Congenital heart disease (CHD) is the most common birth defect and a leading cause of death and chronic illness in newborns, infants, and children. Prenatal screening and identification of CHD are critically important for the management and treatment of CHD, but its availability and accuracy are confined by the limited resolutions of current fetal imaging techniques. Personalized flow modeling has been widely used to augment medical imaging modalities for adult and pediatric heart diseases. However, to date, no validated models have been developed for fetal circulation. This project will focus on coarctation of the aorta (CoA), a common CHD accounting for 6-8% of live births with CHD. CoA occurs when a portion of the aorta is narrowed, usually at the isthmus, and blood flow through it is obstructed. Both false positive and false negative diagnoses frequently occur in contemporary prenatal screening and identification of CoA. 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. There is an emerging need for a novel technique that provides new metrics and knowledge of the fetal aorta. The proposed work aims to (1) develop a novel, personalized flow modeling paradigm based on routinely used fetal echocardiography that assesses high-fidelity hemodynamics of the fetal aorta. (2) validate this novel paradigm in comparison with cutting-edge fetal magnetic resonance imaging techniques, including both phase-contrast and 4D flow sequences. (3) use this paradigm to conduct pilot studies identifying novel hemodynamic metrics that discriminate normal aorta and CoA in fetuses. This project will focus on wall shear stress, which was linked to vessel dilation and remodeling in general and recurrent coarctation in pediatric and adult patients with repaired CoA but has scarcely been discussed in the fetal aorta with CoA. The proposed work will address the challenges and gaps in the research of fetal circulation and fetal heart disease by producing a novel, validated cardiovascular flow modeling paradigm for personalized hemodynamics in the fetal aorta. This project represents the first-of-its-kind endeavor to develop a rigorously validated personalized flow model for fetal circulation. Our long-term goal is to develop paradigm-shifting computational models for fetal circulation that can be used to uncover the pathogenesis of all critical CHDs to improve diagnosis/prognosis and to aid in the personalized treatment/prevention of CoA and other critical CHDs. Additionally, this project will yield new data and knowledge on fetal aortic hemodynamics, which may enable a better understanding of etiology and improved diagnosis and prognosis of CoA. The tools and knowledge generated by this project will lay a solid foundation for future translational studies that could lead to improved screening, diagnosis, and outcomes for children with CoA.

Prenatal screening secures the earliest window of opportunity for proper management and treatment of congenital heart diseases; however, both false positive and false negative diagnoses frequently occur primarily because of the low resolution of the fetal imaging technique. Personalized flow modeling has been widely used to augment medical imaging modalities for adult and pediatric heart diseases; however, no models have been developed for fetal circulation. This project will develop the first validated computational flow model for fetal circulation and focus on the aorta, which could contribute to shifting the translational paradigm for understanding hemodynamics and etiology, improving diagnosis and prognosis, and examining the safety and efficacy of therapies for coarctation of the aorta and other congenital heart diseases.