Multimodal Clinical Data

This paper introduces a new benchmark test, Medical-Checklist, for assessing medical multimodal models. The recent advancements in multimodal models have demonstrated significant potential in the field of medical vision-language tasks. However, it is becoming increasingly clear that evaluating these models' performance, whether they are applied to natural or medical images, is challenging. The critical question is whether the models can accurately understand an input image while associating it with relevant input text. To address this, Medical-Checklist imposes a binary test on the models: they are given an image and two captions, where one is correct and the other incorrect, and the model must select the correct one. The incorrect caption contains a single medical concept (word or phrase) that is inaccurately substituted from the correct caption. Although the task is simple, this simplicity enables the unified assessment of diverse multimodal models designed and learned on different principles. It also enables us to verify whether models correctly understand a wide range of medical concepts across various medical sub-domains. Medical-Checklist is designed to reduce potential biases in data and to enable evaluation of the models' ability to handle out-of-distribution inputs, which were difficult in existing datasets. When evaluating four state-of-the-art medical multimodal models with Medical-Checklist, it was revealed that despite their excellent performance in specific tasks such as Med-VQA, they may not correctly understand images, suggesting a long journey ahead for clinical application. The dataset and code will be made public upon acceptance.

Although artificial intelligence (AI) has shown promising performance in several medical tasks, accurate dementia etiology diagnosis with AI remains challenging due to complex overlapping symptoms among diseases. Scaling up the dataset size by combining the cross-center samples may bring a gain in the pursuit of performance, while the inherent data heterogeneity across centers or populations induces the conflict. Conventional multi-task learning paradigms offer a promising framework; however, they fail to consider critical meta information (e.g., site-specific acquisition and modality availability) to combat the heterogeneity. To address this challenge, we propose a Collaborative Meta Knowledge Enhancement (COME) framework for dementia etiology diagnosis, which injects multi-center acquisition semantics, source identifiers, and modality indicators as heterogeneity-aware embeddings into a unified Transformer architecture for scale-up training, enabling explicit modeling of heterogeneity. Besides, a trust-region constrained optimization scheme is designed to regularize the model from spurious correlations during training through a reference model. Across seven independent cohorts, our method achieves state-of-the-art in-domain performance with a mean macro-averaged AUC of 85.62% and a 4.29-point gain over the strongest baseline, while maintaining superior out-of-domain generalization under both cross-center and cross-sequence evaluations. Extensive validation also confirms the alignment between model predictions and established biomarkers (amyloid, tau) and clinical severity, highlighting the potential of COME to enable robust and interpretable dementia diagnostics in real-world settings.

Integrating heterogeneous biomedical data, including clinical metadata, histopathology images, and molecular profiles, is crucial for comprehensive disease understanding. However, gene expression data acquisition remains constrained by high costs and privacy concerns, limiting its use in multimodal research and AI-driven applications. We present MultiModal Molecular Generation (M$^3$-Gen), a novel framework for the generation of gene expression profiles by conditioning a Generative Adversarial Network on histopathology images and clinical metadata. M$^3$-Gen learns a unified latent representation from the clinical variables and the images, leveraging contrastive learning, and exploits the embeddings of the two modalities to guide a generative model in producing biologically coherent gene expression profiles. Evaluations on the TCGA dataset demonstrate that M$^3$-Gen generates realistic and functionally meaningful gene expression data. Importantly, by integrating multiple modalities in an attention-based mechanism, M$^3$-Gen provides intrinsic explainability: it allows the identification of which regions of the histopathology images most strongly influenced the generation of specific gene expression profiles, making the model's decisions interpretable by design.

Pathology vision-language models (VLMs) have recently progressed rapidly and are commonly evaluated by answer accuracy on pathology VQA benchmarks. However, we dig into current evaluations and identify three overlooked issues: 1) Visual evidence is not always necessary. For instance, Gemini-3-Pro achieves 53.5% average accuracy across 5 VQA benchmarks without any visual input. 2) Domain training can improve accuracy without proportional gains in visual binding. Compared with Qwen2.5-VL-7B, Patho-R1-7B exhibits a 5.8-point lower multimodal gain and a 3.7-point lower attention IoU. 3) Entity-level attention is diffuse and weakly query-specific. On PathVG, attention maps remain highly correlated across different entity queries. These issues can lead to substantial misjudgments of pathology VLMs' actual multimodal capabilities. To this end, we present PathBind, a benchmark comprising 2,600 samples: PathBind-VQA with 1,500 questions across six dimensions, PathBind-PTA with 600 questions from a private pathology teaching atlas, and PathBind-Grounding with 500 expert-curated region-level samples. Each component undergoes task-specific automated filtering and expert review to reduce textual shortcuts and improve entity-region correspondence. We evaluate 18 representative VLMs on VQA samples of PathBind and five existing pathology VQA benchmarks, and further evaluate 10 VLMs on PathBind-Grounding and PathVG. Results show that current pathology VLMs still exhibit a substantial gap between answer-side performance and visual-semantic binding.

Accurate emergency triage decision is critical to avoid clinical deterioration, morbidity, and mortality. Machine learning-based triage system involves acquiring the main presenting complaint in text form and assessing vital signs in numerical data, enabling an automated and efficient analysis of patient information for timely and accurate prioritization of medical attention. However, modelling the intricacies of both data types requires a comprehensive understanding of the temporal structure and dependencies within the data. Thus, the aim of this study is to propose a multimodal deep learning architecture that can effectively handle both tabular and textual data. Furthermore, the proposed model exploits self-attention to to capture both local and global relationships between the features. A dataset consisting of 11,102 triage data collected from emergency department of Hospital Universiti Sains Malaysia is used for model development and validation. The proposed model demonstrated an increase of 1.95% in accuracy, 2.49% in F1-score, and 1.41% in ROC AUC compared to the baseline model. The experimental results demonstrated the potential of the proposed model in predicting triage decisions.

Optical coherence tomography (OCT) imaging is essential for the diagnosis and treatment of retinal diseases. Although multimodal large language models (MLLMs) have demonstrated considerable potential in medical image analysis, existing benchmarks largely reduce OCT understanding to coarse-grained disease classification or isolated visual question answering, leaving the complete cognitive process from visual perception to clinical reasoning insufficiently evaluated. To address this limitation, we introduce OCT-Bench, a comprehensive benchmark dedicated to OCT image understanding. OCT-Bench comprises 10,076 high-quality multiple-choice questions constructed from 4,137 OCT images across seven public datasets. Following the real-world clinical interpretation workflow, we establish a hierarchical capability taxonomy consisting of 20 fine-grained tasks across three dimensions: Perception, Cognition, and Reasoning. These tasks cover a broad range of capabilities, including imaging attributes, retinal anatomy, lesion characteristics, spatial relationships, disease assessment, therapeutic decision-making, and prognostic management. We systematically evaluate 20 representative MLLMs, including proprietary models, open-source general-purpose models, and medical-domain models. Experimental results demonstrate that current models remain substantially short of reliable OCT understanding. Moreover, neither medical-domain adaptation nor increased model scale consistently improves performance across capability levels. OCT-Bench enables comprehensive and fine-grained evaluation of MLLMs, providing a foundation for identifying capability bottlenecks and advancing clinically grounded OCT understanding.

Large vision-language models (LVLMs) can be adapted to specialized medical imaging tasks via parameter-efficient fine-tuning approaches such as low-rank adaptation (LoRA), leading to a growing ecosystem of expert models tailored to specific imaging modalities and clinical scenarios. However, deploying multiple expert LVLMs in practice incurs substantial computational and operational overhead. Model merging provides a promising solution by consolidating multiple experts into a single model without retraining, yet it remains largely unexplored in the medical domain. In this work, we present the first systematic study of model merging for medical LVLMs. We introduce MergeMedBench, a comprehensive benchmark spanning eight imaging modalities and diverse clinical task types, comprising 16 LoRA fine-tuned models built upon two mainstream architectures. We conduct an extensive evaluation of existing merging methods and further propose winner-take-all, a simple and hyperparameter-free approach that retains only the most dominant parameters across expert models. By preserving the critical parameters that govern model behavior and discarding weaker ones, our method avoids the information dilution inherent in averaging- or alignment-based strategies. Despite its simplicity, winner-take-all consistently outperforms existing approaches, offering both a new perspective on LoRA merging and a strong practical baseline for future research.

We study interaction-aware mixture-of-experts for post-stroke rigidity prediction using multi-level views of structured health records. Despite minimal performance gains, routing attribution reveals systematic importance differences across views, underscoring view construction as key to interpretability.

Preparing for job interviews is important for securing desired positions, yet realistic practice remains difficult to access: real interviews are infrequent, expert mock coaching is costly, and self-practice offers neither adaptive dialogue nor structured assessment. Existing systems typically address only parts of this need through fixed question sequences, limited communication channels, or feedback with little supporting evidence. We present PolyInterview, an LLM-based platform for immersive mock interview practice with comprehensive multimodal assessment. PolyInterview uses the target job description and CV to generate questions tailored to the role and candidate, conducts multi-turn spoken interviews with a lip-synced digital human interviewer that asks answer-aware follow-up questions, and evaluates response content, vocal delivery, and non-verbal behavior. Four parallel evaluators produce 13 behavior-level features that are aggregated into 10 assessment aspects and two competency tracks. Guided by the KSA and STAR frameworks, the report links each score to behavioral evidence and actionable recommendations. PolyInterview is publicly accessible. Its current all-account snapshot contains 101 accounts, 1,564 interview sessions, 7,665 generated questions, and 1,422 five-stage question sets. Generated questions are more closely aligned with their matched job description than with cross-role job descriptions in 93.7% of sessions. An evaluation by ten experts found strong question plans and actionable feedback.

Electronic health record (EHR) data are inherently multimodal, and leveraging multiple modalities can improve predictive performance. However, most existing approaches rely on deep fusion, which obscures how individual modalities contribute to predictions and limits the interpretability of multimodal reasoning. We propose an explicit multimodal routing framework for clinical prediction that enables interpretable, robust, and auditable reasoning across three EHR modalities: structured longitudinal variables (L), clinical notes (N), and chest X-rays (I). Our model constructs discrete unimodal, directional bimodal, and trimodal routes to capture both individual modality signals and asymmetric cross-modal interactions. To audit multimodal reasoning and assess robustness, we introduce inference-time route masking, which simulates missing modalities and reweights the remaining routes without retraining. We analyze changes in performance and routing weights under these scenarios to understand model decision-making. We evaluate our framework on multi-label phenotype prediction (K = 25) and binary ICU mortality prediction using trimodal patient stays from MIMIC-IV, revealing systematic differences in modality reliance across clinical condition groups. Overall, our framework offers a transparent, auditable, and practical approach to multimodal clinical prediction, providing interpretability, robustness, and insights into how different data sources drive model decisions.

Cardiac amyloidosis (CA) is increasingly recognized but remains substantially underdiagnosed, because its clinical and imaging phenotype overlaps with more common cardiomyopathies. Definitive subtype assignment and management further require integration of multimodal evidence to distinguish transthyretin from light chain disease. Machine learning and deep learning have been applied across the diagnostic and management pathway. These applications span ECG, echocardiography, and health record-based case finding, as well as CMR and nuclear interpretation, including SPECT/CT biomarker quantification, prognostic modeling, and treatment response assessment. This narrative review synthesizes these studies by clinical tasks, namely screening, detection, quantification, prognosis, and treatment response monitoring, rather than by input modality. This task-based organization clarifies why apparently similar AI models require different cohorts, reference standards, evaluation metrics, and implementation thresholds. The evidence reveals a maturity gradient. Binary detection and AI assisted quantification on bone scintigraphy and SPECT/CT are closest to clinical translation. Detection is supported by large externally validated cohorts, and quantification by interpretable, outcome linked measurement of myocardial tracer burden. By contrast, subtype aware classification, prognostic risk stratification, and treatment response monitoring remain at an early stage. These tasks are limited by small cohorts, enriched retrospective designs, heterogeneous labels, incomplete external validation, and uncertain calibration in realistic prevalence settings. Across tasks, high discrimination alone is insufficient.

Multimodal medical models often degrade when inputs are missing, a common scenario in real-world clinical workflows. Separately, even when all modalities are present, modality dominance is observed during training, where optimization over-relies on a highly predictive modality and undertrains complementary sources, resulting in poor robustness under partial availability. While training-time modality knockout improves missing-modality robustness, existing approaches use static masking rates that cannot adapt to evolving modality utility during training. We introduce ShapKO (Shapley-Adaptive Modality Knockout), a dynamic training strategy that learns modality-specific knockout probabilities based on validation utility. ShapKO periodically evaluates performance across modality subsets, estimates modality importance via Shapley values, and updates masking probabilities to suppress dominant modalities more frequently. This adaptive process promotes complementary representations, while requiring no architectural modifications. We evaluate ShapKO on three datasets covering multitask clinical classification, survival prediction, and cancer detection. ShapKO consistently improves performance under modality absence and yields interpretable trajectories of learned masking behavior. Code is available at: https://github.com/sumona00/ShapKO

Does every cancer patient truly need a complete diagnostic workup for accurate survival prediction? In multimodal clinical oncology, diagnostic modalities follow a clinically mandated order of escalating burden -- from demographics collected at intake to genomic profiling requiring specialized tissue analysis. Current multimodal survival methods either assume all modalities are available or passively handle missing data, but none actively reason about whether acquiring the next modality is justified for a given patient along this ordered workflow. We formulate this as a sequential decision problem and propose SAGEAgent (Sequential Acquisition Guided by Experience), a self-evolving LLM-based clinical agent that decides which diagnostic modalities to acquire for each patient, balancing predictive accuracy against clinical invasiveness. SAGEAgent reasons about each patient's evolving diagnostic state through clinical tools that translate numerical predictions into text, an episodic memory that retrieves similar past cases, and a semantic memory that accumulates reusable decision patterns from experience. Experiments on a glioma cohort combining TCGA-LGG, TCGA-GBM, and BraTS with four diagnostic modalities demonstrate that SAGEAgent achieves competitive survival prediction accuracy while reducing average acquisition burden by 55%.

Large language models (LLMs) are increasingly deployed in online medical consultation, yet existing benchmarks remain poorly aligned with real clinical practice. Many rely on synthetic conversations or patient simulators, omit patient-uploaded medical images, or evaluate open-ended clinical responses using multiple-choice or lexical-overlap metrics that poorly reflect clinical quality. We introduce \textbf{MedRealMM}, a large-scale benchmark for multimodal online medical consultation built from de-identified patient-doctor interactions collected from a nationwide Chinese internet hospital. MedRealMM uses a Multimodal Clinical Challenge Point (MCCP) extraction framework to identify clinically demanding moments in authentic consultation trajectories and converts each into a standardized next-response generation task while preserving the preceding text-image context. Each instance is paired with a case-specific rubric refined by physicians that rewards clinically desirable behaviors and penalizes unsafe, unsupported, or contradictory responses. The current release contains 5,620 real-world multimodal cases spanning 64 clinical departments. We evaluate 19 general-purpose and medical-specialized LLMs, including text-only and multimodal systems. Our results show that image information is critical for reliable clinical performance and that current frontier models remain below the online physician response. Although some frontier models satisfy as many or more positive clinical criteria than physicians, they trigger more negative criteria, indicating that safety-sensitive error avoidance remains a central bottleneck. MedRealMM offers a realistic and reproducible benchmark for evaluating multimodal medical reasoning in real-world online consultation. The dataset will be publicly available on Hugging Face at https://huggingface.co/datasets/jdh-algo/MedRealMM.

Accurate prognosis prediction is important for treatment planning in lung cancer, but deep learning-driven survival modelling is often limited by the scarcity of curated imaging cohorts with reliable outcome data. This study evaluates whether representations from a domain-specific foundation model can be used for multimodal survival prediction in data-constrained clinical settings. We assess the foundation model CT-CLIP as a feature extractor for pretreatment computed tomography images and clinical variables from 242 diagnosed lung cancer patients. The evaluation includes adaptation strategies based on frozen encoders, full fine-tuning, and low-rank adaptation, together with modality ablations and comparisons with clinical and multimodal baselines. The results show that a frozen CT-CLIP model combined with a trainable lightweight survival head outperforms the clinical baseline and achieves comparable or improved performance relative to other multimodal approaches, and separates patients into clinically meaningful high- and low-risk groups.

Medicine is inherently multimodal, requiring clinicians to synthesize information across diverse data streams. Yet the development of multimodal foundation models is constrained by limited access to large-scale, high-quality clinical data. Although PubMed Central (PMC) offers a complementary source of expert-authored image-text data, existing PMC-derived resources remain limited in fidelity, reproducibility, and clinical validation. We introduce MedPMC, an automated, continuously updatable framework that transforms permissively licensed literature into high-fidelity infrastructure for medical multimodal models. Applied to 6.1 million PMC articles, MedPMC curated 11 million medical image-text pairs. Component evaluations showed strong performance for initial screening (F1 = 93.2), multi-panel figure detection (F1 = 96.5), figure separation (mAP = 89.8), caption separation and alignment (F1 = 81.4; ROUGE-L = 85.3), and medical figure classification (F1 = 96.5). Manual review by five annotators, three with medical training, found 95.3% of MedPMC images medically relevant, versus 19.7% in a prior PMC-derived dataset. Across 26 benchmarks spanning 11 specialties, a MedPMC-trained CLIP-style model improved average zero-shot AUC by 7.1 percentage points over the strongest architecture-matched biomedical CLIP baseline despite using fewer than half as many image-text pairs. As the vision encoder in a multimodal large language model, it improved medical visual question-answering by 1.9 and 16.9 percentage points across two benchmarks. In 10,524 Yale New Haven Health System dermatology photographs, it improved morphology-to-image retrieval Recall@5 by 11.7 percentage points. These findings show that high-fidelity literature curation strengthens medical multimodal foundation models across benchmark and clinical settings. We publicly release the framework, corpus, benchmarks, and pretrained models.

In longitudinal Alzheimer's disease (AD) diagnosis support, clinical and imaging information is often collected at irregular visits. Integrating these multimodal observations may improve diagnostic assessment, but naive fusion can degrade performance when MRI is noisy or intermittently unavailable. We propose AT-Attn, a temporal-aware multimodal framework that combines Change-and-Time encoding, time-biased asymmetric cross-attention, and gated fusion to integrate MRI with longitudinal clinical information. We evaluate AT-Attn on an MRI-retained ADNI cohort of 1,520 patients using structural MRI, six cognitive-scale trajectories, and seven static clinical variables under patient-level five-fold cross-validation. The main asymmetric AT-Attn model achieves accuracy 0.719+/-0.024, macro F1 0.721+/-0.023, ROC-AUC 0.873+/-0.013, and PR-AUC 0.783+/-0.018, outperforming unimodal and naive multimodal fusion baselines while remaining competitive with strong tabular baselines. These results suggest that a temporal-aware and constrained fusion strategy can help structural MRI contribute clinically relevant complementary information for patient-level AD diagnosis support.

Accurate quantification of lung disease severity from chest imaging is critical for clinical decision-making and resource allocation. We propose a tri-modal deep learning framework, TMF-RSE (Tri-Modal Fusion with Regional Semantics and Evidential Uncertainty), that combines appearance features from two-dimensional chest inputs, structural features from lung segmentation masks, and semantic features from vision-language models (VLMs) for severity quantification. Our approach employs complementary fusion mechanisms that integrate semantic guidance, structural priors, and hierarchical interactions across modalities. The model employs evidential regression to provide both severity predictions and uncertainty estimates. Experiments on the Per-COVID-19 CT and RALO datasets show that TMF-RSE outperforms recent transformer-based baselines, achieving MAE of 4.02 and Pearson correlation of 0.9629 on Per-COVID-19 validation, and 0.339 MAE / 0.973 PC on RALO geographic extent.

Imaging demand is growing faster than the radiology workforce can expand, and reporting backlogs cannot be resolved through training and recruitment alone. The most direct opportunity is reducing the time and effort radiologists spend producing reports, a task that requires interpreting images, integrating clinical history and prior studies, and drafting structured findings. We present Harrison.Rad 1.5 (HR1.5), a radiology-specific multimodal large language model that accepts interleaved text and visual inputs and generates structured and unstructured text across plain-film radiology, spanning computed radiography, chest, musculoskeletal, abdominal, spine, and pelvic x-rays, and mammography. HR1.5 is trained through a three-stage pipeline: domain adaptation of a base language model on radiology reports, contrastive vision-encoder training with curriculum-based hard negatives on ~6 million image-report instances, and visual-question-answering fine-tuning on multi-turn conversations. We evaluate it with a Findings-Diagnosis scoring framework that extends RadGraph-XL entity extraction with ontology-based synonym matching and polarity-contradiction detection, benchmarked on RadBench, a simulated FRCR 2B Short Case examination scored against Angoff-method thresholds, ReXGradient, and internal multi-modality datasets. HR1.5 is the only system evaluated to meet the simulated FRCR passing standard and achieves the highest accuracy on closed-format clinical questions, across anatomical regions, on internal multi-body-part and mammography reporting, and on the primary clinically-aligned score for public chest reporting. We further examine explainability and model behaviour, including question-sensitive Grad-CAM heatmaps, attention analysis, and confidence estimation, to support responsible future evaluation toward clinical use, and a framework for clinically grounded assessment of report quality.

Wound monitoring is a critical yet underserved clinical challenge, where timely identification of severe adverse events (SAEs) such as infection, tissue deterioration, and delayed healing can significantly impact patient outcomes. While vision-language models (VLMs) show strong multimodal reasoning, they often lack domain-specific grounding to integrate wound imagery with heterogeneous clinical information, and provide limited mechanisms for detecting cases that diverge from the training distribution. We present a multimodal framework for automated wound monitoring and SAE detection. Our approach leverages paired clinical notes and wound descriptions capturing visual characteristics such as appearance, surrounding skin condition, color changes, and signs of inflammation or healing progression, encoded through a dual-stream Low-Rank Adaptation (LoRA) framework built on a frozen BiomedCLIP backbone. We introduce a cross-contextual LoRA fusion mechanism enabling information exchange between clinical semantics and visual wound descriptors, producing context-aware multimodal representations without full model fine-tuning. To identify personalized SAEs, we propose a wound-specific out-of-distribution (OOD) detection framework combining semantic matching, visual typicality, caption-text alignment, and caption-visual alignment into a unified SAE (OOD) score. To capture healing dynamics, we incorporate covariate consistency and temporal drift penalties that leverage changes in wound characteristics across visits. Experiments on a longitudinal wound dataset collected through clinical visits show promising performance on both wound healing assessment and SAE detection, highlighting the potential of semantically enriched, temporally aware vision-language systems for clinical wound monitoring and early risk identification.

Automated chest X-ray classification remains challenging due to severe class imbalance, co-occurring pathologies, and the loss of localized features in conventional architectures. To address these, we propose an explainable hierarchical multi-view ensemble framework for the robust classification of 14 thoracic pathologies. The framework employs view-specific training by independently modeling frontal and lateral radiographs using an ensemble of five complementary convolutional neural networks. Replacing global average pooling, a multi-scale feature fusion strategy augmented with Convolutional Block Attention Modules (CBAM) preserves fine-grained intermediate representations while emphasizing high-level pathology-specific semantic features. To mitigate positive-negative imbalance and varying inter-class difficulty, models are optimized using a novel hybrid objective combining Asymmetric Loss with Adaptive Focal Loss. Beyond simple probability averaging, the framework incorporates a hierarchical meta-learning strategy where test-time augmentation (TTA) predictions and cross-model uncertainty measures are integrated into Level-1 gradient-boosting meta-learners (XGBoost, LightGBM, and CatBoost), followed by Level-2 stacking with optimized alpha blending. Evaluated on a large-scale CheXpert-style dataset, the framework achieves state-of-the-art macro-average AUROC scores of 0.9319 for frontal and 0.9154 for lateral radiographs. Furthermore, comprehensive explainability analysis using seven post-hoc attribution techniques demonstrates strong anatomical consistency and clinically meaningful decision localization. By integrating architectural diversity, multi-scale attention, hierarchical meta-learning, and rigorous explainability, the proposed framework provides a transparent, highly accurate, and clinically practical computer-aided diagnosis system for thoracic disease classification.

Uterine diseases represent an important category of gynecologic pathology and require accurate histopathological assessment for diagnosis and treatment planning. Whole-slide images (WSI) have enabled the digital transformation of pathology workflows and provided new opportunities for artificial intelligence (AI) in computational pathology. In particular, multimodal models that jointly analyze histopathology images and pathology reports have shown promising potential for automated pathology report generation and AI-assisted diagnosis. However, the development of such systems remains limited by the scarcity of datasets that pair whole-slide images with clinically meaningful pathology reports. Instead, existing pathology datasets focus on patch- or slide-level annotations of a single endpoint (e.g., disease class), which do not fully capture the rich information in full clinical diagnostic workflow reports. Here, we introduce TUM-Uteria, a uterine pathology dataset comprising WSIs paired with diagnostic pathology reports at both the case and slide levels, collected from a tertiary medical center. The dataset contains 216 clinical cases, comprising 455 slide-level WSI-report pairs. The dataset underwent a structured multi-stage validation procedure involving board-certified pathologists to ensure reliable annotations. TUM-Uteria supports research in computational pathology, including whole-slide image analysis, multimodal learning, and automated pathology report generation.

Microbial keratitis requires rapid pathogen identification to guide treatment, but culture- and PCR-based diagnostics are slow and resource-intensive. We developed a triple-phase multimodal framework for bacterial-versus-fungal keratitis classification using slit-lamp photographs acquired under blue-light, sclerotic-scatter, and white-light illumination, together with clinical metadata. The model combines cross-modality contrastive learning, modality-specific fine-tuning, and feature-level multimodal ensemble learning for patient-level prediction. We evaluated the framework on a multicenter dataset of 1,645 patients and 17,158 images from India and the United States. The model achieved 85.84% accuracy, 84.46% average F1-score, and 0.885 AUC. Site-specific evaluation showed that pooled results were overly optimistic, whereas resampling- and balance-based re-evaluation provided a more realistic assessment of cross-site generalization. Under all settings, our framework remained the top-performing approach. The code is available at https://github.com/yqwang01/TPMKA and dataset access will be provided subject to University of Michigan data-sharing clearance.

Medical imaging models often degrade when deployed at new clinical sites due to differences in imaging equipment, protocols, and patient populations. Test-time adaptation (TTA) addresses this by updating a pretrained model using only unlabeled target data, without access to source data. However, existing TTA methods were designed for single-label classification on natural image benchmarks, minimizing entropy uniformly across all samples without considering label dependencies. This overlooks a key property of multi-label medical imaging: pathologies do not occur independently but exhibit structured co-occurrence patterns. In this work, we propose Co-occurrence Weighted Adaptation (CoWA), which leverages disease co-occurrence patterns as a reliability signal for adaptation. CoWA estimates label co-occurrence structure from model predictions and downweights samples that deviate from expected patterns, enabling adaptation to rely more on consistent predictions while reducing the impact of noisy ones. We evaluate CoWA on chest X-ray benchmarks under domain shifts and demonstrate consistent improvements over established baselines.

Radiologists routinely compare current and prior chest X-rays to track disease progression, producing follow-up reports that describe multiple findings, each localised to an anatomical region and annotated with a temporal change status. Existing automated methods either generate reports from a single image without modelling temporal context, or incorporate temporal information but do not ground their outputs spatially. The few approaches that combine temporal reasoning with spatial grounding are restricted to single-finding descriptions, leaving multi-finding reports with mixed change directions unaddressed. We present GRCD, a framework for grounded report generation from chest X-ray pairs in the multi-finding setting. We first construct a rigorously cleaned dataset of temporal chest X-ray pairs by identifying and correcting two systematic labelling errors in the source annotations. We then introduce a Region-Guided Change Token module that encodes per-region temporal change across anatomical structures and injects this signal into a language model through a dual-pathway strategy combining prepended spatial tokens with gated cross-attention. On a multi-finding test set, GRCD outperforms existing baselines on text generation and clinical accuracy metrics, with gains in change detection. Ablation studies confirm that the dual-pathway design outperforms either integration strategy in isolation on text and clinical metrics, and that region-level change encoding is necessary for multi-finding generation. Code is available at https://github.com/UTSA-VIRLab/GRCD

Breast fibroadenoma (FA) and phyllodes tumor (PT) are fibroepithelial breast lesions with highly overlapping appearances on B-mode ultrasound, making benign and borderline PT prone to being misclassified as FA and complicating preoperative decision-making. Existing computer-aided diagnosis methods commonly rely on single-modal imaging features and insufficiently exploit complementary clinical and textual information. To address this limitation, we construct the FAPT-M Dataset, a pathology-confirmed multimodal dataset comprising 910 patients with strictly reviewed ultrasound images, structured clinical attributes, and ultrasound diagnostic descriptions. Based on this dataset, we propose a clinically guided multimodal framework that integrates DenseNet-based visual encoding, CLIP-inspired text encoding, and lightweight clinical encoding, and further introduces clinical-conditioned adaptive modulation, cross-modal Transformer fusion, and dual-path representation learning to improve feature alignment and multimodal interaction. Under patient-level five-fold cross-validation, the proposed method achieves an accuracy of 77.64%, F1-score of 73.38%, and AUC of 89.74%, outperforming representative CNN-, Transformer-, and vision-language-based baselines. Ablation studies and class-balanced evaluations further confirm the contribution of three-modality fusion and the key architectural components. Overall, this work provides an effective multimodal approach for fine-grained FA-PT classification and establishes a high-quality benchmark for multimodal breast ultrasound analysis.

Large vision-language models (LVLMs) have achieved strong performance across many medical imaging tasks, yet their application to ultrasound remains limited due to its inherent complexity and variability. In this work, we revisit what is truly needed to enable real-world ultrasound understanding. Instead of introducing complex architectures or elaborate training strategies, we show that data scale and clinically faithful data alignment are the key factors. We construct a large-scale dataset of 1.5M real-world ultrasound examinations, containing 17.7M images, multi-organ coverage, and paired uncurated clinical reports. Crucially, we organize the data at the examination level, aligning multiple images with their corresponding reports to reflect real clinical workflows. We then fine-tune a standard LVLM using low-rank adaptation (LoRA) on this dataset without task-specific modifications. Surprisingly, this simple recipe already leads to strong performance across diverse ultrasound understanding tasks, outperforming prior methods designed with more complex pipelines. Beyond these results, we present model and data scaling analyses that provide insights into the role of scale in ultrasound LVLMs.

Traditional Chinese Medicine (TCM) diagnosis, particularly through tongue inspection, faces persistent challenges in subjectivity and reproducibility. The application of multimodal artificial intelligence to TCM clinical tasks, such as syndrome differentiation and prescription generation, is significantly hampered by the semantic gap between visual tongue features and textual reasoning, as well as the lack of large-scale, standardized datasets. To address these challenges, we introduce MMIR-TCM, a novel framework that emulates the diagnostic process of TCM experts by integrating multimodal large language model(MLLM) with memory-augmented segmentation and retrieval-augmented generation (RAG). Employing a three-stage architecture, MMIR-TCM integrates a training-free Memory-SAM module for robust tongue extraction, a fine-tuned Qwen3-VL model for structured tongue diagnosis generation, and a Qwen3-based RAG component for evidence-grounded clinical decision support generation. The framework was developed and validated using MedTCM, a new large-scale multimodal dataset that we introduce specifically for advanced TCM research. To properly evaluate our framework's clinical accuracy, which existing metrics fail to capture, we also developed TDEU, a domain-specific evaluation metric incorporating semantic understanding and diagnostic importance. Our comprehensive experiments demonstrate that MMIR-TCM significantly outperforms leading models, including GPT-4o and Gemini 2.5 Flash.

INTRODUCTION: Accurate MRI-based identification of Alzheimer's disease (AD), mild cognitive impairment (MCI), and related dementias remains challenging because disease-related structural changes are often subtle and heterogeneous. We developed NeuroBridge, a clinically guided multi-task MRI framework for neurodegenerative disease diagnosis. METHODS: NeuroBridge integrates large-scale self-supervised MRI pretraining with hippocampal segmentation, hippocampal atrophy classification, and reconstruction objectives, followed by gated fusion fine-tuning. Performance was evaluated across ADNI and OASIS cohorts, including cross-cohort transfer, probability-based analysis, and opportunistic screening. RESULTS: NeuroBridge achieved the highest performance across evaluated classification tasks, reaching 88.17% accuracy for AD versus cognitively normal controls in ADNI and 82.78% in OASIS. The largest gains occurred in MCI-related and mixed-diagnosis settings. The framework demonstrated strong cross-cohort generalization, systematic associations between predicted-class probability and accuracy, and the feasibility of probability-based opportunistic screening. DISCUSSION: Clinically guided multi-task representation learning improves neurodegenerative MRI diagnosis beyond conventional single-task approaches. NeuroBridge provides a robust and scalable framework for dementia assessment and MRI-based opportunistic screening.

Deep learning models for medical diagnosis frequently exhibit substantial performance disparities across sensitive subgroups (e.g., race, sex), even when average accuracy is high. While generative data augmentation offers a route to mitigate this, existing strategies are suboptimal; they typically address only one or two dependency channels between sensitive attributes and image features. We formalize the medical image formation process via a structural causal model, revealing that sensitive attributes actually influence image content through four distinct pathways-a structural complexity neglected by prior works. Based on this insight, we introduce CIPHER (Causal Intervention Pathways for Healthcare Equity and Robustness), a framework designed to systematically intervene on all four causal paths. To achieve this, CIPHER utilizes a diffusion backbone equipped with classifier-free guidance and null-text inversion. This technical design enables the faithful reconstruction of patient-specific anatomy while allowing for the precise, editable synthesis of counterfactuals required to break sensitive dependency chains. We tested CIPHER using chest X-ray and dermoscopy benchmarks across both standard and shifted data distributions. By employing a multi-pathway intervention strategy, our model reduced worst-group disparities by an average of 35.8% compared to disease-conditioned synthesis baselines, while also improving total diagnostic accuracy

Recent multimodal large language models have shown great promise in clinical image reasoning, but existing post-training pipelines remain predominantly outcome-centric, relying on final answer correctness or sequence-level preferences. This suffers from sparse credit assignment, making it difficult to optimize the reasoning process essential for clinical applications. Our analysis reveals that cascading errors from early-stage reasoning failures are a leading cause of incorrect predictions in medical visual question answering (VQA) benchmarks. Motivated by this, we propose Medical Reasoning-aware Policy Optimization (MRPO), an RL algorithm that incorporates step-wise process rewards. When the final answer is incorrect, MRPO assigns exponentially larger penalties to tokens in earlier invalid reasoning steps, breaking failure cascades without compromising successful paths. Across three multimodal LLM backbones, MRPO consistently outperforms standard GRPO and a recent RL baseline, and on Qwen3-VL-8B-Instruct even surpasses substantially larger medical MLLMs such as HuatuoGPT-Vision-34B by 2.79 points. Moreover, MRPO reduces early-stage reasoning failures from 64.0% to 13.0%, showing that targeted mitigation of cascading failures improves both reasoning quality and final answer accuracy. Our code is available at https://github.com/dmis-lab/MRPO

Vision-language models (VLMs) combining reinforcement learning (RL) ignite remarkable progress in multimodal reasoning, yet still struggle with medical images, which typically exhibit extremely sparse visual evidence to inform clinical decision-making. We recognize that pruning visual tokens outside the grounding region greatly enhances medical reasoning. However, a united RL framework for active visual token pruning (VTP) and medical multimodal reasoning remains unestablished. Here, we propose a dual-stream RL framework, ViToS, to fulfill token pruning and question answering. ViToS trains one policy model with two task branches, where one focuses on grounding while the other conducts token-sparse reasoning after VTP. Furthermore, we solve the coupled policy learning problem by introducing the cross-feedback sequential optimization, avoiding gradient conflict and facilitating convergence of the shared policy model. Evaluated on seven medical benchmarks, our method reduces visual tokens to 77% of the original sequence length while achieving a 108.27% relative performance on Lingshu-7B and 104.16% relative performance on HuatuoGPT-Vision-7B. Overall, ViToS delivers superior performance and inference speedup, establishing an efficient paradigm for medical multimodal reasoning.

Recent years have seen substantial advances in radiology report generation (RRG), yet existing approaches predominantly adopt direct feature fusion when handling multi-view X-ray images. Such approaches overlook the potential clinical inconsistencies and inaccuracies arising when a single model processes different views, adversely impacting performance and clinical reliability. To this end, we introduce View-PNDF (View-specific Pattern Neuron Detection and Fine-tuning), a parameter-efficient framework that fosters view-consistent report generation from a neuronal perspective. Specifically, View-PNDF comprises: (i) a view-specific neuron detection module identifying neurons responsive to particular views, (ii) a verification module quantifying the existence of these neurons, and (iii) a selective fine-tuning strategy strengthening detected neurons while preserving view-agnostic representations. By updating only view-specific neurons, View-PNDF achieves consistent diagnoses across different views with reduced computational costs. Subsequently, we employ Large Language Models (LLMs) to consolidate the view-specific reports into a complete radiology report. Furthermore, we use traditional Natural Language Generation (NLG) metrics-based assessment on integrated reports for baseline comparison and employ LLM-based assessment (e.g., GPT-4o) on view-specific reports to capture clinical significance. Extensive experiments on two medical RRG benchmarks demonstrate that View-PNDF substantially improves view-specific chest X-ray report generation quality while maintaining robust general-view performance.

Prototype-based medical image classifiers present three clinical limitations: they treat findings as independent, silently amplify unsafe physician feedback, and require full retraining whenever a new finding is needed. We present GRAPE (Graph-Augmented Prototype Explanations), a unified architecture that addresses all three challenges. First, a Graph Attention Task Head models anatomical concept co-occurrence, boosting macro-F1 by +13.8,pp over the prototype baseline on TBX11K. Second, a Concept-Mismatch Safety Check - the first such mechanism in prototype-based medical classifiers - warns when the model's dominant finding inside a doctor-drawn region conflicts with the claimed label, catching 85% of erroneous annotations versus 51% for MC-Dropout with no extra inference cost. Third, Open-Vocabulary Prototype Anchoring aligns visual prototypes to clinical text, allowing a new finding to be added from a single labeled image without modifying any other component. On NIH ChestX-ray14, one Effusion example recovers full-supervision localization accuracy; on TBX11K, prototype maps achieve 2.6x better lesion localization than end-to-end baselines. All three capabilities add only +1~ms latency at interactive batch size. The project page is https://github.com/KurbanIntelligenceLab/GRAPE.

Color Fundus Photography (CFP) offers a low-cost and non-invasive route for ischemic heart disease (IHD) screening, but current studies are limited by scarce public benchmarks and ineffective fusion of retinal images with sparse clinical variables. We propose IDNet, a multimodal framework with a Cross-Modal Distillation Aggregator (CDA) that uses learnable queries to sequentially integrate left-eye, right-eye, and clinical features, mitigating the imbalance between high-dimensional visual features and low-dimensional tabular inputs. We also construct a reproducible UK Biobank benchmark with open-source curation and quality-control pipelines, yielding 50,410 images from 25,205 subjects. On this benchmark, IDNet outperforms image-only, clinical-only, and several multimodal baselines, and CDA consistently improves multiple visual encoders as a plug-in fusion module.

Objective: ICD codes are central to reimbursement, research, and population health surveillance, yet automated coding systems often struggle to integrate diagnostic signals from both clinical narratives and structured electronic health record (EHR) variables. We evaluated whether frozen medical large language model (LLM) representations can serve as a shared embedding space for multimodal primary diagnosis category prediction. Materials and Methods: We constructed a MIMIC-IV cohort of 13,645 admissions from the 10 most frequent primary ICD-10 codes, consolidated into seven categories. Structured variables were serialized into clinical narratives and combined with leakage-pruned discharge notes. Using a frozen MedFound-Llama3-8B-finetuned backbone, we extracted hidden states from five transformer layers and trained linear probes for structured-only, unstructured-only, and combined inputs, comparing against XGBoost and information-matched PLM-ICD baselines and evaluating MIMIC-III adaptation with a compact bottleneck adapter. Results: The combined probe performed best on MIMIC-IV (87.69% strict; 91.45% medical accuracy), exceeding both single-modality probes and baselines. The structured-only probe outperformed its standard baseline by 6.19 points in medical accuracy. Diagnostic information became increasingly linearly separable in deeper layers, and a 2M-parameter adapter restored cross-dataset transfer to MIMIC-III using only 5% of target labels. Discussion: LLM embeddings can unify structured and narrative EHR information for multimodal diagnosis prediction, supporting efficient reuse of clinical representations across modalities and datasets through a small representation-level module. Conclusion: Multimodal probing of frozen medical LLM representations provides a practical approach for studying EHR modalities and adapting clinical representations across datasets.

Pathology foundation models (PFMs) have demonstrated strong potential across clinical and scientific applications, yet their performance is often hindered by batch effects, which are non-biological variations across tissue source institutions (TSIs) that distort learned feature representations and impair generalization. Conventional mitigation strategies, such as stain normalization, offer limited success in addressing these high-dimensional, complex artifacts. We present GLMP (General-purpose LLM-Mediated Pathology model), a novel framework that generates robust numerical embeddings from histology image patches through an intermediate textual representation. By leveraging pretrained general-purpose multimodal large language models (MLLMs) and text encoders, GLMP effectively prioritizes biologically meaningful signals over TSI-specific artifacts, thereby improving cross-institutional generalization. To our knowledge, GLMP is the first pathology model to use text descriptions of histological features as an intermediate representation for generating numerical embeddings from histology images. Our results highlight the untapped potential of broad-domain, non-specialized MLLMs in computational pathology and introduce a new paradigm for building versatile, generalizable, and robust pathology models.

Recent advances in large language models and vision-language models have enabled reasoning over multimodal data, offering opportunities for clinical applications such as decision support and triaging. However, existing medical AI benchmarks are fragmented: some support multi-turn dialogues but lack images, while others provide multimodal inputs but focus on single-turn QA tasks. To address this gap, we introduce IMCBench, an image-grounded, multi-turn medical conversation benchmark that pairs real, publicly available clinical images with synthetic patient profiles to simulate realistic patient-clinician interactions. Each conversation is evaluated across three clinical dimensions: safety, accuracy, and appropriate use of uncertainty in diagnosis. We benchmark eight multimodal frontier models across four model families (Claude, GPT, Nova, and Llama), scoring each on a 1-5 scale using LLM-as-Jury scoring calibrated against expert clinician annotations. Our results show that Claude Opus 4.6 achieves the highest overall score (3.61), followed by Claude Sonnet 4.6 (3.30) and GPT-5.2 (3.29), though no model dominates all dimensions and safety degrades for both malignant and rare conditions ($Δ$ = -0.27 each). Ablation studies further reveal that both visual input and EHR context contribute to safe guidance (safety drops of 0.18 and 0.23 on average when each is removed), with stronger models leveraging visual features more effectively. Together, these findings demonstrate that accurate clinical description does not guarantee safe patient guidance, motivating the need for multi-dimensional evaluation frameworks in medical AI.

Echocardiography is the most widely used non-invasive cardiac imaging modality, providing essential information for cardiovascular diagnosis. Interpreting an echocardiogram requires synthesizing complementary evidence across multiple heart views to identify abnormalities and produce structured clinical reports. While recent efforts focus on improving classification performance, most models lack explicit diagnostic reasoning and spatially grounded anatomical evidence, limiting clinician trust. We present EchoSonar-R, a multi-view reasoning-enabled vision-language model that jointly performs multi-label disease classification and report generation from echocardiography studies. EchoSonar-R combines a spatiotemporal video encoder with a structure-aware cardiac detector that provides spatially grounded anatomical cues to improve interpretability and clinician trust during cross-view reasoning. EchoSonar-R is trained in two stages: supervised fine-tuning (SFT) on reasoning-annotated targets, followed by Group Relative Policy Optimization (GRPO) with task-specific rewards that jointly align classification and report generation within a unified reinforcement-learning framework. Across a private multi-view dataset and two public benchmarks, EchoSonar-R improves macro balanced accuracy by 17.1% on the private set and 6.1% on MIMICEchoQA over the strongest baseline, achieves a GREEN clinical faithfulness score of 0.800, and produces interpretable reasoning traces grounded in multi-view visual evidence.

Large Vision-Language Models (LVLMs) specialized in healthcare are emerging as a promising research direction due to their potential impact in clinical and biomedical applications. However, progress is constrained by the scarcity of high-quality medical multimodal data, concerns about robustness in safety-critical settings, and the narrow and potentially contaminated evaluation benchmarks that limit reliable assessment. To address these issues, the field requires state-of-the-art solutions to be fully open and reproducible systems in which all components can be inspected, evaluated, and improved. This work introduces Aloe-Vision-Data, a large-scale, quality-filtered mixture which integrates both medical and general domains across multimodal and text-only sources, designed for direct use in model fine-tuning. Building on this dataset, we train the Aloe-Vision family of medical LVLMs, openly released with full weights, training recipes and data, in two scales (7B and 72B). Through comprehensive benchmarking, we demonstrate that high quality training mixtures produce balanced LVLMs which yield significant gains over the baseline models without compromising general capabilities, achieving competitive performance with respect to state-of-the-art alternatives. To support reliable evaluation, we introduce CareQA-Vision, a carefully curated vision benchmark derived from MIR and EIR exams, the residency entrance exams for medical and nursing specialists in Spain, offering novel vision questions with low likelihood of contamination. Finally, we show that current LVLMs remain vulnerable to adversarial and misleading inputs, underscoring reliability challenges in clinical contexts.

Multimodal large language models (MLLMs) applied to Medical Visual Question Answering (VQA) tend to produce overconfident outputs regardless of actual correctness, and existing verbalized confidence calibration methods, developed primarily for text only LLMs, do not account for the multimodal nature of medical image understanding. This work proposes a training based framework that finetunes MLLMs to improve their calibration using a composite loss function combining a Brier style calibration term, an anchor regularizer that prevents confidence collapse toward extreme values, a contrastive image text alignment term, and a KL based model stabilization term. The alignment signal is derived from a $2 \times 2$ factorial perturbation design that crosses image presence with text integrity, probing the reliance of the model on visual modality input versus language priors. Finally, a top K KL divergence regularizer is used to protect the answering ability of the model during finetuning. Across three Medical VQA benchmarks and two architectures (MedGemma 4B IT and Qwen2 VL 7B Instruct), our method reduces calibration error by 60% or more, and improves discrimination by 26% or more, while preserving predictive accuracy. On average across benchmarks, the technique outperforms prompting based, sampling based, and training based approaches, and ablation experiments confirm that each component of the loss function is indeed necessary for improving the calibration. All code for the experiments is publicly available.

Data scarcity is a major bottleneck in medical Multiple Instance Learning (MIL), especially for rare diseases or expensive modalities. We introduce a statistically grounded patient augmentation approach that generates realistic patients directly in embedding space. Using Gaussian Mixture Models as a probabilistic clustering approach on pooled instance embeddings from all patients, our method learns disease-specific "recipes"-statistical distributions of instances across unsupervised clusters. New patients are then generated by sampling embeddings from clusters based on learned recipes. Unlike existing methods that require examples from all categories, our method can generate patients offline by re-mixing pooled embeddings. Generated patients are further selected based on uncertainty quantification to improve MIL performance. We evaluate our method across three clinically relevant scarcity scenarios: (i) cross-dataset transfer, where an entirely missing "healthy" class is generated using statistics from an external cohort; (ii) low-data regimes, where class sizes are extremely limited; and (iii) small-cohort non-image tasks, including single-cell RNA-seq and flow cytometry. Across all experiments, our method improves performance over baseline, often outperforming other bag-mixing strategies. Notably, in the missing-class scenario, a performance comparable to full-dataset training is achieved, demonstrating its potential for rare disease diagnostic and privacy-preserving patient augmentation. The code is available at https://github.com/marrlab/RECIPE

Learning causal models from fragmented biomedical data is challenging because clinical, molecular, and imaging variables are often incomplete or not jointly observed. We propose RetiSEM, a domain-constrained structural equation modelling (SEM) framework for causal graph recovery and mediation analysis under limited multimodal resources. This proposed work organises variables into biologically informed blocks, applies forbidden-edge constraints, and decomposes pathway-level effects into TE, NDE, and NIE components. We evaluate RetiSEM across ten synthetic benchmark scenarios that vary in dimensionality, nonlinearity, causal depth, and pathway structure, together with a fragmented real-world setting that combines NHANES clinical variables with externally derived retinal representations. This approach achieves lower structural error and higher causal accuracy than unconstrained baselines across the synthetic benchmarks. In the real-data analysis, retinal variables behave mainly as downstream biomarker-like indicators, with smaller but detectable indirect effects. These findings support our strategy as an interpretable framework for testing structured causal hypotheses in limited-resource biomedical AI. The code and resources for this work are publicly available at: https://github.com/Inamullah-Colab/ReitSEM.

Existing medical AI benchmarks lack process visibility, atomic skill evaluation, and integrated hallucination detection. We introduce MedBench v5, a redesigned benchmark for clinical multimodal models (language, vision-language, and agent systems) that moves from static QA to dynamic, process-oriented evaluation. MedBench v5 features: (1) a dual-dimensional framework combining Clinical Cognitive Responsiveness (13 sub-dimensions) and Medical Atomic Skills (4 agent environments), covering 63 tasks; (2) three switchable information-flow stressors (omission, contradiction, evidence delay) for factorized degradation analysis; (3) a dynamic process audit protocol with five reasoning nodes that produces model-specific failure fingerprints; (4) hallucination propagation monitoring across initiation, propagation, anchoring, and contradiction interaction-capturing silent hallucination. Experiments on frontier models show that strong overall task performance does not guarantee process stability: stressors mainly disrupt contradiction detection, diagnosis updating, hallucination propagation, and contradiction-based self-correction, while final evidence grounding can remain superficially stable. MedBench v5 provides a unified infrastructure for capability profiling, controllable stress testing, process auditing, and hallucination trajectory analysis in clinical AI evaluation.

While Vision-Language Models (VLMs) show great promise in volumetric medical report generation, they frequently suffer from visual hallucinations and a lack of grounding in 3D CT data. Current Supervised Fine-Tuning (SFT) and Reinforcement Learning (RL) strategies typically optimize text fidelity alone, essentially rewarding correct diagnoses derived from language priors rather than genuine visual perception. To address this, we propose cross-view aligned Evidence-driven Multimodal Reinforcement Learning (Evidence-MRL, noted as E-MRL), a reliable RL reasoning framework that formulates the generation process as a Markov Decision Process of "diagnosis-localization-verification". Unlike standard approaches, our model is explicitly trained to identify a "key evidence slice" alongside the global diagnostic report, grounding its findings in verifiable visual evidence. Crucially, we introduce a novel cross-view consistency reward, which validates the semantic alignment between the golden-standard report and a local visual re-query of the selected key slice, providing additional rewards for correctly-localized reasoning. Experiments on large-scale 3D CT tumor datasets demonstrate that E-MRL significantly reduces hallucinations and improves diagnostic accuracy compared to SFT and RL baselines, offering a clinically interpretable solution for visually-grounded and tumor analysis.

Large-scale pretrained foundation models have revolutionized general medical screening, but often falter on rare diseases because such conditions are underrepresented in real-world clinical datasets. While retrieval-augmented diagnosis attempts to mitigate this, conventional static methods frequently succumb to the hubness problem, retrieving visually similar but semantically incorrect common diseases. To address this, we propose Evo-RAD, a self-evolving agentic framework that transforms evidence acquisition into a dynamic decision-making task. We formulate retrieval as a Markov Decision Process (MDP) where a graphbased agent observes the reference set state and executes actions to purge discordant evidence (DELETE), acquire pathologically consistent samples (INSERT), or conclude the evolution (TERMINATE). Optimized via Group Relative Policy Optimization (GRPO) with a homogeneityaware reward, the agent learns to maximize the diagnostic homogeneity of the support reference set. Experiments on retinal disease benchmarks show that Evo-RAD substantially improves rare-disease diagnosis, outperforming retinal foundation models by +21.04%, while also surpassing retrieval-based and parameter-efficient fine-tuning methods by +3.56%. Code is available at https://github.com/SDH-Lab/Evo-RAD.

Multimodal large language models (LLMs) are increasingly adopted to interpret 12-lead ECG images, though the interpretations often lack validation. However, ECG image understanding significantly differs from general images as it depends on precise waveform morphology, lead relationships and accurate interval measurements. This study investigated whether zero-shot multimodal LLMs can reliably distinguish normal and abnormal ECG images and, in parallel, evaluated CNN-based models for clinically grounded references. Standard 12-lead ECG recordings were rendered as single-page images for a binary normal-abnormal classification task. Three prominent LLMs (GPT-5.2, GPT-4.1, and Gemini-2.5 Pro) were tested using a fixed zero-shot prompt across multiple runs. In parallel, a physiology-aware CNN-based model was developed with the capability to aggregate features from the predefined anatomical lead groups. The model was compared with ResNet18, DenseNet121, VGG16 baselines, and all the models were evaluated on an internal test set and external PTB-XL dataset. Across seeds, CNN-based models demonstrated stable discrimination, with average internal ROC-AUC of 0.92-0.94, and external ROC-AUC of 0.85-0.86. The proposed LeadGroupECG model significantly improved over its backbone internally without compromising external generalization. It remained competitive with other baselines, while consistently highlighting anatomical lead-group contributions. In contrast, zero-shot LLM discrimination remained near-chance (ROC-AUC around 0.5). The PR-AUC improved slightly when ECGs used a grid-based calibration background compared with the grid-free ECGs. Although multimodal LLMs can generate reasonable ECG narratives, their zero-shot diagnostic discrimination remains limited. Therefore, clinically framed, domain-specific architectures remain essential for AI-based ECG interpretation.

Pulmonary embolism (PE) is a high risk cardiopulmonary condition whose management requires both timely diagnosis and reliable assessment of future clinical risk. Because PE care routinely combines computed tomography pulmonary angiography (CTPA), radiology interpretation, and longitudinal electronic health record (EHR) evidence, it provides a clinically meaningful setting for evaluating compact multimodal language models. In this work, we build a benchmark using efficient multimodal large language models (MLLMs) on INSPECT, a multimodal PE dataset containing 23,248 CTPA studies from 19,402 patients. We formulate eight diagnostic and prognostic tasks as structured clinical question answering problems and evaluate on typical efficient MLLMs under CTPA-Only, EHR-Only, and CTPA+EHR settings with zero-shot and few-shot prompting. Results show that Gemma4 E4B and Gemma4 E2B perform more strongly when EHR evidence is available, especially under CTPA+EHR input. Task level analysis further shows that PE diagnosis achieves higher performance than prognostic tasks, particularly readmission prediction. These observations suggest that compact multimodal models have the great potential in early stage PE risk detection and explanation.

Gastrointestinal cancers represent a growing health burden in the South Asian region, driven largely by rapid changes in socio-economic conditions & lifestyle habits. However, early diagnosis of such malignancies remains a significant challenge, largely due to a lack of modern equipment, lack of financial support, and a scarcity of GI experts. AI-assisted diagnosis & report generation, show great promise in alleviating this problem by providing low-skill manpower the technical expertise to perform diagnosis. However, almost all open-source, publicly available datasets are predominantly collected from the European region, with no representation from the South Asian region. The lack of open-source GI datasets from diverse geographic regions has made it difficult to assess whether population bias is present in existing models, and to develop geographically inclusive AI tools for automated GI diagnosis. To address this gap, we introduce SAGE: An Expert-Annotated South Asian GI Endoscopy dataset for image captioning, multi-label classification, and visual question answering (VQA) tasks. It consists of 1,300 images, their captions along with hallucination tag, 18 labels and 14,726 question-answer pairs making it well-suited for diverse range of tasks including classification, benchmarking, and fine-tuning large multimodal models (LMMs). We further conducted benchmarking of multi-class classifiers on the effect of population shift in GI imaging AI tasks, and contemporary LMMs on their performance. Our study reveals that task-specific models, such as multi-class classification models, suffer the most, with an average performance drop of 58% when evaluated on the South Asian dataset. For contemporary LMMs, benchmarking reveals a substantial drop in the average GREEN score for anatomical landmark detection (0.308) and abnormality detection (0.410).

Precision medicine in ophthalmology requires accurate longitudinal predictions, but the fragmented nature of multimodal clinical data remains a barrier to forecasting. We introduce OphthaDT, an LLM-based digital twin for ophthalmology that serializes longitudinal patient histories from 3,220 patients across four Phase III clinical trials into structured narratives to forecast best corrected visual acuity (BCVA). In benchmarks spanning up to 100 weeks, OphthaDT demonstrated the lowest prediction error in neovascular age-related macular degeneration (nAMD), achieving an average mean absolute error (MAE) reduction of 6.0% compared to all baselines. In diabetic macular edema (DME), OphthaDT demonstrated competitive performance against all baselines while outperforming Random Forest and XGBoost by an average MAE reduction of 2.6% and 6.9%, respectively. Results reveal that OphthaDT's predictive advantage scales with trajectory complexity: whereas linear models remain effective for the more stable treatment responses of DME, OphthaDT's capacity is better suited for capturing the high longitudinal variability of nAMD. Finally, OphthaDT handles irregular sampling without imputation, positioning LLM-based clinical trajectory modeling as a methodology that could reduce patient burden and accelerate drug development.

Diagnosing mobile crashes in ultra-large-scale industrial applications is a formidable challenge due to the sheer volume of code, the complexity of mixed-language environments, and the inability to reproduce failures locally. Traditional static analysis struggles with scalability, while existing LLM-based agents often rely on reproducible environments unavailable in post-mortem scenarios. We present Holmes, a multi-agent system that automates root cause analysis by synthesizing multimodal runtime signals--stack traces, logs, and thread states--to reconstruct failure contexts without reproduction. Holmes introduces a hierarchical Retrieve-Explore-Reason architecture that leverages low-level artifacts (e.g., registers, assembly) to bridge the semantic gap between open-source business logic and closed-source system frameworks. By dynamically compressing the search space using runtime clues, Holmes precisely navigates 70-million-line codebases to identify non-local defects. Evaluated on real-world crashes from WeChat, Holmes achieves 87.6% accuracy in function-level fault localization and reduces average investigation time by over 98% (to ~77 seconds), demonstrating its effectiveness in transforming labor-intensive debugging into an efficient verification workflow.

Automated chest X-ray report generation requires precise cross-modal grounding to ensure clinically reliable descriptions. However, existing vision-language models rely on implicit attention mechanisms that fail to enforce explicit region-word correspondence and disease-level consistency. We propose Game-Theoretic Alignment Network (GTA-Net), a vision-language framework that formulates report generation as a cooperative game-theoretic alignment problem. The model introduces a BinaryGameAligner that models interactions between image regions and text tokens using similarity-based payoff matrices with Shapley-inspired importance weighting. To enforce clinical semantics, we further develop a Disease-Aware Ternary Aligner, which captures joint interactions among images, reports, and structured disease concepts. GTA-Net combines a Swin-based visual encoder with a LoRA-adapted large language model and is trained with a unified objective for generation and alignment. Experiments on CheXpertPlus and IU-XRay demonstrate state-of-the-art performance across standard generation metrics and improved clinical consistency, highlighting the effectiveness of explicit game-theoretic alignment for medical vision-language generation.

Dementia diagnosis requires integrating multi-modal clinical assessments from diverse informants and clinicians under incomplete and heterogeneous data conditions. Yet most AI-driven approaches remain Alzheimer's disease (AD)-centric, framing the problem as binary AD detection or three-stage AD progression modeling within well-curated research settings. This pathology-driven paradigm overlooks the broader, syndrome-level nature of dementia, which spans multiple stages, phenotypes, and etiologies. In this paper, we propose Dementia-Agents, a clinically aligned multi-agent framework for real-world dementia staging and phenotyping. The framework follows a three-step workflow: (1) a data agent translates structured clinical records into semantically faithful textual representations that preserve missing-data signals and routes them to domain-aligned experts; (2) five fine-tuned expert agents generate domain-level predictions; and (3) a coordinator agent performs probabilistic aggregation to produce final staging and phenotyping decisions. We develop and evaluate Dementia-Agents on a real-world clinical cohort of 1,066 patients from two cognitive neurology services. Compared with monolithic multi-modal large language models (MLLMs) and prior medical multi-agent systems, our approach achieves consistent improvements in diagnostic performance for real-world syndrome-level dementia staging and phenotyping, while preserving domain-level interpretability.

Real-world clinical decision support requires reasoning over heterogeneous and longitudinal patient information rather than answering isolated medical questions. However, current medical large language models and retrieval-augmented generation systems often rely on single-step prompting or retrieval, which can be fragile when clinical evidence is distributed across long electronic health records, medical images, sensor streams, guidelines, and referral constraints. This paper proposes MedRLM, a Recursive Multimodal Health Intelligence framework for long-context clinical reasoning, sensor-guided screening, and community-to-tertiary referral support. Instead of compressing all patient information into one prompt, MedRLM treats the patient case as an external clinical environment that can be recursively inspected, decomposed, retrieved, verified, and synthesized. The framework coordinates specialized agents for clinical text, longitudinal EHR, medical imaging, physiological sensor signals, guideline retrieval, uncertainty auditing, and referral planning. It further introduces a Clinical Evidence Graph Memory to connect patient-specific observations with retrieved evidence, standardized definitions, sensor-derived biomarkers, and referral criteria. A sensor-guided recursive triggering mechanism activates deeper reasoning when abnormal physiological or behavioral patterns are detected, while uncertainty-gated refinement supports clinician review for high-risk or low-confidence cases. We also outline a real-data evaluation design using public and credentialed clinical datasets spanning EHR, radiology, ECG, ICU time series, and referral-proxy outcomes. MedRLM aims to move medical AI from static question answering toward auditable, multimodal, and workflow-aware clinical decision support.

Multimodal Large Language Models (MLLMs) show great potential in medical tasks, but their elicited confidence often misaligns with actual accuracy, potentially leading to misdiagnosis or overlooking correct advice. This study presents the first comprehensive analysis of the relationship between accuracy and confidence in medical MLLMs. It proposes a novel method that combines Multi-Strategy Fusion-Based Interrogation (MS-FBI) with auxiliary expert LLM assessment, aiming to improve confidence calibration in Medical Visual Question Answering (VQA). Experiments demonstrate that our method reduces the Expected Calibration Error (ECE) by an average of 40% across three Medical VQA datasets, significantly enhancing MLLMs' reliability. The findings highlight the importance of domain-specific calibration for MLLMs in healthcare, offering a more trustworthy solution for AI-assisted diagnosis.

This article presents a complementary approach for integrating multimodal medical data in cancer classification, based on state space models represented by the Mamba architecture. To this end, a mixed multimodal fusion architecture, called Mixed Fusion, was employed and developed to enhance the interpretability of the decision-making process. The proposed approach explores two variants of Mamba: one dedicated to visual processing, responsible for classifying the lesion image and generating probabilities associated with the target classes, and another focused on tabular processing, which uses these probabilities together with clinical and/or sociodemographic data to produce the final diagnosis. The experiments were conducted on two medical datasets: PAD-UFES-20, composed of clinical images and information associated with skin lesions, and NDB-UFES, consisting of histopathological images and sociodemographic data related to oral cancer. The results indicate slightly lower performance in balanced accuracy, compared with Transformer-based approaches, on PAD-UFES-20, and superior performance on NDB-UFES. Additionally, substantial gains were observed in the recall metric. Furthermore, the adoption of the Mixed Fusion architecture enables the application of the Shapley Additive Explanations (SHAP) method, increasing the interpretability of the results. These findings indicate that Mamba-based models constitute a suitable alternative for multimodal classification in medical data, especially in scenarios in which sensitivity is a relevant requirement.

Accurate survival prediction is essential for personalized treatment planning in head and neck cancer, yet remains challenging due to the heterogeneous and high-dimensional nature of multimodal clinical data. While deep survival models have improved predictive performance over classical statistical approaches, existing methods typically rely on static fusion strategies or temporally agnostic modeling, limiting their ability to capture structured clinical workflows. In this work, we propose ChronoSurv, a heterogeneous hierarchical directed graph framework for multimodal survival analysis. ChronoSurv represents patient care as a progression-aware clinical trajectory using directed graphs aligned with key diagnostic steps. A hierarchical topology incorporates fine-grained, coarse, and global representations, further supporting flexible adaptation to missing modalities, while heterogeneous message passing models complex and asymmetric relationships across modalities and clinical steps. Experimental results on two public datasets demonstrate that ChronoSurv achieves state-of-the-art discriminative performance while maintaining statistically reliable calibration. Comprehensive ablation studies further confirm the contribution of each architectural component, highlighting the potential of trajectory-aware graph modeling for multimodal survival prediction.

Chronic wound assessment remains a clinically challenging task that requires accurate interpretation of wound morphology, tissue composition, vascular characteristics, and infection risk. Recent advances in Vision-Language Models (VLMs) have introduced the possibility of automated multimodal wound analysis through image understanding combined with clinical reasoning. This study evaluates the performance of several general-purpose and medically specialized open-source and proprietary VLMs for clinical wound assessment using an expanded, curated dataset of 20 clinically diverse wounds spanning vascular, surgical, ischemic, venous, lymphedema, and amputation-related etiologies. Six VLMs were evaluated using a structured twelve-question clinical framework covering wound classification, infection risk, vascular intervention recommendations, debridement urgency, wound therapy selection, and advanced management planning. Across 20 wound cases and 240 clinician-graded wound-analysis decisions, ChatGPT achieved the highest overall performance with 174/240 correct responses (72.50%), followed by Claude with 149/240 (62.08%). Among the open-source and medically specialized models, HuluMed achieved the strongest performance with 96/240 correct responses (40.00%), followed by Gemma 3 (81/240, 33.75%), MedGemma 4B (62/240, 25.83%), and MedGemma 27B (42/240, 17.50%). The findings suggest that frontier general-purpose multimodal systems currently demonstrate substantially stronger wound-analysis performance than medically specialized alternatives, highlighting the continued importance of broad multimodal reasoning capabilities alongside domain-specific medical knowledge. Although current VLMs demonstrate promising potential for clinical decision support, substantial limitations remain in advanced wound-management reasoning, procedural planning, and autonomous clinical reliability.

Predicting immune biomarkers associated with the tumor immune microenvironment (TIME) is critical for advancing precision oncology, yet existing approaches are largely limited to single image modalities and suffer from insufficient resolution and incomplete utilization of complementary clinical and biological information. Here we introduce MixTIME, a multimodal foundation model that leverages a mixture-of-experts (MoE) architecture to integrate pathology foundation models trained across distinct modalities: image only (UNIv2), image text (CONCHv1.5), and image transcriptomic (STPath) representations for pixel-level and slide-level prediction of multiplex immunofluorescence (mIF) protein expression from hematoxylin and eosin (HE) whole-slide images. MixTIME employs a learnable router to dynamically weight expert contributions and is trained with a distribution- and tendency-aware loss function. Benchmarked on two datasets of different scales, MixTIME achieves state-of-the-art performance across 17 protein markers as measured by correlation metrics. The predicted mIF profiles substantially enhance downstream tasks, including spatial domain identification, survival prediction, and AI-assisted pathology report generation validated by expert pathologists from multiple institutes across the world. Furthermore, MixTIME enables longitudinal tracking of protein expression dynamics across clinical time points and reveals protein gene interaction patterns linked to drug resistance and immune suppression in tumor microenvironments. Collectively, MixTIME provides a scalable framework for multimodal biomarker discovery and clinical translation in computational pathology.