Aortic Arch Morphogenesis and Flow Modeling in the Chick Embryo |
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Authors: | Yajuan Wang Onur Dur Michael J Patrick Joseph P Tinney Kimimasa Tobita Bradley B Keller and Kerem Pekkan |
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Institution: | (1) Department of Biomedical Engineering, Carnegie Mellon University, 2100 Doherty Hall, Pittsburgh, PA, USA;(2) Molecular Biosensor and Imaging Center, Carnegie Mellon University, Pittsburgh, PA, USA;(3) Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA;(4) Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA |
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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.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. |
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Keywords: | Aortic arches Cardiac development Computational fluid dynamics (CFD) Congenital heart disease (CHD) Flow visualization Wall shear stress (WSS) |
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