title: Axonal loss in multiple sclerosis lesions: magnetic resonance imaging insights into substrates of disability.
abstract: Magnetic resonance imaging (MRI) monitoring of disease progression in multiple sclerosis is limited by the lack of correlation of abnormalities seen on T2-weighted imaging, and disability. We studied the histopathology of multiple sclerosis lesions, as depicted by MRI, in a large postmortem sample, focusing on axonal loss. Tissue samples from 17 patients were selected immediately postmortem for histopathological analysis on the basis of T2-weighted imaging, including normal appearing white matter and T1 hypointense lesions. In each region, we measured magnetization transfer ratios (MTR), T1 contrast ratio, myelin, and axonal density. T2 lesions (109 samples) were heterogeneous with regard to MRI appearance on T1 and MTR, whereas axonal density ranged from 0% (no residual axons) to 100% (normal axonal density). Of 64 T2 lesions, 17 were reactive (mild perivascular inflammation only), 21 active, 15 chronically active, and 11 chronically inactive. MTR and T1 contrast ratio correlated strongly with axonal density. Also in normal appearing white matter (24 samples), MTR correlated with axonal density. In conclusion, postmortem tissue sampling by using MRI revealed a range of pathology, illustrating the high sensitivity and low specificity of T2-weighted imaging. T1 hypointensity and MTR were strongly associated with axonal density, emphasizing their role in monitoring progression in multiple sclerosis.
authors.affiliation: MS-MR Centre and Department of Radiology, Academic Hospital Vrije Universiteit, Amsterdam, The Netherlands.
authors.forename: J H
authors.initials: JH
authors.lastname: van Waesberghe
authors.forename: W
authors.initials: W
authors.lastname: Kamphorst
authors.forename: C J
authors.initials: CJ
authors.lastname: De Groot
authors.forename: M A
authors.initials: MA
authors.lastname: van Walderveen
authors.forename: J A
authors.initials: JA
authors.lastname: Castelijns
authors.forename: R
authors.initials: R
authors.lastname: Ravid
authors.forename: G J
authors.initials: GJ
authors.lastname: Lycklama à Nijeholt
authors.forename: P
authors.initials: P
authors.lastname: van der Valk
authors.forename: C H
authors.initials: CH
authors.lastname: Polman
authors.forename: A J
authors.initials: AJ
authors.lastname: Thompson
authors.forename: F
authors.initials: F
authors.lastname: Barkhof
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001344:Autopsy; D001369:Axons / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D004396:Coloring Agents; D005260:Female; D006801:Humans; D007249:Inflammation; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology*
chemical_list: D004396:Coloring Agents