title: Association of brain metabolism with sulcation and corpus callosum development assessed by MRI in late-onset small fetuses.
abstract: OBJECTIVE
  We sought to determine the relationship between fetal brain metabolism and microstructure expressed by brain sulcation, and corpus callosum (CC) development assessed by fetal brain magnetic resonance (MR) imaging and proton MR spectroscopy ((1)H-MRS).
  
  
  METHODS
  A total of 119 fetuses, 64 that were small for gestational age (estimated fetal weight <10th centile and normal umbilical artery Doppler) and 55 controls underwent a 3T MR imaging/(1)H-MRS exam at 37 weeks. Anatomical T2-weighted images were obtained in the 3 orthogonal planes and long echo time (TE) (1)H-MRS acquired from the frontal lobe. Head biometrics, cortical fissure depths (insula, Sylvian, parietooccipital, cingulate, and calcarine), and CC area and biometries were blindly performed by manual and semiautomated delineation using Analyze software and corrected creating ratios for biparietal diameter and frontooccipital diameter, respectively, for group comparison. Spectroscopic data were processed using LCModel software and analyzed as metabolic ratios of N-acetylaspartate (NAA) to choline (Cho), Cho to creatine (Cr), and myo-inositol (Ino) to Cho. Differences between cases and controls were assessed. To test for the association between metabolic ratios and microstructural parameters, bivariate correlation analyses were performed.
  
  
  RESULTS
  Spectroscopic findings showed decreased NAA/Cho and increased Cho/Cr ratios in small fetuses. They also presented smaller head biometrics, shorter and smaller CC, and greater insular and cingulate depths. Frontal lobe NAA/Cho significantly correlated with biparietal diameter (r = 0.268; P = .021), head circumference (r = 0.259; P = .026), CC length (r = 0.265; P = .026), CC area (r = 0.317; P = .007), and the area of 6 from the 7 CC subdivisions. It did not correlate with any of the cortical sulcation parameters evaluated. None of the other metabolic ratios presented significant correlations with cortical development or CC parameters.
  
  
  CONCLUSIONS
  Frontal lobe NAA/Cho levels-which are considered a surrogate marker of neuronal activity-show a strong association with CC development. These results suggest that both metabolic and callosal alterations may be part of the same process of impaired brain development associated with intrauterine growth restriction.
authors: Fetal i+D Fetal Medicine Research Center, BCNatal-Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), Institut d'Investigacions Biomediques August Pi i Sunyer, University of Barcelona, Centre for Biomedical Research on Rare Diseases, Barcelona, Spain. Electronic address: msanz1@clinic.ub.es.
authors: Magdalena
authors: M
authors: Sanz-Cortes
authors: Fetal i+D Fetal Medicine Research Center, BCNatal-Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), Institut d'Investigacions Biomediques August Pi i Sunyer, University of Barcelona, Centre for Biomedical Research on Rare Diseases, Barcelona, Spain.
authors: Gabriela
authors: G
authors: Egaña-Ugrinovic
authors: Fetal i+D Fetal Medicine Research Center, BCNatal-Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), Institut d'Investigacions Biomediques August Pi i Sunyer, University of Barcelona, Centre for Biomedical Research on Rare Diseases, Barcelona, Spain.
authors: Rui V
authors: RV
authors: Simoes
authors: Department of Obstetrics and Gynecology, Hospital italiano de Buenos Aires, Buenos Aires, Argentina.
authors: Lucia
authors: L
authors: Vazquez
authors: Department of Radiology, Centre de Diagnostic per la Imatge, Hospital Clínic, Barcelona, Spain; Medical Image platform, Institut d'Investigacions Biomediques August Pi i Sunyer, Barcelona, Spain.
authors: Nuria
authors: N
authors: Bargallo
authors: Fetal i+D Fetal Medicine Research Center, BCNatal-Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), Institut d'Investigacions Biomediques August Pi i Sunyer, University of Barcelona, Centre for Biomedical Research on Rare Diseases, Barcelona, Spain.
authors: Eduard
authors: E
authors: Gratacos
mesh_terms: D000328:Adult; D001921:Brain / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism*; D003337:Corpus Callosum / Q000254:growth & development / Q000378:metabolism; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism*; D006801:Humans; D008279:Magnetic Resonance Imaging; D011247:Pregnancy; D011446:Prospective Studies; D066244:Proton Magnetic Resonance Spectroscopy
keywords: fetal brain metabolism; fetal magnetic resonance imaging; intrauterine growth restriction; magnetic resonance spectroscopy; small for gestational age