NSB-H2GAN: "Negative Sample"-boosted Hierarchical Heterogeneous Graph Attention Network for Interpretable Classification of Whole-Slide Images

Gigapixel whole-slide image (WSI) prediction and region-of-interest localization present considerable challenges due to the diverse range of features both across different slides and within individual slides. Most current methods rely on weakly supervised learning using homogeneous graphs to establish context-aware relevance within slides, often neglecting the rich diversity of heterogeneous information inherent in pathology images. Inspired by the negative sampling strategy of the Determinantal Point Process (DPP) and the hierarchical structure of pathology slides, we introduce the Negative Sample Boosted Hierarchical Heterogeneous Graph Attention Network (NSB-H2GAN). This model addresses the over-smoothing issue typically encountered in classical Graph Convolutional Networks (GCNs) when applied to pathology slides. By incorporating "negative samples" at multiple scales and utilizing hierarchical, heterogeneous feature discrimination, NSB-H2GAN more effectively captures the unique features of each patch, leading to an improved representation of gigapixel WSIs. We evaluated the performance of NSB-H2GAN on three publicly available datasets: CAMELYON16, TCGA-NSCLC and TCGA-COAD. The results show that NSB-H2GAN significantly outperforms existing state-of-the-art methods in both qualitative and quantitative evaluations. Moreover, NSB-H2GAN generates more detailed and interpretable heatmaps, allowing for precise localization of tiny lesions as small as 200 μm × 200μm that are often missed by the human eye. The robust performance of NSB-H2GAN offers a new paradigm for computer-aided pathology diagnosis and holds great potential for advancing the clinical applications of computational pathology.