Daily Papers

Text-to-image (T2I) diffusion models such as SDXL and FLUX have achieved impressive photorealism, yet small-scale distortions remain pervasive in limbs, face, text and so on. Existing refinement approaches either perform costly iterative re-generation or rely on vision-language models (VLMs) with weak spatial grounding, leading to semantic drift and unreliable local edits. To close this gap, we propose Agentic Retoucher, a hierarchical decision-driven framework that reformulates post-generation correction as a human-like perception-reasoning-action loop. Specifically, we design (1) a perception agent that learns contextual saliency for fine-grained distortion localization under text-image consistency cues, (2) a reasoning agent that performs human-aligned inferential diagnosis via progressive preference alignment, and (3) an action agent that adaptively plans localized inpainting guided by user preference. This design integrates perceptual evidence, linguistic reasoning, and controllable correction into a unified, self-corrective decision process. To enable fine-grained supervision and quantitative evaluation, we further construct GenBlemish-27K, a dataset of 6K T2I images with 27K annotated artifact regions across 12 categories. Extensive experiments demonstrate that Agentic Retoucher consistently outperforms state-of-the-art methods in perceptual quality, distortion localization and human preference alignment, establishing a new paradigm for self-corrective and perceptually reliable T2I generation.

Traditionally, AI research in medical diagnosis has largely centered on image analysis. While this has led to notable advancements, the absence of patient-reported symptoms continues to hinder diagnostic accuracy. To address this, we propose a Pre-Consultation Dialogue Framework (PCDF) that mimics real-world diagnostic procedures, where doctors iteratively query patients before reaching a conclusion. Specifically, we simulate diagnostic dialogues between two vision-language models (VLMs): a DocVLM, which generates follow-up questions based on the image and dialogue history, and a PatientVLM, which responds using a symptom profile derived from the ground-truth diagnosis. We additionally conducted a small-scale clinical validation of the synthetic symptoms generated by our framework, with licensed clinicians confirming their clinical relevance, symptom coverage, and overall realism. These findings indicate that the resulting DocVLM-PatientVLM interactions form coherent, multi-turn consultations paired with images and diagnoses, which we then use to fine-tune the DocVLM. This dialogue-based supervision leads to substantial gains over image-only training, highlighting the value of realistic symptom elicitation for diagnosis.

Rare diseases affect hundreds of millions worldwide, yet diagnosis often spans years. Convectional pipelines decouple noisy evidence extraction from downstream inferential diagnosis, and general/medical large language models (LLMs) face scarce real world electronic health records (EHRs), stale domain knowledge, and hallucinations. We assemble a large, domain specialized clinical corpus and a clinician validated reasoning set, and develop RareSeek R1 via staged instruction tuning, chain of thought learning, and graph grounded retrieval. Across multicenter EHR narratives and public benchmarks, RareSeek R1 attains state of the art accuracy, robust generalization, and stability under noisy or overlapping phenotypes. Augmented retrieval yields the largest gains when narratives pair with prioritized variants by resolving ambiguity and aligning candidates to mechanisms. Human studies show performance on par with experienced physicians and consistent gains in assistive use. Notably, transparent reasoning highlights decisive non phenotypic evidence (median 23.1%, such as imaging, interventions, functional tests) underpinning many correct diagnoses. This work advances a narrative first, knowledge integrated reasoning paradigm that shortens the diagnostic odyssey and enables auditable, clinically translatable decision support.

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.

Medical vision-language models (VLMs) excel at image-text understanding but typically rely on a single-pass reasoning that neglects localized visual cues. In clinical practice, however, human experts iteratively scan, focus, and refine the regions of interest before reaching a final diagnosis. To narrow this machine-human perception gap, we introduce ViTAR, a novel VLM framework that emulates the iterative reasoning process of human experts through a cognitive chain of "think-act-rethink-answer". ViTAR treats medical images as interactive objects, enabling models to engage multi-step visual reasoning. To support this approach, we curate a high-quality instruction dataset comprising 1K interactive examples that encode expert-like diagnostic behaviors. In addition, a 16K visual question answering training data has been curated towards fine-grained visual diagnosis. We introduce a two-stage training strategy that begins with supervised fine-tuning to guide cognitive trajectories, followed by the reinforcement learning to optimize decision-making. Extensive evaluations demonstrate that ViTAR outperforms strong state-of-the-art models. Visual attention analysis reveals that from the "think" to "rethink" rounds, ViTAR increasingly anchors visual grounding to clinically critical regions and maintains high attention allocation to visual tokens during reasoning, providing mechanistic insight into its improved performance. These findings demonstrate that embedding expert-style iterative thinking chains into VLMs enhances both performance and trustworthiness of medical AI.

Human-interpretable predictions are essential for deploying AI in medical imaging, yet most interpretable-by-design (IBD) frameworks require concept annotations for training data, which are costly and impractical to obtain in clinical contexts. Recent attempts to bypass annotation, such as zero-shot vision-language models or concept-generation frameworks, struggle to capture domain-specific medical features, leading to poor reliability. In this paper, we propose a novel Prior-guided Concept Predictor (PCP), a weakly supervised framework that enables concept answer prediction without explicit supervision or reliance on language models. PCP leverages class-level concept priors as weak supervision and incorporates a refinement mechanism with KL divergence and entropy regularization to align predictions with clinical reasoning. Experiments on PH2 (dermoscopy) and WBCatt (hematology) show that PCP improves concept-level F1-score by over 33% compared to zero-shot baselines, while delivering competitive classification performance on four medical datasets (PH2, WBCatt, HAM10000, and CXR4) relative to fully supervised concept bottleneck models (CBMs) and V-IP.

Recent advancements in general-purpose AI have highlighted the importance of guiding AI systems towards the intended goals, ethical principles, and values of individuals and groups, a concept broadly recognized as alignment. However, the lack of clarified definitions and scopes of human-AI alignment poses a significant obstacle, hampering collaborative efforts across research domains to achieve this alignment. In particular, ML- and philosophy-oriented alignment research often views AI alignment as a static, unidirectional process (i.e., aiming to ensure that AI systems' objectives match humans) rather than an ongoing, mutual alignment problem [429]. This perspective largely neglects the long-term interaction and dynamic changes of alignment. To understand these gaps, we introduce a systematic review of over 400 papers published between 2019 and January 2024, spanning multiple domains such as Human-Computer Interaction (HCI), Natural Language Processing (NLP), Machine Learning (ML), and others. We characterize, define and scope human-AI alignment. From this, we present a conceptual framework of "Bidirectional Human-AI Alignment" to organize the literature from a human-centered perspective. This framework encompasses both 1) conventional studies of aligning AI to humans that ensures AI produces the intended outcomes determined by humans, and 2) a proposed concept of aligning humans to AI, which aims to help individuals and society adjust to AI advancements both cognitively and behaviorally. Additionally, we articulate the key findings derived from literature analysis, including discussions about human values, interaction techniques, and evaluations. To pave the way for future studies, we envision three key challenges for future directions and propose examples of potential future solutions.

Clinical diagnosis is a highly specialized discipline requiring both domain expertise and strict adherence to rigorous guidelines. While current AI-driven medical research predominantly focuses on knowledge graphs or natural text pretraining paradigms to incorporate medical knowledge, these approaches primarily rely on implicitly encoded knowledge within model parameters, neglecting task-specific knowledge required by diverse downstream tasks. To address this limitation, we propose Retrieval-Augmented Diagnosis (RAD), a novel framework that explicitly injects external knowledge into multimodal models directly on downstream tasks. Specifically, RAD operates through three key mechanisms: retrieval and refinement of disease-centered knowledge from multiple medical sources, a guideline-enhanced contrastive loss that constrains the latent distance between multi-modal features and guideline knowledge, and the dual transformer decoder that employs guidelines as queries to steer cross-modal fusion, aligning the models with clinical diagnostic workflows from guideline acquisition to feature extraction and decision-making. Moreover, recognizing the lack of quantitative evaluation of interpretability for multimodal diagnostic models, we introduce a set of criteria to assess the interpretability from both image and text perspectives. Extensive evaluations across four datasets with different anatomies demonstrate RAD's generalizability, achieving state-of-the-art performance. Furthermore, RAD enables the model to concentrate more precisely on abnormal regions and critical indicators, ensuring evidence-based, trustworthy diagnosis. Our code is available at https://github.com/tdlhl/RAD.

The clinical translation of dermatological AI is hindered by opaque reasoning and systematic performance disparities across skin tones. Here we present SkinGPT-R1, a multimodal large language model that integrates chain-of-thought diagnostic reasoning with a fairness-aware mixture-of-experts architecture for interpretable and equitable skin disease diagnosis. Through parameter-efficient adaptation of a frozen reasoning backbone, SkinGPT-R1 generates structured diagnostic reports comprising visual findings, differential reasoning, and final diagnosis. Across seven external datasets spanning diverse pathologies and imaging conditions, SkinGPT-R1 achieves state-of-the-art accuracy on six benchmarks, including 82.50\% on a challenging 40-class long-tail classification task (+19.30\% over leading baselines). Blinded evaluation by five board-certified dermatologists on 1,000 phenotypically balanced cases yields a mean score of 3.6 out of 5, with the highest ratings in safety (3.8) and reasoning coherence (3.6), indicating that the generated rationales are clinically safe, logically grounded, and suitable for supporting diagnostic decision-making. Critically, SkinGPT-R1 mitigates algorithmic bias across the full Fitzpatrick spectrum, achieving a robust worst-group performance of 41.40\% on the Fitz17k benchmark and a five-fold relative improvement in lower-bound accuracy on the DDI dataset compared to standard multimodal baselines. These results establish a framework for trustworthy, fair, and explainable AI-assisted dermatological diagnosis.

We introduce a novel framework for incorporating human expertise into algorithmic predictions. Our approach leverages human judgment to distinguish inputs which are algorithmically indistinguishable, or "look the same" to predictive algorithms. We argue that this framing clarifies the problem of human-AI collaboration in prediction tasks, as experts often form judgments by drawing on information which is not encoded in an algorithm's training data. Algorithmic indistinguishability yields a natural test for assessing whether experts incorporate this kind of "side information", and further provides a simple but principled method for selectively incorporating human feedback into algorithmic predictions. We show that this method provably improves the performance of any feasible algorithmic predictor and precisely quantify this improvement. We find empirically that although algorithms often outperform their human counterparts on average, human judgment can improve algorithmic predictions on specific instances (which can be identified ex-ante). In an X-ray classification task, we find that this subset constitutes nearly 30% of the patient population. Our approach provides a natural way of uncovering this heterogeneity and thus enabling effective human-AI collaboration.

Accurate disease interpretation from radiology remains challenging due to imaging heterogeneity. Achieving expert-level diagnostic decisions requires integration of subtle image features with clinical knowledge. Yet major vision-language models (VLMs) treat images as holistic entities and overlook fine-grained image details that are vital for disease diagnosis. Clinicians analyze images by utilizing their prior medical knowledge and identify anatomical structures as important region of interests (ROIs). Inspired from this human-centric workflow, we introduce Anatomy-VLM, a fine-grained, vision-language model that incorporates multi-scale information. First, we design a model encoder to localize key anatomical features from entire medical images. Second, these regions are enriched with structured knowledge for contextually-aware interpretation. Finally, the model encoder aligns multi-scale medical information to generate clinically-interpretable disease prediction. Anatomy-VLM achieves outstanding performance on both in- and out-of-distribution datasets. We also validate the performance of Anatomy-VLM on downstream image segmentation tasks, suggesting that its fine-grained alignment captures anatomical and pathology-related knowledge. Furthermore, the Anatomy-VLM's encoder facilitates zero-shot anatomy-wise interpretation, providing its strong expert-level clinical interpretation capabilities.

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

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.

Deep neural networks have demonstrated promising performance on image recognition tasks. However, they may heavily rely on confounding factors, using irrelevant artifacts or bias within the dataset as the cue to improve performance. When a model performs decision-making based on these spurious correlations, it can become untrustable and lead to catastrophic outcomes when deployed in the real-world scene. In this paper, we explore and try to solve this problem in the context of skin cancer diagnosis. We introduce a human-in-the-loop framework in the model training process such that users can observe and correct the model's decision logic when confounding behaviors happen. Specifically, our method can automatically discover confounding factors by analyzing the co-occurrence behavior of the samples. It is capable of learning confounding concepts using easily obtained concept exemplars. By mapping the black-box model's feature representation onto an explainable concept space, human users can interpret the concept and intervene via first order-logic instruction. We systematically evaluate our method on our newly crafted, well-controlled skin lesion dataset and several public skin lesion datasets. Experiments show that our method can effectively detect and remove confounding factors from datasets without any prior knowledge about the category distribution and does not require fully annotated concept labels. We also show that our method enables the model to focus on clinical-related concepts, improving the model's performance and trustworthiness during model inference.

Vision-Language Models (VLMs) are advancing computational pathology with superior visual understanding capabilities. However, current systems often reduce diagnosis to directly output conclusions without verifiable evidence-linked reasoning, which severely limits clinical trust and hinders expert error rectification. To address these barriers, we construct PathReasoner, the first large-scale dataset of whole-slide image (WSI) reasoning. Unlike previous work reliant on unverified distillation, we develop a rigorous knowledge-guided generation pipeline. By leveraging medical knowledge graphs, we explicitly align structured pathological findings and clinical reasoning with diagnoses, generating over 20K high-quality instructional samples. Based on the database, we propose PathReasoner-R1, which synergizes trajectory-masked supervised fine-tuning with reasoning-oriented reinforcement learning to instill structured chain-of-thought capabilities. To ensure medical rigor, we engineer a knowledge-aware multi-granular reward function incorporating an Entity Reward mechanism strictly aligned with knowledge graphs. This effectively guides the model to optimize for logical consistency rather than mere outcome matching, thereby enhancing robustness. Extensive experiments demonstrate that PathReasoner-R1 achieves state-of-the-art performance on both PathReasoner and public benchmarks across various image scales, equipping pathology models with transparent, clinically grounded reasoning capabilities. Dataset and code are available at https://github.com/cyclexfy/PathReasoner-R1.

Medical Image Quality Assessment (IQA) serves as the first-mile safety gate for clinical AI, yet existing approaches remain constrained by scalar, score-based metrics and fail to reflect the descriptive, human-like reasoning process central to expert evaluation. To address this gap, we introduce MedQ-Bench, a comprehensive benchmark that establishes a perception-reasoning paradigm for language-based evaluation of medical image quality with Multi-modal Large Language Models (MLLMs). MedQ-Bench defines two complementary tasks: (1) MedQ-Perception, which probes low-level perceptual capability via human-curated questions on fundamental visual attributes; and (2) MedQ-Reasoning, encompassing both no-reference and comparison reasoning tasks, aligning model evaluation with human-like reasoning on image quality. The benchmark spans five imaging modalities and over forty quality attributes, totaling 2,600 perceptual queries and 708 reasoning assessments, covering diverse image sources including authentic clinical acquisitions, images with simulated degradations via physics-based reconstructions, and AI-generated images. To evaluate reasoning ability, we propose a multi-dimensional judging protocol that assesses model outputs along four complementary axes. We further conduct rigorous human-AI alignment validation by comparing LLM-based judgement with radiologists. Our evaluation of 14 state-of-the-art MLLMs demonstrates that models exhibit preliminary but unstable perceptual and reasoning skills, with insufficient accuracy for reliable clinical use. These findings highlight the need for targeted optimization of MLLMs in medical IQA. We hope that MedQ-Bench will catalyze further exploration and unlock the untapped potential of MLLMs for medical image quality evaluation.

Multimodal large language models (MLLMs) demonstrate significant potential in the field of medical diagnosis. However, they face critical challenges in specialized domains such as ophthalmology, particularly the fragmentation of annotation granularity and inconsistencies in clinical reasoning logic, which hinder precise cross-modal understanding. This paper introduces FundusExpert, an ophthalmology-specific MLLM with integrated positioning-diagnosis reasoning capabilities, along with FundusGen, a dataset constructed through the intelligent Fundus-Engine system. Fundus-Engine automates localization and leverages MLLM-based semantic expansion to integrate global disease classification, local object detection, and fine-grained feature analysis within a single fundus image. Additionally, by constructing a clinically aligned cognitive chain, it guides the model to generate interpretable reasoning paths. FundusExpert, fine-tuned with instruction data from FundusGen, achieves the best performance in ophthalmic question-answering tasks, surpassing the average accuracy of the 40B MedRegA by 26.6%. It also excels in zero-shot report generation tasks, achieving a clinical consistency of 77.0%, significantly outperforming GPT-4o's 47.6%. Furthermore, we reveal a scaling law between data quality and model capability (L propto N^{0.068}), demonstrating that the cognitive alignment annotations in FundusGen enhance data utilization efficiency. By integrating region-level localization with diagnostic reasoning chains, our work develops a scalable, clinically-aligned MLLM and explores a pathway toward bridging the visual-language gap in specific MLLMs. Our project can be found at https://github.com/MeteorElf/FundusExpert.

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.

For safety, medical AI systems undergo thorough evaluations before deployment, validating their predictions against a ground truth which is assumed to be fixed and certain. However, this ground truth is often curated in the form of differential diagnoses. While a single differential diagnosis reflects the uncertainty in one expert assessment, multiple experts introduce another layer of uncertainty through disagreement. Both forms of uncertainty are ignored in standard evaluation which aggregates these differential diagnoses to a single label. In this paper, we show that ignoring uncertainty leads to overly optimistic estimates of model performance, therefore underestimating risk associated with particular diagnostic decisions. To this end, we propose a statistical aggregation approach, where we infer a distribution on probabilities of underlying medical condition candidates themselves, based on observed annotations. This formulation naturally accounts for the potential disagreements between different experts, as well as uncertainty stemming from individual differential diagnoses, capturing the entire ground truth uncertainty. Our approach boils down to generating multiple samples of medical condition probabilities, then evaluating and averaging performance metrics based on these sampled probabilities. In skin condition classification, we find that a large portion of the dataset exhibits significant ground truth uncertainty and standard evaluation severely over-estimates performance without providing uncertainty estimates. In contrast, our framework provides uncertainty estimates on common metrics of interest such as top-k accuracy and average overlap, showing that performance can change multiple percentage points. We conclude that, while assuming a crisp ground truth can be acceptable for many AI applications, a more nuanced evaluation protocol should be utilized in medical diagnosis.

Developing reliable AI systems to assist human clinicians in multi-modal medical diagnosis has long been a key objective for researchers. Recently, Multi-modal Large Language Models (MLLMs) have gained significant attention and achieved success across various domains. With strong reasoning capabilities and the ability to perform diverse tasks based on user instructions, they hold great potential for enhancing medical diagnosis. However, directly applying MLLMs to the medical domain still presents challenges. They lack detailed perception of visual inputs, limiting their ability to perform quantitative image analysis, which is crucial for medical diagnostics. Additionally, MLLMs often exhibit hallucinations and inconsistencies in reasoning, whereas clinical diagnoses must adhere strictly to established criteria. To address these challenges, we propose MedAgent-Pro, an evidence-based reasoning agentic system designed to achieve reliable, explainable, and precise medical diagnoses. This is accomplished through a hierarchical workflow: at the task level, knowledge-based reasoning generate reliable diagnostic plans for specific diseases following retrieved clinical criteria. While at the case level, multiple tool agents process multi-modal inputs, analyze different indicators according to the plan, and provide a final diagnosis based on both quantitative and qualitative evidence. Comprehensive experiments on both 2D and 3D medical diagnosis tasks demonstrate the superiority and effectiveness of MedAgent-Pro, while case studies further highlight its reliability and interpretability. The code is available at https://github.com/jinlab-imvr/MedAgent-Pro.

Vision-language pre-training for chest X-rays has made significant strides, primarily by utilizing paired radiographs and radiology reports. However, existing approaches often face challenges in encoding medical knowledge effectively. While radiology reports provide insights into the current disease manifestation, medical definitions (as used by contemporary methods) tend to be overly abstract, creating a gap in knowledge. To address this, we propose DeViDe, a novel transformer-based method that leverages radiographic descriptions from the open web. These descriptions outline general visual characteristics of diseases in radiographs, and when combined with abstract definitions and radiology reports, provide a holistic snapshot of knowledge. DeViDe incorporates three key features for knowledge-augmented vision language alignment: First, a large-language model-based augmentation is employed to homogenise medical knowledge from diverse sources. Second, this knowledge is aligned with image information at various levels of granularity. Third, a novel projection layer is proposed to handle the complexity of aligning each image with multiple descriptions arising in a multi-label setting. In zero-shot settings, DeViDe performs comparably to fully supervised models on external datasets and achieves state-of-the-art results on three large-scale datasets. Additionally, fine-tuning DeViDe on four downstream tasks and six segmentation tasks showcases its superior performance across data from diverse distributions.

Deep neural networks have achieved success across a wide range of applications, including as models of human behavior in vision tasks. However, neural network training and human learning differ in fundamental ways, and neural networks often fail to generalize as robustly as humans do, raising questions regarding the similarity of their underlying representations. What is missing for modern learning systems to exhibit more human-like behavior? We highlight a key misalignment between vision models and humans: whereas human conceptual knowledge is hierarchically organized from fine- to coarse-scale distinctions, model representations do not accurately capture all these levels of abstraction. To address this misalignment, we first train a teacher model to imitate human judgments, then transfer human-like structure from its representations into pretrained state-of-the-art vision foundation models. These human-aligned models more accurately approximate human behavior and uncertainty across a wide range of similarity tasks, including a new dataset of human judgments spanning multiple levels of semantic abstractions. They also perform better on a diverse set of machine learning tasks, increasing generalization and out-of-distribution robustness. Thus, infusing neural networks with additional human knowledge yields a best-of-both-worlds representation that is both more consistent with human cognition and more practically useful, thus paving the way toward more robust, interpretable, and human-like artificial intelligence systems.

The rapid advancement of large-scale vision-language models has showcased remarkable capabilities across various tasks. However, the lack of extensive and high-quality image-text data in medicine has greatly hindered the development of large-scale medical vision-language models. In this work, we present a diagnosis-guided bootstrapping strategy that exploits both image and label information to construct vision-language datasets. Based on the constructed dataset, we developed MedDr, a generalist foundation model for healthcare capable of handling diverse medical data modalities, including radiology, pathology, dermatology, retinography, and endoscopy. Moreover, during inference, we propose a simple but effective retrieval-augmented medical diagnosis strategy, which enhances the model's generalization ability. Extensive experiments on visual question answering, medical report generation, and medical image diagnosis demonstrate the superiority of our method.

As AI capabilities increasingly surpass human proficiency in complex tasks, current alignment techniques including SFT and RLHF face fundamental challenges in ensuring reliable oversight. These methods rely on direct human assessment and become untenable when AI outputs exceed human cognitive thresholds. In response to this challenge, we explore two hypotheses: (1) critique of critique can be easier than critique itself, extending the widely-accepted observation that verification is easier than generation to the critique domain, as critique itself is a specialized form of generation; (2) this difficulty relationship is recursively held, suggesting that when direct evaluation is infeasible, performing high-order critiques (e.g., critique of critique of critique) offers a more tractable supervision pathway. To examine these hypotheses, we perform Human-Human, Human-AI, and AI-AI experiments across multiple tasks. Our results demonstrate encouraging evidence supporting these hypotheses and suggest that recursive self-critiquing is a promising direction for scalable oversight.

Recent advancements in Large Language Models (LLMs) have demonstrated significant promise in clinical diagnosis. However, current models struggle to emulate the iterative, diagnostic hypothesis-driven reasoning of real clinical scenarios. Specifically, current LLMs suffer from three critical limitations: (1) generating hallucinated medical content due to weak grounding in verified knowledge, (2) asking redundant or inefficient questions rather than discriminative ones that hinder diagnostic progress, and (3) losing coherence over multi-turn dialogues, leading to contradictory or inconsistent conclusions. To address these challenges, we propose MedKGI, a diagnostic framework grounded in clinical practices. MedKGI integrates a medical knowledge graph (KG) to constrain reasoning to validated medical ontologies, selects questions based on information gain to maximize diagnostic efficiency, and adopts an OSCE-format structured state to maintain consistent evidence tracking across turns. Experiments on clinical benchmarks show that MedKGI outperforms strong LLM baselines in both diagnostic accuracy and inquiry efficiency, improving dialogue efficiency by 30% on average while maintaining state-of-the-art accuracy.

Multimodal large language models (MLLMs) have made significant strides, yet they face challenges in the medical domain due to limited specialized knowledge. While recent medical MLLMs demonstrate strong performance in lab settings, they often struggle in real-world applications, highlighting a substantial gap between research and practice. In this paper, we seek to address this gap at various stages of the end-to-end learning pipeline, including data collection, model fine-tuning, and evaluation. At the data collection stage, we introduce SemiHVision, a dataset that combines human annotations with automated augmentation techniques to improve both medical knowledge representation and diagnostic reasoning. For model fine-tuning, we trained PMC-Cambrian-8B-AN over 2400 H100 GPU hours, resulting in performance that surpasses public medical models like HuatuoGPT-Vision-34B (79.0% vs. 66.7%) and private general models like Claude3-Opus (55.7%) on traditional benchmarks such as SLAKE and VQA-RAD. In the evaluation phase, we observed that traditional benchmarks cannot accurately reflect realistic clinical task capabilities. To overcome this limitation and provide more targeted guidance for model evaluation, we introduce the JAMA Clinical Challenge, a novel benchmark specifically designed to evaluate diagnostic reasoning. On this benchmark, PMC-Cambrian-AN achieves state-of-the-art performance with a GPT-4 score of 1.29, significantly outperforming HuatuoGPT-Vision-34B (1.13) and Claude3-Opus (1.17), demonstrating its superior diagnostic reasoning abilities.

Multimodal Large Language Models (MLLMs) show promise for medical applications, yet progress in dermatology lags due to limited training data, narrow task coverage, and lack of clinically-grounded supervision that mirrors expert diagnostic workflows. We present a comprehensive framework to address these gaps. First, we introduce DermoInstruct, a large-scale morphology-anchored instruction corpus comprising 211,243 images and 772,675 trajectories across five task formats, capturing the complete diagnostic pipeline from morphological observation and clinical reasoning to final diagnosis. Second, we establish DermoBench, a rigorous benchmark evaluating 11 tasks across four clinical axes: Morphology, Diagnosis, Reasoning, and Fairness, including a challenging subset of 3,600 expert-verified open-ended instances and human performance baselines. Third, we develop DermoGPT, a dermatology reasoning MLLM trained via supervised fine-tuning followed by our Morphologically-Anchored Visual-Inference-Consistent (MAVIC) reinforcement learning objective, which enforces consistency between visual observations and diagnostic conclusions. At inference, we deploy Confidence-Consistency Test-time adaptation (CCT) for robust predictions. Experiments show DermoGPT significantly outperforms 16 representative baselines across all axes, achieving state-of-the-art performance while substantially narrowing the human-AI gap. DermoInstruct, DermoBench and DermoGPT will be made publicly available at https://github.com/mendicant04/DermoGPT upon acceptance.

The emergence of groundbreaking large language models capable of performing complex reasoning tasks holds significant promise for addressing various scientific challenges, including those arising in complex clinical scenarios. To enable their safe and effective deployment in real-world healthcare settings, it is urgently necessary to benchmark the diagnostic capabilities of current models systematically. Given the limitations of existing medical benchmarks in evaluating advanced diagnostic reasoning, we present DiagnosisArena, a comprehensive and challenging benchmark designed to rigorously assess professional-level diagnostic competence. DiagnosisArena consists of 1,113 pairs of segmented patient cases and corresponding diagnoses, spanning 28 medical specialties, deriving from clinical case reports published in 10 top-tier medical journals. The benchmark is developed through a meticulous construction pipeline, involving multiple rounds of screening and review by both AI systems and human experts, with thorough checks conducted to prevent data leakage. Our study reveals that even the most advanced reasoning models, o3-mini, o1, and DeepSeek-R1, achieve only 45.82%, 31.09%, and 17.79% accuracy, respectively. This finding highlights a significant generalization bottleneck in current large language models when faced with clinical diagnostic reasoning challenges. Through DiagnosisArena, we aim to drive further advancements in AIs diagnostic reasoning capabilities, enabling more effective solutions for real-world clinical diagnostic challenges. We provide the benchmark and evaluation tools for further research and development https://github.com/SPIRAL-MED/DiagnosisArena.

Accurate estimation of item (question or task) difficulty is critical for educational assessment but suffers from the cold start problem. While Large Language Models demonstrate superhuman problem-solving capabilities, it remains an open question whether they can perceive the cognitive struggles of human learners. In this work, we present a large-scale empirical analysis of Human-AI Difficulty Alignment for over 20 models across diverse domains such as medical knowledge and mathematical reasoning. Our findings reveal a systematic misalignment where scaling up model size is not reliably helpful; instead of aligning with humans, models converge toward a shared machine consensus. We observe that high performance often impedes accurate difficulty estimation, as models struggle to simulate the capability limitations of students even when being explicitly prompted to adopt specific proficiency levels. Furthermore, we identify a critical lack of introspection, as models fail to predict their own limitations. These results suggest that general problem-solving capability does not imply an understanding of human cognitive struggles, highlighting the challenge of using current models for automated difficulty prediction.

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.

Medical diagnostic applications require models that can process multimodal medical inputs (images, patient histories, lab results) and generate diverse outputs including both textual reports and visual content (annotations, segmentation masks, and images). Despite this need, existing medical AI systems disrupt this unified process: medical image understanding models interpret images but cannot generate visual outputs, while medical image generation models synthesize images but cannot provide textual explanations. This leads to gaps in data representation, feature integration, and task-level multimodal capabilities. To this end, we propose a multi-level framework that draws inspiration from diagnostic workflows through the Observation-Knowledge-Analysis (OKA) paradigm. Specifically, at the observation level, we construct UniMed-5M, a dataset comprising over 5.6M samples that reformat diverse unimodal data into multimodal pairs for foundational observation. At the knowledge level, we propose Progressive Curriculum Learning that systematically introduces medical multimodal knowledge. At the analysis level, we introduce UniMedVL, the first medical unified multimodal model for the simultaneous analysis of image understanding and generation tasks within a single architecture. UniMedVL achieves superior performance on five medical image understanding benchmarks, while matching specialized models in generation quality across eight medical imaging modalities. Crucially, our unified architecture enables bidirectional knowledge sharing: generation tasks enhance visual understanding features, demonstrating that integrating traditionally separate capabilities within a single medical framework unlocks improvements across diverse medical vision-language tasks. Code is available at https://github.com/uni-medical/UniMedVL.

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.

The field of medical diagnosis has undergone a significant transformation with the advent of large language models (LLMs), yet the challenges of interpretability within these models remain largely unaddressed. This study introduces Chain-of-Diagnosis (CoD) to enhance the interpretability of LLM-based medical diagnostics. CoD transforms the diagnostic process into a diagnostic chain that mirrors a physician's thought process, providing a transparent reasoning pathway. Additionally, CoD outputs the disease confidence distribution to ensure transparency in decision-making. This interpretability makes model diagnostics controllable and aids in identifying critical symptoms for inquiry through the entropy reduction of confidences. With CoD, we developed DiagnosisGPT, capable of diagnosing 9604 diseases. Experimental results demonstrate that DiagnosisGPT outperforms other LLMs on diagnostic benchmarks. Moreover, DiagnosisGPT provides interpretability while ensuring controllability in diagnostic rigor.

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.

Large language models (LLMs) offer a promising pre-screening tool, improving early disease detection and providing enhanced healthcare access for underprivileged communities. The early diagnosis of various diseases continues to be a significant challenge in healthcare, primarily due to the nonspecific nature of early symptoms, the shortage of expert medical practitioners, and the need for prolonged clinical evaluations, all of which can delay treatment and adversely affect patient outcomes. With impressive accuracy in prediction across a range of diseases, LLMs have the potential to revolutionize clinical pre-screening and decision-making for various medical conditions. In this work, we study the diagnostic capability of LLMs for Rheumatoid Arthritis (RA) with real world patients data. Patient data was collected alongside diagnoses from medical experts, and the performance of LLMs was evaluated in comparison to expert diagnoses for RA disease prediction. We notice an interesting pattern in disease diagnosis and find an unexpected misalignment between prediction and explanation. We conduct a series of multi-round analyses using different LLM agents. The best-performing model accurately predicts rheumatoid arthritis (RA) diseases approximately 95\% of the time. However, when medical experts evaluated the reasoning generated by the model, they found that nearly 68\% of the reasoning was incorrect. This study highlights a clear misalignment between LLMs high prediction accuracy and its flawed reasoning, raising important questions about relying on LLM explanations in clinical settings. LLMs provide incorrect reasoning to arrive at the correct answer for RA disease diagnosis.

Deep learning based automated pathological diagnosis has markedly improved diagnostic efficiency and reduced variability between observers, yet its clinical adoption remains limited by opaque model decisions and a lack of traceable rationale. To address this, recent multimodal visual reasoning architectures provide a unified framework that generates segmentation masks at the pixel level alongside semantically aligned textual explanations. By localizing lesion regions and producing expert style diagnostic narratives, these models deliver the transparent and interpretable insights necessary for dependable AI assisted pathology. Building on these advancements, we propose PathMR, a cell-level Multimodal visual Reasoning framework for Pathological image analysis. Given a pathological image and a textual query, PathMR generates expert-level diagnostic explanations while simultaneously predicting cell distribution patterns. To benchmark its performance, we evaluated our approach on the publicly available PathGen dataset as well as on our newly developed GADVR dataset. Extensive experiments on these two datasets demonstrate that PathMR consistently outperforms state-of-the-art visual reasoning methods in text generation quality, segmentation accuracy, and cross-modal alignment. These results highlight the potential of PathMR for improving interpretability in AI-driven pathological diagnosis. The code will be publicly available in https://github.com/zhangye-zoe/PathMR.

Healthcare data now span EHRs, medical imaging, genomics, and wearable sensors, but most diagnostic models still process these modalities in isolation. This limits their ability to capture early, cross-modal disease signatures. This paper introduces a multimodal foundation model built on a transformer architecture that integrates heterogeneous clinical data through modality-specific encoders and cross-modal attention. Each modality is mapped into a shared latent space and fused using multi-head attention with residual normalization. We implement the framework using a multimodal dataset that simulates early-stage disease patterns across EHR sequences, imaging patches, genomic profiles, and wearable signals, including missing-modality scenarios and label noise. The model is trained using supervised classification together with self-supervised reconstruction and contrastive alignment to improve robustness. Experimental evaluation demonstrates strong performance in early-detection settings, with stable classification metrics, reliable uncertainty estimates, and interpretable attention patterns. The approach moves toward a flexible, pretrain-and-fine-tune foundation model that supports precision diagnostics, handles incomplete inputs, and improves early disease detection across oncology, cardiology, and neurology applications.

Diagnosing a whole-slide image is an interactive, multi-stage process involving changes in magnification and movement between fields. Although recent pathology foundation models are strong, practical agentic systems that decide what field to examine next, adjust magnification, and deliver explainable diagnoses are still lacking. The blocker is data: scalable, clinically aligned supervision of expert viewing behavior that is tacit and experience-based, not written in textbooks or online, and therefore absent from large language model training. We introduce the AI Session Recorder, which works with standard WSI viewers to unobtrusively record routine navigation and convert the viewer logs into standardized behavioral commands (inspect or peek at discrete magnifications) and bounding boxes. A lightweight human-in-the-loop review turns AI-drafted rationales into the Pathology-CoT dataset, a form of paired "where to look" and "why it matters" supervision produced at roughly six times lower labeling time. Using this behavioral data, we build Pathologist-o3, a two-stage agent that first proposes regions of interest and then performs behavior-guided reasoning. On gastrointestinal lymph-node metastasis detection, it achieved 84.5% precision, 100.0% recall, and 75.4% accuracy, exceeding the state-of-the-art OpenAI o3 model and generalizing across backbones. To our knowledge, this constitutes one of the first behavior-grounded agentic systems in pathology. Turning everyday viewer logs into scalable, expert-validated supervision, our framework makes agentic pathology practical and establishes a path to human-aligned, upgradeable clinical AI.

Despite recent advances in medical vision-language pretraining, existing models still struggle to capture the diagnostic workflow: radiographs are typically treated as context-agnostic images, while radiologists' gaze -- a crucial cue for visual reasoning -- remains largely underexplored by existing methods. These limitations hinder the modeling of disease-specific patterns and weaken cross-modal alignment. To bridge this gap, we introduce CoGaze, a Context- and Gaze-guided vision-language pretraining framework for chest X-rays. We first propose a context-infused vision encoder that models how radiologists integrate clinical context -- including patient history, symptoms, and diagnostic intent -- to guide diagnostic reasoning. We then present a multi-level supervision paradigm that (1) enforces intra- and inter-modal semantic alignment through hybrid-positive contrastive learning, (2) injects diagnostic priors via disease-aware cross-modal representation learning, and (3) leverages radiologists' gaze as probabilistic priors to guide attention toward diagnostically salient regions. Extensive experiments demonstrate that CoGaze consistently outperforms state-of-the-art methods across diverse tasks, achieving up to +2.0% CheXbertF1 and +1.2% BLEU2 for free-text and structured report generation, +23.2% AUROC for zero-shot classification, and +12.2% Precision@1 for image-text retrieval. Code is available at https://github.com/mk-runner/CoGaze.

AI alignment refers to models acting towards human-intended goals, preferences, or ethical principles. Given that most large-scale deep learning models act as black boxes and cannot be manually controlled, analyzing the similarity between models and humans can be a proxy measure for ensuring AI safety. In this paper, we focus on the models' visual perception alignment with humans, further referred to as AI-human visual alignment. Specifically, we propose a new dataset for measuring AI-human visual alignment in terms of image classification, a fundamental task in machine perception. In order to evaluate AI-human visual alignment, a dataset should encompass samples with various scenarios that may arise in the real world and have gold human perception labels. Our dataset consists of three groups of samples, namely Must-Act (i.e., Must-Classify), Must-Abstain, and Uncertain, based on the quantity and clarity of visual information in an image and further divided into eight categories. All samples have a gold human perception label; even Uncertain (severely blurry) sample labels were obtained via crowd-sourcing. The validity of our dataset is verified by sampling theory, statistical theories related to survey design, and experts in the related fields. Using our dataset, we analyze the visual alignment and reliability of five popular visual perception models and seven abstention methods. Our code and data is available at https://github.com/jiyounglee-0523/VisAlign.

We present a principled approach to provide LLM-based evaluation with a rigorous guarantee of human agreement. We first propose that a reliable evaluation method should not uncritically rely on model preferences for pairwise evaluation, but rather assess the confidence of judge models and selectively decide when to trust its judgement. We then show that under this selective evaluation framework, human agreement can be provably guaranteed -- such that the model evaluation aligns with that of humans to a user-specified agreement level. As part of our framework, we also introduce Simulated Annotators, a novel confidence estimation method that significantly improves judge calibration and thus enables high coverage of evaluated instances. Finally, we propose Cascaded Selective Evaluation, where we use cheaper models as initial judges and escalate to stronger models only when necessary -- again, while still providing a provable guarantee of human agreement. Experimental results show that Cascaded Selective Evaluation guarantees strong alignment with humans, far beyond what LLM judges could achieve without selective evaluation. For example, on a subset of Chatbot Arena where GPT-4 almost never achieves 80% human agreement, our method, even while employing substantially cost-effective models such as Mistral-7B, guarantees over 80% human agreement with almost 80% test coverage.

Multimodal large language models (MLLMs) have demonstrated promising prospects in healthcare, particularly for addressing complex medical tasks, supporting multidisciplinary treatment (MDT), and enabling personalized precision medicine. However, their practical deployment faces critical challenges in resource efficiency, diagnostic accuracy, clinical considerations, and ethical privacy. To address these limitations, we propose Infi-Med, a comprehensive framework for medical MLLMs that introduces three key innovations: (1) a resource-efficient approach through curating and constructing high-quality supervised fine-tuning (SFT) datasets with minimal sample requirements, with a forward-looking design that extends to both pretraining and posttraining phases; (2) enhanced multimodal reasoning capabilities for cross-modal integration and clinical task understanding; and (3) a systematic evaluation system that assesses model performance across medical modalities and task types. Our experiments demonstrate that Infi-Med achieves state-of-the-art (SOTA) performance in general medical reasoning while maintaining rapid adaptability to clinical scenarios. The framework establishes a solid foundation for deploying MLLMs in real-world healthcare settings by balancing model effectiveness with operational constraints.

Counterfactual medical image generation enables clinicians to explore clinical hypotheses, such as predicting disease progression, facilitating their decision-making. While existing methods can generate visually plausible images from disease progression prompts, they produce silent predictions that lack interpretation to verify how the generation reflects the hypothesized progression -- a critical gap for medical applications that require traceable reasoning. In this paper, we propose Interpretable Counterfactual Generation (ICG), a novel task requiring the joint generation of counterfactual images that reflect the clinical hypothesis and interpretation texts that outline the visual changes induced by the hypothesis. To enable ICG, we present ICG-CXR, the first dataset pairing longitudinal medical images with hypothetical progression prompts and textual interpretations. We further introduce ProgEmu, an autoregressive model that unifies the generation of counterfactual images and textual interpretations. We demonstrate the superiority of ProgEmu in generating progression-aligned counterfactuals and interpretations, showing significant potential in enhancing clinical decision support and medical education. Project page: https://progemu.github.io.

Artificial intelligence holds great promise for expanding access to expert medical knowledge and reasoning. However, most evaluations of language models rely on static vignettes and multiple-choice questions that fail to reflect the complexity and nuance of evidence-based medicine in real-world settings. In clinical practice, physicians iteratively formulate and revise diagnostic hypotheses, adapting each subsequent question and test to what they've just learned, and weigh the evolving evidence before committing to a final diagnosis. To emulate this iterative process, we introduce the Sequential Diagnosis Benchmark, which transforms 304 diagnostically challenging New England Journal of Medicine clinicopathological conference (NEJM-CPC) cases into stepwise diagnostic encounters. A physician or AI begins with a short case abstract and must iteratively request additional details from a gatekeeper model that reveals findings only when explicitly queried. Performance is assessed not just by diagnostic accuracy but also by the cost of physician visits and tests performed. We also present the MAI Diagnostic Orchestrator (MAI-DxO), a model-agnostic orchestrator that simulates a panel of physicians, proposes likely differential diagnoses and strategically selects high-value, cost-effective tests. When paired with OpenAI's o3 model, MAI-DxO achieves 80% diagnostic accuracy--four times higher than the 20% average of generalist physicians. MAI-DxO also reduces diagnostic costs by 20% compared to physicians, and 70% compared to off-the-shelf o3. When configured for maximum accuracy, MAI-DxO achieves 85.5% accuracy. These performance gains with MAI-DxO generalize across models from the OpenAI, Gemini, Claude, Grok, DeepSeek, and Llama families. We highlight how AI systems, when guided to think iteratively and act judiciously, can advance diagnostic precision and cost-effectiveness in clinical care.

The differential diagnosis of neurodegenerative dementias is a challenging clinical task, mainly because of the overlap in symptom presentation and the similarity of patterns observed in structural neuroimaging. To improve diagnostic efficiency and accuracy, deep learning-based methods such as Convolutional Neural Networks and Vision Transformers have been proposed for the automatic classification of brain MRIs. However, despite their strong predictive performance, these models find limited clinical utility due to their opaque decision making. In this work, we propose a framework that integrates two core components to enhance diagnostic transparency. First, we introduce a modular pipeline for converting 3D T1-weighted brain MRIs into textual radiology reports. Second, we explore the potential of modern Large Language Models (LLMs) to assist clinicians in the differential diagnosis between Frontotemporal dementia subtypes, Alzheimer's disease, and normal aging based on the generated reports. To bridge the gap between predictive accuracy and explainability, we employ reinforcement learning to incentivize diagnostic reasoning in LLMs. Without requiring supervised reasoning traces or distillation from larger models, our approach enables the emergence of structured diagnostic rationales grounded in neuroimaging findings. Unlike post-hoc explainability methods that retrospectively justify model decisions, our framework generates diagnostic rationales as part of the inference process-producing causally grounded explanations that inform and guide the model's decision-making process. In doing so, our framework matches the diagnostic performance of existing deep learning methods while offering rationales that support its diagnostic conclusions.

Chest X-ray plays a central role in thoracic diagnosis, and its interpretation inherently requires multi-step, evidence-grounded reasoning. However, large vision-language models (LVLMs) often generate plausible responses that are not faithfully grounded in diagnostic evidence and provide limited visual evidence for verification, while also requiring costly retraining to support new diagnostic tasks, limiting their reliability and adaptability in clinical settings. To address these limitations, we present CXReasonAgent, a diagnostic agent that integrates a large language model (LLM) with clinically grounded diagnostic tools to perform evidence-grounded diagnostic reasoning using image-derived diagnostic and visual evidence. To evaluate these capabilities, we introduce CXReasonDial, a multi-turn dialogue benchmark with 1,946 dialogues across 12 diagnostic tasks, and show that CXReasonAgent produces faithfully grounded responses, enabling more reliable and verifiable diagnostic reasoning than LVLMs. These findings highlight the importance of integrating clinically grounded diagnostic tools, particularly in safety-critical clinical settings.

Artificial Intelligence (AI) has demonstrated significant potential in healthcare, particularly in disease diagnosis and treatment planning. Recent progress in Medical Large Vision-Language Models (Med-LVLMs) has opened up new possibilities for interactive diagnostic tools. However, these models often suffer from factual hallucination, which can lead to incorrect diagnoses. Fine-tuning and retrieval-augmented generation (RAG) have emerged as methods to address these issues. However, the amount of high-quality data and distribution shifts between training data and deployment data limit the application of fine-tuning methods. Although RAG is lightweight and effective, existing RAG-based approaches are not sufficiently general to different medical domains and can potentially cause misalignment issues, both between modalities and between the model and the ground truth. In this paper, we propose a versatile multimodal RAG system, MMed-RAG, designed to enhance the factuality of Med-LVLMs. Our approach introduces a domain-aware retrieval mechanism, an adaptive retrieved contexts selection method, and a provable RAG-based preference fine-tuning strategy. These innovations make the RAG process sufficiently general and reliable, significantly improving alignment when introducing retrieved contexts. Experimental results across five medical datasets (involving radiology, ophthalmology, pathology) on medical VQA and report generation demonstrate that MMed-RAG can achieve an average improvement of 43.8% in the factual accuracy of Med-LVLMs. Our data and code are available in https://github.com/richard-peng-xia/MMed-RAG.

Despite achieving high accuracy on medical benchmarks, LLMs exhibit the Einstellung Effect in clinical diagnosis--relying on statistical shortcuts rather than patient-specific evidence, causing misdiagnosis in atypical cases. Existing benchmarks fail to detect this critical failure mode. We introduce MedEinst, a counterfactual benchmark with 5,383 paired clinical cases across 49 diseases. Each pair contains a control case and a "trap" case with altered discriminative evidence that flips the diagnosis. We measure susceptibility via Bias Trap Rate--probability of misdiagnosing traps despite correctly diagnosing controls. Extensive Evaluation of 17 LLMs shows frontier models achieve high baseline accuracy but severe bias trap rates. Thus, we propose ECR-Agent, aligning LLM reasoning with Evidence-Based Medicine standard via two components: (1) Dynamic Causal Inference (DCI) performs structured reasoning through dual-pathway perception, dynamic causal graph reasoning across three levels (association, intervention, counterfactual), and evidence audit for final diagnosis; (2) Critic-Driven Graph and Memory Evolution (CGME) iteratively refines the system by storing validated reasoning paths in an exemplar base and consolidating disease-specific knowledge into evolving illness graphs. Source code is to be released.

Explaining deep learning models is essential for clinical integration of medical image analysis systems. A good explanation highlights if a model depends on spurious features that undermines generalization and harms a subset of patients or, conversely, may present novel biological insights. Although techniques like GradCAM can identify influential features, they are measurement tools that do not themselves form an explanation. We propose a human-machine-VLM interaction system tailored to explaining classifiers in computational pathology, including multi-instance learning for whole-slide images. Our proof of concept comprises (1) an AI-integrated slide viewer to run sliding-window experiments to test claims of an explanation, and (2) quantification of an explanation's predictiveness using general-purpose vision-language models. The results demonstrate that this allows us to qualitatively test claims of explanations and can quantifiably distinguish competing explanations. This offers a practical path from explainable AI to explained AI in digital pathology and beyond. Code and prompts are available at https://github.com/nki-ai/x2x.

General-purpose Large Vision-Language Models (LVLMs), despite their massive scale, often falter in dermatology due to "diffuse attention" - the inability to disentangle subtle pathological lesions from background noise. In this paper, we challenge the assumption that parameter scaling is the only path to medical precision. We introduce SkinFlow, a framework that treats diagnosis as an optimization of visual information transmission efficiency. Our approach utilizes a Virtual-Width Dynamic Vision Encoder (DVE) to "unfold" complex pathological manifolds without physical parameter expansion, coupled with a two-stage Reinforcement Learning strategy. This strategy sequentially aligns explicit medical descriptions (Stage I) and reconstructs implicit diagnostic textures (Stage II) within a constrained semantic space. Furthermore, we propose a clinically grounded evaluation protocol that prioritizes diagnostic safety and hierarchical relevance over rigid label matching. Empirical results are compelling: our 7B model establishes a new state-of-the-art on the Fitzpatrick17k benchmark, achieving a +12.06% gain in Top-1 accuracy and a +28.57% boost in Top-6 accuracy over the massive general-purpose models (e.g., Qwen3VL-235B and GPT-5.2). These findings demonstrate that optimizing geometric capacity and information flow yields superior diagnostic reasoning compared to raw parameter scaling.

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.

Clinical diagnosis prediction models, when provided with a patient's medical history, aim to detect potential diseases early, facilitating timely intervention and improving prognostic outcomes. However, the inherent scarcity of patient data and large disease candidate space often pose challenges in developing satisfactory models for this intricate task. The exploration of leveraging Large Language Models (LLMs) for encapsulating clinical decision processes has been limited. We introduce MERA, a clinical diagnosis prediction model that bridges pertaining natural language knowledge with medical practice. We apply hierarchical contrastive learning on a disease candidate ranking list to alleviate the large decision space issue. With concept memorization through fine-tuning, we bridge the natural language clinical knowledge with medical codes. Experimental results on MIMIC-III and IV datasets show that MERA achieves the state-of-the-art diagnosis prediction performance and dramatically elevates the diagnosis prediction capabilities of generative LMs.

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.

The emergence of vision-language models (VLMs) has opened new possibilities for clinical reasoning and has shown promising performance in dermatological diagnosis. However, their trustworthiness and clinical utility are often limited by three major factors: (1) Data heterogeneity, where diverse datasets lack consistent diagnostic labels and clinical concept annotations; (2) Absence of grounded diagnostic rationales, leading to a scarcity of reliable reasoning supervision; and (3) Limited scalability and generalization, as models trained on small, densely annotated datasets struggle to transfer nuanced reasoning to large, sparsely-annotated ones. To address these limitations, we propose SkinR1, a novel dermatological VLM that combines deep, textbook-based reasoning with the broad generalization capabilities of reinforcement learning (RL). SkinR1 systematically resolves the key challenges through a unified, end-to-end framework. First, we design a textbook-based reasoning generator that synthesizes high-fidelity, hierarchy-aware, and differential-diagnosis (DDx)-informed trajectories, providing reliable expert-level supervision. Second, we leverage the constructed trajectories for supervised fine-tuning (SFT) empowering the model with grounded reasoning ability. Third, we develop a novel RL paradigm that, by incorporating the hierarchical structure of diseases, effectively transfers these grounded reasoning patterns to large-scale, sparse data. Extensive experiments on multiple dermatology datasets demonstrate that SkinR1 achieves superior diagnostic accuracy. The ablation study demonstrates the importance of the reasoning foundation instilled by SFT.

We introduce a benchmark to directly evaluate the alignment between human observers and vision models on a 3D shape inference task. We leverage an experimental design from the cognitive sciences which requires zero-shot visual inferences about object shape: given a set of images, participants identify which contain the same/different objects, despite considerable viewpoint variation. We draw from a diverse range of images that include common objects (e.g., chairs) as well as abstract shapes (i.e., procedurally generated `nonsense' objects). After constructing over 2000 unique image sets, we administer these tasks to human participants, collecting 35K trials of behavioral data from over 500 participants. This includes explicit choice behaviors as well as intermediate measures, such as reaction time and gaze data. We then evaluate the performance of common vision models (e.g., DINOv2, MAE, CLIP). We find that humans outperform all models by a wide margin. Using a multi-scale evaluation approach, we identify underlying similarities and differences between models and humans: while human-model performance is correlated, humans allocate more time/processing on challenging trials. All images, data, and code can be accessed via our project page.

Advances in artificial intelligence (AI) have achieved expert-level performance in medical imaging applications. Notably, self-supervised vision-language foundation models can detect a broad spectrum of pathologies without relying on explicit training annotations. However, it is crucial to ensure that these AI models do not mirror or amplify human biases, thereby disadvantaging historically marginalized groups such as females or Black patients. The manifestation of such biases could systematically delay essential medical care for certain patient subgroups. In this study, we investigate the algorithmic fairness of state-of-the-art vision-language foundation models in chest X-ray diagnosis across five globally-sourced datasets. Our findings reveal that compared to board-certified radiologists, these foundation models consistently underdiagnose marginalized groups, with even higher rates seen in intersectional subgroups, such as Black female patients. Such demographic biases present over a wide range of pathologies and demographic attributes. Further analysis of the model embedding uncovers its significant encoding of demographic information. Deploying AI systems with these biases in medical imaging can intensify pre-existing care disparities, posing potential challenges to equitable healthcare access and raising ethical questions about their clinical application.

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.

The meaningful use of electronic health records (EHR) continues to progress in the digital era with clinical decision support systems augmented by artificial intelligence. A priority in improving provider experience is to overcome information overload and reduce the cognitive burden so fewer medical errors and cognitive biases are introduced during patient care. One major type of medical error is diagnostic error due to systematic or predictable errors in judgment that rely on heuristics. The potential for clinical natural language processing (cNLP) to model diagnostic reasoning in humans with forward reasoning from data to diagnosis and potentially reduce the cognitive burden and medical error has not been investigated. Existing tasks to advance the science in cNLP have largely focused on information extraction and named entity recognition through classification tasks. We introduce a novel suite of tasks coined as Diagnostic Reasoning Benchmarks, DR.BENCH, as a new benchmark for developing and evaluating cNLP models with clinical diagnostic reasoning ability. The suite includes six tasks from ten publicly available datasets addressing clinical text understanding, medical knowledge reasoning, and diagnosis generation. DR.BENCH is the first clinical suite of tasks designed to be a natural language generation framework to evaluate pre-trained language models. Experiments with state-of-the-art pre-trained generative language models using large general domain models and models that were continually trained on a medical corpus demonstrate opportunities for improvement when evaluated in DR. BENCH. We share DR. BENCH as a publicly available GitLab repository with a systematic approach to load and evaluate models for the cNLP community.

Large language models (LLMs) hold immense promise to serve complex health information needs but also have the potential to introduce harm and exacerbate health disparities. Reliably evaluating equity-related model failures is a critical step toward developing systems that promote health equity. In this work, we present resources and methodologies for surfacing biases with potential to precipitate equity-related harms in long-form, LLM-generated answers to medical questions and then conduct an empirical case study with Med-PaLM 2, resulting in the largest human evaluation study in this area to date. Our contributions include a multifactorial framework for human assessment of LLM-generated answers for biases, and EquityMedQA, a collection of seven newly-released datasets comprising both manually-curated and LLM-generated questions enriched for adversarial queries. Both our human assessment framework and dataset design process are grounded in an iterative participatory approach and review of possible biases in Med-PaLM 2 answers to adversarial queries. Through our empirical study, we find that the use of a collection of datasets curated through a variety of methodologies, coupled with a thorough evaluation protocol that leverages multiple assessment rubric designs and diverse rater groups, surfaces biases that may be missed via narrower evaluation approaches. Our experience underscores the importance of using diverse assessment methodologies and involving raters of varying backgrounds and expertise. We emphasize that while our framework can identify specific forms of bias, it is not sufficient to holistically assess whether the deployment of an AI system promotes equitable health outcomes. We hope the broader community leverages and builds on these tools and methods towards realizing a shared goal of LLMs that promote accessible and equitable healthcare for all.

Human readers or radiologists routinely perform full-body multi-organ multi-disease detection and diagnosis in clinical practice, while most medical AI systems are built to focus on single organs with a narrow list of a few diseases. This might severely limit AI's clinical adoption. A certain number of AI models need to be assembled non-trivially to match the diagnostic process of a human reading a CT scan. In this paper, we construct a Unified Tumor Transformer (UniT) model to detect (tumor existence and location) and diagnose (tumor characteristics) eight major cancer-prevalent organs in CT scans. UniT is a query-based Mask Transformer model with the output of multi-organ and multi-tumor semantic segmentation. We decouple the object queries into organ queries, detection queries and diagnosis queries, and further establish hierarchical relationships among the three groups. This clinically-inspired architecture effectively assists inter- and intra-organ representation learning of tumors and facilitates the resolution of these complex, anatomically related multi-organ cancer image reading tasks. UniT is trained end-to-end using a curated large-scale CT images of 10,042 patients including eight major types of cancers and occurring non-cancer tumors (all are pathology-confirmed with 3D tumor masks annotated by radiologists). On the test set of 631 patients, UniT has demonstrated strong performance under a set of clinically relevant evaluation metrics, substantially outperforming both multi-organ segmentation methods and an assembly of eight single-organ expert models in tumor detection, segmentation, and diagnosis. Such a unified multi-cancer image reading model (UniT) can significantly reduce the number of false positives produced by combined multi-system models. This moves one step closer towards a universal high-performance cancer screening tool.

Recent advances in medical multi-modal models focus on specialized image analysis like dermatology, pathology, or radiology. However, they do not fully capture the complexity of real-world clinical diagnostics, which involve heterogeneous inputs and require ongoing contextual understanding during patient-physician interactions. To bridge this gap, we introduce PulseMind, a new family of multi-modal diagnostic models that integrates a systematically curated dataset, a comprehensive evaluation benchmark, and a tailored training framework. Specifically, we first construct a diagnostic dataset, MediScope, which comprises 98,000 real-world multi-turn consultations and 601,500 medical images, spanning over 10 major clinical departments and more than 200 sub-specialties. Then, to better reflect the requirements of real-world clinical diagnosis, we develop the PulseMind Benchmark, a multi-turn diagnostic consultation benchmark with a four-dimensional evaluation protocol comprising proactiveness, accuracy, usefulness, and language quality. Finally, we design a training framework tailored for multi-modal clinical diagnostics, centered around a core component named Comparison-based Reinforcement Policy Optimization (CRPO). Compared to absolute score rewards, CRPO uses relative preference signals from multi-dimensional com-parisons to provide stable and human-aligned training guidance. Extensive experiments demonstrate that PulseMind achieves competitive performance on both the diagnostic consultation benchmark and public medical benchmarks.

Large language models (LLMs) have demonstrated impressive capabilities in natural language understanding and generation, but the quality bar for medical and clinical applications is high. Today, attempts to assess models' clinical knowledge typically rely on automated evaluations on limited benchmarks. There is no standard to evaluate model predictions and reasoning across a breadth of tasks. To address this, we present MultiMedQA, a benchmark combining six existing open question answering datasets spanning professional medical exams, research, and consumer queries; and HealthSearchQA, a new free-response dataset of medical questions searched online. We propose a framework for human evaluation of model answers along multiple axes including factuality, precision, possible harm, and bias. In addition, we evaluate PaLM (a 540-billion parameter LLM) and its instruction-tuned variant, Flan-PaLM, on MultiMedQA. Using a combination of prompting strategies, Flan-PaLM achieves state-of-the-art accuracy on every MultiMedQA multiple-choice dataset (MedQA, MedMCQA, PubMedQA, MMLU clinical topics), including 67.6% accuracy on MedQA (US Medical License Exam questions), surpassing prior state-of-the-art by over 17%. However, human evaluation reveals key gaps in Flan-PaLM responses. To resolve this we introduce instruction prompt tuning, a parameter-efficient approach for aligning LLMs to new domains using a few exemplars. The resulting model, Med-PaLM, performs encouragingly, but remains inferior to clinicians. We show that comprehension, recall of knowledge, and medical reasoning improve with model scale and instruction prompt tuning, suggesting the potential utility of LLMs in medicine. Our human evaluations reveal important limitations of today's models, reinforcing the importance of both evaluation frameworks and method development in creating safe, helpful LLM models for clinical applications.

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.

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.

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.

Depression poses significant challenges to patients and healthcare organizations, necessitating efficient assessment methods. Existing paradigms typically focus on a patient-doctor way that overlooks multi-role interactions, such as family involvement in the evaluation and caregiving process. Moreover, current automatic depression detection (ADD) methods usually model depression detection as a classification or regression task, lacking interpretability for the decision-making process. To address these issues, we developed InterMind, a doctor-patient-family interactive depression assessment system empowered by large language models (LLMs). Our system enables patients and families to contribute descriptions, generates assistive diagnostic reports for doctors, and provides actionable insights, improving diagnostic precision and efficiency. To enhance LLMs' performance in psychological counseling and diagnostic interpretability, we integrate retrieval-augmented generation (RAG) and chain-of-thoughts (CoT) techniques for data augmentation, which mitigates the hallucination issue of LLMs in specific scenarios after instruction fine-tuning. Quantitative experiments and professional assessments by clinicians validate the effectiveness of our system.

Chain-of-Thought (CoT) reasoning has proven effective in enhancing large language models by encouraging step-by-step intermediate reasoning, and recent advances have extended this paradigm to Multimodal Large Language Models (MLLMs). In the medical domain, where diagnostic decisions depend on nuanced visual cues and sequential reasoning, CoT aligns naturally with clinical thinking processes. However, Current benchmarks for medical image understanding generally focus on the final answer while ignoring the reasoning path. An opaque process lacks reliable bases for judgment, making it difficult to assist doctors in diagnosis. To address this gap, we introduce a new M3CoTBench benchmark specifically designed to evaluate the correctness, efficiency, impact, and consistency of CoT reasoning in medical image understanding. M3CoTBench features 1) a diverse, multi-level difficulty dataset covering 24 examination types, 2) 13 varying-difficulty tasks, 3) a suite of CoT-specific evaluation metrics (correctness, efficiency, impact, and consistency) tailored to clinical reasoning, and 4) a performance analysis of multiple MLLMs. M3CoTBench systematically evaluates CoT reasoning across diverse medical imaging tasks, revealing current limitations of MLLMs in generating reliable and clinically interpretable reasoning, and aims to foster the development of transparent, trustworthy, and diagnostically accurate AI systems for healthcare. Project page at https://juntaojianggavin.github.io/projects/M3CoTBench/.

Radiology reporting generative AI holds significant potential to alleviate clinical workloads and streamline medical care. However, achieving high clinical accuracy is challenging, as radiological images often feature subtle lesions and intricate structures. Existing systems often fall short, largely due to their reliance on fixed size, patch-level image features and insufficient incorporation of pathological information. This can result in the neglect of such subtle patterns and inconsistent descriptions of crucial pathologies. To address these challenges, we propose an innovative approach that leverages pathology-aware regional prompts to explicitly integrate anatomical and pathological information of various scales, significantly enhancing the precision and clinical relevance of generated reports. We develop an anatomical region detector that extracts features from distinct anatomical areas, coupled with a novel multi-label lesion detector that identifies global pathologies. Our approach emulates the diagnostic process of radiologists, producing clinically accurate reports with comprehensive diagnostic capabilities. Experimental results show that our model outperforms previous state-of-the-art methods on most natural language generation and clinical efficacy metrics, with formal expert evaluations affirming its potential to enhance radiology practice.

Dermatological diagnosis represents a complex multimodal challenge that requires integrating visual features with specialized clinical knowledge. While vision-language pretraining (VLP) has advanced medical AI, its effectiveness in dermatology is limited by text length constraints and the lack of structured texts. In this paper, we introduce MAKE, a Multi-Aspect Knowledge-Enhanced vision-language pretraining framework for zero-shot dermatological tasks. Recognizing that comprehensive dermatological descriptions require multiple knowledge aspects that exceed standard text constraints, our framework introduces: (1) a multi-aspect contrastive learning strategy that decomposes clinical narratives into knowledge-enhanced sub-texts through large language models, (2) a fine-grained alignment mechanism that connects subcaptions with diagnostically relevant image features, and (3) a diagnosis-guided weighting scheme that adaptively prioritizes different sub-captions based on clinical significance prior. Through pretraining on 403,563 dermatological image-text pairs collected from education resources, MAKE significantly outperforms state-of-the-art VLP models on eight datasets across zero-shot skin disease classification, concept annotation, and cross-modal retrieval tasks. Our code will be made publicly available at https: //github.com/SiyuanYan1/MAKE.

Immunohistochemistry (IHC) provides information on protein expression in tissue sections and is commonly used to support pathology diagnosis and disease triage. While AI models for H\&E-stained slides show promise, their applicability to IHC is limited due to domain-specific variations. Here we introduce HPA10M, a dataset that contains 10,495,672 IHC images from the Human Protein Atlas with comprehensive metadata included, and encompasses 45 normal tissue types and 20 major cancer types. Based on HPA10M, we trained iSight, a multi-task learning framework for automated IHC staining assessment. iSight combines visual features from whole-slide images with tissue metadata through a token-level attention mechanism, simultaneously predicting staining intensity, location, quantity, tissue type, and malignancy status. On held-out data, iSight achieved 85.5\% accuracy for location, 76.6\% for intensity, and 75.7\% for quantity, outperforming fine-tuned foundation models (PLIP, CONCH) by 2.5--10.2\%. In addition, iSight demonstrates well-calibrated predictions with expected calibration errors of 0.0150-0.0408. Furthermore, in a user study with eight pathologists evaluating 200 images from two datasets, iSight outperformed initial pathologist assessments on the held-out HPA dataset (79\% vs 68\% for location, 70\% vs 57\% for intensity, 68\% vs 52\% for quantity). Inter-pathologist agreement also improved after AI assistance in both held-out HPA (Cohen's κ increased from 0.63 to 0.70) and Stanford TMAD datasets (from 0.74 to 0.76), suggesting expert--AI co-assessment can improve IHC interpretation. This work establishes a foundation for AI systems that can improve IHC diagnostic accuracy and highlights the potential for integrating iSight into clinical workflows to enhance the consistency and reliability of IHC assessment.

Zero-shot medical detection can further improve detection performance without relying on annotated medical images even upon the fine-tuned model, showing great clinical value. Recent studies leverage grounded vision-language models (GLIP) to achieve this by using detailed disease descriptions as prompts for the target disease name during the inference phase. However, these methods typically treat prompts as equivalent context to the target name, making it difficult to assign specific disease knowledge based on visual information, leading to a coarse alignment between images and target descriptions. In this paper, we propose StructuralGLIP, which introduces an auxiliary branch to encode prompts into a latent knowledge bank layer-by-layer, enabling more context-aware and fine-grained alignment. Specifically, in each layer, we select highly similar features from both the image representation and the knowledge bank, forming structural representations that capture nuanced relationships between image patches and target descriptions. These features are then fused across modalities to further enhance detection performance. Extensive experiments demonstrate that StructuralGLIP achieves a +4.1\% AP improvement over prior state-of-the-art methods across seven zero-shot medical detection benchmarks, and consistently improves fine-tuned models by +3.2\% AP on endoscopy image datasets.

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.

In this paper, we present a framework for training large language models (LLMs) as diagnostic agents with reinforcement learning, enabling them to manage multi-turn diagnostic processes, adaptively select examinations, and commit to final diagnoses. Unlike instruction-tuned models trained on static case summaries, our method acquires diagnostic strategies through interactive exploration and outcome-based feedback. Our contributions are fourfold: (i) We present DiagGym, a diagnostics world model trained with electronic health records that emits examination outcomes conditioned on patient history and recommended examination, serving as a virtual clinical environment for realistic diagnosis training and evaluation; (ii) We train DiagAgent via end-to-end, multi-turn reinforcement learning to learn diagnostic policies that optimize both information yield and diagnostic accuracy; (iii) We introduce DiagBench, a diagnostic benchmark comprising 750 cases with physician-validated examination recommendations and 99 cases annotated with 973 physician-written rubrics on diagnosis process; (iv) we demonstrate superior performance across diverse diagnostic settings. DiagAgent significantly outperforms 10 state-of-the-art LLMs, including DeepSeek-v3 and GPT-4o, as well as two prompt-engineered agents. In single-turn settings, DiagAgent achieves 9.34% higher diagnostic accuracy and 44.03% improvement in examination recommendation hit ratio. In end-to-end settings, it delivers 15.12% increase in diagnostic accuracy and 23.09% boost in examination recommendation F1 score. In rubric-based evaluation, it surpasses the next-best model, Claude-sonnet-4, by 7.1% in weighted rubric score. These findings indicate that learning policies in interactive clinical environments confers dynamic and clinically meaningful diagnostic management abilities unattainable through passive training alone.

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.

Accurate and interpretable multi-disease diagnosis remains a critical challenge in medical research, particularly when leveraging heterogeneous multimodal medical data. Current approaches often rely on single-modal data, limiting their ability to comprehensively understand complex diseases. To address this, we propose MedTVT-R1, a novel Multimodal Large Language Model (MLLM) framework designed to integrate clinical multimodal data for reasoning and diagnosing multiple diseases. We construct MedTVT-QA, a curated instruction dataset that provides question-answer pairs for physiological-level interpretations and disease-level diagnoses with a Chain of Evidence approach. MedTVT-R1 incorporates a modality perception layer to capture inter-modal dependencies and adaptively weight modality contributions. Additionally, we employ Group Relative Policy Optimization (GRPO)-based Reinforcement Fine-Tuning with a Jaccard Reward function to enhance diagnostic reasoning. Experimental results demonstrate MedTVT-R1's superiority in multimodal feature utilization and multi-disease diagnosis, offering significant potential for clinical applications such as diagnostic report generation and comorbidity reasoning. The dataset and code are available at https://github.com/keke-nice/MedTVT-R1.

Common methods for aligning already-capable models with desired behavior rely on the ability of humans to provide supervision. However, future superhuman models will surpass the capability of humans. Therefore, humans will only be able to weakly supervise superhuman models. This expected deficiency of human evaluation would weaken the safety of future AI systems. Scalable oversight and weak-to-strong generalization are two complementary approaches to tackle this issue. In this paper, we attempt to combine the strengths of these two approaches to further improve alignment. Specifically, we investigate ways of improving human supervision with a strong pretrained model and then supervise the strong model with enhanced weak human supervision. To make iterative empirical progress, we consider an analogy: can we use a strong model to improve weak model supervision and then use it to supervise the strong model? We empirically test it by finetuning a small weak model on ground truth labels with the additional help from a large strong model, and then finetuning the strong model on labels generated by the weak model. We find that debate can assist a weak model in extracting trustworthy information from an untrustworthy strong model, which provides leverage as context on samples when training a weak model. We also show that an ensemble of weak models helps exploit long arguments generated by strong model debaters and obtain a more robust supervision estimate. Extensive experiments on the OpenAI weak-to-strong NLP benchmarks show that the combination approach leads to better alignment, which indicates that debate has the potential to help weak-to-strong generalization.

Large language models (LLMs) are becoming deeply embedded in human communication and decision-making, yet they inherit the ambiguity, bias, and lack of direct access to truth inherent in language itself. While their outputs are fluent, emotionally resonant, and coherent, they are generated through statistical prediction rather than grounded reasoning. This creates the risk of hallucination, responses that sound convincing but lack factual validity. Building on Geoffrey Hinton's observation that AI mirrors human intuition rather than reasoning, this paper argues that LLMs operationalize System 1 cognition at scale: fast, associative, and persuasive, but without reflection or falsification. To address this, we introduce the Rose-Frame, a three-dimensional framework for diagnosing cognitive and epistemic drift in human-AI interaction. The three axes are: (i) Map vs. Territory, which distinguishes representations of reality (epistemology) from reality itself (ontology); (ii) Intuition vs. Reason, drawing on dual-process theory to separate fast, emotional judgments from slow, reflective thinking; and (iii) Conflict vs. Confirmation, which examines whether ideas are critically tested through disagreement or simply reinforced through mutual validation. Each dimension captures a distinct failure mode, and their combination amplifies misalignment. Rose-Frame does not attempt to fix LLMs with more data or rules. Instead, it offers a reflective tool that makes both the model's limitations and the user's assumptions visible, enabling more transparent and critically aware AI deployment. It reframes alignment as cognitive governance: intuition, whether human or artificial, must remain governed by human reason. Only by embedding reflective, falsifiable oversight can we align machine fluency with human understanding.

Current AI alignment methodologies rely on human-provided demonstrations or judgments, and the learned capabilities of AI systems would be upper-bounded by human capabilities as a result. This raises a challenging research question: How can we keep improving the systems when their capabilities have surpassed the levels of humans? This paper answers this question in the context of tackling hard reasoning tasks (e.g., level 4-5 MATH problems) via learning from human annotations on easier tasks (e.g., level 1-3 MATH problems), which we term as easy-to-hard generalization. Our key insight is that an evaluator (reward model) trained on supervisions for easier tasks can be effectively used for scoring candidate solutions of harder tasks and hence facilitating easy-to-hard generalization over different levels of tasks. Based on this insight, we propose a novel approach to scalable alignment, which firstly trains the process-supervised reward models on easy problems (e.g., level 1-3), and then uses them to evaluate the performance of policy models on hard problems. We show that such easy-to-hard generalization from evaluators can enable easy-to-hard generalizations in generators either through re-ranking or reinforcement learning (RL). Notably, our process-supervised 7b RL model achieves an accuracy of 34.0\% on MATH500, despite only using human supervision on easy problems. Our approach suggests a promising path toward AI systems that advance beyond the frontier of human supervision.

The 7-point checklist (7PCL) is a widely used diagnostic tool in dermoscopy for identifying malignant melanoma by assigning point values to seven specific attributes. However, the traditional 7PCL is limited to distinguishing between malignant melanoma and melanocytic Nevi, and falls short in scenarios where multiple skin diseases with appearances similar to melanoma coexist. To address this limitation, we propose a novel diagnostic framework that integrates a clinical knowledge-based topological graph (CKTG) with a gradient diagnostic strategy featuring a data-driven weighting system (GD-DDW). The CKTG captures both the internal and external relationships among the 7PCL attributes, while the GD-DDW emulates dermatologists' diagnostic processes, prioritizing visual observation before making predictions. Additionally, we introduce a multimodal feature extraction approach leveraging a dual-attention mechanism to enhance feature extraction through cross-modal interaction and unimodal collaboration. This method incorporates meta-information to uncover interactions between clinical data and image features, ensuring more accurate and robust predictions. Our approach, evaluated on the EDRA dataset, achieved an average AUC of 88.6%, demonstrating superior performance in melanoma detection and feature prediction. This integrated system provides data-driven benchmarks for clinicians, significantly enhancing the precision of melanoma diagnosis.

Automated diagnosis prediction from medical images is a valuable resource to support clinical decision-making. However, such systems usually need to be trained on large amounts of annotated data, which often is scarce in the medical domain. Zero-shot methods address this challenge by allowing a flexible adaption to new settings with different clinical findings without relying on labeled data. Further, to integrate automated diagnosis in the clinical workflow, methods should be transparent and explainable, increasing medical professionals' trust and facilitating correctness verification. In this work, we introduce Xplainer, a novel framework for explainable zero-shot diagnosis in the clinical setting. Xplainer adapts the classification-by-description approach of contrastive vision-language models to the multi-label medical diagnosis task. Specifically, instead of directly predicting a diagnosis, we prompt the model to classify the existence of descriptive observations, which a radiologist would look for on an X-Ray scan, and use the descriptor probabilities to estimate the likelihood of a diagnosis. Our model is explainable by design, as the final diagnosis prediction is directly based on the prediction of the underlying descriptors. We evaluate Xplainer on two chest X-ray datasets, CheXpert and ChestX-ray14, and demonstrate its effectiveness in improving the performance and explainability of zero-shot diagnosis. Our results suggest that Xplainer provides a more detailed understanding of the decision-making process and can be a valuable tool for clinical diagnosis.

Evaluating explanations of image classifiers regarding ground truth, e.g. segmentation masks defined by human perception, primarily evaluates the quality of the models under consideration rather than the explanation methods themselves. Driven by this observation, we propose a framework for jointly evaluating the robustness of safety-critical systems that combine a deep neural network with an explanation method. These are increasingly used in real-world applications like medical image analysis or robotics. We introduce a fine-tuning procedure to (mis)align modelx2013explanation pipelines with ground truth and use it to quantify the potential discrepancy between worst and best-case scenarios of human alignment. Experiments across various model architectures and post-hoc local interpretation methods provide insights into the robustness of vision transformers and the overall vulnerability of such AI systems to potential adversarial attacks.

Vision-Language Models (VLMs) frequently "hallucinate" - generate plausible yet factually incorrect statements - posing a critical barrier to their trustworthy deployment. In this work, we propose a new paradigm for diagnosing hallucinations, recasting them from static output errors into dynamic pathologies of a model's computational cognition. Our framework is grounded in a normative principle of computational rationality, allowing us to model a VLM's generation as a dynamic cognitive trajectory. We design a suite of information-theoretic probes that project this trajectory onto an interpretable, low-dimensional Cognitive State Space. Our central discovery is a governing principle we term the geometric-information duality: a cognitive trajectory's geometric abnormality within this space is fundamentally equivalent to its high information-theoretic surprisal. Hallucination detection is counts as a geometric anomaly detection problem. Evaluated across diverse settings - from rigorous binary QA (POPE) and comprehensive reasoning (MME) to unconstrained open-ended captioning (MS-COCO) - our framework achieves state-of-the-art performance. Crucially, it operates with high efficiency under weak supervision and remains highly robust even when calibration data is heavily contaminated. This approach enables a causal attribution of failures, mapping observable errors to distinct pathological states: perceptual instability (measured by Perceptual Entropy), logical-causal failure (measured by Inferential Conflict), and decisional ambiguity (measured by Decision Entropy). Ultimately, this opens a path toward building AI systems whose reasoning is transparent, auditable, and diagnosable by design.

Whole Slide Images (WSIs) exhibit hierarchical structure, where diagnostic information emerges from cellular morphology, regional tissue organization, and global context. Existing Computational Pathology (CPath) Multimodal Large Language Models (MLLMs) typically compress an entire WSI into a single embedding, which hinders fine-grained grounding and ignores how pathologists synthesize evidence across different scales. We introduce MLLM-HWSI, a Hierarchical WSI-level MLLM that aligns visual features with pathology language at four distinct scales, cell as word, patch as phrase, region as sentence, and WSI as paragraph to support interpretable evidence-grounded reasoning. MLLM-HWSI decomposes each WSI into multi-scale embeddings with scale-specific projectors and jointly enforces (i) a hierarchical contrastive objective and (ii) a cross-scale consistency loss, preserving semantic coherence from cells to the WSI. We compute diagnostically relevant patches and aggregate segmented cell embeddings into a compact cellular token per-patch using a lightweight Cell-Cell Attention Fusion (CCAF) transformer. The projected multi-scale tokens are fused with text tokens and fed to an instruction-tuned LLM for open-ended reasoning, VQA, report, and caption generation tasks. Trained in three stages, MLLM-HWSI achieves new SOTA results on 13 WSI-level benchmarks across six CPath tasks. By aligning language with multi-scale visual evidence, MLLM-HWSI provides accurate, interpretable outputs that mirror diagnostic workflows and advance holistic WSI understanding. Code is available at: https://github.com/BasitAlawode/HWSI-MLLM{GitHub}.

At the heart of medicine lies the physician-patient dialogue, where skillful history-taking paves the way for accurate diagnosis, effective management, and enduring trust. Artificial Intelligence (AI) systems capable of diagnostic dialogue could increase accessibility, consistency, and quality of care. However, approximating clinicians' expertise is an outstanding grand challenge. Here, we introduce AMIE (Articulate Medical Intelligence Explorer), a Large Language Model (LLM) based AI system optimized for diagnostic dialogue. AMIE uses a novel self-play based simulated environment with automated feedback mechanisms for scaling learning across diverse disease conditions, specialties, and contexts. We designed a framework for evaluating clinically-meaningful axes of performance including history-taking, diagnostic accuracy, management reasoning, communication skills, and empathy. We compared AMIE's performance to that of primary care physicians (PCPs) in a randomized, double-blind crossover study of text-based consultations with validated patient actors in the style of an Objective Structured Clinical Examination (OSCE). The study included 149 case scenarios from clinical providers in Canada, the UK, and India, 20 PCPs for comparison with AMIE, and evaluations by specialist physicians and patient actors. AMIE demonstrated greater diagnostic accuracy and superior performance on 28 of 32 axes according to specialist physicians and 24 of 26 axes according to patient actors. Our research has several limitations and should be interpreted with appropriate caution. Clinicians were limited to unfamiliar synchronous text-chat which permits large-scale LLM-patient interactions but is not representative of usual clinical practice. While further research is required before AMIE could be translated to real-world settings, the results represent a milestone towards conversational diagnostic AI.

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.

Chest X-ray imaging is crucial for diagnosing pulmonary and cardiac diseases, yet its interpretation demands extensive clinical experience and suffers from inter-observer variability. While deep learning models offer high diagnostic accuracy, their black-box nature hinders clinical adoption in high-stakes medical settings. To address this, we propose X-Ray-CoT (Chest X-Ray Chain-of-Thought), a novel framework leveraging Vision-Language Large Models (LVLMs) for intelligent chest X-ray diagnosis and interpretable report generation. X-Ray-CoT simulates human radiologists' "chain-of-thought" by first extracting multi-modal features and visual concepts, then employing an LLM-based component with a structured Chain-of-Thought prompting strategy to reason and produce detailed natural language diagnostic reports. Evaluated on the CORDA dataset, X-Ray-CoT achieves competitive quantitative performance, with a Balanced Accuracy of 80.52% and F1 score of 78.65% for disease diagnosis, slightly surpassing existing black-box models. Crucially, it uniquely generates high-quality, explainable reports, as validated by preliminary human evaluations. Our ablation studies confirm the integral role of each proposed component, highlighting the necessity of multi-modal fusion and CoT reasoning for robust and transparent medical AI. This work represents a significant step towards trustworthy and clinically actionable AI systems in medical imaging.

Automatic radiology report generation is booming due to its huge application potential for the healthcare industry. However, existing computer vision and natural language processing approaches to tackle this problem are limited in two aspects. First, when extracting image features, most of them neglect multi-view reasoning in vision and model single-view structure of medical images, such as space-view or channel-view. However, clinicians rely on multi-view imaging information for comprehensive judgment in daily clinical diagnosis. Second, when generating reports, they overlook context reasoning with multi-modal information and focus on pure textual optimization utilizing retrieval-based methods. We aim to address these two issues by proposing a model that better simulates clinicians' perspectives and generates more accurate reports. Given the above limitation in feature extraction, we propose a Globally-intensive Attention (GIA) module in the medical image encoder to simulate and integrate multi-view vision perception. GIA aims to learn three types of vision perception: depth view, space view, and pixel view. On the other hand, to address the above problem in report generation, we explore how to involve multi-modal signals to generate precisely matched reports, i.e., how to integrate previously predicted words with region-aware visual content in next word prediction. Specifically, we design a Visual Knowledge-guided Decoder (VKGD), which can adaptively consider how much the model needs to rely on visual information and previously predicted text to assist next word prediction. Hence, our final Intensive Vision-guided Network (IVGN) framework includes a GIA-guided Visual Encoder and the VKGD. Experiments on two commonly-used datasets IU X-Ray and MIMIC-CXR demonstrate the superior ability of our method compared with other state-of-the-art approaches.

Vision-Language Models (VLMs) show promise in medical image analysis, yet their capacity for structured reasoning in complex domains like dermatology is often limited by data scarcity and the high computational cost of advanced training techniques. To address these challenges, we introduce DermIQ-VLM, a VLM developed through a multi-stage, resource-efficient methodology designed to emulate a dermatologist's diagnostic process. Our primary contribution is a modified version of Grouped Relative Policy Optimization (GRPO), called GRPO++, which stabilizes the powerful but data-intensive GRPO framework. Our proposed training pipeline first employs GRPO++ for reasoning-oriented disease recognition, followed by supervised fine-tuning for conversational ability. To mitigate factual errors introduced during this step, we then align the model using Direct Preference Optimization (DPO), leveraging a Knowledge Graph-based system as a scalable proxy for expert preference. A preliminary evaluation on a curated dermatological dataset demonstrates that our proposed methodology yields notable performance gains over standard fine-tuning approaches. These findings validate the potential of our pipeline as a feasible pathway for developing specialized, reliable VLMs in resource-constrained environments.

Foundation vision-language models are currently transforming computer vision, and are on the rise in medical imaging fueled by their very promising generalization capabilities. However, the initial attempts to transfer this new paradigm to medical imaging have shown less impressive performances than those observed in other domains, due to the significant domain shift and the complex, expert domain knowledge inherent to medical-imaging tasks. Motivated by the need for domain-expert foundation models, we present FLAIR, a pre-trained vision-language model for universal retinal fundus image understanding. To this end, we compiled 37 open-access, mostly categorical fundus imaging datasets from various sources, with up to 97 different target conditions and 284,660 images. We integrate the expert's domain knowledge in the form of descriptive textual prompts, during both pre-training and zero-shot inference, enhancing the less-informative categorical supervision of the data. Such a textual expert's knowledge, which we compiled from the relevant clinical literature and community standards, describes the fine-grained features of the pathologies as well as the hierarchies and dependencies between them. We report comprehensive evaluations, which illustrate the benefit of integrating expert knowledge and the strong generalization capabilities of FLAIR under difficult scenarios with domain shifts or unseen categories. When adapted with a lightweight linear probe, FLAIR outperforms fully-trained, dataset-focused models, more so in the few-shot regimes. Interestingly, FLAIR outperforms by a large margin more generalist, larger-scale image-language models, which emphasizes the potential of embedding experts' domain knowledge and the limitations of generalist models in medical imaging.

Integrating Large Language Models (LLMs) in healthcare diagnosis demands systematic frameworks that can handle complex medical scenarios while maintaining specialized expertise. We present KG4Diagnosis, a novel hierarchical multi-agent framework that combines LLMs with automated knowledge graph construction, encompassing 362 common diseases across medical specialties. Our framework mirrors real-world medical systems through a two-tier architecture: a general practitioner (GP) agent for initial assessment and triage, coordinating with specialized agents for in-depth diagnosis in specific domains. The core innovation lies in our end-to-end knowledge graph generation methodology, incorporating: (1) semantic-driven entity and relation extraction optimized for medical terminology, (2) multi-dimensional decision relationship reconstruction from unstructured medical texts, and (3) human-guided reasoning for knowledge expansion. KG4Diagnosis serves as an extensible foundation for specialized medical diagnosis systems, with capabilities to incorporate new diseases and medical knowledge. The framework's modular design enables seamless integration of domain-specific enhancements, making it valuable for developing targeted medical diagnosis systems. We provide architectural guidelines and protocols to facilitate adoption across medical contexts.

Human-like personality traits have recently been discovered in large language models, raising the hypothesis that their (known and as yet undiscovered) biases conform with human latent psychological constructs. While large conversational models may be tricked into answering psychometric questionnaires, the latent psychological constructs of thousands of simpler transformers, trained for other tasks, cannot be assessed because appropriate psychometric methods are currently lacking. Here, we show how standard psychological questionnaires can be reformulated into natural language inference prompts, and we provide a code library to support the psychometric assessment of arbitrary models. We demonstrate, using a sample of 88 publicly available models, the existence of human-like mental health-related constructs (including anxiety, depression, and Sense of Coherence) which conform with standard theories in human psychology and show similar correlations and mitigation strategies. The ability to interpret and rectify the performance of language models by using psychological tools can boost the development of more explainable, controllable, and trustworthy models.

Building upon our previous investigations of O1 replication (Part 1: Journey Learning [Qin et al., 2024] and Part 2: Distillation [Huang et al., 2024]), this work explores the potential of inference-time scaling in large language models (LLMs) for medical reasoning tasks, ranging from diagnostic decision-making to treatment planning. Through extensive experiments on medical benchmarks of varying complexity (MedQA, Medbullets, and JAMA Clinical Challenges), our investigation reveals several key insights: (1) Increasing inference time does lead to improved performance. With a modest training set of 500 samples, our model yields substantial performance improvements of 6%-11%. (2) Task complexity directly correlates with the required length of reasoning chains, confirming the necessity of extended thought processes for challenging problems. (3) The differential diagnoses generated by our model adhere to the principles of the hypothetico-deductive method, producing a list of potential conditions that may explain a patient's symptoms and systematically narrowing these possibilities by evaluating the evidence. These findings demonstrate the promising synergy between inference-time scaling and journey learning in advancing LLMs' real-world clinical reasoning capabilities.

We introduce MentalBench, a benchmark for evaluating psychiatric diagnostic decision-making in large language models (LLMs). Existing mental health benchmarks largely rely on social media data, limiting their ability to assess DSM-grounded diagnostic judgments. At the core of MentalBench is MentalKG, a psychiatrist-built and validated knowledge graph encoding DSM-5 diagnostic criteria and differential diagnostic rules for 23 psychiatric disorders. Using MentalKG as a golden-standard logical backbone, we generate 24,750 synthetic clinical cases that systematically vary in information completeness and diagnostic complexity, enabling low-noise and interpretable evaluation. Our experiments show that while state-of-the-art LLMs perform well on structured queries probing DSM-5 knowledge, they struggle to calibrate confidence in diagnostic decision-making when distinguishing between clinically overlapping disorders. These findings reveal evaluation gaps not captured by existing benchmarks.

Current medical retrieval benchmarks primarily emphasize lexical or shallow semantic similarity, overlooking the reasoning-intensive demands that are central to clinical decision-making. In practice, physicians often retrieve authoritative medical evidence to support diagnostic hypotheses. Such evidence typically aligns with an inferred diagnosis rather than the surface form of a patient's symptoms, leading to low lexical or semantic overlap between queries and relevant documents. To address this gap, we introduce R2MED, the first benchmark explicitly designed for reasoning-driven medical retrieval. It comprises 876 queries spanning three tasks: Q&A reference retrieval, clinical evidence retrieval, and clinical case retrieval. These tasks are drawn from five representative medical scenarios and twelve body systems, capturing the complexity and diversity of real-world medical information needs. We evaluate 15 widely-used retrieval systems on R2MED and find that even the best model achieves only 31.4 nDCG@10, demonstrating the benchmark's difficulty. Classical re-ranking and generation-augmented retrieval methods offer only modest improvements. Although large reasoning models improve performance via intermediate inference generation, the best results still peak at 41.4 nDCG@10. These findings underscore a substantial gap between current retrieval techniques and the reasoning demands of real clinical tasks. We release R2MED as a challenging benchmark to foster the development of next-generation medical retrieval systems with enhanced reasoning capabilities. Data and code are available at https://github.com/R2MED/R2MED

Pulmonary embolism (PE) is a life-threatening condition where rapid and accurate diagnosis is imperative yet difficult due to predominantly atypical symptomatology. Computed tomography pulmonary angiography (CTPA) is acknowledged as the gold standard imaging tool in clinics, yet it can be contraindicated for emergency department (ED) patients and represents an onerous procedure, thus necessitating PE identification through non-contrast CT (NCT) scans. In this work, we explore the feasibility of applying a deep-learning approach to NCT scans for PE identification. We propose a novel Cross-Phase Mutual learNing framework (CPMN) that fosters knowledge transfer from CTPA to NCT, while concurrently conducting embolism segmentation and abnormality classification in a multi-task manner. The proposed CPMN leverages the Inter-Feature Alignment (IFA) strategy that enhances spatial contiguity and mutual learning between the dual-pathway network, while the Intra-Feature Discrepancy (IFD) strategy can facilitate precise segmentation of PE against complex backgrounds for single-pathway networks. For a comprehensive assessment of the proposed approach, a large-scale dual-phase dataset containing 334 PE patients and 1,105 normal subjects has been established. Experimental results demonstrate that CPMN achieves the leading identification performance, which is 95.4\% and 99.6\% in patient-level sensitivity and specificity on NCT scans, indicating the potential of our approach as an economical, accessible, and precise tool for PE identification in clinical practice.

Robust benchmarks are crucial for evaluating Multimodal Large Language Models (MLLMs). Yet we find that models can ace many multimodal benchmarks without strong visual understanding, instead exploiting biases, linguistic priors, and superficial patterns. This is especially problematic for vision-centric benchmarks that are meant to require visual inputs. We adopt a diagnostic principle for benchmark design: if a benchmark can be gamed, it will be. Designers should therefore try to ``game'' their own benchmarks first, using diagnostic and debiasing procedures to systematically identify and mitigate non-visual biases. Effective diagnosis requires directly ``training on the test set'' -- probing the released test set for its intrinsic, exploitable patterns. We operationalize this standard with two components. First, we diagnose benchmark susceptibility using a ``Test-set Stress-Test'' (TsT) methodology. Our primary diagnostic tool involves fine-tuning a powerful Large Language Model via k-fold cross-validation on exclusively the non-visual, textual inputs of the test set to reveal shortcut performance and assign each sample a bias score s(x). We complement this with a lightweight Random Forest-based diagnostic operating on hand-crafted features for fast, interpretable auditing. Second, we debias benchmarks by filtering high-bias samples using an ``Iterative Bias Pruning'' (IBP) procedure. Applying this framework to four benchmarks -- VSI-Bench, CV-Bench, MMMU, and VideoMME -- we uncover pervasive non-visual biases. As a case study, we apply our full framework to create VSI-Bench-Debiased, demonstrating reduced non-visual solvability and a wider vision-blind performance gap than the original.

Medical phrase grounding is crucial for identifying relevant regions in medical images based on phrase queries, facilitating accurate image analysis and diagnosis. However, current methods rely on manual extraction of key phrases from medical reports, reducing efficiency and increasing the workload for clinicians. Additionally, the lack of model confidence estimation limits clinical trust and usability. In this paper, we introduce a novel task called Medical Report Grounding (MRG), which aims to directly identify diagnostic phrases and their corresponding grounding boxes from medical reports in an end-to-end manner. To address this challenge, we propose uMedGround, a robust and reliable framework that leverages a multimodal large language model to predict diagnostic phrases by embedding a unique token, <BOX>, into the vocabulary to enhance detection capabilities. A vision encoder-decoder processes the embedded token and input image to generate grounding boxes. Critically, uMedGround incorporates an uncertainty-aware prediction model, significantly improving the robustness and reliability of grounding predictions. Experimental results demonstrate that uMedGround outperforms state-of-the-art medical phrase grounding methods and fine-tuned large visual-language models, validating its effectiveness and reliability. This study represents a pioneering exploration of the MRG task, marking the first-ever endeavor in this domain. Additionally, we demonstrate the applicability of uMedGround in medical visual question answering and class-based localization tasks, where it highlights visual evidence aligned with key diagnostic phrases, supporting clinicians in interpreting various types of textual inputs, including free-text reports, visual question answering queries, and class labels.

Artificial intelligence has advanced in Medical Visual Question Answering (Med-VQA), but prevalent research tends to focus on the accuracy of the answers, often overlooking the reasoning paths and interpretability, which are crucial in clinical settings. Besides, current Med-VQA algorithms, typically reliant on singular models, lack the robustness needed for real-world medical diagnostics which usually require collaborative expert evaluation. To address these shortcomings, this paper presents MedCoT, a novel hierarchical expert verification reasoning chain method designed to enhance interpretability and accuracy in biomedical imaging inquiries. MedCoT is predicated on two principles: The necessity for explicit reasoning paths in Med-VQA and the requirement for multi-expert review to formulate accurate conclusions. The methodology involves an Initial Specialist proposing diagnostic rationales, followed by a Follow-up Specialist who validates these rationales, and finally, a consensus is reached through a vote among a sparse Mixture of Experts within the locally deployed Diagnostic Specialist, which then provides the definitive diagnosis. Experimental evaluations on four standard Med-VQA datasets demonstrate that MedCoT surpasses existing state-of-the-art approaches, providing significant improvements in performance and interpretability.

In the field of chest X-ray (CXR) diagnosis, existing works often focus solely on determining where a radiologist looks, typically through tasks such as detection, segmentation, or classification. However, these approaches are often designed as black-box models, lacking interpretability. In this paper, we introduce Interpretable Artificial Intelligence (I-AI) a novel and unified controllable interpretable pipeline for decoding the intense focus of radiologists in CXR diagnosis. Our I-AI addresses three key questions: where a radiologist looks, how long they focus on specific areas, and what findings they diagnose. By capturing the intensity of the radiologist's gaze, we provide a unified solution that offers insights into the cognitive process underlying radiological interpretation. Unlike current methods that rely on black-box machine learning models, which can be prone to extracting erroneous information from the entire input image during the diagnosis process, we tackle this issue by effectively masking out irrelevant information. Our proposed I-AI leverages a vision-language model, allowing for precise control over the interpretation process while ensuring the exclusion of irrelevant features. To train our I-AI model, we utilize an eye gaze dataset to extract anatomical gaze information and generate ground truth heatmaps. Through extensive experimentation, we demonstrate the efficacy of our method. We showcase that the attention heatmaps, designed to mimic radiologists' focus, encode sufficient and relevant information, enabling accurate classification tasks using only a portion of CXR. The code, checkpoints, and data are at https://github.com/UARK-AICV/IAI

Vision-language models (VLMs) often produce chain-of-thought (CoT) explanations that sound plausible yet fail to reflect the underlying decision process, undermining trust in high-stakes clinical use. Existing evaluations rarely catch this misalignment, prioritizing answer accuracy or adherence to formats. We present a clinically grounded framework for chest X-ray visual question answering (VQA) that probes CoT faithfulness via controlled text and image modifications across three axes: clinical fidelity, causal attribution, and confidence calibration. In a reader study (n=4), evaluator-radiologist correlations fall within the observed inter-radiologist range for all axes, with strong alignment for attribution (Kendall's tau_b=0.670), moderate alignment for fidelity (tau_b=0.387), and weak alignment for confidence tone (tau_b=0.091), which we report with caution. Benchmarking six VLMs shows that answer accuracy and explanation quality are decoupled, acknowledging injected cues does not ensure grounding, and text cues shift explanations more than visual cues. While some open-source models match final answer accuracy, proprietary models score higher on attribution (25.0% vs. 1.4%) and often on fidelity (36.1% vs. 31.7%), highlighting deployment risks and the need to evaluate beyond final answer accuracy.

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.

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/}}.

Visual Language Models (VLMs) have demonstrated impressive capabilities in visual grounding tasks. However, their effectiveness in the medical domain, particularly for abnormality detection and localization within medical images, remains underexplored. A major challenge is the complex and abstract nature of medical terminology, which makes it difficult to directly associate pathological anomaly terms with their corresponding visual features. In this work, we introduce a novel approach to enhance VLM performance in medical abnormality detection and localization by leveraging decomposed medical knowledge. Instead of directly prompting models to recognize specific abnormalities, we focus on breaking down medical concepts into fundamental attributes and common visual patterns. This strategy promotes a stronger alignment between textual descriptions and visual features, improving both the recognition and localization of abnormalities in medical images.We evaluate our method on the 0.23B Florence-2 base model and demonstrate that it achieves comparable performance in abnormality grounding to significantly larger 7B LLaVA-based medical VLMs, despite being trained on only 1.5% of the data used for such models. Experimental results also demonstrate the effectiveness of our approach in both known and previously unseen abnormalities, suggesting its strong generalization capabilities.

The latest breakthroughs in large vision-language models, such as Bard and GPT-4, have showcased extraordinary abilities in performing a wide range of tasks. Such models are trained on massive datasets comprising billions of public image-text pairs with diverse tasks. However, their performance on task-specific domains, such as radiology, is still under-investigated and potentially limited due to a lack of sophistication in understanding biomedical images. On the other hand, conversational medical models have exhibited remarkable success but have mainly focused on text-based analysis. In this paper, we introduce XrayGPT, a novel conversational medical vision-language model that can analyze and answer open-ended questions about chest radiographs. Specifically, we align both medical visual encoder (MedClip) with a fine-tuned large language model (Vicuna), using a simple linear transformation. This alignment enables our model to possess exceptional visual conversation abilities, grounded in a deep understanding of radiographs and medical domain knowledge. To enhance the performance of LLMs in the medical context, we generate ~217k interactive and high-quality summaries from free-text radiology reports. These summaries serve to enhance the performance of LLMs through the fine-tuning process. Our approach opens up new avenues the research for advancing the automated analysis of chest radiographs. Our open-source demos, models, and instruction sets are available at: https://github.com/mbzuai-oryx/XrayGPT.

Medical report generation has achieved remarkable advancements yet has still been faced with several challenges. First, the inherent imbalance in the distribution of normal and abnormal cases may lead models to exhibit a biased focus on normal samples, resulting in unreliable diagnoses. Second, the frequent occurrence of common template sentences in the reports may overwhelm the critical abnormal information. Moreover, existing works focus on 2D chest X-rays, leaving CT report generation underexplored due to the high-dimensional nature of CT images and the limited availability of CT-report pairs. Recently, LLM has shown a great ability to generate reliable answers with appropriate prompts, which shed light on addressing the aforementioned challenges. In this paper, we propose Dia-LLaMA, a framework to adapt the LLaMA2-7B for CT report generation by incorporating diagnostic information as guidance prompts. Considering the high dimension of CT, we leverage a pre-trained ViT3D with perceiver to extract the visual information. To tailor the LLM for report generation and emphasize abnormality, we extract additional diagnostic information by referring to a disease prototype memory bank, which is updated during training to capture common disease representations. Furthermore, we introduce disease-aware attention to enable the model to adjust attention for different diseases. Experiments on the chest CT dataset demonstrated that our proposed method outperformed previous methods and achieved state-of-the-art on both clinical efficacy performance and natural language generation metrics. The code will be made publically available.

With the emergence of large-scale vision language models (VLM), it is now possible to produce realistic-looking radiology reports for chest X-ray images. However, their clinical translation has been hampered by the factual errors and hallucinations in the produced descriptions during inference. In this paper, we present a novel phrase-grounded fact-checking model (FC model) that detects errors in findings and their indicated locations in automatically generated chest radiology reports. Specifically, we simulate the errors in reports through a large synthetic dataset derived by perturbing findings and their locations in ground truth reports to form real and fake findings-location pairs with images. A new multi-label cross-modal contrastive regression network is then trained on this dataset. We present results demonstrating the robustness of our method in terms of accuracy of finding veracity prediction and localization on multiple X-ray datasets. We also show its effectiveness for error detection in reports of SOTA report generators on multiple datasets achieving a concordance correlation coefficient of 0.997 with ground truth-based verification, thus pointing to its utility during clinical inference in radiology workflows.

Faithful reasoning in medical vision-language models (VLMs) requires not only accurate predictions but also transparent alignment between textual rationales and visual evidence. While Chain-of-Thought (CoT) prompting has shown promise in medical visual question answering (VQA), no large-scale expert-level dataset has captured stepwise reasoning with precise visual grounding. We introduce S-Chain, the first large-scale dataset of 12,000 expert-annotated medical images with bounding boxes and structured visual CoT (SV-CoT), explicitly linking visual regions to reasoning steps. The dataset further supports 16 languages, totaling over 700k VQA pairs for broad multilingual applicability. Using S-Chain, we benchmark state-of-the-art medical VLMs (ExGra-Med, LLaVA-Med) and general-purpose VLMs (Qwen2.5-VL, InternVL2.5), showing that SV-CoT supervision significantly improves interpretability, grounding fidelity, and robustness. Beyond benchmarking, we study its synergy with retrieval-augmented generation, revealing how domain knowledge and visual grounding interact during autoregressive reasoning. Finally, we propose a new mechanism that strengthens the alignment between visual evidence and reasoning, improving both reliability and efficiency. S-Chain establishes a new benchmark for grounded medical reasoning and paves the way toward more trustworthy and explainable medical VLMs.

Large language models (LLMs) have recently showcased remarkable capabilities, spanning a wide range of tasks and applications, including those in the medical domain. Models like GPT-4 excel in medical question answering but may face challenges in the lack of interpretability when handling complex tasks in real clinical settings. We thus introduce the diagnostic reasoning dataset for clinical notes (DiReCT), aiming at evaluating the reasoning ability and interpretability of LLMs compared to human doctors. It contains 511 clinical notes, each meticulously annotated by physicians, detailing the diagnostic reasoning process from observations in a clinical note to the final diagnosis. Additionally, a diagnostic knowledge graph is provided to offer essential knowledge for reasoning, which may not be covered in the training data of existing LLMs. Evaluations of leading LLMs on DiReCT bring out a significant gap between their reasoning ability and that of human doctors, highlighting the critical need for models that can reason effectively in real-world clinical scenarios.

Empathy requires perspective-taking: empathetic responses require a person to reason about what another has experienced and communicate that understanding in language. However, most NLP approaches to empathy do not explicitly model this alignment process. Here, we introduce a new approach to recognizing alignment in empathetic speech, grounded in Appraisal Theory. We introduce a new dataset of over 9.2K span-level annotations of different types of appraisals of a person's experience and over 3K empathetic alignments between a speaker's and observer's speech. Through computational experiments, we show that these appraisals and alignments can be accurately recognized. In experiments in over 9.2M Reddit conversations, we find that appraisals capture meaningful groupings of behavior but that most responses have minimal alignment. However, we find that mental health professionals engage with substantially more empathetic alignment.

This paper presents our team's participation in the MEDIQA-ClinicalNLP2024 shared task B. We present a novel approach to diagnosing clinical dermatology cases by integrating large multimodal models, specifically leveraging the capabilities of GPT-4V under a retriever and a re-ranker framework. Our investigation reveals that GPT-4V, when used as a retrieval agent, can accurately retrieve the correct skin condition 85% of the time using dermatological images and brief patient histories. Additionally, we empirically show that Naive Chain-of-Thought (CoT) works well for retrieval while Medical Guidelines Grounded CoT is required for accurate dermatological diagnosis. Further, we introduce a Multi-Agent Conversation (MAC) framework and show its superior performance and potential over the best CoT strategy. The experiments suggest that using naive CoT for retrieval and multi-agent conversation for critique-based diagnosis, GPT-4V can lead to an early and accurate diagnosis of dermatological conditions. The implications of this work extend to improving diagnostic workflows, supporting dermatological education, and enhancing patient care by providing a scalable, accessible, and accurate diagnostic tool.

Recently computer-aided diagnosis has demonstrated promising performance, effectively alleviating the workload of clinicians. However, the inherent sample imbalance among different diseases leads algorithms biased to the majority categories, leading to poor performance for rare categories. Existing works formulated this challenge as a long-tailed problem and attempted to tackle it by decoupling the feature representation and classification. Yet, due to the imbalanced distribution and limited samples from tail classes, these works are prone to biased representation learning and insufficient classifier calibration. To tackle these problems, we propose a new Long-tailed Medical Diagnosis (LMD) framework for balanced medical image classification on long-tailed datasets. In the initial stage, we develop a Relation-aware Representation Learning (RRL) scheme to boost the representation ability by encouraging the encoder to capture intrinsic semantic features through different data augmentations. In the subsequent stage, we propose an Iterative Classifier Calibration (ICC) scheme to calibrate the classifier iteratively. This is achieved by generating a large number of balanced virtual features and fine-tuning the encoder using an Expectation-Maximization manner. The proposed ICC compensates for minority categories to facilitate unbiased classifier optimization while maintaining the diagnostic knowledge in majority classes. Comprehensive experiments on three public long-tailed medical datasets demonstrate that our LMD framework significantly surpasses state-of-the-art approaches. The source code can be accessed at https://github.com/peterlipan/LMD.

Radiological imaging is central to diagnosis, treatment planning, and clinical decision-making. Vision-language foundation models have spurred interest in automated radiology report generation (RRG), but safe deployment requires reliable clinical evaluation of generated reports. Existing metrics often rely on surface-level similarity or behave as black boxes, lacking interpretability. We introduce ICARE (Interpretable and Clinically-grounded Agent-based Report Evaluation), an interpretable evaluation framework leveraging large language model agents and dynamic multiple-choice question answering (MCQA). Two agents, each with either the ground-truth or generated report, generate clinically meaningful questions and quiz each other. Agreement on answers captures preservation and consistency of findings, serving as interpretable proxies for clinical precision and recall. By linking scores to question-answer pairs, ICARE enables transparent, and interpretable assessment. Clinician studies show ICARE aligns significantly more with expert judgment than prior metrics. Perturbation analyses confirm sensitivity to clinical content and reproducibility, while model comparisons reveal interpretable error patterns.

There has been a rapidly growing interest in Automatic Symptom Detection (ASD) and Automatic Diagnosis (AD) systems in the machine learning research literature, aiming to assist doctors in telemedicine services. These systems are designed to interact with patients, collect evidence about their symptoms and relevant antecedents, and possibly make predictions about the underlying diseases. Doctors would review the interactions, including the evidence and the predictions, collect if necessary additional information from patients, before deciding on next steps. Despite recent progress in this area, an important piece of doctors' interactions with patients is missing in the design of these systems, namely the differential diagnosis. Its absence is largely due to the lack of datasets that include such information for models to train on. In this work, we present a large-scale synthetic dataset of roughly 1.3 million patients that includes a differential diagnosis, along with the ground truth pathology, symptoms and antecedents for each patient. Unlike existing datasets which only contain binary symptoms and antecedents, this dataset also contains categorical and multi-choice symptoms and antecedents useful for efficient data collection. Moreover, some symptoms are organized in a hierarchy, making it possible to design systems able to interact with patients in a logical way. As a proof-of-concept, we extend two existing AD and ASD systems to incorporate the differential diagnosis, and provide empirical evidence that using differentials as training signals is essential for the efficiency of such systems or for helping doctors better understand the reasoning of those systems.

Current vision-language models (VLMs) in medicine are primarily designed for categorical question answering (e.g., "Is this normal or abnormal?") or qualitative descriptive tasks. However, clinical decision-making often relies on quantitative assessments, such as measuring the size of a tumor or the angle of a joint, from which physicians draw their own diagnostic conclusions. This quantitative reasoning capability remains underexplored and poorly supported in existing VLMs. In this work, we introduce MedVision, a large-scale dataset and benchmark specifically designed to evaluate and improve VLMs on quantitative medical image analysis. MedVision spans 22 public datasets covering diverse anatomies and modalities, with 30.8 million image-annotation pairs. We focus on three representative quantitative tasks: (1) detection of anatomical structures and abnormalities, (2) tumor/lesion (T/L) size estimation, and (3) angle/distance (A/D) measurement. Our benchmarks show that current off-the-shelf VLMs perform poorly on these tasks. However, with supervised fine-tuning on MedVision, we significantly enhance their performance across detection, T/L estimation, and A/D measurement, demonstrating reduced error rates and improved precision. This work provides a foundation for developing VLMs with robust quantitative reasoning capabilities in medical imaging. Code and data are available at https://medvision-vlm.github.io.

Endoscopic procedures are essential for diagnosing and treating internal diseases, and multi-modal large language models (MLLMs) are increasingly applied to assist in endoscopy analysis. However, current benchmarks are limited, as they typically cover specific endoscopic scenarios and a small set of clinical tasks, failing to capture the real-world diversity of endoscopic scenarios and the full range of skills needed in clinical workflows. To address these issues, we introduce EndoBench, the first comprehensive benchmark specifically designed to assess MLLMs across the full spectrum of endoscopic practice with multi-dimensional capacities. EndoBench encompasses 4 distinct endoscopic scenarios, 12 specialized clinical tasks with 12 secondary subtasks, and 5 levels of visual prompting granularities, resulting in 6,832 rigorously validated VQA pairs from 21 diverse datasets. Our multi-dimensional evaluation framework mirrors the clinical workflow--spanning anatomical recognition, lesion analysis, spatial localization, and surgical operations--to holistically gauge the perceptual and diagnostic abilities of MLLMs in realistic scenarios. We benchmark 23 state-of-the-art models, including general-purpose, medical-specialized, and proprietary MLLMs, and establish human clinician performance as a reference standard. Our extensive experiments reveal: (1) proprietary MLLMs outperform open-source and medical-specialized models overall, but still trail human experts; (2) medical-domain supervised fine-tuning substantially boosts task-specific accuracy; and (3) model performance remains sensitive to prompt format and clinical task complexity. EndoBench establishes a new standard for evaluating and advancing MLLMs in endoscopy, highlighting both progress and persistent gaps between current models and expert clinical reasoning. We publicly release our benchmark and code.

Current work on human-machine alignment aims at understanding machine-learned latent spaces and their correspondence to human representations. G{\"a}rdenfors' conceptual spaces is a prominent framework for understanding human representations. Convexity of object regions in conceptual spaces is argued to promote generalizability, few-shot learning, and interpersonal alignment. Based on these insights, we investigate the notion of convexity of concept regions in machine-learned latent spaces. We develop a set of tools for measuring convexity in sampled data and evaluate emergent convexity in layered representations of state-of-the-art deep networks. We show that convexity is robust to basic re-parametrization and, hence, meaningful as a quality of machine-learned latent spaces. We find that approximate convexity is pervasive in neural representations in multiple application domains, including models of images, audio, human activity, text, and medical images. Generally, we observe that fine-tuning increases the convexity of label regions. We find evidence that pretraining convexity of class label regions predicts subsequent fine-tuning performance.

As AI technology is increasingly applied to high-impact, high-risk domains, there have been a number of new methods aimed at making AI models more human interpretable. Despite the recent growth of interpretability work, there is a lack of systematic evaluation of proposed techniques. In this work, we introduce HIVE (Human Interpretability of Visual Explanations), a novel human evaluation framework that assesses the utility of explanations to human users in AI-assisted decision making scenarios, and enables falsifiable hypothesis testing, cross-method comparison, and human-centered evaluation of visual interpretability methods. To the best of our knowledge, this is the first work of its kind. Using HIVE, we conduct IRB-approved human studies with nearly 1000 participants and evaluate four methods that represent the diversity of computer vision interpretability works: GradCAM, BagNet, ProtoPNet, and ProtoTree. Our results suggest that explanations engender human trust, even for incorrect predictions, yet are not distinct enough for users to distinguish between correct and incorrect predictions. We open-source HIVE to enable future studies and encourage more human-centered approaches to interpretability research.

While text-to-image (T2I) generative models have become ubiquitous, they do not necessarily generate images that align with a given prompt. While previous work has evaluated T2I alignment by proposing metrics, benchmarks, and templates for collecting human judgements, the quality of these components is not systematically measured. Human-rated prompt sets are generally small and the reliability of the ratings -- and thereby the prompt set used to compare models -- is not evaluated. We address this gap by performing an extensive study evaluating auto-eval metrics and human templates. We provide three main contributions: (1) We introduce a comprehensive skills-based benchmark that can discriminate models across different human templates. This skills-based benchmark categorises prompts into sub-skills, allowing a practitioner to pinpoint not only which skills are challenging, but at what level of complexity a skill becomes challenging. (2) We gather human ratings across four templates and four T2I models for a total of >100K annotations. This allows us to understand where differences arise due to inherent ambiguity in the prompt and where they arise due to differences in metric and model quality. (3) Finally, we introduce a new QA-based auto-eval metric that is better correlated with human ratings than existing metrics for our new dataset, across different human templates, and on TIFA160.

As we consider entrusting Large Language Models (LLMs) with key societal and decision-making roles, measuring their alignment with human cognition becomes critical. This requires methods that can assess how these systems represent information and facilitate comparisons to human understanding across diverse tasks. To meet this need, we developed Turing Representational Similarity Analysis (RSA), a method that uses pairwise similarity ratings to quantify alignment between AIs and humans. We tested this approach on semantic alignment across text and image modalities, measuring how different Large Language and Vision Language Model (LLM and VLM) similarity judgments aligned with human responses at both group and individual levels. GPT-4o showed the strongest alignment with human performance among the models we tested, particularly when leveraging its text processing capabilities rather than image processing, regardless of the input modality. However, no model we studied adequately captured the inter-individual variability observed among human participants. This method helped uncover certain hyperparameters and prompts that could steer model behavior to have more or less human-like qualities at an inter-individual or group level. Turing RSA enables the efficient and flexible quantification of human-AI alignment and complements existing accuracy-based benchmark tasks. We demonstrate its utility across multiple modalities (words, sentences, images) for understanding how LLMs encode knowledge and for examining representational alignment with human cognition.

Medical imaging plays a pivotal role in modern healthcare, with computed tomography pulmonary angiography (CTPA) being a critical tool for diagnosing pulmonary embolism and other thoracic conditions. However, the complexity of interpreting CTPA scans and generating accurate radiology reports remains a significant challenge. This paper introduces Abn-BLIP (Abnormality-aligned Bootstrapping Language-Image Pretraining), an advanced diagnosis model designed to align abnormal findings to generate the accuracy and comprehensiveness of radiology reports. By leveraging learnable queries and cross-modal attention mechanisms, our model demonstrates superior performance in detecting abnormalities, reducing missed findings, and generating structured reports compared to existing methods. Our experiments show that Abn-BLIP outperforms state-of-the-art medical vision-language models and 3D report generation methods in both accuracy and clinical relevance. These results highlight the potential of integrating multimodal learning strategies for improving radiology reporting. The source code is available at https://github.com/zzs95/abn-blip.