title: Motor and cortico-striatal-thalamic connectivity alterations in intrauterine growth restriction.
abstract: Intrauterine growth restriction is associated with short- and long-term neurodevelopmental problems. Structural brain changes underlying these alterations have been described with the use of different magnetic resonance-based methods that include changes in whole structural brain networks. However, evaluation of specific brain circuits and its correlation with related functions has not been investigated in intrauterine growth restriction.
  
  
  
  In this study, we aimed to investigate differences in tractography-related metrics in cortico-striatal-thalamic and motor networks in intrauterine growth restricted children and whether these parameters were related with their specific function in order to explore its potential use as an imaging biomarker of altered neurodevelopment.
  
  
  
  We included a group of 24 intrauterine growth restriction subjects and 27 control subjects that were scanned at 1 year old; we acquired T1-weighted and 30 directions diffusion magnetic resonance images. Each subject brain was segmented in 93 regions with the use of anatomical automatic labeling atlas, and deterministic tractography was performed. Brain regions included in motor and cortico-striatal-thalamic networks were defined based in functional and anatomic criteria. Within the streamlines that resulted from the whole brain tractography, those belonging to each specific circuit were selected and tractography-related metrics that included number of streamlines, fractional anisotropy, and integrity were calculated for each network. We evaluated differences between both groups and further explored the correlation of these parameters with the results of socioemotional, cognitive, and motor scales from Bayley Scale at 2 years of age.
  
  
  
  Reduced fractional anisotropy (cortico-striatal-thalamic, 0.319 ± 0.018 vs 0.315 ± 0.015; P = .010; motor, 0.322 ± 0.019 vs 0.319 ± 0.020; P = .019) and integrity cortico-striatal-thalamic (0.407 ± 0.040 vs 0.399 ± 0.034; P = .018; motor, 0.417 ± 0.044 vs 0.409 ± 0.046; P = .016) in both networks were observed in the intrauterine growth restriction group, with no differences in number of streamlines. More importantly, strong specific correlation was found between tractography-related metrics and its relative function in both networks in intrauterine growth restricted children. Motor network metrics were correlated specifically with motor scale results (fractional anisotropy: rho = 0.857; integrity: rho = 0.740); cortico-striatal-thalamic network metrics were correlated with cognitive (fractional anisotropy: rho = 0.793; integrity, rho = 0.762) and socioemotional scale (fractional anisotropy: rho = 0.850; integrity: rho = 0.877).
  
  
  
  These results support the existence of altered brain connectivity in intrauterine growth restriction demonstrated by altered connectivity in motor and cortico-striatal-thalamic networks, with reduced fractional anisotropy and integrity. The specific correlation between tractography-related metrics and neurodevelopmental outcomes in intrauterine growth restriction shows the potential to use this approach to develop imaging biomarkers to predict specific neurodevelopmental outcome in infants who are at risk because of intrauterine growth restriction and other prenatal diseases.
authors.affiliation: Fetal i+D Fetal Medicine Research Center, BCNatal-Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), IDIBAPS, University of Barcelona, Barcelona, Spain; Centre for Biomedical Research on Rare Diseases, Barcelona, Spain. Electronic address: eixarch@clinic.ub.es.
authors.forename: Elisenda
authors.initials: E
authors.lastname: Eixarch
authors.affiliation: Fetal i+D Fetal Medicine Research Center, BCNatal-Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Emma
authors.initials: E
authors.lastname: Muñoz-Moreno
authors.affiliation: Department of Radiology, Centre de Diagnòstic per la Imatge Clínic, Hospital Clínic, and the Magnetic Resonance core facility, Institut d'Investigacions Biomediques August Pi i Sunyer, Barcelona, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Bargallo
authors.affiliation: Fetal i+D Fetal Medicine Research Center, BCNatal-Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), IDIBAPS, University of Barcelona, Barcelona, Spain; Centre for the Developing Brain, Division of Imaging Sciences & Biomedical Engineering, King's College London, London, United Kingdom.
authors.forename: Dafnis
authors.initials: D
authors.lastname: Batalle
authors.affiliation: Fetal i+D Fetal Medicine Research Center, BCNatal-Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), IDIBAPS, University of Barcelona, Barcelona, Spain; Centre for Biomedical Research on Rare Diseases, Barcelona, Spain.
authors.forename: Eduard
authors.initials: E
authors.lastname: Gratacos
mesh_terms: D016022:Case-Control Studies; D015331:Cohort Studies; D003342:Corpus Striatum / Q000000981:diagnostic imaging*; D038524:Diffusion Magnetic Resonance Imaging; D056324:Diffusion Tensor Imaging; D005260:Female; D005317:Fetal Growth Retardation / Q000503:physiopathology*; D006801:Humans; D007223:Infant; D008297:Male; D009044:Motor Cortex / Q000000981:diagnostic imaging*; D009434:Neural Pathways / Q000502:physiology*; D011247:Pregnancy; D013788:Thalamus / Q000000981:diagnostic imaging*
keywords: brain network; connectivity; fractional anisotropy; intrauterine growth restriction; magnetic resonance imaging; tractography-related metrics