Hao Chen

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.

Jinghui Yuan, Hao Chen, Renwei Luo et al.

Ensemble learning has achieved remarkable success in machine learning, but its reliance on numerous base learners limits its application in resource-constrained environments. This paper introduces an innovative "Margin-Maximizing Fine-Grained Ensemble Method" that achieves performance surpassing large-scale ensembles by meticulously optimizing a small number of learners and enhancing generalization capability. We propose a novel learnable confidence matrix, quantifying each classifier's confidence for each category, precisely capturing category-specific advantages of individual learners. Furthermore, we design a margin-based loss function, constructing a smooth and partially convex objective using the logsumexp technique. This approach improves optimization, eases convergence, and enables adaptive confidence allocation. Finally, we prove that the loss function is Lipschitz continuous, based on which we develop an efficient gradient optimization algorithm that simultaneously maximizes margins and dynamically adjusts learner weights. Extensive experiments demonstrate that our method outperforms traditional random forests using only one-tenth of the base learners and other state-of-the-art ensemble methods.

Wenhao Tang, Rong Qin, Heng Fang et al.

Pre-trained encoders for offline feature extraction followed by multiple instance learning (MIL) aggregators have become the dominant paradigm in computational pathology (CPath), benefiting cancer diagnosis and prognosis. However, performance limitations arise from the absence of encoder fine-tuning for downstream tasks and disjoint optimization with MIL. While slide-level supervised end-to-end (E2E) learning is an intuitive solution to this issue, it faces challenges such as high computational demands and suboptimal results. These limitations motivate us to revisit E2E learning. We argue that prior work neglects inherent E2E optimization challenges, leading to performance disparities compared to traditional two-stage methods. In this paper, we pioneer the elucidation of optimization challenge caused by sparse-attention MIL and propose a novel MIL called ABMILX. It mitigates this problem through global correlation-based attention refinement and multi-head mechanisms. With the efficient multi-scale random patch sampling strategy, an E2E trained ResNet with ABMILX surpasses SOTA foundation models under the two-stage paradigm across multiple challenging benchmarks, while remaining computationally efficient (<10 RTX3090 hours). We show the potential of E2E learning in CPath and calls for greater research focus in this area. The code is https://github.com/DearCaat/E2E-WSI-ABMILX.

Qichen Sun, Zhengrui Guo, Rui Peng et al.

Recent advances in computational pathology and artificial intelligence have significantly enhanced the utilization of gigapixel whole-slide images and and additional modalities (e.g., genomics) for pathological diagnosis. Although deep learning has demonstrated strong potential in pathology, several key challenges persist: (1) fusing heterogeneous data types requires sophisticated strategies beyond simple concatenation due to high computational costs; (2) common scenarios of missing modalities necessitate flexible strategies that allow the model to learn robustly in the absence of certain modalities; (3) the downstream tasks in CPath are diverse, ranging from unimodal to multimodal, cnecessitating a unified model capable of handling all modalities. To address these challenges, we propose ALTER, an any-to-any tri-modal pretraining framework that integrates WSIs, genomics, and pathology reports. The term "any" emphasizes ALTER's modality-adaptive design, enabling flexible pretraining with any subset of modalities, and its capacity to learn robust, cross-modal representations beyond WSI-centric approaches. We evaluate ALTER across extensive clinical tasks including survival prediction, cancer subtyping, gene mutation prediction, and report generation, achieving superior or comparable performance to state-of-the-art baselines.