title: The spinal cord in multiple sclerosis: relationship of high-spatial-resolution quantitative MR imaging findings to histopathologic results.
abstract: OBJECTIVE
  To correlate quantitative magnetic resonance (MR) imaging data (ie, relaxation times and magnetization transfer ratios [MTRs]) with histopathologic findings of demyelination and axonal disease in cervical spinal cord specimens from patients with multiple sclerosis (MS) and control subjects.
  
  
  METHODS
  Formaldehyde-fixed cervical spinal cord specimens from 11 patients with MS-three men and eight women (mean age at death, 66 years +/- 11.3 [standard deviation])-and two female control subjects without neurologic disease (83 and 41 years of age at death) were examined at 4.7 T. Relaxation time measurements and MTR mapping were performed. Analyses included the whole cord area and region-of-interest measurements. Histopathologic analyses included semiquantitative myelin and quantitative axonal analysis.
  
  
  RESULTS
  Compared with control specimens (P < .001, analysis of variance), specimens from patients with MS had smaller cord areas (mean area, 59.0 mm(2) +/- 12.5 vs 72.7 mm(2) +/- 10.0), significant prolongation of T1 (mean prolongation, 30%) and T2 (mean prolongation, 13%), and decreased MTRs (mean, 10.5%). Within MS specimens, 58% of the white matter area displayed signal intensity abnormalities on intermediate-weighted MR images. The number of axons in normal-appearing white matter in MS specimens was, on average, 46% lower than the number of axons in white matter in control specimens. All quantitative MR parameters correlated well with demyelination; the correlation with T2 relaxation time was the strongest (r = 0.77, Spearman and Kendall nonparametric correlations). By contrast, quantitative MR parameters correlated less well with axonal density; the correlation with T2 relaxation time was the strongest (r = -0.44, Spearman and Kendall nonparametric correlations). Multilevel analysis, corrected for age and MS phenotype, could not result in a model explaining axonal density on the basis of quantitative MR parameters when myelin density was included as a predictor.
  
  
  CONCLUSIONS
  Changes in quantitative MR imaging parameters in the cervical spinal cord in MS are mainly determined by demyelination and do not reflect axonal disease well.
authors.affiliation: Department of Radiology, VU Medical Center, PO Box 7057, 1007 MB Amsterdam, the Netherlands. j.bot@vumc.nl
authors.forename: Joseph C J
authors.initials: JC
authors.lastname: Bot
authors.forename: Erwin L A
authors.initials: EL
authors.lastname: Blezer
authors.forename: Wouter
authors.initials: W
authors.lastname: Kamphorst
authors.forename: Geert J
authors.initials: GJ
authors.lastname: Lycklama A Nijeholt
authors.forename: Herman J
authors.initials: HJ
authors.lastname: Ader
authors.forename: Jonas A
authors.initials: JA
authors.lastname: Castelijns
authors.forename: Klaas Nicolay
authors.initials: KN
authors.lastname: Ig
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Bergers
authors.forename: Rivka
authors.initials: R
authors.lastname: Ravid
authors.forename: Chris
authors.initials: C
authors.lastname: Polman
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001369:Axons / Q000473:pathology; D003711:Demyelinating Diseases / Q000473:pathology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis* / Q000473:pathology; D013116:Spinal Cord / Q000473:pathology