Quantitative MRI phenotypes capture biological heterogeneity in multiple sclerosis patients

• Published in: Scientific reports Vol. 11; no. 1; p. 1573
• Main Authors: Smets, Ide, Goris, An, Vandebergh, Marijne, Demeestere, Jelle, Sunaert, Stefan, Dupont, Patrick, Dubois, Bénédicte
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15.01.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 692/617/375; 692/617/375/1666; Adult; Aged; Autoimmune diseases; Biological Variation, Individual; Brain - diagnostic imaging; Brain - pathology; Cerebral Cortex - pathology; Cohort Studies; Cross-Sectional Studies; Demyelination; Female; Gray Matter - pathology; Heterogeneity; Humanities and Social Sciences; Humans; Inflammation; Lesions; Longitudinal Studies; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Male; Middle Aged; multidisciplinary; Multiple sclerosis; Multiple Sclerosis - diagnostic imaging; Multiple Sclerosis - physiopathology; Neurodegeneration; Neuroimaging; Phenotype; Phenotypes; Polygenic inheritance; Science; Science (multidisciplinary); Substantia alba; Substantia grisea; White Matter - pathology
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-81035-8

Magnetization transfer ratio (MTR) and brain volumetric imaging are (semi-)quantitative MRI markers capturing demyelination, axonal degeneration and/or inflammation. However, factors shaping variation in these traits are largely unknown. In this study, we collected a longitudinal cohort of 33 multiple sclerosis (MS) patients and extended it cross-sectionally to 213. We measured MTR in lesions, normal-appearing white matter (NAWM), normal-appearing grey matter (NAGM) and total brain, grey matter, white matter and lesion volume. We also calculated the polygenic MS risk score. Longitudinally, inter-patient differences at inclusion and intra-patient changes during follow-up together explained > 70% of variance in MRI, with inter-patient differences at inclusion being the predominant source of variance. Cross-sectionally, we observed a moderate correlation of MTR between NAGM and NAWM and, less pronounced, with lesions. Age and gender explained about 30% of variance in total brain and grey matter volume. However, they contributed less than 10% to variance in MTR measures. There were no significant associations between MRI traits and the genetic risk score. In conclusion, (semi-)quantitative MRI traits change with ongoing disease activity but this change is modest in comparison to pre-existing inter-patient differences. These traits reflect individual variation in biological processes, which appear different from those involved in genetic MS susceptibility.