title: Characterization of white matter damage in animal models of multiple sclerosis by magnetization transfer ratio and quantitative mapping of the apparent bound proton fraction f.
abstract: Quantitative magnetization transfer magnetic resonance imaging (qMT-MRI) can be used to improve detection of white matter tissue damage in multiple sclerosis (MS) and animal models thereof. To study the correlation between MT parameters and tissue damage, the magnetization transfer ratio (MTR), the parameter f* (closely related to the bound proton fraction) and the bound proton transverse relaxation time T(2B) of lesions in a model of focal experimental autoimmune encephalomyelitis (EAE) were measured on a 7T animal scanner and data were compared with histological markers indicative for demyelination, axonal density, and tissue damage. A clear spatial correspondence was observed between reduced values of MTR and demyelination in this animal model. We observed two different levels of MTR and f* reduction for these lesions. One was characterized by a pronounced demyelination and the other corresponded to a more severe loss of the cellular matrix. Changes in f* were generally more pronounced than those of MTR in areas of demyelination. Moreover, a reduction of f* was already observed for tissue where MTR was virtually normal. No changes in T(2B) were observed for the lesions. We conclude that MTR and qMT mapping are efficient and reliable readouts for studying demyelination in animal models of MS, and that the analysis of regional f* might be even superior to the analysis of MTR values. Therefore, quantitative mapping of f* from human brains might also improve the detection of white matter damage in MS.
authors.affiliation: Novartis Institutes for Biomedical Research, Basel, Switzerland. martin.rausch@novartis.com
authors.forename: M
authors.initials: M
authors.lastname: Rausch
authors.forename: Ps
authors.initials: P
authors.lastname: Tofts
authors.forename: P
authors.initials: P
authors.lastname: Lervik
authors.forename: Ar
authors.initials: A
authors.lastname: Walmsley
authors.forename: A
authors.initials: A
authors.lastname: Mir
authors.forename: A
authors.initials: A
authors.lastname: Schubart
authors.forename: T
authors.initials: T
authors.lastname: Seabrook
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D003711:Demyelinating Diseases / Q000473:pathology*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology*; D005260:Female; D008279:Magnetic Resonance Imaging / Q000379:methods* / Q000592:standards; D008962:Models, Theoretical; D009103:Multiple Sclerosis / Q000473:pathology*; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D011522:Protons; D051381:Rats; D011917:Rats, Inbred Lew; D015203:Reproducibility of Results; D014867:Water
chemical_list: D011522:Protons; D014867:Water