Cluster-Level Sparse Multi-Instance Learning for Whole-Slide Images

Abstract

Multi-Instance Learning (MIL) is pivotal for analyzing complex, weakly labeled datasets, such as whole-slide images (WSIs) in computational pathology, where bags comprise unordered collections of instances with sparse diagnostic relevance. Traditional MIL approaches, including early statistical methods and recent attention-based frameworks, struggle with instance redundancy and lack explicit mechanisms for discarding non-informative instances, limiting their robustness and interpretability. We propose Cluster-level Sparse MIL (csMIL), a novel framework that integrates global-local instance clustering, within-cluster attention, and cluster-level sparsity induction to address these challenges. Our csMIL first performs global clustering across all bags to establish $K$ cluster centers, followed by local clustering within each bag to assign cluster labels. Attention scores are computed within each cluster, and sparse regularization is applied to cluster weights, enabling the selective retention of diagnostically relevant clusters while discarding irrelevant ones. This approach enhances robustness to noisy instances, improves interpretability by identifying critical regions, and reduces computational complexity. Theoretical analysis demonstrates that csMIL requires $O(s log K)$ bags to recover $s$ relevant clusters, aligning with compressed sensing principles. Empirically, csMIL achieves state-of-the-art performance on two public histopathology benchmarks (CAMELYON16, TCGA-NSCLC).