title: In Vivo Detection of Perinatal Brain Metabolite Changes in a Rabbit Model of Intrauterine Growth Restriction (IUGR).
abstract: BACKGROUND
  Intrauterine growth restriction (IUGR) is a risk factor for abnormal neurodevelopment. We studied a rabbit model of IUGR by magnetic resonance imaging (MRI) and spectroscopy (MRS), to assess in vivo brain structural and metabolic consequences, and identify potential metabolic biomarkers for clinical translation.
  
  
  METHODS
  IUGR was induced in 3 pregnant rabbits at gestational day 25, by 40-50% uteroplacental vessel ligation in one horn; the contralateral horn was used as control. Fetuses were delivered at day 30 and weighted. A total of 6 controls and 5 IUGR pups underwent T2-w MRI and localized proton MRS within the first 8 hours of life, at 7T. Changes in brain tissue volumes and respective contributions to each MRS voxel were estimated by semi-automated registration of MRI images with a digital atlas of the rabbit brain. MRS data were used for: (i) absolute metabolite quantifications, using linear fitting; (ii) local temperature estimations, based on the water chemical shift; and (iii) classification, using spectral pattern analysis.
  
  
  RESULTS
  Lower birth weight was associated with (i) smaller brain sizes, (ii) slightly lower brain temperatures, and (iii) differential metabolite profile changes in specific regions of the brain parenchyma. Specifically, we found estimated lower levels of aspartate and N-acetylaspartate (NAA) in the cerebral cortex and hippocampus (suggesting neuronal impairment), and higher glycine levels in the striatum (possible marker of brain injury). Our results also suggest that the metabolic changes in cortical regions are more prevalent than those detected in hippocampus and striatum.
  
  
  CONCLUSIONS
  IUGR was associated with brain metabolic changes in vivo, which correlate well with the neurostructural changes and neurodevelopment problems described in IUGR. Metabolic parameters could constitute non invasive biomarkers for the diagnosis and abnormal neurodevelopment of perinatal origin.
authors.affiliation: BCNatal-Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), Fetal i+D Fetal Medicine Research Center, IDIBAPS, University of Barcelona, Centre for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain.
authors.forename: Rui V
authors.initials: RV
authors.lastname: Simões
authors.affiliation: BCNatal-Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), Fetal i+D Fetal Medicine Research Center, IDIBAPS, University of Barcelona, Centre for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain.
authors.forename: Emma
authors.initials: E
authors.lastname: Muñoz-Moreno
authors.affiliation: Structural Biochemistry Laboratory, Centro de Investigación Príncipe Felipe, Valencia, Spain.
authors.forename: Rodrigo J
authors.initials: RJ
authors.lastname: Carbajo
authors.affiliation: BCNatal-Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), Fetal i+D Fetal Medicine Research Center, IDIBAPS, University of Barcelona, Centre for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: González-Tendero
authors.affiliation: BCNatal-Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), Fetal i+D Fetal Medicine Research Center, IDIBAPS, University of Barcelona, Centre for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain.
authors.forename: Miriam
authors.initials: M
authors.lastname: Illa
authors.affiliation: BCNatal-Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), Fetal i+D Fetal Medicine Research Center, IDIBAPS, University of Barcelona, Centre for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Sanz-Cortés
authors.affiliation: Structural Biochemistry Laboratory, Centro de Investigación Príncipe Felipe, Valencia, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Pineda-Lucena
authors.affiliation: BCNatal-Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), Fetal i+D Fetal Medicine Research Center, IDIBAPS, University of Barcelona, Centre for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain.
authors.forename: Eduard
authors.initials: E
authors.lastname: Gratacós
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001724:Birth Weight; D001921:Brain / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D005260:Female; D005317:Fetal Growth Retardation / Q000175:diagnosis / Q000378:metabolism*; D005865:Gestational Age; D005998:Glycine / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D023421:Models, Animal; D036801:Parturition; D011247:Pregnancy; D011817:Rabbits; D050497:Stillbirth / Q000662:veterinary
chemical_list: D015415:Biomarkers; D001224:Aspartic Acid; C000179:N-acetylaspartate; D005998:Glycine