Li Liang

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.

Hao Wang, Jiatai Lin, Danyi Li et al.

Mitosis detection is one of the fundamental tasks in computational pathology, which is extremely challenging due to the heterogeneity of mitotic cell. Most of the current studies solve the heterogeneity in the technical aspect by increasing the model complexity. However, lacking consideration of the biological knowledge and the complex model design may lead to the overfitting problem while limited the generalizability of the detection model. In this paper, we systematically study the morphological appearances in different mitotic phases as well as the ambiguous non-mitotic cells and identify that balancing the data and feature diversity can achieve better generalizability. Based on this observation, we propose a novel generalizable framework (MitDet) for mitosis detection. The data diversity is considered by the proposed diversity-guided sample balancing (DGSB). And the feature diversity is preserved by inter- and intra- class feature diversity-preserved module (InCDP). Stain enhancement (SE) module is introduced to enhance the domain-relevant diversity of both data and features simultaneously. Extensive experiments have demonstrated that our proposed model outperforms all the SOTA approaches in several popular mitosis detection datasets in both internal and external test sets using minimal annotation efforts with point annotations only. Comprehensive ablation studies have also proven the effectiveness of the rethinking of data and feature diversity balancing. By analyzing the results quantitatively and qualitatively, we believe that our proposed model not only achieves SOTA performance but also might inspire the future studies in new perspectives. Source code is at https://github.com/Onehour0108/MitDet.

Li Liang, Jinbiao Chen, Zizhen Zhang

Neural asymmetric routing models increasingly encode directionality through matrix representations and asymmetry-aware attention. The final routing action, however, is not a node in isolation but a directed transition chosen under the current partial route. This creates a representation--decision mismatch: pairwise cost information may be encoded upstream while the final candidate logit is still largely parameterized as context--node compatibility. We propose a decoder-design principle for neural asymmetric routing: the final score should explicitly expose transition-level quantities suggested by the problem's cost-to-go structure. We instantiate this principle with an edge-aware decoder that adds candidate-specific terms for the current directed edge, return-to-start closure, and static lightweight lookahead, while keeping the representation backbone fixed. On a controlled SVD/Sinkhorn asymmetric backbone, the decoder improves over the RADAR reference when trained on ATSP-100 and evaluated zero-shot on ATSP-100/200/500/1000, reducing the ATSP-1000 gap from $4.13\%$ to $2.73\%$. On ACVRP, the same score-level modification shows the same qualitative trend under a richer routing state. ATSP ablations and directed-transition diagnostics sharpen the mechanism: the strongest evidence concerns sensitivity to the current directed edge, while closure and static lookahead act as heuristic continuation cues. The results support a mechanism study: a key decoder-side signal in neural asymmetric routing is decision-time exposure of transition-level edge information.

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.

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.

Hongcheng Gao, Jiashu Qu, Jingyi Tang et al. · tsinghua

The hallucination of large multimodal models (LMMs), providing responses that appear correct but are actually incorrect, limits their reliability and applicability. This paper aims to study the hallucination problem of LMMs in video modality, which is dynamic and more challenging compared to static modalities like images and text. From this motivation, we first present a comprehensive benchmark termed HAVEN for evaluating hallucinations of LMMs in video understanding tasks. It is built upon three dimensions, i.e., hallucination causes, hallucination aspects, and question formats, resulting in 6K questions. Then, we quantitatively study 7 influential factors on hallucinations, e.g., duration time of videos, model sizes, and model reasoning, via experiments of 16 LMMs on the presented benchmark. In addition, inspired by recent thinking models like OpenAI o1, we propose a video-thinking model to mitigate the hallucinations of LMMs via supervised reasoning fine-tuning (SRFT) and direct preference optimization (TDPO)-- where SRFT enhances reasoning capabilities while TDPO reduces hallucinations in the thinking process. Extensive experiments and analyses demonstrate the effectiveness. Remarkably, it improves the baseline by 7.65% in accuracy on hallucination evaluation and reduces the bias score by 4.5%. The code and data are public at https://github.com/Hongcheng-Gao/HAVEN.

Na Gao, Chenfei Ye, Yanwu Yang et al.

Accurate characterization of hippocampal substructure is crucial for detecting subtle structural changes and identifying early neurodegenerative biomarkers. However, high inter-subject variability and complex folding pattern of human hippocampus hinder consistent cross-subject and longitudinal analysis. Most existing approaches rely on subject-specific modelling and lack a stable intrinsic coordinate system to accommodate anatomical variability, which limits their ability to establish reliable inter- and intra-individual correspondence. To address this, we propose HippMetric, a skeletal representation (s-rep)-based framework for hippocampal substructural morphometry and point-wise correspondence across individuals and scans. HippMetric builds on the Axis-Referenced Morphometric Model (ARMM) and employs a deformable skeletal coordinate system aligned with hippocampal anatomy and function, providing a biologically grounded reference for correspondence. Our framework comprises two core modules: a skeletal-based coordinate system that respects the hippocampus' conserved longitudinal lamellar architecture, in which functional units (lamellae) are stacked perpendicular to the long-axis, enabling anatomically consistent localization across subjects and time; and individualized s-reps generated through surface reconstruction, deformation, and geometrically constrained spoke refinement, enforcing boundary adherence, orthogonality and non-intersection to produce mathematically valid skeletal geometry. Extensive experiments on two international cohorts demonstrate that HippMetric achieves higher accuracy, reliability, and correspondence stability compared to existing shape models.

Li Liang, Naveed Akhtar, Jordan Vice et al.

3D semantic scene completion is critical for multiple downstream tasks in autonomous systems. It estimates missing geometric and semantic information in the acquired scene data. Due to the challenging real-world conditions, this task usually demands complex models that process multi-modal data to achieve acceptable performance. We propose a unique neural model, leveraging advances from the state space and diffusion generative modeling to achieve remarkable 3D semantic scene completion performance with monocular image input. Our technique processes the data in the conditioned latent space of a variational autoencoder where diffusion modeling is carried out with an innovative state space technique. A key component of our neural network is the proposed Skimba (Skip Mamba) denoiser, which is adept at efficiently processing long-sequence data. The Skimba diffusion model is integral to our 3D scene completion network, incorporating a triple Mamba structure, dimensional decomposition residuals and varying dilations along three directions. We also adopt a variant of this network for the subsequent semantic segmentation stage of our method. Extensive evaluation on the standard SemanticKITTI and SSCBench-KITTI360 datasets show that our approach not only outperforms other monocular techniques by a large margin, it also achieves competitive performance against stereo methods. The code is available at https://github.com/xrkong/skimba

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

Li Liang, Liu Jiannan, Wan Huaqing

The problem of estimating parameters of linear control valve with hysteresis is considered. The hysteretic behavior of control valve is formulated as a switched linear model. An indicator vector, which shows the switching epochs of switched linear model, is explored by subspace decomposition on measurements. With the help of indicator vector, the noisy measurements are classified into separate groups, each corresponding to up-stroke and down-stroke of control valve respectively. The least squares technique is adopted to estimate the parameters of control valve. It is shown that the proposed technique exactly estimates the parameters and switching epochs in absence of noise and exhibits dominant advantage in noisy case.

Li Liang, Bo Miao, Xinyu Wang et al.

Outdoor 3D semantic scene generation produces realistic and semantically rich environments for applications such as urban simulation and autonomous driving. However, advances in this direction are constrained by the absence of publicly available, well-annotated datasets. We introduce SketchSem3D, the first large-scale benchmark for generating 3D outdoor semantic scenes from abstract freehand sketches and pseudo-labeled annotations of satellite images. SketchSem3D includes two subsets, Sketch-based SemanticKITTI and Sketch-based KITTI-360 (containing LiDAR voxels along with their corresponding sketches and annotated satellite images), to enable standardized, rigorous, and diverse evaluations. We also propose Cylinder Mamba Diffusion (CymbaDiff) that significantly enhances spatial coherence in outdoor 3D scene generation. CymbaDiff imposes structured spatial ordering, explicitly captures cylindrical continuity and vertical hierarchy, and preserves both physical neighborhood relationships and global context within the generated scenes. Extensive experiments on SketchSem3D demonstrate that CymbaDiff achieves superior semantic consistency, spatial realism, and cross-dataset generalization. The code and dataset will be available at https://github.com/Lillian-research-hub/CymbaDiff

Zheng Wang, Hong Liu, Zheng Wang et al.

Survival analysis based on Whole Slide Images (WSIs) is crucial for evaluating cancer prognosis, as they offer detailed microscopic information essential for predicting patient outcomes. However, traditional WSI-based survival analysis usually faces noisy features and limited data accessibility, hindering their ability to capture critical prognostic features effectively. Although pathology reports provide rich patient-specific information that could assist analysis, their potential to enhance WSI-based survival analysis remains largely unexplored. To this end, this paper proposes a novel Report-auxiliary self-distillation (Rasa) framework for WSI-based survival analysis. First, advanced large language models (LLMs) are utilized to extract fine-grained, WSI-relevant textual descriptions from original noisy pathology reports via a carefully designed task prompt. Next, a self-distillation-based pipeline is designed to filter out irrelevant or redundant WSI features for the student model under the guidance of the teacher model's textual knowledge. Finally, a risk-aware mix-up strategy is incorporated during the training of the student model to enhance both the quantity and diversity of the training data. Extensive experiments carried out on our collected data (CRC) and public data (TCGA-BRCA) demonstrate the superior effectiveness of Rasa against state-of-the-art methods. Our code is available at https://github.com/zhengwang9/Rasa.

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).

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.

Yu Ming, Zihao Wu, Jie Yang et al.

Nucleus instance segmentation from histopathology images suffers from the extremely laborious and expert-dependent annotation of nucleus instances. As a promising solution to this task, annotation-efficient deep learning paradigms have recently attracted much research interest, such as weakly-/semi-supervised learning, generative adversarial learning, etc. In this paper, we propose to formulate annotation-efficient nucleus instance segmentation from the perspective of few-shot learning (FSL). Our work was motivated by that, with the prosperity of computational pathology, an increasing number of fully-annotated datasets are publicly accessible, and we hope to leverage these external datasets to assist nucleus instance segmentation on the target dataset which only has very limited annotation. To achieve this goal, we adopt the meta-learning based FSL paradigm, which however has to be tailored in two substantial aspects before adapting to our task. First, since the novel classes may be inconsistent with those of the external dataset, we extend the basic definition of few-shot instance segmentation (FSIS) to generalized few-shot instance segmentation (GFSIS). Second, to cope with the intrinsic challenges of nucleus segmentation, including touching between adjacent cells, cellular heterogeneity, etc., we further introduce a structural guidance mechanism into the GFSIS network, finally leading to a unified Structurally-Guided Generalized Few-Shot Instance Segmentation (SGFSIS) framework. Extensive experiments on a couple of publicly accessible datasets demonstrate that, SGFSIS can outperform other annotation-efficient learning baselines, including semi-supervised learning, simple transfer learning, etc., with comparable performance to fully supervised learning with less than 5% annotations.

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.

Huajun Zhou, Fengtao Zhou, Jiabo Ma et al.

Multimodal data provides heterogeneous information for a holistic understanding of the tumor microenvironment. However, existing AI models often struggle to harness the rich information within multimodal data and extract poorly generalizable representations. Here we present MICE (Multimodal data Integration via Collaborative Experts), a multimodal foundation model that effectively integrates pathology images, clinical reports, and genomics data for precise pan-cancer prognosis prediction. Instead of conventional multi-expert modules, MICE employs multiple functionally diverse experts to comprehensively capture both cross-cancer and cancer-specific insights. Leveraging data from 11,799 patients across 30 cancer types, we enhanced MICE's generalizability by coupling contrastive and supervised learning. MICE outperformed both unimodal and state-of-the-art multi-expert-based multimodal models, demonstrating substantial improvements in C-index ranging from 3.8% to 11.2% on internal cohorts and 5.8% to 8.8% on independent cohorts, respectively. Moreover, it exhibited remarkable data efficiency across diverse clinical scenarios. With its enhanced generalizability and data efficiency, MICE establishes an effective and scalable foundation for pan-cancer prognosis prediction, holding strong potential to personalize tailored therapies and improve treatment outcomes.

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.

Bingchao Zhao, Jiatai Lin, Changhong Liang et al.

Color inconsistency is an inevitable challenge in computational pathology, which generally happens because of stain intensity variations or sections scanned by different scanners. It harms the pathological image analysis methods, especially the learning-based models. A series of approaches have been proposed for stain normalization. However, most of them are lack flexibility in practice. In this paper, we formulated stain normalization as a digital re-staining process and proposed a self-supervised learning model, which is called RestainNet. Our network is regarded as a digital restainer which learns how to re-stain an unstained (grayscale) image. Two digital stains, Hematoxylin (H) and Eosin (E) were extracted from the original image by Beer-Lambert's Law. We proposed a staining loss to maintain the correctness of stain intensity during the restaining process. Thanks to the self-supervised nature, paired training samples are no longer necessary, which demonstrates great flexibility in practical usage. Our RestainNet outperforms existing approaches and achieves state-of-the-art performance with regard to color correctness and structure preservation. We further conducted experiments on the segmentation and classification tasks and the proposed RestainNet achieved outstanding performance compared with SOTA methods. The self-supervised design allows the network to learn any staining style with no extra effort.

Jiatai Lin, Guoqiang Han, Xipeng Pan et al.

Histopathological tissue classification is a fundamental task in pathomics cancer research. Precisely differentiating different tissue types is a benefit for the downstream researches, like cancer diagnosis, prognosis and etc. Existing works mostly leverage the popular classification backbones in computer vision to achieve histopathological tissue classification. In this paper, we proposed a super lightweight plug-and-play module, named Pyramidal Deep-Broad Learning (PDBL), for any well-trained classification backbone to further improve the classification performance without a re-training burden. We mimic how pathologists observe pathology slides in different magnifications and construct an image pyramid for the input image in order to obtain the pyramidal contextual information. For each level in the pyramid, we extract the multi-scale deep-broad features by our proposed Deep-Broad block (DB-block). We equipped PDBL in three popular classification backbones, ShuffLeNetV2, EfficientNetb0, and ResNet50 to evaluate the effectiveness and efficiency of our proposed module on two datasets (Kather Multiclass Dataset and the LC25000 Dataset). Experimental results demonstrate the proposed PDBL can steadily improve the tissue-level classification performance for any CNN backbones, especially for the lightweight models when given a small among of training samples (less than 10%), which greatly saves the computational time and annotation efforts.

Li Liang, Zheng Zhao, Bonnie Webber

The PDTB-3 contains many more Implicit discourse relations than the previous PDTB-2. This is in part because implicit relations have now been annotated within sentences as well as between them. In addition, some now co-occur with explicit discourse relations, instead of standing on their own. Here we show that while this can complicate the problem of identifying the location of implicit discourse relations, it can in turn simplify the problem of identifying their senses. We present data to support this claim, as well as methods that can serve as a non-trivial baseline for future state-of-the-art recognizers for implicit discourse relations.