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February 14, 2017; 88 (7) Article

Quantitative assessment of white matter injury in preterm neonates

Association with outcomes

Ting Guo, Emma G. Duerden, Elysia Adams, Vann Chau, Helen M. Branson, M. Mallar Chakravarty, Kenneth J. Poskitt, Anne Synnes, Ruth E. Grunau, Steven P. Miller
First published January 18, 2017, DOI: https://doi.org/10.1212/WNL.0000000000003606
Ting Guo
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.
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Emma G. Duerden
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.
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Elysia Adams
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.
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Vann Chau
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.
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Helen M. Branson
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.
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M. Mallar Chakravarty
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.
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Kenneth J. Poskitt
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.
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Anne Synnes
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.
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Ruth E. Grunau
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.
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Steven P. Miller
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.
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Citation
Quantitative assessment of white matter injury in preterm neonates
Association with outcomes
Ting Guo, Emma G. Duerden, Elysia Adams, Vann Chau, Helen M. Branson, M. Mallar Chakravarty, Kenneth J. Poskitt, Anne Synnes, Ruth E. Grunau, Steven P. Miller
Neurology Feb 2017, 88 (7) 614-622; DOI: 10.1212/WNL.0000000000003606

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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.

GLOSSARY

CA=
corrected age;
GA=
gestational age;
IQR=
interquartile range;
IVH=
intraventricular hemorrhage;
IZ=
intermediate zone;
OR=
odds ratio;
PMA=
postmenstrual age;
PVL=
periventricular leukomalacia;
SVZ=
subventricular zone;
TEA=
term-equivalent age;
WMI=
white matter injury

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Supplemental data at Neurology.org

  • Editorial, page 610

  • Received February 23, 2016.
  • Accepted in final form September 29, 2016.
  • © 2017 American Academy of Neurology
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