Linghan Cai

Qi Zhao, Shuchang Lyu, Wenpei Bai et al.

Ovarian cancer is one of the most harmful gynecological diseases. Detecting ovarian tumors in early stage with computer-aided techniques can efficiently decrease the mortality rate. With the improvement of medical treatment standard, ultrasound images are widely applied in clinical treatment. However, recent notable methods mainly focus on single-modality ultrasound ovarian tumor segmentation or recognition, which means there still lacks researches on exploring the representation capability of multi-modality ultrasound ovarian tumor images. To solve this problem, we propose a Multi-Modality Ovarian Tumor Ultrasound (MMOTU) image dataset containing 1469 2d ultrasound images and 170 contrast enhanced ultrasonography (CEUS) images with pixel-wise and global-wise annotations. Based on MMOTU, we mainly focus on unsupervised cross-domain semantic segmentation task. To solve the domain shift problem, we propose a feature alignment based architecture named Dual-Scheme Domain-Selected Network (DS2Net). Specifically, we first design source-encoder and target-encoder to extract two-style features of source and target images. Then, we propose Domain-Distinct Selected Module (DDSM) and Domain-Universal Selected Module (DUSM) to extract the distinct and universal features in two styles (source-style or target-style). Finally, we fuse these two kinds of features and feed them into the source-decoder and target-decoder to generate final predictions. Extensive comparison experiments and analysis on MMOTU image dataset show that DS2Net can boost the segmentation performance for bidirectional cross-domain adaptation of 2d ultrasound images and CEUS images. Our proposed dataset and code are all available at https://github.com/cv516Buaa/MMOTU_DS2Net.

Linghan Cai, Jianhao Huang, Zihang Zhu et al.

Fluorodeoxyglucose (FDG) positron emission tomography (PET) combined with computed tomography (CT) is considered the primary solution for detecting some cancers, such as lung cancer and melanoma. Automatic segmentation of tumors in PET/CT images can help reduce doctors' workload, thereby improving diagnostic quality. However, precise tumor segmentation is challenging due to the small size of many tumors and the similarity of high-uptake normal areas to the tumor regions. To address these issues, this paper proposes a localization-to-segmentation framework (L2SNet) for precise tumor segmentation. L2SNet first localizes the possible lesions in the lesion localization phase and then uses the location cues to shape the segmentation results in the lesion segmentation phase. To further improve the segmentation performance of L2SNet, we design an adaptive threshold scheme that takes the segmentation results of the two phases into consideration. The experiments with the MICCAI 2023 Automated Lesion Segmentation in Whole-Body FDG-PET/CT challenge dataset show that our method achieved a competitive result and was ranked in the top 7 methods on the preliminary test set. Our work is available at: https://github.com/MedCAI/L2SNet.

Songhan Jiang, Fengchun Liu, Ziyue Wang et al.

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.

Ye Zhang, Yifeng Wang, Zijie Fang et al.

Weakly supervised segmentation methods have gained significant attention due to their ability to reduce the reliance on costly pixel-level annotations during model training. However, the current weakly supervised nuclei segmentation approaches typically follow a two-stage pseudo-label generation and network training process. The performance of the nuclei segmentation heavily relies on the quality of the generated pseudo-labels, thereby limiting its effectiveness. This paper introduces a novel domain-adaptive weakly supervised nuclei segmentation framework using cross-task interaction strategies to overcome the challenge of pseudo-label generation. Specifically, we utilize weakly annotated data to train an auxiliary detection task, which assists the domain adaptation of the segmentation network. To enhance the efficiency of domain adaptation, we design a consistent feature constraint module integrating prior knowledge from the source domain. Furthermore, we develop pseudo-label optimization and interactive training methods to improve the domain transfer capability. To validate the effectiveness of our proposed method, we conduct extensive comparative and ablation experiments on six datasets. The results demonstrate the superiority of our approach over existing weakly supervised approaches. Remarkably, our method achieves comparable or even better performance than fully supervised methods. Our code will be released in https://github.com/zhangye-zoe/DAWN.

Ziyue Wang, Junde Wu, Linghan Cai et al.

In modern medicine, clinical diagnosis relies on the comprehensive analysis of primarily textual and visual data, drawing on medical expertise to ensure systematic and rigorous reasoning. Recent advances in large Vision-Language Models (VLMs) and agent-based methods hold great potential for medical diagnosis, thanks to the ability to effectively integrate multi-modal patient data. However, they often provide direct answers and draw empirical-driven conclusions without quantitative analysis, which reduces their reliability and clinical usability. We propose MedAgent-Pro, a new agentic reasoning paradigm that follows the diagnosis principle in modern medicine, to decouple the process into sequential components for step-by-step, evidence-based reasoning. Our MedAgent-Pro workflow presents a hierarchical diagnostic structure to mirror this principle, consisting of disease-level standardized plan generation and patient-level personalized step-by-step reasoning. To support disease-level planning, an RAG-based agent is designed to retrieve medical guidelines to ensure alignment with clinical standards. For patient-level reasoning, we propose to integrate professional tools such as visual models to enable quantitative assessments. Meanwhile, we propose to verify the reliability of each step to achieve evidence-based diagnosis, enforcing rigorous logical reasoning and a well-founded conclusion. Extensive experiments across a wide range of anatomical regions, imaging modalities, and diseases demonstrate the superiority of MedAgent-Pro to mainstream VLMs, agentic systems and state-of-the-art expert models. Ablation studies and human evaluation by clinical experts further validate its robustness and clinical relevance. Code is available at https://github.com/jinlab-imvr/MedAgent-Pro.

Linghan Cai, Shenjin Huang, Ye Zhang et al.

Multiple instance learning (MIL) is a robust paradigm for whole-slide pathological image (WSI) analysis, processing gigapixel-resolution images with slide-level labels. As pioneering efforts, attention-based MIL (ABMIL) and its variants are increasingly becoming popular due to the characteristics of simultaneously handling clinical diagnosis and tumor localization. However, the attention mechanism exhibits limitations in discriminating between instances, which often misclassifies tissues and potentially impairs MIL performance. This paper proposes an Attribute-Driven MIL (AttriMIL) framework to address these issues. Concretely, we dissect the calculation process of ABMIL and present an attribute scoring mechanism that measures the contribution of each instance to bag prediction effectively, quantifying instance attributes. Based on attribute quantification, we develop a spatial attribute constraint and an attribute ranking constraint to model instance correlations within and across slides, respectively. These constraints encourage the network to capture the spatial correlation and semantic similarity of instances, improving the ability of AttriMIL to distinguish tissue types and identify challenging instances. Additionally, AttriMIL employs a histopathology adaptive backbone that maximizes the pre-trained model's feature extraction capability for collecting pathological features. Extensive experiments on three public benchmarks demonstrate that our AttriMIL outperforms existing state-of-the-art frameworks across multiple evaluation metrics. The implementation code is available at https://github.com/MedCAI/AttriMIL.

Jinpeng Lu, Jingyun Chen, Linghan Cai et al.

Positron emission tomography (PET) combined with computed tomography (CT) imaging is routinely used in cancer diagnosis and prognosis by providing complementary information. Automatically segmenting tumors in PET/CT images can significantly improve examination efficiency. Traditional multi-modal segmentation solutions mainly rely on concatenation operations for modality fusion, which fail to effectively model the non-linear dependencies between PET and CT modalities. Recent studies have investigated various approaches to optimize the fusion of modality-specific features for enhancing joint representations. However, modality-specific encoders used in these methods operate independently, inadequately leveraging the synergistic relationships inherent in PET and CT modalities, for example, the complementarity between semantics and structure. To address these issues, we propose a Hierarchical Adaptive Interaction and Weighting Network termed H2ASeg to explore the intrinsic cross-modal correlations and transfer potential complementary information. Specifically, we design a Modality-Cooperative Spatial Attention (MCSA) module that performs intra- and inter-modal interactions globally and locally. Additionally, a Target-Aware Modality Weighting (TAMW) module is developed to highlight tumor-related features within multi-modal features, thereby refining tumor segmentation. By embedding these modules across different layers, H2ASeg can hierarchically model cross-modal correlations, enabling a nuanced understanding of both semantic and structural tumor features. Extensive experiments demonstrate the superiority of H2ASeg, outperforming state-of-the-art methods on AutoPet-II and Hecktor2022 benchmarks. The code is released at https://github.com/JinPLu/H2ASeg.

Fengchun Liu, Songhan Jiang, Linghan Cai et al.

While Vision-Language Models (VLMs) have achieved notable progress in computational pathology (CPath), the gigapixel scale and spatial heterogeneity of Whole Slide Images (WSIs) continue to pose challenges for multimodal understanding. Existing alignment methods struggle to capture fine-grained correspondences between textual descriptions and visual cues across thousands of patches from a slide, compromising their performance on downstream tasks. In this paper, we propose PathFLIP (Pathology Fine-grained Language-Image Pretraining), a novel framework for holistic WSI interpretation. PathFLIP decomposes slide-level captions into region-level subcaptions and generates text-conditioned region embeddings to facilitate precise visual-language grounding. By harnessing Large Language Models (LLMs), PathFLIP can seamlessly follow diverse clinical instructions and adapt to varied diagnostic contexts. Furthermore, it exhibits versatile capabilities across multiple paradigms, efficiently handling slide-level classification and retrieval, fine-grained lesion localization, and instruction following. Extensive experiments demonstrate that PathFLIP outperforms existing large-scale pathological VLMs on four representative benchmarks while requiring significantly less training data, paving the way for fine-grained, instruction-aware WSI interpretation in clinical practice.

Ziyue Wang, Linghan Cai, Chang Han Low et al.

3D CT analysis spans a continuum from low-level perception to high-level clinical understanding. Existing 3D-oriented analysis methods adopt either isolated task-specific modeling or task-agnostic end-to-end paradigms to produce one-hop outputs, impeding the systematic accumulation of perceptual evidence for downstream reasoning. In parallel, recent multimodal large language models (MLLMs) exhibit improved visual perception and can integrate visual and textual information effectively, yet their predominantly 2D-oriented designs fundamentally limit their ability to perceive and analyze volumetric medical data. To bridge this gap, we propose 3DMedAgent, a unified agent that enables 2D MLLMs to perform general 3D CT analysis without 3D-specific fine-tuning. 3DMedAgent coordinates heterogeneous visual and textual tools through a flexible MLLM agent, progressively decomposing complex 3D analysis into tractable subtasks that transition from global to regional views, from 3D volumes to informative 2D slices, and from visual evidence to structured textual representations. Central to this design, 3DMedAgent maintains a long-term structured memory that aggregates intermediate tool outputs and supports query-adaptive, evidence-driven multi-step reasoning. We further introduce the DeepChestVQA benchmark for evaluating unified perception-to-understanding capabilities in 3D thoracic imaging. Experiments across over 40 tasks demonstrate that 3DMedAgent consistently outperforms general, medical, and 3D-specific MLLMs, highlighting a scalable path toward general-purpose 3D clinical assistants.Code and data are available at \href{https://github.com/jinlab-imvr/3DMedAgent}{https://github.com/jinlab-imvr/3DMedAgent}.

Jinpeng Lu, Linghan Cai, Yinda Chen et al.

Lightweight 3D medical image segmentation remains constrained by a fundamental "efficiency / robustness conflict", particularly when processing complex anatomical structures and heterogeneous modalities. In this paper, we study how to redesign the framework based on the characteristics of high-dimensional 3D images, and explore data synergy to overcome the fragile representation of lightweight methods. Our approach, VeloxSeg, begins with a deployable and extensible dual-stream CNN-Transformer architecture composed of Paired Window Attention (PWA) and Johnson-Lindenstrauss lemma-guided convolution (JLC). For each 3D image, we invoke a "glance-and-focus" principle, where PWA rapidly retrieves multi-scale information, and JLC ensures robust local feature extraction with minimal parameters, significantly enhancing the model's ability to operate with low computational budget. Followed by an extension of the dual-stream architecture that incorporates modal interaction into the multi-scale image-retrieval process, VeloxSeg efficiently models heterogeneous modalities. Finally, Spatially Decoupled Knowledge Transfer (SDKT) via Gram matrices injects the texture prior extracted by a self-supervised network into the segmentation network, yielding stronger representations than baselines at no extra inference cost. Experimental results on multimodal benchmarks show that VeloxSeg achieves a 26% Dice improvement, alongside increasing GPU throughput by 11x and CPU by 48x. Codes are available at https://github.com/JinPLu/VeloxSeg.

Songhan Jiang, Zhengyu Gan, Linghan Cai et al.

Survival prediction, utilizing pathological images and genomic profiles, is increasingly important in cancer analysis and prognosis. Despite significant progress, precise survival analysis still faces two main challenges: (1) The massive pixels contained in whole slide images (WSIs) complicate the process of pathological images, making it difficult to generate an effective representation of the tumor microenvironment (TME). (2) Existing multimodal methods often rely on alignment strategies to integrate complementary information, which may lead to information loss due to the inherent heterogeneity between pathology and genes. In this paper, we propose a Multimodal Cross-Task Interaction (MCTI) framework to explore the intrinsic correlations between subtype classification and survival analysis tasks. Specifically, to capture TME-related features in WSIs, we leverage the subtype classification task to mine tumor regions. Simultaneously, multi-head attention mechanisms are applied in genomic feature extraction, adaptively performing genes grouping to obtain task-related genomic embedding. With the joint representation of pathological images and genomic data, we further introduce a Transport-Guided Attention (TGA) module that uses optimal transport theory to model the correlation between subtype classification and survival analysis tasks, effectively transferring potential information. Extensive experiments demonstrate the superiority of our approaches, with MCTI outperforming state-of-the-art frameworks on three public benchmarks. \href{https://github.com/jsh0792/MCTI}{https://github.com/jsh0792/MCTI}.

Ziyue Wang, Ye Zhang, Yifeng Wang et al.

Deep learning has achieved impressive results in nuclei segmentation, but the massive requirement for pixel-wise labels remains a significant challenge. To alleviate the annotation burden, existing methods generate pseudo masks for model training using point labels. However, the generated masks are inevitably different from the ground truth, and these dissimilarities are not handled reasonably during the network training, resulting in the subpar performance of the segmentation model. To tackle this issue, we propose a framework named DoNuSeg, enabling \textbf{D}ynamic pseudo label \textbf{O}ptimization in point-supervised \textbf{Nu}clei \textbf{Seg}mentation. Specifically, DoNuSeg takes advantage of class activation maps (CAMs) to adaptively capture regions with semantics similar to annotated points. To leverage semantic diversity in the hierarchical feature levels, we design a dynamic selection module to choose the optimal one among CAMs from different encoder blocks as pseudo masks. Meanwhile, a CAM-guided contrastive module is proposed to further enhance the accuracy of pseudo masks. In addition to exploiting the semantic information provided by CAMs, we consider location priors inherent to point labels, developing a task-decoupled structure for effectively differentiating nuclei. Extensive experiments demonstrate that DoNuSeg outperforms state-of-the-art point-supervised methods. The code is available at https://github.com/shinning0821/MICCAI24-DoNuSeg.

Ye Zhang, Linghan Cai, Ziyue Wang et al.

Nuclei instance segmentation in histopathological images is of great importance for biological analysis and cancer diagnosis but remains challenging for two reasons. (1) Similar visual presentation of intranuclear and extranuclear regions of chromophobe nuclei often causes under-segmentation, and (2) current methods lack the exploration of nuclei structure, resulting in fragmented instance predictions. To address these problems, this paper proposes a structure encoding and interaction network, termed SEINE, which develops the structure modeling scheme of nuclei and exploits the structure similarity between nuclei to improve the integrality of each segmented instance. Concretely, SEINE introduces a contour-based structure encoding (SE) that considers the correlation between nuclei structure and semantics, realizing a reasonable representation of the nuclei structure. Based on the encoding, we propose a structure-guided attention (SGA) module that takes the clear nuclei as prototypes to enhance the structure learning for the fuzzy nuclei. To strengthen the structural learning ability, a semantic feature fusion (SFF) is presented to boost the semantic consistency of semantic and structure branches. Furthermore, a position enhancement (PE) method is applied to suppress incorrect nuclei boundary predictions. Extensive experiments demonstrate the superiority of our approaches, and SEINE achieves state-of-the-art (SOTA) performance on four datasets. The code is available at https://github.com/zhangye-zoe/SEINE.

Che Liu, Yinda Chen, Haoyuan Shi et al.

The advent of large-scale vision foundation models, pre-trained on diverse natural images, has marked a paradigm shift in computer vision. However, how the frontier vision foundation models' efficacies transfer to specialized domains remains such as medical imaging remains an open question. This report investigates whether DINOv3, a state-of-the-art self-supervised vision transformer (ViT) that features strong capability in dense prediction tasks, can directly serve as a powerful, unified encoder for medical vision tasks without domain-specific pre-training. To answer this, we benchmark DINOv3 across common medical vision tasks, including 2D/3D classification and segmentation on a wide range of medical imaging modalities. We systematically analyze its scalability by varying model sizes and input image resolutions. Our findings reveal that DINOv3 shows impressive performance and establishes a formidable new baseline. Remarkably, it can even outperform medical-specific foundation models like BiomedCLIP and CT-Net on several tasks, despite being trained solely on natural images. However, we identify clear limitations: The model's features degrade in scenarios requiring deep domain specialization, such as in Whole-Slide Pathological Images (WSIs), Electron Microscopy (EM), and Positron Emission Tomography (PET). Furthermore, we observe that DINOv3 does not consistently obey scaling law in the medical domain; performance does not reliably increase with larger models or finer feature resolutions, showing diverse scaling behaviors across tasks. Ultimately, our work establishes DINOv3 as a strong baseline, whose powerful visual features can serve as a robust prior for multiple complex medical tasks. This opens promising future directions, such as leveraging its features to enforce multiview consistency in 3D reconstruction.

Ye Zhang, Ziyue Wang, Yifeng Wang et al.

Semi-supervised segmentation methods have demonstrated promising results in natural scenarios, providing a solution to reduce dependency on manual annotation. However, these methods face significant challenges when directly applied to pathological images due to the subtle color differences between nuclei and tissues, as well as the significant morphological variations among nuclei. Consequently, the generated pseudo-labels often contain much noise, especially at the nuclei boundaries. To address the above problem, this paper proposes a boundary-aware contrastive learning network to denoise the boundary noise in a semi-supervised nuclei segmentation task. The model has two key designs: a low-resolution denoising (LRD) module and a cross-RoI contrastive learning (CRC) module. The LRD improves the smoothness of the nuclei boundary by pseudo-labels denoising, and the CRC enhances the discrimination between foreground and background by boundary feature contrastive learning. We conduct extensive experiments to demonstrate the superiority of our proposed method over existing semi-supervised instance segmentation methods.

Jingyun Chen, Linghan Cai, Zhikang Wang et al.

Analyzing whole-slide images (WSIs) requires an iterative, evidence-driven reasoning process that parallels how pathologists dynamically zoom, refocus, and self-correct while collecting the evidence. However, existing computational pipelines often lack this explicit reasoning trajectory, resulting in inherently opaque and unjustifiable predictions. To bridge this gap, we present PathAgent, a training-free, large language model (LLM)-based agent framework that emulates the reflective, stepwise analytical approach of human experts. PathAgent can autonomously explore WSI, iteratively and precisely locating significant micro-regions using the Navigator module, extracting morphology visual cues using the Perceptor, and integrating these findings into the continuously evolving natural language trajectories in the Executor. The entire sequence of observations and decisions forms an explicit chain-of-thought, yielding fully interpretable predictions. Evaluated across five challenging datasets, PathAgent exhibits strong zero-shot generalization, surpassing task-specific baselines in both open-ended and constrained visual question-answering tasks. Moreover, a collaborative evaluation with human pathologists confirms PathAgent's promise as a transparent and clinically grounded diagnostic assistant.

Guo Tang, Songhan Jiang, Jinpeng Lu et al.

Pathological images play an essential role in cancer prognosis, while survival analysis, which integrates computational techniques, can predict critical clinical events such as patient mortality or disease recurrence from whole-slide images (WSIs). Recent advancements in multiple instance learning have significantly improved the efficiency of survival analysis. However, existing methods often struggle to balance the modeling of long-range spatial relationships with local contextual dependencies and typically lack inherent interpretability, limiting their clinical utility. To address these challenges, we propose the Interpretable Pathology Graph-Transformer (IPGPhormer), a novel framework that captures the characteristics of the tumor microenvironment and models their spatial dependencies across the tissue. IPGPhormer uniquely provides interpretability at both tissue and cellular levels without requiring post-hoc manual annotations, enabling detailed analyses of individual WSIs and cross-cohort assessments. Comprehensive evaluations on four public benchmark datasets demonstrate that IPGPhormer outperforms state-of-the-art methods in both predictive accuracy and interpretability. In summary, our method, IPGPhormer, offers a promising tool for cancer prognosis assessment, paving the way for more reliable and interpretable decision-support systems in pathology. The code is publicly available at https://anonymous.4open.science/r/IPGPhormer-6EEB.

Fengchun Liu, Linghan Cai, Zhikang Wang et al.

Histo-genomic multimodal survival prediction has garnered growing attention for its remarkable model performance and potential contributions to precision medicine. However, a significant challenge in clinical practice arises when only unimodal data is available, limiting the usability of these advanced multimodal methods. To address this issue, this study proposes a prototype-guided cross-modal knowledge enhancement (ProSurv) framework, which eliminates the dependency on paired data and enables robust learning and adaptive survival prediction. Specifically, we first introduce an intra-modal updating mechanism to construct modality-specific prototype banks that encapsulate the statistics of the whole training set and preserve the modality-specific risk-relevant features/prototypes across intervals. Subsequently, the proposed cross-modal translation module utilizes the learned prototypes to enhance knowledge representation for multimodal inputs and generate features for missing modalities, ensuring robust and adaptive survival prediction across diverse scenarios. Extensive experiments on four public datasets demonstrate the superiority of ProSurv over state-of-the-art methods using either unimodal or multimodal input, and the ablation study underscores its feasibility for broad applicability. Overall, this study addresses a critical practical challenge in computational pathology, offering substantial significance and potential impact in the field.