Intervention-based Mixup Augmentation for Multiple Instance Learning in Whole-Slide Image Survival Analysis

In the field of computational pathology, multiple instance learning (MIL) has become a critical modeling framework for analyzing gigapixel whole-slide images (WSIs). Data scarcity, particularly in survival analyses requiring long-term follow-up, is a prevalent challenge that is often mitigated through data augmentation. Although data augmentation methods for multi-instance classification have progressed, they remain insufficient for multi-instance regression in survival analysis. Compared to classification tasks, data augmentation for survival analysis faces two major challenges: i) higher quality requirements for pseudo-labels on newly generated samples, and ii) imbalanced data distribution, exhibiting the long-tail distribution. To address these challenges, this paper introduces InterMix, a novel plug-and-play multi-instance data augmentation scheme inspired by the concept of intervention. To provide high-quality pseudo-labels, sub-bag assessment rules are proposed to screen out stable and consistent sub-bags before mixing. To alleviate the long-tail problem, this paper proposes the complementary mix strategy to generate minority-augmented instances with high diversity based on the risk distribution of patients. Extensive experiments are conducted on three datasets to demonstrate the superiority of InterMix. In addition, it enables the model to focus more on key areas of concern for pathologists. Our source code has been made available at github.com/lingzhi-T/InterMIx.