Introduction: Inter-scanner variability in magnetic resonance imaging (MRI) adversely affects the diagnostic and prognostic quality of scans and necessitates the development of models that are robust to domain shift arising from the unseen scanner data. A review of recent advances in domain adaptation and domain generalization showed that the efficacy of strategies involving modifications or constraints on the latent space appears to be contingent upon the level and/or depth of supervision during model training. Methods: We propose an adaptive multi-stage domain unlearning (ADMU) technique to improve robustness to unseen scanner domains. Building on the state-of-the-art segmentation framework nnU-Net, we employ deep supervision at deep encoder stages by applying domain classifier unlearning, sequentially across these stages to reduce domain-discriminative latent features. Following the self-configurable approach of nnU-Net, the auxiliary feedback loop implements an adaptive backpropagation schedule for unlearning. Experiments were conducted on four public datasets (one for training, three for testing) to benchmark white-matter lesion segmentation methods. Five benchmark models and/or strategies, spanning passive to active domain-robust training strategies, were tested, and five state-of-the-art methods were compared. Results: AMDU demonstrated consistent, robust and improved cross-dataset segmentation performance on three test sets versus baseline nn-Unet variants. The advantage of AMDU was in enhanced lesion sensitivity with balanced false detections, resulting in good overall segmentation quality, as measured by segmentation overlap and relative lesion volume error. Compared to continuous domain unlearning, the adaptive scheduling balanced the adverse impact of unlearning onto the main segmentation task. Intensity-based preprocessing was found to be detrimental to segmentation performance. Discussion: The proposed AMDU strategy was shown to be complementary to data augmentation. Demonstrated for white-matter lesion segmentation it relied only the FLAIR modality, simplifying preprocessing to spatial normalization to brain atlas, with no intensity harmonization, for best cross-dataset segmentation performance. The source code is available at
https://github.com/Pubec/ nnunetv2-unlearning.
