Exploring in vivo multiple sclerosis brain microstructural damage through T1w/T2w ratio: a multicentre study

Objectives To evaluate white matter and grey matter T1-weighted (w)/T2w ratio (T1w/T2w ratio) in healthy controls and patients with multiple sclerosis, and its association with clinical disability. Methods In this cross-sectional study, 270 healthy controls and 434 patients with multiple sclerosis were retrospectively selected from 7 European sites. T1w/T2w ratio was obtained from brain T2w and T1w scans after intensity calibration using eyes and temporal muscle. Results In healthy controls, T1w/T2w ratio increased until 50-60 years both in white and grey matter. Compared with healthy controls, T1w/T2w ratio was significantly lower in white matter lesions of all multiple sclerosis phenotypes, and in normal-appearing white matter and cortex of patients with relapsing-remitting and secondary progressive multiple sclerosis (p <= 0.026), but it was significantly higher in the striatum and pallidum of patients with relapsing-remitting, secondary progressive and primary progressive multiple sclerosis (p <= 0.042). In relapse-onset multiple sclerosis, T1w/T2w ratio was significantly lower in white matter lesions and normal-appearing white matter already at Expanded Disability Status Scale (EDSS) <3.0 and in the cortex only for EDSS >= 3.0 (p <= 0.023). Conversely, T1w/T2w ratio was significantly higher in the striatum and pallidum for EDSS >= 4.0 (p <= 0.005). In primary progressive multiple sclerosis, striatum and pallidum showed significantly higher T1w/T2w ratio beyond EDSS=6.0 (p <= 0.001). In multiple sclerosis, longer disease duration, higher EDSS, higher brain lesional volume and lower normalised brain volume were associated with lower lesional and cortical T1w/T2w ratio and a higher T1w/T2w ratio in the striatum and pallidum (beta from -1.168 to 0.286, p <= 0.040). Conclusions T1w/T2w ratio may represent a clinically relevant marker sensitive to demyelination, neurodegeneration and iron accumulation occurring at the different multiple sclerosis phases.