A Novel Flow Modeling Paradigm for Hemodynamics in Fetal Aorta and Its Application to the Diagnosis of Fetal Coarctation of the Aorta

About This Grant

Coarctation of the aorta (CoA) is a common congenital heart defect, accounting for 6-8% of live births with CHD. If the CoA is significant and is not diagnosed and treated in a timely fashion, the newborn or young infant may develop cardiogenic shock or may die. Contemporary prenatal screening and diagnosis of CoA rely on anatomic and blood flow conditions acquired by the fetal imaging technique. The limited resolution of the imaging technique confines the anatomical and hemodynamic metrics available for prenatal screening and diagnosis. Both false positive and false negative diagnoses occur frequently. Hence, there is an emerging need for a novel technique that provides new metrics and knowledge of the fetal aorta. Personalized flow modeling offers a cost-effective approach to evaluating high-fidelity hemodynamics in the cardiovascular system. It has led to paradigm shifts in uncovering mechanisms, improving diagnosis and prognosis, and developing and optimizing medical devices and treatments for heart disease. However, few models have been developed for fetal circulation. Therefore, the proposed work aims to develop novel, personalized flow models that assess high-fidelity hemodynamics of the fetal aorta and to use the models to evaluate novel flow metrics for the improved diagnosis of CoA in fetuses, leveraging an existing, large cohort of fetuses (n=250 normal aortas and 250 CoA in fetuses) from the Fetal Heart Society. We aim to (1) develop a novel personalized, computational flow model of the fetal aorta using a clinically routine imaging technique and validate it against in vivo measurements; (2) develop a novel in vitro flow model of the fetal aorta for the validation of novel flow metrics; and (3) evaluate novel flow metrics for the improved diagnosis of CoA in the fetus. The metrics of interest include (1) wall shear stress (WSS), an important flow stimulus for the maturation and remodeling of embryonic and postnatal vessels, and linked to recurrent coarctation after surgical repair in CoA patients, (2) fractional flow reserve (FFR) and flow resistance, well- recognized markers of vascular obstruction. However, these flow metrics have rarely been explored in fetal CoA. This project builds upon our extensive experience in developing and applying blood flow modeling in congenital heart defects, unique clinical expertise in fetal imaging, and access to a comprehensive clinical database (n = 500) from the Fetal Heart Society. The proposed work will address the challenges and gaps in the research on fetal circulation and CHDs in fetuses. The project will yield new data and knowledge on improved diagnosis of CoA in fetuses. Additionally, we will deliver the first-of-its-kind, validated computational and in vitro flow models for the fetal aorta. The findings and technology obtained through this project will lay a solid foundation for future clinical studies that could lead to improved screening, diagnosis, and outcomes for children with CoA. In alignment with the NIH’s mission statement, the proposed work aims to improve lifelong health for CoA patients and reduce the burden on these patients and their families.