Characterization of the developing venous vascular system and its connection to cardiac outflow hemodynamics

Congenital heart defects involving venous malformation is a complex class of diseases with largely unclear etiologies. Here, through hemodynamic simulations, we study the development of the cardinal and pharyngeal veins and how they are altered by perturbations to systemic circulation by means of pharyngeal arch arteries (PAA) ablation. Using the chick embryo animal model, we obtain 3D reconstruction of PAAs and surrounding veins from high-resolution nano-CT scans. We perform multiscale computational fluid dynamic simulations of day 3 and day 4 embryos using the open source platform SimVascular. We use Doppler velocity and pressure measurements to generate the appropriate inlet and outlet boundary conditions. From here we calculate flow distributions and wall shear stress maps. We perform the analyses first on control embryos to establish the natural variabilities in venous circulation. Then, we repeat the analyses on embryos with ablated PAAs to characterize venous response to such mechanical alteration of systemic flow. This study addresses the interdependence of the developing systemic and venous vascular systems and serves as a basis for understanding the role of blood flow in venous growth, adaptation, and malformation.