title: Deep gray matter demyelination detected by magnetization transfer ratio in the cuprizone model.
abstract: In multiple sclerosis (MS), the correlation between lesion load on conventional magnetic resonance imaging (MRI) and clinical disability is weak. This clinico-radiological paradox might partly be due to the low sensitivity of conventional MRI to detect gray matter demyelination. Magnetization transfer ratio (MTR) has previously been shown to detect white matter demyelination in mice. In this study, we investigated whether MTR can detect gray matter demyelination in cuprizone exposed mice. A total of 54 female C57BL/6 mice were split into one control group () and eight cuprizone exposed groups ([Formula: see text]). The mice were exposed to [Formula: see text] (w/w) cuprizone for up to six weeks. MTR images were obtained at a 7 Tesla Bruker MR-scanner before cuprizone exposure, weekly for six weeks during cuprizone exposure, and once two weeks after termination of cuprizone exposure. Immunohistochemistry staining for myelin (anti-Proteolopid Protein) and oligodendrocytes (anti-Neurite Outgrowth Inhibitor Protein A) was obtained after each weekly scanning. Rates of MTR change and correlations between MTR values and histological findings were calculated in five brain regions. In the corpus callosum and the deep gray matter a significant rate of MTR value decrease was found, [Formula: see text] per week ([Formula: see text]) and [Formula: see text] per week ([Formula: see text]) respectively. The MTR values correlated to myelin loss as evaluated by immunohistochemistry (Corpus callosum: [Formula: see text]. Deep gray matter: [Formula: see text]), but did not correlate to oligodendrocyte density. Significant results were not found in the cerebellum, the olfactory bulb or the cerebral cortex. This study shows that MTR can be used to detect demyelination in the deep gray matter, which is of particular interest for imaging of patients with MS, as deep gray matter demyelination is common in MS, and is not easily detected on conventional clinical MRI.
authors.affiliation: KG Jebsen Centre for MS-Research, Department of Clinical Medicine, University of Bergen, Bergen, Norway ; The Norwegian Multiple Sclerosis Competence Centre, Department of Neurology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Sveinung
authors.initials: S
authors.lastname: Fjær
authors.affiliation: KG Jebsen Centre for MS-Research, Department of Clinical Medicine, University of Bergen, Bergen, Norway ; The Norwegian Multiple Sclerosis Competence Centre, Department of Neurology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Lars
authors.initials: L
authors.lastname: Bø
authors.affiliation: Neuroinformatics and Image Analysis Laboratory, Department of Biomedicine, University of Bergen, Bergen, Norway ; Department of Radiology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Arvid
authors.initials: A
authors.lastname: Lundervold
authors.affiliation: KG Jebsen Centre for MS-Research, Department of Clinical Medicine, University of Bergen, Bergen, Norway ; The Norwegian Multiple Sclerosis Competence Centre, Department of Neurology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Kjell-Morten
authors.initials: KM
authors.lastname: Myhr
authors.affiliation: Molecular Imaging Center, Department of Biomedicine, University of Bergen, Bergen, Norway ; Department of Radiology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Tina
authors.initials: T
authors.lastname: Pavlin
authors.affiliation: KG Jebsen Centre for MS-Research, Department of Clinical Medicine, University of Bergen, Bergen, Norway ; The Norwegian Multiple Sclerosis Competence Centre, Department of Neurology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Oivind
authors.initials: O
authors.lastname: Torkildsen
authors.affiliation: KG Jebsen Centre for MS-Research, Department of Clinical Medicine, University of Bergen, Bergen, Norway ; The Norwegian Multiple Sclerosis Competence Centre, Department of Neurology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Stig
authors.initials: S
authors.lastname: Wergeland
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology*; D003471:Cuprizone / Q000633:toxicity*; D003711:Demyelinating Diseases / Q000139:chemically induced* / Q000175:diagnosis / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D013997:Time Factors
chemical_list: D003471:Cuprizone