Fang Yan

Zhongying Deng, Cheng Tang, Ziyan Huang et al. · pku

Foundation models have demonstrated remarkable success across diverse domains and tasks, primarily due to the thrive of large-scale, diverse, and high-quality datasets. However, in the field of medical imaging, the curation and assembling of such medical datasets are highly challenging due to the reliance on clinical expertise and strict ethical and privacy constraints, resulting in a scarcity of large-scale unified medical datasets and hindering the development of powerful medical foundation models. In this work, we present the largest survey to date of medical image datasets, covering over 1,000 open-access datasets with a systematic catalog of their modalities, tasks, anatomies, annotations, limitations, and potential for integration. Our analysis exposes a landscape that is modest in scale, fragmented across narrowly scoped tasks, and unevenly distributed across organs and modalities, which in turn limits the utility of existing medical image datasets for developing versatile and robust medical foundation models. To turn fragmentation into scale, we propose a metadata-driven fusion paradigm (MDFP) that integrates public datasets with shared modalities or tasks, thereby transforming multiple small data silos into larger, more coherent resources. Building on MDFP, we release an interactive discovery portal that enables end-to-end, automated medical image dataset integration, and compile all surveyed datasets into a unified, structured table that clearly summarizes their key characteristics and provides reference links, offering the community an accessible and comprehensive repository. By charting the current terrain and offering a principled path to dataset consolidation, our survey provides a practical roadmap for scaling medical imaging corpora, supporting faster data discovery, more principled dataset creation, and more capable medical foundation models.

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.

Shengyi Hua, Fang Yan, Tianle Shen et al.

Large amounts of digitized histopathological data display a promising future for developing pathological foundation models via self-supervised learning methods. Foundation models pretrained with these methods serve as a good basis for downstream tasks. However, the gap between natural and histopathological images hinders the direct application of existing methods. In this work, we present PathoDuet, a series of pretrained models on histopathological images, and a new self-supervised learning framework in histopathology. The framework is featured by a newly-introduced pretext token and later task raisers to explicitly utilize certain relations between images, like multiple magnifications and multiple stains. Based on this, two pretext tasks, cross-scale positioning and cross-stain transferring, are designed to pretrain the model on Hematoxylin and Eosin (H&E) images and transfer the model to immunohistochemistry (IHC) images, respectively. To validate the efficacy of our models, we evaluate the performance over a wide variety of downstream tasks, including patch-level colorectal cancer subtyping and whole slide image (WSI)-level classification in H&E field, together with expression level prediction of IHC marker, tumor identification and slide-level qualitative analysis in IHC field. The experimental results show the superiority of our models over most tasks and the efficacy of proposed pretext tasks. The codes and models are available at https://github.com/openmedlab/PathoDuet.

Jiaxuan Lu, Fang Yan, Xiaofan Zhang et al.

As natural image understanding moves towards the pretrain-finetune era, research in pathology imaging is concurrently evolving. Despite the predominant focus on pretraining pathological foundation models, how to adapt foundation models to downstream tasks is little explored. For downstream adaptation, we propose the existence of two domain gaps, i.e., the Foundation-Task Gap and the Task-Instance Gap. To mitigate these gaps, we introduce PathoTune, a framework designed to efficiently adapt pathological or even visual foundation models to pathology-specific tasks via multi-modal prompt tuning. The proposed framework leverages Task-specific Visual Prompts and Task-specific Textual Prompts to identify task-relevant features, along with Instance-specific Visual Prompts for encoding single pathological image features. Results across multiple datasets at both patch-level and WSI-level demonstrate its superior performance over single-modality prompt tuning approaches. Significantly, PathoTune facilitates the direct adaptation of natural visual foundation models to pathological tasks, drastically outperforming pathological foundation models with simple linear probing. The code is available at https://github.com/openmedlab/PathoDuet.

Kaitao Chen, Mianxin Liu, Fang Yan et al.

The advent of vision-language models fosters the interactive conversations between AI-enabled models and humans. Yet applying these models into clinics must deal with daunting challenges around large-scale training data, financial, and computational resources. Here we propose a cost-effective instruction learning framework for conversational pathology named as CLOVER. CLOVER only trains a lightweight module and uses instruction tuning while freezing the parameters of the large language model. Instead of using costly GPT-4, we propose well-designed prompts on GPT-3.5 for building generation-based instructions, emphasizing the utility of pathological knowledge derived from the Internet source. To augment the use of instructions, we construct a high-quality set of template-based instructions in the context of digital pathology. From two benchmark datasets, our findings reveal the strength of hybrid-form instructions in the visual question-answer in pathology. Extensive results show the cost-effectiveness of CLOVER in answering both open-ended and closed-ended questions, where CLOVER outperforms strong baselines that possess 37 times more training parameters and use instruction data generated from GPT-4. Through the instruction tuning, CLOVER exhibits robustness of few-shot learning in the external clinical dataset. These findings demonstrate that cost-effective modeling of CLOVER could accelerate the adoption of rapid conversational applications in the landscape of digital pathology.

Ming Hu, Chenglong Ma, Wei Li et al. · pku

Scientific Large Language Models (Sci-LLMs) are transforming how knowledge is represented, integrated, and applied in scientific research, yet their progress is shaped by the complex nature of scientific data. This survey presents a comprehensive, data-centric synthesis that reframes the development of Sci-LLMs as a co-evolution between models and their underlying data substrate. We formulate a unified taxonomy of scientific data and a hierarchical model of scientific knowledge, emphasizing the multimodal, cross-scale, and domain-specific challenges that differentiate scientific corpora from general natural language processing datasets. We systematically review recent Sci-LLMs, from general-purpose foundations to specialized models across diverse scientific disciplines, alongside an extensive analysis of over 270 pre-/post-training datasets, showing why Sci-LLMs pose distinct demands -- heterogeneous, multi-scale, uncertainty-laden corpora that require representations preserving domain invariance and enabling cross-modal reasoning. On evaluation, we examine over 190 benchmark datasets and trace a shift from static exams toward process- and discovery-oriented assessments with advanced evaluation protocols. These data-centric analyses highlight persistent issues in scientific data development and discuss emerging solutions involving semi-automated annotation pipelines and expert validation. Finally, we outline a paradigm shift toward closed-loop systems where autonomous agents based on Sci-LLMs actively experiment, validate, and contribute to a living, evolving knowledge base. Collectively, this work provides a roadmap for building trustworthy, continually evolving artificial intelligence (AI) systems that function as a true partner in accelerating scientific discovery.

Fang Yan, Jianfeng Wu, Jiawen Li et al.

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.

Yuan Tian, Shuo Wang, Rongzhao Zhang et al.

Medical imaging has significantly advanced computer-aided diagnosis, yet its re-identification (ReID) risks raise critical privacy concerns, calling for de-identification (DeID) techniques. Unfortunately, existing DeID methods neither particularly preserve medical semantics, nor are flexibly adjustable towards different privacy levels. To address these issues, we propose a divide-and-conquer framework comprising two steps: (1) Identity-Blocking, which blocks varying proportions of identity-related regions, to achieve different privacy levels; and (2) Medical-Semantics-Compensation, which leverages pre-trained Medical Foundation Models (MFMs) to extract medical semantic features to compensate the blocked regions. Moreover, recognizing that features from MFMs may still contain residual identity information, we introduce a Minimum Description Length principle-based feature decoupling strategy, to effectively decouple and discard such identity components. Extensive evaluations against existing approaches across seven datasets and three downstream tasks, demonstrates our state-of-the-art performance.

Jiaxuan Lu, Yuhui Lin, Junyan Shi et al.

Whole Slide Images (WSIs) in histopathology pose a significant challenge for extensive medical image analysis due to their ultra-high resolution, massive scale, and intricate spatial relationships. Although existing Multiple Instance Learning (MIL) approaches like Graph Neural Networks (GNNs) and Transformers demonstrate strong instance-level modeling capabilities, they encounter constraints regarding scalability and computational expenses. To overcome these limitations, we introduce the WSI-HGMamba, a novel framework that unifies the high-order relational modeling capabilities of the Hypergraph Neural Networks (HGNNs) with the linear-time sequential modeling efficiency of the State Space Models. At the core of our design is the HGMamba block, which integrates message passing, hypergraph scanning & flattening, and bidirectional state space modeling (Bi-SSM), enabling the model to retain both relational and contextual cues while remaining computationally efficient. Compared to Transformer and Graph Transformer counterparts, WSI-HGMamba achieves superior performance with up to 7* reduction in FLOPs. Extensive experiments on multiple public and private WSI benchmarks demonstrate that our method provides a scalable, accurate, and efficient solution for slide-level understanding, making it a promising backbone for next-generation pathology AI systems.

Zuqi Huang, Mengxin Tian, Huan Liu et al.

Accurate cell counting in immunohistochemistry (IHC) images is critical for quantifying protein expression and aiding cancer diagnosis. However, the task remains challenging due to the chromogen overlap, variable biomarker staining, and diverse cellular morphologies. Regression-based counting methods offer advantages over detection-based ones in handling overlapped cells, yet rarely support end-to-end multi-class counting. Moreover, the potential of foundation models remains largely underexplored in this paradigm. To address these limitations, we propose a rank-aware agglomeration framework that selectively distills knowledge from multiple strong foundation models, leveraging their complementary representations to handle IHC heterogeneity and obtain a compact yet effective student model, CountIHC. Unlike prior task-agnostic agglomeration strategies that either treat all teachers equally or rely on feature similarity, we design a Rank-Aware Teacher Selecting (RATS) strategy that models global-to-local patch rankings to assess each teacher's inherent counting capacity and enable sample-wise teacher selection. For multi-class cell counting, we introduce a fine-tuning stage that reformulates the task as vision-language alignment. Discrete semantic anchors derived from structured text prompts encode both category and quantity information, guiding the regression of class-specific density maps and improving counting for overlapping cells. Extensive experiments demonstrate that CountIHC surpasses state-of-the-art methods across 12 IHC biomarkers and 5 tissue types, while exhibiting high agreement with pathologists' assessments. Its effectiveness on H&E-stained data further confirms the scalability of the proposed method.

Fan Li, Yongming Li, Pin Wang et al.

Machine-learning-based age estimation has received lots of attention. Traditional age estimation mechanism focuses estimation age error, but ignores that there is a deviation between the estimated age and real age due to disease. Pathological age estimation mechanism the author proposed before introduces age deviation to solve the above problem and improves classification capability of the estimated age significantly. However,it does not consider the age estimation error of the normal control (NC) group and results in a larger error between the estimated age and real age of NC group. Therefore, an integrated age estimation mechanism based on Decision-Level fusion of error and deviation orientation model is proposed to solve the problem.Firstly, the traditional age estimation and pathological age estimation mechanisms are weighted together.Secondly, their optimal weights are obtained by minimizing mean absolute error (MAE) between the estimated age and real age of normal people. In the experimental section, several representative age-related datasets are used for verification of the proposed method. The results show that the proposed age estimation mechanism achieves a good tradeoff effect of age estimation. It not only improves the classification ability of the estimated age, but also reduces the age estimation error of the NC group. In general, the proposed age estimation mechanism is effective. Additionally, the mechanism is a framework mechanism that can be used to construct different specific age estimation algorithms, contributing to relevant research.