Yihui Wang

Yonghui Yang, Yihui Wang, Junwei Li et al.

Aligning large language models (LLMs) with human values has become increasingly important as their influence on human behavior and decision-making expands. However, existing steering-based alignment methods suffer from limited controllability: steering a target value often unintentionally activates other, non-target values. To characterize this limitation, we introduce value leakage, a diagnostic notion that captures the unintended activation of non-target values during value steering, along with a normalized leakage metric grounded in Schwartz's value theory. In light of this analysis, we propose NeVA, a neuron-level editing framework for controllable value alignment in LLMs. NeVA identifies sparse, value-relevant neurons and performs inference-time activation editing, enabling fine-grained control without parameter updates or retraining. Experiments show that NeVA achieves stronger target value alignment while incurring smaller performance degradation on general capability. Moreover, NeVA significantly reduces the average leakage, with residual effects largely confined to semantically related value classes. Overall, NeVA offers a more controllable and interpretable mechanism for value alignment.

Fengtao Zhou, Yingxue Xu, Zhengyu Zhang et al.

Comprehensive molecular profiling is essential for modern precision oncology but remains hindered by prohibitive costs, specimen exhaustion, and protracted turnaround times. While pathology foundation models (PFMs) have demonstrated potential for inferring molecular phenotypes from routine hematoxylin and eosin (H&E) whole-slide images (WSIs), current architectures primarily rely on vision-centric self-supervised learning or vision-language alignment, lacking the spatially resolved molecular supervision required to connect subtle morphological features with underlying genomic alterations. Spatial transcriptomics (ST) emerges as a transformative technology that enables transcriptomic quantification within intact tissue sections, thereby preserving the precise spatial link between histology and molecular profiles. In this study, we present a Spatial Transcriptomics-guided Alignment framework for Molecular Profiling (STAMP), which endows PFMs with intrinsic molecular awareness. To support this paradigm, we curated HumanST-1k, a human ST dataset spanning diverse anatomical organs and sequencing platforms. This atlas yields 1.8 million pairs of H&E patches and corresponding transcriptomic profiles, providing a corpus that links histological structures with their molecular states. To mitigate the technical noise inherent to raw transcriptomics, STAMP applies a pathway-informed alignment strategy that aggregates transcriptomic data into biologically functional pathways, which are subsequently integrated into PFMs via parameter-efficient fine-tuning. This alignment enriches the representation space of PFMs and unlocks their capacity to resolve sub-visual molecular signatures. The clinical utility of these augmented representations was validated through a multi-tier evaluation framework.

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.

Yihui Wang, Yonghui Yang, Jilong Liu et al.

Deepfake detection suffers from poor generalization across forgery methods, as existing models tend to rely on spurious method-specific shortcuts that fail to transfer to unseen manipulations. While recent approaches attempt to improve generalization, they lack an explicit mechanism to identify and suppress such shortcuts in learned representations. In this work, we propose Shortcut Subspace Suppression (S^3) framework that explicitly characterizes and suppresses method-specific shortcuts via subspace modeling. Our key insight is that variations distinguishing different forgery methods capture method-specific artifacts and thus serve as an effective proxy for method-specific shortcuts. To this end, we train a lightweight linear probe for forgery method classification and perform Singular Value Decomposition (SVD) to extract the dominant shortcut subspace. Building on this formulation, we develop two complementary strategies to reduce shortcut reliance. During training, we softly suppress the shortcut subspace in feature representations, encouraging the model to rely on more generalizable cues for real/fake discrimination. At inference time, we introduce a training-free counterpart that attenuates neurons aligned with the identified shortcut directions, enabling plug-and-play generalization enhancement with improved interpretability. Extensive experiments on multiple benchmarks demonstrate that our method significantly improves cross-method generalization while maintaining strong in-domain performance. The code will be released upon acceptance of the submission.

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.

Zhengrui Guo, Zhengyu Zhang, Jiabo Ma et al.

Pathological assessment guides lung cancer diagnosis, treatment selection, and prognostic evaluation, yet current CPath approaches rely on task-specific models for isolated objectives. Although pan-cancer foundation models offer versatility, they lack subspecialty-level depth and have not been evaluated across clinical workflows or prospectively validated in real-world settings. We introduce PulmoFoundation, a multi-center, prospectively validated, randomized controlled trial (RCT)-evaluated foundation model for comprehensive lung pathology assessment across pre-operative, intra-operative, and post-operative care. Built upon Virchow2 via subspecialty-specific pretraining using ~40,000 diagnostic H&E-stained whole-slide images (WSIs), PulmoFoundation was systematically evaluated on ~26,000 WSIs across 32 clinically relevant tasks. In addition to accurately predicting molecular markers and patient survival, our model achieves clinical-grade performance in core diagnostic tasks across biopsy, frozen section, and surgical resection slides. In a registered prospective study of 1,357 patients across 11 diagnostic tasks, our model achieved an average AUC of 92.3%. Using pre-specified triage thresholds, PulmoFoundation could reduce additional second-review burden for 68.8% of biopsies and 83.0% of frozen sections, and defer 44.5% of IHC stain orders, with PPVs of 1.0, 0.991, and 0.966. Beyond prospective validation, we conducted a crossover RCT with eight pathologists, in which AI assistance improved diagnostic accuracy across 4,928 case-reader pairs (91.7% w/ AI vs. 83.8% w/o AI). AI assistance also reduced median diagnostic time by 19.6%, increased diagnostic confidence by 8.7%, and improved inter-rater agreement from moderate (kappa = 0.56) to substantial (kappa = 0.76). Together, these evaluations support PulmoFoundation as a clinically validated decision-support system for lung pathology.

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.

Shu Yang, Yihui Wang, Hao Chen

Multiple Instance Learning (MIL) has emerged as a dominant paradigm to extract discriminative feature representations within Whole Slide Images (WSIs) in computational pathology. Despite driving notable progress, existing MIL approaches suffer from limitations in facilitating comprehensive and efficient interactions among instances, as well as challenges related to time-consuming computations and overfitting. In this paper, we incorporate the Selective Scan Space State Sequential Model (Mamba) in Multiple Instance Learning (MIL) for long sequence modeling with linear complexity, termed as MambaMIL. By inheriting the capability of vanilla Mamba, MambaMIL demonstrates the ability to comprehensively understand and perceive long sequences of instances. Furthermore, we propose the Sequence Reordering Mamba (SR-Mamba) aware of the order and distribution of instances, which exploits the inherent valuable information embedded within the long sequences. With the SR-Mamba as the core component, MambaMIL can effectively capture more discriminative features and mitigate the challenges associated with overfitting and high computational overhead. Extensive experiments on two public challenging tasks across nine diverse datasets demonstrate that our proposed framework performs favorably against state-of-the-art MIL methods. The code is released at https://github.com/isyangshu/MambaMIL.

Rui Xu, Shu Yang, Yihui Wang et al.

Mamba, a recent selective structured state space model, excels in long sequence modeling, which is vital in the large model era. Long sequence modeling poses significant challenges, including capturing long-range dependencies within the data and handling the computational demands caused by their extensive length. Mamba addresses these challenges by overcoming the local perception limitations of convolutional neural networks and the quadratic computational complexity of Transformers. Given its advantages over these mainstream foundation architectures, Mamba exhibits great potential to be a visual foundation architecture. Since January 2024, Mamba has been actively applied to diverse computer vision tasks, yielding numerous contributions. To help keep pace with the rapid advancements, this paper reviews visual Mamba approaches, analyzing over 200 papers. This paper begins by delineating the formulation of the original Mamba model. Subsequently, it delves into representative backbone networks, and applications categorized using different modalities, including image, video, point cloud, and multi-modal data. Particularly, we identify scanning techniques as critical for adapting Mamba to vision tasks, and decouple these scanning techniques to clarify their functionality and enhance their flexibility across various applications. Finally, we discuss the challenges and future directions, providing insights into new outlooks in this fast evolving area. A comprehensive list of visual Mamba models reviewed in this work is available at https://github.com/Ruixxxx/Awesome-Vision-Mamba-Models.

Zhengrui Guo, Jiabo Ma, Yingxue Xu et al.

Histopathology serves as the gold standard in cancer diagnosis, with clinical reports being vital in interpreting and understanding this process, guiding cancer treatment and patient care. The automation of histopathology report generation with deep learning stands to significantly enhance clinical efficiency and lessen the labor-intensive, time-consuming burden on pathologists in report writing. In pursuit of this advancement, we introduce HistGen, a multiple instance learning-empowered framework for histopathology report generation together with the first benchmark dataset for evaluation. Inspired by diagnostic and report-writing workflows, HistGen features two delicately designed modules, aiming to boost report generation by aligning whole slide images (WSIs) and diagnostic reports from local and global granularity. To achieve this, a local-global hierarchical encoder is developed for efficient visual feature aggregation from a region-to-slide perspective. Meanwhile, a cross-modal context module is proposed to explicitly facilitate alignment and interaction between distinct modalities, effectively bridging the gap between the extensive visual sequences of WSIs and corresponding highly summarized reports. Experimental results on WSI report generation show the proposed model outperforms state-of-the-art (SOTA) models by a large margin. Moreover, the results of fine-tuning our model on cancer subtyping and survival analysis tasks further demonstrate superior performance compared to SOTA methods, showcasing strong transfer learning capability. Dataset, model weights, and source code are available in https://github.com/dddavid4real/HistGen.

Hanna Hoffmann, Setareh Bady, Claas de Boer et al.

Achieving high levels of surgical skill through effective training is essential for optimal patient outcomes. Automated, data-driven skill assessment holds significant potential to improve surgical training. While machine learning-based methods are increasingly popular for assessing skills in minimally invasive surgery, their application to open surgery remains limited. We present the results of a dedicated MICCAI challenge designed to benchmark and advance vision-based skill assessment in open surgery. The challenge dataset comprises videos of an open suturing training task recorded with a static GoPro camera in a dry-lab setting, with instrument trajectories available in addition to the primary video modality. The OSS Challenge was hosted over two consecutive years, comprising two and three independent tasks, respectively: (1) classifying skill level into four classes, (2) predicting the full Objective Structured Assessment of Technical Skills across eight categories, and (3) tracking hands and surgical tools. Participants submitted diverse solutions including deep learning-based video models, tracking-driven methods, and hybrid approaches. General-purpose spatiotemporal video models consistently achieved the strongest performance, though conceptually diverse approaches reached competitive levels when well-executed. Predicting fine-grained OSATS scores remains challenging but benefits substantially from increased training data. Keypoint tracking proves difficult given frequent occlusions and out-of-frame instances, limiting current applicability for motion-based skill analysis. This work benchmarks innovative and diverse solutions for surgical skill assessment, highlighting both the promise and current limitations of video-based evaluation in open surgery and identifying critical directions for advancing automated skill assessment toward clinical impact.

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, Fengtao Zhou, Chenyu Zhao et al.

The integration of multimodal data including pathology images and gene profiles is widely applied in precise survival prediction. Despite recent advances in multimodal survival models, collecting complete modalities for multimodal fusion still poses a significant challenge, hindering their application in clinical settings. Current approaches tackling incomplete modalities often fall short, as they typically compensate for only a limited part of the knowledge of missing modalities. To address this issue, we propose a Distilled Prompt Learning framework (DisPro) to utilize the strong robustness of Large Language Models (LLMs) to missing modalities, which employs two-stage prompting for compensation of comprehensive information for missing modalities. In the first stage, Unimodal Prompting (UniPro) distills the knowledge distribution of each modality, preparing for supplementing modality-specific knowledge of the missing modality in the subsequent stage. In the second stage, Multimodal Prompting (MultiPro) leverages available modalities as prompts for LLMs to infer the missing modality, which provides modality-common information. Simultaneously, the unimodal knowledge acquired in the first stage is injected into multimodal inference to compensate for the modality-specific knowledge of the missing modality. Extensive experiments covering various missing scenarios demonstrated the superiority of the proposed method. The code is available at https://github.com/Innse/DisPro.

Qian Zeng, Yihui Wang, Shu Yang et al.

Whole-slide images (WSIs) are an important data modality in computational pathology, yet their gigapixel resolution and lack of fine-grained annotations challenge conventional deep learning models. Multiple instance learning (MIL) offers a solution by treating each WSI as a bag of patch-level instances, but effectively modeling ultra-long sequences with rich spatial context remains difficult. Recently, Mamba has emerged as a promising alternative for long sequence learning, scaling linearly to thousands of tokens. However, despite its efficiency, it still suffers from limited spatial context modeling and memory decay, constraining its effectiveness to WSI analysis. To address these limitations, we propose MambaMIL+, a new MIL framework that explicitly integrates spatial context while maintaining long-range dependency modeling without memory forgetting. Specifically, MambaMIL+ introduces 1) overlapping scanning, which restructures the patch sequence to embed spatial continuity and instance correlations; 2) a selective stripe position encoder (S2PE) that encodes positional information while mitigating the biases of fixed scanning orders; and 3) a contextual token selection (CTS) mechanism, which leverages supervisory knowledge to dynamically enlarge the contextual memory for stable long-range modeling. Extensive experiments on 20 benchmarks across diagnostic classification, molecular prediction, and survival analysis demonstrate that MambaMIL+ consistently achieves state-of-the-art performance under three feature extractors (ResNet-50, PLIP, and CONCH), highlighting its effectiveness and robustness for large-scale computational pathology

Chenyu Zhao, Yingxue Xu, Fengtao Zhou et al.

Current multimodal survival prediction methods typically rely on pathology images (WSIs) and genomic data, both of which are high-dimensional and redundant, making it difficult to extract discriminative features from them and align different modalities. Moreover, using a simple survival follow-up label is insufficient to supervise such a complex task. To address these challenges, we propose KEMM, an LLM-driven Knowledge-Enhanced Multimodal Model for cancer survival prediction, which integrates expert reports and prognostic background knowledge. 1) Expert reports, provided by pathologists on a case-by-case basis and refined by large language model (LLM), offer succinct and clinically focused diagnostic statements. This information may typically suggest different survival outcomes. 2) Prognostic background knowledge (PBK), generated concisely by LLM, provides valuable prognostic background knowledge on different cancer types, which also enhances survival prediction. To leverage these knowledge, we introduce the knowledge-enhanced cross-modal (KECM) attention module. KECM can effectively guide the network to focus on discriminative and survival-relevant features from highly redundant modalities. Extensive experiments on five datasets demonstrate that KEMM achieves state-of-the-art performance. The code will be released upon acceptance.

Jiarui Ouyang, Yihui Wang, Yihang Gao et al.

Spatial Transcriptomics (ST) offers spatially resolved gene expression but remains costly. Predicting expression directly from widely available Hematoxylin and Eosin (H&E) stained images presents a cost-effective alternative. However, most computational approaches (i) predict each gene independently, overlooking co-expression structure, and (ii) cast the task as continuous regression despite expression being discrete counts. This mismatch can yield biologically implausible outputs and complicate downstream analyses. We introduce GenAR, a multi-scale autoregressive framework that refines predictions from coarse to fine. GenAR clusters genes into hierarchical groups to expose cross-gene dependencies, models expression as codebook-free discrete token generation to directly predict raw counts, and conditions decoding on fused histological and spatial embeddings. From an information-theoretic perspective, the discrete formulation avoids log-induced biases and the coarse-to-fine factorization aligns with a principled conditional decomposition. Extensive experimental results on four Spatial Transcriptomics datasets across different tissue types demonstrate that GenAR achieves state-of-the-art performance, offering potential implications for precision medicine and cost-effective molecular profiling. Code is publicly available at https://github.com/oyjr/genar.

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.

Shu Yang, Fengtao Zhou, Leon Mayer et al.

Computer-Assisted Intervention (CAI) has the potential to revolutionize modern surgery, with surgical scene understanding serving as a critical component in supporting decision-making, improving procedural efficacy, and ensuring intraoperative safety. While existing AI-driven approaches alleviate annotation burdens via self-supervised spatial representation learning, their lack of explicit temporal modeling during pre-training fundamentally restricts the capture of dynamic surgical contexts, resulting in incomplete spatiotemporal understanding. In this work, we introduce the first video-level surgical pre-training framework that enables joint spatiotemporal representation learning from large-scale surgical video data. To achieve this, we constructed a large-scale surgical video dataset comprising 3,650 videos and approximately 3.55 million frames, spanning more than 20 surgical procedures and over 10 anatomical structures. Building upon this dataset, we propose SurgVISTA (Surgical Video-level Spatial-Temporal Architecture), a reconstruction-based pre-training method that captures intricate spatial structures and temporal dynamics through joint spatiotemporal modeling. Additionally, SurgVISTA incorporates image-level knowledge distillation guided by a surgery-specific expert to enhance the learning of fine-grained anatomical and semantic features. To validate its effectiveness, we established a comprehensive benchmark comprising 13 video-level datasets spanning six surgical procedures across four tasks. Extensive experiments demonstrate that SurgVISTA consistently outperforms both natural- and surgical-domain pre-trained models, demonstrating strong potential to advance intelligent surgical systems in clinically meaningful scenarios.

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.

Yihui Wang, Sheng-Yu Peng, Sahil Shah

This paper presents a fully synthesizable, treebased Address-Event Representation (AER) encoder designed for scalable neuromorphic computing systems. To achieve high throughput while maintaining strict compatibility with commercial EDA workflows, the asynchronous design employs a bundled-data protocol within a semi-decoupled micropipeline. The architecture replaces traditional transparent latches with standard edge-triggered flip-flops, enabling digital synthesis and place-and-route (PnR) using Cadence toolkits. A cross-coupled NAND-based random-priority arbiter is embedded within the encoder of each tree node to resolve event collisions efficiently. An 8-event AER prototype is fabricated in 65 nm CMOS technology utilizing a purely digital standard-cell flow. Post-fabrication silicon measurements validate the design, demonstrating a peak throughput of 33 MEvent/s and an average event latency of 50 ns, equating to a propagation delay of 17 ns/(event-bit). The design consumes only 435 fJ per encoded event.

Zhe Xu, Cheng Jin, Yihui Wang et al.

Multimodal pathological image understanding has garnered widespread interest due to its potential to improve diagnostic accuracy and enable personalized treatment through integrated visual and textual data. However, existing methods exhibit limited reasoning capabilities, which hamper their ability to handle complex diagnostic scenarios. Additionally, the enormous size of pathological images leads to severe computational burdens, further restricting their practical deployment. To address these limitations, we introduce a novel bilateral reinforcement learning framework comprising two synergistic branches. One reinforcement branch enhances the reasoning capability by enabling the model to learn task-specific decision processes, i.e., pathology rationales, directly from labels without explicit reasoning supervision. While the other branch dynamically allocates a tailored number of tokens to different images based on both their visual content and task context, thereby optimizing computational efficiency. We apply our method to various pathological tasks such as visual question answering, cancer subtyping, and lesion detection. Extensive experiments show an average +41.7 absolute performance improvement with 70.3% lower inference costs over the base models, achieving both reasoning accuracy and computational efficiency.

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.

Zihan Zhao, Fengtao Zhou, Ronggang Li et al.

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.

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.

Tobias Rueckert, David Rauber, Raphaela Maerkl et al.

Reliable recognition and localization of surgical instruments in endoscopic video recordings are foundational for a wide range of applications in computer- and robot-assisted minimally invasive surgery (RAMIS), including surgical training, skill assessment, and autonomous assistance. However, robust performance under real-world conditions remains a significant challenge. Incorporating surgical context - such as the current procedural phase - has emerged as a promising strategy to improve robustness and interpretability. To address these challenges, we organized the Surgical Procedure Phase, Keypoint, and Instrument Recognition (PhaKIR) sub-challenge as part of the Endoscopic Vision (EndoVis) challenge at MICCAI 2024. We introduced a novel, multi-center dataset comprising thirteen full-length laparoscopic cholecystectomy videos collected from three distinct medical institutions, with unified annotations for three interrelated tasks: surgical phase recognition, instrument keypoint estimation, and instrument instance segmentation. Unlike existing datasets, ours enables joint investigation of instrument localization and procedural context within the same data while supporting the integration of temporal information across entire procedures. We report results and findings in accordance with the BIAS guidelines for biomedical image analysis challenges. The PhaKIR sub-challenge advances the field by providing a unique benchmark for developing temporally aware, context-driven methods in RAMIS and offers a high-quality resource to support future research in surgical scene understanding.

Cheng Jin, Fengtao Zhou, Yunfang Yu et al.

Precision oncology requires accurate molecular insights, yet obtaining these directly from genomics is costly and time-consuming for broad clinical use. Predicting complex molecular features and patient prognosis directly from routine whole-slide images (WSI) remains a major challenge for current deep learning methods. Here we introduce PathLUPI, which uses transcriptomic privileged information during training to extract genome-anchored histological embeddings, enabling effective molecular prediction using only WSIs at inference. Through extensive evaluation across 49 molecular oncology tasks using 11,257 cases among 20 cohorts, PathLUPI demonstrated superior performance compared to conventional methods trained solely on WSIs. Crucially, it achieves AUC $\geq$ 0.80 in 14 of the biomarker prediction and molecular subtyping tasks and C-index $\geq$ 0.70 in survival cohorts of 5 major cancer types. Moreover, PathLUPI embeddings reveal distinct cellular morphological signatures associated with specific genotypes and related biological pathways within WSIs. By effectively encoding molecular context to refine WSI representations, PathLUPI overcomes a key limitation of existing models and offers a novel strategy to bridge molecular insights with routine pathology workflows for wider clinical application.