Longitudinal Visualization Tools for Advanced Characterization of Multiple Sclerosis Lesions Using Diffusion MRI and Magnetization Transfer Imaging Metrics

Multiple sclerosis (MS) is a complex neuro-inflammatory disease characterized by heterogeneous lesion formation, demyelination, and axonal injury. Advanced neuroimaging techniques, particularly diffusion MRI (dMRI) and magnetization transfer imaging (MTI), provide sensitive biomarkers of microstructural changes. However, the high dimensionality and longitudinal nature of these datasets pose significant challenges for effective lesion analysis and visualization. We introduce five complementary visualization tools designed to integrate fixel-based multi-tensor, magnetization transfer, and free water metrics across multiple time points in MS patients. The framework supports patient-level, tract-specific, bundle-section, lesion-specific, and new arising lesions, facilitating both individual and cohort-wide investigations. We apply these tools to longitudinal datasets from multiple MS patients, analyzing microstructural changes in lesions, penumbra, and normal-appearing white matter (NAWM) over five scanning periods. The proposed framework reveals consistent spatial tissue gradients of microstructural disruption extending from lesions into penumbra and NAWM. It highlights substantial heterogeneity in lesion dynamics, where partial MTsat recovery was observed in a subset of lesions. Pre-lesional abnormalities in fixel-based fractional anisotropy (fixel-FA), radial diffusivity (fixel-RD), magnetization transfer saturation (MTsat), and isotropic volume fraction (MRDS-ISOVF) were consistently detected before new lesion appearance. Cohort-wide analysis confirmed the consistency of these patterns and underscored the importance of individualized lesion monitoring. This multi-metric longitudinal visualization framework enables exploration of multi-dimensional MS lesion data. By integrating advanced dMRI and MTI metrics, it supports different points of view of lesion heterogeneity, pre-lesional pathology, and tissue repair, offering valuable insights for disease monitoring.