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Deep learning (DL) methods for white matter lesion (WML) segmentation in MRI suffer a reduction in performance when applied on data from a scanner or centre that is out-of-distribution (OOD) from the training data. This is critical for translation and widescale adoption, since current models cannot be readily applied to data from new institutions. In this work, we evaluate several intensity standardization methods for MRI as a preprocessing step for WML segmentation in multi-centre Fluid-Attenuated Inversion Recovery (FLAIR) MRI. We evaluate a method specifically developed for FLAIR MRI called IAMLAB along with other popular normalization techniques such as White-strip, Nyul and Z-score. We proposed an Ensemble model that combines predictions from each of these models. A skip-connection UNet (SC UNet) was trained on the standardized images, as well as the original data and segmentation performance was evaluated over several dimensions. The training (in-distribution) data consists of a single study, of 60 volumes, and the test (OOD) data is 128 unseen volumes from three clinical cohorts. Results show IAMLAB and Ensemble provide higher WML segmentation performance compared to models from original data or other normalization methods. IAMLAB & Ensemble have the highest dice similarity coefficient (DSC) on the in-distribution data (0.78 & 0.80) and on clinical OOD data. DSC was significantly higher for IAMLAB compared to the original data (p<0.05) for all lesion categories (LL>25mL: 0.77 vs. 0.71; 10mL<= LL<25mL: 0.66 vs. 0.61; LL<10mL: 0.53 vs. 0.52). The IAMLAB and Ensemble normalization methods are mitigating MRI domain shift and are optimal for DL-based WML segmentation in unseen FLAIR data.
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