title: Early MRI changes in a mouse model of multiple sclerosis are predictive of severe inflammatory tissue damage.
abstract: MRI is routinely used for in vivo detection of multiple sclerosis (MS) lesions. Histopathological correlates of MRI signal alterations are still poorly defined. In the present study, we describe a mouse model of MS presenting with inflammatory brain lesions. During the acute disease phase, two independent lesion patterns were identified by T1- and T2-weighted high-resolution 3D MRI: lesions with reduced signal intensity on both T1- and T2-weighted images (type A) and lesions with slightly reduced signal intensity on T1-weighted images and increased signal intensity on T2-weighted images (type B). Type A lesions were characterized by significantly denser inflammatory cell infiltrates and more myelin loss than type B lesions. Lesion cellularity, myelin loss and immunoglobulin deposition correlated with MRI signal intensities in both lesion types. Gd-DTPA enhancement correlated with Ig deposition and spacially matched to areas with abundant activated microglia cells at the lesion border. Using serial MRI, type A lesions revealed a persistent hypointense pattern reflecting axon and myelin loss. Signal intensity increases on T2-weighted images of type B lesions decreased during lesion evolution, and no significant T1 signal alterations developed. Taken together, MRI of mouse EAE models with brain lesions provide new insights into lesion pathology and evolution and may prove useful for the in vivo assessment of new therapeutic strategies in MS.
authors.affiliation: Department of Neurology, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Nessler
authors.forename: Susann
authors.initials: S
authors.lastname: Boretius
authors.forename: Christine
authors.initials: C
authors.lastname: Stadelmann
authors.forename: Alwina
authors.initials: A
authors.lastname: Bittner
authors.forename: Doron
authors.initials: D
authors.lastname: Merkler
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hartung
authors.forename: Thomas
authors.initials: T
authors.lastname: Michaelis
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Brück
authors.forename: Jens
authors.initials: J
authors.lastname: Frahm
authors.forename: Norbert
authors.initials: N
authors.lastname: Sommer
authors.forename: Bernhard
authors.initials: B
authors.lastname: Hemmer
mesh_terms: D000208:Acute Disease; D019264:Adoptive Transfer; D000818:Animals; D001253:Astrocytes / Q000473:pathology; D001921:Brain / Q000473:pathology*; D001933:Brain Stem / Q000473:pathology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology*; D005260:Female; D008279:Magnetic Resonance Imaging; D051379:Mice; D008815:Mice, Inbred Strains; D017628:Microglia / Q000473:pathology; D009103:Multiple Sclerosis / Q000276:immunology / Q000473:pathology*; D009186:Myelin Sheath / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology