用分子信息指导组织分区,让病理模型更懂真实病灶结构。
CARE: A Molecular-Guided Foundation Model with Adaptive Region Modeling for Whole Slide Image Analysis
- 通过双阶段预训练,自动划分组织切片为生物学相关的区域。
- 仅用十分之一数据量,33项任务平均表现超越主流模型。
- 适合需要高解释性病理分析的临床研究与药物开发人员。
基础模型在计算病理学中表现出色,但现有方法依赖自然图像骨干网络,忽视了病理区域的异质性和非均匀性,难以捕捉整体组织架构,限制了可解释性和临床价值。为此,我们提出跨模态自适应区域编码器(CARE),一种面向病理学的基础模型,能自动将全切片图像(WSI)划分为多个形态学相关区域。CARE采用两阶段预训练:(1) 在无分割标注的情况下,基于34,277张全切片图像进行自监督单模态预训练,学习组织形态表征;(2) 利用RNA和蛋白表达谱进行跨模态对齐,优化区域构建与表征。分子引导使CARE识别出生物相关模式,生成不规则但连贯的组织区域,并选出最具代表性区域作为感兴趣区(ROI)。CARE支持多种病理任务,可使用ROI特征或聚合自适应区域的切片级特征。仅使用主流模型十分之一的预训练数据,其在33个下游基准上平均表现更优,涵盖形态分类、分子预测与生存分析,整体优于其他基础模型基线。
原文摘要 · Abstract (English)
Foundation models have recently achieved impressive success in computational pathology, demonstrating strong generalization across diverse histopathology tasks. However, existing models overlook the heterogeneous and non-uniform organization of pathological regions of interest (ROIs) because they rely on natural image backbones not tailored for tissue morphology. Consequently, they often fail to capture the coherent tissue architecture beyond isolated patches, limiting interpretability and clinical relevance. To address these challenges, we present Cross-modal Adaptive Region Encoder (CARE), a foundation model for pathology that automatically partitions WSIs into several morphologically relevant regions. Specifically, CARE employs a two-stage pretraining strategy: (1) a self-supervised unimodal pretraining stage that learns morphological representations from 34,277 whole-slide images (WSIs) without segmentation annotations, and (2) a cross-modal alignment stage that leverages RNA and protein profiles to refine the construction and representation of adaptive regions. This molecular guidance enables CARE to identify biologically relevant patterns and generate irregular yet coherent tissue regions, selecting the most representative area as ROI. CARE supports a broad range of pathology-related tasks, using either the ROI feature or the slide-level feature obtained by aggregating adaptive regions. Based on only one-tenth of the pretraining data typically used by mainstream foundation models, CARE achieves superior average performance across 33 downstream benchmarks, including morphological classification, molecular prediction, and survival analysis, and outperforms other foundation model baselines overall.
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