Multimodal Clinical Data

Though artificial intelligence (AI) increasingly transforms modern medicine, its integration into Traditional Chinese Medicine (TCM) has been relatively slow, primarily due to TCM's reliance on holistic, subjective diagnostic methods---namely Inspection, Auscultation and Olfaction, Inquiry, and Palpation(I-AOI-P)---which are difficult to align with quantitative, standardized medical systems. In this work, we introduce a Unification Framework for Multimodal Data (UFMD), which automatically processes tongue and pulse images into structured, clinically standard descriptions, integrating multi-source diagnostic information into a unified digital record of I-AOI-P process. Building on this structured data, we create LingLan-14B, a TCM-specific large language model fine-tuned via supervised learning to emulate the diagnostic logic and workflow of I-AOI-P process. Experimental results show that our method significantly enhances diagnostic accuracy, achieving a relative improvement of 103.5% over the baseline (62.72% vs. 30.82%) and reaching an F1-score of up to 82%.

Artificial intelligence (AI) has advanced at a rapid pace in recent years. Initially, breakthroughs in large language models caught widespread attention. However, recent generations of frontier AI models have adopted multimodal capabilities as a first class citizen, with vision capabilities being central to that. In this paper, we evaluate three recently released models on the task of diagnosing dermatological conditions from patient-submitted images. The models chosen are at the low to mid tier in terms of pricing and thus represent a floor on current AI capabilities, not a ceiling. We evaluate AI performance relative to a panel of three certified dermatologists, who grade each image, and we present four interesting findings. Firstly, depending on the metric, the tested AI models are either on par or slightly trail humans in terms of inter-clinician agreement. Secondly, we find that asking AI models for a confidence rating produces poorly calibrated answers, meaning use of confidence thresholds should not be relied upon in a clinical setting. Thirdly, the effect of providing additional patient metadata is strongly model-specific, with one of the three models degrading on every metric considered. Finally, model cost is not predictive of performance. The best-performing model we tested costs on average $0.0045 per case.

Medical image interpretation is central to diagnosis and care, yet adapting general-purpose multimodal large language models (MLLMs) often requires resource-intensive domain-specific fine-tuning. Here we introduce representation-guided in-context learning (RG-ICL), a training-free inference framework that retrieves query-aligned demonstrations using frozen encoders, without task-specific parameter updates. Across eight datasets spanning histopathology, radiology and retinal fundoscopy, RG-ICL improved classification (mean gain 20 percentage points) and visual question answering (VQA) (mean gain 13 percentage points) over no-context and conventional ICL, approaching or exceeding training-based comparators. Which cases were retrieved mattered more than how many: 6 query-aligned cases outperformed up to 32 randomly selected ones, whereas fixed or random cases often reduced accuracy below baseline. For VQA, aligning reference cases with both image content and question intent produced further gains. These findings indicate that for medical image interpretation, curating which reference cases an MLLM sees is a practical alternative to retraining it.

Clinical multimodal models must often predict before all chest X-ray (CXR) and electronic health record (EHR) inputs are available. Existing approaches align observed representations, model missingness, or reconstruct across modalities, but do not jointly exploit within-patient and clinically similar inter-patient evidence. We propose GLR-MM, a Graph-Based Global-Local Reconstruction framework for early ICU mortality prediction. It maps five CXR-EHR modalities to a shared space, reconstructs missing embeddings through complementary local cross-modal and global graph-attention branches, adaptively fuses their estimates, and optimizes class-balanced prediction, reconstruction, and contrastive objectives. On 9,620 MIMIC-derived ICU stays, we evaluate 10%, 30%, and 50% random modality missingness with shared deterministic masks. MUSE performs better under mild and moderate missingness, whereas GLR-MM achieves higher AUROC and AUPRC at 50% by 0.0088 and 0.0249, respectively. These results indicate that graph-guided reconstruction is most useful when inputs are severely incomplete.

Federated learning enables collaborative training without sharing patient-level data, but most studies remain simulations. Based on five requirements derived from the literature, we analyzed 14 FL frameworks and found that none fully satisfied these requirements. We present FL-Net, a novel federated clinical research framework to fulfill all requirements. It integrates modular data harmonization, data discovery, disclosure control, securely built versioned FL-Net-Tools and containerized federated workflow execution into a persistent network. It enables the re-use of harmonized data and workflows across studies. FL-Net's end-to-end capabilities were evaluated through harmonization, cross-study patient discovery across MIMIC and US-130, and reproducible, audited federated workflows with up to 50 concurrent clients. FL-Net is being developed within the dAIbetes and Microb-AI-ome EU projects and will cover over 800,000 patients across 10 hospitals in 9 countries covering longitudinal and single point in time data, FL-Net provides a practical foundation for interoperable, reproducible, and privacy-preserving multicenter clinical research.

Deep learning models for multi-modal breast cancer diagnosis achieve high predictive accuracy but remain clinically unacceptable without actionable, counterfactual explanations. Attribution-based methods (LIME, SHAP) are categorically inapplicable to this purpose, as they generate no alternative instances and thus cannot be evaluated on counterfactual quality metrics. This investigation provides empirical evidence that FCA-Guided Counterfactual (FCA-CF) framework that uses a Formal Concept Analysis (FCA) concept lattice as a hard structural constraint on counterfactual search, operating over a multi-modal TCGA-BRCA dataset. We benchmark against four genuine counterfactual methods: Wachter-style CF, DiCE, FACE, and NICE, evaluated on 60 benign-predicted TCGA-BRCA instances. The FCA-CF framework achieves Validity = 1.0000 (100% of counterfactuals successfully flip the prediction), Sparsity = 2.37 features changed (best among all valid methods), and Proximity = 0.900 (normalised L2-based, matching NICE as joint best). The classifier achieves Accuracy = 0.980, F1 = 0.976, ROC-AUC = 0.9947. Ablation analysis confirms that the FCA lattice constraint is the primary sparsity driver (removing it increases sparsity by +40%, p < 0.001, Cohen's d = 0.78), while Phase C greedy refinement accounts for the largest individual contribution (+113% sparsity increase when disabled, p < 0.001, d = 5.01). FCA-guided counterfactual generation achieves a clinically important Pareto-dominant outcome; it is simultaneously the sparsest and among the most proximate of all valid methods, with perfect validity. The emergent sparsity property arising from lattice topology rather than numerical penalty terms constitutes a structurally novel contribution to the counterfactual explanation literature.

Artificial intelligence for plant disease analysis has advanced from task-specific classifiers to multi-modal models capable of jointly interpreting visual and textual information. However, practical deployment in precision agriculture remains limited because most existing approaches treat disease understanding as isolated prediction tasks, failing to capture the complementary relationships among symptom recognition, severity assessment, and question-driven diagnostic reasoning. In tomato pathology, accurate interpretation of diseased leaves requires more than label prediction; it demands integrating visual symptoms with semantic context to support a comprehensive and explainable understanding. Here, we present SOLAR, a multimodal generative model that understands tomato disease spanning six question-answering tasks. SOLAR learns to align visual features with task-aware language representations by Fusion Expert module based on mixture-of-expert, enabling it to generate contextually relevant answers across diverse diagnostic tasks. By formulating tomato disease analysis as a generative Visual Question Answering (VQA) task, SOLAR provides a flexible framework that supports multi-task inference within a single model while improving performance and cross-task knowledge sharing. We evaluate SOLAR on $41,677$ images, including $216,209$ Question-Answering (QA) pairs to understand tomato leaf disease under both closed and open-ended QA settings. Experimental results show that SOLAR consistently outperforms state-of-the-art vision-only, vision-language, and task-specific models across all tasks, demonstrating superior accuracy, robustness, and multimodal reasoning. These findings highlight the potential of generative multimodal modeling as an effective direction for understanding of plant disease. The code for this study is available at https://github.com/EnalisUs/SOLAR.

AI models for multimodal medical imaging must balance modality-specific specialization with cross-modal shared representations, a trade-off that pure Mixture-of-Experts (MoE) architectures currently fail to satisfy. Expert-based routing improves in-domain learning but may sacrifice cross-modal signals, which appear particularly important for rare (low-prevalence) pathologies in our experiments. To resolve this, we introduce Generalist-Specialist-MoE (GS-MoE), a two-branch (MoE) architecture that couples a cross-modal generalist model with distinct modality-specific specialists (experts) via domain-constrained feature fusion. On RadImageNet (1.35M images, 165 pathologies, three modalities), GS-MoE recovers detection of six low-prevalence pathologies on which every baseline scores F1 $=$ 0, with per-class gains up to +0.60 F1. It attains this while even slightly exceeding dense and specialist-only MoE aggregate baselines (MCC 0.770), while using ${\sim}53\%$ fewer active parameters at inference than the strongest investigated dense model.

Medical imaging modalities such as ultrasound and X-ray are widely used in clinical practice, where diagnosis follows a structured, evidence-driven workflow aligned with standardized criteria. While multimodal large language models (MLLMs) show promise for automated medical report generation, most existing systems rely on end-to-end multimodal fusion without modeling clinically defined intermediate attributes, leading to limited grounding and interpretability. To address this issue, we propose CORAL (COncept-grounded ReAsoning with Localization), a multimodal framework that integrates spatial grounding and concept-level supervision into a unified reasoning process. CORAL employs a prompt-driven medical segmentation model to localize lesions and predicts multi-class clinical attributes through a Concept Bottleneck module. The resulting textual concept tokens are combined with mask-modulated visual features within an MLLM to enable structured report generation and diagnostic prediction. Experiments on BUS-CoT and IU X-ray datasets demonstrate consistent improvements in diagnostic accuracy, concept consistency, and report quality over strong general-purpose and medical MLLMs, indicating that concept-grounded reasoning better aligns generation with clinical decision processes.

Dementia is a major and growing global health burden, with Alzheimer's disease (AD) accounting for most cases. Timely and accurate diagnosis is central to managing this burden and increasingly depends on integrating complementary clinical and imaging information. Multimodal deep learning can combine these modalities for AD diagnosis, but how its explanations behave across modalities, fusion strategies, and cohorts remains unclear. We developed an explainable multimodal framework pairing a 3D CNN encoder for T1-weighted MRI with a feedforward network for harmonized clinical and demographic data, comparing varied model setups on three-way and pairwise diagnostic tasks using 6,479 internal records from the ADNI and 1,703 independent records from the OASIS-3. On ADNI, the tabular-only model achieved the highest three-class AUC-ROC of 0.879 and best discriminated cognitively normal (CN) versus mild cognitive impairment (MCI; 0.903), while cross-attention performed best for MCI versus AD (0.861); CN versus AD was highly discriminative overall. On OASIS-3, the vision-only model performed best (three-class AUC-ROC 0.910); CN versus MCI remained difficult, and no fusion strategy consistently outperformed single modalities across tasks and cohorts. SHAP and Integrated Gradients identified the MMSE as the dominant tabular feature in both cohorts, with global feature rankings agreeing strongly in ADNI ($\rho=0.94$) and OASIS-3 ($\rho=0.96$); CAM-based explanations, however, changed with model configuration and cohort. These findings show that multimodal performance and explanations are task, modality, fusion, and cohort-dependent: a dominant cognitive signal persisted across cohorts, but feature contributions and CAM explanations did not, underscoring the need to evaluate explainability under cohort shift rather than as a stable, intrinsic property.

Multimodal clinical decision-making requires reliable reasoning over heterogeneous evidence from electronic health records, medical images, and physiological signals. Existing models typically map these inputs directly to diagnoses without explicitly assessing evidence sufficiency, tool-use requirements, or diagnostic uncertainty. This paper presents MedTRACE, a tool-augmented multimodal clinical reasoning agent for evidence-grounded decision-making. MedTRACE uses modality-specific encoders to construct a unified patient-state representation and performs an iterative loop of hypothesis formation, toolaware deliberation, and evidence verification. It dynamically invokes visual grounding, evidence retrieval, and structured parsing tools to locate diagnosis-relevant regions, retrieve clinical knowledge and similar cases, and extract structured findings. The acquired evidence enters an evidence memory, where a consistency verifier confirms or revises the current hypothesis. MedTRACE outputs a diagnosis together with supporting evidence, an auditable reasoning trace, and calibrated confidence. Experiments on multiple multimodal clinical diagnosis benchmarks show that MedTRACE improves diagnostic accuracy by 5.4% and AUROC by 4.7 percentage points over the strongest baseline. It also improves evidenceselection F1 by 8.2 percentage points and visual-grounding IoU by 6.5 percentage points, reduces expected calibration error by 31.6%, and decreases unsupported diagnostic errors by 27.8%. These results demonstrate that active evidence acquisition and verification improve the accuracy, interpretability, and reliability of multimodal clinical decisionmaking.

Simultaneous assessment of medical imaging and patient records is often required in clinical diagnosis. However, standard machine learning algorithms cannot analyze these data types together. Meanwhile, compliance with HIPAA and GDPR can constrain centralized aggregation of sensitive patient data. This leaves a crucial void of secure fusion of visual and textual context across distant networks. Thus, we present OmniMed-FL, a controlled systems study of multimodal federated learning for five-class clinical condition classification (Normal, Pneumonia, COVID-19, Pleural Effusion, Cardiomegaly). Our proxy corpus pairs 3,000 public chest radiographs with 3,000 class-conditioned synthetic notes, matched by class, not by patient. The framework benchmarks eight fusion strategies, three initializations, four missing-text imputation rules, and matched federated baselines under non-IID Dirichlet partitioning across 3 to 20 hospital clients. As all notes are synthetic and pairing is not patient-level, these are descriptive proxy comparisons, not estimates of diagnostic performance or deployment readiness. Within those limits with clients ($K=5$) and severe skew ($α=0.1$), local-only training achieves a macro-F1 score of 0.297, FedAvg achieves $0.662\pm0.074$, FedProx $0.737\pm0.085$, a matched FedMME-style one-shot ensemble $0.647\pm0.080$, and our SCAFFOLD-AdamW adaptation $0.070\pm0.015$, the 0.075 FedProx-FedAvg gap falling inside the wider of the two two-seed standard deviations. Over a $4\times3$ grid, label skew costs up to 0.27 F1 whereas a near-sevenfold client increase costs at most 0.10, while bidirectional volume grows linearly to 183.5 GiB at $K=20$. Multimodal fusion leads on both corpora, scoring 0.956 against 0.934 for text and 0.664 for images on the synthetic corpus and 0.906 against 0.880 and 0.737 on the radiograph corpus, for $2.3\times$ the model state of text alone.

High-risk non-muscle-invasive bladder cancer (HR-NMIBC) carries substantial risks of recurrence and progression, while current clinical risk stratification remains limited. CHIMERA was established as a multimodal AI challenge to benchmark prediction in HR-NMIBC under standardized evaluation. Task BRS predicts RNA-seq-defined BCG Response Subtypes from histopathology and structured clinicopathological data, whereas Task Progression models time-to-progression using histopathology, structured data, and RNA sequencing. A multimodal dataset of 368 patients was divided into public training and hidden validation and test sets. In total, 159 submissions were made, and 13 top-performing models were selected for benchmarking. The best models achieved a weighted F1 score of 0.73 for Task BRS and a C-index of 0.68 for Task Progression. Post-challenge analyses revealed task-dependent modality contributions, cohort-dependent performance degradation, and sensitivity to missing structured data. In Task BRS, histopathology partly compensated for pathology-derived structured variables, whereas progression models showed greater dependence on complementary inputs. Cross-model error analysis further identified patients that were consistently difficult across different architectures, with T1 substage associated with prediction difficulty. These findings highlight barriers to transportability and the importance of missingness-aware modeling and independent multi-institutional validation. CHIMERA provides a standardized multimodal benchmark for bladder cancer and a framework for studying not only model performance, but also robustness, information sufficiency, and patient-level prediction failure.

The digitization of healthcare has generated vast, longitudinal, and multimodal patient records over a lifetime, yet fully exploiting these data to represent and predict patient state trajectories remains a critical challenge. Current AI models often struggle to capture the complex, irregular temporal dynamics and inherent stochasticity of real-world multimodal patient data. Existing AI approaches for modeling longitudinal patient records are predominantly discriminative, limited to a few modalities, constrained by closed categorical vocabularies, treating time as a monotonic inductive bias, or they are limited in forecasting future patient states. We introduce NOAH, a time-aware, task-agnostic, generative transformer model representing and forecasting the full multimodal patient journey. NOAH features a novel bidirectional time integration and a variational latent space to capture the continuous evolution of patient states and the stochasticity of clinical trajectories. Built from over 559 million clinical events from 431,000 hospital visits of 299,000 patients across the MIMIC dataset family, NOAH natively processes medical images, time-series and numeric signals, categorical events, as well as structured and unstructured clinical records. NOAH is the first truly holistic generative model in its field, enabling autoregressive forecasting with optional time control, zero-shot classification, and counterfactual intervention simulation. It generates highly informative and predictive patient state representations that demonstrate strong performance in probing for clinical outcomes, 15 ICD chapters, and 29 comorbidities, as well as in time-to-event prediction. Seamlessly handling diverse modalities and complex temporal dynamics, NOAH provides a versatile, task-agnostic, scalable foundation for intelligent predictive systems in personalized clinical care and digital medicine.

We present EmoMed - a multimodal medical consultation agent that adapts its responses based on users' emotional states while maintaining clinical accuracy. The system processes text and medical images, detects affect indicators (anxiety, confusion, urgency) from user input, and adjusts response tone, structure, and detail level accordingly. To ensure factual reliability, the agent grounds clinical information through a dual retrieval mechanism: web-based fact-checking and an API-connected, continuously updated medical knowledge base. We evaluate our approach across seven state-of-the-art language models (GPT-4/5, Qwen3, Llama 4, Gemini 2.5, Grok4, Claude3) using comprehensive metrics including LLM-as-judge assessments, MedQA style accuracy tests, BERT Score, safety/helpfulness ratings, and multimodal medical benchmarks. The results demonstrate that emotionally adaptive responses consistently outperform neutral baseline across evaluation dimensions, without compromising clinical accuracy. A controlled user study validated these findings, with participants reporting improved perceived empathy and communication clarity, while maintaining trust in factual accuracy. Source code: https://github.com/NasonovIvan/EmoMed-Agent

The joint interpretation of metabolic function and anatomical structure is essential for clinical diagnosis in whole-body PET/CT. Although recent advances in 3D medical vision-language models have demonstrated remarkable progress, current efforts are limited to regional CT imaging, leaving a critical void in comprehensive whole-body PET/CT analysis. In this work, we introduce MetaStructAtlas, a large-scale dataset for grounded whole-body PET/CT interpretation that synthesizes multimodal imaging with integrated anatomical, metabolic, and semantic annotations. MetaStructAtlas provides 490 co-registered 3D PET and CT volumes with 50,470 organ-level segmentation masks and grounded radiology reports. To facilitate interactive reasoning, we further developed MetaStructVQA, a standardized 3D grounded visual question-answering benchmark containing 100,565 QA pairs. This framework explicitly links diagnostic queries to visual evidence across modalities, encompassing anatomical, morphological, and metabolic characteristics. Finally, we evaluate state-of-the-art 3D medical VLMs on MetaStructVQA, establishing a robust foundation for multimodal representation learning and integrated whole-body reasoning in nuclear medicine.

Neonatal respiratory diseases are a major cause of neonatal morbidity and mortality, posing substantial challenges in clinical practice. Despite recent advances, existing Multimodal Large Language Models (MLLMs) face two key limitations in neonatal diagnosis: (1) domain gap arising from predominantly adult training data; (2) insufficient integration of multidimensional clinical context for accurate diagnosis. To address these challenges, we collect two real-world clinical datasets (NeoCXR and NeoCXR-EV) and propose NeoRed, to the best of our knowledge, the first MLLM tailored for neonatal respiratory disease, filling the gap in neonatal diagnostic reports generation. To enhance joint diagnosis from heterogeneous clinical context and chest X-rays, we design a novel Knowledge-Logic-Alignment (KLA) framework which constrains model behavior from three perspectives: 1) Knowledge Prior Injection (KPI) incorporates neonatologist-inspired diagnostic priors into multimodal representations, guiding disease-specific attention across modalities; 2) Diagnostic Logic Constraint (DLC) aligns the semantics of generated reports with multimodal diagnostic logic; and 3) Visual Semantic Alignment (VSA) establishes semantic correspondence between visual features and imaging conclusions. Extensive experiments demonstrate that NeoRed enables accurate neonatal diagnostic reports generation, achieving ROUGE-L of 53.29% and Clinical Efficacy F1 score of 65.19% on NeoCXR, outperforming existing MLLMs. NeoRed also preserves competitive report generation performance on adult benchmarks (MIMIC-CXR and IU-Xray). Datasets will be available upon application.

A benchmark score credits final answers, but not the route by which an item can be answered. In medical multimodal multiple-choice questions (MCQs), this distinction matters because a correct answer can be supported by the intended image finding or by benchmark-preserved cues in the wording of answers, non-visual clinical text, visible image text, artificial annotations, or device/context artifacts. We call the resulting score-level overinterpretation reasoning inflation. Here, a route is an observable input path that can support answer selection, not a claim about the model's hidden cognition. Across six medical multimodal MCQ datasets, we separate candidate cues from behavioral evidence through prompt- and image-side audits, modality ablations, and matched repairs that preserve the medical target and answer key. In a 13-configuration open-model panel, full-input accuracy is 62.63%, while text-only and options-only settings achieve 53.96% and 29.71%, respectively. Removing length-gap, absolute/conspicuous, and spatial/prepositional cues lowers accuracy by 6.58, 3.50, and 4.77 percentage points. We also construct MedQA-MM, a 1,000-item shortcut-mitigated subset, where text-only and options-only accuracy fall to 5.21% and 12.33%. This does not imply that models never use images; it shows that medical image-reasoning claims require route-level evidence.

The rapid advancement of vision-language models (VLMs) has accelerated progress in computational pathology; however, whole-slide image (WSI)-based pathology report generation remains limited by the scarcity of large-scale WSI--report datasets and the complexity of mapping spatially distributed visual patterns to structured clinical text. To address this, we introduce a clinically curated Pan-Asia WSI--report dataset of approximately 10,500 pairs from five institutions and establish the REG 2025 benchmark through a MICCAI challenge for systematic evaluation of multimodal models. We analyze submitted methods spanning pretrained VLMs, multiple-instance learning frameworks, hierarchical expert models, retrieval-augmented generation, and cross-modal Transformers. Rather than indicating that VLM use alone was sufficient for superior performance, the results suggest that top-performing methods benefited from structured report representations, hierarchical diagnostic decomposition, and effective multimodal grounding. We identify key limitations, including instability in quantitative attribute estimation (e.g., numeric hallucination) and a tendency toward diagnostic overspecification, with some errors resembling known diagnostic pitfalls in routine pathology. These findings establish REG 2025 as a benchmark for evaluating WSI-based structured report generation and vision-language understanding in computational pathology, providing insights for the design of clinically grounded multimodal pathology models.

Depression and anxiety in older adults with Mild Cognitive Impairment (MCI) are frequently underdiagnosed due to limited access to care. Multimodal analysis of remote clinical interviews is a scalable screening approach, but existing methods have three limitations. First, they do not correct temporal misalignment across multimodal features extracted at different resolutions, inducing spurious cross-modal associations. Second, remote recordings exhibit uneven modality dropout, but missing values are often zero-filled, making them indistinguishable from valid near-zero measurements. Finally, they do not jointly attribute predictions to modalities, questions, and interview moments, limiting fine-grained clinical interpretation. We propose a Temporally-Aligned, Missingness-Aware, Interpretable (TAMI) multimodal fusion framework. TAMI aligns speech, language, facial, and physiological features within question-answer segments on a shared timeline, encodes modality-level missingness over time, and conditions fusion on question context. In interviews with 49 older adults with MCI, TAMI achieved area under the receiver operating characteristic curve (AUROC) scores of 0.68 (depression) and 0.69 (anxiety). Fine-grained temporal alignment of multimodal features produced the largest performance gain ($Δ{\geq}0.1$). Multi-level interpretability analysis revealed that depression classification relied on eyegaze and open-ended questions, while anxiety classification depended on eyegaze and head pose, with attribution uniformly distributed across questions. Using only responses to the open-ended questions (5.1min), the depression model achieved an AUROC score of 0.67, which was not significantly different from using the full interview (19min) ($p>0.05$). Our findings support designing interview protocols centered on open-ended questions for depression screening in older adults with MCI.

Combining whole-body magnetic resonance imaging (WB-MRI) with clinical variables has the potential to improve systemic disease diagnosis by leveraging complementary sources of patient information. However, structured clinical variables are often incomplete or missing, limiting the applicability of conventional multimodal fusion methods that assume fixed inputs. In this work, we propose TACTIC (Tabular-Attribute Conditioned Transformer for Image Classification), a prompt-based multimodal framework that integrates WB-MRI and structured clinical data through conditional visual feature learning. By encoding clinical attributes as prompts, TACTIC supports an arbitrary number of tabular inputs and naturally handles missing data without requiring imputation or fixed input structures. We evaluate TACTIC on five WB-MRI classification tasks spanning systemic and oncologic applications, including diabetes, chronic obstructive pulmonary disease (COPD), breast cancer, prostate cancer, and metastasis diagnosis. Across all tasks, TACTIC consistently improves performance over image-only baselines when clinical information is available while maintaining strong predictive capability under incomplete tabular inputs. Our results demonstrate the effectiveness of prompt-based models as a flexible approach for improving WB-MRI analysis using clinical context. The model weights and code are available at https://github.com/lauradaza/TACTIC

Clinical AI often optimizes predictive performance without engaging how clinicians decide where to look and what to write. We present Co-Annotator, which distills expert gaze and dictation into two guidance components: a gaze-aligned Vision Transformer producing fixation-aligned areas of interest (AOIs), and an ontology-bounded vision-language model (VLM) that pre-fills editable biomarker summaries for retinal optical coherence tomography (OCT). We first collect expert gaze and dictations (US1) to train the models, significantly improving diagnostic accuracy and biomarker generation. We then deploy the system with ophthalmology residents: a controlled resident study (US2) confirmed each modality is safe and independently beneficial, with AOI guidance producing lasting perceptual efficiency gains through post-guidance carryover and VLM guidance more than doubling biomarker documentation breadth. In a combined deployment across two academic institutions (US3), providing both modalities simultaneously produced efficiency gains that substantially exceeded either modality alone: correct diagnoses per minute increased by 40% and comment editing time fell by 67%, without compromising diagnostic accuracy. Notably, neither modality improved efficiency during guidance in US2, which makes the in-guidance efficiency gain under combined guidance in US3 the more striking result. Expert-distilled multimodal guidance can remove two distinct clinical workflow bottlenecks at once (visual search overhead and documentation burden) without compromising the diagnostic accuracy clinicians already achieve.

Digital mobility outcomes (DMOs) derived from wearable sensors characterise mobility in daily life and offer a promising means of monitoring disease progression. However, existing DMO studies have typically focused on either a single disease or a single visit. To the best of our knowledge, this is the first study to systematically model and analyse longitudinal multivariate DMOs across diverse mobility-limiting diseases. Specifically, we propose DeMMO, an interpretable framework for longitudinal, multi-disease, and multi-outcome learning. DeMMO represents each disease--outcome objective using a longitudinal DMO coefficient matrix and combines temporal regularisation with stable and visit-specific feature selection. Its central technical contribution is an automatic cross-disease and cross-outcome relation-learning mechanism that infers signed relations directly from these longitudinal mappings, thereby enabling selective information sharing across cohorts without requiring paired participants. We evaluate DeMMO on the recently released, large-scale, multicentre Mobilise-D dataset, which comprises four participant-disjoint cohorts representing distinct mobility-limiting diseases, with each cohort contributing one or more clinical measurement outcomes. Compared with eight strong structural longitudinal and deep-regression baselines, DeMMO achieves the best overall predictive performance and outperforms the baselines for most individual outcomes. Stability selection further identifies reliable longitudinal DMO patterns that can inform subsequent clinical validation and disease monitoring. The implementation code is available at https://github.com/menghui-zhou/DeMMO.

Lung cancer tissue diagnostics is complex, as therapy decisions in precision oncology rely on the integration of histomorphological, immunohistochemical, and molecular features. Yet pathological assessment remains largely visual and semi-quantitative and shows interobserver variability, while existing artificial intelligence (AI) tools cover only selected tasks, rarely reach generalizable expert-level performance, and lack prospective clinical validation. To address these challenges, we developed and clinically validated LUCAID, an agentic AI system for precision lung cancer pathology. An integrative agent couples diagnostic reasoning with nine modules that cover the full routine workflow, from quality control, tumor detection and segmentation, histological subtyping, tumor microenvironment profiling, tumor cellularity quantification, and predictive biomarker scoring (PD-L1, MET, TROP-2) to automated structured report generation. LUCAID enables users to interactively query the module outputs and generate reports that contextualize the results. Against large-scale expert ground-truth annotations, the analysis modules achieved F1 scores of 0.82-0.95. In prospective clinical validation, LUCAID reached 93.0% concordance with an expert-panel adjudicated reference standard across clinically actionable decisions, compared with 68.3-81.1% for five experienced thoracic pathologists.

Clinical intelligence requires estimating a patient's underlying condition from incomplete observations rather than learning isolated mappings from scans to answers. Volumetric medical images provide dense observations of anatomy, attenuation, and lesions, whereas clinical language provides sparse but complementary semantic observations. We formulate CT-centered intelligence as inference over a shared latent patient state, under which readout, reconstruction, and simulation all become state-dependent prediction problems. To operationalize this view, we introduce HounsBench, a computed tomography (CT) centric patient-state benchmark that unifies these three task families with patient-disjoint splits and per-family metrics, and HounsWorld, a 3B multimodal world model that treats volumetric scans and language as observations of the shared state through Joint Understanding-Generation Learning. A shared transformer forms an implicit patient-state estimate and supports three outputs: query-conditioned answers that read out the state, reports and captions that reconstruct it in language, and condition-specific CT volumes for low-dose denoising, virtual contrast enhancement, and anatomy-constrained text-and-mask-to-volume generation. Zero-initialized CT adapters preserve pretrained multimodal mappings, while condition-explicit Hounsfield-unit window sampling exposes clinically meaningful density observations. HounsWorld shows strong performance across all three task families while consistently improving CT understanding through clinically structured completion. Our project is available at https://github.com/byhwhite/HounsWorld.git

Continuous physiological time series underpin modern clinical monitoring, yet many of the most informative signals are invasive, expensive, or simply unavailable for a given patient. Conditional generation offers a remedy: an absent signal can be synthesized from co-recorded signals and routine clinical variables. Existing generators, however, are built around a single conditioning modality and degrade when forced to handle the heterogeneous, irregularly missing mix of time-variant signals and static covariates seen in practice. We propose ReCoGen (Represent Conditions, then Generate), a two-stage framework that decouples multimodal condition representation from target generation. Stage I trains one masked autoencoder per modality, distilling each time-variant condition into a compact and missingness-tolerant token sequence. Stage II trains a flow-matching generator that fuses these tokens with static conditions to synthesize the target signal. Across three physiological benchmarks, including continuous glucose monitoring on AI-READI and arterial blood pressure generation on MIMIC-III and MIMIC-IV, ReCoGen attains the best downstream utility on all sixteen (dataset, task, metric) settings, surpassing six representative conditional generators; on thirteen of them its utility also reaches or exceeds the utility measured on the real signal, a reference we read as an approximate anchor rather than a ceiling. Ablations trace the gains to the conditioning path: learnable cross-attention over the frozen per-modality encoders, and a dual token-plus-AdaLN route for the static conditions. ReCoGen thus turns routinely collected signals into informative surrogates for invasive or unavailable ones, a step toward less invasive, lower-cost continuous clinical monitoring.

In medical imaging, the clinical value of Computed Tomography (CT) lies not only in depicting current disease status, but crucially in enabling longitudinal comparison of serial scans to determine disease evolution, a process that underpins response assessment, recurrence detection, and ongoing patient management. Yet, despite this central role of temporal comparison in clinical decision-making, existing medical foundation models remain largely confined to single-study understanding, leaving temporally grounded cross-examination insufficiently addressed. To address this gap, we study longitudinal imaging difference reporting, a task in which a model takes two temporally separated scans from the same patient and generates a clinically meaningful report describing interval changes between them. We introduce CT-$Δ$Bench, a dedicated benchmark for this task with patient-level splitting to prevent information leakage. To better evaluate this task beyond surface-level text similarity, we further develop change-aware metrics specifically designed to capture clinically meaningful longitudinal changes, and conduct an independent physician validation to assess the reliability of the synthesized references and event extraction pipeline. We also compare direct paired-CT reasoning with an indirect two-stage pipeline that first generates single-timepoint reports and then performs textual differencing. Finally, we propose DeltaMed, a baseline model for direct paired-CT difference reporting, and train it on the benchmark training set. Together, these contributions lay the groundwork for temporally aware medical foundation models that better reflect real-world longitudinal clinical reasoning.

Clinical text can narrow down what to segment, but recent text-guided designs emphasize spatial alignment while overlooking frequency content that governs texture and boundaries. We propose Dual-Domain Cross-Modal Decoding (DD-CMD) for clinical text-guided pulmonary infection segmentation, integrating two complementary forms of language guidance during decoding. In the spatial domain, Text-Guided Spatial Cross-Attention (TGSA) aligns multi-scale visual tokens with text semantics and updates features through gated residual fusion. In the frequency domain, Spectral-Text Adaptive Modulation (STAM) applies a 2D DCT to compute learnable band-energy statistics and predicts text-conditioned FiLM parameters to recalibrate decoder channels for frequency-aware decoding. DD-CMD embeds TGSA and STAM into a coarse-to-fine decoder (7x7 to 56x56) and restores full-resolution masks using a lightweight two-stage refinement module. Experiments on QaTa-COV19 and MosMedData+ show that DD-CMD achieves 91.46% Dice / 84.26% mIoU and 81.95% Dice / 69.42% mIoU, respectively, with average gains of +1.96 Dice and +2.67 mIoU over the strongest prior baselines. Code: https://github.com/maklachur/DD-CMD.

While vision-language models dominate medical representation learning, unstructured text lacks the dense, quantitative diagnostic phenotypes inherent in structured clinical tables. However, existing multimodal pre-training methods underutilize this potential due to semantic-agnostic designs that treat tabular inputs as flat vectors and employ unstable continuous regression objectives. To overcome this, we propose a novel semantic-aware framework explicitly modeling the intrinsic two-dimensional structure of tabular data. First, addressing the inter-feature hierarchy of varying diagnostic importance, we introduce Importance-Aware Adaptive Masking to construct a label-free curriculum prioritizing salient features. Second, addressing the intra-feature continuity-discreteness duality, we propose a Soft-Label Discretized Module that replaces unstable numerical regression with stable distribution matching, thereby mathematically preserving ordinal relationships. Extensive experiments across large-scale dermatology (SLICE-3D, HOP) and ophthalmology (EyePACS) datasets establish a new state-of-the-art (SOTA), demonstrating exceptional robustness and cross-domain generalizability.

Multi-modal learning combining medical images and clinical text is promising for disease diagnosis. However, standard multi-modal training leads to shortcut learning: models exploit the easier modality (e.g., diagnostic cues in text) while neglecting harder-to-learn features (e.g., subtle visual patterns). We propose UniMod, a framework that mitigates shortcut learning by requiring each modality to predict the diagnosis on its own. It supervises image-only, text-only, and multi-modal classification simultaneously, so each modality must extract diagnostic features. We add cross-modality alignment for knowledge transfer and within-modality supervised contrastive alignment over same-diagnosis patients. On Harvard-Glaucoma, UniMod reaches 0.850 AUC, outperforming OGM-GE and Gradient Blending by 1.6-1.8%; on CheXpert Plus, it reaches 0.966 AUC, surpassing them by over 5%. UniMod also extends to 5-class multi-label diagnosis without architectural change, improving mean AUC by 0.097 over CGGM.

Imaging device downtime is a major barrier to healthcare delivery in low- and middle-income countries (LMICs), often driven by limited access to specialized biomedical engineering support. We present a multi-modality medical equipment maintenance question-answering (QA) framework and demonstrate the fine-tuning of a medical foundation model for specialized technical troubleshooting tasks. Guided by a multi-country survey across nine LMICs, we curated technical manuals from MRI and ultrasound systems to generate the INGENZI_DatasetV1, containing 10,294 high-quality, filtered QA-context pairs. Using QLoRA-based parameter-efficient fine-tuning, we adapted the MedGemma-4b-it model to interpret system error logs and generate step-by-step equipment repair instructions. Compared to the baseline model, the fine-tuned system achieved substantial improvements across metrics, including F1 score (0.22 to 0.38), ROUGE-2 (0.18 to 0.41), and BERTScore F1 (0.86 to 0.91). These metric gains demonstrate that the model generates significantly more precise and procedurally accurate technical responses to new troubleshooting queries. This work establishes a reliable foundation for AI-assisted diagnostic and maintenance tools in resource-constrained settings.

Despite significant advances in Medical Report Generation (MRG), the reliability remains constrained by the prevalence of factual errors. While Direct Preference Optimization (DPO) has emerged as a promising post-training paradigm to enhance the performance of Supervised Fine-Tuned (SFT) MRG models, existing DPO-based MRG methods typically adopt a naive preference construction that directly pairs model-generated reports with ground truth reports. This strategy inadvertently entangles critical clinical findings with clinically irrelevant linguistic characteristics, and fundamentally lacks explicit vision-language alignment. To address these challenges, we propose DPO-Clin, a novel post-training framework that focuses preference optimization on clinical findings and cross-modal alignment. First, we introduce the Entity-level Clinical Diagnostic (ECD) module to perform a precise entity-level factual diagnosis. ECD guides the generation of linguistically-aligned report preference pairs, isolating clinical discrepancies from linguistic variations. Second, to achieve fine-grained cross-modal alignment, we develop M2DPO, a retrieval-augmented multi-modal DPO variant that enforces textual preference inversion triggered by visual context switches. Third, we locate correct yet highly uncertain predicted entities and apply counterfactual modifications to construct targeted preference data for latent risk mitigation, thereby further enhancing the model reliability. Extensive experiments on two public chest X-ray datasets (MIMIC-CXR and IU X-Ray) and an in-house endoscopy dataset demonstrate that DPO-Clin significantly improves the SFT baselines on clinical-aware metrics. Furthermore, it achieves superior performance over existing DPO-based MRG methods, exhibiting robust generalizability across distinct baseline architectures and diverse medical imaging modalities.

Medical Visual Question Answering (VQA) requires aligning subtle visual evidence, including lesion texture, boundary sharpness, and diffuse density changes, with clinical language. Existing multimodal fusion approaches operating in the spatial domain may not fully exploit complementary frequency information present in visual and textual representations. We introduce a dual-branch frequency-domain fusion module that conditions spectral filtering on the input question, enabling adaptive selection of global low-frequency structure and fine-grained high-frequency detail before reconstructing the spatial representation for answer generation. To provide a richer spectrum for filtering, we extract complementary features from early texture-sensitive and final semantic layers of a frozen BiomedCLIP encoder and align both with the question representation using a symmetric InfoNCE objective prior to staged joint training with a BioBART decoder. We pretrain the proposed model on PMC-VQA and fine-tune it on the VQA-RAD and SLAKE benchmarks, demonstrating that frequency-aware multimodal fusion improves medical VQA performance while maintaining a lightweight and efficient architecture.

Large language models (LLMs) show promise in medical image interpretation but suffer from hallucination, limited accuracy, and run-to-run inconsistency. We developed and validated an agentic AI framework integrating LLMs with specialized deep learning tools for glaucoma detection from fundus photography. The workflow had three steps: (1) LLM initial assessment; (2) function calling to invoke specialized tools for image quality (QAModel, FundaQ-8), glaucoma classification (SwinV2-Tiny), and optic disc/cup segmentation (SegFormer-B0); and (3) LLM reflection integrating the initial impression with tool outputs. Two LLMs (Gemini 2.5 Flash, GPT-5.4 mini) were evaluated on two public datasets (ORIGA, n=100; RIM-ONE-v3, n=100) under uncropped and cropped fields of view; all images were independently graded by a masked fellowship-trained glaucoma specialist. The agentic workflow improved classification accuracy by 16 to 47 percentage points across all conditions, reaching within 6 points of the specialist; on RIM-ONE-v3 the best configurations matched the specialist accuracy of 88%. LLM-alone approaches failed in two ways: GPT-5.4 mini showed positive bias (sensitivity 95-100%, specificity 0-5%), while Gemini 2.5 Flash varied stochastically between runs; the agentic workflow corrected both. Cup-to-disc ratio error fell 15-50% (MAE 0.156-0.228 to 0.104-0.132), and correlation with specialist grading rose from weak (r=0.12-0.39) to moderate-strong (r=0.59-0.84). Run-to-run consistency rose from near-random (kappa as low as -0.01) to near-perfect (kappa up to 0.96). Integrating LLMs with specialized tools addressed key limitations of LLM-alone approaches, including over-diagnosis and run-to-run variability. Gains held for both LLMs, suggesting generalizability across backbones, and may signal a shift from monolithic models toward orchestrated multi-agent systems in medical AI.

Image mixup is a widely adopted data augmentation strategy, yet it is ill-suited for ordinal classification tasks such as medical disease grading, where labels encode a progression of severity. By indiscriminately blending disease-severity cues (ordinal) with appearance-level variation (non-ordinal), standard mixup produces samples that distort the very ordinal structure that underpins clinical severity grading. We introduce DisMix, an order-aware mixup framework for ordinal classification. DisMix disentangles ordinal and non-ordinal features via a dual-codebook VQ-VAE, allowing each subspace to be mixed independently: ordinal codes are interpolated to produce meaningful intermediate ranks, while non-ordinal codes are varied to introduce appearance diversity without corrupting the ordinal signal. Across four medical imaging datasets, DisMix shows the best aggregate performance among six image mixup baselines paired with six ordinal classifiers and remains effective under data scarcity and clinical grading variability.

Background: Respiratory specialty care requires multimodal interpretation, longitudinal risk assessment, guideline-concordant intervention, and whole-course management, which are poorly represented by examination-oriented medical benchmarks. Objective: To develop RESPClinBench, a real-world scenario-based benchmark for respiratory clinical decision-making, and evaluate seven contemporary large language models across AECOPD-PIM and PNBIM. Methods: RESPClinBench cases were adapted from de-identified respiratory clinical data. Three attending-level respiratory physicians revised cases, reference answers, and atomic clinical-action points, while one senior respiratory specialist performed cross-review and final adjudication. AECOPD-PIM comprised 427 open-ended COPD cases, and PNBIM comprised 196 multimodal pulmonary nodule cases combining chest CT with structured clinical information. Seven models generated 4,361 responses through standardized API inference with temperature 0 and a maximum output length of 8192 tokens. An automated framework calculated the final score as the arithmetic mean of atomic-action recall and rubric-based LLM-as-a-Judge assessment. Results: Across 623 cases, the mean final score was 68.58. Qwen3.6-27B ranked first overall at 71.22, Qwen3.5-397B-A17B led PNBIM at 72.48, and Qwen3.6-27B led AECOPD-PIM at 71.11. Imaging hallucination and serious medical risk occurred in 31.85% and 8.16% of PNBIM responses; medication-safety risk and serious medical risk occurred in 26.93% and 1.44% of AECOPD-PIM responses. Conclusions: RESPClinBench identifies task-specific limitations in multimodal pulmonary nodule assessment and longitudinal COPD management. Combining explicit clinical-action coverage, holistic evaluation, and independent safety flags provides a clinically grounded basis for model selection and prospective validation.

Medical visual grounding connects free-form clinical queries to spatial evidence in medical images and is an important component of interpretable medical artificial intelligence. However, general-purpose grounding models are predominantly trained on natural images, while existing medical localization resources remain fragmented across imaging modalities, datasets, and task formulations. To address this gap, we construct LocAnyMed-200K, a multimodal medical visual grounding dataset containing approximately 200K image-query-answer examples across computed tomography, optical medical imaging, ultrasound, and X-ray. We harmonize heterogeneous detection and localization resources into a unified free-form instruction format that supports one or multiple bounding boxes, point coordinates, and no-target outputs for negative queries. Full-parameter fine-tuning of LocateAnything-3B on LocAnyMed-200K improves F1@IoU 0.50 from 10.64 to 85.59 on a held-out evaluation split, demonstrating that large-scale domain-specific supervision can equip a general grounding model with effective medical localization capabilities. Beyond spatial coordinates, a clinically interpretable grounding system should also communicate the evidence supporting its prediction. We therefore derive LocAnyMed-CoT-20K, a rationale-augmented subset that connects anatomical context, visual observations, and spatial conclusions through structured reasoning and further improves cross-source generalization through fine-tuning. Together, these resources provide a unified foundation for studying both localization accuracy and rationale quality across heterogeneous medical imaging modalities. The code is publicly available at https://github.com/MiliLab/LocAnyMed.

Multimodal learning has significantly advanced survival prediction by integrating pathology images with genomic data. However, clinical information, despite its critical role in reflecting a patient' s overall health, remains underutilized due to its discrete, sparse, and low-dimensional nature. Furthermore, the inherent heterogeneity across these modalities pose significant challenges in modeling cross-modal interactions. In this paper, we propose CIGTSurv, a Clinical Information Guided Tri-modal framework for Survival prediction. Specifically, we first design a holistic text template and use pretrained foundation models to transform clinical tabular data into high-dimensional tokenized embeddings. Using clinical information as an anchor, we then introduce a dual-level interaction mechanism: 1) a local prototype association (LPA) module based on cross-attention to explicitly learn token-level correspondences between different modalities, and 2) a global feature alignment (GFA) loss based on Maximum Mean Discrepancy (MMD) to implicitly enhance cross-modal distribution consistency. Extensive experiments on five TCGA cancer cohorts demonstrate that CIGTSurv achieves state-of-the-art (SOTA) survival prediction performance. Our source code is publicly available at https://github.com/Daijing-ai/CIGT-Surv.git.

Human-interpretable computer-aided diagnosis is crucial for clinical decision making. Concept-based models excel by providing transparent reasoning and enabling post-hoc, clinician-in-the-loop interventions. However, their rigid dataset-specific adaptation inherently restricts cross-site generalization. Applying them across diverse modalities, such as dermoscopic and clinical photographs, is challenging due to heterogeneous concept taxonomies varying in availability, granularity, and semantics across cohorts. Consequently, adapting Foundation Vision-Language Models (FVLMs) demands costly label engineering and repeated post-training. Existing intervention mechanisms remain rigidly tied to predefined concepts, lacking adaptability and hindering scalable dermatology CAD deployment. To address these bottlenecks, we propose UniCon, an open-linguistic unified concept learning framework for multimodal interpretable vision-language diagnosis. UniCon resolves these challenges through three contributions: (1) A shared semantic representation space via a unified concept prototype codebook, seamlessly coordinating heterogeneous concept systems across modalities without dataset-specific retraining. (2) Open-linguistic based multi-faceted semantic specifications to overcome sparse textual label limitations, improving boundary sensitivity in uncertain clinical contexts. (3) A robust, cross-site adjustable intervention interface powered by reliability-gated bottleneck aggregation, enabling consistent reasoning and transferable clinician corrections. Extensive experiments demonstrate that beyond securing top-tier diagnostic accuracy, UniCon successfully bridges disparate clinical taxonomies, unlocking unprecedented cross-site intervention capabilities. Code is available at https://github.com/wuchengyu123/UniCon.

Multimodal medical large language models remain structurally weak for neuro-oncology because volumetric evidence is compressed into generic visual tokens and diagnostic conclusions often lack an auditable link to MRI regions. We present NeuroMosaic, a 3D multimodal language model that converts multi-sequence brain MRI into anatomy-indexed regional tokens, aligns them with clinical narrative and molecular concepts, and generates evidence-linked outputs. The architecture combines a multi-resolution volumetric tokenizer, a neuroanatomical graph router, a molecular concept memory, and selective risk control. Across four glioma cohorts, NeuroMosaic achieved an internal subtype macro-F1 of 0.827 and external macro-F1 values of 0.784, 0.761, and 0.742. On UPenn-GBM, it improved over the strongest matched-input baseline by 3.6 percentage points (95% CI: 1.8 to 5.4, adjusted p = 0.0018), with IDH, 1p/19q, and MGMT AUROCs of 0.918, 0.861, and 0.781. Evidence pointing accuracy reached 0.703, and targeted evidence deletion reduced correct-answer probability by 0.187, compared with 0.046 for random deletion. These results establish anatomy-indexed routing as a measurable mechanism for accurate, grounded, and calibrated volumetric medical-language reasoning.

Electronic health record foundation models are limited by institutionally siloed data and substantial performance degradation under cross-site transfer. We evaluated federated training of tokenized generative event models (GEMs) across 122,251 intensive care hospitalizations from three independent health systems harmonized to the Common Longitudinal ICU Data Format. Models were assessed on 12 post-24-hour clinical prediction tasks using within-site, cross-site, centralized, and federated training configurations. GEMs achieved the highest mean within-site and cross-site ROC-AUC and were substantially more transportable than conventional supervised models: their average cross-site penalties were 0.025 ROC-AUC and 0.027 PR-AUC, compared with 0.079 and 0.089 for LightGBM. Federated Learning (FedAvg and FedAvgM) approached the performance of centralized GEM training, with most gains obtained within 5-10 communication rounds. However, centralized multi-site training provided only modest improvements over complete local training. Multi-site models were most useful when local training data were limited, with their advantage narrowing as institutional data accumulated. These findings show that federated GEM training is technically feasible and preserves most centralized performance, but that the main open challenge is learning transportable representations to translate larger, but heterogeneous data from multiple health systems into a reliable target-site benefit.

Recent vision-language models for chest X-ray understanding are largely built on image-report alignment and therefore rely heavily on MIMIC-CXR as the dominant pretraining source. While effective at scale, this paradigm underexplores an important alternative source of supervision: a range of existing multi-label classification datasets, which provide cleaner and more explicit disease signals than free-text reports, and can offer broader pathology coverage when combined across sources. However, learning from such heterogeneous datasets is nontrivial, as differences in label ontologies, annotation protocols, acquisition pipelines, and report styles can cause models to entangle clinical semantics with dataset identity, leading to poor transfer despite increased scale. In this work, we revisit radiology VLM construction from the perspective of harmonized multi-source learning. We propose HarMoE, a dataset-aware mixture-of-experts framework that learns shared cross-dataset medical semantics while confining source-specific variation to lightweight residual experts in deeper decoder layers. To further exploit clean supervision from labeled datasets, we train in a unified disease vocabulary with masked multi-dataset supervision, enabling the model to leverage complementary annotations without introducing false negatives. Experiments on large-scale chest X-ray benchmarks show that HarMoE consistently improves zero-shot classification, out-of-distribution transfer, and grounding over strong baselines. Our results suggest that building robust radiology VLMs requires moving beyond single-source image-report alignment toward structured knowledge construction from heterogeneous datasets with cleaner supervision and broader coverage. Code and the 873k harmonized dataset will be released at https://github.com/Roypic/harmoe.

Access to holistic, multimodal data improves the performance of Artificial Intelligence (AI) in medical classification tasks compared to utilizing single modalities or data sources. However, the inherent heterogeneity and complexity of clinical real-world data pose significant challenges to structured data analysis and AI application. This heterogeneity includes missing values, multiple time points, diverse modalities, and inconsistent formats and semantics. Data harmonization prior to data integration tackles this challenge but remains resource-intensive and error-prone, limiting the scalability and reproducibility of holistic, AI-driven decision support on clinical real-world data. We therefore propose PatTree, a graph-based, holistic representation of patients that can be derived from real-world clinical data through the automated structuring of multimodal clinical data. PatTree enables early-stage data integration without relying on pre-standardized inputs. While representing heterogeneous clinical data within a unified knowledge graph, PatTree preserves the semantic relationships between data elements across modalities and data sources, facilitating interoperability and machine-interpretable data access. Using a subset of the ADNI-1 cohort (n = 763), we demonstrate that classification of patients is directly feasible on PatTree reaching state-of-the-art classification performance. In the three-class classification task distinguishing Alzheimer's disease, mild cognitive impairment, and cognitively normal individuals, we achieve a balanced accuracy of 98.5% and an F$_1$ score of 0.987 on the held-out test set. Our results show that assumption-free, automated structuring of multimodal medical data can serve as a scalable foundation for clinical AI pipelines bypassing tedious data preparation and standardization.

Multimodal clinical models are usually judged on accuracy with every modality present, but deployment removes modalities; an echocardiogram is often unavailable where an ECG is routine. Two questions then matter beyond the size of the accuracy loss: which modality was responsible, and whether the model fails loudly or silently once that modality is dropped. The distinction is per-example and modality-level, and is separate from post-hoc feature attribution (e.g. SHAP). Models are replaced often; the evaluation that answers these questions is reused. We present a model-agnostic modality-failure framework: given N modality embeddings, any mask-aware probe, and labels, it returns a per-example failure taxonomy, a per-modality complementarity matrix that attributes error to modalities, and a loud-vs-silent dropout profile separating monitorable failures from those that pass unflagged far from the decision boundary, using only deployment-observable signals. We release it as a small, unit-tested harness and validate it against planted ground truth. Across seeds it recovers that planted modality dominance and complementary subset, reports per-modality loud-vs-silent rates, and scales to a three-modality complementarity matrix; because the planted structure is known by construction, this validates recovery of per-example attribution rather than clinical performance. We then instantiate the framework on frozen EchoJEPA and HuBERT-ECG embeddings for LVEF and the EF <= 40% HFrEF gate over a paired MIMIC-IV cohort, where on the held-out test split (n = 245) dropping echo nearly doubles error. The narrow echo-to-ECG overlap that bounds cohort size is itself a deployment finding for cardiac foundation models. All of our work can be found at https://github.com/criticaldata/PRIMED-AI.

Background and Study Aims: Accurate optical diagnosis of colorectal polyps guides resection strategy and surveillance, with multimodal large language models (MLLMs) showing potential for image-based diagnosis. We aimed to evaluate the diagnostic accuracy of MLLMs in classifying colorectal polyps and predicting histology. Methods: We conducted a retrospective diagnostic performance study using the PRIME dataset, a curated set of white light and narrow-band imaging (NBI) images. We evaluated Claude Opus 4, Google Gemini 2.5 Pro, GPT-o3, GPT-4o, and GPT-5. For Paris, Narrow-band Imaging Colorectal Endoscopic (NICE), and predicted histology, we calculated F1 scores, percent correct scores, and accuracy of each MLLM compared to expert responses for 132 cases. Cochran's Q and McNemar's Test were used to determine differences between predicted values of each MLLM. Results: The F1 scores among MLLMs were >0.9 for all models for neoplastic vs. non-neoplastic polyps. Gemini 2.5 Pro demonstrated the highest F1 scores for invasive vs. non-invasive polyps and low- vs. high-grade adenoma, at 0.560 and 0.492 respectively. Claude Opus 4 and GPT-5 had statistically significantly higher percent correct scores than other MLLMs at 41.7%, using Paris classification. Conclusions: Claude Opus 4 and Gemini 2.5 Pro showed the highest accuracy in differentiating polyp subtypes, performing closest to expert consensus. Sensitivity and specificity, however, did not meet ESGE standards, highlighting the need for prospective multicenter trials and the design of human-in-the-loop workflows before clinical deployment.

Multimodal large language models (MLLMs) are increasingly used to analyze pathology images. However, dominant multimodal benchmarks in pathology mainly score final diagnostic answers, captions, or reports. These evaluations provide limited insight into whether a model understands the multiscale visual content needed for pathology reasoning and decision-making. We introduce PathVU, a vision-anchored benchmark for fine-grained and multiscale visual understanding in computational pathology. Built from 23 public pathology imaging datasets with human-supervised labels and spatial annotations, PathVU evaluates MLLM understanding in two fields of view: Region FOV for high-resolution local regions and Slide FOV for macro whole-slide views. By converting raw annotations into deterministic task targets, PathVU enables programmatic scoring of region localization, visual recognition, quantity estimation, spatial reasoning, and insufficient-context judgment. The benchmark contains 14 VQA-style tasks, 61,673 images, and 308,070 samples across 28 organs and 7,253,526 annotations. Evaluating 18 representative general-purpose, medical-domain, and pathology-oriented MLLMs, we observe substantial limitations even in advanced models on fine-grained visual tasks across multiscale pathology images. PathVU provides a reproducible basis for developing and evaluating pathology MLLMs with explicit multiscale visual understanding.

In clinical practice, patients often undergo multiple imaging examinations over successive visits, yielding longitudinal data. Modeling such temporal information is crucial for reliable assessment of disease progression and treatment response. However, despite the rapid advancement of multimodal large language models (MLLMs), longitudinal medical visual reasoning remains largely underexplored. To fill this gap, we propose LoMeVQA, a comprehensive benchmark consisting of 206K longitudinal visual question answering (VQA) pairs for temporal medical image analysis. LoMeVQA covers five tasks: progress classification, progress description, progress report generation, differential region grounding, and differential region description. To construct the dataset, we develop an automated pipeline that (1) organizes patient records chronologically, (2) extracts clinically meaningful entities via a medical knowledge graph, and (3) models their temporal evolution to guide large language models in generating high-quality longitudinal VQA pairs. Extensive evaluations demonstrate that both general-purpose and medical-domain MLLMs perform poorly on LoMeVQA, revealing substantial limitations in temporal reasoning. To address these limitations, we introduce MedLong-8B, which achieves state-of-the-art performance across all tasks. Beyond benchmarking, we conduct detailed analyses that uncover key failure modes and shed light on how to improve longitudinal medical visual reasoning. Our data is available at: https://github.com/pepperbubble/LoMeVQA

Medical imaging has served as primary proving ground for clinical artificial intelligence (AI), yet a decade of intense research has not translated into proportionate bedside impact. We argue that this gap is not primarily a product of insufficient algorithmic performance, inadequate regulation, or limited explainability. Rather, it reflects a structural misalignment, between how AI systems are designed and evaluated, and how clinical decisions are made. This Perspective identifies six interconnected dimensions of this misalignment: the dominance of pixel-only models in a multimodal clinical world; the erosion of physician trust through opaque and inflexible systems; the unfulfilled promise of foundation models in data-sparse medical domains; the persistent bottleneck of non-shareable, under-curated datasets; the gap between validated algorithms and deployable clinical platforms; and the failure of prediction-centric AI to generate actionable clinical guidance. For each dimension, we reframe the problem and propose a path forward, culminating in a vision of agentic, physician-aligned AI that extends, rather than replaces, clinical judgment.

Vision-language pre-training (VLP) serves as a cornerstone for medical multimodal representation learning. However, existing medical VLP frameworks are often constrained by the limited context windows and shallow representational capacities of lightweight text encoders when processing lengthy, terminology-dense clinical reports. While integrating medical large language models (LLMs) offers unprecedented clinical reasoning capabilities, it introduces three major bottlenecks: (i) the anisotropic representational collapse of generative LLMs under standard contrastive objectives, (ii) the prohibitive memory overhead of joint end-to-end training with large batch sizes, and (iii) the medical hallucinations induced by vanilla contrastive losses that ignore fine-grained anatomical laterality and negation modifiers. To address these challenges, we propose \textbf{SCALPEL}, a \textbf{S}emantic \textbf{C}ross-modal \textbf{A}lignment framework via \textbf{L}LM-\textbf{P}owered \textbf{E}ncoder \textbf{L}earning. First, Clinical Report Contrastive fine-tuning converts a generative LLM into an isotropic encoder via domain-specific clinical text adaptation. Second, an asymmetric alignment strategy leverages offline feature caching to enable efficient training. Critically, we formulate an Anatomy-Negation Aware Objective that explicitly penalizes mismatched image-text pairs involving laterality confusion or false negations. Extensive experiments across MIMIC-CXR, CheXpert, and IU X-Ray benchmarks demonstrate that SCALPEL achieves state-of-the-art performance in cross-modal retrieval, zero-shot disease classification and medical visual question answering.

Clinical data-science agents must transform heterogeneous longitudinal records into auditable analyses, yet existing benchmarks largely isolate medical question answering, structured-table reasoning, or generic scientific repositories. We introduce CLINLENS, a benchmark of 200 executable tasks over five linked MIMIC resources spanning structured electronic health records, notes, electrocardiograms, chest radiographs, and echocardiograms. A 4 x 5 taxonomy crosses four patient-time scopes with five analysis capabilities. Program-first reverse synthesis pairs each bounded semi-raw package with an evaluator-private reference workflow and checks required artifacts, cohort and temporal semantics, and the final answer. On a fixed 126-task suite, the strongest of 24 standardized model-scaffold configurations achieves 56.3% scope-macro STRICTPASS despite 100% EXECSUCCESS. For reference, a separately configured coding agent solves 83 of 126 tasks, while five biomedical systems adapted to GPT-4o-mini reach at most 2.9% scope-macro STRICTPASS. These results expose a substantial gap between runnable submissions and correct clinical analyses.

We present VetClaw, an edge-cloud multimodal agentic system for early veterinary disease screening. VetClaw uses a camera module as an edge sensing device and sends captured images, together with optional symptom descriptions, to a server-hosted vision-language model for zero-shot disease classification. The system separates agent interaction from workflow orchestration: OpenClaw provides scheduling, tool access, user interaction, and notification services on the edge device, while LangGraph manages the stateful screening workflow, including input validation, image transmission, model invocation, safety checks, conditional routing, failure handling, and structured logging. This design moves beyond static image classification by enabling the system to collect visual evidence, invoke external models, apply deterministic safety rules, and generate diagnostic-support alerts. Results show that image-only VLM prediction remains limited, whereas symptom-guided and multimodal inputs improve zero-shot classification performance. Thus, VetClaw transforms a static prediction model into a coordinated, safety-aware system that can use tools, manage workflows, handle failures, and escalate uncertain cases.

Question answering (QA) over irregular clinical time series (ICTS) plays a pivotal role in a wide range of healthcare applications. Although recent multimodal time-series large language models (LLMs) have shown considerable promise in general-purpose time-series QA, they remain poorly equipped to model the sparsity, asynchrony, and irregular sampling patterns of clinical observations. To fill this gap, we propose ClinPRISM, a cost-effective multimodal LLM reasoning framework for question answering over ICTS data. First, we devise an irregularity-aware multi-scale encoder to capture sparse clinical evidence at diverse temporal scales. Then, we propose a temporal evidence distiller to integrate representations across these scales and compress them into a small number of LLM-compatible tokens. Moreover, we introduce a progressive alignment strategy that sequentially aligns the irregular trajectories with the LLM's textual embedding space. To facilitate training, we construct 30,000 clinical time series paired with multi-scale descriptions, together with 41,000 instruction-tuning instances spanning 11 tasks. Using a 4-billion-parameter LLM backbone, ClinPRISM achieves state-of-the-art performance on the held-out evaluation benchmark while using only 16 time-series tokens and achieving an average inference latency of 0.15 seconds per question.

Clinical diagnostic evaluation should not only assess whether models can provide correct diagnoses, but also reflect the realities of clinical practice, including progressive disclosure of multimodal information, dynamic updating of diagnostic hypotheses, and continuous refinement of clinical reasoning. However, existing evaluations of multimodal large language models (MLLMs) typically rely on single-turn or isolated tasks, making it difficult to fully capture the complexity of real-world clinical diagnosis. To bridge this gap, we developed ClinMM-Bench, the largest multi-turn multimodal clinical diagnostic evaluation benchmark to date. ClinMM-Bench contains 1,089 challenging real-world clinical cases and 3,760 medical images across eight specialties. We systematically evaluated 15 representative MLLMs using a two-level evaluation framework that assessed both diagnostic accuracy and diagnostic reasoning quality. Results showed that proprietary models achieved the highest overall diagnostic accuracy, but the proportion of completely correct diagnoses remained limited across all models. In terms of diagnostic reasoning quality, current models can identify plausible diagnostic directions but still have considerable limitations in generating reliable diagnostic reasoning. Error analysis further identified five representative failure modes: information synthesis failure, knowledge mapping error, perception error, premature closure, and visual hallucination.

Histopathological examination primarily relies on hematoxylin and eosin (H&E) and immunohistochemistry (IHC) staining. Although IHC provides critical molecular information, it is costly and requires specialized expertise. Stain transfer provides an efficient alternative by computationally generating IHC from H&E images, but remains challenged by unified and interpretable modeling for heterogeneous biomarkers under pixel-unaligned supervision. We propose DMCoStain, a novel Data-Model Co-optimization framework for Stain transfer. It iteratively co-refines training data and model capability, improving staining accuracy and interpretability in both pathological and structural consistency. To refine training data in a clinically meaningful manner, it incorporates the Multimodal Expert-Guided Finer Selection (MEGFS) strategy, built upon a pioneering IHC-positive-expression (IPE) vision-language model (VLM) that emulates pathologist reasoning. To support MEGFS, we construct ImmunoInstruction, the first large-scale IPE instruction-following dataset with 150K VQA samples. Extensive experiments on multiple tissues and biomarkers demonstrate that DMCoStain achieves state-of-the-art (SOTA) accuracy. This paradigm offers strong practical value, and MEGFS also functions as a specialized evaluation tool for future model development. Dataset, code, and more details are in https://github.com/SikangSHU/DMCoStain.

Multimodal large language models (MLLMs) hold immense potential to revolutionize clinical practice, yet deploying them in the medical domain is fundamentally a vision-centric challenge: models must absorb knowledge from heterogeneous 2D and 3D medical images, and evaluation protocols must align with radiologists' clinical practice and provide an accurate, fine-grained and factualness-driven assessment. In this paper, we introduce ClinFusion, a vision-centric MLLM designed for holistic medical understanding that systematically addresses these limitations. We propose a compositional and cascaded vision encoder architecture featuring a Cascade Spatial-Aware Locality Fusion operator that unifies diverse 2D and native 3D medical image understanding within a fused encoder. We further introduce a vision-grounded evaluation framework, including MedIF-Bench for instruction-following assessment and a region-of-interest-grounded method for clinically aligned and factualness-driven report generation evaluation. We show that ClinFusion sets a new state-of-the-art across a comprehensive suite of 2D and 3D multimodal medical benchmarks---spanning visual question answering, report generation, and instruction following---as well as textual medical tasks, outperforming leading open-source medical MLLMs (\textit{e.g.}, Hulu-Med, Lingshu) on 20 out of 24 benchmarks and demonstrating multimodal capabilities better than powerful proprietary models such as GPT-5.2 and Gemini-3-Flash on 13 out of 16 benchmarks, and can be further augmented with agentic tool use for retrieval-augmented and tool-assisted clinical workflows. A blinded evaluation by board-certified radiologists confirms that ClinFusion produces the highest-ranked reports, and validates our RoI-grounded metric as achieving the strongest correlation with expert judgment among all automatic evaluation metrics examined.

Color Fundus Photography (CFP) is a primary non-invasive imaging modality for large-scale screening of ophthalmic and systemic diseases. Existing surveys mainly summarize task-specific algorithms, datasets, or preprocessing techniques independently, lacking a unified perspective on their co-evolution with modern artificial intelligence. This review provides an integrated overview of CFP AI through the interplay of dataset evolution, preprocessing paradigms, and modeling frameworks. We show that CFP datasets have evolved from small single-center collections with task-specific labels to large multi-center resources featuring multimodal pairings and longitudinal clinical records. Preprocessing has progressed from conventional image enhancement to neural data-engineering pipelines, hardware-aware token optimization, and self-supervised imputation for incomplete electronic health records (EHRs). Meanwhile, modeling has advanced from convolutional neural networks (CNNs) to vision foundation models, state space models (SSMs), and multimodal expert architectures. At the multimodal frontier, CFP is increasingly integrated with EHRs and longitudinal patient information, enabling more comprehensive clinical reasoning beyond isolated image analysis. We conclude that future progress depends on the collaborative optimization of datasets, preprocessing, and multimodal modeling, providing a roadmap toward robust clinical deployment, improved cross-domain generalization, and resource-efficient edge intelligence.

Pathological diagnosis is inherently multi-scale, requiring the integration of global tissue architecture at low magnification with cellular morphology at higher magnification. However, existing pathology benchmarks and vision-language models (VLMs) are still largely developed under single-scale settings, limiting their ability to learn clinically meaningful multi-magnification reasoning. Moreover, naively constructed visual question answering (VQA) tasks may be susceptible to text-only or superficial visual shortcuts, leading to unreliable assessments of visual understanding. To address these limitations, we introduce a benchmark and training framework for shortcut-resistant cross-scale pathology reasoning. We design an Adversarial Text-only Screening strategy for semantic reasoning questions and a Structure-controlled Distractor Sampling strategy for visual grounding questions, encouraging models to rely on cross-scale visual evidence. Based on this pipeline, we construct PathScale-VQA, a high-quality cross-scale pathology VQA benchmark with 10,373 multiple-choice questions grounded in 1,368 diagnostic paths across multiple magnification levels. Building on the semantic reasoning set, PathScale-R1 is optimized through Difficulty-driven Reasoning Distillation supervised fine-tuning followed by reinforcement learning with a Scale-aware Reasoning Structure reward, which encourages the use of evidence across magnifications. Extensive experiments demonstrate state-of-the-art performance of PathScale-R1 on cross-scale reasoning tasks and effective transfer to conventional single-scale pathology VQA. Our code is available at https://github.com/iMVR-PL/PathScale-R1.

Medical multimodal large language models (MLLMs) are increasingly expected to perform complex image understanding tasks, yet their reliability is often compromised by frequent errors in visual interpretation. To systematically trace these failures, we traverse the hierarchy from high-level clinical tasks down to fundamental visual perception. We therefore introduce Perception-Bench, a large-scale benchmark comprising 1.13 million samples that assesses medical MLLMs across six dimensions: attribute judgment, spatial grounding, spatial understanding, disease prediction, anomaly detection, and report generation, spanning both 2D and 3D radiology images. Our analysis on Perception-Bench reveals that existing MLLMs lack the ability to capture even the most basic lesion attributes, such as location, size, and density. This inability to ground clinical outputs in primary visual evidence reveals that the models' diagnostic unreliability is rooted in a critical but overlooked bottleneck in low-level visual perception. Motivated by this, we propose RadSight, a perception-driven MLLM built upon a dual 2D/3D encoder architecture that preserves native imaging spatial structures. RadSight formulates medical image understanding as a four-stage progressive process: visual-language alignment, fine-grained visual perception, clinical diagnosis, and diagnostic interpretation. The model is trained on an 8.37 million perception-oriented corpus using progressive curriculum learning. On Perception-Bench, RadSight consistently outperforms existing MLLMs across all six evaluation dimensions, with particularly strong gains in spatial grounding and clinical diagnosis. It also achieves consistent improvements on public 2D and 3D medical benchmarks, further demonstrating that robust low-level visual perception is a critical foundation for reliable clinical understanding. Code and model will be publicly available.

Autoregressive foundation models trained on tokenized electronic health records (EHRs) can support zero-shot clinical prediction, yet most operate on structured event codes alone, and do not incorporate multiple modalities in a principled way. We present a framework for conditioning such models on auxiliary clinical modalities, including ECG waveforms, chest X-ray images, and clinical notes, using modality-specific latent compression and gated cross-attention with temporal alignment. We investigate two key design choices: (1) how to compress long per-modality sequences (e.g., ECG time series) before they enter the multi-modal cross-attention. This feature may be essential to reduce compute overheads and may be beneficial for generalization; (2) how the choice of pretrained encoder for each modality impacts downstream performance. Through controlled ablations on MIMIC-IV, we show that the best latent-compression configurations outperforms both uncompressed cross-attention and mean pooling. Encoder choice has a clear within-modality effect, with stronger pretrained encoders consistently outperforming weaker alternatives. We further show that merely adding auxiliary modalities does not guarantee improvement on ICU mortality prediction over an EHR-only baseline. This implies that careful design of the fusion architecture and an appropriate evaluation in the clinical context are required.

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.