title: White matter proton MR spectroscopy in children with isolated developmental delay: does it mean delayed myelination?
abstract: OBJECTIVE
  Isolated developmental delay (IDD) is a common disorder in preschool and school-age children. Conventional magnetic resonance imaging (MRI) usually does not disclose abnormalities, but a myelination delay is suspected as causative or associated factor. N-acetyl-aspartate is a surrogate marker of neuronal integrity but also of axonal integrity. The goal of our study is to determine whether magnetic resonance spectroscopy (MRS) is able to detect alterations in the white matter supporting the hypothesis of delayed myelination in children with IDD and normal MRI.
  
  
  METHODS
  In this cross-sectional study, we enrolled 12 consecutive children meeting the criteria if IDD and aged between 3 and 12 years (mean 7.25 years) and 11 healthy children as control group (mean age 7.18, range 3-12 years) on whom we performed conventional MRI and MRS. We did not include children with abnormal MRI. Single voxel (8 cm(3)) was placed in the white matter of the left centrum semiovale. The mode of acquisition was probe-p (PRESS technique) with a TR of 2500 milliseconds and a TE of 30 milliseconds. We measured the metabolite concentration of n-acetyl-aspartate (NAA), choline (Ch), creatine (Cr) y myo-inositol (mI), and ratios of NAA, Ch, and mI to creatine.
  
  
  RESULTS
  In children with IDD, we found a significant decrease of the following ratios: NAA/Cr (P < .016), NAA/Ch (P < .026), and NAA/mI (P < .023) in relation to controls. The mean NAA/Cr ratio in IDD children was 1.92 (SD 0.14), and in controls it was 2.09 (SD 0.14); t = 2.62, fd (freedom degrees) = 21, P < .016. No differences were seen in the remaining ratios.
  
  
  CONCLUSIONS
  The lower NAA/Cr ratio in children with IDD in relation to controls may be a promising marker of this disorder and supports the hypothesis of delayed myelination. MRS can provide important information in children with neurodevelopmental disorders.
authors.affiliation: Magnetic Resonance Unit, Clínica Quirón, Avda de la Ilustración 12, C39, 50012 Zaragoza, Spain.
authors.forename: Nicolás
authors.initials: N
authors.lastname: Fayed
authors.forename: Humberto
authors.initials: H
authors.lastname: Morales
authors.forename: Pedro J
authors.initials: PJ
authors.lastname: Modrego
authors.forename: Juan
authors.initials: J
authors.lastname: Muñoz-Mingarro
mesh_terms: D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002794:Choline / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D003430:Cross-Sectional Studies; D002658:Developmental Disabilities / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007294:Inositol / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D011522:Protons
chemical_list: D015415:Biomarkers; D011522:Protons; D001224:Aspartic Acid; D007294:Inositol; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline