title: Assessment of adrenoleukodystrophy lesions by high field MRS in non-sedated pediatric patients.
abstract: BACKGROUND
  Early detection of white matter lesions in childhood-onset cerebral adrenoleukodystrophy (ALD) is important as hematopoietic cell transplantation (HCT), currently the only effective treatment, is beneficial only if performed early in the disease course.
  
  
  OBJECTIVE
  To establish reliable biochemical markers of cerebral disease progression in patients with ALD to aid in treatment planning.
  
  
  METHODS
  The authors used proton magnetic resonance spectroscopy (MRS) in combination with LCModel analysis to quantify brain metabolites in small volumes (3 to 16 mL) in the occipital and frontal white matter and the splenium of the corpus callosum of 17 unsedated patients and 26 healthy volunteers (adult n = 21, age-matched n = 5) at 4 tesla.
  
  
  RESULTS
  Absolute concentrations of 12 metabolites were reliably determined, seven of which were established as markers of lesion development. Among these, creatine and choline containing compounds were the weakest markers while N-acetylaspartate, glutamine, and lipids + lactate were the strongest. The large extent of changes in the markers enabled detection of early neurochemical changes in lesion formation prior to detection of abnormalities by conventional MRI. Concentrations of a number of metabolites were also significantly different between normal appearing white matter of patients and controls indicating biochemical alterations in the absence of cerebral disease. Neurochemical improvements following HCT were measured in six patients.
  
  
  CONCLUSIONS
  The progression of adrenoleukodystrophy, as well as effectiveness of its treatment, can be assessed with high precision using high field 1H magnetic resonance spectroscopy in individual patients without the need for sedation.
authors.affiliation: Center for MR Research, University of Minnesota, Minneapolis, MN 55455, USA. gulin@cmrr.umn.edu
authors.forename: G
authors.initials: G
authors.lastname: Oz
authors.forename: I
authors.initials: I
authors.lastname: Tkác
authors.forename: L R
authors.initials: LR
authors.lastname: Charnas
authors.forename: I Y
authors.initials: IY
authors.lastname: Choi
authors.forename: K J
authors.initials: KJ
authors.lastname: Bjoraker
authors.forename: E G
authors.initials: EG
authors.lastname: Shapiro
authors.forename: R
authors.initials: R
authors.lastname: Gruetter
mesh_terms: D000293:Adolescent; D000326:Adrenoleukodystrophy / Q000145:classification / Q000175:diagnosis / Q000378:metabolism / Q000628:therapy*; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000032:analysis; D001923:Brain Chemistry; D002648:Child; D002675:Child, Preschool; D003401:Creatine / Q000032:analysis; D018450:Disease Progression; D005500:Follow-Up Studies; D005973:Glutamine / Q000032:analysis; D018380:Hematopoietic Stem Cell Transplantation / Q000401:mortality; D006801:Humans; D007294:Inositol / Q000032:analysis; D007773:Lactates / Q000032:analysis; D008055:Lipids / Q000032:analysis; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D009483:Neuropsychological Tests; D011379:Prognosis
chemical_list: D007773:Lactates; D008055:Lipids; D005973:Glutamine; D001224:Aspartic Acid; D007294:Inositol; C000179:N-acetylaspartate; D003401:Creatine