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

Einar A Høgestøl; Daniel A Rinker; Ivan Maximov; Piotr Sowa; Elisabeth G Celius; Tuva R Hope; Atle Bjørnerud; Fuaad M Sofia; Eloy Martinez de Las Heras; Elisabeth Solana; Sara Llufriu; Juan Francisco Corral Gamez; Julio Alonso Farre; Deborah Pareto; Sara Collorone; Elisabetta Pagani; Gabriel Gonzalez-Escamilla; Sergiu Groppa; Jaume Sastre-Garriga; Àlex Rovira; Ahmed Toosy; Massimo Filippi; Maria Assunta Rocca; Lars T Westlye; Hanne F Harbo; Mona K Beyer; MAGNIMS study group

doi:10.1016/j.msard.2025.106435

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

Mult Scler Relat Disord. 2025 Jun:98:106435. doi: 10.1016/j.msard.2025.106435. Epub 2025 Apr 6.

Authors

Einar A Høgestøl¹, Daniel A Rinker², Ivan Maximov³, Piotr Sowa⁴, Elisabeth G Celius⁵, Tuva R Hope⁶, Atle Bjørnerud⁷, Fuaad M Sofia², Eloy Martinez de Las Heras⁸, Elisabeth Solana⁸, Sara Llufriu⁸, Juan Francisco Corral Gamez⁹, Julio Alonso Farre⁹, Deborah Pareto⁹, Sara Collorone¹⁰, Elisabetta Pagani¹¹, Gabriel Gonzalez-Escamilla¹², Sergiu Groppa¹², Jaume Sastre-Garriga¹³, Àlex Rovira⁹, Ahmed Toosy¹⁴, Massimo Filippi¹⁵, Maria Assunta Rocca¹⁵, Lars T Westlye¹⁶, Hanne F Harbo⁵, Mona K Beyer¹⁷; MAGNIMS study group

Affiliations

¹ Department of Neurology, Oslo University Hospital, Oslo, Norway; Department of Psychology, University of Oslo, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway. Electronic address: einar.august@gmail.com.
² Department of Neurology, Oslo University Hospital, Oslo, Norway.
³ Department of Psychology, University of Oslo, Oslo, Norway; NORMENT, Division of Mental Health and Addiction, Oslo University Hospital; Department of Health and Functioning, Western Norway University of Applied Sciences, Bergen, Norway.
⁴ Division of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway.
⁵ Department of Neurology, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁶ Department of Physics, University of Oslo, Oslo, Norway.
⁷ Department of Physics, University of Oslo, Oslo, Norway; Unit for Computational Radiology and Artificial Intelligence, Oslo University Hospital, Oslo, Norway; Department of Psychology, Faculty for Social Sciences, University of Oslo, Oslo, Norway.
⁸ Neuroimmunology and Multiple Sclerosis Unit and Laboratory of Advanced Imaging in Neuroimmunological Diseases (ImaginEM), Hospital Clinic Barcelona, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS) and Universitat de Barcelona, Barcelona, Spain.
⁹ Section of Neuroradiology, Department of Radiology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
¹⁰ Queen Square MS Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, University College London, London, London, UK.
¹¹ Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
¹² Department of Neurology, Focus Program Translational Neuroscience (FTN), University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
¹³ Servei de Neurologia-Neuroinmunologia. Centre d'Esclerosis Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
¹⁴ Queen Square MS Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, University College London, London, London, UK; Translational Imaging Group, Centre for Medical Image Computing (CMIC), Department of Medical Physics and Bioengineering, University College London, London, London, UK.
¹⁵ Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy.
¹⁶ Department of Psychology, University of Oslo, Oslo, Norway; NORMENT, Division of Mental Health and Addiction, Oslo University Hospital; KG Jebsen Centre for Neurodevelopmental Disorders, University of Oslo, Oslo, Norway.
¹⁷ Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Division of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway.

PMID: 40233645
DOI: 10.1016/j.msard.2025.106435

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.

Publication types

Multicenter Study

MeSH terms

Adult
Cross-Sectional Studies
Diffusion Magnetic Resonance Imaging* / methods
Diffusion Tensor Imaging / methods
Female
Humans
Male
Middle Aged
Multiple Sclerosis* / diagnostic imaging
Multiple Sclerosis* / pathology
Multiple Sclerosis, Relapsing-Remitting* / diagnostic imaging
White Matter* / diagnostic imaging
White Matter* / pathology