title: Seven-Tesla proton magnetic resonance spectroscopic imaging in adult X-linked adrenoleukodystrophy.
abstract: BACKGROUND
  Adults with X-linked adrenoleukodystrophy (X-ALD) remain at risk for progressive neurological deterioration. Phenotypes vary in their pathology, ranging from axonal degeneration to inflammatory demyelination. The severity of symptoms is poorly explained by conventional imaging.
  
  
  OBJECTIVE
  To test the hypothesis that neurochemistry in normal-appearing brains differs in adult phenotypes of X-ALD and that neurochemical changes correlate with the severity of symptoms.
  
  
  METHODS
  Using a 7-Tesla scanner, we performed structural and proton magnetic resonance spectroscopic imaging in 13 adult patients with X-ALD: 4 patients with adult cerebral ALD, 5 patients with adrenomyeloneuropathy (AMN), and 4 female heterozygotes. Nine healthy controls were included.
  
  
  RESULTS
  Among adult X-ALD phenotypes, the myo-inositol to creatine ratio was 46% higher and the choline to creatine ratio was 21% higher in normal-appearing white matter of those with adult cerebral ALD compared with those with AMN (P < .05). Both N-acetylaspartate to creatine (P = .03) and glutamate to creatine (P = .04) ratios were lower in AMN patients than in controls. There were no significant differences between patients with AMN and female heterozygotes. In the cortex, patients with adult cerebral ALD had lower N-acetylaspartate to creatine ratios compared with female heterozygotes and controls (P = .02). The global myo-inositol to creatine ratio demonstrated a significant association with Expanded Disability Status Scale score (Spearman rho = 0.66, P = .04).
  
  
  CONCLUSIONS
  Seven-Tesla proton magnetic resonance spectroscopic imaging reveals differences in the neurochemistry of adult cerebral ALD but cannot distinguish AMN patients from female heterozygotes. Myo-inositol to creatine ratio correlates with the severity of the symptoms and may be a meaningful biomarker in adult X-ALD.
authors.affiliation: Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Eva
authors.initials: E
authors.lastname: Ratai
authors.forename: Trina
authors.initials: T
authors.lastname: Kok
authors.forename: Christopher
authors.initials: C
authors.lastname: Wiggins
authors.forename: Graham
authors.initials: G
authors.lastname: Wiggins
authors.forename: Ellen
authors.initials: E
authors.lastname: Grant
authors.forename: Borjan
authors.initials: B
authors.lastname: Gagoski
authors.forename: Gilmore
authors.initials: G
authors.lastname: O'Neill
authors.forename: Elfar
authors.initials: E
authors.lastname: Adalsteinsson
authors.forename: Florian
authors.initials: F
authors.lastname: Eichler
mesh_terms: D000326:Adrenoleukodystrophy / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D000328:Adult; D000368:Aged; D001921:Brain / Q000378:metabolism*; D002794:Choline / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D004185:Disability Evaluation; D005227:Fatty Acids / Q000097:blood / Q000737:chemistry; D005260:Female; D006579:Heterozygote; D006801:Humans; D007294:Inositol / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D010487:Periaqueductal Gray / Q000378:metabolism; D010641:Phenotype; D012720:Severity of Illness Index; D012737:Sex Factors; D055815:Young Adult
chemical_list: D005227:Fatty Acids; D007294:Inositol; D003401:Creatine; D002794:Choline