Quantitative T₁ brain mapping in early relapsing-remitting multiple sclerosis: longitudinal changes, lesion heterogeneity and disability.

Abstract

To quantify brain microstructural changes in recently diagnosed relapsing-remitting multiple sclerosis (RRMS) using longitudinal T₁ measures, and determine their associations with clinical disability. Seventy-nine people with recently diagnosed (< 6 months) RRMS were recruited from a single-centre cohort sub-study, and underwent baseline and 1-year brain MRI, including variable flip angle T₁ mapping. Median T₁ was measured in white matter lesions (WML), normal-appearing white matter (NAWM), cortical/deep grey matter (GM), thalami, basal ganglia and medial temporal regions. Prolonged T₁ (≥ 2.00 s) and supramedian T₁ (relative to cohort WML values) WML voxel counts were also measured. Longitudinal change was assessed with paired t-tests and compared with Bland-Altman limits of agreement from healthy control test-retest data. Regression analyses determined relationships with Expanded Disability Status Scale (EDSS) score and dichotomised EDSS outcomes (worsening or stable/improving). Sixty-two people with RRMS (mean age 37.2 ± 10.9 [standard deviation], 48 female) and 11 healthy controls (age 44 ± 11, 7 female) contributed data. Prolonged and supramedian T₁ WML components increased longitudinally (176 and 463 voxels, respectively; p < .001), and were associated with EDSS score at baseline (p < .05) and follow-up (supramedian: p < .01; prolonged: p < .05). No cohort-wide median T₁ changes were found; however, increasing T₁ in WML, NAWM, cortical/deep GM, basal ganglia and thalami was positively associated with EDSS worsening (p < .05). T₁ is sensitive to brain microstructure changes in early RRMS. Prolonged WML T₁ components and subtle changes in NAWM and GM structures are associated with disability. MRI T₁ brain mapping quantifies disability-associated white matter lesion heterogeneity and subtle microstructural damage in normal-appearing brain parenchyma in recently diagnosed RRMS, and shows promise for early objective disease characterisation and stratification. • Quantitative T₁ mapping detects brain microstructural damage and lesion heterogeneity in recently diagnosed relapsing-remitting multiple sclerosis. • T₁ increases in lesions and normal-appearing parenchyma, indicating microstructural damage, are associated with worsening disability. • Brain T₁ measures are objective markers of disability-relevant pathology in early multiple sclerosis.