Abstract

Motivation: Conventional MRI struggles to capture heterogeneous histopathological subtypes within multiple sclerosis (MS) lesions, mainly due to a lack of microstructural specificity. Goal(s): (i) To unveil distinct subtypes of microstructural alteration MS lesions using advanced multi-contrast microstructural MRI; (ii) increase sensitivity to individual microstructure. Approach: K-means clustering was applied to multi-contrast microstructural MRI quantities, including parameters from diffusometry (μFA [axonal integrity marker], MD), susceptometry (QSM, 𝜒dia [demyelination marker] 𝜒para [marker for iron-laden microglia]), and relaxometry (R2*, R2, T1). Results: Five MRI-driven lesion subtypes, each with unique microstructural property combinations, revealed potential histopathological features of MS lesions and showed enhanced sensitivities to clinical outcomes. Impact: We used a novel imaging multi-biomarker for in-vivo MS pathology to assess lesion types for potential treatment monitoring in MS. Some MS subtypes with microstructure alterations, potentially related to disease histopathology, showed improved clinical sensitivity over conventional imaging markers.