title: Corpus callosum axonal injury in multiple sclerosis measured by proton magnetic resonance spectroscopic imaging.
abstract: BACKGROUND
  Axonal damage has been observed in normal-appearing white matter (NAWM) for patients with multiple sclerosis (MS).
  
  
  OBJECTIVE
  To investigate changes in brain metabolite ratios in a region of normal-appearing corpus callosum (CC) for patients with MS and to test its relationship to changes in other regions of NAWM.
  
  
  METHODS
  Data were collected from 24 patients with MS and 15 control subjects. Two-dimensional proton magnetic resonance spectroscopic imaging was performed centered at the CC. Regions of interest from normal-appearing CC were manually segmented using anatomical images. The NAWM outside the CC region was segmented based on the signal intensity in T1- and T2-weighted images.
  
  
  RESULTS
  The N-acetylaspartate-creatine-phosphocreatine ratio was lower in both regions for patients with secondary progressive MS compared with the controls; the N-acetylaspartate-creatine-phosphocreatine was lower only in the normal-appearing CC region for patients with relapsing-remitting MS (P<.001) compared with the controls. The ratio of choline-containing compound compared with the creatine-phosphocreatine ratio was also lower in the region of normal-appearing CC for patients with relapsing-remitting MS (P =.003) compared with the controls. There was a correlation between the N-acetylaspartate-creatine-phosphocreatine ratio in the normal-appearing CC and T1 lesions (r = -0.53, P =.01) for all patients.
  
  
  CONCLUSIONS
  The CC was a more sensitive location for depicting axonal injury than other regions of NAWM. A correlation between the reduction of the N-acetylaspartate-creatine-phosphocreatine ratio in the normal-appearing CC and the T1 lesions may suggest that transection of axons in lesions may cause distant axonal damage and/or dysfunction that are expressed and more sensitively detectable in the CC.
authors.affiliation: Magnetic Resonance Science Center, Department of Radiology, University of California-San Francisco, 185 Berry Street, Suite 350, San Francisco, CA 94107, USA. joonmi@mrsc.ucsf.edu
authors.forename: Joonmi
authors.initials: J
authors.lastname: Oh
authors.forename: Daniel
authors.initials: D
authors.lastname: Pelletier
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Nelson
mesh_terms: D000328:Adult; D001369:Axons / Q000378:metabolism / Q000473:pathology*; D003337:Corpus Callosum / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism / Q000473:pathology*; D011522:Protons; D018709:Statistics, Nonparametric
chemical_list: D011522:Protons