Aortic Arch Morphogenesis and Flow Modeling in the Chick Embryo

Abstract

Morphogenesis of the "immature symmetric embryonic aortic arches" into the "mature and asymmetric aortic arches" involves a delicate sequence of cell and tissue migration, proliferation, and remodeling within an active biomechanical environment. Both patient-derived and experimental animal model data support a significant role for biomechanical forces during arch development. The objective of the present study is to quantify changes in geometry, blood flow, and shear stress patterns (WSS) during a period of normal arch morphogenesis. Composite three-dimensional (3D) models of the chick embryo aortic arches were generated at the Hamburger-Hamilton (HH) developmental stages HH18 and HH24 using fluorescent dye injection, micro-CT, Doppler velocity recordings, and pulsatile subject-specific computational fluid dynamics (CFD). India ink and fluorescent dyes were injected into the embryonic ventricle or atrium to visualize right or left aortic arch morphologies and flows. 3D morphology of the developing great vessels was obtained from polymeric casting followed by micro-CT scan. Inlet aortic arch flow and cerebral-to-lower body flow split was obtained from 20 MHz pulsed Doppler velocity measurements and literature data. Statistically significant variations of the individual arch diameters along the developmental timeline are reported and correlated with WSS calculations from CFD. CFD simulations quantified pulsatile blood flow distribution from the outflow tract through the aortic arches at stages HH18 and HH24. Flow perfusion to all three arch pairs are correlated with the in vivo observations of common pharyngeal arch defect progression. The complex spatial WSS and velocity distributions in the early embryonic aortic arches shifted between stages HH18 and HH24, consistent with increased flow velocities and altered anatomy. The highest values for WSS were noted at sites of narrowest arch diameters. Altered flow and WSS within individual arches could be simulated using altered distributions of inlet flow streams. Thus, inlet flow stream distributions, 3D aortic sac and aortic arch geometries, and local vascular biologic responses to spatial variations in WSS are all likely to be important in the regulation of arch morphogenesis.