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

Monica Margoni, Elisabetta Pagani, Alessandro Meani, Loredana Storelli, Sarlota Mesaros, Jelena Drulovic, Frederik Barkhof, Hugo Vrenken, Antonio Gallo, Alvino Bisecco, Deborah Pareto, Jaume Sastre-Garriga, Olga Ciccarelli, Marios Yiannakas, Jacqueline Palace, Paolo Preziosa, Maria A. Rocca, Massimo Filippi

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10 Citations (Scopus)


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 (β 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.

Original languageEnglish
Article number328908
Pages (from-to)741-752
Number of pages12
JournalJournal of Neurology, Neurosurgery and Psychiatry
Issue number7
Early online date2022
Publication statusPublished - 1 Jul 2022


  • MRI
  • T1w/T2w-ratio
  • multiple sclerosis

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