annotations, (i) generates accurate and visually grounded reports -- outperforming state-of-the-art methods by 10\% in lexical accuracy and 25\% in clinical efficacy, and (ii) achieves competitive performance on various downstream visual tasks, surpassing current leading visual foundation models by 8\% in zero-shot visual grounding.

Fairness in artificial intelligence models has gained significantly more attention in recent years, especially in the area of medicine, as fairness in medical models is critical to people's well-being and lives. High-quality medical fairness datasets are needed to promote fairness learning research. Existing medical fairness datasets are all for classification tasks, and no fairness datasets are available for medical segmentation, while medical segmentation is an equally important clinical task as classifications, which can provide detailed spatial information on organ abnormalities ready to be assessed by clinicians. In this paper, we propose the first fairness dataset for medical segmentation named Harvard-FairSeg with 10,000 subject samples. In addition, we propose a fair error-bound scaling approach to reweight the loss function with the upper error-bound in each identity group, using the segment anything model (SAM). We anticipate that the segmentation performance equity can be improved by explicitly tackling the hard cases with high training errors in each identity group. To facilitate fair comparisons, we utilize a novel equity-scaled segmentation performance metric to compare segmentation metrics in the context of fairness, such as the equity-scaled Dice coefficient. Through comprehensive experiments, we demonstrate that our fair error-bound scaling approach either has superior or comparable fairness performance to the state-of-the-art fairness learning models. The dataset and code are publicly accessible via https://ophai.hms.harvard.edu/datasets/harvard-fairseg10k.

Specialized clinical AI assistants are rapidly entering medical practice, often framed as safer or more reliable than general-purpose large language models (LLMs). Yet, unlike frontier models, these clinical tools are rarely subjected to independent, quantitative evaluation, creating a critical evidence gap despite their growing influence on diagnosis, triage, and guideline interpretation. We assessed two widely deployed clinical AI systems (OpenEvidence and UpToDate Expert AI) against three state-of-the-art generalist LLMs (GPT-5, Gemini 3 Pro, and Claude Sonnet 4.5) using a 1,000-item mini-benchmark combining MedQA (medical knowledge) and HealthBench (clinician-alignment) tasks. Generalist models consistently outperformed clinical tools, with GPT-5 achieving the highest scores, while OpenEvidence and UpToDate demonstrated deficits in completeness, communication quality, context awareness, and systems-based safety reasoning. These findings reveal that tools marketed for clinical decision support may often lag behind frontier LLMs, underscoring the urgent need for transparent, independent evaluation before deployment in patient-facing workflows.

In response to the pressing need for advanced clinical problem-solving tools in healthcare, we introduce BooksMed, a novel framework based on a Large Language Model (LLM). BooksMed uniquely emulates human cognitive processes to deliver evidence-based and reliable responses, utilizing the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) framework to effectively quantify evidence strength. For clinical decision-making to be appropriately assessed, an evaluation metric that is clinically aligned and validated is required. As a solution, we present ExpertMedQA, a multispecialty clinical benchmark comprised of open-ended, expert-level clinical questions, and validated by a diverse group of medical professionals. By demanding an in-depth understanding and critical appraisal of up-to-date clinical literature, ExpertMedQA rigorously evaluates LLM performance. BooksMed outperforms existing state-of-the-art models Med-PaLM 2, Almanac, and ChatGPT in a variety of medical scenarios. Therefore, a framework that mimics human cognitive stages could be a useful tool for providing reliable and evidence-based responses to clinical inquiries.

Clinical decision-making relies heavily on understanding relative positions of anatomical structures and anomalies. Therefore, for Vision-Language Models (VLMs) to be applicable in clinical practice, the ability to accurately determine relative positions on medical images is a fundamental prerequisite. Despite its importance, this capability remains highly underexplored. To address this gap, we evaluate the ability of state-of-the-art VLMs, GPT-4o, Llama3.2, Pixtral, and JanusPro, and find that all models fail at this fundamental task. Inspired by successful approaches in computer vision, we investigate whether visual prompts, such as alphanumeric or colored markers placed on anatomical structures, can enhance performance. While these markers provide moderate improvements, results remain significantly lower on medical images compared to observations made on natural images. Our evaluations suggest that, in medical imaging, VLMs rely more on prior anatomical knowledge than on actual image content for answering relative position questions, often leading to incorrect conclusions. To facilitate further research in this area, we introduce the MIRP , Medical Imaging Relative Positioning, benchmark dataset, designed to systematically evaluate the capability to identify relative positions in medical images.

Developing 3D vision-language models with robust clinical reasoning remains a challenge due to the inherent complexity of volumetric medical imaging, the tendency of models to overfit superficial report patterns, and the lack of interpretability-aware reward designs. In this paper, we propose Med3D-R1, a reinforcement learning framework with a two-stage training process: Supervised Fine-Tuning (SFT) and Reinforcement Learning (RL). During SFT stage, we introduce a residual alignment mechanism to bridge the gap between high-dimensional 3D features and textual embeddings, and an abnormality re-weighting strategy to emphasize clinically informative tokens and reduce structural bias in reports. In RL stage, we redesign the consistency reward to explicitly promote coherent, step-by-step diagnostic reasoning. We evaluate our method on medical multiple-choice visual question answering using two 3D diagnostic benchmarks, CT-RATE and RAD-ChestCT, where our model attains state-of-the-art accuracies of 41.92\% on CT-RATE and 44.99\% on RAD-ChestCT. These results indicate improved abnormality diagnosis and clinical reasoning and outperform prior methods on both benchmarks. Overall, our approach holds promise for enhancing real-world diagnostic workflows by enabling more reliable and transparent 3D medical vision-language systems.

Objective. Clinical AI documentation systems require evaluation methodologies that are clinically valid, economically viable, and sensitive to iterative changes. Methods requiring expert review per scoring instance are too slow and expensive for safe, iterative deployment. We present a case-specific, clinician-authored rubric methodology for clinical AI evaluation and examine whether LLM-generated rubrics can approximate clinician agreement. Materials and Methods. Twenty clinicians authored 1,646 rubrics for 823 clinical cases (736 real-world, 87 synthetic) across primary care, psychiatry, oncology, and behavioral health. Each rubric was validated by confirming that an LLM-based scoring agent consistently scored clinician-preferred outputs higher than rejected ones. Seven versions of an EHR-embedded AI agent for clinicians were evaluated across all cases. Results. Clinician-authored rubrics discriminated effectively between high- and low-quality outputs (median score gap: 82.9%) with high scoring stability (median range: 0.00%). Median scores improved from 84% to 95%. In later experiments, clinician-LLM ranking agreement (tau: 0.42-0.46) matched or exceeded clinician-clinician agreement (tau: 0.38-0.43), attributable to both ceiling compression and LLM rubric improvement. Discussion. This convergence supports incorporating LLM rubrics alongside clinician-authored ones. At roughly 1,000 times lower cost, LLM rubrics enable substantially greater evaluation coverage, while continued clinical authorship grounds evaluation in expert judgment. Ceiling compression poses a methodological challenge for future inter-rater agreement studies. Conclusion. Case-specific rubrics offer a path for clinical AI evaluation that preserves expert judgment while enabling automation at three orders lower cost. Clinician-authored rubrics establish the baseline against which LLM rubrics are validated.

Clinical trial matching is the task of identifying trials for which patients may be potentially eligible. Typically, this task is labor-intensive and requires detailed verification of patient electronic health records (EHRs) against the stringent inclusion and exclusion criteria of clinical trials. This process is manual, time-intensive, and challenging to scale up, resulting in many patients missing out on potential therapeutic options. Recent advancements in Large Language Models (LLMs) have made automating patient-trial matching possible, as shown in multiple concurrent research studies. However, the current approaches are confined to constrained, often synthetic datasets that do not adequately mirror the complexities encountered in real-world medical data. In this study, we present the first, end-to-end large-scale empirical evaluation of clinical trial matching using real-world EHRs. Our study showcases the capability of LLMs to accurately match patients with appropriate clinical trials. We perform experiments with proprietary LLMs, including GPT-4 and GPT-3.5, as well as our custom fine-tuned model called OncoLLM and show that OncoLLM, despite its significantly smaller size, not only outperforms GPT-3.5 but also matches the performance of qualified medical doctors. All experiments were carried out on real-world EHRs that include clinical notes and available clinical trials from a single cancer center in the United States.

Medical image segmentation poses challenges due to domain gaps, data modality variations, and dependency on domain knowledge or experts, especially for low- and middle-income countries (LMICs). Whereas for humans, given a few exemplars (with corresponding labels), we are able to segment different medical images even without exten-sive domain-specific clinical training. In addition, current SAM-based medical segmentation models use fine-grained visual prompts, such as the bounding rectangle generated from manually annotated target segmentation mask, as the bounding box (bbox) prompt during the testing phase. However, in actual clinical scenarios, no such precise prior knowledge is available. Our experimental results also reveal that previous models nearly fail to predict when given coarser bbox prompts. Considering these issues, in this paper, we introduce a domain-aware selective adaptation approach to adapt the general knowledge learned from a large model trained with natural images to the corresponding medical domains/modalities, with access to only a few (e.g. less than 5) exemplars. Our method mitigates the aforementioned limitations, providing an efficient and LMICs-friendly solution. Extensive experimental analysis showcases the effectiveness of our approach, offering potential advancements in healthcare diagnostics and clinical applications in LMICs.

Understanding causal narratives communicated in clinical notes can help make strides towards personalized healthcare. Extracted causal information from clinical notes can be combined with structured EHR data such as patients' demographics, diagnoses, and medications. This will enhance healthcare providers' ability to identify aspects of a patient's story communicated in the clinical notes and help make more informed decisions. In this work, we propose annotation guidelines, develop an annotated corpus and provide baseline scores to identify types and direction of causal relations between a pair of biomedical concepts in clinical notes; communicated implicitly or explicitly, identified either in a single sentence or across multiple sentences. We annotate a total of 2714 de-identified examples sampled from the 2018 n2c2 shared task dataset and train four different language model based architectures. Annotation based on our guidelines achieved a high inter-annotator agreement i.e. Fleiss' kappa (kappa) score of 0.72, and our model for identification of causal relations achieved a macro F1 score of 0.56 on the test data. The high inter-annotator agreement for clinical text shows the quality of our annotation guidelines while the provided baseline F1 score sets the direction for future research towards understanding narratives in clinical texts.

Reliable end-to-end clinical report generation has been a longstanding goal of medical ML research. The end goal for this process is to alleviate radiologists' workloads and provide second opinions to clinicians or patients. Thus, a necessary prerequisite for report generation models is a strong general performance and some type of innate grounding capability, to convince clinicians or patients of the veracity of the generated reports. In this paper, we present ASaRG (Automatic Segmentation-assisted Report Generation), an extension of the popular LLaVA architecture that aims to tackle both of these problems. ASaRG proposes to fuse intermediate features and fine-grained segmentation maps created by specialist radiological models into LLaVA's multi-modal projection layer via simple concatenation. With a small number of added parameters, our approach achieves a +0.89\% performance gain (p=0.012) in CE F1 score compared to the LLaVA baseline when using only intermediate features, and +2.77\% performance gain (p<0.001) when adding a combination of intermediate features and fine-grained segmentation maps. Compared with COMG and ORID, two other report generation methods that utilize segmentations, the performance gain amounts to 6.98\% and 6.28\% in F1 score, respectively. ASaRG is not mutually exclusive with other changes made to the LLaVA architecture, potentially allowing our method to be combined with other advances in the field. Finally, the use of an arbitrary number of segmentations as part of the input demonstrably allows tracing elements of the report to the corresponding segmentation maps and verifying the groundedness of assessments. Our code will be made publicly available at a later date.

For the immanent challenge of insufficiently annotated samples in the medical field, semi-supervised medical image segmentation (SSMIS) offers a promising solution. Despite achieving impressive results in delineating primary target areas, most current methodologies struggle to precisely capture the subtle details of boundaries. This deficiency often leads to significant diagnostic inaccuracies. To tackle this issue, we introduce C3S3, a novel semi-supervised segmentation model that synergistically integrates complementary competition and contrastive selection. This design significantly sharpens boundary delineation and enhances overall precision. Specifically, we develop an Outcome-Driven Contrastive Learning module dedicated to refining boundary localization. Additionally, we incorporate a Dynamic Complementary Competition module that leverages two high-performing sub-networks to generate pseudo-labels, thereby further improving segmentation quality. The proposed C3S3 undergoes rigorous validation on two publicly accessible datasets, encompassing the practices of both MRI and CT scans. The results demonstrate that our method achieves superior performance compared to previous cutting-edge competitors. Especially, on the 95HD and ASD metrics, our approach achieves a notable improvement of at least 6%, highlighting the significant advancements. The code is available at https://github.com/Y-TARL/C3S3.

Large language models (LLMs) show promise in drafting responses to patient portal messages, yet their integration into clinical workflows raises various concerns, including whether they would actually save clinicians time and effort in their portal workload. We investigate LLM alignment with individual clinicians through a comprehensive evaluation of the patient message response drafting task. We develop a novel taxonomy of thematic elements in clinician responses and propose a novel evaluation framework for assessing clinician editing load of LLM-drafted responses at both content and theme levels. We release an expert-annotated dataset and conduct large-scale evaluations of local and commercial LLMs using various adaptation techniques including thematic prompting, retrieval-augmented generation, supervised fine-tuning, and direct preference optimization. Our results reveal substantial epistemic uncertainty in aligning LLM drafts with clinician responses. While LLMs demonstrate capability in drafting certain thematic elements, they struggle with clinician-aligned generation in other themes, particularly question asking to elicit further information from patients. Theme-driven adaptation strategies yield improvements across most themes. Our findings underscore the necessity of adapting LLMs to individual clinician preferences to enable reliable and responsible use in patient-clinician communication workflows.

Med42-v2 introduces a suite of clinical large language models (LLMs) designed to address the limitations of generic models in healthcare settings. These models are built on Llama3 architecture and fine-tuned using specialized clinical data. They underwent multi-stage preference alignment to effectively respond to natural prompts. While generic models are often preference-aligned to avoid answering clinical queries as a precaution, Med42-v2 is specifically trained to overcome this limitation, enabling its use in clinical settings. Med42-v2 models demonstrate superior performance compared to the original Llama3 models in both 8B and 70B parameter configurations and GPT-4 across various medical benchmarks. These LLMs are developed to understand clinical queries, perform reasoning tasks, and provide valuable assistance in clinical environments. The models are now publicly available at https://huggingface.co/m42-health{https://huggingface.co/m42-health}.

In semi-supervised medical image segmentation, there exist empirical mismatch problems between labeled and unlabeled data distribution. The knowledge learned from the labeled data may be largely discarded if treating labeled and unlabeled data separately or in an inconsistent manner. We propose a straightforward method for alleviating the problem - copy-pasting labeled and unlabeled data bidirectionally, in a simple Mean Teacher architecture. The method encourages unlabeled data to learn comprehensive common semantics from the labeled data in both inward and outward directions. More importantly, the consistent learning procedure for labeled and unlabeled data can largely reduce the empirical distribution gap. In detail, we copy-paste a random crop from a labeled image (foreground) onto an unlabeled image (background) and an unlabeled image (foreground) onto a labeled image (background), respectively. The two mixed images are fed into a Student network and supervised by the mixed supervisory signals of pseudo-labels and ground-truth. We reveal that the simple mechanism of copy-pasting bidirectionally between labeled and unlabeled data is good enough and the experiments show solid gains (e.g., over 21% Dice improvement on ACDC dataset with 5% labeled data) compared with other state-of-the-arts on various semi-supervised medical image segmentation datasets. Code is available at https://github.com/DeepMed-Lab-ECNU/BCP}.

With the growing use of language models (LMs) in clinical environments, there is an immediate need to evaluate the accuracy and safety of LM-generated medical text. Currently, such evaluation relies solely on manual physician review. However, detecting errors in LM-generated text is challenging because 1) manual review is costly and 2) expert-composed reference outputs are often unavailable in real-world settings. While the "LM-as-judge" paradigm (a LM evaluating another LM) offers scalable evaluation, even frontier LMs can miss subtle but clinically significant errors. To address these challenges, we propose MedVAL, a self-supervised framework that leverages synthetic data to train evaluator LMs to assess whether LM-generated medical outputs are factually consistent with inputs, without requiring physician labels or reference outputs. To evaluate LM performance, we introduce MedVAL-Bench, a dataset containing 840 outputs annotated by physicians, following a physician-defined taxonomy of risk levels and error categories. Across 6 diverse medical tasks and 10 state-of-the-art LMs spanning open-source, proprietary, and medically adapted models, MedVAL fine-tuning significantly improves (p < 0.001) alignment with physicians on both seen and unseen tasks, increasing average F1 scores from 66% to 83%, with per-sample safety classification scores up to 86%. MedVAL improves the performance of even the best-performing proprietary LM (GPT-4o) by 8%. To support a scalable, risk-aware pathway towards clinical integration, we open-source the 1) codebase ( https://github.com/StanfordMIMI/MedVAL ), 2) MedVAL-Bench ( https://huggingface.co/datasets/stanfordmimi/MedVAL-Bench ), and 3) MedVAL-4B ( https://huggingface.co/stanfordmimi/MedVAL-4B ), the best-performing open-source LM. Our research provides the first evidence of LMs approaching expert-level validation ability for medical text.

Large language models(LLMs) increasingly match expert performance on licensing examinations, yet routine clinical use remains limited because governance requires auditable reasoning, safety and ethics alignment, and resilience to adversarial misuse. Here we present SafeMed-R1, trained with a traceable Clinical Trust Signals(CTS) pipeline that links each reasoning instance to clinician rubric scores and edit histories, and aligned through safety and ethics supervision and red team stress testing. SafeMed-R1 attains a macro-averaged accuracy of 79.6% across clinical benchmarks. Under adversarial safety testing, it shows the lowest aggregated risk and reduces unsafe outputs by about 3 to 5% relative to its baseline. In a paired expert study of 30 medication safety vignettes, SafeMed-R1 matches PGY1 and PGY2 residents on medical correctness and scores higher for medication safety, guideline consistency, and clinical usefulness. Collectively, these results suggest that clinician-audited supervision provenance, together with domain-tailored safety and ethics alignment, can strengthen governance-relevant evidence without relying on inference-time retrieval or citation grounding.

Medication reconciliation at clinical handoffs is a high-stakes, error-prone process. Large language models are increasingly proposed to assist with this task using FHIR-structured patient records, but a fundamental and largely unstudied variable is how the FHIR data is serialised before being passed to the model. We present the first systematic comparison of four FHIR serialisation strategies (Raw JSON, Markdown Table, Clinical Narrative, and Chronological Timeline) across five open-weight models (Phi-3.5-mini, Mistral-7B, BioMistral-7B, Llama-3.1-8B, Llama-3.3-70B) on a controlled benchmark of 200 synthetic patients, totalling 4,000 inference runs. We find that serialisation strategy has a large, statistically significant effect on performance for models up to 8B parameters: Clinical Narrative outperforms Raw JSON by up to 19 F1 points for Mistral-7B (r = 0.617, p < 10^{-10}). This advantage reverses at 70B, where Raw JSON achieves the best mean F1 of 0.9956. In all 20 model and strategy combinations, mean precision exceeds mean recall: omission is the dominant failure mode, with models more often missing an active medication than fabricating one, which changes how clinical safety auditing priorities should be set. Smaller models plateau at roughly 7-10 concurrent active medications, leaving polypharmacy patients, the patients most at risk from reconciliation errors, systematically underserved. BioMistral-7B, a domain-pretrained model without instruction tuning, produces zero usable output in all conditions, showing that domain pretraining alone is not sufficient for structured extraction. These results offer practical, evidence-based format recommendations for clinical LLM deployment: Clinical Narrative for models up to 8B, Raw JSON for 70B and above. The complete pipeline is reproducible on open-source tools running on an AWS g6e.xlarge instance (NVIDIA L40S, 48 GB VRAM).

Current benchmarks for AI clinician systems, often based on multiple-choice exams or manual rubrics, fail to capture the depth, robustness, and safety required for real-world clinical practice. To address this, we introduce the GAPS framework, a multidimensional paradigm for evaluating Grounding (cognitive depth), Adequacy (answer completeness), Perturbation (robustness), and Safety. Critically, we developed a fully automated, guideline-anchored pipeline to construct a GAPS-aligned benchmark end-to-end, overcoming the scalability and subjectivity limitations of prior work. Our pipeline assembles an evidence neighborhood, creates dual graph and tree representations, and automatically generates questions across G-levels. Rubrics are synthesized by a DeepResearch agent that mimics GRADE-consistent, PICO-driven evidence review in a ReAct loop. Scoring is performed by an ensemble of large language model (LLM) judges. Validation confirmed our automated questions are high-quality and align with clinician judgment. Evaluating state-of-the-art models on the benchmark revealed key failure modes: performance degrades sharply with increased reasoning depth (G-axis), models struggle with answer completeness (A-axis), and they are highly vulnerable to adversarial perturbations (P-axis) as well as certain safety issues (S-axis). This automated, clinically-grounded approach provides a reproducible and scalable method for rigorously evaluating AI clinician systems and guiding their development toward safer, more reliable clinical practice.

Clinical diagnosis is critical in medical practice, typically requiring a continuous and evolving process that includes primary diagnosis, differential diagnosis, and final diagnosis. However, most existing clinical diagnostic tasks are single-step processes, which does not align with the complex multi-step diagnostic procedures found in real-world clinical settings. In this paper, we propose a multi-step diagnostic task and annotate a clinical diagnostic dataset (MSDiagnosis). This dataset includes primary diagnosis, differential diagnosis, and final diagnosis questions. Additionally, we propose a novel and effective framework. This framework combines forward inference, backward inference, reflection, and refinement, enabling the LLM to self-evaluate and adjust its diagnostic results. To assess the effectiveness of our proposed method, we design and conduct extensive experiments. The experimental results demonstrate the effectiveness of the proposed method. We also provide a comprehensive experimental analysis and suggest future research directions for this task.

The integration of artificial intelligence in image-guided interventions holds transformative potential, promising to extract 3D geometric and quantitative information from conventional 2D imaging modalities during complex procedures. Achieving this requires the rapid and precise alignment of 2D intraoperative images (e.g., X-ray) with 3D preoperative volumes (e.g., CT, MRI). However, current 2D/3D registration methods fail across the broad spectrum of procedures dependent on X-ray guidance: traditional optimization techniques require custom parameter tuning for each subject, whereas neural networks trained on small datasets do not generalize to new patients or require labor-intensive manual annotations, increasing clinical burden and precluding application to new anatomical targets. To address these challenges, we present xvr, a fully automated framework for training patient-specific neural networks for 2D/3D registration. xvr uses physics-based simulation to generate abundant high-quality training data from a patient's own preoperative volumetric imaging, thereby overcoming the inherently limited ability of supervised models to generalize to new patients and procedures. Furthermore, xvr requires only 5 minutes of training per patient, making it suitable for emergency interventions as well as planned procedures. We perform the largest evaluation of a 2D/3D registration algorithm on real X-ray data to date and find that xvr robustly generalizes across a diverse dataset comprising multiple anatomical structures, imaging modalities, and hospitals. Across surgical tasks, xvr achieves submillimeter-accurate registration at intraoperative speeds, improving upon existing methods by an order of magnitude. xvr is released as open-source software freely available at https://github.com/eigenvivek/xvr.

Precise delineation of meningiomas is crucial for effective radiotherapy (RT) planning, directly influencing treatment efficacy and preservation of adjacent healthy tissues. While automated deep learning approaches have demonstrated considerable potential, achieving consistently accurate clinical segmentation remains challenging due to tumor heterogeneity. Interactive Medical Image Segmentation (IMIS) addresses this challenge by integrating advanced AI techniques with clinical input. However, generic segmentation tools, despite widespread applicability, often lack the specificity required for clinically critical and disease-specific tasks like meningioma RT planning. To overcome these limitations, we introduce Interactive-MEN-RT, a dedicated IMIS tool specifically developed for clinician-assisted 3D meningioma segmentation in RT workflows. The system incorporates multiple clinically relevant interaction methods, including point annotations, bounding boxes, lasso tools, and scribbles, enhancing usability and clinical precision. In our evaluation involving 500 contrast-enhanced T1-weighted MRI scans from the BraTS 2025 Meningioma RT Segmentation Challenge, Interactive-MEN-RT demonstrated substantial improvement compared to other segmentation methods, achieving Dice similarity coefficients of up to 77.6\% and Intersection over Union scores of 64.8\%. These results emphasize the need for clinically tailored segmentation solutions in critical applications such as meningioma RT planning. The code is publicly available at: https://github.com/snuh-rad-aicon/Interactive-MEN-RT

High computation costs and latency of large language models such as GPT-4 have limited their deployment in clinical settings. Small language models (SLMs) offer a cost-effective alternative, but their limited capacity requires biomedical domain adaptation, which remains challenging. An additional bottleneck is the unavailability and high sensitivity of clinical data. To address these challenges, we propose a novel framework for adapting SLMs into high-performing clinical models. We introduce the MediPhi collection of 3.8B-parameter SLMs developed with our novel framework: pre-instruction tuning of experts on relevant medical and clinical corpora (PMC, Medical Guideline, MedWiki, etc.), model merging, and clinical-tasks alignment. To cover most clinical tasks, we extended the CLUE benchmark to CLUE+, doubling its size. Our expert models deliver relative improvements on this benchmark over the base model without any task-specific fine-tuning: 64.3% on medical entities, 49.5% on radiology reports, and 44% on ICD-10 coding (outperforming GPT-4-0125 by 14%). We unify the expert models into MediPhi via model merging, preserving gains across benchmarks. Furthermore, we built the MediFlow collection, a synthetic dataset of 2.5 million high-quality instructions on 14 medical NLP tasks, 98 fine-grained document types, and JSON format support. Alignment of MediPhi using supervised fine-tuning and direct preference optimization achieves further gains of 18.9% on average.

Large Language Models (LLMs) are increasingly used for clinical decision support, where hallucinations and unsafe suggestions may pose direct risks to patient safety. These risks are particularly challenging as they often manifest as subtle clinical errors that evade detection by generic metrics, while expert-authored fine-grained rubrics remain costly to construct and difficult to scale. In this paper, we propose a retrieval-augmented multi-agent framework designed to automate the generation of instance-specific evaluation rubrics. Our approach grounds evaluation in authoritative medical evidence by decomposing retrieved content into atomic facts and synthesizing them with user interaction constraints to form verifiable, fine-grained evaluation criteria. Evaluated on HealthBench, our framework achieves a Clinical Intent Alignment (CIA) score of 60.12%, a statistically significant improvement over the GPT-4o baseline (55.16%). In discriminative tests, our rubrics yield a mean score delta (μ_Δ = 8.658) and an AUROC of 0.977, nearly doubling the quality separation achieved by GPT-4o baseline (4.972). Beyond evaluation, our rubrics effectively guide response refinement, improving quality by 9.2% (from 59.0% to 68.2%). This provides a scalable and transparent foundation for both evaluating and improving medical LLMs. The code is available at https://anonymous.4open.science/r/Automated-Rubric-Generation-AF3C/.

Clinical trial matching is a key process in health delivery and discovery. In practice, it is plagued by overwhelming unstructured data and unscalable manual processing. In this paper, we conduct a systematic study on scaling clinical trial matching using large language models (LLMs), with oncology as the focus area. Our study is grounded in a clinical trial matching system currently in test deployment at a large U.S. health network. Initial findings are promising: out of box, cutting-edge LLMs, such as GPT-4, can already structure elaborate eligibility criteria of clinical trials and extract complex matching logic (e.g., nested AND/OR/NOT). While still far from perfect, LLMs substantially outperform prior strong baselines and may serve as a preliminary solution to help triage patient-trial candidates with humans in the loop. Our study also reveals a few significant growth areas for applying LLMs to end-to-end clinical trial matching, such as context limitation and accuracy, especially in structuring patient information from longitudinal medical records.

Learning medical visual representations directly from paired radiology reports has become an emerging topic in representation learning. However, existing medical image-text joint learning methods are limited by instance or local supervision analysis, ignoring disease-level semantic correspondences. In this paper, we present a novel Multi-Granularity Cross-modal Alignment (MGCA) framework for generalized medical visual representation learning by harnessing the naturally exhibited semantic correspondences between medical image and radiology reports at three different levels, i.e., pathological region-level, instance-level, and disease-level. Specifically, we first incorporate the instance-wise alignment module by maximizing the agreement between image-report pairs. Further, for token-wise alignment, we introduce a bidirectional cross-attention strategy to explicitly learn the matching between fine-grained visual tokens and text tokens, followed by contrastive learning to align them. More important, to leverage the high-level inter-subject relationship semantic (e.g., disease) correspondences, we design a novel cross-modal disease-level alignment paradigm to enforce the cross-modal cluster assignment consistency. Extensive experimental results on seven downstream medical image datasets covering image classification, object detection, and semantic segmentation tasks demonstrate the stable and superior performance of our framework.

In this work, we address the problem of grounding abnormalities in medical images, where the goal is to localize clinical findings based on textual descriptions. While generalist Vision-Language Models (VLMs) excel in natural grounding tasks, they often struggle in the medical domain due to rare, compositional, and domain-specific terms that are poorly aligned with visual patterns. Specialized medical VLMs address this challenge via large-scale domain pretraining, but at the cost of substantial annotation and computational resources. To overcome these limitations, we propose Knowledge to Sight (K2Sight), a framework that introduces structured semantic supervision by decomposing clinical concepts into interpretable visual attributes, such as shape, density, and anatomical location. These attributes are distilled from domain ontologies and encoded into concise instruction-style prompts, which guide region-text alignment during training. Unlike conventional report-level supervision, our approach explicitly bridges domain knowledge and spatial structure, enabling data-efficient training of compact models. We train compact models with 0.23B and 2B parameters using only 1.5\% of the data required by state-of-the-art medical VLMs. Despite their small size and limited training data, these models achieve performance on par with or better than 7B+ medical VLMs, with up to 9.82\% improvement in mAP_{50}. Code and models: https://lijunrio.github.io/K2Sight/{SOTAPink{https://lijunrio.github.io/K2Sight/}}.

Large language models (LLMs) have shown substantial progress in natural language understanding and generation, proving valuable especially in the medical field. Despite advancements, challenges persist due to the complexity and diversity inherent in medical tasks, which can be categorized as knowledge-intensive tasks and alignment-required tasks. Previous approaches either ignore the latter task or focus on a minority of tasks and hence lose generalization. To address these drawbacks, we propose a progressive fine-tuning pipeline. This pipeline employs a Knowledge Aggregator and a Noise aggregator to encode diverse knowledge in the first stage and filter out detrimental information. In the second stage, we drop the Noise Aggregator to avoid the interference of suboptimal representation and leverage an additional alignment module optimized towards an orthogonal direction to the knowledge space to mitigate knowledge forgetting. Based on this two-stage paradigm, we proposed a Medical LLM through decoupling Clinical Alignment and Knowledge Aggregation (MedCare), which is designed to achieve state-of-the-art (SOTA) performance on over 20 medical tasks, as well as SOTA results on specific medical alignment tasks. Various model sizes of MedCare (1.8B, 7B, 14B) all demonstrate significant improvements over existing models with similar model sizes.

Current Vision-Language Models (VLMs) struggle to ground anatomical regions in 3D medical images and reason about them in a step-by-step manner, a key requirement of real-world diagnostic assessment. This ability is essential for aligning model outputs with the diagnostic workflows clinicians use in practice, enabling trustworthy clinician-AI collaboration. Existing 3D datasets provide localization labels, but none support this "grounded reasoning" ability. To address this gap, we introduce 3DReasonKnee, the first 3D grounded reasoning dataset for medical images, which provides 494k high-quality quintuples derived from 7,970 3D knee MRI volumes. Each quintuple includes: (1) the 3D MRI volume, (2) a diagnostic question targeting a specific anatomical region (3) a 3D bounding box localizing the relevant anatomical structures, (4) clinician-generated diagnostic reasoning steps that explicitly detail the 3D reasoning process, and (5) structured severity assessments for the relevant anatomical region. The creation and validation of 3DReasonKnee, involving over 450 hours of expert clinician time for manually segmenting MRIs and generating reasoning chains, ensures its superior quality and clinical relevance. We establish ReasonKnee-Bench to evaluate localization and diagnostic accuracy, providing insight into VLM ability to perform grounding and severity assessment across anatomical regions and diagnostic inquiries. We benchmark five state-of-the-art VLMs, providing baseline performance for ReasonKnee-Bench. By providing this unique resource of expert-annotated 3D reasoning pathways, 3DReasonKnee serves as a repository of orthopedic surgeons' diagnostic expertise and offers a vital testbed for advancing multimodal medical AI systems towards 3D, clinically aligned, localized decision-making capabilities. The dataset can be found in: https://huggingface.co/datasets/rajpurkarlab/3DReasonKnee

AI alignment aims to make AI systems behave in line with human intentions and values. As AI systems grow more capable, so do risks from misalignment. To provide a comprehensive and up-to-date overview of the alignment field, in this survey, we delve into the core concepts, methodology, and practice of alignment. First, we identify four principles as the key objectives of AI alignment: Robustness, Interpretability, Controllability, and Ethicality (RICE). Guided by these four principles, we outline the landscape of current alignment research and decompose them into two key components: forward alignment and backward alignment. The former aims to make AI systems aligned via alignment training, while the latter aims to gain evidence about the systems' alignment and govern them appropriately to avoid exacerbating misalignment risks. On forward alignment, we discuss techniques for learning from feedback and learning under distribution shift. On backward alignment, we discuss assurance techniques and governance practices. We also release and continually update the website (www.alignmentsurvey.com) which features tutorials, collections of papers, blog posts, and other resources.

Radiographic assessment of lower-limb alignment (LLA) is important for predicting joint health and surgical outcomes in total knee arthroplasty. Traditional measurement methods are manual and time-consuming, while recent machine learning approaches typically rely on locating a fixed set of anatomical landmarks. This dependence limits flexibility and may require re-annotation when clinical definitions change. To address this, we propose an automated workflow using Implicit Neural Shape Functions (INSF). Rather than relying on explicit landmark coordinates, we encode the anatomy into a compact latent space and regress clinical alignment measurements directly from these latent codes. This architecture allows for rapid extendability to new tasks without altering the backbone representation. We trained our method on an internal dataset of 566 knee radiographs, each annotated with the outline of the femur and tibia. We evaluated it on both an internal test dataset of 50 patients and a separate external set of 402 preoperative cases from the MRKR dataset. Manual clinical measurements are available for these data, and the MRKR measurements will be made publicly accessible. Performance was comparable to state-of-the-art landmark-based methods and manual agreement, while offering a flexible shape representation that can be extended to additional measurement tasks.

3D medical image generation is essential for data augmentation and patient privacy, calling for reliable and efficient models suited for clinical practice. However, current methods suffer from limited anatomical fidelity, restricted axial length, and substantial computational cost, placing them beyond reach for regions with limited resources and infrastructure. We introduce TRACE, a framework that generates 3D medical images with spatiotemporal alignment using a 2D multimodal-conditioned diffusion approach. TRACE models sequential 2D slices as video frame pairs, combining segmentation priors and radiology reports for anatomical alignment, incorporating optical flow to sustain temporal coherence. During inference, an overlapping-frame strategy links frame pairs into a flexible length sequence, reconstructed into a spatiotemporally and anatomically aligned 3D volume. Experimental results demonstrate that TRACE effectively balances computational efficiency with preserving anatomical fidelity and spatiotemporal consistency. Code is available at: https://github.com/VinyehShaw/TRACE.

Medical Vision-Language Models (Med-VLMs) have achieved expert-level proficiency in interpreting diagnostic imaging. However, current models are predominantly trained on professional literature, limiting their ability to communicate findings in the lay register required for patient-centered care. While text-centric research has actively developed resources for simplifying medical jargon, there is a critical absence of large-scale multimodal benchmarks designed to facilitate lay-accessible medical image understanding. To bridge this resource gap, we introduce MedLayBench-V, the first large-scale multimodal benchmark dedicated to expert-lay semantic alignment. Unlike naive simplification approaches that risk hallucination, our dataset is constructed via a Structured Concept-Grounded Refinement (SCGR) pipeline. This method enforces strict semantic equivalence by integrating Unified Medical Language System (UMLS) Concept Unique Identifiers (CUIs) with micro-level entity constraints. MedLayBench-V provides a verified foundation for training and evaluating next-generation Med-VLMs capable of bridging the communication divide between clinical experts and patients.

Medical image registration is a critical task that estimates the spatial correspondence between pairs of images. However, current traditional and deep-learning-based methods rely on similarity measures to generate a deforming field, which often results in disproportionate volume changes in dissimilar regions, especially in tumor regions. These changes can significantly alter the tumor size and underlying anatomy, which limits the practical use of image registration in clinical diagnosis. To address this issue, we have formulated image registration with tumors as a constraint problem that preserves tumor volumes while maximizing image similarity in other normal regions. Our proposed strategy involves a two-stage process. In the first stage, we use similarity-based registration to identify potential tumor regions by their volume change, generating a soft tumor mask accordingly. In the second stage, we propose a volume-preserving registration with a novel adaptive volume-preserving loss that penalizes the change in size adaptively based on the masks calculated from the previous stage. Our approach balances image similarity and volume preservation in different regions, i.e., normal and tumor regions, by using soft tumor masks to adjust the imposition of volume-preserving loss on each one. This ensures that the tumor volume is preserved during the registration process. We have evaluated our strategy on various datasets and network architectures, demonstrating that our method successfully preserves the tumor volume while achieving comparable registration results with state-of-the-art methods. Our codes is available at: https://dddraxxx.github.io/Volume-Preserving-Registration/.

Large language models (LLMs) are increasingly envisioned as decision-support tools in clinical practice, yet safe clinical reasoning demands integrating heterogeneous knowledge bases -- trials, primary studies, regulatory documents, and cost data -- under strict accuracy constraints. Existing evaluations often rely on synthetic prompts, reduce the task to single-hop factoid queries, or conflate reasoning with open-ended generation, leaving their real-world utility unclear. To close this gap, we present MedBrowseComp, the first benchmark that systematically tests an agent's ability to reliably retrieve and synthesize multi-hop medical facts from live, domain-specific knowledge bases. MedBrowseComp contains more than 1,000 human-curated questions that mirror clinical scenarios where practitioners must reconcile fragmented or conflicting information to reach an up-to-date conclusion. Applying MedBrowseComp to frontier agentic systems reveals performance shortfalls as low as ten percent, exposing a critical gap between current LLM capabilities and the rigor demanded in clinical settings. MedBrowseComp therefore offers a clear testbed for reliable medical information seeking and sets concrete goals for future model and toolchain upgrades. You can visit our project page at: https://moreirap12.github.io/mbc-browse-app/

The segmentation of pelvic fracture fragments in CT and X-ray images is crucial for trauma diagnosis, surgical planning, and intraoperative guidance. However, accurately and efficiently delineating the bone fragments remains a significant challenge due to complex anatomy and imaging limitations. The PENGWIN challenge, organized as a MICCAI 2024 satellite event, aimed to advance automated fracture segmentation by benchmarking state-of-the-art algorithms on these complex tasks. A diverse dataset of 150 CT scans was collected from multiple clinical centers, and a large set of simulated X-ray images was generated using the DeepDRR method. Final submissions from 16 teams worldwide were evaluated under a rigorous multi-metric testing scheme. The top-performing CT algorithm achieved an average fragment-wise intersection over union (IoU) of 0.930, demonstrating satisfactory accuracy. However, in the X-ray task, the best algorithm achieved an IoU of 0.774, which is promising but not yet sufficient for intra-operative decision-making, reflecting the inherent challenges of fragment overlap in projection imaging. Beyond the quantitative evaluation, the challenge revealed methodological diversity in algorithm design. Variations in instance representation, such as primary-secondary classification versus boundary-core separation, led to differing segmentation strategies. Despite promising results, the challenge also exposed inherent uncertainties in fragment definition, particularly in cases of incomplete fractures. These findings suggest that interactive segmentation approaches, integrating human decision-making with task-relevant information, may be essential for improving model reliability and clinical applicability.

Fine-grained visual representations are essential for medical image analysis, particularly when diagnostically relevant evidence is subtle and spatially localized. Modern transformer-based medical vision encoders must therefore learn patch-level representations that are both clinically meaningful and spatially consistent. Without these properties, large vision-language models (LVLMs) operate on an ambiguous visual foundation, limiting their ability to generate clinically reliable and spatially grounded responses. However, existing training strategies for medical vision encoders rarely achieve both objectives. Image-text alignment provides clinically meaningful supervision primarily at the image level, leaving the spatial localization of diagnostic evidence weakly constrained. In contrast, self-supervised learning promotes spatial consistency but lacks the semantic supervision needed to distinguish visually similar yet clinically distinct regions. To address this gap, we present LoFi, a medical vision foundation model built on location-aware fine-grained representation learning. LoFi trains a vision encoder with a lightweight large language model under grounding and grounded captioning objectives. Because these objectives require predicting location from clinical text and vice versa, spatial consistency emerges without any explicit patch-level regularization. To enable training at scale, we construct MedG, a large-scale medical grounding dataset of 4.48M image-text-box triplets curated from 84 datasets spanning 7 modalities. Across phrase grounding, visual question answering, and region-based organ classification under perturbations, LoFi consistently outperforms general-purpose and medical vision foundation models as well as state-of-the-art LVLMs. Code is available at https://github.com/myeongkyunkang/lofi-medg.

Pre-trained audio models excel at detecting acoustic patterns in auscultation sounds but often fail to grasp their clinical significance, limiting their use and performance in diagnostic tasks. To bridge this gap, we introduce AcuLa (Audio-Clinical Understanding via Language Alignment), a lightweight post-training framework that instills semantic understanding into any audio encoder by aligning it with a medical language model, which acts as a "semantic teacher." To enable alignment at scale, we construct a large-scale dataset by leveraging off-the-shelf large language models to translate the rich, structured metadata accompanying existing audio recordings into coherent clinical reports. Our alignment strategy combines a representation-level contrastive objective with a self-supervised modeling, ensuring that the model learns clinical semantics while preserving fine-grained temporal cues. AcuLa achieves state-of-the-art results across 18 diverse cardio-respiratory tasks from 10 different datasets, improving the mean AUROC on classification benchmarks from 0.68 to 0.79 and, on the most challenging COVID-19 cough detection task, boosting the AUROC from 0.55 to 0.89. Our work demonstrates that this audio-language alignment transforms purely acoustic models into clinically-aware diagnostic tools, establishing a novel paradigm for enhancing physiological understanding in audio-based health monitoring.

Medical image segmentation faces critical challenges in semi-supervised learning scenarios due to severe annotation scarcity requiring expert radiological knowledge, significant inter-annotator variability across different viewpoints and expertise levels, and inadequate multi-scale feature integration for precise boundary delineation in complex anatomical structures. Existing semi-supervised methods demonstrate substantial performance degradation compared to fully supervised approaches, particularly in small target segmentation and boundary refinement tasks. To address these fundamental challenges, we propose SASNet (Scale-aware Adaptive Supervised Network), a dual-branch architecture that leverages both low-level and high-level feature representations through novel scale-aware adaptive reweight mechanisms. Our approach introduces three key methodological innovations, including the Scale-aware Adaptive Reweight strategy that dynamically weights pixel-wise predictions using temporal confidence accumulation, the View Variance Enhancement mechanism employing 3D Fourier domain transformations to simulate annotation variability, and segmentation-regression consistency learning through signed distance map algorithms for enhanced boundary precision. These innovations collectively address the core limitations of existing semi-supervised approaches by integrating spatial, temporal, and geometric consistency principles within a unified optimization framework. Comprehensive evaluation across LA, Pancreas-CT, and BraTS datasets demonstrates that SASNet achieves superior performance with limited labeled data, surpassing state-of-the-art semi-supervised methods while approaching fully supervised performance levels. The source code for SASNet is available at https://github.com/HUANGLIZI/SASNet.

Predictive artificial intelligence (AI) offers an opportunity to improve clinical practice and patient outcomes, but risks perpetuating biases if fairness is inadequately addressed. However, the definition of "fairness" remains unclear. We conducted a scoping review to identify and critically appraise fairness metrics for clinical predictive AI. We defined a "fairness metric" as a measure quantifying whether a model discriminates (societally) against individuals or groups defined by sensitive attributes. We searched five databases (2014-2024), screening 820 records, to include 41 studies, and extracted 62 fairness metrics. Metrics were classified by performance-dependency, model output level, and base performance metric, revealing a fragmented landscape with limited clinical validation and overreliance on threshold-dependent measures. Eighteen metrics were explicitly developed for healthcare, including only one clinical utility metric. Our findings highlight conceptual challenges in defining and quantifying fairness and identify gaps in uncertainty quantification, intersectionality, and real-world applicability. Future work should prioritise clinically meaningful metrics.

Accurate delineation of anatomical structures in volumetric CT scans is crucial for diagnosis and treatment planning. While AI has advanced automated segmentation, current approaches typically target individual structures, creating a fragmented landscape of incompatible models with varying performance and disparate evaluation protocols. Foundational segmentation models address these limitations by providing a holistic anatomical view through a single model. Yet, robust clinical deployment demands comprehensive training data, which is lacking in existing whole-body approaches, both in terms of data heterogeneity and, more importantly, anatomical coverage. In this work, rather than pursuing incremental optimizations in model architecture, we present CADS, an open-source framework that prioritizes the systematic integration, standardization, and labeling of heterogeneous data sources for whole-body CT segmentation. At its core is a large-scale dataset of 22,022 CT volumes with complete annotations for 167 anatomical structures, representing a significant advancement in both scale and coverage, with 18 times more scans than existing collections and 60% more distinct anatomical targets. Building on this diverse dataset, we develop the CADS-model using established architectures for accessible and automated full-body CT segmentation. Through comprehensive evaluation across 18 public datasets and an independent real-world hospital cohort, we demonstrate advantages over SoTA approaches. Notably, thorough testing of the model's performance in segmentation tasks from radiation oncology validates its direct utility for clinical interventions. By making our large-scale dataset, our segmentation models, and our clinical software tool publicly available, we aim to advance robust AI solutions in radiology and make comprehensive anatomical analysis accessible to clinicians and researchers alike.

Radiologists play a crucial role by translating medical images into medical reports. However, the field faces staffing shortages and increasing workloads. While automated approaches using vision-language models (VLMs) show promise as assistants, they require exceptionally high accuracy. Most current VLMs in radiology rely solely on supervised fine-tuning (SFT). Meanwhile, in the general domain, additional preference fine-tuning has become standard practice. The challenge in radiology lies in the prohibitive cost of obtaining radiologist feedback. We propose a scalable automated preference alignment technique for VLMs in radiology, focusing on chest X-ray (CXR) report generation. Our method leverages publicly available datasets with an LLM-as-a-Judge mechanism, eliminating the need for additional expert radiologist feedback. We evaluate and benchmark five direct alignment algorithms (DAAs). Our results show up to a 57.4% improvement in average GREEN scores, a LLM-based metric for evaluating CXR reports, and a 9.2% increase in an average across six metrics (domain specific and general), compared to the SFT baseline. We study reward overoptimization via length exploitation, with reports lengthening by up to 3.2x. To assess a potential alignment tax, we benchmark on six additional diverse tasks, finding no significant degradations. A reader study involving four board-certified radiologists indicates win rates of up to 0.62 over the SFT baseline, while significantly penalizing verbosity. Our analysis provides actionable insights for the development of VLMs in high-stakes fields like radiology.

Clinical case formulation organizes patient symptoms and psychosocial factors into causal models, often using the 5P framework. However, constructing such graphs from therapy transcripts is time consuming and varies across clinicians. We present InsightFlow, an LLM based approach that automatically generates 5P aligned causal graphs from patient-therapist dialogues. Using 46 psychotherapy intake transcripts annotated by clinical experts, we evaluate LLM generated graphs against human formulations using structural (NetSimile), semantic (embedding similarity), and expert rated clinical criteria. The generated graphs show structural similarity comparable to inter annotator agreement and high semantic alignment with human graphs. Expert evaluations rate the outputs as moderately complete, consistent, and clinically useful. While LLM graphs tend to form more interconnected structures compared to the chain like patterns of human graphs, overall complexity and content coverage are similar. These results suggest that LLMs can produce clinically meaningful case formulation graphs within the natural variability of expert practice. InsightFlow highlights the potential of automated causal modeling to augment clinical workflows, with future work needed to improve temporal reasoning and reduce redundancy.

Across medical specialties, clinical practice is anchored in evidence-based guidelines that codify best studied diagnostic and treatment pathways. These pathways routinely fall short for the long tail of real-world care not covered by guidelines. Most medical large language models (LLMs), however, are trained to encode common, guideline-focused medical knowledge in their parameters. Current evaluations test models primarily on recalling and reasoning with this memorized content, often in multiple-choice settings. Given the fundamental importance of evidence-based reasoning in medicine, it is neither feasible nor reliable to depend on memorization in practice. To address this gap, we introduce OGCaReBench, a free-form retrieval-focused benchmark aimed at evaluating LLMs at answering clinical questions that require going beyond typical guidelines. Extracted from published medical case reports and validated by medical experts, OGCaReBench contains long-form clinical questions requiring free-text answers, providing a systematic framework for assessing open-ended medical reasoning in rare, case-based scenarios. Our experiments reveal that even the best-performing baseline (GPT-5.2) correctly answers only 56% of our benchmark with specialized models only reaching 42%. Augmenting models with retrieved medical articles improves this performance to up to 82% (using GPT-5.2) highlighting the importance of evidence-grounding for real-world medical reasoning tasks. This work thus establishes a foundation for benchmarking and advancing both general-purpose and medical LLMs to produce reliable answers in challenging clinical contexts.

Multimodal large language models (MLLMs) have advanced clinical tasks for common conditions, but their performance on rare diseases remains largely untested. In rare-disease scenarios, clinicians often lack prior clinical knowledge, forcing them to rely strictly on case-level evidence for clinical judgments. Existing benchmarks predominantly evaluate common-condition, single-image settings, leaving multimodal and multi-image evidence integration under rare-disease data scarcity systematically unevaluated. We introduce MMRareBench, to our knowledge the first rare-disease benchmark jointly evaluating multimodal and multi-image clinical capability across four workflow-aligned tracks: diagnosis, treatment planning, cross-image evidence alignment, and examination suggestion. The benchmark comprises 1,756 question-answer pairs with 7,958 associated medical images curated from PMC case reports, with Orphanet-anchored ontology alignment, track-specific leakage control, evidence-grounded annotations, and a two-level evaluation protocol. A systematic evaluation of 23 MLLMs reveals fragmented capability profiles and universally low treatment-planning performance, with medical-domain models trailing general-purpose MLLMs substantially on multi-image tracks despite competitive diagnostic scores. These patterns are consistent with a capacity dilution effect: medical fine-tuning can narrow the diagnostic gap but may erode the compositional multi-image capability that rare-disease evidence integration demands.

Unstructured clinical notes contain essential patient information but are challenging for physicians to search and interpret efficiently. Although large language models (LLMs) have shown promise in question answering (QA), most existing systems lack transparency, usability, and alignment with clinical workflows. This work introduces an interactive QA system that enables physicians to query clinical notes via text or voice and receive extractive answers highlighted directly in the note for traceability. The system was built using OpenAI models with zero-shot prompting and evaluated across multiple metrics, including exact string match, word overlap, SentenceTransformer similarity, and BERTScore. Results show that while exact match scores ranged from 47 to 62 percent, semantic similarity scores exceeded 87 percent, indicating strong contextual alignment even when wording varied. To assess usability, the system was also evaluated using simulated clinical personas. Seven diverse physician and nurse personas interacted with the system across scenario-based tasks and provided structured feedback. The evaluations highlighted strengths in intuitive design and answer accessibility, alongside opportunities for enhancing explanation clarity.

Reliable pelvic bone segmentation (PBS) from CT is essential for robot-assisted pelvic trauma surgery, yet deploying a source-trained model to a new hospital suffers from severe performance degradation due to cross-center domain shifts. While test-time adaptation (TTA) enables online model adaptation without accessing source data, existing methods show limited effectiveness for PBS, facing challenges including boundary degradation, anatomical inconsistency under domain shifts, and voxel-level class imbalance. To address these challenges, we propose a novel closed-loop dynamic Reliability-Guided TTA framework (ReGA) for PBS. Specifically, we introduce a pseudo-label reliability criterion termed Segmentation Inference Consistency Evaluation (SICE), which jointly measures region overlap and boundary deviation via dropout-based ensemble predictions. Based on SICE, a trust-weighted refinement module adaptively updates features to mitigate boundary errors in pseudo-labels. Furthermore, a confidence-weighted region-level contrastive learning strategy is proposed to enforce anatomical consistency. Finally, ReGA follows the teacher-student (TS) scheme to alleviate voxel-level class imbalance. Experiments on three heterogeneous 3D pelvic CT datasets demonstrate that ReGA consistently outperforms state-of-the-art TTA methods, enabling effective adaptation of the source-trained PBS model to unseen clinical domains. The code is available at https://github.com/Ren-ling/ReGA.

Predicting cancer treatment outcomes requires models that are both accurate and interpretable, particularly in the presence of heterogeneous clinical data. While large language models (LLMs) have shown strong performance in biomedical NLP, they often lack structured reasoning capabilities critical for high-stakes decision support. We present a unified, multi-task learning framework that aligns autoregressive LLMs with clinical reasoning for outcome prediction on the MSK-CHORD dataset. Our models are trained to jointly perform binary survival classification, continuous survival time regression, and natural language rationale generation. We evaluate three alignment strategies: (1) standard supervised fine-tuning (SFT), (2) SFT with Chain-of-Thought (CoT) prompting to elicit step-by-step reasoning, and (3) Group Relative Policy Optimization (GRPO), a reinforcement learning method that aligns model outputs to expert-derived reasoning trajectories. Experiments with LLaMa3-8B and Med42-8B backbones demonstrate that CoT prompting improves F1 by +6.0 and reduces MAE by 12%, while GRPO achieves state-of-the-art interpretability and predictive performance across BLEU, ROUGE, and BERTScore. We further show that existing biomedical LLMs often fail to produce valid reasoning traces due to architectural constraints. Our findings underscore the importance of reasoning-aware alignment in multi-task clinical modeling and set a new benchmark for interpretable, trustworthy LLMs in precision oncology.

With the proliferation of Large Language Models (LLMs) in diverse domains, there is a particular need for unified evaluation standards in clinical medical scenarios, where models need to be examined very thoroughly. We present CliMedBench, a comprehensive benchmark with 14 expert-guided core clinical scenarios specifically designed to assess the medical ability of LLMs across 7 pivot dimensions. It comprises 33,735 questions derived from real-world medical reports of top-tier tertiary hospitals and authentic examination exercises. The reliability of this benchmark has been confirmed in several ways. Subsequent experiments with existing LLMs have led to the following findings: (i) Chinese medical LLMs underperform on this benchmark, especially where medical reasoning and factual consistency are vital, underscoring the need for advances in clinical knowledge and diagnostic accuracy. (ii) Several general-domain LLMs demonstrate substantial potential in medical clinics, while the limited input capacity of many medical LLMs hinders their practical use. These findings reveal both the strengths and limitations of LLMs in clinical scenarios and offer critical insights for medical research.

Unsupervised domain adaptation for medical image segmentation remains a significant challenge due to substantial domain shifts across imaging modalities, such as CT and MRI. While recent vision-language representation learning methods have shown promise, their potential in UDA segmentation tasks remains underexplored. To address this gap, we propose TCSA-UDA, a Text-driven Cross-Semantic Alignment framework that leverages domain-invariant textual class descriptions to guide visual representation learning. Our approach introduces a vision-language covariance cosine loss to directly align image encoder features with inter-class textual semantic relations, encouraging semantically meaningful and modality-invariant feature representations. Additionally, we incorporate a prototype alignment module that aligns class-wise pixel-level feature distributions across domains using high-level semantic prototypes. This mitigates residual category-level discrepancies and enhances cross-modal consistency. Extensive experiments on challenging cross-modality cardiac, abdominal, and brain tumor segmentation benchmarks demonstrate that our TCSA-UDA framework significantly reduces domain shift and consistently outperforms state-of-the-art UDA methods, establishing a new paradigm for integrating language-driven semantics into domain-adaptive medical image analysis.

Although the preservation of shape continuity and physiological anatomy is a natural assumption in the segmentation of medical images, it is often neglected by deep learning methods that mostly aim for the statistical modeling of input data as pixels rather than interconnected structures. In biological structures, however, organs are not separate entities; for example, in reality, a severed vessel is an indication of an underlying problem, but traditional segmentation models are not designed to strictly enforce the continuity of anatomy, potentially leading to inaccurate medical diagnoses. To address this issue, we propose a graph-based approach that enforces the continuity and connectivity of anatomical topology in medical images. Our method encodes the continuity of shapes as a graph constraint, ensuring that the network's predictions maintain this continuity. We evaluate our method on two public benchmarks on retinal vessel segmentation, showing significant improvements in connectivity metrics compared to traditional methods while getting better or on-par performance on segmentation metrics.

The detailed images produced by Magnetic Resonance Imaging (MRI) provide life-critical information for the diagnosis and treatment of prostate cancer. To provide standardized acquisition, interpretation and usage of the complex MRI images, the PI-RADS v2 guideline was proposed. An automated segmentation following the guideline facilitates consistent and precise lesion detection, staging and treatment. The guideline recommends a division of the prostate into four zones, PZ (peripheral zone), TZ (transition zone), DPU (distal prostatic urethra) and AFS (anterior fibromuscular stroma). Not every zone shares a boundary with the others and is present in every slice. Further, the representations captured by a single model might not suffice for all zones. This motivated us to design a dual-branch convolutional neural network (CNN), where each branch captures the representations of the connected zones separately. Further, the representations from different branches act complementary to each other at the second stage of training, where they are fine-tuned through an unsupervised loss. The loss penalises the difference in predictions from the two branches for the same class. We also incorporate multi-task learning in our framework to further improve the segmentation accuracy. The proposed approach improves the segmentation accuracy of the baseline (mean absolute symmetric distance) by 7.56%, 11.00%, 58.43% and 19.67% for PZ, TZ, DPU and AFS zones respectively.

Vision Language Models (VLMs) are increasingly used for tasks like medical report generation and visual question answering. However, fluent diagnostic text does not guarantee safe visual understanding. In clinical practice, interpretation begins with pre-diagnostic sanity checks: verifying that the input is valid to read (correct modality and anatomy, plausible viewpoint and orientation, and no obvious integrity violations). Existing benchmarks largely assume this step is solved, and therefore miss a critical failure mode: a model can produce plausible narratives even when the input is inconsistent or invalid. We introduce MedObvious, a 1,880-task benchmark that isolates input validation as a set-level consistency capability over small multi-panel image sets: the model must identify whether any panel violates expected coherence. MedObvious spans five progressive tiers, from basic orientation/modality mismatches to clinically motivated anatomy/viewpoint verification and triage-style cues, and includes five evaluation formats to test robustness across interfaces. Evaluating 17 different VLMs, we find that sanity checking remains unreliable: several models hallucinate anomalies on normal (negative-control) inputs, performance degrades when scaling to larger image sets, and measured accuracy varies substantially between multiple-choice and open-ended settings. These results show that pre-diagnostic verification remains unsolved for medical VLMs and should be treated as a distinct, safety-critical capability before deployment.

In computer vision, reference datasets have been highly successful in promoting algorithmic development in stereo reconstruction. Surgical scenes gives rise to specific problems, including the lack of clear corner features, highly specular surfaces and the presence of blood and smoke. Publicly available datasets have been produced using CT and either phantom images or biological tissue samples covering a relatively small region of the endoscope field-of-view. We present a stereo-endoscopic reconstruction validation dataset based on CT (SERV-CT). Two {\it ex vivo} small porcine full torso cadavers were placed within the view of the endoscope with both the endoscope and target anatomy visible in the CT scan. Orientation of the endoscope was manually aligned to the stereoscopic view. Reference disparities and occlusions were calculated for 8 stereo pairs from each sample. For the second sample an RGB surface was acquired to aid alignment of smooth, featureless surfaces. Repeated manual alignments showed an RMS disparity accuracy of ~2 pixels and a depth accuracy of ~2mm. The reference dataset includes endoscope image pairs with corresponding calibration, disparities, depths and occlusions covering the majority of the endoscopic image and a range of tissue types. Smooth specular surfaces and images with significant variation of depth are included. We assessed the performance of various stereo algorithms from online available repositories. There is a significant variation between algorithms, highlighting some of the challenges of surgical endoscopic images. The SERV-CT dataset provides an easy to use stereoscopic validation for surgical applications with smooth reference disparities and depths with coverage over the majority of the endoscopic images. This complements existing resources well and we hope will aid the development of surgical endoscopic anatomical reconstruction algorithms.

The deployment of Large Language Models (LLMs) in high-stakes clinical settings demands rigorous and reliable evaluation. However, existing medical benchmarks remain static, suffering from two critical limitations: (1) data contamination, where test sets inadvertently leak into training corpora, leading to inflated performance estimates; and (2) temporal misalignment, failing to capture the rapid evolution of medical knowledge. Furthermore, current evaluation metrics for open-ended clinical reasoning often rely on either shallow lexical overlap (e.g., ROUGE) or subjective LLM-as-a-Judge scoring, both inadequate for verifying clinical correctness. To bridge these gaps, we introduce LiveMedBench, a continuously updated, contamination-free, and rubric-based benchmark that weekly harvests real-world clinical cases from online medical communities, ensuring strict temporal separation from model training data. We propose a Multi-Agent Clinical Curation Framework that filters raw data noise and validates clinical integrity against evidence-based medical principles. For evaluation, we develop an Automated Rubric-based Evaluation Framework that decomposes physician responses into granular, case-specific criteria, achieving substantially stronger alignment with expert physicians than LLM-as-a-Judge. To date, LiveMedBench comprises 2,756 real-world cases spanning 38 medical specialties and multiple languages, paired with 16,702 unique evaluation criteria. Extensive evaluation of 38 LLMs reveals that even the best-performing model achieves only 39.2%, and 84% of models exhibit performance degradation on post-cutoff cases, confirming pervasive data contamination risks. Error analysis further identifies contextual application-not factual knowledge-as the dominant bottleneck, with 35-48% of failures stemming from the inability to tailor medical knowledge to patient-specific constraints.

We participated in the SynthRAD2025 challenge (Tasks 1 and 2) with a unified pipeline for synthetic CT (sCT) generation from MRI and CBCT, implemented using the KonfAI framework. Our model is a 2.5D U-Net++ with a ResNet-34 encoder, trained jointly across anatomical regions and fine-tuned per region. The loss function combined pixel-wise L1 loss with IMPACT-Synth, a perceptual loss derived from SAM and TotalSegmentator to enhance structural fidelity. Training was performed using AdamW (initial learning rate = 0.001, halved every 25k steps) on patch-based, normalized, body-masked inputs (320x320 for MRI, 256x256 for CBCT), with random flipping as the only augmentation. No post-processing was applied. Final predictions leveraged test-time augmentation and five-fold ensembling. The best model was selected based on validation MAE. Two registration strategies were evaluated: (i) Elastix with mutual information, consistent with the challenge pipeline, and (ii) IMPACT, a feature-based similarity metric leveraging pretrained segmentation networks. On the local test sets, IMPACT-based registration achieved more accurate and anatomically consistent alignments than mutual-information-based registration, resulting in improved sCT synthesis with lower MAE and more realistic anatomical structures. On the public validation set, however, models trained with Elastix-aligned data achieved higher scores, reflecting a registration bias favoring alignment strategies consistent with the evaluation pipeline. This highlights how registration errors can propagate into supervised learning, influencing both training and evaluation, and potentially inflating performance metrics at the expense of anatomical fidelity. By promoting anatomically consistent alignment, IMPACT helps mitigate this bias and supports the development of more robust and generalizable sCT synthesis models.

Current medical language models, adapted from large language models (LLMs), typically predict ICD code-based diagnosis from electronic health records (EHRs) because these labels are readily available. However, ICD codes do not capture the nuanced, context-rich reasoning clinicians use for diagnosis. Clinicians synthesize diverse patient data and reference clinical practice guidelines (CPGs) to make evidence-based decisions. This misalignment limits the clinical utility of existing models. We introduce GARMLE-G, a Generation-Augmented Retrieval framework that grounds medical language model outputs in authoritative CPGs. Unlike conventional Retrieval-Augmented Generation based approaches, GARMLE-G enables hallucination-free outputs by directly retrieving authoritative guideline content without relying on model-generated text. It (1) integrates LLM predictions with EHR data to create semantically rich queries, (2) retrieves relevant CPG knowledge snippets via embedding similarity, and (3) fuses guideline content with model output to generate clinically aligned recommendations. A prototype system for hypertension diagnosis was developed and evaluated on multiple metrics, demonstrating superior retrieval precision, semantic relevance, and clinical guideline adherence compared to RAG-based baselines, while maintaining a lightweight architecture suitable for localized healthcare deployment. This work provides a scalable, low-cost, and hallucination-free method for grounding medical language models in evidence-based clinical practice, with strong potential for broader clinical deployment.

The PI-CAI (Prostate Imaging: Cancer AI) challenge led to expert-level diagnostic algorithms for clinically significant prostate cancer detection. The algorithms receive biparametric MRI scans as input, which consist of T2-weighted and diffusion-weighted scans. These scans can be misaligned due to multiple factors in the scanning process. Image registration can alleviate this issue by predicting the deformation between the sequences. We investigate the effect of image registration on the diagnostic performance of AI-based prostate cancer diagnosis. First, the image registration algorithm, developed in MeVisLab, is analyzed using a dataset with paired lesion annotations. Second, the effect on diagnosis is evaluated by comparing case-level cancer diagnosis performance between using the original dataset, rigidly aligned diffusion-weighted scans, or deformably aligned diffusion-weighted scans. Rigid registration showed no improvement. Deformable registration demonstrated a substantial improvement in lesion overlap (+10% median Dice score) and a positive yet non-significant improvement in diagnostic performance (+0.3% AUROC, p=0.18). Our investigation shows that a substantial improvement in lesion alignment does not directly lead to a significant improvement in diagnostic performance. Qualitative analysis indicated that jointly developing image registration methods and diagnostic AI algorithms could enhance diagnostic accuracy and patient outcomes.

Self-supervised learning in vision-language processing exploits semantic alignment between imaging and text modalities. Prior work in biomedical VLP has mostly relied on the alignment of single image and report pairs even though clinical notes commonly refer to prior images. This does not only introduce poor alignment between the modalities but also a missed opportunity to exploit rich self-supervision through existing temporal content in the data. In this work, we explicitly account for prior images and reports when available during both training and fine-tuning. Our approach, named BioViL-T, uses a CNN-Transformer hybrid multi-image encoder trained jointly with a text model. It is designed to be versatile to arising challenges such as pose variations and missing input images across time. The resulting model excels on downstream tasks both in single- and multi-image setups, achieving state-of-the-art performance on (I) progression classification, (II) phrase grounding, and (III) report generation, whilst offering consistent improvements on disease classification and sentence-similarity tasks. We release a novel multi-modal temporal benchmark dataset, MS-CXR-T, to quantify the quality of vision-language representations in terms of temporal semantics. Our experimental results show the advantages of incorporating prior images and reports to make most use of the data.

The integration of Computer-Assisted Diagnosis (CAD) with Large Language Models (LLMs) holds great potential in clinical applications, specifically in the roles of virtual family doctors and clinic assistants. However, current works in this field are plagued by limitations, specifically a restricted scope of applicable image domains and the provision of unreliable medical advice. This restricts their overall processing capabilities. Furthermore, the mismatch in writing style between LLMs and radiologists undermines their practical usefulness. To tackle these challenges, we introduce ChatCAD+, which is designed to be universal and reliable. It is capable of handling medical images from diverse domains and leveraging up-to-date information from reputable medical websites to provide reliable medical advice. Additionally, it incorporates a template retrieval system that improves report generation performance via exemplar reports. This approach ensures greater consistency with the expertise of human professionals. The source code is available at https://github.com/zhaozh10/ChatCAD.

The advancement of natural language processing (NLP) systems in healthcare hinges on language model ability to interpret the intricate information contained within clinical notes. This process often requires integrating information from various time points in a patient's medical history. However, most earlier clinical language models were pretrained with a context length limited to roughly one clinical document. In this study, We introduce ClinicalMamba, a specialized version of the Mamba language model, pretrained on a vast corpus of longitudinal clinical notes to address the unique linguistic characteristics and information processing needs of the medical domain. ClinicalMamba, with 130 million and 2.8 billion parameters, demonstrates a superior performance in modeling clinical language across extended text lengths compared to Mamba and clinical Llama. With few-shot learning, ClinicalMamba achieves notable benchmarks in speed and accuracy, outperforming existing clinical language models and general domain large models like GPT-4 in longitudinal clinical notes information extraction tasks.

In the radiation therapy of nasopharyngeal carcinoma (NPC), clinicians typically delineate the gross tumor volume (GTV) using non-contrast planning computed tomography to ensure accurate radiation dose delivery. However, the low contrast between tumors and adjacent normal tissues necessitates that radiation oncologists manually delineate the tumors, often relying on diagnostic MRI for guidance. % In this study, we propose a novel approach to directly segment NPC gross tumors on non-contrast planning CT images, circumventing potential registration errors when aligning MRI or MRI-derived tumor masks to planning CT. To address the low contrast issues between tumors and adjacent normal structures in planning CT, we introduce a 3D Semantic Asymmetry Tumor segmentation (SATs) method. Specifically, we posit that a healthy nasopharyngeal region is characteristically bilaterally symmetric, whereas the emergence of nasopharyngeal carcinoma disrupts this symmetry. Then, we propose a Siamese contrastive learning segmentation framework that minimizes the voxel-wise distance between original and flipped areas without tumor and encourages a larger distance between original and flipped areas with tumor. Thus, our approach enhances the sensitivity of features to semantic asymmetries. % Extensive experiments demonstrate that the proposed SATs achieves the leading NPC GTV segmentation performance in both internal and external testing, e.g., with at least 2\% absolute Dice score improvement and 12\% average distance error reduction when compared to other state-of-the-art methods in the external testing.

Pediatric medical imaging presents unique challenges due to significant anatomical and developmental differences compared to adults. Direct application of segmentation models trained on adult data often yields suboptimal performance, particularly for small or rapidly evolving structures. To address these challenges, several strategies leveraging the nnU-Net framework have been proposed, differing along four key axes: (i) the fingerprint dataset (adult, pediatric, or a combination thereof) from which the Training Plan -including the network architecture-is derived; (ii) the Learning Set (adult, pediatric, or mixed), (iii) Data Augmentation parameters, and (iv) the Transfer learning method (finetuning versus continual learning). In this work, we introduce PSAT (Pediatric Segmentation Approaches via Adult Augmentations and Transfer learning), a systematic study that investigates the impact of these axes on segmentation performance. We benchmark the derived strategies on two pediatric CT datasets and compare them with state-of-theart methods, including a commercial radiotherapy solution. PSAT highlights key pitfalls and provides actionable insights for improving pediatric segmentation. Our experiments reveal that a training plan based on an adult fingerprint dataset is misaligned with pediatric anatomy-resulting in significant performance degradation, especially when segmenting fine structures-and that continual learning strategies mitigate institutional shifts, thus enhancing generalization across diverse pediatric datasets. The code is available at https://github.com/ICANS-Strasbourg/PSAT.

Longitudinal clinical notes contain rich evidence of how patients evolve over time, but converting this signal into training supervision for clinical prediction remains challenging. We extend Foresight Learning to clinical prediction by converting time-ordered MIMIC-III notes into examples consisting of past patient context, a natural-language question about a possible future event, and a label resolved from later documentation. This process yields 6,900 prediction examples from 702 admissions across medications, procedures, organ support, microbiology, and mortality. A small LoRA adapter trained on these examples improves over the prompted base model, reducing expected calibration error from 0.1269 to 0.0398 and Brier score from 0.199 to 0.145, while slightly outperforming GPT-5 point estimates on held-out questions. The approach enables reusable clinical prediction supervision from longitudinal notes without hand-engineered structured features or endpoint-specific classifiers.

Multi-modal interpretation of biomedical images opens up novel opportunities in biomedical image analysis. Conventional AI approaches typically rely on disjointed training, i.e., Large Language Models (LLMs) for clinical text generation and segmentation models for target extraction, which results in inflexible real-world deployment and a failure to leverage holistic biomedical information. To this end, we introduce UniBiomed, the first universal foundation model for grounded biomedical image interpretation. UniBiomed is based on a novel integration of Multi-modal Large Language Model (MLLM) and Segment Anything Model (SAM), which effectively unifies the generation of clinical texts and the segmentation of corresponding biomedical objects for grounded interpretation. In this way, UniBiomed is capable of tackling a wide range of biomedical tasks across ten diverse biomedical imaging modalities. To develop UniBiomed, we curate a large-scale dataset comprising over 27 million triplets of images, annotations, and text descriptions across ten imaging modalities. Extensive validation on 84 internal and external datasets demonstrated that UniBiomed achieves state-of-the-art performance in segmentation, disease recognition, region-aware diagnosis, visual question answering, and report generation. Moreover, unlike previous models that rely on clinical experts to pre-diagnose images and manually craft precise textual or visual prompts, UniBiomed can provide automated and end-to-end grounded interpretation for biomedical image analysis. This represents a novel paradigm shift in clinical workflows, which will significantly improve diagnostic efficiency. In summary, UniBiomed represents a novel breakthrough in biomedical AI, unlocking powerful grounded interpretation capabilities for more accurate and efficient biomedical image analysis.

Image segmentation plays an essential role in medicine for both diagnostic and interventional tasks. Segmentation approaches are either manual, semi-automated or fully-automated. Manual segmentation offers full control over the quality of the results, but is tedious, time consuming and prone to operator bias. Fully automated methods require no human effort, but often deliver sub-optimal results without providing users with the means to make corrections. Semi-automated approaches keep users in control of the results by providing means for interaction, but the main challenge is to offer a good trade-off between precision and required interaction. In this paper we present a deep learning (DL) based semi-automated segmentation approach that aims to be a "smart" interactive tool for region of interest delineation in medical images. We demonstrate its use for segmenting multiple organs on computed tomography (CT) of the abdomen. Our approach solves some of the most pressing clinical challenges: (i) it requires only one to a few user clicks to deliver excellent 2D segmentations in a fast and reliable fashion; (ii) it can generalize to previously unseen structures and "corner cases"; (iii) it delivers results that can be corrected quickly in a smart and intuitive way up to an arbitrary degree of precision chosen by the user and (iv) ensures high accuracy. We present our approach and compare it to other techniques and previous work to show the advantages brought by our method.

We introduce Metric-Fair Prompting, a fairness-aware prompting framework that guides large language models (LLMs) to make decisions under metric-fairness constraints. In the application of multiple-choice medical question answering, each {(question, option)} pair is treated as a binary instance with label +1 (correct) or -1 (incorrect). To promote {individual fairness}~--~treating similar instances similarly~--~we compute question similarity using NLP embeddings and solve items in joint pairs of similar questions rather than in isolation. The prompt enforces a global decision protocol: extract decisive clinical features, map each \((question, option)\) to a score f(x) that acts as confidence, and impose a Lipschitz-style constraint so that similar inputs receive similar scores and, hence, consistent outputs. Evaluated on the {MedQA (US)} benchmark, Metric-Fair Prompting is shown to improve performance over standard single-item prompting, demonstrating that fairness-guided, confidence-oriented reasoning can enhance LLM accuracy on high-stakes clinical multiple-choice questions.

LLMs for clinical decision support often fail under small but clinically meaningful input shifts such as masking a symptom or negating a finding, despite high performance on static benchmarks. These reasoning failures frequently go undetected by standard NLP metrics, which are insensitive to latent representation shifts that drive diagnosis instability. We propose a geometry-aware evaluation framework, LAPD (Latent Agentic Perturbation Diagnostics), which systematically probes the latent robustness of clinical LLMs under structured adversarial edits. Within this framework, we introduce Latent Diagnosis Flip Rate (LDFR), a model-agnostic diagnostic signal that captures representational instability when embeddings cross decision boundaries in PCA-reduced latent space. Clinical notes are generated using a structured prompting pipeline grounded in diagnostic reasoning, then perturbed along four axes: masking, negation, synonym replacement, and numeric variation to simulate common ambiguities and omissions. We compute LDFR across both foundation and clinical LLMs, finding that latent fragility emerges even under minimal surface-level changes. Finally, we validate our findings on 90 real clinical notes from the DiReCT benchmark (MIMIC-IV), confirming the generalizability of LDFR beyond synthetic settings. Our results reveal a persistent gap between surface robustness and semantic stability, underscoring the importance of geometry-aware auditing in safety-critical clinical AI.

The advancement of Large Vision-Language Models (LVLMs) has propelled their application in the medical field. However, Medical LVLMs (Med-LVLMs) encounter factuality challenges due to modality misalignment, where the models prioritize textual knowledge over visual input, leading to hallucinations that contradict information in medical images. Previous attempts to enhance modality alignment in Med-LVLMs through preference optimization have inadequately mitigated clinical relevance in preference data, making these samples easily distinguishable and reducing alignment effectiveness. To address this challenge, we propose MMedPO, a novel multimodal medical preference optimization approach that considers the clinical relevance of preference samples to enhance Med-LVLM alignment. MMedPO curates multimodal preference data by introducing two types of dispreference: (1) plausible hallucinations injected through target Med-LVLMs or GPT-4o to produce medically inaccurate responses, and (2) lesion region neglect achieved through local lesion-noising, disrupting visual understanding of critical areas. We then calculate clinical relevance for each sample based on scores from multiple Med-LLMs and visual tools, and integrate these scores into the preference optimization process as weights, enabling effective alignment. Our experiments demonstrate that MMedPO significantly enhances factual accuracy in Med-LVLMs, achieving substantial improvements over existing preference optimization methods by averaging 14.2% and 51.7% across the Med-VQA and report generation tasks. Our code are available in https://github.com/aiming-lab/MMedPO.

Post-training alignment optimizes language models to match human preference signals, but this objective is not equivalent to modeling observed human behavior. We compare 120 base-aligned model pairs on more than 10,000 real human decisions in multi-round strategic games - bargaining, persuasion, negotiation, and repeated matrix games. In these settings, base models outperform their aligned counterparts in predicting human choices by nearly 10:1, robustly across model families, prompt formulations, and game configurations. This pattern reverses, however, in settings where human behavior is more likely to follow normative predictions: aligned models dominate on one-shot textbook games across all 12 types tested and on non-strategic lottery choices - and even within the multi-round games themselves, at round one, before interaction history develops. This boundary-condition pattern suggests that alignment induces a normative bias: it improves prediction when human behavior is relatively well captured by normative solutions, but hurts prediction in multi-round strategic settings, where behavior is shaped by descriptive dynamics such as reciprocity, retaliation, and history-dependent adaptation. These results reveal a fundamental trade-off between optimizing models for human use and using them as proxies for human behavior.

Medical image segmentation has immense clinical applicability but remains a challenge despite advancements in deep learning. The Segment Anything Model (SAM) exhibits potential in this field, yet the requirement for expertise intervention and the domain gap between natural and medical images poses significant obstacles. This paper introduces a novel training-free evidential prompt generation method named EviPrompt to overcome these issues. The proposed method, built on the inherent similarities within medical images, requires only a single reference image-annotation pair, making it a training-free solution that significantly reduces the need for extensive labeling and computational resources. First, to automatically generate prompts for SAM in medical images, we introduce an evidential method based on uncertainty estimation without the interaction of clinical experts. Then, we incorporate the human prior into the prompts, which is vital for alleviating the domain gap between natural and medical images and enhancing the applicability and usefulness of SAM in medical scenarios. EviPrompt represents an efficient and robust approach to medical image segmentation, with evaluations across a broad range of tasks and modalities confirming its efficacy.

Clinical information extraction, which involves structuring clinical concepts from unstructured medical text, remains a challenging problem that could benefit from the inclusion of tabular background information available in electronic health records. Existing open-source datasets lack explicit links between structured features and clinical concepts in the text, motivating the need for a new research dataset. We introduce SimSUM, a benchmark dataset of 10,000 simulated patient records that link unstructured clinical notes with structured background variables. Each record simulates a patient encounter in the domain of respiratory diseases and includes tabular data (e.g., symptoms, diagnoses, underlying conditions) generated from a Bayesian network whose structure and parameters are defined by domain experts. A large language model (GPT-4o) is prompted to generate a clinical note describing the encounter, including symptoms and relevant context. These notes are annotated with span-level symptom mentions. We conduct an expert evaluation to assess note quality and run baseline predictive models on both the tabular and textual data. The SimSUM dataset is primarily designed to support research on clinical information extraction in the presence of tabular background variables, which can be linked through domain knowledge to concepts of interest to be extracted from the text -- namely, symptoms in the case of SimSUM. Secondary uses include research on the automation of clinical reasoning over both tabular data and text, causal effect estimation in the presence of tabular and/or textual confounders, and multi-modal synthetic data generation. SimSUM is not intended for training clinical decision support systems or production-grade models, but rather to facilitate reproducible research in a simplified and controlled setting.

Objective: Using natural language processing (NLP) to find sentences that state treatment plans in a clinical note, would automate plan extraction and would further enable their use in tools that help providers and care managers. However, as in the most NLP tasks on clinical text, creating gold standard to train and test NLP models is tedious and expensive. Fortuitously, sometimes but not always clinical notes contain sections with a heading that identifies the section as a plan. Leveraging contents of such labeled sections as a noisy training data, we assessed accuracy of NLP models trained with the data. Methods: We used common variations of plan headings and rule-based heuristics to find plan sections with headings in clinical notes, and we extracted sentences from them and formed a noisy training data of plan sentences. We trained Support Vector Machine (SVM) and Convolutional Neural Network (CNN) models with the data. We measured accuracy of the trained models on the noisy dataset using ten-fold cross validation and separately on a set-aside manually annotated dataset. Results: About 13% of 117,730 clinical notes contained treatment plans sections with recognizable headings in the 1001 longitudinal patient records that were obtained from Cleveland Clinic under an IRB approval. We were able to extract and create a noisy training data of 13,492 plan sentences from the clinical notes. CNN achieved best F measures, 0.91 and 0.97 in the cross-validation and set-aside evaluation experiments respectively. SVM slightly underperformed with F measures of 0.89 and 0.96 in the same experiments. Conclusion: Our study showed that the training supervised learning models using noisy plan sentences was effective in identifying them in all clinical notes. More broadly, sections with informal headings in clinical notes can be a good source for generating effective training data.

Surgical resection remains the only potentially curative treatment for pancreatic ductal adenocarcinoma (PDAC), and eligibility depends on accurate assessment of vascular invasion (VI), i.e., tumor extension into adjacent critical vessels. Despite its importance for preoperative staging and surgical planning, computational VI assessment remains underexplored. Two major challenges are the lack of public datasets and the diagnostic ambiguity at the tumor-vessel interface, which leads to substantial inter-rater variability even among expert radiologists. To address these limitations, we introduce the CURVAS-PDACVI Dataset and Challenge, an open benchmark for uncertainty-aware AI in PDAC staging based on a densely annotated dataset with five independent expert annotations per scan. We also propose a multi-metric evaluation framework that extends beyond spatial overlap to include probabilistic calibration and VI assessment. Evaluation of six state-of-the-art methods shows that strong global volumetric overlap does not necessarily translate into reliable performance at clinically critical tumor-vessel interfaces. In particular, methods optimized for binary segmentation perform competitively on average overlap metrics, but often degrade in high-complexity cases with low expert consensus, either collapsing in volume or overextending at uncertain boundaries. In contrast, methods that model inter-rater disagreement produce better calibrated probabilistic maps and show greater robustness in these ambiguous cases. The benchmark highlights the limitations of volumetric accuracy as a proxy for localized surgical utility, motivating uncertainty-aware probabilistic models for preoperative decision-making.

BalancedBio is a theoretically grounded framework for parameter-efficient biomedical reasoning, addressing multi-capability integration in domain-specific AI alignment. It establishes the Biomedical Multi-Capability Convergence Theorem, proving orthogonal gradient spaces are essential to prevent capability interference for safe deployment. Key innovations include: (1) Medical Knowledge Grounded Synthetic Generation (MKGSG), extending Source2Synth with clinical workflow constraints and medical ontology validation for factual accuracy and safety; and (2) Capability Aware Group Relative Policy Optimization, deriving optimal hybrid reward weighting to maintain orthogonality in RL, using a reward model with rule-based and model-based scores adapted to biomedical tasks. Mathematical analysis proves Pareto-optimal convergence, preserving performance across capabilities. It achieves state-of-the-art results in its parameter class: domain expertise (80.95% BIOMED-MMLU, +15.32% over baseline), reasoning (61.94%, +7.75%), instruction following (67.95%, +6.44%), and integration (86.7%, +18.5%). Theoretical safety guarantees include bounds on capability preservation and clinical accuracy. Real-world deployment yields 78% cost reduction, 23% improved diagnostic accuracy, and 89% clinician acceptance. This work provides a principled methodology for biomedical AI alignment, enabling efficient reasoning with essential safety and reliability, with the 0.5B model version to be released.

Clinical dialogue represents a complex duality requiring both the empathetic fluency of natural conversation and the rigorous precision of evidence-based medicine. While Large Language Models possess unprecedented linguistic capabilities, their architectural reliance on reactive and stateless processing often favors probabilistic plausibility over factual veracity. This structural limitation has catalyzed a paradigm shift in medical AI from generative text prediction to agentic autonomy, where the model functions as a central reasoning engine capable of deliberate planning and persistent memory. Moving beyond existing reviews that primarily catalog downstream applications, this survey provides a first-principles analysis of the cognitive architecture underpinning this shift. We introduce a novel taxonomy structured along the orthogonal axes of knowledge source and agency objective to delineate the provenance of clinical knowledge against the system's operational scope. This framework facilitates a systematic analysis of the intrinsic trade-offs between creativity and reliability by categorizing methods into four archetypes: Latent Space Clinicians, Emergent Planners, Grounded Synthesizers, and Verifiable Workflow Automators. For each paradigm, we deconstruct the technical realization across the entire cognitive pipeline, encompassing strategic planning, memory management, action execution, collaboration, and evolution to reveal how distinct architectural choices balance the tension between autonomy and safety.

International challenges have become the de facto standard for comparative assessment of image analysis algorithms given a specific task. Segmentation is so far the most widely investigated medical image processing task, but the various segmentation challenges have typically been organized in isolation, such that algorithm development was driven by the need to tackle a single specific clinical problem. We hypothesized that a method capable of performing well on multiple tasks will generalize well to a previously unseen task and potentially outperform a custom-designed solution. To investigate the hypothesis, we organized the Medical Segmentation Decathlon (MSD) - a biomedical image analysis challenge, in which algorithms compete in a multitude of both tasks and modalities. The underlying data set was designed to explore the axis of difficulties typically encountered when dealing with medical images, such as small data sets, unbalanced labels, multi-site data and small objects. The MSD challenge confirmed that algorithms with a consistent good performance on a set of tasks preserved their good average performance on a different set of previously unseen tasks. Moreover, by monitoring the MSD winner for two years, we found that this algorithm continued generalizing well to a wide range of other clinical problems, further confirming our hypothesis. Three main conclusions can be drawn from this study: (1) state-of-the-art image segmentation algorithms are mature, accurate, and generalize well when retrained on unseen tasks; (2) consistent algorithmic performance across multiple tasks is a strong surrogate of algorithmic generalizability; (3) the training of accurate AI segmentation models is now commoditized to non AI experts.

Large Language Models (LLMs) present immense potential in the medical field, yet concerns over data privacy, regulatory compliance, and model stability restrict their widespread adoption. Although the distillation of high-performing closed-source LLMs has proven effective for general tasks, their application in healthcare is limited due to reduced domain knowledge and remnants of alignment behavior hindering clinical tasks. To address these challenges, we propose Dialogue-Based Knowledge Encoding (DBKE). DBKE enhances models' implicit knowledge base and primes them for conversational recall, augmenting their conversational capabilities and enabling a soft alignment for subsequent use cases. By transforming dense academic source text into synthetic dialogue, DBKE broadens the model's knowledge base and enables a soft alignment that guides downstream behaviours. We present Clinical Camel, an open-source, healthcare-focused conversational model, to showcase the effectiveness of DBKE. Clinical Camel outperforms GPT-3.5 on the United States Medical Licensing Examination (USMLE) Step 1 and Step 3 with scores of 53.2 % and 58.2 %, respectively, compared to GPT-3.5's scores of 36.1 % and 55.7 %. Clinical Camel adeptly handles multi-stage clinical case problems, provides adaptive counseling, and generates clinical notes. However, it is prone to hallucinations, which pose a significant obstacle in safety-critical settings. The performance of Clinical Camel underscores the importance of continued research and development of open-source models for the safe and effective integration of LLMs in healthcare settings.

Current Large Language Models (LLMs) exhibit significant limitations, notably in structured, interpretable, and verifiable medical reasoning, alongside practical deployment challenges related to computational resources and data privacy. This report focused on the development of WiNGPT-3.0, the 32-billion parameter LLMs, engineered with the objective of enhancing its capacity for medical reasoning and exploring its potential for effective integration within healthcare IT infrastructures. The broader aim is to advance towards clinically applicable models. The approach involved a multi-stage training pipeline tailored for general, medical, and clinical reasoning. This pipeline incorporated supervised fine-tuning (SFT) and reinforcement learning (RL), leveraging curated Long Chain-of-Thought (CoT) datasets, auxiliary reward models, and an evidence-based diagnostic chain simulation. WiNGPT-3.0 demonstrated strong performance: specific model variants achieved scores of 66.6 on MedCalc and 87.1 on MedQA-USMLE. Furthermore, targeted training improved performance on a clinical reasoning task from a baseline score of 58.1 to 62.5. These findings suggest that reinforcement learning, even when applied with a limited dataset of only a few thousand examples, can enhance medical reasoning accuracy. Crucially, this demonstration of RL's efficacy with limited data and computation paves the way for more trustworthy and practically deployable LLMs within clinical workflows and health information infrastructures.

Medical imaging plays a significant role in clinical practice of medical diagnosis, where the text reports of the images are essential in understanding them and facilitating later treatments. By generating the reports automatically, it is beneficial to help lighten the burden of radiologists and significantly promote clinical automation, which already attracts much attention in applying artificial intelligence to medical domain. Previous studies mainly follow the encoder-decoder paradigm and focus on the aspect of text generation, with few studies considering the importance of cross-modal mappings and explicitly exploit such mappings to facilitate radiology report generation. In this paper, we propose a cross-modal memory networks (CMN) to enhance the encoder-decoder framework for radiology report generation, where a shared memory is designed to record the alignment between images and texts so as to facilitate the interaction and generation across modalities. Experimental results illustrate the effectiveness of our proposed model, where state-of-the-art performance is achieved on two widely used benchmark datasets, i.e., IU X-Ray and MIMIC-CXR. Further analyses also prove that our model is able to better align information from radiology images and texts so as to help generating more accurate reports in terms of clinical indicators.

Respiratory motion and the associated deformations of abdominal organs and tumors are essential information in clinical applications. However, inter- and intra-patient multi-organ deformations are complex and have not been statistically formulated, whereas single organ deformations have been widely studied. In this paper, we introduce a multi-organ deformation library and its application to deformation reconstruction based on the shape features of multiple abdominal organs. Statistical multi-organ motion/deformation models of the stomach, liver, left and right kidneys, and duodenum were generated by shape matching their region labels defined on four-dimensional computed tomography images. A total of 250 volumes were measured from 25 pancreatic cancer patients. This paper also proposes a per-region-based deformation learning using the reproducing kernel to predict the displacement of pancreatic cancer for adaptive radiotherapy. The experimental results show that the proposed concept estimates deformations better than general per-patient-based learning models and achieves a clinically acceptable estimation error with a mean distance of 1.2 pm 0.7 mm and a Hausdorff distance of 4.2 pm 2.3 mm throughout the respiratory motion.

Vision-language pretraining has advanced image-text alignment, yet progress in radiology remains constrained by the heterogeneity of clinical reports, including abbreviations, impression-only notes, and stylistic variability. Unlike general-domain settings where more data often leads to better performance, naively scaling to large collections of noisy reports can plateau or even degrade model learning. We ask whether large language model (LLM) encoders can provide robust clinical representations that transfer across diverse styles and better guide image-text alignment. We introduce LLM2VEC4CXR, a domain-adapted LLM encoder for chest X-ray reports, and LLM2CLIP4CXR, a dual-tower framework that couples this encoder with a vision backbone. LLM2VEC4CXR improves clinical text understanding over BERT-based baselines, handles abbreviations and style variation, and achieves strong clinical alignment on report-level metrics. LLM2CLIP4CXR leverages these embeddings to boost retrieval accuracy and clinically oriented scores, with stronger cross-dataset generalization than prior medical CLIP variants. Trained on 1.6M CXR studies from public and private sources with heterogeneous and noisy reports, our models demonstrate that robustness -- not scale alone -- is the key to effective multimodal learning. We release models to support further research in medical image-text representation learning.

Reliable medical image understanding requires models to connect clinical language and visual reasoning with pixel-level grounding. Yet medical vision-language models often lack precise localization, whereas medical segmenters typically rely on explicit target categories or precise spatial prompts. This divide is reinforced by a supervision mismatch: segmentation datasets provide precise masks but little language supervision, whereas medical vision-language data rarely pair language with dense spatial annotations. To address this gap, we present MedPixel, a unified medical pixel-language model built around a shared language--mask interface. To provide scalable supervision, we introduce MedPLG-440K, comprising approximately 440K pixel-language task samples constructed through a clinically motivated synthesis process without external LLM annotation. MedPixel is trained with joint multi-task supervised fine-tuning followed by Pixel-Level Preference Optimization, which uses ground-truth masks as offline verifiers to derive response preferences from mask quality. MedPixel supports a broad spectrum of tasks spanning explicit grounding, implicit reasoning, spatial interaction, grounded explanation, and medical VQA. Across this task spectrum, MedPixel achieves strong performance in both pixel-level prediction and response generation, together with effective zero-shot transfer to external grounding benchmarks and robustness to imperfect spatial prompts. Code and model checkpoints will be released at https://github.com/yhy-whu/Medpixel.

Longitudinal multimodal data, including electronic health records (EHR) and sequential chest X-rays (CXRs), is critical for modeling disease progression, yet remains underutilized due to two key challenges: (1) redundancy in consecutive CXR sequences, where static anatomical regions dominate over clinically-meaningful dynamics, and (2) temporal misalignment between sparse, irregular imaging and continuous EHR data. We introduce DiPro, a novel framework that addresses these challenges through region-aware disentanglement and multi-timescale alignment. First, we disentangle static (anatomy) and dynamic (pathology progression) features in sequential CXRs, prioritizing disease-relevant changes. Second, we hierarchically align these static and dynamic CXR features with asynchronous EHR data via local (pairwise interval-level) and global (full-sequence) synchronization to model coherent progression pathways. Extensive experiments on the MIMIC dataset demonstrate that DiPro could effectively extract temporal clinical dynamics and achieve state-of-the-art performance on both disease progression identification and general ICU prediction tasks.

In clinical radiology reports, doctors capture important information about the patient's health status. They convey their observations from raw medical imaging data about the inner structures of a patient. As such, formulating reports requires medical experts to possess wide-ranging knowledge about anatomical regions with their normal, healthy appearance as well as the ability to recognize abnormalities. This explicit grasp on both the patient's anatomy and their appearance is missing in current medical image-processing systems as annotations are especially difficult to gather. This renders the models to be narrow experts e.g. for identifying specific diseases. In this work, we recover this missing link by adding human anatomy into the mix and enable the association of content in medical reports to their occurrence in associated imagery (medical phrase grounding). To exploit anatomical structures in this scenario, we present a sophisticated automatic pipeline to gather and integrate human bodily structures from computed tomography datasets, which we incorporate in our PAXRay: A Projected dataset for the segmentation of Anatomical structures in X-Ray data. Our evaluation shows that methods that take advantage of anatomical information benefit heavily in visually grounding radiologists' findings, as our anatomical segmentations allow for up to absolute 50% better grounding results on the OpenI dataset as compared to commonly used region proposals. The PAXRay dataset is available at https://constantinseibold.github.io/paxray/.

This study demonstrates that incorporating a consistency heuristic into the point-matching algorithm yerebakan2023hierarchical improves robustness in matching anatomical locations across pairs of medical images. We validated our approach on diverse longitudinal internal and public datasets spanning CT and MRI modalities. Notably, it surpasses state-of-the-art results on the Deep Lesion Tracking dataset. Additionally, we show that the method effectively addresses landmark localization. The algorithm operates efficiently on standard CPU hardware and allows configurable trade-offs between speed and robustness. The method enables high-precision navigation between medical images without requiring a machine learning model or training data.

Large Language Models (LLMs) constitute a breakthrough state-of-the-art Artificial Intelligence (AI) technology which is rapidly evolving and promises to aid in medical diagnosis either by assisting doctors or by simulating a doctor's workflow in more advanced and complex implementations. In this technical paper, we outline Cognitive Network Evaluation Toolkit for Medical Domains (COGNET-MD), which constitutes a novel benchmark for LLM evaluation in the medical domain. Specifically, we propose a scoring-framework with increased difficulty to assess the ability of LLMs in interpreting medical text. The proposed framework is accompanied with a database of Multiple Choice Quizzes (MCQs). To ensure alignment with current medical trends and enhance safety, usefulness, and applicability, these MCQs have been constructed in collaboration with several associated medical experts in various medical domains and are characterized by varying degrees of difficulty. The current (first) version of the database includes the medical domains of Psychiatry, Dentistry, Pulmonology, Dermatology and Endocrinology, but it will be continuously extended and expanded to include additional medical domains.

Continuity of care is crucial to ensuring positive health outcomes for patients discharged from an inpatient hospital setting, and improved information sharing can help. To share information, caregivers write discharge notes containing action items to share with patients and their future caregivers, but these action items are easily lost due to the lengthiness of the documents. In this work, we describe our creation of a dataset of clinical action items annotated over MIMIC-III, the largest publicly available dataset of real clinical notes. This dataset, which we call CLIP, is annotated by physicians and covers 718 documents representing 100K sentences. We describe the task of extracting the action items from these documents as multi-aspect extractive summarization, with each aspect representing a type of action to be taken. We evaluate several machine learning models on this task, and show that the best models exploit in-domain language model pre-training on 59K unannotated documents, and incorporate context from neighboring sentences. We also propose an approach to pre-training data selection that allows us to explore the trade-off between size and domain-specificity of pre-training datasets for this task.

Medical decision-making requires integrating diverse medical information, from imaging to clinical narratives. These medical modalities are often acquired in a many-to-many manner. However, current medical vision-language pretraining models (Med-VLPMs) fail to directly account for this many-to-many mapping in their model training and embeddings. To address this, we present Probabilistic Modality-Enhanced Diagnosis (ProbMED), a multimodal Med-VLPM that employs probabilistic contrastive learning to model distributions over embeddings rather than deterministic estimates. ProbMED aligns four distinct modalities -- chest X-rays, electrocardiograms, echocardiograms, and clinical text -- into a unified probabilistic embedding space. We use InfoNCE loss with Hellinger distance to integrate inter-modality distributions. We introduce a probabilistic synthetic sampling loss that captures modality-specific mean and variance to improve intra-modality binding. Extensive experiments across 13 medical datasets demonstrate that our model outperforms current Med-VLPMs in cross-modality retrieval, zero-shot, and few-shot classification. We also demonstrate the robust integration of multiple modalities for prognostication, showing improved intra- and inter-medical modality binding.

Recent advances in AI foundation models have significant potential for lightening the clinical workload by mimicking the comprehensive and multi-faceted approaches used by medical professionals. In the field of radiation oncology, the integration of multiple modalities holds great importance, so the opportunity of foundational model is abundant. Inspired by this, here we present RO-LMM, a multi-purpose, comprehensive large multimodal model (LMM) tailored for the field of radiation oncology. This model effectively manages a series of tasks within the clinical workflow, including clinical context summarization, radiation treatment plan suggestion, and plan-guided target volume segmentation by leveraging the capabilities of LMM. In particular, to perform consecutive clinical tasks without error accumulation, we present a novel Consistency Embedding Fine-Tuning (CEFTune) technique, which boosts LMM's robustness to noisy inputs while preserving the consistency of handling clean inputs. We further extend this concept to LMM-driven segmentation framework, leading to a novel Consistency Embedding Segmentation~(CESEG) techniques. Experimental results including multi-centre validation confirm that our RO-LMM with CEFTune and CESEG results in promising performance for multiple clinical tasks with generalization capabilities.

Recent advancements in prompt-based medical image segmentation have enabled clinicians to identify tumors using simple input like bounding boxes or text prompts. However, existing methods face challenges when doctors need to interact through natural language or when position reasoning is required - understanding spatial relationships between anatomical structures and pathologies. We present PRS-Med, a framework that integrates vision-language models with segmentation capabilities to generate both accurate segmentation masks and corresponding spatial reasoning outputs. Additionally, we introduce the MMRS dataset (Multimodal Medical in Positional Reasoning Segmentation), which provides diverse, spatially-grounded question-answer pairs to address the lack of position reasoning data in medical imaging. PRS-Med demonstrates superior performance across six imaging modalities (CT, MRI, X-ray, ultrasound, endoscopy, RGB), significantly outperforming state-of-the-art methods in both segmentation accuracy and position reasoning. Our approach enables intuitive doctor-system interaction through natural language, facilitating more efficient diagnoses. Our dataset pipeline, model, and codebase will be released to foster further research in spatially-aware multimodal reasoning for medical applications.

Rare diseases collectively affect an estimated 3.5% to 5.9% of the population, yet more than 70% of patients are misdiagnosed and many endure years of evaluation before a diagnosis is reached, because early presentations are nonspecific and relevant expertise is scarce and unevenly distributed. Artificial intelligence could provide support, but existing systems address isolated stages of care, overwhelmingly diagnosis. They typically depend on the results of downstream investigations, and they treat the variability between models as noise to be eliminated. Here we present RareLens, a system that supports clinical decision-making across the entire rare disease trajectory by exploiting this variability. When heterogeneous large language models evaluate the same case, they generate divergent but complementary reasoning, which RareLens aligns and calibrates into a single convergent, actionable decision at each stage. Four coordinated modules perform primary-visit risk screening, diagnosis, treatment planning and prognosis. Developed and evaluated on RareBench, a real-world dataset of 157,525 cases spanning all 33 Orphanet categories and more than 7,000 conditions, RareLens outperformed every frontier model tested, including GPT-5, DeepSeek-R1, Claude-3.7-Sonnet and Gemini-2.5-Pro, at each stage. It achieved an area under the curve of 0.917 for screening and top-1 accuracies of 65.5% and 89.8% for diagnosis and treatment. In an external study spanning 1,287 cases and 23 physicians, autonomous RareLens and physicians assisted by RareLens both substantially outperformed unaided physicians. These findings indicate that aligning divergent model reasoning, rather than scaling a single model, offers a generalizable strategy for high-uncertainty clinical decision-making.

Several studies showed that Large Language Models (LLMs) can answer medical questions correctly, even outperforming the average human score in some medical exams. However, to our knowledge, no study has been conducted to assess the ability of language models to validate existing or generated medical text for correctness and consistency. In this paper, we introduce MEDEC (https://github.com/abachaa/MEDEC), the first publicly available benchmark for medical error detection and correction in clinical notes, covering five types of errors (Diagnosis, Management, Treatment, Pharmacotherapy, and Causal Organism). MEDEC consists of 3,848 clinical texts, including 488 clinical notes from three US hospital systems that were not previously seen by any LLM. The dataset has been used for the MEDIQA-CORR shared task to evaluate seventeen participating systems [Ben Abacha et al., 2024]. In this paper, we describe the data creation methods and we evaluate recent LLMs (e.g., o1-preview, GPT-4, Claude 3.5 Sonnet, and Gemini 2.0 Flash) for the tasks of detecting and correcting medical errors requiring both medical knowledge and reasoning capabilities. We also conducted a comparative study where two medical doctors performed the same task on the MEDEC test set. The results showed that MEDEC is a sufficiently challenging benchmark to assess the ability of models to validate existing or generated notes and to correct medical errors. We also found that although recent LLMs have a good performance in error detection and correction, they are still outperformed by medical doctors in these tasks. We discuss the potential factors behind this gap, the insights from our experiments, the limitations of current evaluation metrics, and share potential pointers for future research.

Large-scale multi-modal deep learning models have revolutionized domains such as healthcare, highlighting the importance of computational power. However, in resource-constrained regions like Low and Middle-Income Countries (LMICs), limited access to GPUs and data poses significant challenges, often leaving CPUs as the sole resource. To address this, we advocate for leveraging vector embeddings to enable flexible and efficient computational methodologies, democratizing multimodal deep learning across diverse contexts. Our paper investigates the efficiency and effectiveness of using vector embeddings from single-modal foundation models and multi-modal Vision-Language Models (VLMs) for multimodal deep learning in low-resource environments, particularly in healthcare. Additionally, we propose a simple yet effective inference-time method to enhance performance by aligning image-text embeddings. Comparing these approaches with traditional methods, we assess their impact on computational efficiency and model performance using metrics like accuracy, F1-score, inference time, training time, and memory usage across three medical modalities: BRSET (ophthalmology), HAM10000 (dermatology), and SatelliteBench (public health). Our findings show that embeddings reduce computational demands without compromising model performance. Furthermore, our alignment method improves performance in medical tasks. This research promotes sustainable AI practices by optimizing resources in constrained environments, highlighting the potential of embedding-based approaches for efficient multimodal learning. Vector embeddings democratize multimodal deep learning in LMICs, particularly in healthcare, enhancing AI adaptability in varied use cases.

Large language models (LLMs) integrated into agent-driven workflows hold immense promise for healthcare, yet a significant gap exists between their potential and practical implementation within clinical settings. To address this, we present a practitioner-oriented field manual for deploying generative agents that use electronic health record (EHR) data. This guide is informed by our experience deploying the "irAE-Agent", an automated system to detect immune-related adverse events from clinical notes at Mass General Brigham, and by structured interviews with 21 clinicians, engineers, and informatics leaders involved in the project. Our analysis reveals a critical misalignment in clinical AI development: less than 20% of our effort was dedicated to prompt engineering and model development, while over 80% was consumed by the sociotechnical work of implementation. We distill this effort into five "heavy lifts": data integration, model validation, ensuring economic value, managing system drift, and governance. By providing actionable solutions for each of these challenges, this field manual shifts the focus from algorithmic development to the essential infrastructure and implementation work required to bridge the "valley of death" and successfully translate generative AI from pilot projects into routine clinical care.

Clinical LLMs are often scaled by increasing model size, context length, retrieval complexity, or inference-time compute, with the implicit expectation that higher accuracy implies safer behavior. This assumption is incomplete in medicine, where a few confident, high-risk, or evidence-contradicting errors can matter more than average benchmark performance. We introduce SaFE-Scale, a framework for measuring how clinical LLM safety changes across model scale, evidence quality, retrieval strategy, context exposure, and inference-time compute. To instantiate this framework, we introduce RadSaFE-200, a Radiology Safety-Focused Evaluation benchmark of 200 multiple-choice questions with clinician-defined clean evidence, conflict evidence, and option-level labels for high-risk error, unsafe answer, and evidence contradiction. We evaluated 34 locally deployed LLMs across six deployment conditions: closed-book prompting (zero-shot), clean evidence, conflict evidence, standard RAG, agentic RAG, and max-context prompting. Clean evidence produced the strongest improvement, increasing mean accuracy from 73.5% to 94.1%, while reducing high-risk error from 12.0% to 2.6%, contradiction from 12.7% to 2.3%, and dangerous overconfidence from 8.0% to 1.6%. Standard RAG and agentic RAG did not reproduce this safety profile: agentic RAG improved accuracy over standard RAG and reduced contradiction, but high-risk error and dangerous overconfidence remained elevated. Max-context prompting increased latency without closing the safety gap, and additional inference-time compute produced only limited gains. Worst-case analysis showed that clinically consequential errors concentrated in a small subset of questions. Clinical LLM safety is therefore not a passive consequence of scaling, but a deployment property shaped by evidence quality, retrieval design, context construction, and collective failure behavior.

Integrating large language models (LLMs) like DeepSeek R1 into healthcare requires rigorous evaluation of their reasoning alignment with clinical expertise. This study assesses DeepSeek R1's medical reasoning against expert patterns using 100 MedQA clinical cases. The model achieved 93% diagnostic accuracy, demonstrating systematic clinical judgment through differential diagnosis, guideline-based treatment selection, and integration of patient-specific factors. However, error analysis of seven incorrect cases revealed persistent limitations: anchoring bias, challenges reconciling conflicting data, insufficient exploration of alternatives, overthinking, knowledge gaps, and premature prioritization of definitive treatment over intermediate care. Crucially, reasoning length correlated with accuracy - shorter responses (<5,000 characters) were more reliable, suggesting extended explanations may signal uncertainty or rationalization of errors. While DeepSeek R1 exhibits foundational clinical reasoning capabilities, recurring flaws highlight critical areas for refinement, including bias mitigation, knowledge updates, and structured reasoning frameworks. These findings underscore LLMs' potential to augment medical decision-making through artificial reasoning but emphasize the need for domain-specific validation, interpretability safeguards, and confidence metrics (e.g., response length thresholds) to ensure reliability in real-world applications.