Rationale and design of the brain magnetic resonance imaging protocol for FutureMS: a longitudinal multi-centre study of newly diagnosed patients with relapsing-remitting multiple sclerosis in Scotland

IntroductionMultiple sclerosis (MS) is a chronic neuroinflammatory and neurodegenerative disease. MS prevalence varies geographically and is notably high in Scotland. Disease trajectory varies significantly between individuals and the causes for this are largely unclear. Biomarkers predictive of disease course are urgently needed to allow improved stratification for current disease modifying therapies and future targeted treatments aimed at neuroprotection and remyelination. MRI can detect disease activity and underlying damage non-invasively in vivo at the micro and macrostructural level. FutureMS is a prospective Scottish longitudinal multi-centre cohort study, which focuses on deeply phenotyping patients with recently diagnosed relapsing-remitting MS (RRMS). Neuroimaging is a central component of the study and provides two main primary endpoints for disease activity and neurodegeneration. FutureMS aims to reduce uncertainty around disease course and allow for targeted treatment in RRMS by exploring the role of conventional and advanced MRI measures as biomarkers of disease severity and progression. This paper provides an overview of MRI data acquisition, management and processing in FutureMS. Methods and analysisMRI is acquired at baseline (N=431) and 1-year follow-up, in Dundee, Glasgow and Edinburgh (3T Siemens) and in Aberdeen (3T Philips), and managed and processed in Edinburgh. The core structural MRI protocol comprises T1-weighted, T2-weighted, FLAIR and proton density images. Primary imaging outcome measures are new/enlarging white matter lesions (WML) and reduction in brain volume over one year. Secondary imaging outcome measures comprise WML volume as an additional quantitative structural MRI measure, rim lesions on susceptibility-weighted imaging, and microstructural MRI measures, including diffusion tensor imaging and neurite orientation dispersion and density imaging metrics, relaxometry, magnetisation transfer (MT) ratio, MT saturation and derived g-ratio measures. Ethics and disseminationThe study received ethical approval from the South East Scotland Research Ethics Committee 02 (reference 15/SS/0233). Results will be made available to study participants and funders. STRENGTHS AND LIMITATIONS OF THE STUDYO_LIBrain imaging acquired within six months after relapsing-remitting multiple sclerosis (RRMS) diagnosis allows for detection of abnormalities at a very early stage of disease. C_LIO_LILongitudinal structural and microstructural brain MRI are integrated with multi-modal clinical, blood biomarker, genetic and retinal imaging data to allow comprehensive evaluation of early RRMS stratifiers. C_LIO_LIMR protocol optimization was implemented mid-study to improved image quality and protocol harmonization, resulting in some between-subject protocol variation. C_LIO_LIMultiplatform MRI acquisition required to allow access for a large MS population across Scotland introduces inevitable inter-site data variance. C_LIO_LIContrast enhanced MRI was not acquired, limiting imaging evaluation of active inflammatory lesions. C_LI