title: Axon density and axon orientation dispersion in children born preterm.
abstract: Very preterm birth (VPT, <32 weeks' gestation) is associated with altered white matter fractional anisotropy (FA), the biological basis of which is uncertain but may relate to changes in axon density and/or dispersion, which can be measured using Neurite Orientation Dispersion and Density Imaging (NODDI). This study aimed to compare whole brain white matter FA, axon dispersion, and axon density between VPT children and controls (born ≥37 weeks' gestation), and to investigate associations with perinatal factors and neurodevelopmental outcomes.
  
  
  
  FA, neurite dispersion, and neurite density were estimated from multishell diffusion magnetic resonance images for 145 VPT and 33 control 7-year-olds. Diffusion values were compared between groups and correlated with perinatal factors (gestational age, birthweight, and neonatal brain abnormalities) and neurodevelopmental outcomes (IQ, motor, academic, and behavioral outcomes) using Tract-Based Spatial Statistics.
  
  
  
  Compared with controls, VPT children had lower FA and higher axon dispersion within many major white matter fiber tracts. Neonatal brain abnormalities predicted lower FA and higher axon dispersion in many major tracts in VPT children. Lower FA, higher axon dispersion, and lower axon density in various tracts correlated with poorer neurodevelopmental outcomes in VPT children.
  
  
  
  FA and NODDI measures distinguished VPT children from controls and were associated with neonatal brain abnormalities and neurodevelopmental outcomes. This study provides a more detailed and biologically meaningful interpretation of white matter microstructure changes associated with prematurity. Hum Brain Mapp 37:3080-3102, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Murdoch Childrens Research Institute, Melbourne, Australia.
authors.forename: Claire E
authors.initials: CE
authors.lastname: Kelly
authors.affiliation: Murdoch Childrens Research Institute, Melbourne, Australia.|Florey Institute of Neuroscience and Mental Health, Melbourne, Australia.|Department of Paediatrics, University of Melbourne, Melbourne, Australia.
authors.forename: Deanne K
authors.initials: DK
authors.lastname: Thompson
authors.affiliation: Murdoch Childrens Research Institute, Melbourne, Australia.|Department of Medicine, Monash Medical Centre, Monash University, Melbourne, Australia.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.affiliation: Image Sciences Institute, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Alexander
authors.initials: A
authors.lastname: Leemans
authors.affiliation: Murdoch Childrens Research Institute, Melbourne, Australia.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Adamson
authors.affiliation: Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Terrie E
authors.initials: TE
authors.lastname: Inder
authors.affiliation: Murdoch Childrens Research Institute, Melbourne, Australia.|Royal Women's Hospital, Melbourne, Australia.|Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Australia.
authors.forename: Jeanie L Y
authors.initials: JL
authors.lastname: Cheong
authors.affiliation: Murdoch Childrens Research Institute, Melbourne, Australia.|Department of Paediatrics, University of Melbourne, Melbourne, Australia.|Royal Women's Hospital, Melbourne, Australia.|Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Australia.
authors.forename: Lex W
authors.initials: LW
authors.lastname: Doyle
authors.affiliation: Murdoch Childrens Research Institute, Melbourne, Australia.|Department of Paediatrics, University of Melbourne, Melbourne, Australia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Anderson
mesh_terms: D016880:Anisotropy; D001369:Axons / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D001931:Brain Mapping / Q000379:methods*; D002648:Child; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D006801:Humans; D062071:Infant, Extremely Premature; D007231:Infant, Newborn; D008297:Male; D065886:Neurodevelopmental Disorders / Q000209:etiology / Q000473:pathology; D066127:White Matter / Q000473:pathology*
keywords: NODDI; diffusion tensor imaging; diffusion-weighted imaging; magnetic resonance imaging; neurodevelopment; preterm birth; white matter