Towards reliable WMH segmentation under domain shift: An application study using maximum entropy regularization to improve uncertainty estimation

Abstract

Background: Accurate segmentation of white matter hyperintensities (WMH) is crucial for clinical decisionmaking, particularly in the context of multiple sclerosis. However, domain shifts, such as variations in MRI machine types or acquisition parameters, pose significant challenges to model calibration and uncertainty estimation. This comparative study investigates the impact of domain shift on WMH segmentation, proposing maximum-entropy regularization techniques to enhance model calibration and uncertainty estimation. The purpose is to identify errors appearing after model deployment in clinical scenarios using predictive uncertainty as a proxy measure, since it does not require ground-truth labels to be computed. Methods: We conducted experiments using a classic U-Net architecture and evaluated maximum entropy regularization schemes to improve model calibration under domain shift on two publicly available datasets: the WMH Segmentation Challenge and the 3D-MR-MS dataset. Performance is assessed with Dice coefficient, Hausdorff distance, expected calibration error, and entropy-based uncertainty estimates. Results: Entropy-based uncertainty estimates can anticipate segmentation errors, both in-distribution and out-ofdistribution, with maximum-entropy regularization further strengthening the correlation between uncertainty and segmentation performance, while also improving model calibration under domain shift. Conclusions: Maximum-entropy regularization improves uncertainty estimation for WMH segmentation under domain shift. By strengthening the relationship between predictive uncertainty and segmentation errors, these methods allow models to better flag unreliable predictions without requiring ground-truth annotations. Additionally, maximum-entropy regularization contributes to better model calibration, supporting more reliable and safer deployment of deep learning models in multi-center and heterogeneous clinical environments.