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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 Open the ORCID record for Kendall M. Lawrence [Opens in a new window] ,
Enrico Radaelli ,
Patrick E. McGovern ,
Daniel J. Licht ,
Marcus G. Davey ,
Alan W. Flake ,
J. William Gaynor  and
Arastoo Vossough
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.
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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.

Keywords

CHDwhite matter injuryMRI
Type
Original Article
Information
Cardiology in the Young , Volume 33 , Issue 3 , March 2023 , pp. 432 - 436
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Copyright
© The Author(s), 2022. Published by Cambridge University Press

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References

Licht, DJ, Shera, DM, Clancy, RR, et al. Brain maturation is delayed in infants with complex congenital heart defects. J Thorac Cardiovasc Surg 2009; 137: 529–536; discussion 536.CrossRefGoogle ScholarPubMed
Miller, SP, McQuillen, PS, Hamrick, S, et al. Abnormal brain development in newborns with congenital heart disease. N Engl J Med 2007; 357: 1928–1938.CrossRefGoogle ScholarPubMed
Beca, J, Gunn, JK, Coleman, L, et al. New white matter brain injury after infant heart surgery is associated with diagnostic group and the use of circulatory arrest. Circulation 2013; 127: 971–979.CrossRefGoogle ScholarPubMed
Dimitropoulos, A, McQuillen, PS, Sethi, V, et al. Brain injury and development in newborns with critical congenital heart disease. Neurology 2013; 81: 241–248.CrossRefGoogle ScholarPubMed
McQuillen, PS. Magnetic resonance imaging in congenital heart disease. Circulation 2009; 119: 660–662.CrossRefGoogle ScholarPubMed
Petit, CJ, Rome, JJ, Wernovsky, G, et al. Preoperative brain injury in transposition of the great arteries is associated with oxygenation and time to surgery, not balloon atrial septostomy. Circulation 2009; 119: 709–716.CrossRefGoogle Scholar
Mahle, WT, Tavani, F, Zimmerman, RA, et al. An MRI study of neurological injury before and after congenital heart surgery. Circulation 2002; 106: I109–14.CrossRefGoogle ScholarPubMed
Guo, T, Chau, V, Peyvandi, S, et al. White matter injury in term neonates with congenital heart diseases: topology & comparison with preterm newborns. Neuroimage 2019; 185: 742–749.CrossRefGoogle ScholarPubMed
Claessens, NHP, Khalili, N, Isgum, I, et al. Brain and CSF volumes in fetuses and neonates with antenatal diagnosis of critical congenital heart disease: a longitudinal MRI study. AJNR Am J Neuroradiol 2019; 40: 885–891.CrossRefGoogle ScholarPubMed
Tusor, N, Benders, MJ, Counsell, SJ, et al. Punctate white matter lesions associated with altered brain development and adverse motor outcome in preterm infants. Sci Rep 2017; 7: 13250.CrossRefGoogle ScholarPubMed
Peyvandi, S, Chau, V, Guo, T, et al. Neonatal brain injury and timing of neurodevelopmental assessment in patients with congenital heart disease. J Am Coll Cardiol 2018; 71: 1986–1996.CrossRefGoogle ScholarPubMed
Lawrence, KM, McGovern, PE, Mejaddam, A, et al. Prenatal hypoxemia alters microglial morphology in fetal sheep. J Thorac Cardiovasc Surg Published online August 28, 2019.Google ScholarPubMed
Lawrence, KM, McGovern, PE, Mejaddam, A, et al. Chronic intrauterine hypoxia alters neurodevelopment in fetal sheep. J Thorac Cardiovasc Surg 2019; 157: 1982–1991.CrossRefGoogle ScholarPubMed
Partridge, EA, Davey, MG, Hornick, MA, et al. An extra-uterine system to physiologically support the extreme premature lamb. Nat Commun 2017; 8: 15112.CrossRefGoogle ScholarPubMed
Sun, L, Macgowan, CK, Sled, JG, et al. Reduced fetal cerebral oxygen consumption is associated with smaller brain size in fetuses with congenital heart disease. Circulation 2015; 131: 1313–1323.CrossRefGoogle ScholarPubMed
Lim, JM, Kingdom, T, Saini, B, et al. Cerebral oxygen delivery is reduced in newborns with congenital heart disease. J Thorac Cardiovasc Surg 2016; 152: 1095–1103.CrossRefGoogle ScholarPubMed
Prophet, EB. Laboratory Methods in Histotechnology. books.google.com; 1992.Google Scholar
Claessens, NHP, Breur, JMPJ, Groenendaal, F, et al. Brain microstructural development in neonates with critical congenital heart disease: an atlas-based diffusion tensor imaging study. Neuroimage Clin 2019; 21: 101672.CrossRefGoogle ScholarPubMed
Riddle, A, Dean, J, Buser, JR, et al. Histopathological correlates of magnetic resonance imaging-defined chronic perinatal white matter injury. Ann Neurol 2011; 70: 493–507.CrossRefGoogle ScholarPubMed
Brossard-Racine, M, du Plessis, A, Vezina, G, et al. Brain injury in neonates with complex Congenital Heart Disease: what Is the predictive value of MRI in the fetal period? AJNR Am J Neuroradiol 2016; 37: 1338–1346.CrossRefGoogle ScholarPubMed
Peyvandi, S, Lim, JM, Marini, D, et al. Fetal brain growth and risk of postnatal white matter injury in critical congenital heart disease. J Thorac Cardiovasc Surg 2021; 162: 1007–1014.e1.CrossRefGoogle ScholarPubMed
Usuda, H, Watanabe, S, Saito, M, et al. Successful use of an artificial placenta to support extremely preterm ovine fetuses at the border of viability. Am J Obstet Gynecol 2019; 221: 69.e1–69.e17.CrossRefGoogle ScholarPubMed