Chenglong Zhao

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.

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.

Jiancheng Yang, Yangzhou Jiang, Xiaoyang Huang et al.

This paper addresses the challenging black-box adversarial attack problem, where only classification confidence of a victim model is available. Inspired by consistency of visual saliency between different vision models, a surrogate model is expected to improve the attack performance via transferability. By combining transferability-based and query-based black-box attack, we propose a surprisingly simple baseline approach (named SimBA++) using the surrogate model, which significantly outperforms several state-of-the-art methods. Moreover, to efficiently utilize the query feedback, we update the surrogate model in a novel learning scheme, named High-Order Gradient Approximation (HOGA). By constructing a high-order gradient computation graph, we update the surrogate model to approximate the victim model in both forward and backward pass. The SimBA++ and HOGA result in Learnable Black-Box Attack (LeBA), which surpasses previous state of the art by considerable margins: the proposed LeBA significantly reduces queries, while keeping higher attack success rates close to 100% in extensive ImageNet experiments, including attacking vision benchmarks and defensive models. Code is open source at https://github.com/TrustworthyDL/LeBA.

Jianlong Jin, Chenglong Zhao, Ruixin Zhang et al.

Palmprint recognition is significantly limited by the lack of large-scale publicly available datasets. Previous methods have adopted Bézier curves to simulate the palm creases, which then serve as input for conditional GANs to generate realistic palmprints. However, without employing real data fine-tuning, the performance of the recognition model trained on these synthetic datasets would drastically decline, indicating a large gap between generated and real palmprints. This is primarily due to the utilization of an inaccurate palm crease representation and challenges in balancing intra-class variation with identity consistency. To address this, we introduce a polynomial-based palm crease representation that provides a new palm crease generation mechanism more closely aligned with the real distribution. We also propose the palm creases conditioned diffusion model with a novel intra-class variation control method. By applying our proposed $K$-step noise-sharing sampling, we are able to synthesize palmprint datasets with large intra-class variation and high identity consistency. Experimental results show that, for the first time, recognition models trained solely on our synthetic datasets, without any fine-tuning, outperform those trained on real datasets. Furthermore, our approach achieves superior recognition performance as the number of generated identities increases.

Sheng Shang, Chenglong Zhao, Ruixin Zhang et al.

Palm vein recognition is an emerging biometric technology that offers enhanced security and privacy. However, acquiring sufficient palm vein data for training deep learning-based recognition models is challenging due to the high costs of data collection and privacy protection constraints. This has led to a growing interest in generating pseudo-palm vein data using generative models. Existing methods, however, often produce unrealistic palm vein patterns or struggle with controlling identity and style attributes. To address these issues, we propose a novel palm vein generation framework named PVTree. First, the palm vein identity is defined by a complex and authentic 3D palm vascular tree, created using an improved Constrained Constructive Optimization (CCO) algorithm. Second, palm vein patterns of the same identity are generated by projecting the same 3D vascular tree into 2D images from different views and converting them into realistic images using a generative model. As a result, PVTree satisfies the need for both identity consistency and intra-class diversity. Extensive experiments conducted on several publicly available datasets demonstrate that our proposed palm vein generation method surpasses existing methods and achieves a higher TAR@FAR=1e-4 under the 1:1 Open-set protocol. To the best of our knowledge, this is the first time that the performance of a recognition model trained on synthetic palm vein data exceeds that of the recognition model trained on real data, which indicates that palm vein image generation research has a promising future.

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.

Ruoxi Shi, Borui Yang, Yangzhou Jiang et al.

In this work we propose Energy Attack, a transfer-based black-box $L_\infty$-adversarial attack. The attack is parameter-free and does not require gradient approximation. In particular, we first obtain white-box adversarial perturbations of a surrogate model and divide these perturbations into small patches. Then we extract the unit component vectors and eigenvalues of these patches with principal component analysis (PCA). Base on the eigenvalues, we can model the energy distribution of adversarial perturbations. We then perform black-box attacks by sampling from the perturbation patches according to their energy distribution, and tiling the sampled patches to form a full-size adversarial perturbation. This can be done without the available access to victim models. Extensive experiments well demonstrate that the proposed Energy Attack achieves state-of-the-art performance in black-box attacks on various models and several datasets. Moreover, the extracted distribution is able to transfer among different model architectures and different datasets, and is therefore intrinsic to vision architectures.

Yunxiang Zhang, Chenglong Zhao, Bingbing Ni et al.

To address the limitations of existing magnitude-based pruning algorithms in cases where model weights or activations are of large and similar magnitude, we propose a novel perspective to discover parameter redundancy among channels and accelerate deep CNNs via channel pruning. Precisely, we argue that channels revealing similar feature information have functional overlap and that most channels within each such similarity group can be removed without compromising model's representational power. After deriving an effective metric for evaluating channel similarity through probabilistic modeling, we introduce a pruning algorithm via hierarchical clustering of channels. In particular, the proposed algorithm does not rely on sparsity training techniques or complex data-driven optimization and can be directly applied to pre-trained models. Extensive experiments on benchmark datasets strongly demonstrate the superior acceleration performance of our approach over prior arts. On ImageNet, our pruned ResNet-50 with 30% FLOPs reduced outperforms the baseline model.