Multimodal Clinical Data

Recent tool-use frameworks powered by vision-language models (VLMs) improve image understanding by grounding model predictions with specialized tools. Broadly, these frameworks leverage VLMs and a pre-specified toolbox to decompose the prediction task into multiple tool calls (often deep learning models) which are composed to make a prediction. The dominant approach to composing tools is using text, via function calls embedded in VLM-generated code or natural language. However, these methods often perform poorly on medical image understanding, where salient information is encoded as spatially-localized features that are difficult to compose or fuse via text alone. To address this, we propose a tool-use framework for medical image understanding called the Tool Bottleneck Framework (TBF), which composes VLM-selected tools using a learned Tool Bottleneck Model (TBM). For a given image and task, TBF leverages an off-the-shelf medical VLM to select tools from a toolbox that each extract clinically-relevant features. Instead of text-based composition, these tools are composed by the TBM, which computes and fuses the tool outputs using a neural network before outputting the final prediction. We propose a simple and effective strategy for TBMs to make predictions with any arbitrary VLM tool selection. Overall, our framework not only improves tool-use in medical imaging contexts, but also yields more interpretable, clinically-grounded predictors. We evaluate TBF on tasks in histopathology and dermatology and find that these advantages enable our framework to perform on par with or better than deep learning-based classifiers, VLMs, and state-of-the-art tool-use frameworks, with particular gains in data-limited regimes. The project details and the code are available at https://christinaliu2020.github.io/tbm/.

Vision-language models (VLMs) are increasingly integrated into clinical workflows. However, existing benchmarks primarily assess performance on common anatomical presentations and fail to capture the challenges posed by rare variants. To address this gap, we introduce AdversarialAnatomyBench, the first benchmark comprising naturally occurring rare anatomical variants across diverse imaging modalities and anatomical regions. We call such variants that violate learned priors about "typical" human anatomy natural adversarial anatomy. Benchmarking 25 state-of-the-art VLMs with AdversarialAnatomyBench yielded three key insights. First, when queried with basic medical perception tasks, mean accuracy dropped from 71% on typical to 28% on atypical anatomy. Even the best-performing models, GPT-5, Gemini 2.5 Pro, and Llama 4 Maverick, showed performance drops of 41-51%. Second, model errors closely mirrored expected anatomical biases. Third, neither model scaling nor interventions, including bias-aware prompting and test-time reasoning, resolved these issues. These findings highlight a critical limitation in current VLMs: their poor generalization to rare anatomical presentations. AdversarialAnatomyBench provides a foundation for systematically measuring and mitigating anatomical bias in multimodal medical artificial intelligence (AI) systems.

Despite notable progress in text-guided medical image segmentation nowadays, these methods are limited to single-round dialogues and fail to support multi-round reasoning, which is important for medical education scenarios. In this work, we introduce Multi-Round Entity-Level Medical Reasoning Segmentation (MEMR-Seg), a new task that requires generating segmentation masks through multi-round queries with entity-level reasoning, helping learners progressively develop their understanding of medical knowledge. To support this task, we construct MR-MedSeg, a large-scale dataset of 177K multi-round medical segmentation dialogues, featuring entity-based reasoning across rounds. Furthermore, we propose MediRound, an effective baseline model designed for multi-round medical reasoning segmentation. To mitigate the inherent error propagation within the chain-like pipeline of multi-round segmentation, we introduce a lightweight yet effective Judgment & Correction Mechanism during model inference. Experimental results demonstrate that our method effectively addresses the MEMR-Seg task and outperforms conventional medical referring segmentation methods. The project is available at https://github.com/Edisonhimself/MediRound.

The rapid digitization of histopathology slides has opened new opportunities for computational tools in clinical and research workflows. Content-based slide retrieval can help pathologists identify morphologically and semantically related precedent cases, supporting expert diagnosis and example-based education. Effective retrieval of whole-slide images (WSIs), however, remains challenging because gigapixel slides contain abundant irrelevant content, focal diagnostic patterns and slide-level semantic information that must be represented at a practicable search cost. Here we present PathSearch, a retrieval framework that combines fine-grained attentive mosaics with slide-level embeddings aligned through vision-language contrastive learning. Trained on 6,926 slide-report pairs, PathSearch captures both fine-grained morphological cues and high-level semantic patterns to enable accurate and flexible retrieval. The framework supports two key functionalities: (1) mosaic-based image-to-image (I2I) retrieval, ensuring accurate and efficient slide search; and (2) multimodal retrieval, where text queries can directly retrieve relevant slides. PathSearch was evaluated on eight tasks comprising 5,021 evaluation slides, spanning malignancy assessment on frozen and hematoxylin and eosin (H&E)-stained slides, lymph-node metastasis detection, tumor subtyping, mixed-gallery rare-cancer retrieval, and hepatocellular carcinoma (HCC) risk stratification. Internal and external experimental results demonstrate that PathSearch consistently outperforms the strongest existing methods without compromising multimodal accuracy. A multi-center reader study further demonstrated increases in task-level mean diagnostic accuracy, confidence, and inter-observer agreement with PathSearch's support. Together, these results support the effectiveness of PathSearch across diverse retrieval tasks and evaluation settings.

Multimodal large language models (MLLMs) have recently demonstrated remarkable reasoning abilities under reinforcement learning (RL) paradigm. However, most existing multimodal medical reasoning models focus on basic reasoning, which refers to shallow inference based on visual feature matching. In contrast, real-world clinical diagnosis extends beyond basic reasoning, demanding complex reasoning that integrates heterogeneous clinical information (such as chief complaints and medical history) with multimodal medical imaging data. To bridge this gap, we introduce MM-Retinal-Reason, an ophthalmic multimodal dataset covering the full spectrum of perception and reasoning. Specifically, it is the first dataset in ophthalmology to encompass both basic and complex reasoning tasks with Chain-of-Thought (CoT) trajectories, aiming to enhance visual-centric reasoning and emulate realistic clinical decision-making. Building upon MM-Retinal-Reason, we propose OphthaReason, the first RL-enhanced ophthalmic multimodal reasoning model with step-by-step reasoning traces. To enable flexible adaptation to both basic and complex reasoning tasks, we further introduce Uncertainty-Aware Dynamic Thinking (UADT), which estimates sample-level uncertainty via entropy and dynamically modulates exploration depth through a shaped advantage mechanism. Comprehensive experiments demonstrate the effectiveness of our model on both basic and complex reasoning tasks, outperforming general-purpose MLLMs, medical MLLMs, RL-based medical MLLMs, and ophthalmic MLLMs by at least 15.47%. Project Page: \href{https://github.com/lxirich/OphthaReason}{link}.

Current CT report generation frameworks predominantly rely on global feature representations, often failing to capture region-specific details and potentially missing certain abnormalities. To overcome this limitation, we propose MedRegion-CT, a region-focused multimodal large language model framework featuring three key innovations. First, we revisit the SlowFast strategy to jointly model global and fine-grained information and adapt it to the medical domain via a Region-based SlowFast Tokenizer that extracts tokens guided by clinically meaningful regions. Second, generated pseudo-masks guide the model to attend to diagnostically important anatomical regions, facilitating a systematic understanding of the overall scan context. Third, quantitative lesion information, including size, diameter, and spatial location, is encoded as structured textual prompts, enabling context-aware and clinically informed report generation. To enable rigorous evaluation, we validate our framework on multi-institutional structured report generation benchmarks. Experimental results demonstrate that MedRegion-CT achieves state-of-the-art performance, outperforming existing approaches in both linguistic quality and clinical accuracy. All code is publicly available at: https://github.com/babbu3682/MedRegion-CT.

Multimodal Large Language Models (MLLMs) have demonstrated impressive capabilities in understanding common visual elements, largely due to their large-scale datasets and advanced training strategies. However, their effectiveness in medical applications remains limited due to the inherent discrepancies between data and tasks in medical scenarios and those in the general domain. Concretely, existing medical MLLMs face the following critical limitations: (1) limited coverage of medical knowledge beyond imaging, (2) heightened susceptibility to hallucinations due to suboptimal data curation processes, (3) lack of reasoning capabilities tailored for complex medical scenarios. To address these challenges, we first propose a comprehensive data curation procedure that (1) efficiently acquires rich medical knowledge data not only from medical imaging but also from extensive medical texts and general-domain data; and (2) synthesizes accurate medical captions, visual question answering (VQA), and reasoning samples. As a result, we build a multimodal dataset enriched with extensive medical knowledge. Building on the curated data, we introduce our medical-specialized MLLM: Lingshu. Lingshu undergoes multi-stage training to embed medical expertise and enhance its task-solving capabilities progressively. Besides, we preliminarily explore the potential of applying reinforcement learning with verifiable rewards paradigm to enhance Lingshu's medical reasoning ability. Additionally, we develop MedEvalKit, a unified evaluation framework that consolidates leading multimodal and textual medical benchmarks for standardized, fair, and efficient model assessment. We evaluate the performance of Lingshu on three fundamental medical tasks, multimodal QA, text-based QA, and medical report generation. The results show that Lingshu consistently outperforms the existing open-source multimodal models on most tasks ...

To overcome the black-box nature of predictive AI and the hallucination risks of generative models, retrieval-based models offer an interpretable, evidence-based paradigm for pathology clinical workflow. However, real-world clinical queries are inherently interleaved (e.g., pathology images and text). Current dual-encoders suffer from an \textbf{Architectural Mismatch}, lacking the mechanism to fuse such composed queries. To address this, we formalize the task of Pathology Composed Retrieval (PCR). While Multimodal Large Language Models (MLLMs) offer deep-fusion capabilities, directly applying them exposes a \textbf{Task Mismatch} and a \textbf{Domain Mismatch}. To resolve these challenges, we propose HOMIE, a model-agnostic adaptation framework that transforms any generative MLLM into a specialized pathology retrieval expert. Evaluated on our newly introduced PCR Benchmark, a lightweight 2B-parameter HOMIE variant substantially outperforms existing paradigms, surpassing specialized 7B pathology MLLMs and dual-encoders by large margins on composed retrieval, while maintaining strong performance on traditional simple retrieval. The project page is available at https://qfchou.github.io/HOMIE_page/.

Radiology report generation (RRG) has attracted significant attention due to its potential to reduce the workload of radiologists. The performance of current RRG approaches remains unsatisfactory against clinical standards. This paper introduces a novel RRG method, MLLM-RRG, that integrates multimodal large language models (MLLMs) with various types of clinical knowledge to generate accurate and comprehensive chest X-ray reports. Our method first designs a referring anatomical feature extractor that leverages anatomical knowledge to analyze different regions of the chest X-ray image and extract visual features without explicitly detecting regions. Next, based on the MLLM's decoder, we develop a multimodal report generator that leverages multimodal prompts constructed from dedicated visual features and textual instructions to produce the radiology report in an auto-regressive way. Finally, we introduce a disease-oriented clinical classification and alignment scheme in a multi-task learning manner to leverage disease knowledge to better preserve the clinical relevance among the generated reports. Once the model is trained, we also introduce a novel clinical quality reinforcement learning strategy to enhance the MLLM with report knowledge, further refining the tones of the generated reports towards radiologists. Extensive experiments on the MIMIC-CXR and IU X-Ray datasets demonstrate the superiority of our method over the state of the art. Our codes will be available at https://github.com/viscom-tongji/MLLM-RRG.

Individuals with suspected rare genetic disorders often undergo multiple clinical evaluations, imaging studies, laboratory tests, and genetic tests over a prolonged period of time, a process commonly described as the diagnostic odyssey. Addressing this odyssey has substantial clinical, psychosocial, and economic benefits. Many rare genetic diseases have distinctive facial features that artificial intelligence algorithms can use to facilitate clinical diagnosis, to prioritize candidate diseases for further laboratory or genetic testing, and to support the phenotype-driven reinterpretation of genome or exome sequencing data. Existing methods that use frontal facial photographs were built on conventional convolutional neural networks, rely exclusively on facial images, and cannot capture non-facial phenotypic traits or demographic information that are essential for accurate diagnosis. Here we introduce GestaltMML, a multimodal machine learning approach based solely on the Transformer architecture. It integrates facial images, demographic information (age, sex, ethnicity), and clinical notes (optionally a list of Human Phenotype Ontology terms) to improve prediction accuracy. We evaluate GestaltMML on 528 diseases from the GestaltMatcher Database and on several in-house and published cohorts, including Beckwith-Wiedemann syndrome, Sotos syndrome, NAA10-related neurodevelopmental syndrome, Cornelia de Lange syndrome, and KBG syndrome. GestaltMML improves on the state-of-the-art image-only ensembled model, narrows the diagnostic accuracy gap for patients from under-represented ancestries, and clarifies when multimodal fusion is beneficial and when image-only inference is preferable. The results suggest that GestaltMML can greatly narrow the candidate diagnoses of rare diseases and may facilitate the reinterpretation of sequencing data.

As vision-language models (VLMs) are increasingly applied to medical AI, existing benchmarks mainly focus on evaluating their diagnostic ability over given medical images and texts, implicitly assuming that standardized medical images, texts, or question-answer pairs are already prepared. However, this assumption does not hold when we apply VLMs in real clinical practice, where medical data is often raw, heterogeneous, and fragmented across different sources. In this paper, we study this missing step, i.e., raw medical data standardization. Specifically, models are given raw dataset folders and evaluated on their ability to identify source formats, convert raw medical images into VLM-compatible visual inputs, extract relevant textual information, and organize the results into structured image-text pairs. To construct this Medical Data Standardization Benchmark (MDS-Bench), we manually annotate 1,939 raw medical data standardization tasks covering diverse clinical practice, radiology modalities, annotation formats, and directory layouts. Extensive experiments show that even the best performing VLM, i.e., Gemini 3 Flash, achieves only a 48.6% end-to-end success rate. Our research highlights raw medical data standardization as a critical bottleneck for medical AI diagnosis in real practice.

Medical vision-language models (VLMs) are increasingly expected to support clinical workflows through diagnostic text and relevant medical images. However, current medical visual benchmarks have three recurring limitations: query-image misalignment from queries weakly grounded in specific image instances, closed-ended formats that narrow answer space and encourage shortcut-based prediction, and text-centric output paradigms that limit evaluation of image-generation and image-editing capabilities. We introduce MedGEN-Bench, a benchmark for open-ended multimodal medical generation. The evaluation snapshot reported in this manuscript comprises 6,422 image-text pairs reviewed by clinical experts and models, spanning 6 canonical imaging modalities, 15 clinical tasks, and 27 named subtasks. It includes 1,100 Visual Question Answering (VQA) pairs, 3,872 Image Editing pairs, and 1,450 Contextual Multimodal Generation pairs. MedGEN-Bench centers on contextual entanglement: dependence of an instruction's intended output on the particular image instance rather than on task wording alone. The benchmark operationalizes this concept through image-grounded instructions and extends evaluation to open-ended multimodal outputs. Its tiered evaluation protocol combines reproducible reference-based fidelity and similarity measures with a structured, checklist-guided assessment by a medical VLM judge. We evaluate 10 compositional frameworks, 2 dedicated image-editing models, 3 unified models, and 5 VLMs. The results show image-output tasks remain unsaturated. Contextual augmentation increases mean image-instruction similarity from 0.273 to 0.372, while a 1,000-case medical-expert audit shows moderate agreement between judge scores and clinician ratings. Source code and dataset are available at https://yangjj007.github.io/medgen.