title: Diffusion-tensor magnetic resonance imaging detects normal-appearing white matter damage unrelated to short-term disease activity in patients at the earliest clinical stage of multiple sclerosis.
abstract: BACKGROUND
  Diffusion-tensor (DT) magnetic resonance imaging (MRI) has the potential to elucidate some characteristics of tissue microstructure inaccessible to other MRI techniques.
  
  
  OBJECTIVE
  To investigate whether normal-appearing brain tissue abnormalities occur in patients with multiple sclerosis at the earliest clinical stage and whether their severity is predictive of a short-term disease evolution by using DT MRI.
  
  
  METHODS
  Forty-five patients and 22 healthy control subjects were studied. All patients had had a clinically isolated syndrome within the 3 months preceding study enrollment and paraclinical evidence of disease dissemination in space. During a single session, dual-echo, pulsed-gradient spin-echo echo-planar, and postgadolinium T1-weighted images of the brain were obtained from each subject. In patients, dual-echo and enhanced images were obtained after 3 and 12 months, to detect MRI signs of disease dissemination in time. An on-study neurological examination was also conducted to ascertain the occurrence of clinical relapses. Mean diffusivity and fractional anisotropy maps were derived from DT images. Normal-appearing white matter (NAWM) and normal-appearing gray matter mean diffusivity and fractional anisotropy histograms were produced and analyzed.
  
  
  RESULTS
  During the study period, 29 patients showed MRI evidence of disease dissemination in time. When compared with healthy controls, patients showed higher average NAWM mean diffusivity (P = .01), lower average NAWM mean diffusivity peak height (P < .001), and fractional anisotropy (P < .001). The DT MRI characteristics of patients did not differ between those with and those without disease dissemination in time at follow-up.
  
  
  CONCLUSIONS
  In patients with multiple sclerosis at the earliest clinical stage, the severity of NAWM damage does not predict new lesion formation in the short term, suggesting that the "diffuse" component of tissue damage is, at least partially, independent of the "discrete," predominantly inflammatory aspects of the disease since its clinical onset.
authors.affiliation: Neuroimaging Research Unit, Scientific Institute and University Ospedale San Raffaele, Milan, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Gallo
authors.forename: Marco
authors.initials: M
authors.lastname: Rovaris
authors.forename: Roberto
authors.initials: R
authors.lastname: Riva
authors.forename: Angelo
authors.initials: A
authors.lastname: Ghezzi
authors.forename: Beatrice
authors.initials: B
authors.lastname: Benedetti
authors.forename: Vittorio
authors.initials: V
authors.lastname: Martinelli
authors.forename: Andrea
authors.initials: A
authors.lastname: Falini
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Comi
authors.forename: Massimo
authors.initials: M
authors.lastname: Filippi
mesh_terms: D000328:Adult; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000473:pathology*; D038524:Diffusion Magnetic Resonance Imaging; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D009103:Multiple Sclerosis / Q000378:metabolism / Q000473:pathology*; D012720:Severity of Illness Index; D013997:Time Factors