Contrastive Integrated Gradients: A Feature Attribution-Based Method for Explaining Whole Slide Image Classification

Interpretability is essential in Whole Slide Image (WSI) analysis for computational pathology, where understanding model predictions helps build trust in AI-assisted diagnostics. While Integrated Gradients (IG) and related attribution methods have shown promise, applying them directly to WSIs introduces challenges due to their high-resolution nature. These methods capture model decision patterns but may overlook class-discriminative signals that are crucial for distinguishing between tumor subtypes. In this work, we introduce Contrastive Integrated Gradients (CIG), a novel attribution method that enhances interpretability by computing contrastive gradients in logit space. First, CIG highlights class-discriminative regions by comparing feature importance relative to a reference class, offering sharper differentiation between tumor and non-tumor areas. Second, CIG satisfies the axioms of integrated attribution, ensuring consistency and theoretical soundness. Third, we propose two attribution quality metrics, MIL-AIC and MIL-SIC, which measure how predictive information and model confidence evolve with access to salient regions, particularly under weak supervision. We validate CIG across three datasets spanning distinct cancer types: CAMELYON16 (breast cancer metastasis in lymph nodes), TCGA-RCC (renal cell carcinoma), and TCGA-Lung (lung cancer). Experimental results demonstrate that CIG yields more informative attributions both quantitatively, using MIL-AIC and MIL-SIC, and qualitatively, through visualizations that align closely with ground truth tumor regions, underscoring its potential for interpretable and trustworthy WSI-based diagnostics

Anh Mai Vu, Tuan L. Vo, Ngoc Lam Quang Bui, Nam Nguyen Le Binh, Akash Awasthi, Huy Quoc Vo, Thanh-Huy Nguyen, Zhu Han, Chandra Mohan, Hien Van Nguyen · 2025