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

Abstract

Objectives: To quantify brain microstructural changes in recently diagnosed relapsing-remitting multiple sclerosis (RRMS) using longitudinal T₁ measures, and determine their associations with clinical disability.

Methods: 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).

Results: 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).

Conclusion: 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.

Clinical relevance statement: 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.

Key points: • 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.

Keywords: Brain; Longitudinal studies; Magnetic resonance imaging; Multiparametric magnetic resonance imaging; Multiple sclerosis (Relapsing-Remitting).

Fig. 1

Flowchart showing inclusion and exclusion criteria for FutureMS quantitative T₁ sub-study

Fig. 2

An axial T₁ map with superimposed brain tissue segmentations: normal-appearing white matter (yellow), white matter lesions (red), cortical grey matter (light blue), thalami (dark blue), basal ganglia (green) and medial temporal regions (pink)

Fig. 3

Axial T₁ (colour) map brain slices for a person with recently diagnosed relapsing-remitting multiple sclerosis taking part in FutureMS. The colour bar represents T₁ in seconds of the colour scale

Fig. 4

White matter lesion T₁ heterogeneity in our cohort of people with recently diagnosed relapsing-remitting multiple sclerosis (RRMS) (n = 62). Each bar represents one participant with RRMS. The colours of the stacked plot relate to the proportion of a given participant’s white matter lesion voxels within a given T₁ range at (a) baseline and (b) 1-year follow-up

Fig. 5

Spatial distribution (a–c) of prolonged T₁ (i.e. ≥ 2.00 s) white matter lesion (WML) voxels (red) superimposed on all WML voxels (yellow) and whole-brain T₁ maps (greyscale) in three representative relapsing-remitting multiple sclerosis study participants, with corresponding T₁-weighted MPRAGE structural images (d–f)

Fig. 6

One-year change in T₁ in our recently diagnosed relapsing-remitting multiple sclerosis cohort (n = 62). Boxplots are shown for normal-appearing white matter (NAWM), cortical grey matter (cGM), global deep grey matter (DGM), thalami, medial temporal regions, basal ganglia and white matter lesions (WML, b) including only WML voxel present at baseline. Boxplots are grouped according to dichotomised change in Expanded Disability Status Scale (EDSS) score over 1 year of  < / ≥ 0.5 points. Asterisk (*) denotes significant (p < .05 with False Detection Rate correction) association between difference over 1 year in T₁ and disability group after adjusting for age, baseline T₁, 1-year change in lesion load, disease-modifying therapy status and any significant interaction effects (see text for details); n.s., not significant