title: Evidence for grey matter MTR abnormality in minimally disabled patients with early relapsing-remitting multiple sclerosis.
abstract: OBJECTIVE
  To establish whether magnetisation transfer ratio (MTR) histograms are sensitive to change in normal appearing grey matter (NAGM) in early relapsing-remitting multiple sclerosis (RRMS) in the absence of significant disability; and to assess whether grey or white matter MTR measures are associated with clinical measures of impairment in early RRMS METHODS: 38 patients were studied (mean disease duration 1.9 years (range 0.5 to 3.7); median expanded disability status scale (EDSS) 1.5 (0 to 3)), along with 35 healthy controls. MTR was determined from proton density weighted images with and without MT presaturation. SPM99 was used to generate normal appearing white matter (NAWM) and NAGM segments of the MTR map, and partial voxels were minimised with a 10 pu threshold and voxel erosions. Mean MTR was calculated from the tissue segments. Atrophy measures were determined using a 3D fast spoiled gradient recall sequence from 37 patients and 17 controls.
  
  
  RESULTS
  Mean NAGM and NAWM MTR were both reduced in early RRMS (NAGM MTR: 31.9 pu in patients v 32.2 pu in controls; p<0.001; NAWM MTR: 37.9 v 38.3 pu, p = 0.001). Brain parenchymal fraction (BPF) correlated with NAGM MTR, but when BPF was included as a covariate NAGM MTR was still lower in the patients (p = 0.009). EDSS correlated with NAGM MTR (r = 0.446 p = 0.005).
  
  
  CONCLUSIONS
  In early RRMS, grey matter MTR abnormality is apparent. The correlation with mild clinical impairment (in this essentially non-disabled cohort) suggests that NAGM MTR could be a clinically relevant surrogate marker in therapeutic trials.
authors.affiliation: NMR Research Unit, Institute of Neurology, University College London, Queen Square, London, UK.
authors.forename: G R
authors.initials: GR
authors.lastname: Davies
authors.forename: L
authors.initials: L
authors.lastname: Ramió-Torrentà
authors.forename: A
authors.initials: A
authors.lastname: Hadjiprocopis
authors.forename: D T
authors.initials: DT
authors.lastname: Chard
authors.forename: C M B
authors.initials: CM
authors.lastname: Griffin
authors.forename: W
authors.initials: W
authors.lastname: Rashid
authors.forename: G J
authors.initials: GJ
authors.lastname: Barker
authors.forename: R
authors.initials: R
authors.lastname: Kapoor
authors.forename: A J
authors.initials: AJ
authors.lastname: Thompson
authors.forename: D H
authors.initials: DH
authors.lastname: Miller
mesh_terms: D000328:Adult; D001284:Atrophy / Q000473:pathology; D001921:Brain / Q000473:pathology*; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000473:pathology*; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires