Recent animal studies have provided evidence that prenatal blood flow fluid mechanics may play a role in the pathogenesis of congenital cardiovascular malformations. To further these researches, it is important to have an imaging technique for small animal embryos with sufficient resolution to support computational fluid dynamics studies, and that is also non-invasive and non-destructive to allow for subject-specific, longitudinal studies. In the current study, we developed such a technique, based on ultrasound biomicroscopy scans on chick embryos. Our technique included a motion cancelation algorithm to negate embryonic body motion, a temporal averaging algorithm to differentiate blood spaces from tissue spaces, and 3D reconstruction of blood volumes in the embryo. The accuracy of the reconstructed models was validated with direct stereoscopic measurements. A computational fluid dynamics simulation was performed to model fluid flow in the generated construct of a Hamburger-Hamilton (HH) stage 27 embryo. Simulation results showed that there were divergent streamlines and a low shear region at the carotid duct, which may be linked to the carotid duct's eventual regression and disappearance by HH stage 34. We show that our technique has sufficient resolution to produce accurate geometries for computational fluid dynamics simulations to quantify embryonic cardiovascular fluid mechanics.
Past literature has provided evidence that a normal mechanical force environment of blood flow may guide normal development while an abnormal environment can lead to congenital malformations, thus warranting further studies on embryonic cardiovascular flow dynamics. In the current study, we developed a non-invasive 4D high-frequency ultrasound technique, and use it to analyze cardiovascular organ dynamics and flow dynamics. Three chick embryos at stage HH25 were scanned with high frequency ultrasound in cine-B-mode at multiple planes spaced at 0.05 mm. 4D images of the heart and nearby arteries were generated via temporal and spatial correlation coupled with quadratic mean ensemble averaging. Dynamic mesh CFD was performed to understand the flow dynamics in the ventricle of the 2 hearts. Our imaging technique has sufficiently high resolution to enable organ dynamics quantification and CFD. Fine structures such as the aortic arches and details such as the cyclic distension of the carotid arteries were captured. The outflow tract completely collapsed during ventricular diastole, possible serving the function of a valve to prevent regurgitation. CFD showed that ventricular wall shear stress (WSS) were in the range of 0.1-0.5 Pa, and that the left side of the common ventricle experienced lower WSS than the right side. The pressure gradient from the inlet to the outlet of the ventricle was positive over most of the cardiac cycle, and minimal regurgitation flow was observed, despite the absence of heart valves. We developed a new image-based CFD method to elucidate cardiac organ dynamics and flow dynamics of embryonic hearts. The embryonic heart appeared to be optimized to generate net forward flow despite the absence of valves, and the WSS environment appeared to be side-specific.
There were alterations to both the geometry and the flow mechanics of the carotid siphons of Moyamoya patients but it is unclear whether hemodynamics is the cause or the effect of morphological changes observed.
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