Quantitative magnetisation transfer imaging in relapsing-remitting multiple sclerosis: a systematic review and meta-analysis
Authors: York Elizabeth N. , Thrippleton Michael J. , Meijboom Rozanna , Hunt David P.J. , Waldman Adam D. 
Published: July 2021

AbstractMyelin-sensitive MRI such as magnetisation transfer imaging has been widely used in the clinical context of multiple sclerosis. The influence of methodology and differences in disease subtype on imaging findings is, however, not well established. Here, we aim to review systematically the use of quantitative magnetisation transfer imaging in the brain in relapsing- remitting multiple sclerosis. We examine how methodological differences, disease effects and their interaction influence magnetisation transfer imaging measures.Articles published before 06/01/2021 were retrieved from online databases (PubMed, EMBASE and Web of Science) with search terms including ‘magnetisation transfer’ and ‘brain’ for systematic review. Only studies which used human in vivo quantitative magnetisation transfer imaging in adults with relapsing-remitting multiple sclerosis (with or without healthy controls) were included.Data including sample size, magnetic field strength, MRI acquisition protocol parameters, treatments and clinical findings were extracted and qualitatively synthesised. Where possible, effect sizes were calculated for meta-analyses to determine magnetisation transfer (1) differences between patients and healthy controls; (2) longitudinal change; and, (3) relationships with clinical disability in relapsing-remitting multiple sclerosis.Eighty-six studies met the inclusion/exclusion criteria. MRI acquisition parameters varied widely, and were also underreported. The majority of studies examined MTR (magnetisation transfer ratio) in white matter, but magnetisation transfer metrics, brain regions and results were heterogeneous. Analysis demonstrated a risk of bias due to selective reporting and small sample sizes.A random-effects meta-analysis revealed MTR was 1.1 percent units [95% CI -1.47pu to -0.73pu] lower in relapsing-remitting multiple sclerosis than healthy controls (z-value: -6.04, p<0.001, n=23). Linear mixed-model analysis did not show a significant longitudinal change in MTR across all brain regions (β=-0.14 [-0.9 to 0.61], t-value=-0.38, p=0.71, n=13) or normal-appearing white matter alone (β=-0.082 [-0.13 to -0.29], t-value=0.78, p=0.44, n=7). There was a significant negative association between MTR and clinical disability, as assessed by the Expanded Disability Status Scale (r=-0.30 [95% CI -0.48 to -0.08]; z-value=-2.91, p=0.01, n=8).Evidence suggests that magnetisation transfer imaging is sensitive to pathological changes in relapsing-remitting multiple sclerosis, although the effect of relapsing-remitting multiple sclerosis on magnetisation transfer metrics in different brain tissue types was small in comparison to the inter-study variability. Recommended improvements include: the use of techniques such as MTsat (magnetisation transfer saturation) or ihMTR (inhomogeneous MTR) which provide more robust and specific microstructural measures within clinically feasible acquisition times; detailed methodological reporting standards; and larger, demographically diverse cohorts for comparison, including healthy controls.Abbreviated SummaryYork et al. systematically reviewed 86 studies of magnetisation transfer (MT) brain imaging in relapsing-remitting multiple sclerosis. MT was reduced in patients compared with controls, but results were highly variable, longitudinal change subtle, and associations with clinical disability weak. Use of better harmonised MT acquisition in large cohorts is warranted.