title: Voxel-based analysis of quantitative T1 maps demonstrates that multiple sclerosis acts throughout the normal-appearing white matter.
abstract: OBJECTIVE
  Disease activity in normal-appearing white matter (NAWM) in multiple sclerosis (MS) has been demonstrated in vivo with T1 relaxation time measurements. We aimed to investigate the spatial distribution of T1 increases in MS NAWM without a priori selection of specific regions.
  
  
  METHODS
  Whole-brain quantitative T1 maps were measured in 67 patients with one of the 3 main clinical types of MS (13 primary progressive [PP], 36 relapsing-remitting [RR], and 18 secondary progressive [SP]) and in 23 healthy control subjects. After registration to standard space and segmentation of NAWM, the maps were analyzed by using voxel-based analyses with a cluster-based corrected P threshold of .05.
  
  
  RESULTS
  Group mean T1 relaxation times throughout NAWM increased when going from control subjects to PP to RR to SP MS. In the RR and SP MS groups, the T1 increases compared with control subjects were significant throughout the NAWM, without apparent preference for specific brain regions. In RR MS, 16% of NAWM voxels displayed a significant increase in T1 compared with control subjects, and in SP, this fraction was 49%. The comparison between RR MS and the subsequent phase SP MS revealed that, in these patients, disease progression occurs throughout the NAWM. In patients with PP MS, the spatial extent of significant T1 increases is limited. There were no correlations with clinical disability scales or brain volume in a substantial fraction of voxels.
  
  
  CONCLUSIONS
  This study demonstrates that in patients with RR MS and SP MS, NAWM disease processes have no regional preferences but can occur throughout the brain.
authors.affiliation: MR Center for MS Research, Department of Radiology, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: Vrenken
authors.forename: S A R B
authors.initials: SA
authors.lastname: Rombouts
authors.forename: P J W
authors.initials: PJ
authors.lastname: Pouwels
authors.forename: F
authors.initials: F
authors.lastname: Barkhof
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology*; D001931:Brain Mapping; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology*