Exploring Robustness of Cortical Morphometry in the presence of white matter lesions, using Diffusion Models for Lesion Filling

Cortical thickness measurements from magnetic resonance imaging, an important biomarker in many neurodegenerative and neurological disorders, are derived by many tools from an initial voxel-wise tissue segmentation. White matter (WM) hypointensities in T1-weighted imaging, such as those arising from multiple sclerosis or small vessel disease, are known to affect the output of brain segmentation methods and therefore bias cortical thickness measurements. These effects are well-documented among traditional brain segmentation tools but have not been studied extensively in tools based on deep-learning segmentations, which promise to be more robust. In this paper, we explore the potential of deep learning to enhance the accuracy and efficiency of cortical thickness measurement in the presence of WM lesions, using a high-quality lesion filling algorithm leveraging denoising diffusion networks. A pseudo-3D U-Net architecture trained on the OASIS dataset to generate synthetic healthy tissue, conditioned on binary lesion masks derived from the MSSEG dataset, allows realistic removal of white matter lesions in multiple sclerosis patients. By applying morphometry methods to patient images before and after lesion filling, we analysed robustness of global and regional cortical thickness measurements in the presence of white matter lesions. Methods based on a deep learning-based segmentation of the brain (Fastsurfer, DL+DiReCT, ANTsPyNet) exhibited greater robustness than those using classical segmentation methods (Freesurfer, ANTs).