title: Quantitative assessment of white matter injury in preterm neonates: Association with outcomes.
abstract: OBJECTIVE
  To quantitatively assess white matter injury (WMI) volume and location in very preterm neonates, and to examine the association of lesion volume and location with 18-month neurodevelopmental outcomes.
  
  
  METHODS
  Volume and location of WMI was quantified on MRI in 216 neonates (median gestational age 27.9 weeks) who had motor, cognitive, and language assessments at 18 months corrected age (CA). Neonates were scanned at 32.1 postmenstrual weeks (median) and 68 (31.5%) had WMI; of 66 survivors, 58 (87.9%) had MRI and 18-month outcomes. WMI was manually segmented and transformed into a common image space, accounting for intersubject anatomical variability. Probability maps describing the likelihood of a lesion predicting adverse 18-month outcomes were developed.
  
  
  RESULTS
  WMI occurs in a characteristic topology, with most lesions occurring in the periventricular central region, followed by posterior and frontal regions. Irrespective of lesion location, greater WMI volumes predicted poor motor outcomes (p= 0.001). Lobar regional analysis revealed that greater WMI volumes in frontal, parietal, and temporal lobes have adverse motor outcomes (all,p< 0.05), but only frontal WMI volumes predicted adverse cognitive outcomes (p= 0.002). To account for lesion location and volume, voxel-wise odds ratio (OR) maps demonstrate that frontal lobe lesions predict adverse cognitive and language development, with maximum odds ratios (ORs) of 78.9 and 17.5, respectively, while adverse motor outcomes are predicted by widespread injury, with maximum OR of 63.8.
  
  
  CONCLUSIONS
  The predictive value of frontal lobe WMI volume highlights the importance of lesion location when considering the neurodevelopmental significance of WMI. Frontal lobe lesions are of particular concern.
authors.affiliation: From Neurosciences and Mental Health (T.G., E.G.D., V.C., S.P.M.), The Hospital for Sick Children Research Institute; Departments of Paediatrics (T.G., E.G.D., E.A., V.C., S.P.M.) and Diagnostic Imaging (H.M.B.), The Hospital for Sick Children and the University of Toronto; Cerebral Imaging Centre (M.M.C.), Douglas Mental Health Research Institute, Verdun; Department of Psychiatry (M.M.C.) and Biological and Biomedical Engineering (M.M.C.), McGill University, Montreal; and Department of Pediatrics (K.J.P., A.S., R.E.G.), University of British Columbia, and BC Children's Hospital Research Institute, Vancouver, Canada.
authors.forename: Ting
authors.initials: T
authors.lastname: Guo
authors.affiliation: From Neurosciences and Mental Health (T.G., E.G.D., V.C., S.P.M.), The Hospital for Sick Children Research Institute; Departments of Paediatrics (T.G., E.G.D., E.A., V.C., S.P.M.) and Diagnostic Imaging (H.M.B.), The Hospital for Sick Children and the University of Toronto; Cerebral Imaging Centre (M.M.C.), Douglas Mental Health Research Institute, Verdun; Department of Psychiatry (M.M.C.) and Biological and Biomedical Engineering (M.M.C.), McGill University, Montreal; and Department of Pediatrics (K.J.P., A.S., R.E.G.), University of British Columbia, and BC Children's Hospital Research Institute, Vancouver, Canada.
authors.forename: Emma G
authors.initials: EG
authors.lastname: Duerden
authors.affiliation: From Neurosciences and Mental Health (T.G., E.G.D., V.C., S.P.M.), The Hospital for Sick Children Research Institute; Departments of Paediatrics (T.G., E.G.D., E.A., V.C., S.P.M.) and Diagnostic Imaging (H.M.B.), The Hospital for Sick Children and the University of Toronto; Cerebral Imaging Centre (M.M.C.), Douglas Mental Health Research Institute, Verdun; Department of Psychiatry (M.M.C.) and Biological and Biomedical Engineering (M.M.C.), McGill University, Montreal; and Department of Pediatrics (K.J.P., A.S., R.E.G.), University of British Columbia, and BC Children's Hospital Research Institute, Vancouver, Canada.
authors.forename: Elysia
authors.initials: E
authors.lastname: Adams
authors.affiliation: From Neurosciences and Mental Health (T.G., E.G.D., V.C., S.P.M.), The Hospital for Sick Children Research Institute; Departments of Paediatrics (T.G., E.G.D., E.A., V.C., S.P.M.) and Diagnostic Imaging (H.M.B.), The Hospital for Sick Children and the University of Toronto; Cerebral Imaging Centre (M.M.C.), Douglas Mental Health Research Institute, Verdun; Department of Psychiatry (M.M.C.) and Biological and Biomedical Engineering (M.M.C.), McGill University, Montreal; and Department of Pediatrics (K.J.P., A.S., R.E.G.), University of British Columbia, and BC Children's Hospital Research Institute, Vancouver, Canada.
authors.forename: Vann
authors.initials: V
authors.lastname: Chau
authors.affiliation: From Neurosciences and Mental Health (T.G., E.G.D., V.C., S.P.M.), The Hospital for Sick Children Research Institute; Departments of Paediatrics (T.G., E.G.D., E.A., V.C., S.P.M.) and Diagnostic Imaging (H.M.B.), The Hospital for Sick Children and the University of Toronto; Cerebral Imaging Centre (M.M.C.), Douglas Mental Health Research Institute, Verdun; Department of Psychiatry (M.M.C.) and Biological and Biomedical Engineering (M.M.C.), McGill University, Montreal; and Department of Pediatrics (K.J.P., A.S., R.E.G.), University of British Columbia, and BC Children's Hospital Research Institute, Vancouver, Canada.
authors.forename: Helen M
authors.initials: HM
authors.lastname: Branson
authors.affiliation: From Neurosciences and Mental Health (T.G., E.G.D., V.C., S.P.M.), The Hospital for Sick Children Research Institute; Departments of Paediatrics (T.G., E.G.D., E.A., V.C., S.P.M.) and Diagnostic Imaging (H.M.B.), The Hospital for Sick Children and the University of Toronto; Cerebral Imaging Centre (M.M.C.), Douglas Mental Health Research Institute, Verdun; Department of Psychiatry (M.M.C.) and Biological and Biomedical Engineering (M.M.C.), McGill University, Montreal; and Department of Pediatrics (K.J.P., A.S., R.E.G.), University of British Columbia, and BC Children's Hospital Research Institute, Vancouver, Canada.
authors.forename: M Mallar
authors.initials: MM
authors.lastname: Chakravarty
authors.affiliation: From Neurosciences and Mental Health (T.G., E.G.D., V.C., S.P.M.), The Hospital for Sick Children Research Institute; Departments of Paediatrics (T.G., E.G.D., E.A., V.C., S.P.M.) and Diagnostic Imaging (H.M.B.), The Hospital for Sick Children and the University of Toronto; Cerebral Imaging Centre (M.M.C.), Douglas Mental Health Research Institute, Verdun; Department of Psychiatry (M.M.C.) and Biological and Biomedical Engineering (M.M.C.), McGill University, Montreal; and Department of Pediatrics (K.J.P., A.S., R.E.G.), University of British Columbia, and BC Children's Hospital Research Institute, Vancouver, Canada.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Poskitt
authors.affiliation: From Neurosciences and Mental Health (T.G., E.G.D., V.C., S.P.M.), The Hospital for Sick Children Research Institute; Departments of Paediatrics (T.G., E.G.D., E.A., V.C., S.P.M.) and Diagnostic Imaging (H.M.B.), The Hospital for Sick Children and the University of Toronto; Cerebral Imaging Centre (M.M.C.), Douglas Mental Health Research Institute, Verdun; Department of Psychiatry (M.M.C.) and Biological and Biomedical Engineering (M.M.C.), McGill University, Montreal; and Department of Pediatrics (K.J.P., A.S., R.E.G.), University of British Columbia, and BC Children's Hospital Research Institute, Vancouver, Canada.
authors.forename: Anne
authors.initials: A
authors.lastname: Synnes
authors.affiliation: From Neurosciences and Mental Health (T.G., E.G.D., V.C., S.P.M.), The Hospital for Sick Children Research Institute; Departments of Paediatrics (T.G., E.G.D., E.A., V.C., S.P.M.) and Diagnostic Imaging (H.M.B.), The Hospital for Sick Children and the University of Toronto; Cerebral Imaging Centre (M.M.C.), Douglas Mental Health Research Institute, Verdun; Department of Psychiatry (M.M.C.) and Biological and Biomedical Engineering (M.M.C.), McGill University, Montreal; and Department of Pediatrics (K.J.P., A.S., R.E.G.), University of British Columbia, and BC Children's Hospital Research Institute, Vancouver, Canada.
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Grunau
authors.affiliation: From Neurosciences and Mental Health (T.G., E.G.D., V.C., S.P.M.), The Hospital for Sick Children Research Institute; Departments of Paediatrics (T.G., E.G.D., E.A., V.C., S.P.M.) and Diagnostic Imaging (H.M.B.), The Hospital for Sick Children and the University of Toronto; Cerebral Imaging Centre (M.M.C.), Douglas Mental Health Research Institute, Verdun; Department of Psychiatry (M.M.C.) and Biological and Biomedical Engineering (M.M.C.), McGill University, Montreal; and Department of Pediatrics (K.J.P., A.S., R.E.G.), University of British Columbia, and BC Children's Hospital Research Institute, Vancouver, Canada. steven.miller@sickkids.ca.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Miller
mesh_terms: D001921:Brain / Q000000981:diagnostic imaging*; D002547:Cerebral Palsy / Q000000981:diagnostic imaging; D002657:Child Development; D003072:Cognition Disorders / Q000000981:diagnostic imaging; D002658:Developmental Disabilities / Q000000981:diagnostic imaging; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D007223:Infant; D062071:Infant, Extremely Premature; D007231:Infant, Newborn; D007805:Language Development Disorders / Q000000981:diagnostic imaging; D008279:Magnetic Resonance Imaging; D008297:Male; D009069:Movement Disorders / Q000000981:diagnostic imaging; D015999:Multivariate Analysis; D016017:Odds Ratio; D011379:Prognosis; D066127:White Matter / Q000000981:diagnostic imaging*