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Multicenter Study
. 2025 Jun:98:106435.
doi: 10.1016/j.msard.2025.106435. Epub 2025 Apr 6.

A cross-sectional multicentre study of multishell diffusion MRI in multiple sclerosis

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Free article
Multicenter Study

A cross-sectional multicentre study of multishell diffusion MRI in multiple sclerosis

Einar A Høgestøl et al. Mult Scler Relat Disord. 2025 Jun.
Free article

Abstract

Background and objectives: White matter (WM) microstructural properties from advanced multishell diffusion MRI (dMRI) have been linked to clinical disability in multiple sclerosis (MS). This multicentre study used multishell dMRI to compute WM metrics and test for differences between people with MS (pwMS) and healthy controls (HCs).

Methods: We included multishell dMRI data from 251 pwMS or clinically isolated syndrome (CIS) (mean age 40.7 years, 72.4 % women, 88.8 % relapsing remitting MS) at six MAGNIMS centres and 543 HCs. Eleven scalar metric maps were estimated from multishell dMRI sequences, based on diffusion tensor imaging (DTI) and restriction spectrum imaging (RSI). The maps were analysed using tract-based spatial statistics (TBSS). The diffusion output was submitted to paired sampled t-tests to test for case-control differences and linear regression models to test for associations with Expanded Disability Status Scale (EDSS) scores, while accounting for confounders. In a sub-sample from Oslo, we tested for correlations between EDSS and dMRI metrics within WM lesions.

Results: Significant group differences were found in nine out of eleven dMRI metrics. Linear regression models revealed significant correlations between EDSS and fractional anisotropy (FA) fast (β=-4.54, p = 0.01) and apparent diffusion coefficient (ADC) fast (β=10.92, p = 8.7 × 10-3).

Conclusions: Diffusion MRI based on clinically feasible multishell sequences uncovers WM group differences between pwMS and HCs, but only a selection of the advanced multishell parameters were sensitive to disability, and no statistically significant correlations with disability remained after Bonferroni correction.

Keywords: Diffusion weighted imaging; MRI; Multicentre; Multiple sclerosis.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hanne Flinstad Harbo reports financial support was provided by South Eastern Regional Health Authority of Norway. Sergiu Groppa reports financial support was provided by Deutsche Forschungsgemeinschaft. Einar August Hoegestoel reports a relationship with Biogen that includes: speaking and lecture fees. Einar August Hoegestoel reports a relationship with Merck that includes: funding grants and speaking and lecture fees. Einar August Hoegestoel reports a relationship with Sanofi-Genzyme that includes: board membership and speaking and lecture fees. Piotr Sowa reports a relationship with Merck that includes: speaking and lecture fees and travel reimbursement. Elisabeth Gulowsen Celius reports a relationship with BMS that includes: speaking and lecture fees. Elisabeth Gulowsen Celius reports a relationship with Biogen that includes: speaking and lecture fees. Elisabeth Gulowsen Celius reports a relationship with Janssen that includes: speaking and lecture fees. Elisabeth Gulowsen Celius reports a relationship with Merck that includes: speaking and lecture fees. Elisabeth Gulowsen Celius reports a relationship with Novartis that includes: funding grants and speaking and lecture fees. Elisabeth Gulowsen Celius reports a relationship with Sanofi that includes: funding grants and speaking and lecture fees. Elisabeth Gulowsen Celius reports a relationship with Roche that includes: speaking and lecture fees. Elisabeth Solana reports a relationship with Sanofi that includes: travel reimbursement. Elisabeth Solana reports a relationship with Merck that includes: travel reimbursement. Elisabeth Solana reports a relationship with European Committee for Treatment and Research in Multiple Sclerosis that includes: travel reimbursement. Sara Llufriu reports a relationship with Biogen Idec that includes: consulting or advisory and speaking and lecture fees. Sara Llufriu reports a relationship with Novartis that includes: consulting or advisory and speaking and lecture fees. Sara Llufriu reports a relationship with TEVA that includes: consulting or advisory and speaking and lecture fees. Sara Llufriu reports a relationship with Genzyme that includes: consulting or advisory and speaking and lecture fees. Sara Llufriu reports a relationship with Sanofi that includes: consulting or advisory and speaking and lecture fees. Sara Llufriu reports a relationship with Merck that includes: consulting or advisory and speaking and lecture fees. Deborah Pareto reports a relationship with Novatis that includes: speaking and lecture fees. Deborah Pareto reports a relationship with Sanofi Genzyme that includes: speaking and lecture fees. Deborah Pareto reports a relationship with Biogen Idec that includes: employment. Sara Collorone reports a relationship with Rosetrees Trust that includes: funding grants. Jaume Sastre-Garriga reports a relationship with Biopass that includes: speaking and lecture fees. Jaume Sastre-Garriga reports a relationship with Biogen that includes: speaking and lecture fees. Jaume Sastre-Gariga reports a relationship with Celgene that includes: speaking and lecture fees. Jaume Sastre-Garriga reports a relationship with Sanofi that includes: speaking and lecture fees. Jaume Sastre-Garriga reports a relationship with Merck that includes: speaking and lecture fees. Jaume Sastre-Garriga reports a relationship with Orchid Pharma that includes: speaking and lecture fees. Alex Rovira Canellas reports a relationship with Novartis that includes: board membership and speaking and lecture fees. Alex Rovira Canellas reports a relationship with Sanofi that includes: board membership and speaking and lecture fees. Alex Rovira Canellas reports a relationship with Genzyme that includes: board membership and speaking and lecture fees. Alex Rovira Canellas reports a relationship with Synthetic MR that includes: board membership. Alex Rovira Canellas reports a relationship with Roche that includes: board membership and speaking and lecture fees. Alex Rovira Canellas reports a relationship with Biogen that includes: board membership and speaking and lecture fees. Alex Rovira Canellas reports a relationship with OLEA Medical that includes: board membership. Alex Rovira Canellas reports a relationship with Serono that includes: speaking and lecture fees. Alex Rovira Canellas reports a relationship with Teva Pharmaceutical that includes: speaking and lecture fees. Ahmed Toosy reports a relationship with Merck, Biomedia, Biogen Idex and AtTheLimits for speaker expenses. Ahmed Toosy reports that he was UK PI for two clinical trials sponsored by MEDDAY (MS_ON – NCT0220244 and MS-SPI2 – NCT0220244. Massimo Filippi reports a relationship with Alexion that includes: board membership and consulting or advisory. Massimo Filippi reports a relationship with Almirall that includes: consulting or advisory. Massimo Filippi reports a relationship with Biogen that includes: board membership, consulting or advisory, and speaking and lecture fees. Massimo Filippi reports a relationship with Merck that includes: board membership and speaking and lecture fees. Massimo Filippi reports a relationship with Celgene that includes: speaking and lecture fees. Massimo Filippi reports a relationship with Novartis that includes: board membership, funding grants, and speaking and lecture fees. Massimo Filippi reports a relationship with Roche that includes: consulting or advisory, funding grants, and speaking and lecture fees. Massimo Filippi reports a relationship with Sanofi that includes: board membership and speaking and lecture fees. Massimo Filippi reports a relationship with Bayer that includes: speaking and lecture fees. Massimo Filippi reports a relationship with Chiesi Italia SpA that includes: speaking and lecture fees. Massimo Filippi reports a relationship with Eli Lilly that includes: speaking and lecture fees. Massimo Filippi reports a relationship with Genzyme that includes: speaking and lecture fees. Massimo Filippi reports a relationship with Janssen that includes: speaking and lecture fees. Massimo Filippi reports a relationship with Merck-Serono that includes: funding grants and speaking and lecture fees. Massimo Filippi reports a relationship with Neopharmed Gentili that includes: speaking and lecture fees. Massimo Filippi reports a relationship with Novo Nordisk that includes: speaking and lecture fees. Massimo Filippi reports a relationship with Sanofi-Aventis that includes: board membership. Massimo Filippi reports a relationship with Sanofi-Genzyme that includes: speaking and lecture fees. Massimo Filippi reports a relationship with Takeda that includes: speaking and lecture fees. Massimo Filippi reports a relationship with TEVA that includes: speaking and lecture fees. Massimo Filippi reports a relationship with Bristol-Myers Squibb that includes: board membership. Massimo Filippi reports a relationship with Lilly that includes: speaking and lecture fees. Massimo Filippi reports a relationship with Biogen Idec that includes: funding grants. Massimo Filippi reports a relationship with Merck-Serono that includes: funding grants. Massimo Filippi reports a relationship with Italian Ministry of Health that includes: funding grants. Massimo Filippi reports a relationship with Fondazione Italiana Sclerosi Multipla that includes: funding grants. Maria Assunta Rocca reports a relationship with Biogen that includes: consulting or advisory and speaking and lecture fees. Maria Assunta Rocca reports a relationship with Bristol Myers Squibb that includes: consulting or advisory and speaking and lecture fees. Maria Assunta Rocca reports a relationship with Eli Lilly that includes: consulting or advisory. Maria Assunta Rocca reports a relationship with Janssen that includes: consulting or advisory. Maria Assunta Rocca reports a relationship with Roche that includes: consulting or advisory. Maria Assunta Rocca reports a relationship with AstraZaneca that includes: speaking and lecture fees. Maria Assunta Rocca reports a relationship with Bromatech that includes: speaking and lecture fees. Maria Assunta Rocca reports a relationship with Celgene that includes: speaking and lecture fees. Maria Assunta Rocca reports a relationship with Genzyme that includes: employment. Maria Assunta Rocca reports a relationship with Horizon Therapeutics Italy that includes: speaking and lecture fees. Maria Assunta Rocca reports a relationship with Merck Serono SpA that includes: speaking and lecture fees. Maria Assunta Rocca reports a relationship with Novartis that includes: speaking and lecture fees. Maria Assunta Rocca reports a relationship with Sanofi that includes: speaking and lecture fees. Maria Assunta Rocca reports a relationship with TEVA that includes: speaking and lecture fees. Maria Assunta Rocca reports a relationship with MS Society of Canada that includes: funding grants. Maria Assunta Rocca reports a relationship with Italian Ministry of Health that includes: funding grants. Maria Assunta Rocca reports a relationship with Fondazione Italiana Sclerosi Multipla that includes: funding grants. Mona K. Beyer reports a relationship with Novartis that includes: speaking and lecture fees. Mona K. Beyer reports a relationship with Biogen Idec that includes: speaking and lecture fees. Mona K. Beyer reports a relationship with Biogen that includes: board membership. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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