title: Relapsing-remitting multiple sclerosis: metabolic abnormality in nonenhancing lesions and normal-appearing white matter at MR imaging: initial experience.
abstract: OBJECTIVE
  To quantify, with three-dimensional proton magnetic resonance (MR) spectroscopy, metabolic characteristics of normal-appearing white matter and nonenhancing lesions in patients with relapsing-remitting multiple sclerosis (MS).
  
  
  METHODS
  Institutional review board approval and informed patient consent were obtained. Nine patients with relapsing-remitting MS (six women, three men) and nine age-matched control subjects (seven women, two men) were studied with T1- and T2-weighted MR imaging and three-dimensional proton MR spectroscopy at spatial resolution less than a cubic centimeter. Absolute N-acetylaspartate (NAA), creatine (Cr), and choline (Cho) levels were obtained from 171 voxels: 66 from lesions on T2-weighted MR images (43 hypointense and 23 isointense on T1-weighted MR images), 31 from normal-appearing white matter, and 74 from analogous normal white matter regions on images in control subjects.
  
  
  RESULTS
  Mean NAA level in hypointense lesions (5.30 mmol/L +/- 2.27 [standard deviation]) was significantly lower (P < or = .05) than that in isointense lesions (7.82 mmol/L +/- 2.28), normal-appearing white matter (7.37 mmol/L +/- 1.71), and normal white matter in control subjects (8.89 mmol/L +/- 1.54). Cho (1.79 mmol/L +/- 0.65) and Cr (5.64 mmol/L +/- 1.50) levels in isointense lesions were indistinguishable from those in normal-appearing white matter (1.74 mmol/L +/- 0.46 and 4.99 mmol/L +/- 0.97, respectively) but were significantly higher (Cho, 20%; Cr, 24%) than those in normal white matter in control subjects (1.44 mmol/L +/- 0.40 and 4.30 mmol/L +/- 1.32, respectively). NAA, Cho, and Cr levels in normal-appearing white matter were significantly different than those in normal white matter in control subjects (NAA, 20% lower; Cho, 14% higher; and Cr, 17% higher).
  
  
  CONCLUSIONS
  Abnormal metabolic activity persists in all MS tissue types. Increased Cr and Cho levels suggest (a) ongoing gliosis and attempted remyelination in isointense lesions on T1-weighted MR images and (b) membrane turnover (de- and remyelination), in addition to increased cellularity (gliosis, inflammation) in normal-appearing white matter.
authors.affiliation: Department of Radiology, New York University School of Medicine, 650 First Avenue, New York, NY 10016, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: He
authors.forename: Matilde
authors.initials: M
authors.lastname: Inglese
authors.forename: Belinda S Y
authors.initials: BS
authors.lastname: Li
authors.forename: James S
authors.initials: JS
authors.lastname: Babb
authors.forename: Robert I
authors.initials: RI
authors.lastname: Grossman
authors.forename: Oded
authors.initials: O
authors.lastname: Gonen
mesh_terms: D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D016022:Case-Control Studies; D002794:Choline / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D005260:Female; D006801:Humans; D021621:Imaging, Three-Dimensional; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000378:metabolism*
chemical_list: D001224:Aspartic Acid; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline