Explainable AI for computational pathology identifies model limitations and tissue biomarkers
Introduction: Deep learning models hold great promise for digital pathology, but their opaque decision-making processes undermine trust and hinder clinical adoption. Explainable AI methods are essential to enhance model transparency and reliability. Methods: We developed HIPPO, an explainable AI framework that systematically modifies tissue regions in whole slide images to generate image counterfactuals, enabling quantitative hypothesis testing, bias detection, and model evaluation beyond traditional performance metrics. HIPPO was applied to a variety of clinically important tasks, including breast metastasis detection in axillary lymph nodes, prognostication in breast cancer and melanoma, and IDH mutation classification in gliomas. In computational experiments, HIPPO was compared against traditional metrics and attention-based approaches to assess its ability to identify key tissue elements driving model predictions. Results: In metastasis detection, HIPPO uncovered critical model limitations that were undetectable by standard performance metrics or attention-based methods. For prognostic prediction, HIPPO outperformed attention by providing more nuanced insights into tissue elements influencing outcomes. In a proof-of-concept study, HIPPO facilitated hypothesis generation for identifying melanoma patients who may benefit from immunotherapy. In IDH mutation classification, HIPPO more robustly identified the pathology regions responsible for false negatives compared to attention, suggesting its potential to outperform attention in explaining model decisions. Conclusions: HIPPO expands the explainable AI toolkit for computational pathology by enabling deeper insights into model behavior. This framework supports the trustworthy development, deployment, and regulation of weakly-supervised models in clinical and research settings, promoting their broader adoption in digital pathology.
Code (1)
Tasks
Bias DetectioncounterfactualDecision MakingMultiple Instance Learningwhole slide imagesMethods 이 논문이 사용한 방법론
Similar Papers 제목 키워드 기반
GRAPHITE: Graph-Based Interpretable Tissue Examination for Enhanced Explainability in Breast Cancer Histopathology
Explainable AI (XAI) in medical histopathology is essential for enhancing the interpretability and clinical trustworthiness of deep learning models in cancer diagnosis. However, the black-box nature of these models often…
DiagnosticGraph Attentionwhole slide imagesRobust Interactive Semantic Segmentation of Pathology Images with Minimal User Input
From the simple measurement of tissue attributes in pathology workflow to designing an explainable diagnostic/prognostic AI tool, access to accurate semantic segmentation of tissue regions in histology images is a prereq…
DiagnosticInteractive SegmentationSegmentationSemantic SegmentationTowards Launching AI Algorithms for Cellular Pathology into Clinical & Pharmaceutical Orbits
Computational Pathology (CPath) is an emerging field concerned with the study of tissue pathology via computational algorithms for the processing and analysis of digitized high-resolution images of tissue slides. Recent …
Needle Biopsy And Fiber-Optic Compatible Robotic Insertion Platform
Tissue biopsy is the gold standard for diagnosing many diseases, involving the extraction of diseased tissue for histopathology analysis by expert pathologists. However, this procedure has two main limitations: 1) Manual…
Act Like a Pathologist: Tissue-Aware Whole Slide Image Reasoning
Computational pathology has advanced rapidly in recent years, driven by domain-specific image encoders and growing interest in using vision-language models to answer natural-language questions about diseases. Yet, the co…