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Radiographic and histologic characterisation of white matter injury in a sheep model of CHD

Published online by Cambridge University Press:  19 April 2022

Kendall M. Lawrence*
Affiliation:
Division of Cardiovascular Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA
Enrico Radaelli
Affiliation:
Division of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, USA
Patrick E. McGovern
Affiliation:
The Center for Fetal Research, Department of Surgery, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Daniel J. Licht
Affiliation:
Division of Neurology, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Marcus G. Davey
Affiliation:
The Center for Fetal Research, Department of Surgery, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Alan W. Flake
Affiliation:
The Center for Fetal Research, Department of Surgery, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA
J. William Gaynor
Affiliation:
Division of Cardiothoracic Surgery, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Arastoo Vossough
Affiliation:
Division of Radiology, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA
*
Author for correspondence: Kendall Lawrence, MD, Hospital of the University of Pennsylvania, Division of Cardiovascular Surgery, 3400 Spruce Street, Philadelphia, PA 19104, USA. Tel: +1 215 203 4845. E-mail: Kendall.Lawrence@pennmedicine.upenn.edu.

Abstract

Nearly one in five children with CHD is born with white matter injury that can be recognised on postnatal MRI by the presence of T1 hyperintense lesions. This pattern of white matter injury is known to portend poor neurodevelopmental outcomes, but the exact aetiology and histologic characterisation of these lesions have never been described. A fetal sheep was cannulated at gestational age 110 days onto a pumpless extracorporeal oxygenator via the umbilical vessels and supported in a fluid environment for 14.5 days. The fetus was supported under hypoxic conditions (mean oxygen delivery 16 ml/kg/day) to simulate the in utero conditions of CHD. At necropsy, the brain was fixed, imaged with MRI, and then stained to histologically identify areas of injury. Under hypoxemic in utero conditions, the fetus developed a T1 hyperintense lesion in its right frontal lobe. Histologically, this lesion was characterised by microvascular proliferation and astrocytosis without gliosis. These findings may provide valuable insight into the aetiology of white matter injury in neonates with CHD.

Type
Original Article
Copyright
© The Author(s), 2022. Published by Cambridge University Press

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