Jiabo Ma

Yiping Jiao, Jeroen van der Laak, Shadi Albarqouni et al. · eth-zurich

We introduce LYSTO, the Lymphocyte Assessment Hackathon, which was held in conjunction with the MICCAI 2019 Conference in Shenzen (China). The competition required participants to automatically assess the number of lymphocytes, in particular T-cells, in histopathological images of colon, breast, and prostate cancer stained with CD3 and CD8 immunohistochemistry. Differently from other challenges setup in medical image analysis, LYSTO participants were solely given a few hours to address this problem. In this paper, we describe the goal and the multi-phase organization of the hackathon; we describe the proposed methods and the on-site results. Additionally, we present post-competition results where we show how the presented methods perform on an independent set of lung cancer slides, which was not part of the initial competition, as well as a comparison on lymphocyte assessment between presented methods and a panel of pathologists. We show that some of the participants were capable to achieve pathologist-level performance at lymphocyte assessment. After the hackathon, LYSTO was left as a lightweight plug-and-play benchmark dataset on grand-challenge website, together with an automatic evaluation platform. LYSTO has supported a number of research in lymphocyte assessment in oncology. LYSTO will be a long-lasting educational challenge for deep learning and digital pathology, it is available at https://lysto.grand-challenge.org/.

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.

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.

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.

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).

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.

Zhengrui Guo, Conghao Xiong, Jiabo Ma et al.

Few-shot learning presents a critical solution for cancer diagnosis in computational pathology (CPath), addressing fundamental limitations in data availability, particularly the scarcity of expert annotations and patient privacy constraints. A key challenge in this paradigm stems from the inherent disparity between the limited training set of whole slide images (WSIs) and the enormous number of contained patches, where a significant portion of these patches lacks diagnostically relevant information, potentially diluting the model's ability to learn and focus on critical diagnostic features. While recent works attempt to address this by incorporating additional knowledge, several crucial gaps hinder further progress: (1) despite the emergence of powerful pathology foundation models (FMs), their potential remains largely untapped, with most approaches limiting their use to basic feature extraction; (2) current language guidance mechanisms attempt to align text prompts with vast numbers of WSI patches all at once, struggling to leverage rich pathological semantic information. To this end, we introduce the knowledge-enhanced adaptive visual compression framework, dubbed FOCUS, which uniquely combines pathology FMs with language prior knowledge to enable a focused analysis of diagnostically relevant regions by prioritizing discriminative WSI patches. Our approach implements a progressive three-stage compression strategy: we first leverage FMs for global visual redundancy elimination, and integrate compressed features with language prompts for semantic relevance assessment, then perform neighbor-aware visual token filtering while preserving spatial coherence. Extensive experiments on pathological datasets spanning breast, lung, and ovarian cancers demonstrate its superior performance in few-shot pathology diagnosis. Codes are available at https://github.com/dddavid4real/FOCUS.

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.

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

Zhengrui Guo, Qichen Sun, Jiabo Ma et al.

Whole slide image (WSI) analysis presents significant computational challenges due to the massive number of patches in gigapixel images. While transformer architectures excel at modeling long-range correlations through self-attention, their quadratic computational complexity makes them impractical for computational pathology applications. Existing solutions like local-global or linear self-attention reduce computational costs but compromise the strong modeling capabilities of full self-attention. In this work, we propose Querent, i.e., the query-aware long contextual dynamic modeling framework, which achieves a theoretically bounded approximation of full self-attention while delivering practical efficiency. Our method adaptively predicts which surrounding regions are most relevant for each patch, enabling focused yet unrestricted attention computation only with potentially important contexts. By using efficient region-wise metadata computation and importance estimation, our approach dramatically reduces computational overhead while preserving global perception to model fine-grained patch correlations. Through comprehensive experiments on biomarker prediction, gene mutation prediction, cancer subtyping, and survival analysis across over 10 WSI datasets, our method demonstrates superior performance compared to the state-of-the-art approaches. Codes are available at https://github.com/dddavid4real/Querent.

Fang Yan, Jianfeng Wu, Jiawen Li et al.

The complexity and variability inherent in high-resolution pathological images present significant challenges in computational pathology. While pathology foundation models leveraging AI have catalyzed transformative advancements, their development demands large-scale datasets, considerable storage capacity, and substantial computational resources. Furthermore, ensuring their clinical applicability and generalizability requires rigorous validation across a broad spectrum of clinical tasks. Here, we present PathOrchestra, a versatile pathology foundation model trained via self-supervised learning on a dataset comprising 300K pathological slides from 20 tissue and organ types across multiple centers. The model was rigorously evaluated on 112 clinical tasks using a combination of 61 private and 51 public datasets. These tasks encompass digital slide preprocessing, pan-cancer classification, lesion identification, multi-cancer subtype classification, biomarker assessment, gene expression prediction, and the generation of structured reports. PathOrchestra demonstrated exceptional performance across 27,755 WSIs and 9,415,729 ROIs, achieving over 0.950 accuracy in 47 tasks, including pan-cancer classification across various organs, lymphoma subtype diagnosis, and bladder cancer screening. Notably, it is the first model to generate structured reports for high-incidence colorectal cancer and diagnostically complex lymphoma-areas that are infrequently addressed by foundational models but hold immense clinical potential. Overall, PathOrchestra exemplifies the feasibility and efficacy of a large-scale, self-supervised pathology foundation model, validated across a broad range of clinical-grade tasks. Its high accuracy and reduced reliance on extensive data annotation underline its potential for clinical integration, offering a pathway toward more efficient and high-quality medical services.

Linshan Wu, Jiaxin Zhuang, Yanning Zhou et al.

Tumor is a leading cause of death worldwide, with an estimated 10 million deaths attributed to tumor-related diseases every year. AI-driven tumor recognition unlocks new possibilities for more precise and intelligent tumor screening and diagnosis. However, the progress is heavily hampered by the scarcity of annotated datasets, which demands extensive annotation efforts by radiologists. To tackle this challenge, we introduce FreeTumor, an innovative Generative AI (GAI) framework to enable large-scale tumor synthesis for mitigating data scarcity. Specifically, FreeTumor effectively leverages a combination of limited labeled data and large-scale unlabeled data for tumor synthesis training. Unleashing the power of large-scale data, FreeTumor is capable of synthesizing a large number of realistic tumors on images for augmenting training datasets. To this end, we create the largest training dataset for tumor synthesis and recognition by curating 161,310 publicly available Computed Tomography (CT) volumes from 33 sources, with only 2.3% containing annotated tumors. To validate the fidelity of synthetic tumors, we engaged 13 board-certified radiologists in a Visual Turing Test to discern between synthetic and real tumors. Rigorous clinician evaluation validates the high quality of our synthetic tumors, as they achieved only 51.1% sensitivity and 60.8% accuracy in distinguishing our synthetic tumors from real ones. Through high-quality tumor synthesis, FreeTumor scales up the recognition training datasets by over 40 times, showcasing a notable superiority over state-of-the-art AI methods including various synthesis methods and foundation models. These findings indicate promising prospects of FreeTumor in clinical applications, potentially advancing tumor treatments and improving the survival rates of patients.

Hao Jiang, Cheng Jin, Huangjing Lin et al.

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

Yu Cai, Cheng Jin, Jiabo Ma et al.

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

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.

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.

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.

Jiabo Ma, Sibo Liu, Shenghua Cheng et al.

High-resolution 3D medical images are important for analysis and diagnosis, but axial scanning to acquire them is very time-consuming. In this paper, we propose a fast end-to-end multi-focal plane imaging network (MFPINet) to reconstruct high-resolution multi-focal plane images from a single 2D low-resolution wild filed image without relying on scanning. To acquire realistic MFP images fast, the proposed MFPINet adopts generative adversarial network framework and the strategies of post-sampling and refocusing all focal planes at one time. We conduct a series experiments on cytology microscopy images and demonstrate that MFPINet performs well on both axial refocusing and horizontal super resolution. Furthermore, MFPINet is approximately 24 times faster than current refocusing methods for reconstructing the same volume images. The proposed method has the potential to greatly increase the speed of high-resolution 3D imaging and expand the application of low-resolution wide-field images.

Xiebo Geng, Sibo Liua, Wei Han et al.

Multi-focus image fusion technologies compress different focus depth images into an image in which most objects are in focus. However, although existing image fusion techniques, including traditional algorithms and deep learning-based algorithms, can generate high-quality fused images, they need multiple images with different focus depths in the same field of view. This criterion may not be met in some cases where time efficiency is required or the hardware is insufficient. The problem is especially prominent in large-size whole slide images. This paper focused on the multi-focus image fusion of cytopathological digital slide images, and proposed a novel method for generating fused images from single-focus or few-focus images based on conditional generative adversarial network (GAN). Through the adversarial learning of the generator and discriminator, the method is capable of generating fused images with clear textures and large depth of field. Combined with the characteristics of cytopathological images, this paper designs a new generator architecture combining U-Net and DenseBlock, which can effectively improve the network's receptive field and comprehensively encode image features. Meanwhile, this paper develops a semantic segmentation network that identifies the blurred regions in cytopathological images. By integrating the network into the generative model, the quality of the generated fused images is effectively improved. Our method can generate fused images from only single-focus or few-focus images, thereby avoiding the problem of collecting multiple images of different focus depths with increased time and hardware costs. Furthermore, our model is designed to learn the direct mapping of input source images to fused images without the need to manually design complex activity level measurements and fusion rules as in traditional methods.