MUFASA: An Information Utility-Aware Preprocessing Framework for Reliable Model Reasoning in Computational Pathology
Reliable computational pathology depends on preprocessing methods that identify informative tissue regions while excluding artifacts and low-utility regions from whole-slide images (WSI). However, existing preprocessing pipelines often retain such regions or discard diagnostically relevant tissue, thereby limiting downstream model performance, reliability, and robustness across heterogeneous cohorts. Here, we systematically evaluate how these regions affect downstream AI model performance across multiple clinically relevant applications and introduce MUFASA, a generalizable, information utility-aware preprocessing framework for H&E-stained WSI that excludes artifacts and low-utility regions while preserving biologically meaningful tissue. MUFASA integrates slide-level artifact masking, stain-aware tile filtering, reconstruction-based utility stratification of tiles, and targeted recovery of tissue tiles that are over-filtered by earlier phases. Across tumor diagnosis, tumor subtyping, biomarker status prediction, and survival prognostication tasks in diverse cancer cohorts, MUFASA consistently improves downstream model performance relative to widely used preprocessing baselines. These gains are accompanied by reduced artifact-associated attribution in model heatmaps, indicating improved alignment between retained tissue and model attention. Our findings establish WSI preprocessing as a critical determinant of downstream model performance and validity, revealing that even accurate predictions can conceal important failure modes stemming from anatomically implausible reasoning driven by retained artifact-containing and low information-utility tiles.