07 Apr 22. Featured Paper

Link to paper on Brain Communications

Authors

Elizabeth N. York, Michael J. Thrippleton, Rozanna Meijboom, David P. J. Hunt, Adam D. Waldman

Abstract

Myelin-sensitive MRI such as magnetisation transfer imaging has been widely used in multiple sclerosis. The influence of methodology and differences in disease subtype on imaging findings is, however, not well established. Here, we systematically review magnetisation transfer brain imaging findings 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, according to a pre-defined protocol. 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. Additional data from relapsing-remitting multiple sclerosis subjects acquired in other studies comprising mixed disease subtypes were included in meta-analyses.

Data including sample size, 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 inclusion criteria. MRI acquisition parameters varied widely, and were also underreported. The majority of studies examined the magnetisation transfer ratio in white matter, but magnetisation transfer metrics, brain regions examined and results were heterogeneous. Analysis demonstrated a risk of bias due to selective reporting and small sample sizes.

The pooled random-effects meta-analysis across all brain compartments revealed magnetisation transfer ratio was 1.17 percent units [95% CI -1.42 to -0.91] lower in relapsing-remitting multiple sclerosis than healthy controls (z-value: -8.99, p<0.001, 46 studies). Linear mixed-model analysis did not show a significant longitudinal change in magnetisation transfer ratio across all brain regions (β=0.12 [-0.56 to 0.80], t-value=0.35, p=0.724, 14 studies) or normal-appearing white matter alone (β=0.037 [-0.14 to 0.22], t-value=0.41, p=0.68, 8 studies). There was a significant negative association between the magnetisation transfer ratio and clinical disability, as assessed by the Expanded Disability Status Scale (r=-0.32 [95% CI -0.46 to -0.17]; z-value=-4.33, p<0.001, 13 studies).

Evidence suggests that magnetisation transfer imaging metrics are sensitive to pathological brain changes in relapsing-remitting multiple sclerosis, although effect sizes were small in comparison to inter-study variability. Recommendations include: better harmonised magnetisation transfer acquisition protocols with detailed methodological reporting standards; larger, well-phenotyped cohorts, including healthy controls; and, further exploration of techniques such as magnetisation transfer saturation or inhomogeneous magnetisation transfer ratio.

Keywords

• Brain
• Magnetisation transfer
• Multiple sclerosis
• Relapsing-remitting
• Systematic review