title: Longitudinal changes in diffusion tensor-based quantitative MRI in multiple sclerosis.
abstract: OBJECTIVE
  To estimate longitudinal changes in a quantitative whole-brain and tract-specific MRI study of multiple sclerosis (MS), with the intent of assessing the feasibility of this approach in clinical trials.
  
  
  METHODS
  A total of 78 individuals with MS underwent a median of 3 scans over 2 years. Diffusion tensor imaging indices, magnetization transfer ratio, and T2 relaxation time were analyzed in supratentorial brain, corpus callosum, optic radiations, and corticospinal tracts by atlas-based tractography. Linear mixed-effect models estimated annualized rates of change for each index, and sample size estimates for potential clinical trials were determined.
  
  
  RESULTS
  There were significant changes over time in fractional anisotropy and perpendicular diffusivity in the supratentorial brain and corpus callosum, mean diffusivity in the supratentorial brain, and magnetization transfer ratio in all areas studied. Changes were most rapid in the corpus callosum, where fractional anisotropy decreased 1.7% per year, perpendicular diffusivity increased 1.2% per year, and magnetization transfer ratio decreased 0.9% per year. The T2 relaxation time changed more rapidly than diffusion tensor imaging indices and magnetization transfer ratio but had higher within-participant variability. Magnetization transfer ratio in the corpus callosum and supratentorial brain declined at an accelerated rate in progressive MS relative to relapsing-remitting MS. Power analysis yielded reasonable sample sizes (on the order of 40 participants per arm or fewer) for 1- or 2-year trials.
  
  
  CONCLUSIONS
  Longitudinal changes in whole-brain and tract-specific diffusion tensor imaging indices and magnetization transfer ratio can be reliably quantified, suggesting that small clinical trials using these outcome measures are feasible.
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. dharri90@jhmi.edu
authors.forename: D M
authors.initials: DM
authors.lastname: Harrison
authors.forename: B S
authors.initials: BS
authors.lastname: Caffo
authors.forename: N
authors.initials: N
authors.lastname: Shiee
authors.forename: J A D
authors.initials: JA
authors.lastname: Farrell
authors.forename: P-L
authors.initials: PL
authors.lastname: Bazin
authors.forename: S K
authors.initials: SK
authors.lastname: Farrell
authors.forename: J N
authors.initials: JN
authors.lastname: Ratchford
authors.forename: P A
authors.initials: PA
authors.lastname: Calabresi
authors.forename: D S
authors.initials: DS
authors.lastname: Reich
mesh_terms: D000328:Adult; D016880:Anisotropy; D001921:Brain / Q000473:pathology*; D003337:Corpus Callosum / Q000473:pathology; D038524:Diffusion Magnetic Resonance Imaging; D018450:Disease Progression; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007091:Image Processing, Computer-Assisted; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000473:pathology