title: Progressive gray matter damage in patients with relapsing-remitting multiple sclerosis: a longitudinal diffusion tensor magnetic resonance imaging study.
abstract: BACKGROUND
  Diffusion tensor magnetic resonance imaging (DT MRI) has the potential to provide in vivo information about tissue microstructure. In multiple sclerosis (MS), DT MRI has disclosed the presence of occult structural damage in the normal-appearing brain tissues.
  
  
  OBJECTIVE
  To investigate whether DT MRI is sensitive to longitudinal changes of brain damage that may occur beyond the resolution of T2-weighted images in patients with relapsing-remitting MS.
  
  
  METHODS
  Twenty-six untreated patients with relapsing-remitting MS were followed up for 18 months. Dual-echo, DT and postcontrast T1-weighted MRIs of the brain were obtained at baseline and then every 3 months. Mean diffusivity (D) histograms of normal-appearing gray (GM) and white matter were produced. Total T2-hyperintense and T1-hypointense lesion volumes; normalized whole brain tissue, GM, and white matter volumes; percentage brain volume change between the study entry and exit images; average lesion D; and fractional anisotropy were also calculated.
  
  
  RESULTS
  During the study period, a significant decrease of normalized whole brain tissue, average lesion fractional anisotropy and normal-appearing GM D histogram peak height, and a significant increase of average normal-appearing GM D and T2-hyperintense lesion volumes were observed. Changes of normal-appearing GM diffusivity were independent of the concomitant changes of normalized whole brain tissue and GM volumes.
  
  
  CONCLUSIONS
  The DT MRI findings show progressive microstructural changes in the normal-appearing GM of patients with untreated relapsing-remitting MS. Such changes do not reflect a concomitant development of brain atrophy and confirm the importance of GM pathology in MS.
authors.affiliation: Neuroimaging Unit and Department of Neurology, Scientific Institute and University H San Raffaele, Milan, Italy.
authors.forename: Celia
authors.initials: C
authors.lastname: Oreja-Guevara
authors.forename: Marco
authors.initials: M
authors.lastname: Rovaris
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Iannucci
authors.forename: Paola
authors.initials: P
authors.lastname: Valsasina
authors.forename: Domenico
authors.initials: D
authors.lastname: Caputo
authors.forename: Rosella
authors.initials: R
authors.lastname: Cavarretta
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Sormani
authors.forename: Pasquale
authors.initials: P
authors.lastname: Ferrante
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Comi
authors.forename: Massimo
authors.initials: M
authors.lastname: Filippi
mesh_terms: D000328:Adult; D001369:Axons / Q000473:pathology; D001921:Brain / Q000473:pathology* / Q000503:physiopathology*; D015331:Cohort Studies; D004058:Diffusion; D038524:Diffusion Magnetic Resonance Imaging / Q000592:standards* / Q000706:statistics & numerical data; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis* / Q000503:physiopathology*; D009410:Nerve Degeneration / Q000175:diagnosis / Q000503:physiopathology; D011237:Predictive Value of Tests; D012008:Recurrence
chemical_list: D008775:Methylprednisolone