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Research: The fetal lamb model of congenital diaphragmatic hernia shows altered cerebral perfusion using contrast enhanced ultrasound

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Research: The fetal lamb model of congenital diaphragmatic hernia shows altered cerebral perfusion using contrast enhanced ultrasound

J Pediatr Surg

. 2022 Feb 26;S0022-3468(22)00144-0. doi: 10.1016/j.jpedsurg.2022.02.006. Online ahead of print. https://pubmed.ncbi.nlm.nih.gov/35346482/

The fetal lamb model of congenital diaphragmatic hernia shows altered cerebral perfusion using contrast enhanced ultrasound

Abby C Larson 1Ryne Didier 2Gabriela Daszewska-Smith 1Jonathan Chang 1Anush Sridharan 3Divyansh Agarwal 3Chrystalle Katte Carreon 4Stephen P Sanders 5Shuhei Toba 6Emily Partridge 7Affiliations expand

Abstract

Background: Neurodevelopmental impairment is common in survivors of congenital diaphragmatic hernia (CDH). Altered cerebral perfusion in utero may contribute to abnormal brain development in CDH patients.

Methods: 5 fetal lambs with surgical left-CDH and 5 controls underwent transuterine cranial Doppler and contrast enhanced ultrasound (CEUS). Global and regional perfusion metrics were obtained. Biometric and perfusion data were compared between groups via nonparametric Mann Whitney U test and Spearman’s rank order correlation.

Results: No significant differences in cerebral Doppler measurements were identified between groups. By CEUS, CDH animals demonstrated significantly decreased global brain perfusion and increased transit time. With focal regions-of-interest (ROIs), there was a tendency towards decreased perfusion in the central/thalamic region in CDH but not in the peripheral brain parenchyma. Transit time was significantly increased in both ROIs in CDH, whereas flux rate was decreased in the central/thalamic region but not the peripheral brain parenchyma. Biometric CDH severity was correlated to perfusion deficit. There was no difference in cardiomyocyte histology.

Conclusion: The fetal lamb model of CDH shows altered cerebral perfusion as measured by CEUS, correlating to disease severity. This suggests a physiological abnormality in fetal cerebrovascular perfusion that may contribute to abnormal brain development and neurodevelopmental impairment in survivors.

Keywords: Abbreviations used:; Brain; CDH; CEUS; CHD; Cerebroplacental ratio; Congenital diaphragmatic hernia; Contrast enhanced ultrasound; ECMO; Fetal brain development; GA; LV; MCA; Middle cerebral artery; NDI; Neurodevelopmental impairment; PI; Pulmonary hypoplasia; RI; ROI; RV; UA.

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