Cerebellar magnetization transfer ratio and its relationship to clinical outcomes in radiologically isolated syndrome and multiple sclerosis

Background: Advanced magnetic resonance imaging (MRI) of the cerebellum remains underutilized to detect early microstructural abnormalities associated with multiple sclerosis (MS) clinical disability. Objectives: To examine associations between cerebellar magnetization transfer ratio (MTR) and clinical measures in people with radiologically isolated syndrome (RIS), early relapsing–remitting MS (RRMS), and primary progressive MS (PPMS). Methods: MTR data were acquired at 3.0 T across four sites in 53 RIS, 202 RRMS, 46 PPMS, and 42 control participants, as part of the Canadian Prospective Cohort Study to Understand Progression in MS (CanProCo). Multiple linear regression analyses evaluated associations between cerebellar MTR and clinical measures. Results: Across MS subtypes, lower cerebellar MTR was associated with greater motor disability, most notably with impaired manual dexterity (β = −1.04 to −0.67). After the false discovery rate correction, two associations remained statistically significant ( p < 0.01): lower MTR in the inferior cerebellar peduncles was associated with worse cerebellar function in RRMS, and lower MTR in the anterior lobe was associated with worse manual dexterity in PPMS. Conclusion: This large, multi-center, hypothesis-generating study identified two statistically significant associations between cerebellar MTR and clinical disability, alongside several exploratory findings. These results suggest that cerebellar MTR may capture clinically relevant microstructural abnormalities in early MS.