In this proposal I am interested in developing a computational fluid dynamic (CFD) modeling approach for volumetric assessment of human uteroplacental blood flow in vivo. The placenta is an organ that exchanges nutrients and oxygen between the maternal circulation and the growing fetus. In the United States, about 3.4% of pregnancies per year are affected by hypertensive pregnancy disorders (HPD) such as preeclampsia (PE), which have been found to carry both fetal and maternal risk. Associated placental pathologies are believed to be linked to alterations in maternal arterial remodeling. Currently, Doppler ultrasound (US) is the primary method of assessing flow to the placenta from the uterine artery (UtA). Clinical studies have shown a relationship between high UtA flow resistance and risk of adverse pregnancy outcome late in gestation, but it has not been reliable as an early gestation screening tool. In order to improve predictive technologies for reliable risk assessment assessment of HPD, more research into the relationship between vessel structure and function in the UtA is needed. I hypothesize that CFD modeling can be a useful tool for investigating possible pathophysiological mechanisms of HPD by simulating complex hemodynamics of the maternal vascular system including pressure, wall shear stress, and pulse wave velocity. I plan to set up various 1D CFD simulations to understand the hemodynamic parameters of normal versus abnormal pregnancies. Then, I will validate the simulations with 4D flow MRI acquired from an in vitro flow phantom and a cohort of normal and hypertensive pregnant women. I anticipate that the results of this investigation can advance scientific knowledge regarding the progression of early HPD phenotypes to adverse pregnancy outcomes. This CFD study can also demonstrate the extent to which patient-specific hemodynamic simulations can be reliable for future improvement of clinical management. This training experience will provide opportunities to build my expertise in cardiovascular physiology, fluid mechanics, medical imaging, data analysis, and clinical care. I will be publishing articles on my CFD/4D flow MRI findings and communicating the impact of this work in medicine at various internal and external symposia. This research will be conducted under the mentorship of award-winning experts and the University of Pennsylvania in cardiovascular MRI (Walter Witschey), fluid mechanics and computational modeling (Paris Perdikaris), maternal fetal medicine (Nadav Schwartz) and cardiovascular physiology (Victor Ferrari).
The human placenta is an understudied organ believed to play a critical role in pregnancy health and the pathophysiology of hypertensive pregnancy disorders. Current technologies like ultrasound are limited in its ability to assess complex hemodynamics, and clinical studies have not yet found reliable biomarkers of adverse pregnancy outcomes. We will develop a computational fluid dynamic model of the maternal vessels delivering blood to the placenta and validate it with magnetic resonance imaging to characterize uteroplacental structure and function, providing future avenues for new predictive biomarkers of pregnancy health.
