title: Secondary progressive and relapsing remitting multiple sclerosis leads to motor-related decreased anatomical connectivity.
abstract: Multiple sclerosis (MS) damages central white matter pathways which has considerable impact on disease-related disability. To identify disease-related alterations in anatomical connectivity, 34 patients (19 with relapsing remitting MS (RR-MS), 15 with secondary progressive MS (SP-MS) and 20 healthy subjects underwent diffusion magnetic resonance imaging (dMRI) of the brain. Based on the dMRI, anatomical connectivity mapping (ACM) yielded a voxel-based metric reflecting the connectivity shared between each individual voxel and all other brain voxels. To avoid biases caused by inter-individual brain-shape differences, they were estimated in a spatially normalized space. Voxel-based statistical analyses using ACM were compared with analyses based on the localized microstructural indices of fractional anisotropy (FA). In both RR-MS and SP-MS patients, considerable portions of the motor-related white matter revealed decreases in ACM and FA when compared with healthy subjects. Patients with SP-MS exhibited reduced ACM values relative to RR-MS in the motor-related tracts, whereas there were no consistent decreases in FA between SP-MS and RR-MS patients. Regional ACM statistics exhibited moderate correlation with clinical disability as reflected by the expanded disability status scale (EDSS). The correlation between these statistics and EDSS was either similar to or stronger than the correlation between FA statistics and the EDSS. Together, the results reveal an improved relationship between ACM, the clinical phenotype, and impairment. This highlights the potential of the ACM connectivity indices to be used as a marker which can identify disease related-alterations due to MS which may not be seen using localized microstructural indices.
authors.affiliation: Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark; Department of Applied Mathematics and Computer Science, DTU Compute, Technical University of Denmark, Kongens Lyngby, Denmark.
authors.forename: Mark
authors.initials: M
authors.lastname: Lyksborg
authors.affiliation: Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.
authors.forename: Hartwig R
authors.initials: HR
authors.lastname: Siebner
authors.affiliation: Danish Multiple Sclerosis Center, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Per S
authors.initials: PS
authors.lastname: Sørensen
authors.affiliation: Danish Multiple Sclerosis Center, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Blinkenberg
authors.affiliation: Centre for Imaging Sciences, Biomedical Imaging Institute, University Of Manchester, United Kingdom & Bioxydyn Limited, Manchester, United Kingdom.
authors.forename: Geoff J M
authors.initials: GJ
authors.lastname: Parker
authors.affiliation: Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Dogonowski
authors.affiliation: Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.
authors.forename: Ellen
authors.initials: E
authors.lastname: Garde
authors.affiliation: Department of Applied Mathematics and Computer Science, DTU Compute, Technical University of Denmark, Kongens Lyngby, Denmark.
authors.forename: Rasmus
authors.initials: R
authors.lastname: Larsen
authors.affiliation: Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.
authors.forename: Tim B
authors.initials: TB
authors.lastname: Dyrby
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D001931:Brain Mapping; D016022:Case-Control Studies; D006233:Persons with Disabilities; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis / Q000473:pathology* / Q000503:physiopathology*; D010641:Phenotype; D012720:Severity of Illness Index
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