title: Assessment of normal-appearing white and gray matter in patients with primary progressive multiple sclerosis: a diffusion-tensor magnetic resonance imaging study.
abstract: BACKGROUND
  Diffusion-tensor magnetic resonance imaging is sensitive to the more destructive aspects of multiple sclerosis (MS) evolution occurring outside and within T2-visible lesions and, as a consequence, holds promise for providing a more complete picture of primary progressive (PP) MS-related tissue damage than conventional magnetic resonance imaging.
  
  
  OBJECTIVE
  To improve our understanding of PPMS by assessing the extent of occult pathological features in the normal-appearing white and gray matter of the brain using diffusion-tensor magnetic resonance imaging.
  
  
  METHODS
  Ninety-six patients with PPMS, 47 patients with secondary progressive (SP) MS, and 44 healthy control subjects were studied. T2-hyperintense and T1-hypointense lesion volumes were calculated, and the volume of the whole brain tissue was measured. Diffusion-tensor magnetic resonance imaging scans were postprocessed and analyzed to obtain the mean diffusivity and fractional anisotropy histograms from the brain and from the normal-appearing white and gray matter in isolation.
  
  
  RESULTS
  The mean T2-hyperintense and T1-hypointense lesion volumes were lower in patients with PPMS than in patients with SPMS, while the mean absolute brain volumes were similar in the 2 groups. The average lesion diffusivity was significantly higher in patients with SPMS than in patients with PPMS (P<.001). Histogram-derived metrics of the brain tissue and normal-appearing white and gray matter were significantly different between patients with PPMS and healthy subjects (range, P =.004 to <.001). Average diffusivity values were significantly higher in patients with SPMS than in patients with PPMS for all the tissues studied (range, P =.001 to <.001). Fractional anisotropy histogram-derived quantities did not significantly differ between the 2 patient groups (range, P =.94 to.03).
  
  
  CONCLUSIONS
  This study confirms that, in patients with PPMS, normal-appearing white and gray matter are not spared by disease-related pathological processes, although they are affected to a lesser degree than in patients with SPMS.
authors.affiliation: Neuroimaging Research Unit, Department of Neuroscience, Scientific Institute and University Ospedale San Raffaele, Via Olgettina 60, 20132 Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Rovaris
authors.forename: Marco
authors.initials: M
authors.lastname: Bozzali
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Iannucci
authors.forename: Angelo
authors.initials: A
authors.lastname: Ghezzi
authors.forename: Domenico
authors.initials: D
authors.lastname: Caputo
authors.forename: Enrico
authors.initials: E
authors.lastname: Montanari
authors.forename: Antonio
authors.initials: A
authors.lastname: Bertolotto
authors.forename: Roberto
authors.initials: R
authors.lastname: Bergamaschi
authors.forename: Ruggero
authors.initials: R
authors.lastname: Capra
authors.forename: Giovanni Luigi
authors.initials: GL
authors.lastname: Mancardi
authors.forename: Vittorio
authors.initials: V
authors.lastname: Martinelli
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Comi
authors.forename: Massimo
authors.initials: M
authors.lastname: Filippi
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000473:pathology*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D012595:Scleroderma, Systemic / Q000473:pathology*