title: Proton MR spectroscopic imaging predicts lesion progression on MRI in X-linked adrenoleukodystrophy.
abstract: BACKGROUND
  The phenotypic expression of X-linked adrenoleukodystrophy (X-ALD) ranges from the rapidly progressive childhood cerebral form to the milder adrenomyeloneuropathy in adults. It is not possible to predict phenotype by mutation analysis or biochemical assays. Multislice proton MRS imaging (MRSI) has previously detected more extensive brain abnormalities in X-ALD than conventional MRI, which has been suggested to predict impending demyelination. However, the significance of these changes is unclear.
  
  
  OBJECTIVE
  The purpose of this study was to determine the long-term sensitivity and specificity of MRSI for disease progression in X-ALD.
  
  
  METHODS
  Twenty-five patients with X-ALD were investigated (average age, 15 years; range, 2-43 years) with MRI and proton MRSI at baseline and follow-up MRI over a mean period of 3.5 years. Eight patients had normal MRI findings at baseline and on follow-up (noncerebral group), 11 had abnormal MRI at baseline and no change on follow-up (cerebral nonprogressive group), and 6 had progressive MRI abnormalities (cerebral progressive group). On MRSI, voxels were analyzed in the normal MRI-appearing perilesional white matter, or in the corresponding area in the noncerebral group.
  
  
  RESULTS
  The concentration ratio of N-acetylaspartate (NAA) to choline was the most sensitive indicator of disease progression. The average NAA/choline ratio was 5.99 for the noncerebral group, 5.75 for the cerebral nonprogressive group, and 3.74 for the cerebral progressive group (p = 0.002). At a cut-off point of 5.0, the NAA/choline ratio predicted disease progression in all patients with six cerebral progressive disease (sensitivity 100%). The specificity was 83%, the positive predictive value was 66%, and the negative predictive value was 100%.
  
  
  CONCLUSIONS
  Multislice proton MRS imaging is able to identify impending or beginning degeneration in white matter that still appears normal on conventional MRI. Multislice proton MRSI may be a suitable technique for the prediction of lesion progression on MRI in X-linked adrenoleukodystrophy.
authors.affiliation: F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Johns Hopkins University, Baltimore, MD 21205, USA.
authors.forename: F S
authors.initials: FS
authors.lastname: Eichler
authors.forename: P B
authors.initials: PB
authors.lastname: Barker
authors.forename: C
authors.initials: C
authors.lastname: Cox
authors.forename: D
authors.initials: D
authors.lastname: Edwin
authors.forename: A M
authors.initials: AM
authors.lastname: Ulug
authors.forename: H W
authors.initials: HW
authors.lastname: Moser
authors.forename: G V
authors.initials: GV
authors.lastname: Raymond
mesh_terms: D000293:Adolescent; D000326:Adrenoleukodystrophy / Q000235:genetics / Q000473:pathology*; D000328:Adult; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005500:Follow-Up Studies; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods* / Q000706:statistics & numerical data / Q000639:trends; D009682:Magnetic Resonance Spectroscopy / Q000379:methods* / Q000706:statistics & numerical data; D008297:Male; D010641:Phenotype; D011522:Protons; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric
chemical_list: D011522:Protons