Quantitative magnetic resonance of postmortem multiple sclerosis brain before and after fixation.
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.
Schmierer
Klaus
K
NMR Research Unit, Institute of Neurology, University College London, Queen Square, London, UK. k.schmierer@ion.ucl.ac.uk
Wheeler-Kingshott
Claudia A M
CA
Tozer
Daniel J
DJ
Boulby
Phil A
PA
Parkes
Harold G
HG
Yousry
Tarek A
TA
Scaravilli
Francesco
F
Barker
Gareth J
GJ
Tofts
Paul S
PS
Miller
David H
DH
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