title: Quantitative magnetic resonance of postmortem multiple sclerosis brain before and after fixation.
abstract: Unfixed and fixed postmortem multiple sclerosis (MS) brain is being used to probe pathology underlying quantitative MR (qMR) changes. Effects of fixation on qMR indices in MS brain are unknown. In 15 postmortem MS brain slices T(1), T(2), MT ratio (MTR), macromolecular proton fraction (f(B)), fractional anisotropy (FA), and mean, axial, and radial diffusivity (MD, D(ax), and D(rad)) were assessed in white matter (WM) lesions (WML) and normal appearing WM (NAWM) before and after fixation in formalin. Myelin content, axonal count, and gliosis were quantified histologically. Student's t-test and regression were used for analysis. T(1), T(2), MTR, and f(B) obtained in unfixed MS brain were similar to published values obtained in patients with MS in vivo. Following fixation T(1), T(2) (NAWM, WML) and MTR (NAWM) dropped, whereas f(B) (NAWM, WML) increased. Compared to published in vivo data all diffusivity measures were lower in unfixed MS brain, and dropped further following fixation (except for FA). MTR was the best predictor of T(myelin) (inversely related to myelin) in unfixed MS brain (r = -0.83; P < 0.01) whereas postfixation T(2) (r = 0.92; P < 0.01), T(1) (r = 0.89; P < 0.01), and f(B) (r = -0.86; P < 0.01) were superior. All diffusivity measures (except for D(ax) in unfixed tissue) were predictors of myelin content.
authors.affiliation: NMR Research Unit, Institute of Neurology, University College London, Queen Square, London, UK. k.schmierer@ion.ucl.ac.uk
authors.forename: Klaus
authors.initials: K
authors.lastname: Schmierer
authors.forename: Claudia A M
authors.initials: CA
authors.lastname: Wheeler-Kingshott
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Tozer
authors.forename: Phil A
authors.initials: PA
authors.lastname: Boulby
authors.forename: Harold G
authors.initials: HG
authors.lastname: Parkes
authors.forename: Tarek A
authors.initials: TA
authors.lastname: Yousry
authors.forename: Francesco
authors.initials: F
authors.lastname: Scaravilli
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Barker
authors.forename: Paul S
authors.initials: PS
authors.lastname: Tofts
authors.forename: David H
authors.initials: DH
authors.lastname: Miller
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016880:Anisotropy; D001344:Autopsy; D005260:Female; D006652:Histological Techniques; D006801:Humans; D007091:Image Processing, Computer-Assisted; D016014:Linear Models; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology*; D012189:Retrospective Studies