Evidence map›Paper›PMID 38849480›Full record

ArticlePediatric research2025

Unique model of chronic hypoxia in fetal lambs demonstrates abnormal contrast-enhanced ultrasound brain perfusion.

Divyansh Agarwal, Mallory L Hunt, Anush Sridharan, Abby C Larson, Jack Rychik, Daniel J Licht, Marcus G Davey, Alan W Flake, J William Gaynor, Ryne A Didier

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Article in Pediatric research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1 · What the graph read from it

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3 · Its place in the literature

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1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Divyansh AgarwalPerelman School of Medicine, University of Philadelphia, Philadelphia, PA, USA.
Mallory L HuntDepartment of Surgery, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Anush SridharanDepartment of Radiology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Abby C LarsonDepartment of Surgery, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Jack RychikPerelman School of Medicine, University of Philadelphia, Philadelphia, PA, USA.
Daniel J LichtPerelman School of Medicine, University of Philadelphia, Philadelphia, PA, USA.
Marcus G DaveyCenter for Fetal Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Alan W FlakePerelman School of Medicine, University of Philadelphia, Philadelphia, PA, USA.
J William GaynorPerelman School of Medicine, University of Philadelphia, Philadelphia, PA, USA.
Ryne A DidierPerelman School of Medicine, University of Philadelphia, Philadelphia, PA, USA. didierr@chop.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundChildren with congenital heart disease (CHD) demonstrate long-term neurodevelopmental impairments. We investigated contrast-enhanced ultrasound (CEUS) cerebral perfusion in a fetal animal model exposed to sub-physiologic oxygen at equivalent levels observed in human fetuses with CHD.

methodsFifteen fetal lambs [hypoxic animals (n = 9) and normoxic controls (n = 6)] maintained in an extrauterine environment underwent periodic brain CEUS. Perfusion parameters including microvascular flow velocity (MFV), transit time, and microvascular blood flow (MBF) were extrapolated from a standardized plane; regions of interest (ROI) included whole brain, central/thalami, and peripheral parenchymal analyses. Daily echocardiographic parameters and middle cerebral artery (MCA) pulsatility indices (PIs) were obtained.

resultsHypoxic lambs demonstrated decreased MFV, increased transit time, and decreased MBF (p = 0.026, p = 0.016, and p < 0.001, respectively) by whole brain analyses. MFV and transit time were relatively preserved in the central/thalami (p = 0.11, p = 0.08, p = 0.012, respectively) with differences in the peripheral parenchyma (all p < 0.001). In general, cardiac variables did not correlate with cerebral CEUS perfusion parameters. Hypoxic animals demonstrated decreased MCA PI compared to controls (0.65 vs. 0.78, respectively; p = 0.027).

conclusionAberrations in CEUS perfusion parameters suggest that in environments of prolonged hypoxia, there are regional microvascular differences incompletely characterized by MCA interrogation offering insights into fetal conditions which may contribute to patient outcomes. IMPACT: This work utilizes CEUS to study cerebral microvascular perfusion in a unique fetal animal model subjected to chronic hypoxic conditions equal to fetuses with congenital heart disease. CEUS demonstrates altered parameters with regional differences that are incompletely characterized by MCA Doppler values. These findings show that routine MCA Doppler interrogation may be inadequate in assessing microvascular perfusion differences. To our knowledge, this study is the first to utilize CEUS to assess microvascular perfusion in this model. The results offer insight into underlying conditions and physiological changes which may contribute to known neurodevelopmental impairments in those with congenital heart disease.

Indexed as

BrainCerebrovascular CirculationContrast MediaFetal HypoxiaHypoxiaAnimalsBlood Flow VelocityChronic DiseaseDisease Models, AnimalFemaleFetusHeart Defects, CongenitalMicrocirculationMiddle Cerebral ArteryPregnancySheepContrast Media

Identifiers

PMID38849480
PMCPMC11798845

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.