title: Progressive cerebral atrophy in MS: a serial study using registered, volumetric MRI.
abstract: OBJECTIVE
  To assess the potential of registered volumetric MRI in measuring rates of atrophy in MS.
  
  
  BACKGROUND
  Pathologic and imaging studies suggest that the development of permanent neurologic impairment in MS is associated with progressive brain and spinal cord atrophy. Atrophy has been suggested as a potential marker of disease progression. Conventional atrophy measurements requiring manual outlining are time-consuming and subject to reproducibility problems. Registration of serial MRI may offer a useful alternative in that cerebral losses may be measured directly from automated subtraction of brain volumes.
  
  
  METHODS
  Twenty-six patients with MS and 26 age- and gender-matched controls had two volumetric brain MR studies 1 year apart. Baseline brain and ventricular volumes were measured using semiautomated techniques, and follow-up scans were registered to baseline. Rates of cerebral atrophy were calculated directly from the registered scans.
  
  
  RESULTS
  Baseline brain volumes in the MS group were smaller (mean difference 78 mL [95% CI 13 to 143; p = 0.02]) and ventricular volumes greater (mean difference 12 mL [95% CI 6 to 18; p < 0.001]) than controls. The rate of cerebral atrophy in the MS group (0.8% per year) was over twice that of controls (0.3%), and the rate of ventricular enlargement was five times greater than the controls (1.6 versus 0.3 mL/year).
  
  
  CONCLUSIONS
  Progressive cerebral atrophy is an important feature of MS. Registration-based measurements are sensitive and reproducible, allowing progressive atrophy to be detected within 1 year and may have potential as a marker of progression in monitoring therapeutic trials.
authors.affiliation: Dementia Research Group, Institute of Neurology, London, UK.
authors.forename: N C
authors.initials: NC
authors.lastname: Fox
authors.forename: R
authors.initials: R
authors.lastname: Jenkins
authors.forename: S M
authors.initials: SM
authors.lastname: Leary
authors.forename: V L
authors.initials: VL
authors.lastname: Stevenson
authors.forename: N A
authors.initials: NA
authors.lastname: Losseff
authors.forename: W R
authors.initials: WR
authors.lastname: Crum
authors.forename: R J
authors.initials: RJ
authors.lastname: Harvey
authors.forename: M N
authors.initials: MN
authors.lastname: Rossor
authors.forename: D H
authors.initials: DH
authors.lastname: Miller
authors.forename: A J
authors.initials: AJ
authors.lastname: Thompson
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001284:Atrophy / Q000473:pathology; D001921:Brain / Q000473:pathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology*