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

Abstract

Multiple sclerosis (MS) is a chronic neuroinflammatory and neurodegenerative disease. MS prevalence varies geographically, both between and within countries 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, and as endpoints for clinical trials. Magnetic resonance imaging (MRI) can detect disease activity and underlying neurological damage non-invasively in vivo at the micro and macro structural level. FutureMS is a prospective Scottish longitudinal multi-centre cohort study which focuses on deeply phenotyping and genotyping patients with recently diagnosed relapsing-remitting MS (RRMS) to identify predictors of disease activity and severity. Neuroimaging is a central component of the study and provides two main primary endpoints for disease activity and neurodegeneration. The aim of the current paper is to provide an overview of MRI data acquisition, management and processing in FutureMS. MRI 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, 2D/3D FLAIR and proton density images. The original study primary imaging outcome measures are new/enlarging white matter lesions (WML) assessed by neuroradiological visual read and reduction in brain volume over one year. Secondary imaging outcomes comprise WML volume as an additional quantitative structural MRI outcome measure, rim lesions on susceptibility-weighted imaging (SWI), and microstructural MRI measures, including diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) metrics, relaxometry, magnetisation transfer (MT) ratio, MT saturation and derived g-ratio measures. 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 in a large population of RRMS patients in Scotland.

MRI-derived g-ratio and lesion severity in newly diagnosed multiple sclerosis

“…1C . Hyperintense WML on T 2 Fluid-Attenuated Inversion Recovery were automatically segmented using a combination of FSL (6.0.1, http://www.fmrib.ox.ac.uk/fsl ) and an intensity-based thresholding method 14 ; following automated segmentation, all lesion masks were reviewed and manually edited by a trained technician under supervision of a post-doctoral imaging scientist (5 years experience; R.M.) and an experienced neuroradiologist (20 years experience; A.D.W.).…”

Patterns of brain degeneration in early-stage relapsing-remitting multiple sclerosis

“…Participants with a recent diagnosis of RRMS according to the 2017 McDonald criteria (< 6 months) [10], were recruited across five neurology sites in Scotland: Aberdeen, Dundee, Edinburgh, Inverness and Glasgow, as part of the FutureMS study [42, 43]. Participants were 18 years or older and had the capacity to provide informed consent.…”

“…All participants underwent T1-weighted, T2-weighted, and 2D and 3D FLAIR imaging. Full details have been previously described in Meijboom et al (2021) [43] (see supplement Table 1 for an overview of all MR parameters).…”

“…Image processing methods have been previously described in full in Meijboom et al (2021) [43] and are briefly summarised in the sections below.…”

“…To our knowledge, current literature does not provide detailed insights into regional WM volume loss in very early-stage RRMS, and only a limited number of studies have examined specific GM volume in early stages of the disease [14, 19–21]. The current study uses data from FutureMS [42], a large multicentre cohort of recently-diagnosed RRMS patients in Scotland, which acquired extensive MR imaging [43] at baseline and one-year follow-up. Importantly, study participants were recruited within six months of diagnosis, enabling early-stage detection of neurodegenerative patterns.…”