title: Assessment of lesion pathology in a new animal model of MS by multiparametric MRI and DTI.
abstract: Magnetic resonance imaging (MRI) is the gold standard for the detection of multiple sclerosis (MS) lesions. However, current MRI techniques provide little information about the structural features of a brain lesion with inflammatory cell infiltration, demyelination, gliosis, acute axonal damage and axonal loss. To identify methods for a differentiation of demyelination, inflammation, and axonal damage we developed a novel mouse model combining cuprizone-induced demyelination and experimental autoimmune encephalomyelitis. MS-like brain lesions were assessed by T1-weighted, T2-weighted, and magnetization transfer MRI as well as by diffusion tensor imaging (DTI). T2-weighted MRI differentiated control and diseased mice, while T1-weighted MRI better reflected the extent of inflammation and axonal damage. In DTI, axonal damage and cellular infiltration led to a reduction of the axial diffusivity, whereas primary demyelination after cuprizone treatment was reflected by changes in radial but not axial diffusivity. Importantly, alterations in radial diffusivity were less pronounced in mice with demyelination, inflammation, and acute axonal damage, indicating that radial diffusivity may underestimate demyelination in acute MS lesions. In conclusion, the combined information from different DTI parameters allows for a more precise identification of solely demyelinated lesions versus demyelinated and acutely inflamed lesions. These findings are of relevance for offering individualized, stage-adapted therapies for MS patients.
authors.affiliation: Biomedizinische NMR Forschungs GmbH am Max-Planck-Institut für biophysikalische Chemie, 37070 Göttingen, Germany. sboreti@gwdg.de
authors.forename: Susann
authors.initials: S
authors.lastname: Boretius
authors.forename: Angelika
authors.initials: A
authors.lastname: Escher
authors.forename: Tobias
authors.initials: T
authors.lastname: Dallenga
authors.forename: Claudia
authors.initials: C
authors.lastname: Wrzos
authors.forename: Roland
authors.initials: R
authors.lastname: Tammer
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Brück
authors.forename: Stefan
authors.initials: S
authors.lastname: Nessler
authors.forename: Jens
authors.initials: J
authors.lastname: Frahm
authors.forename: Christine
authors.initials: C
authors.lastname: Stadelmann
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology; D001812:Blood-Brain Barrier / Q000473:pathology; D001921:Brain / Q000473:pathology*; D003471:Cuprizone; D003711:Demyelinating Diseases / Q000473:pathology; D056324:Diffusion Tensor Imaging / Q000379:methods*; D016002:Discriminant Analysis; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000473:pathology*; D005260:Female; D005911:Gliosis / Q000473:pathology; D007091:Image Processing, Computer-Assisted / Q000379:methods; D007249:Inflammation / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D008996:Monoamine Oxidase Inhibitors; D009103:Multiple Sclerosis / Q000139:chemically induced / Q000473:pathology*; D037342:Pertussis Toxin / Q000633:toxicity
chemical_list: D008996:Monoamine Oxidase Inhibitors; D003471:Cuprizone; D037342:Pertussis Toxin