Daily Papers

A critical step in the fight against COVID-19, which continues to have a catastrophic impact on peoples lives, is the effective screening of patients presented in the clinics with severe COVID-19 symptoms. Chest radiography is one of the promising screening approaches. Many studies reported detecting COVID-19 in chest X-rays accurately using deep learning. A serious limitation of many published approaches is insufficient attention paid to explaining decisions made by deep learning models. Using explainable artificial intelligence methods, we demonstrate that model decisions may rely on confounding factors rather than medical pathology. After an analysis of potential confounding factors found on chest X-ray images, we propose a novel method to minimise their negative impact. We show that our proposed method is more robust than previous attempts to counter confounding factors such as ECG leads in chest X-rays that often influence model classification decisions. In addition to being robust, our method achieves results comparable to the state-of-the-art. The source code and pre-trained weights are publicly available at (https://github.com/tomek1911/POTHER).

The emergence of tool-calling-based agent systems introduces a more evidence-driven paradigm for pathology image analysis in contrast to the coarse-grained text-image diagnostic approaches. With the recent large-scale experimental adoption of spatial transcriptomics technologies, molecularly validated pathological diagnosis is becoming increasingly open and accessible. In this work, we propose LAMMI-Pathology (LVLM-Agent System for Molecularly Informed Medical Intelligence in Pathology), a scalable agent framework for domain-specific agent tool-calling. LAMMI-Pathology adopts a tool-centric, bottom-up architecture in which customized domain-adaptive tools serve as the foundation. These tools are clustered by domain style to form component agents, which are then coordinated through a top-level planner hierarchically, avoiding excessively long context lengths that could induce task drift. Based on that, we introduce a novel trajectory construction mechanism based on Atomic Execution Nodes (AENs), which serve as reliable and composable units for building semi-simulated reasoning trajectories that capture credible agent-tool interactions. Building on this foundation, we develop a trajectory-aware fine-tuning strategy that aligns the planner's decision-making process with these multi-step reasoning trajectories, thereby enhancing inference robustness in pathology understanding and its adaptive use of the customized toolset.

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

Over the past decade, computer vision applications in minimally invasive surgery have rapidly increased. Despite this growth, the impact of surgical computer vision remains limited compared to other medical fields like pathology and radiology, primarily due to the scarcity of representative annotated data. Whereas transfer learning from large annotated datasets such as ImageNet has been conventionally the norm to achieve high-performing models, recent advancements in self-supervised learning (SSL) have demonstrated superior performance. In medical image analysis, in-domain SSL pretraining has already been shown to outperform ImageNet-based initialization. Although unlabeled data in the field of surgical computer vision is abundant, the diversity within this data is limited. This study investigates the role of dataset diversity in SSL for surgical computer vision, comparing procedure-specific datasets against a more heterogeneous general surgical dataset across three different downstream surgical applications. The obtained results show that using solely procedure-specific data can lead to substantial improvements of 13.8%, 9.5%, and 36.8% compared to ImageNet pretraining. However, extending this data with more heterogeneous surgical data further increases performance by an additional 5.0%, 5.2%, and 2.5%, suggesting that increasing diversity within SSL data is beneficial for model performance. The code and pretrained model weights are made publicly available at https://github.com/TimJaspers0801/SurgeNet.

Pathology Foundation Models (FMs) hold great promise for healthcare. Before they can be used in clinical practice, it is essential to ensure they are robust to variations between medical centers. We measure whether pathology FMs focus on biological features like tissue and cancer type, or on the well known confounding medical center signatures introduced by staining procedure and other differences. We introduce the Robustness Index. This novel robustness metric reflects to what degree biological features dominate confounding features. Ten current publicly available pathology FMs are evaluated. We find that all current pathology foundation models evaluated represent the medical center to a strong degree. Significant differences in the robustness index are observed. Only one model so far has a robustness index greater than one, meaning biological features dominate confounding features, but only slightly. A quantitative approach to measure the influence of medical center differences on FM-based prediction performance is described. We analyze the impact of unrobustness on classification performance of downstream models, and find that cancer-type classification errors are not random, but specifically attributable to same-center confounders: images of other classes from the same medical center. We visualize FM embedding spaces, and find these are more strongly organized by medical centers than by biological factors. As a consequence, the medical center of origin is predicted more accurately than the tissue source and cancer type. The robustness index introduced here is provided with the aim of advancing progress towards clinical adoption of robust and reliable pathology FMs.

Extraction of relevant pathological terms from radiology reports is important for correct image label generation and disease population studies. In this letter, we compare the performance of some known application program interface (APIs) for the task of thoracic abnormality extraction from radiology reports. We explored several medical domain specific annotation tools like Medical Text Indexer(MTI) with Non-MEDLINE and Mesh On Demand(MOD) options and generic Natural Language Understanding (NLU) API provided by the IBM cloud. Our results show that although MTI and MOD are intended for extracting medical terms, their performance is worst compared to generic extraction API like IBM NLU. Finally, we trained a DNN-based Named Entity Recognition (NER) model to extract the key concept words from radiology reports. Our model outperforms the medical specific and generic API performance by a large margin. Our results demonstrate the inadequacy of generic APIs for pathology extraction task and establish the importance of domain specific model training for improved results. We hope that these results motivate the research community to release larger de-identified radiology reports corpus for building high accuracy machine learning models for the important task of pathology extraction.

Medical image segmentation of anatomical structures and pathology is crucial in modern clinical diagnosis, disease study, and treatment planning. To date, great progress has been made in deep learning-based segmentation techniques, but most methods still lack data efficiency, generalizability, and interactability. Consequently, the development of new, precise segmentation methods that demand fewer labeled datasets is of utmost importance in medical image analysis. Recently, the emergence of foundation models, such as CLIP and Segment-Anything-Model (SAM), with comprehensive cross-domain representation opened the door for interactive and universal image segmentation. However, exploration of these models for data-efficient medical image segmentation is still limited, but is highly necessary. In this paper, we propose a novel framework, called MedCLIP-SAM that combines CLIP and SAM models to generate segmentation of clinical scans using text prompts in both zero-shot and weakly supervised settings. To achieve this, we employed a new Decoupled Hard Negative Noise Contrastive Estimation (DHN-NCE) loss to fine-tune the BiomedCLIP model and the recent gScoreCAM to generate prompts to obtain segmentation masks from SAM in a zero-shot setting. Additionally, we explored the use of zero-shot segmentation labels in a weakly supervised paradigm to improve the segmentation quality further. By extensively testing three diverse segmentation tasks and medical image modalities (breast tumor ultrasound, brain tumor MRI, and lung X-ray), our proposed framework has demonstrated excellent accuracy. Code is available at https://github.com/HealthX-Lab/MedCLIP-SAM.

Patient data from real-world clinical practice often suffers from data scarcity and long-tail imbalances, leading to biased outcomes or algorithmic unfairness. This study addresses these challenges by generating lesion-containing image-segmentation pairs from lesion-free images. Previous efforts in medical imaging synthesis have struggled with separating lesion information from background, resulting in low-quality backgrounds and limited control over the synthetic output. Inspired by diffusion-based image inpainting, we propose LeFusion, a lesion-focused diffusion model. By redesigning the diffusion learning objectives to focus on lesion areas, we simplify the learning process and improve control over the output while preserving high-fidelity backgrounds by integrating forward-diffused background contexts into the reverse diffusion process. Additionally, we tackle two major challenges in lesion texture synthesis: 1) multi-peak and 2) multi-class lesions. We introduce two effective strategies: histogram-based texture control and multi-channel decomposition, enabling the controlled generation of high-quality lesions in difficult scenarios. Furthermore, we incorporate lesion mask diffusion, allowing control over lesion size, location, and boundary, thus increasing lesion diversity. Validated on 3D cardiac lesion MRI and lung nodule CT datasets, LeFusion-generated data significantly improves the performance of state-of-the-art segmentation models, including nnUNet and SwinUNETR. Code and model are available at https://github.com/M3DV/LeFusion.

Is it possible to develop an "AI Pathologist" to pass the board-certified examination of the American Board of Pathology? To achieve this goal, the first step is to create a visual question answering (VQA) dataset where the AI agent is presented with a pathology image together with a question and is asked to give the correct answer. Our work makes the first attempt to build such a dataset. Different from creating general-domain VQA datasets where the images are widely accessible and there are many crowdsourcing workers available and capable of generating question-answer pairs, developing a medical VQA dataset is much more challenging. First, due to privacy concerns, pathology images are usually not publicly available. Second, only well-trained pathologists can understand pathology images, but they barely have time to help create datasets for AI research. To address these challenges, we resort to pathology textbooks and online digital libraries. We develop a semi-automated pipeline to extract pathology images and captions from textbooks and generate question-answer pairs from captions using natural language processing. We collect 32,799 open-ended questions from 4,998 pathology images where each question is manually checked to ensure correctness. To our best knowledge, this is the first dataset for pathology VQA. Our dataset will be released publicly to promote research in medical VQA.

Recent breakthroughs in self-supervised learning have enabled the use of large unlabeled datasets to train visual foundation models that can generalize to a variety of downstream tasks. While this training paradigm is well suited for the medical domain where annotations are scarce, large-scale pre-training in the medical domain, and in particular pathology, has not been extensively studied. Previous work in self-supervised learning in pathology has leveraged smaller datasets for both pre-training and evaluating downstream performance. The aim of this project is to train the largest academic foundation model and benchmark the most prominent self-supervised learning algorithms by pre-training and evaluating downstream performance on large clinical pathology datasets. We collected the largest pathology dataset to date, consisting of over 3 billion images from over 423 thousand microscopy slides. We compared pre-training of visual transformer models using the masked autoencoder (MAE) and DINO algorithms. We evaluated performance on six clinically relevant tasks from three anatomic sites and two institutions: breast cancer detection, inflammatory bowel disease detection, breast cancer estrogen receptor prediction, lung adenocarcinoma EGFR mutation prediction, and lung cancer immunotherapy response prediction. Our results demonstrate that pre-training on pathology data is beneficial for downstream performance compared to pre-training on natural images. Additionally, the DINO algorithm achieved better generalization performance across all tasks tested. The presented results signify a phase change in computational pathology research, paving the way into a new era of more performant models based on large-scale, parallel pre-training at the billion-image scale.

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

Agentic AI is rapidly advancing in healthcare and biomedical research. However, in medical image analysis, their performance and adoption remain limited due to the lack of a robust ecosystem, insufficient toolsets, and the absence of real-time interactive expert feedback. Here we present "TissueLab", a co-evolving agentic AI system that allows researchers to ask direct questions, automatically plan and generate explainable workflows, and conduct real-time analyses where experts can visualize intermediate results and refine them. TissueLab integrates tool factories across pathology, radiology, and spatial omics domains. By standardizing inputs, outputs, and capabilities of diverse tools, the system determines when and how to invoke them to address research and clinical questions. Across diverse tasks with clinically meaningful quantifications that inform staging, prognosis, and treatment planning, TissueLab achieves state-of-the-art performance compared with end-to-end vision-language models (VLMs) and other agentic AI systems such as GPT-5. Moreover, TissueLab continuously learns from clinicians, evolving toward improved classifiers and more effective decision strategies. With active learning, it delivers accurate results in unseen disease contexts within minutes, without requiring massive datasets or prolonged retraining. Released as a sustainable open-source ecosystem, TissueLab aims to accelerate computational research and translational adoption in medical imaging while establishing a foundation for the next generation of medical AI.

Pathology is the study of microscopic inspection of tissue, and a pathology diagnosis is often the medical gold standard to diagnose disease. Pathology images provide a unique challenge for computer-vision-based analysis: a single pathology Whole Slide Image (WSI) is gigapixel-sized and often contains hundreds of thousands to millions of objects of interest across multiple resolutions. In this work, we propose PathoLogy Universal TransfOrmer (PLUTO): a light-weight pathology FM that is pre-trained on a diverse dataset of 195 million image tiles collected from multiple sites and extracts meaningful representations across multiple WSI scales that enable a large variety of downstream pathology tasks. In particular, we design task-specific adaptation heads that utilize PLUTO's output embeddings for tasks which span pathology scales ranging from subcellular to slide-scale, including instance segmentation, tile classification, and slide-level prediction. We compare PLUTO's performance to other state-of-the-art methods on a diverse set of external and internal benchmarks covering multiple biologically relevant tasks, tissue types, resolutions, stains, and scanners. We find that PLUTO matches or outperforms existing task-specific baselines and pathology-specific foundation models, some of which use orders-of-magnitude larger datasets and model sizes when compared to PLUTO. Our findings present a path towards a universal embedding to power pathology image analysis, and motivate further exploration around pathology foundation models in terms of data diversity, architectural improvements, sample efficiency, and practical deployability in real-world applications.

Multiple Instance learning (MIL) models have been extensively used in pathology to predict biomarkers and risk-stratify patients from gigapixel-sized images. Machine learning problems in medical imaging often deal with rare diseases, making it important for these models to work in a label-imbalanced setting. In pathology images, there is another level of imbalance, where given a positively labeled Whole Slide Image (WSI), only a fraction of pixels within it contribute to the positive label. This compounds the severity of imbalance and makes imbalanced classification in pathology challenging. Furthermore, these imbalances can occur in out-of-distribution (OOD) datasets when the models are deployed in the real-world. We leverage the idea that decoupling feature and classifier learning can lead to improved decision boundaries for label imbalanced datasets. To this end, we investigate the integration of supervised contrastive learning with multiple instance learning (SC-MIL). Specifically, we propose a joint-training MIL framework in the presence of label imbalance that progressively transitions from learning bag-level representations to optimal classifier learning. We perform experiments with different imbalance settings for two well-studied problems in cancer pathology: subtyping of non-small cell lung cancer and subtyping of renal cell carcinoma. SC-MIL provides large and consistent improvements over other techniques on both in-distribution (ID) and OOD held-out sets across multiple imbalanced settings.

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

A key component of deep learning (DL) for natural language processing (NLP) is word embeddings. Word embeddings that effectively capture the meaning and context of the word that they represent can significantly improve the performance of downstream DL models for various NLP tasks. Many existing word embeddings techniques capture the context of words based on word co-occurrence in documents and text; however, they often cannot capture broader domain-specific relationships between concepts that may be crucial for the NLP task at hand. In this paper, we propose a method to integrate external knowledge from medical terminology ontologies into the context captured by word embeddings. Specifically, we use a medical knowledge graph, such as the unified medical language system (UMLS), to find connections between clinical terms in cancer pathology reports. This approach aims to minimize the distance between connected clinical concepts. We evaluate the proposed approach using a Multitask Convolutional Neural Network (MT-CNN) to extract six cancer characteristics -- site, subsite, laterality, behavior, histology, and grade -- from a dataset of ~900K cancer pathology reports. The results show that the MT-CNN model which uses our domain informed embeddings outperforms the same MT-CNN using standard word2vec embeddings across all tasks, with an improvement in the overall micro- and macro-F1 scores by 4.97\%and 22.5\%, respectively.

Pathology, the microscopic examination of diseased tissue, is critical for diagnosing various medical conditions, particularly cancers. Traditional methods are labor-intensive and prone to human error. Digital pathology, which converts glass slides into high-resolution digital images for analysis by computer algorithms, revolutionizes the field by enhancing diagnostic accuracy, consistency, and efficiency through automated image analysis and large-scale data processing. Foundational transformer pretraining is crucial for developing robust, generalizable models as it enables learning from vast amounts of unannotated data. This paper introduces the Hibou family of foundational vision transformers for pathology, leveraging the DINOv2 framework to pretrain two model variants, Hibou-B and Hibou-L, on a proprietary dataset of over 1 million whole slide images (WSIs) representing diverse tissue types and staining techniques. Our pretrained models demonstrate superior performance on both patch-level and slide-level benchmarks, surpassing existing state-of-the-art methods. Notably, Hibou-L achieves the highest average accuracy across multiple benchmark datasets. To support further research and application in the field, we have open-sourced the Hibou-B model, which can be accessed at https://github.com/HistAI/hibou

In this paper, we critically evaluate the capabilities of the state-of-the-art multimodal large language model, i.e., GPT-4 with Vision (GPT-4V), on Visual Question Answering (VQA) task. Our experiments thoroughly assess GPT-4V's proficiency in answering questions paired with images using both pathology and radiology datasets from 11 modalities (e.g. Microscopy, Dermoscopy, X-ray, CT, etc.) and fifteen objects of interests (brain, liver, lung, etc.). Our datasets encompass a comprehensive range of medical inquiries, including sixteen distinct question types. Throughout our evaluations, we devised textual prompts for GPT-4V, directing it to synergize visual and textual information. The experiments with accuracy score conclude that the current version of GPT-4V is not recommended for real-world diagnostics due to its unreliable and suboptimal accuracy in responding to diagnostic medical questions. In addition, we delineate seven unique facets of GPT-4V's behavior in medical VQA, highlighting its constraints within this complex arena. The complete details of our evaluation cases are accessible at https://github.com/ZhilingYan/GPT4V-Medical-Report.

Despite being widely used to support clinical care, general-purpose large multimodal models (LMMs) have generally shown poor or inconclusive performance in medical image interpretation, particularly in pathology, where gigapixel images are used. However, prior studies have used either low-resolution thumbnails or random patches, which likely underestimated model performance. Here, we ask whether LMMs can be adapted to reason coherently and accurately in the evaluation of such images. In this study, we introduce Gigapixel Image Agent for Navigating Tissue (GIANT), the first framework that allows LMMs to iteratively navigate whole-slide images (WSIs) like a pathologist. Accompanying GIANT, we release MultiPathQA, a new benchmark, which comprises 934 WSI-level questions, encompassing five clinically-relevant tasks ranging from cancer diagnosis to open-ended reasoning. MultiPathQA also includes 128 questions, authored by two professional pathologists, requiring direct slide interpretation. Using MultiPathQA, we show that our simple agentic system substantially outperforms conventional patch- and thumbnail-based baselines, approaching or surpassing the performance of specialized models trained on millions of images. For example, on pathologist-authored questions, GPT-5 with GIANT achieves 62.5% accuracy, outperforming specialist pathology models such as TITAN (43.8%) and SlideChat (37.5%). Our findings reveal the strengths and limitations of current foundation models and ground future development of LMMs for expert reasoning in pathology.

Recent advances in vision language models (VLMs) have enabled broad progress in the general medical field. However, pathology still remains a more challenging subdomain, with current pathology specific VLMs exhibiting limitations in both diagnostic accuracy and reasoning plausibility. Such shortcomings are largely attributable to the nature of current pathology datasets, which are primarily composed of image description pairs that lack the depth and structured diagnostic paradigms employed by real world pathologists. In this study, we leverage pathology textbooks and real world pathology experts to construct high-quality, reasoning-oriented datasets. Building on this, we introduce Patho-R1, a multimodal RL-based pathology Reasoner, trained through a three-stage pipeline: (1) continued pretraining on 3.5 million image-text pairs for knowledge infusion; (2) supervised fine-tuning on 500k high-quality Chain-of-Thought samples for reasoning incentivizing; (3) reinforcement learning using Group Relative Policy Optimization and Decoupled Clip and Dynamic sAmpling Policy Optimization strategies for multimodal reasoning quality refinement. To further assess the alignment quality of our dataset, we propose PathoCLIP, trained on the same figure-caption corpus used for continued pretraining. Comprehensive experimental results demonstrate that both PathoCLIP and Patho-R1 achieve robust performance across a wide range of pathology-related tasks, including zero-shot classification, cross-modal retrieval, Visual Question Answering, and Multiple Choice Question. Our project is available at the Patho-R1 repository: https://github.com/Wenchuan-Zhang/Patho-R1.

Although Vision Language Models (VLMs) have shown strong generalization in medical imaging, pathology presents unique challenges due to ultra-high resolution, complex tissue structures, and nuanced clinical semantics. These factors make pathology VLMs prone to hallucinations, i.e., generating outputs inconsistent with visual evidence, which undermines clinical trust. Existing RAG approaches in this domain largely depend on text-based knowledge bases, limiting their ability to leverage diagnostic visual cues. To address this, we propose Patho-AgenticRAG, a multimodal RAG framework with a database built on page-level embeddings from authoritative pathology textbooks. Unlike traditional text-only retrieval systems, it supports joint text-image search, enabling direct retrieval of textbook pages that contain both the queried text and relevant visual cues, thus avoiding the loss of critical image-based information. Patho-AgenticRAG also supports reasoning, task decomposition, and multi-turn search interactions, improving accuracy in complex diagnostic scenarios. Experiments show that Patho-AgenticRAG significantly outperforms existing multimodal models in complex pathology tasks like multiple-choice diagnosis and visual question answering. Our project is available at the Patho-AgenticRAG repository: https://github.com/Wenchuan-Zhang/Patho-AgenticRAG.

The growing ability of large language models and vision language models to jointly interpret and reason over images and text is reshaping medical agents, moving them from task specific predictors toward autonomous systems that perceive, reason, plan, remember, and act in clinical environments. This work departs from the capability first perspective of existing literature and instead begins from clinical deployment, asking what tasks, contamination resistant benchmarks, and interactive training environments are required before medical agents can be trusted in practice. Medical agents are formalized as sequential decision making systems under partial observability, together with a three level autonomy taxonomy spanning assisted, cooperative, and fully autonomous operation. The field is organized along a unified scaling spine consisting of framework scaling, capability scaling, and environment scaling. Within this framework, clinical environment scaling, the integration of tools, data, and clinical gyms, is identified as the most actionable yet underexplored direction for agents operating in PACS, EHR, and FHIR ecosystems. Clinical self evolution, where agents improve through interaction with their environments rather than parameter scaling alone, is further positioned as a key research frontier, drawing insights from self improving agents, agent gyms, and test time compute scaling. Applications across radiology, pathology, ophthalmology, and hospital workflows are examined together with deployment challenges including hallucination, cascading failures, and fairness. By consolidating more than 300 references, with particular emphasis on advances from 2025 to 2026, this work provides a roadmap toward trustworthy, self improving medical imaging systems for real clinical practice.

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

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

This paper introduces MedExQA, a novel benchmark in medical question-answering, to evaluate large language models' (LLMs) understanding of medical knowledge through explanations. By constructing datasets across five distinct medical specialties that are underrepresented in current datasets and further incorporating multiple explanations for each question-answer pair, we address a major gap in current medical QA benchmarks which is the absence of comprehensive assessments of LLMs' ability to generate nuanced medical explanations. Our work highlights the importance of explainability in medical LLMs, proposes an effective methodology for evaluating models beyond classification accuracy, and sheds light on one specific domain, speech language pathology, where current LLMs including GPT4 lack good understanding. Our results show generation evaluation with multiple explanations aligns better with human assessment, highlighting an opportunity for a more robust automated comprehension assessment for LLMs. To diversify open-source medical LLMs (currently mostly based on Llama2), this work also proposes a new medical model, MedPhi-2, based on Phi-2 (2.7B). The model outperformed medical LLMs based on Llama2-70B in generating explanations, showing its effectiveness in the resource-constrained medical domain. We will share our benchmark datasets and the trained model.

Localizing the exact pathological regions in a given medical scan is an important imaging problem that traditionally requires a large amount of bounding box ground truth annotations to be accurately solved. However, there exist alternative, potentially weaker, forms of supervision, such as accompanying free-text reports, which are readily available. The task of performing localization with textual guidance is commonly referred to as phrase grounding. In this work, we use a publicly available Foundation Model, namely the Latent Diffusion Model, to perform this challenging task. This choice is supported by the fact that the Latent Diffusion Model, despite being generative in nature, contains cross-attention mechanisms that implicitly align visual and textual features, thus leading to intermediate representations that are suitable for the task at hand. In addition, we aim to perform this task in a zero-shot manner, i.e., without any training on the target task, meaning that the model's weights remain frozen. To this end, we devise strategies to select features and also refine them via post-processing without extra learnable parameters. We compare our proposed method with state-of-the-art approaches which explicitly enforce image-text alignment in a joint embedding space via contrastive learning. Results on a popular chest X-ray benchmark indicate that our method is competitive with SOTA on different types of pathology, and even outperforms them on average in terms of two metrics (mean IoU and AUC-ROC). Source code will be released upon acceptance at https://github.com/vios-s.

Recent advances in generative medical models are constrained by modality-specific scenarios that hinder the integration of complementary evidence from imaging, pathology, and clinical notes. This fragmentation limits their evolution into foundation models that can learn and reason across the full spectrum of biomedical data. We propose MeDiM, the first medical discrete diffusion model that learns shared distributions across modalities without modality-specific components. MeDiM unifies multiple generative tasks: translating between images and text, and jointly producing image-report pairs across domains in response to prompts. Built on a discrete diffusion framework, MeDiM bridges vision and language representations through a shared probabilistic space. To enable unified and flexible medical generation, we employ a multimodal large language model (MLLM) as the diffusion backbone, leveraging its prior knowledge and cross-modal reasoning. Two key designs are introduced: (1) removing the causal attention mask for bidirectional context, and (2) injecting continuous timestep embeddings for diffusion awareness. Experiments demonstrate high-fidelity medical generation (FID 16.60 on MIMIC-CXR and FID 24.19 on PathGen) and accurate report generation (METEOR 0.2650 and 0.2580). Jointly generated image-report pairs further enhance downstream performance (plus6.43 percent BLEU-1, plus18.57 percent BLEU-2, plus31.58 percent BLEU-3, plus4.80 percent METEOR), showing that MeDiM supports coherent and clinically grounded multimodal outputs.

Multi-modal large language models (MM-LLMs) have shown strong performance in medical image understanding and clinical reasoning. Recent medical agent systems extend them with tool use and multi-agent collaboration, enabling complex decision-making. However, these systems rely almost entirely on frontier models (e.g., GPT), whose API-based deployment incurs high cost, high latency, and privacy risks that conflict with on-premise clinical requirements. We present Meissa, a lightweight 4B-parameter medical MM-LLM that brings agentic capability offline. Instead of imitating static answers, Meissa learns both when to engage external interaction (strategy selection) and how to execute multi-step interaction (strategy execution) by distilling structured trajectories from frontier models. Specifically, we propose: (1) Unified trajectory modeling: trajectories (reasoning and action traces) are represented within a single state-action-observation formalism, allowing one model to generalize across heterogeneous medical environments. (2) Three-tier stratified supervision: the model's own errors trigger progressive escalation from direct reasoning to tool-augmented and multi-agent interaction, explicitly learning difficulty-aware strategy selection. (3) Prospective-retrospective supervision: pairing exploratory forward traces with hindsight-rationalized execution traces enables stable learning of effective interaction policies. Trained on 40K curated trajectories, Meissa matches or exceeds proprietary frontier agents in 10 of 16 evaluation settings across 13 medical benchmarks spanning radiology, pathology, and clinical reasoning. Using over 25x fewer parameters than typical frontier models like Gemini-3, Meissa operates fully offline with 22x lower end-to-end latency compared to API-based deployment. Data, models, and environments are released at https://github.com/Schuture/Meissa.

Attention-based Multiple Instance Learning aggregators in medical imaging are prone to attention concentration, producing overconfident and unstable predictions. We introduce QG-MIL, a gated transformer aggregator that addresses this through four synergistic architectural components: RMSNorm-based pre-normalization, per-head QK normalization, fine-grained attention output gating, and SwiGLU-style feed-forward modules. Together, these design choices stabilize training and distribute attention more uniformly across instances without auxiliary losses, masking, or multi-stage regularization. We evaluate QG-MIL across six benchmarks spanning whole-slide pathology and cell-level hematology, covering two fundamentally different MIL scales. The best-performing QG-MIL variants outperform leading baselines on all six benchmarks, with an average improvement of +6.1 mean macro F1 points. Attention overlays and attention mass analysis confirm more distributed instance weighting. Ablation studies show that while individual components can match the full model on specific datasets, the QG-MIL design provides the most consistent cross-domain performance and tightest variance when compared to selected baselines. We release a configurable implementation to support reproducibility at: https://github.com/unica-visual-intelligence-lab/QG-MIL

Interpreting chest X-rays is inherently challenging due to the overlap between anatomical structures and the subtle presentation of many clinically significant pathologies, making accurate diagnosis time-consuming even for experienced radiologists. Recent radiology-focused foundation models, such as LLaVA-Rad and Maira-2, have positioned multi-modal large language models (MLLMs) at the forefront of automated radiology report generation (RRG). However, despite these advances, current foundation models generate reports in a single forward pass. This decoding strategy diminishes attention to visual tokens and increases reliance on language priors as generation proceeds, which in turn introduces spurious pathology co-occurrences in the generated reports. To mitigate these limitations, we propose Category-Wise Contrastive Decoding (CWCD), a novel and modular framework designed to enhance structured radiology report generation (SRRG). Our approach introduces category-specific parameterization and generates category-wise reports by contrasting normal X-rays with masked X-rays using category-specific visual prompts. Experimental results demonstrate that CWCD consistently outperforms baseline methods across both clinical efficacy and natural language generation metrics. An ablation study further elucidates the contribution of each architectural component to overall performance.

Gastrointestinal (GI) diseases represent a clinically significant burden, necessitating precise diagnostic approaches to optimize patient outcomes. Conventional histopathological diagnosis suffers from limited reproducibility and diagnostic variability. To overcome these limitations, we develop Digepath, a specialized foundation model for GI pathology. Our framework introduces a dual-phase iterative optimization strategy combining pretraining with fine-screening, specifically designed to address the detection of sparsely distributed lesion areas in whole-slide images. Digepath is pretrained on over 353 million multi-scale images from 210,043 H&E-stained slides of GI diseases. It attains state-of-the-art performance on 33 out of 34 tasks related to GI pathology, including pathological diagnosis, protein expression status prediction, gene mutation prediction, and prognosis evaluation. We further translate the intelligent screening module for early GI cancer and achieve near-perfect 99.70% sensitivity across nine independent medical institutions. This work not only advances AI-driven precision pathology for GI diseases but also bridge critical gaps in histopathological practice.

Deep learning models have shown promise in histopathology image analysis, but their opaque decision-making process poses challenges in high-risk medical scenarios. Here we introduce HIPPO, an explainable AI method that interrogates attention-based multiple instance learning (ABMIL) models in computational pathology by generating counterfactual examples through tissue patch modifications in whole slide images. Applying HIPPO to ABMIL models trained to detect breast cancer metastasis reveals that they may overlook small tumors and can be misled by non-tumor tissue, while attention mapsx2014widely used for interpretationx2014often highlight regions that do not directly influence predictions. By interpreting ABMIL models trained on a prognostic prediction task, HIPPO identified tissue areas with stronger prognostic effects than high-attention regions, which sometimes showed counterintuitive influences on risk scores. These findings demonstrate HIPPO's capacity for comprehensive model evaluation, bias detection, and quantitative hypothesis testing. HIPPO greatly expands the capabilities of explainable AI tools to assess the trustworthy and reliable development, deployment, and regulation of weakly-supervised models in computational pathology.

Driven by the recent advances in deep learning methods and, in particular, by the development of modern self-supervised learning algorithms, increased interest and efforts have been devoted to build foundation models (FMs) for medical images. In this work, we present our scalable training pipeline for large pathology imaging data, and a comprehensive analysis of various hyperparameter choices and training techniques for building pathology FMs. We release and make publicly available the first batch of our pathology FMs (https://github.com/kaiko-ai/towards_large_pathology_fms) trained on open-access TCGA whole slide images, a commonly used collection of pathology images. The experimental evaluation shows that our models reach state-of-the-art performance on various patch-level downstream tasks, ranging from breast cancer subtyping to colorectal nuclear segmentation. Finally, to unify the evaluation approaches used in the field and to simplify future comparisons of different FMs, we present an open-source framework (https://github.com/kaiko-ai/eva) designed for the consistent evaluation of pathology FMs across various downstream tasks.

The accelerated adoption of digital pathology and advances in deep learning have enabled the development of powerful models for various pathology tasks across a diverse array of diseases and patient cohorts. However, model training is often difficult due to label scarcity in the medical domain and the model's usage is limited by the specific task and disease for which it is trained. Additionally, most models in histopathology leverage only image data, a stark contrast to how humans teach each other and reason about histopathologic entities. We introduce CONtrastive learning from Captions for Histopathology (CONCH), a visual-language foundation model developed using diverse sources of histopathology images, biomedical text, and notably over 1.17 million image-caption pairs via task-agnostic pretraining. Evaluated on a suite of 13 diverse benchmarks, CONCH can be transferred to a wide range of downstream tasks involving either or both histopathology images and text, achieving state-of-the-art performance on histology image classification, segmentation, captioning, text-to-image and image-to-text retrieval. CONCH represents a substantial leap over concurrent visual-language pretrained systems for histopathology, with the potential to directly facilitate a wide array of machine learning-based workflows requiring minimal or no further supervised fine-tuning.

Medical vision-language models (VLMs) have shown increasing potential for clinical image interpretation, including lesion detection and report generation. However, their practical utility remains limited by insufficient sensitivity to subtle lesions, whose visual evidence is often sparse, low-contrast, and embedded within complex anatomical context. As local visual tokens are aggregated, these weak lesion cues can become underrepresented in global image representations, making them difficult for medical VLMs to recognize. Existing efforts to improve lesion sensitivity mainly rely on medical-domain vision-encoder pre-training, clinical-term-guided alignment, or trainable pathological representation enhancement. Although effective, these approaches usually require additional training or model-specific adaptation and may overfit to particular disease morphologies, limiting their applicability to frozen medical VLMs. To address these limitations, we propose EasyLens, a training-free plug-and-play subtle-lesion representation amplifier for medical VLMs. EasyLens first constructs EasyBank, a pathology-anatomy prototype space that provides lesion-related prototypes and anatomy-aware normal references for comparing suspicious patches against both pathological and normal anatomical patterns. To avoid blindly amplifying normal tissues, EasyTag selects lesion-relevant patches through counterfactual prototype reasoning. To counteract the dilution of subtle lesion cues in global image representations, EasyAmplifier strengthens the selected lesion-relevant patch representations through morphology-guided residual enhancement, thereby increasing their contribution to the global image embedding. Experiments on multiple medical image datasets and frozen medical VLM backbones show that EasyLens improves subtle-lesion detection and outperforms existing encoder-enhancement baselines.

In this paper we present a hybrid method for the automatic detection of dermatological pathologies in medical reports. We use a large language model combined with medical ontologies to predict, given a first appointment or follow-up medical report, the pathology a person may suffer from. The results show that teaching the model to learn the type, severity and location on the body of a dermatological pathology, as well as in which order it has to learn these three features, significantly increases its accuracy. The article presents the demonstration of state-of-the-art results for classification of medical texts with a precision of 0.84, micro and macro F1-score of 0.82 and 0.75, and makes both the method and the data set used available to the community.

Biomedical data is inherently multimodal, consisting of electronic health records, medical imaging, digital pathology, genome sequencing, wearable sensors, and more. The application of artificial intelligence tools to these multifaceted sensing technologies has the potential to revolutionize the prognosis, diagnosis, and management of human health and disease. However, current approaches to biomedical AI typically only train and evaluate with one or a small set of medical modalities and tasks. This limitation hampers the development of comprehensive tools that can leverage the rich interconnected information across many heterogeneous biomedical sensors. To address this challenge, we present MultiMed, a benchmark designed to evaluate and enable large-scale learning across a wide spectrum of medical modalities and tasks. MultiMed consists of 2.56 million samples across ten medical modalities such as medical reports, pathology, genomics, and protein data, and is structured into eleven challenging tasks, including disease prognosis, protein structure prediction, and medical question answering. Using MultiMed, we conduct comprehensive experiments benchmarking state-of-the-art unimodal, multimodal, and multitask models. Our analysis highlights the advantages of training large-scale medical models across many related modalities and tasks. Moreover, MultiMed enables studies of generalization across related medical concepts, robustness to real-world noisy data and distribution shifts, and novel modality combinations to improve prediction performance. MultiMed will be publicly available and regularly updated and welcomes inputs from the community.

Multimodal large language models (MLLMs) have rapidly advanced, yet their adoption in medicine remains limited by gaps in domain coverage, modality alignment, and grounded reasoning. In this work, we introduce MedMO, a medical foundation model built upon a generalized MLLM architecture and trained exclusively on large-scale, domain-specific data. MedMO follows a multi-stage training recipe: (i) cross-modal pretraining to align heterogeneous visual encoders with a medical language backbone; (ii) instruction tuning on multi-task supervision that spans captioning, VQA, report generation, retrieval, and grounded disease localization with bounding boxes; and (iii) reinforcement learning with verifiable rewards that combine factuality checks with a box-level GIoU reward to strengthen spatial grounding and step-by-step reasoning in complex clinical scenarios. MedMO consistently outperforms strong open-source medical MLLMs across multiple modalities and tasks. On VQA benchmarks, MedMO achieves an average accuracy improvement of +13.7% over the baseline and performs within 1.9% of the SOTA Fleming-VL. For text-based QA, it attains +6.9% over the baseline and +14.5% over Fleming-VL. In medical report generation, MedMO delivers significant gains in both semantic and clinical accuracy. Moreover, it exhibits strong grounding capability, achieving an IoU improvement of +40.4 over the baseline and +37.0% over Fleming-VL, underscoring its robust spatial reasoning and localization performance. Evaluations across radiology, ophthalmology, and pathology-microscopy confirm MedMO's broad cross-modality generalization. We release two versions of MedMO: 4B and 8B. Project is available at https://genmilab.github.io/MedMO-Page

Biomedical Foundation Models (FMs) are rapidly transforming AI-enabled healthcare research and entering clinical validation. However, their susceptibility to learning non-biological technical features -- including variations in surgical/endoscopic techniques, laboratory procedures, and scanner hardware -- poses risks for clinical deployment. We present the first systematic investigation of pathology FM robustness to non-biological features. Our work (i) introduces measures to quantify FM robustness, (ii) demonstrates the consequences of limited robustness, and (iii) proposes a framework for FM robustification to mitigate these issues. Specifically, we developed PathoROB, a robustness benchmark with three novel metrics, including the robustness index, and four datasets covering 28 biological classes from 34 medical centers. Our experiments reveal robustness deficits across all 20 evaluated FMs, and substantial robustness differences between them. We found that non-robust FM representations can cause major diagnostic downstream errors and clinical blunders that prevent safe clinical adoption. Using more robust FMs and post-hoc robustification considerably reduced (but did not yet eliminate) the risk of such errors. This work establishes that robustness evaluation is essential for validating pathology FMs before clinical adoption and demonstrates that future FM development must integrate robustness as a core design principle. PathoROB provides a blueprint for assessing robustness across biomedical domains, guiding FM improvement efforts towards more robust, representative, and clinically deployable AI systems that prioritize biological information over technical artifacts.

Developing self-supervised learning (SSL) models that can learn universal and transferable representations of H&E gigapixel whole-slide images (WSIs) is becoming increasingly valuable in computational pathology. These models hold the potential to advance critical tasks such as few-shot classification, slide retrieval, and patient stratification. Existing approaches for slide representation learning extend the principles of SSL from small images (e.g., 224 x 224 patches) to entire slides, usually by aligning two different augmentations (or views) of the slide. Yet the resulting representation remains constrained by the limited clinical and biological diversity of the views. Instead, we postulate that slides stained with multiple markers, such as immunohistochemistry, can be used as different views to form a rich task-agnostic training signal. To this end, we introduce Madeleine, a multimodal pretraining strategy for slide representation learning. Madeleine is trained with a dual global-local cross-stain alignment objective on large cohorts of breast cancer samples (N=4,211 WSIs across five stains) and kidney transplant samples (N=12,070 WSIs across four stains). We demonstrate the quality of slide representations learned by Madeleine on various downstream evaluations, ranging from morphological and molecular classification to prognostic prediction, comprising 21 tasks using 7,299 WSIs from multiple medical centers. Code is available at https://github.com/mahmoodlab/MADELEINE.

Intraoperative pathology is pivotal to precision surgery, yet its clinical impact is constrained by diagnostic complexity and the limited availability of high-quality frozen-section data. While computational pathology has made significant strides, the lack of large-scale, prospective validation has impeded its routine adoption in surgical workflows. Here, we introduce CRISP, a clinical-grade foundation model developed on over 100,000 frozen sections from eight medical centers, specifically designed to provide Clinical-grade Robust Intraoperative Support for Pathology (CRISP). CRISP was comprehensively evaluated on more than 15,000 intraoperative slides across nearly 100 retrospective diagnostic tasks, including benign-malignant discrimination, key intraoperative decision-making, and pan-cancer detection, etc. The model demonstrated robust generalization across diverse institutions, tumor types, and anatomical sites-including previously unseen sites and rare cancers. In a prospective cohort of over 2,000 patients, CRISP sustained high diagnostic accuracy under real-world conditions, directly informing surgical decisions in 92.6% of cases. Human-AI collaboration further reduced diagnostic workload by 35%, avoided 105 ancillary tests and enhanced detection of micrometastases with 87.5% accuracy. Together, these findings position CRISP as a clinical-grade paradigm for AI-driven intraoperative pathology, bridging computational advances with surgical precision and accelerating the translation of artificial intelligence into routine clinical practice.

The complexity and variability inherent in high-resolution pathological images present significant challenges in computational pathology. While pathology foundation models leveraging AI have catalyzed transformative advancements, their development demands large-scale datasets, considerable storage capacity, and substantial computational resources. Furthermore, ensuring their clinical applicability and generalizability requires rigorous validation across a broad spectrum of clinical tasks. Here, we present PathOrchestra, a versatile pathology foundation model trained via self-supervised learning on a dataset comprising 300K pathological slides from 20 tissue and organ types across multiple centers. The model was rigorously evaluated on 112 clinical tasks using a combination of 61 private and 51 public datasets. These tasks encompass digital slide preprocessing, pan-cancer classification, lesion identification, multi-cancer subtype classification, biomarker assessment, gene expression prediction, and the generation of structured reports. PathOrchestra demonstrated exceptional performance across 27,755 WSIs and 9,415,729 ROIs, achieving over 0.950 accuracy in 47 tasks, including pan-cancer classification across various organs, lymphoma subtype diagnosis, and bladder cancer screening. Notably, it is the first model to generate structured reports for high-incidence colorectal cancer and diagnostically complex lymphoma-areas that are infrequently addressed by foundational models but hold immense clinical potential. Overall, PathOrchestra exemplifies the feasibility and efficacy of a large-scale, self-supervised pathology foundation model, validated across a broad range of clinical-grade tasks. Its high accuracy and reduced reliance on extensive data annotation underline its potential for clinical integration, offering a pathway toward more efficient and high-quality medical services.

The previous advancements in pathology image understanding primarily involved developing models tailored to specific tasks. Recent studies has demonstrated that the large vision-language model can enhance the performance of various downstream tasks in medical image understanding. In this study, we developed a domain-specific large language-vision assistant (PA-LLaVA) for pathology image understanding. Specifically, (1) we first construct a human pathology image-text dataset by cleaning the public medical image-text data for domain-specific alignment; (2) Using the proposed image-text data, we first train a pathology language-image pretraining (PLIP) model as the specialized visual encoder for pathology image, and then we developed scale-invariant connector to avoid the information loss caused by image scaling; (3) We adopt two-stage learning to train PA-LLaVA, first stage for domain alignment, and second stage for end to end visual question \& answering (VQA) task. In experiments, we evaluate our PA-LLaVA on both supervised and zero-shot VQA datasets, our model achieved the best overall performance among multimodal models of similar scale. The ablation experiments also confirmed the effectiveness of our design. We posit that our PA-LLaVA model and the datasets presented in this work can promote research in field of computational pathology. All codes are available at: https://github.com/ddw2AIGROUP2CQUPT/PA-LLaVA}{https://github.com/ddw2AIGROUP2CQUPT/PA-LLaVA

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

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.

Current artificial intelligence models for medical imaging are predominantly single modality and single disease. Attempts to create multimodal and multi-disease models have resulted in inconsistent clinical accuracy. Furthermore, training these models typically requires large, labour-intensive, well-labelled datasets. We developed MerMED-FM, a state-of-the-art multimodal, multi-specialty foundation model trained using self-supervised learning and a memory module. MerMED-FM was trained on 3.3 million medical images from over ten specialties and seven modalities, including computed tomography (CT), chest X-rays (CXR), ultrasound (US), pathology patches, color fundus photography (CFP), optical coherence tomography (OCT) and dermatology images. MerMED-FM was evaluated across multiple diseases and compared against existing foundational models. Strong performance was achieved across all modalities, with AUROCs of 0.988 (OCT); 0.982 (pathology); 0.951 (US); 0.943 (CT); 0.931 (skin); 0.894 (CFP); 0.858 (CXR). MerMED-FM has the potential to be a highly adaptable, versatile, cross-specialty foundation model that enables robust medical imaging interpretation across diverse medical disciplines.

Medical imaging datasets often vary due to differences in acquisition protocols, patient demographics, and imaging devices. These variations in data distribution, known as domain shift, present a significant challenge in adapting imaging analysis models for practical healthcare applications. Most current domain adaptation (DA) approaches aim either to align the distributions between the source and target domains or to learn an invariant feature space that generalizes well across all domains. However, both strategies require access to a sufficient number of examples, though not necessarily annotated, from the test domain during training. This limitation hinders the widespread deployment of models in clinical settings, where target domain data may only be accessible in real time. In this work, we introduce HyDA, a novel hypernetwork framework that leverages domain characteristics rather than suppressing them, enabling dynamic adaptation at inference time. Specifically, HyDA learns implicit domain representations and uses them to adjust model parameters on-the-fly, effectively interpolating to unseen domains. We validate HyDA on two clinically relevant applications - MRI brain age prediction and chest X-ray pathology classification - demonstrating its ability to generalize across tasks and modalities. Our code is available at TBD.

This paper provides a novel 3D medical image segmentation model structure called nnY-Net. This name comes from the fact that our model adds a cross-attention module at the bottom of the U-net structure to form a Y structure. We integrate the advantages of the two latest SOTA models, MedNeXt and SwinUNETR, and use Swin Transformer as the encoder and ConvNeXt as the decoder to innovatively design the Swin-NeXt structure. Our model uses the lowest-level feature map of the encoder as Key and Value and uses patient features such as pathology and treatment information as Query to calculate the attention weights in a Cross Attention module. Moreover, we simplify some pre- and post-processing as well as data enhancement methods in 3D image segmentation based on the dynUnet and nnU-net frameworks. We integrate our proposed Swin-NeXt with Cross-Attention framework into this framework. Last, we construct a DiceFocalCELoss to improve the training efficiency for the uneven data convergence of voxel classification.

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

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

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

Vision-Language Models (VLMs) trained via contrastive learning have achieved notable success in natural image tasks. However, their application in the medical domain remains limited due to the scarcity of openly accessible, large-scale medical image-text datasets. Existing medical VLMs either train on closed-source proprietary or relatively small open-source datasets that do not generalize well. Similarly, most models remain specific to a single or limited number of medical imaging domains, again restricting their applicability to other modalities. To address this gap, we introduce UniMed, a large-scale, open-source multi-modal medical dataset comprising over 5.3 million image-text pairs across six diverse imaging modalities: X-ray, CT, MRI, Ultrasound, Pathology, and Fundus. UniMed is developed using a data-collection framework that leverages Large Language Models (LLMs) to transform modality-specific classification datasets into image-text formats while incorporating existing image-text data from the medical domain, facilitating scalable VLM pretraining. Using UniMed, we trained UniMed-CLIP, a unified VLM for six modalities that significantly outperforms existing generalist VLMs and matches modality-specific medical VLMs, achieving notable gains in zero-shot evaluations. For instance, UniMed-CLIP improves over BiomedCLIP (trained on proprietary data) by an absolute gain of +12.61, averaged over 21 datasets, while using 3x less training data. To facilitate future research, we release UniMed dataset, training codes, and models at https://github.com/mbzuai-oryx/UniMed-CLIP.

Medical video generation has transformative potential for enhancing surgical understanding and pathology insights through precise and controllable visual representations. However, current models face limitations in controllability and authenticity. To bridge this gap, we propose SurgSora, a motion-controllable surgical video generation framework that uses a single input frame and user-controllable motion cues. SurgSora consists of three key modules: the Dual Semantic Injector (DSI), which extracts object-relevant RGB and depth features from the input frame and integrates them with segmentation cues to capture detailed spatial features of complex anatomical structures; the Decoupled Flow Mapper (DFM), which fuses optical flow with semantic-RGB-D features at multiple scales to enhance temporal understanding and object spatial dynamics; and the Trajectory Controller (TC), which allows users to specify motion directions and estimates sparse optical flow, guiding the video generation process. The fused features are used as conditions for a frozen Stable Diffusion model to produce realistic, temporally coherent surgical videos. Extensive evaluations demonstrate that SurgSora outperforms state-of-the-art methods in controllability and authenticity, showing its potential to advance surgical video generation for medical education, training, and research.

Generative diffusion models are increasingly used for medical imaging data augmentation, but text prompting cannot produce causal training data. Re-prompting rerolls the entire generation trajectory, altering anatomy, texture, and background. Inversion-based editing methods introduce reconstruction error that causes structural drift. We propose MedSteer, a training-free activation-steering framework for endoscopic synthesis. MedSteer identifies a pathology vector for each contrastive prompt pair in the cross-attention layers of a diffusion transformer. At inference time, it steers image activations along this vector, generating counterfactual pairs from scratch where the only difference is the steered concept. All other structure is preserved by construction. We evaluate MedSteer across three experiments on Kvasir v3 and HyperKvasir. On counterfactual generation across three clinical concept pairs, MedSteer achieves flip rates of 0.800, 0.925, and 0.950, outperforming the best inversion-based baseline in both concept flip rate and structural preservation. On dye disentanglement, MedSteer achieves 75% dye removal against 20% (PnP) and 10% (h-Edit). On downstream polyp detection, augmenting with MedSteer counterfactual pairs achieves ViT AUC of 0.9755 versus 0.9083 for quantity-matched re-prompting, confirming that counterfactual structure drives the gain. Code is at link https://github.com/phamtrongthang123/medsteer

Deep learning based medical image classifiers have shown remarkable prowess in various application areas like ophthalmology, dermatology, pathology, and radiology. However, the acceptance of these Computer-Aided Diagnosis (CAD) systems in real clinical setups is severely limited primarily because their decision-making process remains largely obscure. This work aims at elucidating a deep learning based medical image classifier by verifying that the model learns and utilizes similar disease-related concepts as described and employed by dermatologists. We used a well-trained and high performing neural network developed by REasoning for COmplex Data (RECOD) Lab for classification of three skin tumours, i.e. Melanocytic Naevi, Melanoma and Seborrheic Keratosis and performed a detailed analysis on its latent space. Two well established and publicly available skin disease datasets, PH2 and derm7pt, are used for experimentation. Human understandable concepts are mapped to RECOD image classification model with the help of Concept Activation Vectors (CAVs), introducing a novel training and significance testing paradigm for CAVs. Our results on an independent evaluation set clearly shows that the classifier learns and encodes human understandable concepts in its latent representation. Additionally, TCAV scores (Testing with CAVs) suggest that the neural network indeed makes use of disease-related concepts in the correct way when making predictions. We anticipate that this work can not only increase confidence of medical practitioners on CAD but also serve as a stepping stone for further development of CAV-based neural network interpretation methods.

The field of Machine Learning, a subset of Artificial Intelligence, has led to remarkable advancements in many areas, including medicine. Machine Learning algorithms require large datasets to train computer models successfully. Although there are medical image datasets available, more image datasets are needed from a variety of medical entities, especially cancer pathology. Even more scarce are ML-ready image datasets. To address this need, we created an image dataset (LC25000) with 25,000 color images in 5 classes. Each class contains 5,000 images of the following histologic entities: colon adenocarcinoma, benign colonic tissue, lung adenocarcinoma, lung squamous cell carcinoma, and benign lung tissue. All images are de-identified, HIPAA compliant, validated, and freely available for download to AI researchers.

Pathology foundation models substantially advanced the possibilities in computational pathology -- yet tradeoffs in terms of performance, robustness, and computational requirements remained, which limited their clinical deployment. In this report, we present Atlas 2, Atlas 2-B, and Atlas 2-S, three pathology vision foundation models which bridge these shortcomings by showing state-of-the-art performance in prediction performance, robustness, and resource efficiency in a comprehensive evaluation across eighty public benchmarks. Our models were trained on the largest pathology foundation model dataset to date comprising 5.5 million histopathology whole slide images, collected from three medical institutions Charité - Universtätsmedizin Berlin, LMU Munich, and Mayo Clinic.

To generate evidence regarding the safety and efficacy of artificial intelligence (AI) enabled medical devices, AI models need to be evaluated on a diverse population of patient cases, some of which may not be readily available. We propose an evaluation approach for testing medical imaging AI models that relies on in silico imaging pipelines in which stochastic digital models of human anatomy (in object space) with and without pathology are imaged using a digital replica imaging acquisition system to generate realistic synthetic image datasets. Here, we release M-SYNTH, a dataset of cohorts with four breast fibroglandular density distributions imaged at different exposure levels using Monte Carlo x-ray simulations with the publicly available Virtual Imaging Clinical Trial for Regulatory Evaluation (VICTRE) toolkit. We utilize the synthetic dataset to analyze AI model performance and find that model performance decreases with increasing breast density and increases with higher mass density, as expected. As exposure levels decrease, AI model performance drops with the highest performance achieved at exposure levels lower than the nominal recommended dose for the breast type.

Recent advances in multi-modal algorithms have driven and been driven by the increasing availability of large image-text datasets, leading to significant strides in various fields, including computational pathology. However, in most existing medical image-text datasets, the text typically provides high-level summaries that may not sufficiently describe sub-tile regions within a large pathology image. For example, an image might cover an extensive tissue area containing cancerous and healthy regions, but the accompanying text might only specify that this image is a cancer slide, lacking the nuanced details needed for in-depth analysis. In this study, we introduce STimage-1K4M, a novel dataset designed to bridge this gap by providing genomic features for sub-tile images. STimage-1K4M contains 1,149 images derived from spatial transcriptomics data, which captures gene expression information at the level of individual spatial spots within a pathology image. Specifically, each image in the dataset is broken down into smaller sub-image tiles, with each tile paired with 15,000-30,000 dimensional gene expressions. With 4,293,195 pairs of sub-tile images and gene expressions, STimage-1K4M offers unprecedented granularity, paving the way for a wide range of advanced research in multi-modal data analysis an innovative applications in computational pathology, and beyond.

With the advent of the COVID-19 pandemic, ultrasound imaging has emerged as a promising technique for COVID-19 detection, due to its non-invasive nature, affordability, and portability. In response, researchers have focused on developing AI-based scoring systems to provide real-time diagnostic support. However, the limited size and lack of proper annotation in publicly available ultrasound datasets pose significant challenges for training a robust AI model. This paper proposes MeDiVLAD, a novel pipeline to address the above issue for multi-level lung-ultrasound (LUS) severity scoring. In particular, we leverage self-knowledge distillation to pretrain a vision transformer (ViT) without label and aggregate frame-level features via dual-level VLAD aggregation. We show that with minimal finetuning, MeDiVLAD outperforms conventional fully-supervised methods in both frame- and video-level scoring, while offering classification reasoning with exceptional quality. This superior performance enables key applications such as the automatic identification of critical lung pathology areas and provides a robust solution for broader medical video classification tasks.

In this work, we introduce RadImageNet-VQA, a large-scale dataset designed to advance radiologic visual question answering (VQA) on CT and MRI exams. Existing medical VQA datasets are limited in scale, dominated by X-ray imaging or biomedical illustrations, and often prone to text-based shortcuts. RadImageNet-VQA is built from expert-curated annotations and provides 750K images paired with 7.5M question-answer samples. It covers three key tasks - abnormality detection, anatomy recognition, and pathology identification - spanning eight anatomical regions and 97 pathology categories, and supports open-ended, closed-ended, and multiple-choice questions. Extensive experiments show that state-of-the-art vision-language models still struggle with fine-grained pathology identification, particularly in open-ended settings and even after fine-tuning. Text-only analysis further reveals that model performance collapses to near-random without image inputs, confirming that RadImageNet-VQA is free from linguistic shortcuts. The full dataset and benchmark are publicly available at https://huggingface.co/datasets/raidium/RadImageNet-VQA.

Diagnosing lung cancer typically involves physicians identifying lung nodules in Computed tomography (CT) scans and generating diagnostic reports based on their morphological features and medical expertise. Although advancements have been made in using multimodal large language models for analyzing lung CT scans, challenges remain in accurately describing nodule morphology and incorporating medical expertise. These limitations affect the reliability and effectiveness of these models in clinical settings. Collaborative multi-agent systems offer a promising strategy for achieving a balance between generality and precision in medical applications, yet their potential in pathology has not been thoroughly explored. To bridge these gaps, we introduce LungNoduleAgent, an innovative collaborative multi-agent system specifically designed for analyzing lung CT scans. LungNoduleAgent streamlines the diagnostic process into sequential components, improving precision in describing nodules and grading malignancy through three primary modules. The first module, the Nodule Spotter, coordinates clinical detection models to accurately identify nodules. The second module, the Radiologist, integrates localized image description techniques to produce comprehensive CT reports. Finally, the Doctor Agent System performs malignancy reasoning by using images and CT reports, supported by a pathology knowledge base and a multi-agent system framework. Extensive testing on two private datasets and the public LIDC-IDRI dataset indicates that LungNoduleAgent surpasses mainstream vision-language models, agent systems, and advanced expert models. These results highlight the importance of region-level semantic alignment and multi-agent collaboration in diagnosing nodules. LungNoduleAgent stands out as a promising foundational tool for supporting clinical analyses of lung nodules.

Early tumor detection save lives. Each year, more than 300 million computed tomography (CT) scans are performed worldwide, offering a vast opportunity for effective cancer screening. However, detecting small or early-stage tumors on these CT scans remains challenging, even for experts. Artificial intelligence (AI) models can assist by highlighting suspicious regions, but training such models typically requires extensive tumor masks--detailed, voxel-wise outlines of tumors manually drawn by radiologists. Drawing these masks is costly, requiring years of effort and millions of dollars. In contrast, nearly every CT scan in clinical practice is already accompanied by medical reports describing the tumor's size, number, appearance, and sometimes, pathology results--information that is rich, abundant, and often underutilized for AI training. We introduce R-Super, which trains AI to segment tumors that match their descriptions in medical reports. This approach scales AI training with large collections of readily available medical reports, substantially reducing the need for manually drawn tumor masks. When trained on 101,654 reports, AI models achieved performance comparable to those trained on 723 masks. Combining reports and masks further improved sensitivity by +13% and specificity by +8%, surpassing radiologists in detecting five of the seven tumor types. Notably, R-Super enabled segmentation of tumors in the spleen, gallbladder, prostate, bladder, uterus, and esophagus, for which no public masks or AI models previously existed. This study challenges the long-held belief that large-scale, labor-intensive tumor mask creation is indispensable, establishing a scalable and accessible path toward early detection across diverse tumor types. We plan to release our trained models, code, and dataset at https://github.com/MrGiovanni/R-Super

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

Pathology plays a critical role in diagnosing a wide range of diseases, yet existing approaches often rely heavily on task-specific models trained on extensive, well-labeled datasets. These methods face sustainability challenges due to the diversity of pathologies and the labor-intensive nature of data collection. To address these limitations, we highlight the need for universal multimodal embeddings that can support multiple downstream tasks. Previous approaches often involve fine-tuning CLIP-based models, which handle images and text separately, limiting their ability to capture complex multimodal relationships. Additionally, these models are evaluated across diverse datasets without a unified benchmark for assessing multimodal embeddings in pathology. To address these challenges, we propose MLLM4PUE, a novel framework that leverages Multimodal Large Language Models (MLLMs) to generate Pathology Universal Embeddings. The MLLM4PUE framework not only facilitates robust integration of images and text but also enhances understanding and fusion capabilities across various tasks. We further introduce the Pathology Multimodal Embedding Benchmark (PMEB), a comprehensive benchmark designed to assess the quality of pathology multimodal embeddings. PMEB comprises 15 original tasks drawn from 14 datasets, organized into three meta-tasks: retrieval, classification, and composed retrieval. Experimental results demonstrate the superiority of MLLM4PUE, illustrating MLLM-based models can effectively support a wide range of downstream tasks and unify the research direction for foundation models in pathology.

Pathology text mining is a challenging task given the reporting variability and constant new findings in cancer sub-type definitions. However, successful text mining of a large pathology database can play a critical role to advance 'big data' cancer research like similarity-based treatment selection, case identification, prognostication, surveillance, clinical trial screening, risk stratification, and many others. While there is a growing interest in developing language models for more specific clinical domains, no pathology-specific language space exist to support the rapid data-mining development in pathology space. In literature, a few approaches fine-tuned general transformer models on specialized corpora while maintaining the original tokenizer, but in fields requiring specialized terminology, these models often fail to perform adequately. We propose PathologyBERT - a pre-trained masked language model which was trained on 347,173 histopathology specimen reports and publicly released in the Huggingface repository. Our comprehensive experiments demonstrate that pre-training of transformer model on pathology corpora yields performance improvements on Natural Language Understanding (NLU) and Breast Cancer Diagnose Classification when compared to nonspecific language models.

Vision-language models in pathology enable multimodal case retrieval and automated report generation. Many of the models developed so far, however, have been trained on pathology reports that include information which cannot be inferred from paired whole slide images (e.g., patient history), potentially leading to hallucinated sentences in generated reports. To this end, we investigate how the selection of information from pathology reports for vision-language modeling affects the quality of the multimodal representations and generated reports. More concretely, we compare a model trained on full reports against a model trained on preprocessed reports that only include sentences describing the cell and tissue appearances based on the H&E-stained slides. For the experiments, we built upon the BLIP-2 framework and used a cutaneous melanocytic lesion dataset of 42,433 H&E-stained whole slide images and 19,636 corresponding pathology reports. Model performance was assessed using image-to-text and text-to-image retrieval, as well as qualitative evaluation of the generated reports by an expert pathologist. Our results demonstrate that text preprocessing prevents hallucination in report generation. Despite the improvement in the quality of the generated reports, training the vision-language model on full reports showed better cross-modal retrieval performance.

Metadata are general characteristics of the data in a well-curated and condensed format, and have been proven to be useful for decision making, knowledge discovery, and also heterogeneous data organization of biobank. Among all data types in the biobank, pathology is the key component of the biobank and also serves as the gold standard of diagnosis. To maximize the utility of biobank and allow the rapid progress of biomedical science, it is essential to organize the data with well-populated pathology metadata. However, manual annotation of such information is tedious and time-consuming. In the study, we develop a multimodal multitask learning framework to predict four major slide-level metadata of pathology images. The framework learns generalizable representations across tissue slides, pathology reports, and case-level structured data. We demonstrate improved performance across all four tasks with the proposed method compared to a single modal single task baseline on two test sets, one external test set from a distinct data source (TCGA) and one internal held-out test set (TTH). In the test sets, the performance improvements on the averaged area under receiver operating characteristic curve across the four tasks are 16.48% and 9.05% on TCGA and TTH, respectively. Such pathology metadata prediction system may be adopted to mitigate the effort of expert annotation and ultimately accelerate the data-driven research by better utilization of the pathology biobank.

Microscopic interpretation of histopathology images underlies many important diagnostic and treatment decisions. While advances in vision-language modeling raise new opportunities for analysis of such images, the gigapixel-scale size of whole slide images (WSIs) introduces unique challenges. Additionally, pathology reports simultaneously highlight key findings from small regions while also aggregating interpretation across multiple slides, often making it difficult to create robust image-text pairs. As such, pathology reports remain a largely untapped source of supervision in computational pathology, with most efforts relying on region-of-interest annotations or self-supervision at the patch-level. In this work, we develop a vision-language model based on the BLIP-2 framework using WSIs paired with curated text from pathology reports. This enables applications utilizing a shared image-text embedding space, such as text or image retrieval for finding cases of interest, as well as integration of the WSI encoder with a frozen large language model (LLM) for WSI-based generative text capabilities such as report generation or AI-in-the-loop interactions. We utilize a de-identified dataset of over 350,000 WSIs and diagnostic text pairs, spanning a wide range of diagnoses, procedure types, and tissue types. We present pathologist evaluation of text generation and text retrieval using WSI embeddings, as well as results for WSI classification and workflow prioritization (slide-level triaging). Model-generated text for WSIs was rated by pathologists as accurate, without clinically significant error or omission, for 78% of WSIs on average. This work demonstrates exciting potential capabilities for language-aligned WSI embeddings.

Pathological diagnosis remains the definitive standard for identifying tumors. The rise of multimodal large models has simplified the process of integrating image analysis with textual descriptions. Despite this advancement, the substantial costs associated with training and deploying these complex multimodal models, together with a scarcity of high-quality training datasets, create a significant divide between cutting-edge technology and its application in the clinical setting. We had meticulously compiled a dataset of approximately 45,000 cases, covering over 6 different tasks, including the classification of organ tissues, generating pathology report descriptions, and addressing pathology-related questions and answers. We have fine-tuned multimodal large models, specifically LLaVA, Qwen-VL, InternLM, with this dataset to enhance instruction-based performance. We conducted a qualitative assessment of the capabilities of the base model and the fine-tuned model in performing image captioning and classification tasks on the specific dataset. The evaluation results demonstrate that the fine-tuned model exhibits proficiency in addressing typical pathological questions. We hope that by making both our models and datasets publicly available, they can be valuable to the medical and research communities.

Histopathology plays a central role in clinical medicine and biomedical research. While artificial intelligence shows promising results on many pathological tasks, generalization and dealing with rare diseases, where training data is scarce, remains a challenge. Distilling knowledge from unlabeled data into a foundation model before learning from, potentially limited, labeled data provides a viable path to address these challenges. In this work, we extend the state of the art of foundation models for digital pathology whole slide images by semi-automated data curation and incorporating pathologist domain knowledge. Specifically, we combine computational and pathologist domain knowledge (1) to curate a diverse dataset of 103k slides corresponding to 750 million image patches covering data from different fixation, staining, and scanning protocols as well as data from different indications and labs across the EU and US, (2) for grouping semantically similar slides and tissue patches, and (3) to augment the input images during training. We evaluate the resulting model on a set of public and internal benchmarks and show that although our foundation model is trained with an order of magnitude less slides, it performs on par or better than competing models. We expect that scaling our approach to more data and larger models will further increase its performance and capacity to deal with increasingly complex real world tasks in diagnostics and biomedical research.

Forensic pathology is critical in determining the cause and manner of death through post-mortem examinations, both macroscopic and microscopic. The field, however, grapples with issues such as outcome variability, laborious processes, and a scarcity of trained professionals. This paper presents SongCi, an innovative visual-language model (VLM) designed specifically for forensic pathology. SongCi utilizes advanced prototypical cross-modal self-supervised contrastive learning to enhance the accuracy, efficiency, and generalizability of forensic analyses. It was pre-trained and evaluated on a comprehensive multi-center dataset, which includes over 16 million high-resolution image patches, 2,228 vision-language pairs of post-mortem whole slide images (WSIs), and corresponding gross key findings, along with 471 distinct diagnostic outcomes. Our findings indicate that SongCi surpasses existing multi-modal AI models in many forensic pathology tasks, performs comparably to experienced forensic pathologists and significantly better than less experienced ones, and provides detailed multi-modal explainability, offering critical assistance in forensic investigations. To the best of our knowledge, SongCi is the first VLM specifically developed for forensic pathological analysis and the first large-vocabulary computational pathology (CPath) model that directly processes gigapixel WSIs in forensic science.

As advances in large language models (LLMs) and multimodal techniques continue to mature, the development of general-purpose multimodal large language models (MLLMs) has surged, offering significant applications in interpreting natural images. However, the field of pathology has largely remained untapped, particularly in gathering high-quality data and designing comprehensive model frameworks. To bridge the gap in pathology MLLMs, we present PathAsst, a multimodal generative foundation AI assistant to revolutionize diagnostic and predictive analytics in pathology. The development of PathAsst involves three pivotal steps: data acquisition, CLIP model adaptation, and the training of PathAsst's multimodal generative capabilities. Firstly, we collect over 207K high-quality pathology image-text pairs from authoritative sources. Leveraging the advanced power of ChatGPT, we generate over 180K instruction-following samples. Furthermore, we devise additional instruction-following data specifically tailored for invoking eight pathology-specific sub-models we prepared, allowing the PathAsst to effectively collaborate with these models, enhancing its diagnostic ability. Secondly, by leveraging the collected data, we construct PathCLIP, a pathology-dedicated CLIP, to enhance PathAsst's capabilities in interpreting pathology images. Finally, we integrate PathCLIP with the Vicuna-13b and utilize pathology-specific instruction-tuning data to enhance the multimodal generation capacity of PathAsst and bolster its synergistic interactions with sub-models. The experimental results of PathAsst show the potential of harnessing AI-powered generative foundation model to improve pathology diagnosis and treatment processes.

Millions of melanocytic skin lesions are examined by pathologists each year, the majority of which concern common nevi (i.e., ordinary moles). While most of these lesions can be diagnosed in seconds, writing the corresponding pathology report is much more time-consuming. Automating part of the report writing could, therefore, alleviate the increasing workload of pathologists. In this work, we develop a vision-language model specifically for the pathology domain of cutaneous melanocytic lesions. The model follows the Contrastive Captioner framework and was trained and evaluated using a melanocytic lesion dataset of 42,512 H&E-stained whole slide images and 19,645 corresponding pathology reports. Our results show that the quality scores of model-generated reports were on par with pathologist-written reports for common nevi, assessed by an expert pathologist in a reader study. While report generation revealed to be more difficult for rare melanocytic lesion subtypes, the cross-modal retrieval performance for these cases was considerably better.

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.

Remarkable strides in computational pathology have been made in the task-agnostic foundation model that advances the performance of a wide array of downstream clinical tasks. Despite the promising performance, there are still several challenges. First, prior works have resorted to either vision-only or image-caption data, disregarding pathology reports with more clinically authentic information from pathologists and gene expression profiles which respectively offer distinct knowledge for versatile clinical applications. Second, the current progress in pathology FMs predominantly concentrates on the patch level, where the restricted context of patch-level pretraining fails to capture whole-slide patterns. Even recent slide-level FMs still struggle to provide whole-slide context for patch representation. In this study, for the first time, we develop a pathology foundation model incorporating three levels of modalities: pathology slides, pathology reports, and gene expression data, which resulted in 26,169 slide-level modality pairs from 10,275 patients across 32 cancer types, amounting to over 116 million pathological patch images. To leverage these data for CPath, we propose a novel whole-slide pretraining paradigm that injects the multimodal whole-slide context into the patch representation, called Multimodal Self-TAught PRetraining (mSTAR). The proposed paradigm revolutionizes the pretraining workflow for CPath, enabling the pathology FM to acquire the whole-slide context. To the best of our knowledge, this is the first attempt to incorporate three modalities at the whole-slide context for enhancing pathology FMs. To systematically evaluate the capabilities of mSTAR, we built the largest spectrum of oncological benchmark, spanning 7 categories of oncological applications in 15 types of 97 practical oncological tasks.

Foundation models trained with self-supervised learning (SSL) on large-scale histological images have significantly accelerated the development of computational pathology. These models can serve as backbones for region-of-interest (ROI) image analysis or patch-level feature extractors in whole-slide images (WSIs) based on multiple instance learning (MIL). Existing pathology foundation models (PFMs) are typically pre-trained on Hematoxylin-Eosin (H&E) stained pathology images. However, images with special stains, such as immunohistochemistry, are also frequently used in clinical practice. PFMs pre-trained mainly on H\&E-stained images may be limited in clinical applications involving special stains. To address this issue, we propose StainNet, a specialized foundation model for special stains based on the vision transformer (ViT) architecture. StainNet adopts a self-distillation SSL approach and is trained on over 1.4 million patch images cropping from 20,231 publicly available special staining WSIs in the HISTAI database. To evaluate StainNet, we conduct experiments on an in-house slide-level liver malignancy classification task and two public ROI-level datasets to demonstrate its strong ability. We also perform few-ratio learning and retrieval evaluations, and compare StainNet with recently larger PFMs to further highlight its strengths. We have released the StainNet model weights at: https://huggingface.co/JWonderLand/StainNet.

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

Vision Language Models (VLMs) like CLIP have attracted substantial attention in pathology, serving as backbones for applications such as zero-shot image classification and Whole Slide Image (WSI) analysis. Additionally, they can function as vision encoders when combined with large language models (LLMs) to support broader capabilities. Current efforts to train pathology VLMs rely on pathology image-text pairs from platforms like PubMed, YouTube, and Twitter, which provide limited, unscalable data with generally suboptimal image quality. In this work, we leverage large-scale WSI datasets like TCGA to extract numerous high-quality image patches. We then train a large multimodal model to generate captions for these images, creating PathGen-1.6M, a dataset containing 1.6 million high-quality image-caption pairs. Our approach involves multiple agent models collaborating to extract representative WSI patches, generating and refining captions to obtain high-quality image-text pairs. Extensive experiments show that integrating these generated pairs with existing datasets to train a pathology-specific CLIP model, PathGen-CLIP, significantly enhances its ability to analyze pathological images, with substantial improvements across nine pathology-related zero-shot image classification tasks and three whole-slide image tasks. Furthermore, we construct 200K instruction-tuning data based on PathGen-1.6M and integrate PathGen-CLIP with the Vicuna LLM to create more powerful multimodal models through instruction tuning. Overall, we provide a scalable pathway for high-quality data generation in pathology, paving the way for next-generation general pathology models.

We introduce MedGemma 1.5 4B, the latest model in the MedGemma collection. MedGemma 1.5 expands on MedGemma 1 by integrating additional capabilities: high-dimensional medical imaging (CT/MRI volumes and histopathology whole slide images), anatomical localization via bounding boxes, multi-timepoint chest X-ray analysis, and improved medical document understanding (lab reports, electronic health records). We detail the innovations required to enable these modalities within a single architecture, including new training data, long-context 3D volume slicing, and whole-slide pathology sampling. Compared to MedGemma 1 4B, MedGemma 1.5 4B demonstrates significant gains in these new areas, improving 3D MRI condition classification accuracy by 11% and 3D CT condition classification by 3% (absolute improvements). In whole slide pathology imaging, MedGemma 1.5 4B achieves a 47% macro F1 gain. Additionally, it improves anatomical localization with a 35% increase in Intersection over Union on chest X-rays and achieves a 4% macro accuracy for longitudinal (multi-timepoint) chest x-ray analysis. Beyond its improved multimodal performance over MedGemma 1, MedGemma 1.5 improves on text-based clinical knowledge and reasoning, improving by 5% on MedQA accuracy and 22% on EHRQA accuracy. It also achieves an average of 18% macro F1 on 4 different lab report information extraction datasets (EHR Datasets 2, 3, 4, and Mendeley Clinical Laboratory Test Reports). Taken together, MedGemma 1.5 serves as a robust, open resource for the community, designed as an improved foundation on which developers can create the next generation of medical AI systems. Resources and tutorials for building upon MedGemma 1.5 can be found at https://goo.gle/MedGemma.

Computational pathology, which involves analyzing whole slide images for automated cancer diagnosis, relies on multiple instance learning, where performance depends heavily on the feature extractor and aggregator. Recent Pathology Foundation Models (PFMs), pretrained on large-scale histopathology data, have significantly enhanced both the extractor and aggregator, but they lack a systematic analysis framework. In this survey, we present a hierarchical taxonomy organizing PFMs through a top-down philosophy applicable to foundation model analysis in any domain: model scope, model pretraining, and model design. Additionally, we systematically categorize PFM evaluation tasks into slide-level, patch-level, multimodal, and biological tasks, providing comprehensive benchmarking criteria. Our analysis identifies critical challenges in both PFM development (pathology-specific methodology, end-to-end pretraining, data-model scalability) and utilization (effective adaptation, model maintenance), paving the way for future directions in this promising field. Resources referenced in this survey are available at https://github.com/BearCleverProud/AwesomeWSI.

Advancing AI in computational pathology requires large, high-quality, and diverse datasets, yet existing public datasets are often limited in organ diversity, class coverage, or annotation quality. To bridge this gap, we introduce SPIDER (Supervised Pathology Image-DEscription Repository), the largest publicly available patch-level dataset covering multiple organ types, including Skin, Colorectal, and Thorax, with comprehensive class coverage for each organ. SPIDER provides high-quality annotations verified by expert pathologists and includes surrounding context patches, which enhance classification performance by providing spatial context. Alongside the dataset, we present baseline models trained on SPIDER using the Hibou-L foundation model as a feature extractor combined with an attention-based classification head. The models achieve state-of-the-art performance across multiple tissue categories and serve as strong benchmarks for future digital pathology research. Beyond patch classification, the model enables rapid identification of significant areas, quantitative tissue metrics, and establishes a foundation for multimodal approaches. Both the dataset and trained models are publicly available to advance research, reproducibility, and AI-driven pathology development. Access them at: https://github.com/HistAI/SPIDER

The field of computational pathology has been transformed with recent advances in foundation models that encode histopathology region-of-interests (ROIs) into versatile and transferable feature representations via self-supervised learning (SSL). However, translating these advancements to address complex clinical challenges at the patient and slide level remains constrained by limited clinical data in disease-specific cohorts, especially for rare clinical conditions. We propose TITAN, a multimodal whole slide foundation model pretrained using 335,645 WSIs via visual self-supervised learning and vision-language alignment with corresponding pathology reports and 423,122 synthetic captions generated from a multimodal generative AI copilot for pathology. Without any finetuning or requiring clinical labels, TITAN can extract general-purpose slide representations and generate pathology reports that generalize to resource-limited clinical scenarios such as rare disease retrieval and cancer prognosis. We evaluate TITAN on diverse clinical tasks and find that TITAN outperforms both ROI and slide foundation models across machine learning settings such as linear probing, few-shot and zero-shot classification, rare cancer retrieval and cross-modal retrieval, and pathology report generation.

Computational pathology foundation models (CPathFMs) have emerged as a powerful approach for analyzing histopathological data, leveraging self-supervised learning to extract robust feature representations from unlabeled whole-slide images. These models, categorized into uni-modal and multi-modal frameworks, have demonstrated promise in automating complex pathology tasks such as segmentation, classification, and biomarker discovery. However, the development of CPathFMs presents significant challenges, such as limited data accessibility, high variability across datasets, the necessity for domain-specific adaptation, and the lack of standardized evaluation benchmarks. This survey provides a comprehensive review of CPathFMs in computational pathology, focusing on datasets, adaptation strategies, and evaluation tasks. We analyze key techniques, such as contrastive learning and multi-modal integration, and highlight existing gaps in current research. Finally, we explore future directions from four perspectives for advancing CPathFMs. This survey serves as a valuable resource for researchers, clinicians, and AI practitioners, guiding the advancement of CPathFMs toward robust and clinically applicable AI-driven pathology solutions.

Computational pathology can lead to saving human lives, but models are annotation hungry and pathology images are notoriously expensive to annotate. Self-supervised learning has shown to be an effective method for utilizing unlabeled data, and its application to pathology could greatly benefit its downstream tasks. Yet, there are no principled studies that compare SSL methods and discuss how to adapt them for pathology. To address this need, we execute the largest-scale study of SSL pre-training on pathology image data, to date. Our study is conducted using 4 representative SSL methods on diverse downstream tasks. We establish that large-scale domain-aligned pre-training in pathology consistently out-performs ImageNet pre-training in standard SSL settings such as linear and fine-tuning evaluations, as well as in low-label regimes. Moreover, we propose a set of domain-specific techniques that we experimentally show leads to a performance boost. Lastly, for the first time, we apply SSL to the challenging task of nuclei instance segmentation and show large and consistent performance improvements under diverse settings.

Objective:Develop and validate an algorithm for analyzing the layout of PDF clinical documents to improve the performance of downstream natural language processing tasks. Materials and Methods: We designed an algorithm to process clinical PDF documents and extract only clinically relevant text. The algorithm consists of several steps: initial text extraction using a PDF parser, followed by classification into categories such as body text, left notes, and footers using a Transformer deep neural network architecture, and finally an aggregation step to compile the lines of a given label in the text. We evaluated the technical performance of the body text extraction algorithm by applying it to a random sample of documents that were annotated. Medical performance was evaluated by examining the extraction of medical concepts of interest from the text in their respective sections. Finally, we tested an end-to-end system on a medical use case of automatic detection of acute infection described in the hospital report. Results:Our algorithm achieved per-line precision, recall, and F1 score of 98.4, 97.0, and 97.7, respectively, for body line extraction. The precision, recall, and F1 score per document for the acute infection detection algorithm were 82.54 (95CI 72.86-91.60), 85.24 (95CI 76.61-93.70), 83.87 (95CI 76, 92-90.08) with exploitation of the results of the advanced body extraction algorithm, respectively. Conclusion:We have developed and validated a system for extracting body text from clinical documents in PDF format by identifying their layout. We were able to demonstrate that this preprocessing allowed us to obtain better performances for a common downstream task, i.e., the extraction of medical concepts in their respective sections, thus proving the interest of this method on a clinical use case.

The field of computational pathology has recently seen rapid advances driven by the development of modern vision foundation models (FMs), typically trained on vast collections of pathology images. Recent studies demonstrate that increasing the training data set and model size and integrating domain-specific image processing techniques can significantly enhance the model's performance on downstream tasks. Building on these insights, our work incorporates several recent modifications to the standard DINOv2 framework from the literature to optimize the training of pathology FMs. We also apply a post-training procedure for fine-tuning models on higher-resolution images to further enrich the information encoded in the embeddings. We present three novel pathology FMs trained on up to two orders of magnitude fewer WSIs than those used to train other state-of-the-art FMs while demonstrating a comparable or superior performance on downstream tasks. Even the model trained on TCGA alone (12k WSIs) outperforms most existing FMs and, on average, matches Virchow2, the second-best FM published to date. This suggests that there still remains a significant potential for further improving the models and algorithms used to train pathology FMs to take full advantage of the vast data collections.

The recent surge of foundation models in computer vision and natural language processing opens up perspectives in utilizing multi-modal clinical data to train large models with strong generalizability. Yet pathological image datasets often lack biomedical text annotation and enrichment. Guiding data-efficient image diagnosis from the use of biomedical text knowledge becomes a substantial interest. In this paper, we propose to Connect Image and Text Embeddings (CITE) to enhance pathological image classification. CITE injects text insights gained from language models pre-trained with a broad range of biomedical texts, leading to adapt foundation models towards pathological image understanding. Through extensive experiments on the PatchGastric stomach tumor pathological image dataset, we demonstrate that CITE achieves leading performance compared with various baselines especially when training data is scarce. CITE offers insights into leveraging in-domain text knowledge to reinforce data-efficient pathological image classification. Code is available at https://github.com/Yunkun-Zhang/CITE.

Medical images and radiology reports are crucial for diagnosing medical conditions, highlighting the importance of quantitative analysis for clinical decision-making. However, the diversity and cross-source heterogeneity of these data challenge the generalizability of current data-mining methods. Multimodal large language models (MLLMs) have recently transformed many domains, significantly affecting the medical field. Notably, Gemini-Vision-series (Gemini) and GPT-4-series (GPT-4) models have epitomized a paradigm shift in Artificial General Intelligence (AGI) for computer vision, showcasing their potential in the biomedical domain. In this study, we evaluated the performance of the Gemini, GPT-4, and 4 popular large models for an exhaustive evaluation across 14 medical imaging datasets, including 5 medical imaging categories (dermatology, radiology, dentistry, ophthalmology, and endoscopy), and 3 radiology report datasets. The investigated tasks encompass disease classification, lesion segmentation, anatomical localization, disease diagnosis, report generation, and lesion detection. Our experimental results demonstrated that Gemini-series models excelled in report generation and lesion detection but faces challenges in disease classification and anatomical localization. Conversely, GPT-series models exhibited proficiency in lesion segmentation and anatomical localization but encountered difficulties in disease diagnosis and lesion detection. Additionally, both the Gemini series and GPT series contain models that have demonstrated commendable generation efficiency. While both models hold promise in reducing physician workload, alleviating pressure on limited healthcare resources, and fostering collaboration between clinical practitioners and artificial intelligence technologies, substantial enhancements and comprehensive validations remain imperative before clinical deployment.

Recent advancements in Digital Pathology (DP), particularly through artificial intelligence and Foundation Models, have underscored the importance of large-scale, diverse, and richly annotated datasets. Despite their critical role, publicly available Whole Slide Image (WSI) datasets often lack sufficient scale, tissue diversity, and comprehensive clinical metadata, limiting the robustness and generalizability of AI models. In response, we introduce the HISTAI dataset, a large, multimodal, open-access WSI collection comprising over 60,000 slides from various tissue types. Each case in the HISTAI dataset is accompanied by extensive clinical metadata, including diagnosis, demographic information, detailed pathological annotations, and standardized diagnostic coding. The dataset aims to fill gaps identified in existing resources, promoting innovation, reproducibility, and the development of clinically relevant computational pathology solutions. The dataset can be accessed at https://github.com/HistAI/HISTAI.

Multimodal pathology-genomic analysis is critical for cancer survival prediction. However, existing approaches predominantly integrate formalin-fixed paraffin-embedded (FFPE) slides with genomic data, while neglecting the availability of other preservation slides, such as Fresh Froze (FF) slides. Moreover, as the high-resolution spatial nature of pathology data tends to dominate the cross-modality fusion process, it hinders effective multimodal fusion and leads to modality imbalance challenges between pathology and genomics. These methods also typically require complete data modalities, limiting their clinical applicability with incomplete modalities, such as missing either pathology or genomic data. In this paper, we propose a multimodal survival prediction framework that leverages hypergraph learning to effectively integrate multi-WSI information and cross-modality interactions between pathology slides and genomics data while addressing modality imbalance. In addition, we introduce a memory mechanism that stores previously learned paired pathology-genomic features and dynamically compensates for incomplete modalities. Experiments on five TCGA datasets demonstrate that our model outperforms advanced methods by over 2.3% in C-Index. Under incomplete modality scenarios, our approach surpasses pathology-only (3.3%) and gene-only models (7.9%). Code: https://github.com/MCPathology/M2Surv

The increasing interest in developing Artificial Intelligence applications in the medical domain, suffers from the lack of high-quality dataset, mainly due to privacy-related issues. Moreover, the recent rising of Multimodal Large Language Models (MLLM) leads to a need for multimodal medical datasets, where clinical reports and findings are attached to the corresponding CT or MR scans. This paper illustrates the entire workflow for building the data set MedPix 2.0. Starting from the well-known multimodal dataset MedPix\textregistered, mainly used by physicians, nurses and healthcare students for Continuing Medical Education purposes, a semi-automatic pipeline was developed to extract visual and textual data followed by a manual curing procedure where noisy samples were removed, thus creating a MongoDB database. Along with the dataset, we developed a GUI aimed at navigating efficiently the MongoDB instance, and obtaining the raw data that can be easily used for training and/or fine-tuning MLLMs. To enforce this point, we also propose a CLIP-based model trained on MedPix 2.0 for scan classification tasks.

In computational pathology, understanding and generation have evolved along disparate paths: advanced understanding models already exhibit diagnostic-level competence, whereas generative models largely simulate pixels. Progress remains hindered by three coupled factors: the scarcity of large, high-quality image-text corpora; the lack of precise, fine-grained semantic control, which forces reliance on non-semantic cues; and terminological heterogeneity, where diverse phrasings for the same diagnostic concept impede reliable text conditioning. We introduce UniPath, a semantics-driven pathology image generation framework that leverages mature diagnostic understanding to enable controllable generation. UniPath implements Multi-Stream Control: a Raw-Text stream; a High-Level Semantics stream that uses learnable queries to a frozen pathology MLLM to distill paraphrase-robust Diagnostic Semantic Tokens and to expand prompts into diagnosis-aware attribute bundles; and a Prototype stream that affords component-level morphological control via a prototype bank. On the data front, we curate a 2.65M image-text corpus and a finely annotated, high-quality 68K subset to alleviate data scarcity. For a comprehensive assessment, we establish a four-tier evaluation hierarchy tailored to pathology. Extensive experiments demonstrate UniPath's SOTA performance, including a Patho-FID of 80.9 (51% better than the second-best) and fine-grained semantic control achieving 98.7% of the real-image. The meticulously curated datasets, complete source code, and pre-trained model weights developed in this study will be made openly accessible to the public.

Several medical Multimodal Large Languange Models (MLLMs) have been developed to address tasks involving visual images with textual instructions across various medical modalities, achieving impressive results. Most current medical generalist models are region-agnostic, treating the entire image as a holistic representation. However, they struggle to identify which specific regions they are focusing on when generating a sentence. To mimic the behavior of doctors, who typically begin by reviewing the entire image before concentrating on specific regions for a thorough evaluation, we aim to enhance the capability of medical MLLMs in understanding anatomical regions within entire medical scans. To achieve it, we first formulate Region-Centric tasks and construct a large-scale dataset, MedRegInstruct, to incorporate regional information into training. Combining our collected dataset with other medical multimodal corpora for training, we propose a Region-Aware medical MLLM, MedRegA, which is the first bilingual generalist medical AI system to simultaneously handle image-level and region-level medical vision-language tasks across a broad range of modalities. Our MedRegA not only enables three region-centric tasks, but also achieves the best performance for visual question answering, report generation and medical image classification over 8 modalities, showcasing significant versatility. Experiments demonstrate that our model can not only accomplish powerful performance across various medical vision-language tasks in bilingual settings, but also recognize and detect structures in multimodal medical scans, boosting the interpretability and user interactivity of medical MLLMs. Our project page is https://medrega.github.io.

Computational pathology (CPath) digitizes pathology slides into whole slide images (WSIs), enabling analysis for critical healthcare tasks such as cancer diagnosis and prognosis. However, WSIs possess extremely long sequence lengths (up to 200K), significant length variations (from 200 to 200K), and limited supervision. These extreme variations in sequence length lead to high data heterogeneity and redundancy. Conventional methods often compromise on training efficiency and optimization to preserve such heterogeneity under limited supervision. To comprehensively address these challenges, we propose a pack-based MIL framework. It packs multiple sampled, variable-length feature sequences into fixed-length ones, enabling batched training while preserving data heterogeneity. Moreover, we introduce a residual branch that composes discarded features from multiple slides into a hyperslide which is trained with tailored labels. It offers multi-slide supervision while mitigating feature loss from sampling. Meanwhile, an attention-driven downsampler is introduced to compress features in both branches to reduce redundancy. By alleviating these challenges, our approach achieves an accuracy improvement of up to 8% while using only 12% of the training time in the PANDA(UNI). Extensive experiments demonstrate that focusing data challenges in CPath holds significant potential in the era of foundation models. The code is https://github.com/FangHeng/PackMIL

Digital pathology enables automatic analysis of histopathological sections using artificial intelligence (AI). Automatic evaluation could improve diagnostic efficiency and help find associations between morphological features and clinical outcome. For development of such prediction models, identifying invasive epithelial cells, and separating these from benign epithelial cells and in situ lesions would be the first step. In this study, we aimed to develop an AI model for segmentation of epithelial cells in sections from breast cancer. We generated epithelial ground truth masks by restaining hematoxylin and eosin (HE) sections with cytokeratin (CK) AE1/AE3, and by pathologists' annotations. HE/CK image pairs were used to train a convolutional neural network, and data augmentation was used to make the model more robust. Tissue microarrays (TMAs) from 839 patients, and whole slide images from two patients were used for training and evaluation of the models. The sections were derived from four cohorts of breast cancer patients. TMAs from 21 patients from a fifth cohort was used as a second test set. In quantitative evaluation, a mean Dice score of 0.70, 0.79, and 0.75 for invasive epithelial cells, benign epithelial cells, and in situ lesions, respectively, were achieved. In qualitative scoring (0-5) by pathologists, results were best for all epithelium and invasive epithelium, with scores of 4.7 and 4.4. Scores for benign epithelium and in situ lesions were 3.7 and 2.0. The proposed model segmented epithelial cells in HE stained breast cancer slides well, but further work is needed for accurate division between the classes. Immunohistochemistry, together with pathologists' annotations, enabled the creation of accurate ground truths. The model is made freely available in FastPathology and the code is available at https://github.com/AICAN-Research/breast-epithelium-segmentation

Generating clinically useful pathology reports for pathology cases from whole-slide images (WSIs) is challenging due to gigapixel resolution, long visual-token sequences, and the complexity of case-level reasoning, where a single case may contain multiple WSIs with heterogeneous tissues and ambiguous findings. We present a simple token-efficient vision--language model for case-level synoptic report generation that remains practical under constrained GPU memory. Our architecture follows a minimal three-component design: a frozen pathology patch encoder, a lightweight two-layer MLP vision-language aligner, and a large language model decoder, with an explicit WSI marker token to separate slides within a case. Training proceeds in two supervised stages: (1) aligner-only WSI captioning using heterogeneous WSI-text pairs, and (2) case-level supervised fine-tuning on case-report pairs for structured report generation. To reduce sequence length, we represent each slide using 512 times 512 patches at 5times magnification, which reduces the average sequence length by up to 64times times compared to the commonly used 20times patches. Combined with efficient training techniques, we enable practical training with only half a NVIDIA H100 GPU. Across both training stages, our approach achieves high ROUGE-L/METEOR/BLEU-4 scores while being substantially more efficient in memory and runtime. In AI-based evaluations, our model is consistently preferred over strong baselines. Extensive ablations characterize performance-efficiency trade-offs and identify simple choices that improve robustness in multi-WSI settings. Overall, this work provides a strong, reproducible baseline for efficient pathology report generation, lowering the barrier to multi-WSI VLM research under limited compute.

Foundation models in computational pathology promise to unlock the development of new clinical decision support systems and models for precision medicine. However, there is a mismatch between most clinical analysis, which is defined at the level of one or more whole slide images, and foundation models to date, which process the thousands of image tiles contained in a whole slide image separately. The requirement to train a network to aggregate information across a large number of tiles in multiple whole slide images limits these models' impact. In this work, we present a slide-level foundation model for H&E-stained histopathology, PRISM, that builds on Virchow tile embeddings and leverages clinical report text for pre-training. Using the tile embeddings, PRISM produces slide-level embeddings with the ability to generate clinical reports, resulting in several modes of use. Using text prompts, PRISM achieves zero-shot cancer detection and sub-typing performance approaching and surpassing that of a supervised aggregator model. Using the slide embeddings with linear classifiers, PRISM surpasses supervised aggregator models. Furthermore, we demonstrate that fine-tuning of the PRISM slide encoder yields label-efficient training for biomarker prediction, a task that typically suffers from low availability of training data; an aggregator initialized with PRISM and trained on as little as 10% of the training data can outperform a supervised baseline that uses all of the data.

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

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

Hepato-pancreato-biliary (HPB) disorders represent a global public health challenge due to their high morbidity and mortality. Although large language models (LLMs) have shown promising performance in general medical question-answering tasks, the current evaluation benchmarks are mostly derived from standardized examinations or manually designed questions, lacking HPB coverage and clinical cases. To address these issues, we systematically eatablish an HPB disease evaluation benchmark comprising 3,535 closed-ended multiple-choice questions and 337 open-ended real diagnosis cases, which encompasses all the 33 main categories and 465 subcategories of HPB diseases defined in the International Statistical Classification of Diseases, 10th Revision (ICD-10). The multiple-choice questions are curated from public datasets and synthesized data, and the clinical cases are collected from prestigious medical journals, case-sharing platforms, and collaborating hospitals. By evalauting commercial and open-source general and medical LLMs on our established benchmark, namely ClinBench-HBP, we find that while commercial LLMs perform competently on medical exam questions, they exhibit substantial performance degradation on HPB diagnosis tasks, especially on complex, inpatient clinical cases. Those medical LLMs also show limited generalizability to HPB diseases. Our results reveal the critical limitations of current LLMs in the domain of HPB diseases, underscoring the imperative need for future medical LLMs to handle real, complex clinical diagnostics rather than simple medical exam questions. The benchmark will be released at https://clinbench-hpb.github.io.

Computational pathology has made significant progress in recent years, fueling advances in both fundamental disease understanding and clinically ready tools. This evolution is driven by the availability of large amounts of digitized slides and specialized deep learning methods and models. Multiple self-supervised foundation feature extractors have been developed, enabling downstream predictive applications from cell segmentation to tumor sub-typing and survival analysis. In contrast, generative foundation models designed specifically for histopathology remain scarce. Such models could address tasks that are beyond the capabilities of feature extractors, such as virtual staining. In this paper, we introduce CytoSyn, a state-of-the-art foundation latent diffusion model that enables the guided generation of highly realistic and diverse histopathology H&E-stained images, as shown in an extensive benchmark. We explored methodological improvements, training set scaling, sampling strategies and slide-level overfitting, culminating in the improved CytoSyn-v2, and compared our work to PixCell, a state-of-the-art model, in an in-depth manner. This comparison highlighted the strong sensitivity of both diffusion models and performance metrics to preprocessing-specific details such as JPEG compression. Our model has been trained on a dataset obtained from more than 10,000 TCGA diagnostic whole-slide images of 32 different cancer types. Despite being trained only on oncology slides, it maintains state-of-the-art performance generating inflammatory bowel disease images. To support the research community, we publicly release CytoSyn's weights, its training and validation datasets, and a sample of synthetic images in this repository: https://huggingface.co/Owkin-Bioptimus/CytoSyn.

This paper introduces MedTrinity-25M, a comprehensive, large-scale multimodal dataset for medicine, covering over 25 million images across 10 modalities, with multigranular annotations for more than 65 diseases. These enriched annotations encompass both global textual information, such as disease/lesion type, modality, region-specific descriptions, and inter-regional relationships, as well as detailed local annotations for regions of interest (ROIs), including bounding boxes, segmentation masks. Unlike existing approach which is limited by the availability of image-text pairs, we have developed the first automated pipeline that scales up multimodal data by generating multigranular visual and texual annotations (in the form of image-ROI-description triplets) without the need for any paired text descriptions. Specifically, data from over 90 different sources have been collected, preprocessed, and grounded using domain-specific expert models to identify ROIs related to abnormal regions. We then build a comprehensive knowledge base and prompt multimodal large language models to perform retrieval-augmented generation with the identified ROIs as guidance, resulting in multigranular texual descriptions. Compared to existing datasets, MedTrinity-25M provides the most enriched annotations, supporting a comprehensive range of multimodal tasks such as captioning and report generation, as well as vision-centric tasks like classification and segmentation. Pretraining on MedTrinity-25M, our model achieves state-of-the-art performance on VQA-RAD and PathVQA, surpassing both multimodal large language models and other representative SoTA approaches. This dataset can also be utilized to support large-scale pre-training of multimodal medical AI models, contributing to the development of future foundation models in the medical domain.

Deep learning has enabled the development of highly robust foundation models for various pathological tasks across diverse diseases and patient cohorts. Among these models, vision-language pre-training, which leverages large-scale paired data to align pathology image and text embedding spaces, and provides a novel zero-shot paradigm for downstream tasks. However, existing models have been primarily data-driven and lack the incorporation of domain-specific knowledge, which limits their performance in cancer diagnosis, especially for rare tumor subtypes. To address this limitation, we establish a Knowledge-enhanced Pathology (KEEP) foundation model that harnesses disease knowledge to facilitate vision-language pre-training. Specifically, we first construct a disease knowledge graph (KG) that covers 11,454 human diseases with 139,143 disease attributes, including synonyms, definitions, and hypernym relations. We then systematically reorganize the millions of publicly available noisy pathology image-text pairs, into 143K well-structured semantic groups linked through the hierarchical relations of the disease KG. To derive more nuanced image and text representations, we propose a novel knowledge-enhanced vision-language pre-training approach that integrates disease knowledge into the alignment within hierarchical semantic groups instead of unstructured image-text pairs. Validated on 18 diverse benchmarks with more than 14,000 whole slide images (WSIs), KEEP achieves state-of-the-art performance in zero-shot cancer diagnostic tasks. Notably, for cancer detection, KEEP demonstrates an average sensitivity of 89.8% at a specificity of 95.0% across 7 cancer types. For cancer subtyping, KEEP achieves a median balanced accuracy of 0.456 in subtyping 30 rare brain cancers, indicating strong generalizability for diagnosing rare tumors.

Digital hematopathology requires cell-level analysis across diverse disease categories, including malignant disorders (e.g., leukemia), infectious conditions (e.g., malaria), and non-malignant red blood cell disorders (e.g., sickle cell disease). Whether single-task, vision-language, WSI-optimized, or single-cell hematology models, these approaches share a key limitation, they cannot provide unified, multi-task, multi-modal reasoning across the complexities of digital hematopathology. To overcome these limitations, we propose Uni-Hema, a multi-task, unified model for digital hematopathology integrating detection, classification, segmentation, morphology prediction, and reasoning across multiple diseases. Uni-Hema leverages 46 publicly available datasets, encompassing over 700K images and 21K question-answer pairs, and is built upon Hema-Former, a multimodal module that bridges visual and textual representations at the hierarchy level for the different tasks (detection, classification, segmentation, morphology, mask language modeling and visual question answer) at different granularity. Extensive experiments demonstrate that Uni-Hema achieves comparable or superior performance to train on a single-task and single dataset models, across diverse hematological tasks, while providing interpretable, morphologically relevant insights at the single-cell level. Our framework establishes a new standard for multi-task and multi-modal digital hematopathology. The code will be made publicly available.

Medical vision-and-language models (MVLMs) have attracted substantial interest due to their capability to offer a natural language interface for interpreting complex medical data. Their applications are versatile and have the potential to improve diagnostic accuracy and decision-making for individual patients while also contributing to enhanced public health monitoring, disease surveillance, and policy-making through more efficient analysis of large data sets. MVLMS integrate natural language processing with medical images to enable a more comprehensive and contextual understanding of medical images alongside their corresponding textual information. Unlike general vision-and-language models trained on diverse, non-specialized datasets, MVLMs are purpose-built for the medical domain, automatically extracting and interpreting critical information from medical images and textual reports to support clinical decision-making. Popular clinical applications of MVLMs include automated medical report generation, medical visual question answering, medical multimodal segmentation, diagnosis and prognosis and medical image-text retrieval. Here, we provide a comprehensive overview of MVLMs and the various medical tasks to which they have been applied. We conduct a detailed analysis of various vision-and-language model architectures, focusing on their distinct strategies for cross-modal integration/exploitation of medical visual and textual features. We also examine the datasets used for these tasks and compare the performance of different models based on standardized evaluation metrics. Furthermore, we highlight potential challenges and summarize future research trends and directions. The full collection of papers and codes is available at: https://github.com/YtongXie/Medical-Vision-and-Language-Tasks-and-Methodologies-A-Survey.

Pathology foundation models (FMs) have driven significant progress in computational pathology. However, these high-performing models can easily exceed a billion parameters and produce high-dimensional embeddings, thus limiting their applicability for research or clinical use when computing resources are tight. Here, we introduce Pathryoshka, a multi-teacher distillation framework inspired by RADIO distillation and Matryoshka Representation Learning to reduce pathology FM sizes while allowing for adaptable embedding dimensions. We evaluate our framework with a distilled model on ten public pathology benchmarks with varying downstream tasks. Compared to its much larger teachers, Pathryoshka reduces the model size by 86-92% at on-par performance. It outperforms state-of-the-art single-teacher distillation models of comparable size by a median margin of 7.0 in accuracy. By enabling efficient local deployment without sacrificing accuracy or representational richness, Pathryoshka democratizes access to state-of-the-art pathology FMs for the broader research and clinical community.

Medical imaging is critical to the diagnosis and treatment of numerous medical problems, including many forms of cancer. Medical imaging reports distill the findings and observations of radiologists, creating an unstructured textual representation of unstructured medical images. Large-scale use of this text-encoded information requires converting the unstructured text to a structured, semantic representation. We explore the extraction and normalization of anatomical information in radiology reports that is associated with radiological findings. We investigate this extraction and normalization task using a span-based relation extraction model that jointly extracts entities and relations using BERT. This work examines the factors that influence extraction and normalization performance, including the body part/organ system, frequency of occurrence, span length, and span diversity. It discusses approaches for improving performance and creating high-quality semantic representations of radiological phenomena.

Medical image analysis is essential to clinical diagnosis and treatment, which is increasingly supported by multi-modal large language models (MLLMs). However, previous research has primarily focused on 2D medical images, leaving 3D images under-explored, despite their richer spatial information. This paper aims to advance 3D medical image analysis with MLLMs. To this end, we present a large-scale 3D multi-modal medical dataset, M3D-Data, comprising 120K image-text pairs and 662K instruction-response pairs specifically tailored for various 3D medical tasks, such as image-text retrieval, report generation, visual question answering, positioning, and segmentation. Additionally, we propose M3D-LaMed, a versatile multi-modal large language model for 3D medical image analysis. Furthermore, we introduce a new 3D multi-modal medical benchmark, M3D-Bench, which facilitates automatic evaluation across eight tasks. Through comprehensive evaluation, our method proves to be a robust model for 3D medical image analysis, outperforming existing solutions. All code, data, and models are publicly available at: https://github.com/BAAI-DCAI/M3D.

Vision-and-language pretraining (VLP) in the medical field utilizes contrastive learning on image-text pairs to achieve effective transfer across tasks. Yet, current VLP approaches with the masked modeling strategy face two challenges when applied to the medical domain. First, current models struggle to accurately reconstruct key pathological features due to the scarcity of medical data. Second, most methods only adopt either paired image-text or image-only data, failing to exploit the combination of both paired and unpaired data. To this end, this paper proposes the MMCLIP (Masked Medical Contrastive Language-Image Pre-Training) framework to enhance pathological learning and feature learning via unpaired data. First, we introduce the attention-masked image modeling (AttMIM) and entity-driven masked language modeling module (EntMLM), which learns to reconstruct pathological visual and textual tokens via multi-modal feature interaction, thus improving medical-enhanced features. The AttMIM module masks a portion of the image features that are highly responsive to textual features. This allows MMCLIP to improve the reconstruction of highly similar image data in medicine efficiency. Second, our MMCLIP capitalizes unpaired data to enhance multimodal learning by introducing disease-kind prompts. The experimental results show that MMCLIP achieves SOTA for zero-shot and fine-tuning classification performance on five datasets. Our code will be available at https://github.com/AIGeeksGroup/MMCLIP.

Recent advancements in digital pathology have led to the development of numerous foundational models that utilize self-supervised learning on patches extracted from gigapixel whole slide images (WSIs). While this approach leverages vast amounts of unlabeled data, we have discovered a significant issue: features extracted from these self-supervised models tend to cluster by individual WSIs, a phenomenon we term WSI-specific feature collapse. This problem can potentially limit the model's generalization ability and performance on various downstream tasks. To address this issue, we introduce Stain Normalized Pathology Foundational Model, a novel foundational model trained on patches that have undergone stain normalization. Stain normalization helps reduce color variability arising from different laboratories and scanners, enabling the model to learn more consistent features. Stain Normalized Pathology Foundational Model is trained using 285,153,903 patches extracted from a total of 34,795 WSIs, combining data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) project. Our experiments demonstrate that Stain Normalized Pathology Foundational Model significantly mitigates the feature collapse problem, indicating that the model has learned more generalized features rather than overfitting to individual WSI characteristics. We compared Stain Normalized Pathology Foundational Model with state-of-the-art models across six downstream task datasets, and our results show that Stain Normalized Pathology Foundational Model achieves excellent performance relative to the number of WSIs used and the model's parameter count. This suggests that the application of stain normalization has substantially improved the model's efficiency and generalization capabilities.

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

Medical imaging artificial intelligence has achieved strong performance in isolated image interpretation, but remains poorly aligned with radiological practice, where diagnosis and follow-up rely on comparison across prior studies and analogous reference cases. Here we formulate radiological comparison as an entity-aware cross-image reasoning problem and introduce a framework that supports both reference-case retrieval and temporal comparative interpretation. We construct MedReCo-DB, a large-scale comparative imaging resource derived from routine image-report pairs, comprising more than 690,000 images from over 160,000 patients across eight institutions, four countries and seven imaging modalities. Reports are decomposed into anatomical structures, abnormal findings and pathological conditions to provide supervision for entity-conditioned retrieval and comparative visual question answering. Using this resource, we develop MedReCo, an entity-aware visual encoder for controllable retrieval of clinically analogous cases, and MedReCo-VLM, a vision--language extension for generative interpretation of interval change. Across internal, external and cross-center evaluations, MedReCo achieved the highest Recall@1 in all 12 internal retrieval settings and improved external retrieval by a mean of 6.0 percentage points. In clinically confusable differential groups, it consistently outperformed the strongest baselines. MedReCo-VLM achieved the best performance across all comparative generation evaluations and improved longitudinal follow-up accuracy by 14.5-46.5 percentage points on chest radiographs and 13.0-27.9 percentage points on CT. These findings suggest that entity-aware comparative reasoning can be learned from routine clinical data at scale and may provide a more clinically aligned foundation for medical imaging AI.

Considering the increased workload in pathology laboratories today, automated tools such as artificial intelligence models can help pathologists with their tasks and ease the workload. In this paper, we are proposing a segmentation model (DRU-Net) that can provide a delineation of human non-small cell lung carcinomas and an augmentation method that can improve classification results. The proposed model is a fused combination of truncated pre-trained DenseNet201 and ResNet101V2 as a patch-wise classifier followed by a lightweight U-Net as a refinement model. We have used two datasets (Norwegian Lung Cancer Biobank and Haukeland University Hospital lung cancer cohort) to create our proposed model. The DRU-Net model achieves an average of 0.91 Dice similarity coefficient. The proposed spatial augmentation method (multi-lens distortion) improved the network performance by 3%. Our findings show that choosing image patches that specifically include regions of interest leads to better results for the patch-wise classifier compared to other sampling methods. The qualitative analysis showed that the DRU-Net model is generally successful in detecting the tumor. On the test set, some of the cases showed areas of false positive and false negative segmentation in the periphery, particularly in tumors with inflammatory and reactive changes.

Timely and accurate lymphoma diagnosis is essential for guiding cancer treatment. Standard diagnostic practice combines hematoxylin and eosin (HE)-stained whole slide images with immunohistochemistry, flow cytometry, and molecular genetic tests to determine lymphoma subtypes, a process requiring costly equipment, skilled personnel, and causing treatment delays. Deep learning methods could assist pathologists by extracting diagnostic information from routinely available HE-stained slides, yet comprehensive benchmarks for lymphoma subtyping on multicenter data are lacking. In this work, we present the first multicenter lymphoma benchmarking dataset covering four common lymphoma subtypes and healthy control tissue. We systematically evaluate five publicly available pathology foundation models (H-optimus-1, H0-mini, Virchow2, UNI2, Titan) combined with attention-based (AB-MIL) and transformer-based (TransMIL) multiple instance learning aggregators across three magnifications (10x, 20x, 40x). On in-distribution test sets, models achieve multiclass balanced accuracies exceeding 80% across all magnifications, with all foundation models performing similarly and both aggregation methods showing comparable results. The magnification study reveals that 40x resolution is sufficient, with no performance gains from higher resolutions or cross-magnification aggregation. However, on out-of-distribution test sets, performance drops substantially to around 60%, highlighting significant generalization challenges. To advance the field, larger multicenter studies covering additional rare lymphoma subtypes are needed. We provide an automated benchmarking pipeline to facilitate such future research.

The emergence of large multimodal models has unlocked remarkable potential in AI, particularly in pathology. However, the lack of specialized, high-quality benchmark impeded their development and precise evaluation. To address this, we introduce PathMMU, the largest and highest-quality expert-validated pathology benchmark for LMMs. It comprises 33,573 multimodal multi-choice questions and 21,599 images from various sources, and an explanation for the correct answer accompanies each question. The construction of PathMMU capitalizes on the robust capabilities of GPT-4V, utilizing approximately 30,000 gathered image-caption pairs to generate Q\&As. Significantly, to maximize PathMMU's authority, we invite six pathologists to scrutinize each question under strict standards in PathMMU's validation and test sets, while simultaneously setting an expert-level performance benchmark for PathMMU. We conduct extensive evaluations, including zero-shot assessments of 14 open-sourced and three closed-sourced LMMs and their robustness to image corruption. We also fine-tune representative LMMs to assess their adaptability to PathMMU. The empirical findings indicate that advanced LMMs struggle with the challenging PathMMU benchmark, with the top-performing LMM, GPT-4V, achieving only a 51.7\% zero-shot performance, significantly lower than the 71.4\% demonstrated by human pathologists. After fine-tuning, even open-sourced LMMs can surpass GPT-4V with a performance of over 60\%, but still fall short of the expertise shown by pathologists. We hope that the PathMMU will offer valuable insights and foster the development of more specialized, next-generation LLMs for pathology.

The digitization of histology slides has revolutionized pathology, providing massive datasets for cancer diagnosis and research. Contrastive self-supervised and vision-language models have been shown to effectively mine large pathology datasets to learn discriminative representations. On the other hand, generative models, capable of synthesizing realistic and diverse images, present a compelling solution to address unique problems in pathology that involve synthesizing images; overcoming annotated data scarcity, enabling privacy-preserving data sharing, and performing inherently generative tasks, such as virtual staining. We introduce PixCell, the first diffusion-based generative foundation model for histopathology. We train PixCell on PanCan-30M, a vast, diverse dataset derived from 69,184 H\&E-stained whole slide images covering various cancer types. We employ a progressive training strategy and a self-supervision-based conditioning that allows us to scale up training without any annotated data. PixCell generates diverse and high-quality images across multiple cancer types, which we find can be used in place of real data to train a self-supervised discriminative model. Synthetic images shared between institutions are subject to fewer regulatory barriers than would be the case with real clinical images. Furthermore, we showcase the ability to precisely control image generation using a small set of annotated images, which can be used for both data augmentation and educational purposes. Testing on a cell segmentation task, a mask-guided PixCell enables targeted data augmentation, improving downstream performance. Finally, we demonstrate PixCell's ability to use H\&E structural staining to infer results from molecular marker studies; we use this capability to infer IHC staining from H\&E images. Our trained models are publicly released to accelerate research in computational pathology.

Mitotic figures are classified into typical and atypical variants, with atypical counts correlating strongly with tumor aggressiveness. Accurate differentiation is therefore essential for patient prognostication and resource allocation, yet remains challenging even for expert pathologists. Here, we leveraged Pathology Foundation Models (PFMs) pre-trained on large histopathology datasets and applied parameter-efficient fine-tuning via low-rank adaptation. In addition, we incorporated ConvNeXt V2, a state-of-the-art convolutional neural network architecture, to complement PFMs. During training, we employed a fisheye transform to emphasize mitoses and Fourier Domain Adaptation using ImageNet target images. Finally, we ensembled multiple PFMs to integrate complementary morphological insights, achieving competitive balanced accuracy on the Preliminary Evaluation Phase dataset.

Content generation modeling has emerged as a promising direction in computational pathology, offering capabilities such as data-efficient learning, synthetic data augmentation, and task-oriented generation across diverse diagnostic tasks. This review provides a comprehensive synthesis of recent progress in the field, organized into four key domains: image generation, text generation, molecular profile-morphology generation, and other specialized generation applications. By analyzing over 150 representative studies, we trace the evolution of content generation architectures -- from early generative adversarial networks to recent advances in diffusion models and generative vision-language models. We further examine the datasets and evaluation protocols commonly used in this domain and highlight ongoing limitations, including challenges in generating high-fidelity whole slide images, clinical interpretability, and concerns related to the ethical and legal implications of synthetic data. The review concludes with a discussion of open challenges and prospective research directions, with an emphasis on developing integrated and clinically deployable generation systems. This work aims to provide a foundational reference for researchers and practitioners developing content generation models in computational pathology.

Foundation models have recently achieved impressive success in computational pathology, demonstrating strong generalization across diverse histopathology tasks. However, existing models overlook the heterogeneous and non-uniform organization of pathological regions of interest (ROIs) because they rely on natural image backbones not tailored for tissue morphology. Consequently, they often fail to capture the coherent tissue architecture beyond isolated patches, limiting interpretability and clinical relevance. To address these challenges, we present Cross-modal Adaptive Region Encoder (CARE), a foundation model for pathology that automatically partitions WSIs into several morphologically relevant regions. Specifically, CARE employs a two-stage pretraining strategy: (1) a self-supervised unimodal pretraining stage that learns morphological representations from 34,277 whole-slide images (WSIs) without segmentation annotations, and (2) a cross-modal alignment stage that leverages RNA and protein profiles to refine the construction and representation of adaptive regions. This molecular guidance enables CARE to identify biologically relevant patterns and generate irregular yet coherent tissue regions, selecting the most representative area as ROI. CARE supports a broad range of pathology-related tasks, using either the ROI feature or the slide-level feature obtained by aggregating adaptive regions. Based on only one-tenth of the pretraining data typically used by mainstream foundation models, CARE achieves superior average performance across 33 downstream benchmarks, including morphological classification, molecular prediction, and survival analysis, and outperforms other foundation model baselines overall.