Diagnose Like A REAL Pathologist: An Uncertainty-Focused Approach for Trustworthy Multi-Resolution Multiple Instance Learning

With the increasing demand for histopathological specimen examination and diagnostic reporting, Multiple Instance Learning (MIL) has received heightened research focus as a viable solution for AI-centric diagnostic aid. Recently, to improve its performance and make it work more like a pathologist, several MIL approaches based on the use of multiple-resolution images have been proposed, delivering often higher performance than those that use single-resolution images. Despite impressive recent developments of multiple-resolution MIL, previous approaches only focus on improving performance, thereby lacking research on well-calibrated MIL that clinical experts can rely on for trustworthy diagnostic results. In this study, we propose Uncertainty-Focused Calibrated MIL (UFC-MIL), which more closely mimics the pathologists' examination behaviors while providing calibrated diagnostic predictions, using multiple images with different resolutions. UFC-MIL includes a novel patch-wise loss that learns the latent patterns of instances and expresses their uncertainty for classification. Also, the attention-based architecture with a neighbor patch aggregation module collects features for the classifier. In addition, aggregated predictions are calibrated through patch-level uncertainty without requiring multiple iterative inferences, which is a key practical advantage. Against challenging public datasets, UFC-MIL shows superior performance in model calibration while achieving classification accuracy comparable to that of state-of-the-art methods.