Ronald Cheong Kin Chan

Ling Liang, Jiabo Ma, Zhengyu Zhang et al.

Gastric cancer remains a major cause of cancer mortality, yet its histological and molecular heterogeneity complicates diagnosis and risk stratification. General-purpose pathology foundation models (PFMs) often plateau on fine-grained endpoints central to gastric cancer care, and few have undergone rigorous prospective validation or clinical reader studies. We present GRACE, a Gastric-specific foundation model for Real-world Assessment and Clinical dEcision support. GRACE was developed from multicenter gastric pathology datasets totaling 48,364 primarily HE-stained whole-slide images from 37,493 patients. When evaluated on 28 clinically relevant tasks, GRACE consistently outperformed representative pancancer PFMs, achieving a macro-AUC of 0.9188, with strong performance for precancerous lesion diagnosis (macro-AUC 0.9322), tumor histopathological assessment (macro-AUC 0.9119), molecular profiling (macro-AUC 0.8682), and prognostic prediction. Beyond benchmarking, GRACE's translational value was substantiated through a rigorous evidence chain. Under safety-gated criteria requiring 100% NPV for rule-out and 100% PPV for rule-in, GRACE streamlined review for up to 69.6% of malignancy-diagnosis cases and triaged 46.8% of MMR-IHC follow-up requests. This translational feasibility was further strengthened by a randomized crossover reader study of pathologist-AI collaboration. With GRACE assistance, diagnostic accuracy improved from 82.0% to 89.9%, yielding nearly twofold higher adjusted odds of a correct diagnosis (OR 1.987) alongside concurrent gains in sensitivity and specificity. AI assistance also reduced diagnostic time by 14.9%, elevated diagnostic confidence by 9.0%, and markedly improved inter-rater agreement. When calibrated to maintain non-inferior performance to senior pathologists, the AI-assisted workflow could triage 60.7% of atrophy and 82.7% of intestinal metaplasia cases.

Yingxue Xu, Yihui Wang, Fengtao Zhou et al.

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.

Jiabo Ma, Zhengrui Guo, Fengtao Zhou et al.

Foundation models pretrained on large-scale datasets are revolutionizing the field of computational pathology (CPath). The generalization ability of foundation models is crucial for the success in various downstream clinical tasks. However, current foundation models have only been evaluated on a limited type and number of tasks, leaving their generalization ability and overall performance unclear. To address this gap, we established a most comprehensive benchmark to evaluate the performance of off-the-shelf foundation models across six distinct clinical task types, encompassing a total of 72 specific tasks, including slide-level classification, survival prediction, ROI-tissue classification, ROI retrieval, visual question answering, and report generation. Our findings reveal that existing foundation models excel at certain task types but struggle to effectively handle the full breadth of clinical tasks. To improve the generalization of pathology foundation models, we propose a unified knowledge distillation framework consisting of both expert and self-knowledge distillation, where the former allows the model to learn from the knowledge of multiple expert models, while the latter leverages self-distillation to enable image representation learning via local-global alignment. Based on this framework, we curated a dataset of 96,000 whole slide images (WSIs) and developed a Generalizable Pathology Foundation Model (GPFM). This advanced model was trained on a substantial dataset comprising 190 million images extracted from approximately 72,000 publicly available slides, encompassing 34 major tissue types. Evaluated on the established benchmark, GPFM achieves an impressive average rank of 1.6, with 42 tasks ranked 1st, while the second-best model, UNI, attains an average rank of 3.7, with only 6 tasks ranked 1st.

Sunan He, Yuxiang Nie, Hongmei Wang et al.

Generalist foundation models (GFMs) are renowned for their exceptional capability and flexibility in effectively generalizing across diverse tasks and modalities. In the field of medicine, while GFMs exhibit superior generalizability based on their extensive intrinsic knowledge as well as proficiency in instruction following and in-context learning, specialist models excel in precision due to their domain knowledge. In this work, for the first time, we explore the synergy between the GFM and specialist models, to enable precise medical image analysis on a broader scope. Specifically, we propose a cooperative framework, Generalist-Specialist Collaboration (GSCo), which consists of two stages, namely the construction of GFM and specialists, and collaborative inference on downstream tasks. In the construction stage, we develop MedDr, the largest open-source GFM tailored for medicine, showcasing exceptional instruction-following and in-context learning capabilities. Meanwhile, a series of lightweight specialists are crafted for downstream tasks with low computational cost. In the collaborative inference stage, we introduce two cooperative mechanisms, Mixture-of-Expert Diagnosis and Retrieval-Augmented Diagnosis, to harvest the generalist's in-context learning abilities alongside the specialists' domain expertise. For a comprehensive evaluation, we curate a large-scale benchmark featuring 28 datasets and about 250,000 images. Extensive results demonstrate that MedDr consistently outperforms state-of-the-art GFMs on downstream datasets. Furthermore, GSCo exceeds both GFMs and specialists across all out-of-domain disease diagnosis datasets. These findings indicate a significant paradigm shift in the application of GFMs, transitioning from separate models for specific tasks to a collaborative approach between GFMs and specialists, thereby advancing the frontiers of generalizable AI in medicine.

Yingxue Xu, Zhengyu Zhang, Xiuming Zhang et al.

Pathology foundation models have shown strong retrospective performance, but whether such systems can support clinically relevant use remains unclear. This challenge is particularly important in breast cancer, where pathological assessment serves as the gold standard for diagnosis and guides treatment planning, surgical decision-making and risk stratification across pre-, intra- and post-operative stages. Here we present \textbf{BRAVE}, a breast-adaptive pathology foundation model developed and evaluated using a total resource of 101,638 breast whole-slide images from 32 sources across Asia, Europe and North America. We assessed BRAVE across 34 tasks in 82 cohorts spanning pre-operative biopsy, intra-operative frozen section and post-operative resection, using an evidence chain comprising retrospective benchmarking, clinically challenging scenarios, workflow-oriented clinical impact simulations, prospective observational validation with the thresholds locked in the retrospective cohorts and crossover pathologist-AI interaction studies. Across these settings, BRAVE supported practical roles in the clinical workflow, including safe exclusion of low-risk cases from routine review, AI-assisted second-review rescue of initially missed positives and prioritization of cases for further assessment. In prospective validation across three centres, BRAVE excluded 76.9% of negative biopsy cases (NPV 0.953) and 70.1% of negative frozen-section cases (NPV 0.973), and triaged 78.8% of post-operative subtyping cases as high-confidence clear-cut cases (NPV 1.000). In reader studies, AI assistance improved balanced accuracy from 88.5% to 95.1% (OR 3.14, P<0.001), with better efficiency, confidence and inter-rater agreement. BRAVE-derived scores also independently predicted disease-free survival (adjusted HR 4.79, P<0.001) and overall survival (adjusted HR 8.14, P<0.001).

Zhixuan Chen, Junlin Hou, Liqi Lin et al.

Pathology image segmentation is crucial in computational pathology for analyzing histological features relevant to cancer diagnosis and prognosis. However, current methods face major challenges in clinical applications due to limited annotated data and restricted category definitions. To address these limitations, we propose PathSegmentor, the first text-prompted segmentation foundation model designed specifically for pathology images. We also introduce PathSeg, the largest and most comprehensive dataset for pathology segmentation, built from 21 public sources and containing 275k image-mask-label triples across 160 diverse categories. With PathSegmentor, users can perform semantic segmentation using natural language prompts, eliminating the need for laborious spatial inputs such as points or boxes. Extensive experiments demonstrate that PathSegmentor outperforms specialized models with higher accuracy and broader applicability, while maintaining a compact architecture. It significantly surpasses existing spatial- and text-prompted models by 0.145 and 0.429 in overall Dice scores, respectively, showing strong robustness in segmenting complex structures and generalizing to external datasets. Moreover, PathSegmentor's outputs enhance the interpretability of diagnostic models through feature importance estimation and imaging biomarker discovery, offering pathologists evidence-based support for clinical decision-making. This work advances the development of explainable AI in precision oncology.

Yuxiang Nie, Sunan He, Yequan Bie et al.

The clinical adoption of artificial intelligence (AI) in medical imaging requires models that are both diagnostically accurate and interpretable to clinicians. While current multimodal biomedical foundation models prioritize performance, their black-box nature hinders explaining the decision-making process in clinically meaningful concepts. Here, we present ConceptCLIP, the first explainable biomedical foundation model that achieves state-of-the-art diagnostic accuracy while delivering human-interpretable explanations across diverse imaging modalities. We curate MedConcept-23M, the largest pre-training dataset comprising 23 million image-text-concept triplets across diverse medical modalities, where clinical concepts are derived from the Unified Medical Language System. Leveraging this dataset, we develop ConceptCLIP through a novel dual-alignment approach that simultaneously learns global image-text representations and fine-grained region-concept associations for precise and interpretable medical image analysis. We curate the most extensive evaluation benchmark for multimodal biomedical foundation models, covering 52 clinical tasks spanning 10 imaging modalities. Extensive experiments demonstrate that ConceptCLIP outperforms existing state-of-the-art multimodal biomedical foundation models. Importantly, ConceptCLIP demonstrates superior diagnostic performance while providing human-understandable explanations validated by clinical experts. As the first precise and interpretable biomedical foundation model, ConceptCLIP represents a critical milestone toward the widespread clinical adoption of AI, thereby advancing trustworthy AI in medicine.

Linshan Wu, Yuxiang Nie, Sunan He et al.

The integration of AI-assisted biomedical image analysis into clinical practice demands AI-generated findings that are not only accurate but also interpretable to clinicians. However, existing biomedical AI models generally lack the ability to simultaneously generate diagnostic findings and localize corresponding biomedical objects. This limitation makes it challenging for clinicians to correlate AI-generated findings with visual evidence (e.g., tiny lesions) in images and interpret the results of AI models. To address this challenge, we introduce UniBiomed, the first universal foundation model for grounded biomedical image interpretation, which is capable of generating accurate diagnostic findings and simultaneously segmenting the corresponding biomedical targets. UniBiomed is based on a novel integration of Multi-modal Large Language Model and Segment Anything Model, which can effectively unify diverse biomedical tasks in universal training for advancing grounded interpretation. To develop UniBiomed, we curate a large-scale dataset comprising over 27 million triplets of images, region annotations, and text descriptions across ten biomedical imaging modalities. Extensive validation on 70 internal and 14 external datasets demonstrated the state-of-the-art performance of UniBiomed in diverse biomedical tasks, including image segmentation, disease recognition, region-aware diagnosis, vision question answering, and report generation. In summary, UniBiomed is a powerful and versatile biomedical foundation model, unlocking the untapped grounded interpretation capability for optimizing AI-assisted biomedical image analysis.

Jiabo MA, Wenqiang Li, Jinbang Li et al.

Accurate histopathological diagnosis often requires multiple differently stained tissue sections, a process that is time-consuming, labor-intensive, and environmentally taxing due to the use of multiple chemical stains. Recently, virtual staining has emerged as a promising alternative that is faster, tissue-conserving, and environmentally friendly. However, existing virtual staining methods face significant challenges in clinical applications, primarily due to their reliance on well-aligned paired data. Obtaining such data is inherently difficult because chemical staining processes can distort tissue structures, and a single tissue section cannot undergo multiple staining procedures without damage or loss of information. As a result, most available virtual staining datasets are either unpaired or roughly paired, making it difficult for existing methods to achieve accurate pixel-level supervision. To address this challenge, we propose a robust virtual staining framework featuring cascaded registration mechanisms to resolve spatial mismatches between generated outputs and their corresponding ground truth. Experimental results demonstrate that our method significantly outperforms state-of-the-art models across five datasets, achieving an average improvement of 3.2% on internal datasets and 10.1% on external datasets. Moreover, in datasets with substantial misalignment, our approach achieves a remarkable 23.8% improvement in peak signal-to-noise ratio compared to baseline models. The exceptional robustness of the proposed method across diverse datasets simplifies the data acquisition process for virtual staining and offers new insights for advancing its development.

Hao Jiang, Cheng Jin, Huangjing Lin et al.

Cervical cancer is a leading malignancy in female reproductive system. While AI-assisted cytology offers a cost-effective and non-invasive screening solution, current systems struggle with generalizability in complex clinical scenarios. To address this issue, we introduced Smart-CCS, a generalizable Cervical Cancer Screening paradigm based on pretraining and adaptation to create robust and generalizable screening systems. To develop and validate Smart-CCS, we first curated a large-scale, multi-center dataset named CCS-127K, which comprises a total of 127,471 cervical cytology whole-slide images collected from 48 medical centers. By leveraging large-scale self-supervised pretraining, our CCS models are equipped with strong generalization capability, potentially generalizing across diverse scenarios. Then, we incorporated test-time adaptation to specifically optimize the trained CCS model for complex clinical settings, which adapts and refines predictions, improving real-world applicability. We conducted large-scale system evaluation among various cohorts. In retrospective cohorts, Smart-CCS achieved an overall area under the curve (AUC) value of 0.965 and sensitivity of 0.913 for cancer screening on 11 internal test datasets. In external testing, system performance maintained high at 0.950 AUC across 6 independent test datasets. In prospective cohorts, our Smart-CCS achieved AUCs of 0.947, 0.924, and 0.986 in three prospective centers, respectively. Moreover, the system demonstrated superior sensitivity in diagnosing cervical cancer, confirming the accuracy of our cancer screening results by using histology findings for validation. Interpretability analysis with cell and slide predictions further indicated that the system's decision-making aligns with clinical practice. Smart-CCS represents a significant advancement in cancer screening across diverse clinical contexts.

Yu Cai, Cheng Jin, Jiabo Ma et al.

Pathology foundation models (PFMs) have enabled robust generalization in computational pathology through large-scale datasets and expansive architectures, but their substantial computational cost, particularly for gigapixel whole slide images, limits clinical accessibility and scalability. Here, we present LitePath, a deployment-friendly foundational framework designed to mitigate model over-parameterization and patch level redundancy. LitePath integrates LiteFM, a compact model distilled from three large PFMs (Virchow2, H-Optimus-1 and UNI2) using 190 million patches, and the Adaptive Patch Selector (APS), a lightweight component for task-specific patch selection. The framework reduces model parameters by 28x and lowers FLOPs by 403.5x relative to Virchow2, enabling deployment on low-power edge hardware such as the NVIDIA Jetson Orin Nano Super. On this device, LitePath processes 208 slides per hour, 104.5x faster than Virchow2, and consumes 0.36 kWh per 3,000 slides, 171x lower than Virchow2 on an RTX3090 GPU. We validated accuracy using 37 cohorts across four organs and 26 tasks (26 internal, 9 external, and 2 prospective), comprising 15,672 slides from 9,808 patients disjoint from the pretraining data. LitePath ranks second among 19 evaluated models and outperforms larger models including H-Optimus-1, mSTAR, UNI2 and GPFM, while retaining 99.71% of the AUC of Virchow2 on average. To quantify the balance between accuracy and efficiency, we propose the Deployability Score (D-Score), defined as the weighted geometric mean of normalized AUC and normalized FLOP, where LitePath achieves the highest value, surpassing Virchow2 by 10.64%. These results demonstrate that LitePath enables rapid, cost-effective and energy-efficient pathology image analysis on accessible hardware while maintaining accuracy comparable to state-of-the-art PFMs and reducing the carbon footprint of AI deployment.

Ziyi Liu, Zhe Xu, Jiabo Ma et al.

Foundation models have revolutionized computational pathology by achieving remarkable success in high-level diagnostic tasks, yet the critical challenge of low-level image enhancement remains largely unaddressed. Real-world pathology images frequently suffer from degradations such as noise, blur, and low resolution due to slide preparation artifacts, staining variability, and imaging constraints, while the reliance on physical staining introduces significant costs, delays, and inconsistency. Although existing methods target individual problems like denoising or super-resolution, their task-specific designs lack the versatility to handle the diverse low-level vision challenges encountered in practice. To bridge this gap, we propose the first unified Low-level Pathology Foundation Model (LPFM), capable of enhancing image quality in restoration tasks, including super-resolution, deblurring, and denoising, as well as facilitating image translation tasks like virtual staining (H&E and special stains), all through a single adaptable architecture. Our approach introduces a contrastive pre-trained encoder that learns transferable, stain-invariant feature representations from 190 million unlabeled pathology images, enabling robust identification of degradation patterns. A unified conditional diffusion process dynamically adapts to specific tasks via textual prompts, ensuring precise control over output quality. Trained on a curated dataset of 87,810 whole slied images (WSIs) across 34 tissue types and 5 staining protocols, LPFM demonstrates statistically significant improvements (p<0.01) over state-of-the-art methods in most tasks (56/66), achieving Peak Signal-to-Noise Ratio (PSNR) gains of 10-15% for image restoration and Structural Similarity Index Measure (SSIM) improvements of 12-18% for virtual staining.

Zhe Xu, Ziyi Liu, Junlin Hou et al.

Multimodal large language models (MLLMs) have emerged as powerful tools for computational pathology, offering unprecedented opportunities to integrate pathological images with language context for comprehensive diagnostic analysis. These models hold particular promise for automating complex tasks that traditionally require expert interpretation of pathologists. However, current MLLM approaches in pathology demonstrate significantly constrained reasoning capabilities, primarily due to their reliance on expensive chain-of-thought annotations. Additionally, existing methods remain limited to simplex application of visual question answering (VQA) at the region-of-interest (ROI) level, failing to address the full spectrum of diagnostic needs such as ROI classification, detection, segmentation, whole-slide-image (WSI) classification and VQA in clinical practice. In this study, we present SmartPath-R1, a versatile MLLM capable of simultaneously addressing both ROI-level and WSI-level tasks while demonstrating robust pathological reasoning capability. Our framework combines scale-dependent supervised fine-tuning and task-aware reinforcement fine-tuning, which circumvents the requirement for chain-of-thought supervision by leveraging the intrinsic knowledge within MLLM. Furthermore, SmartPath-R1 integrates multiscale and multitask analysis through a mixture-of-experts mechanism, enabling dynamic processing for diverse tasks. We curate a large-scale dataset comprising 2.3M ROI samples and 188K WSI samples for training and evaluation. Extensive experiments across 72 tasks validate the effectiveness and superiority of the proposed approach. This work represents a significant step toward developing versatile, reasoning-enhanced AI systems for precision pathology.