Characterizaton of the Vessel Geometry, Flow Mechanics and Wall Shear Stress in the Great Arteries of Wildtype Prenatal Mouse

Abstract

IntroductionAbnormal fluid mechanical environment in the pre-natal cardiovascular system is hypothesized to play a significant role in causing structural heart malformations. It is thus important to improve our understanding of the prenatal cardiovascular fluid mechanical environment at multiple developmental time-points and vascular morphologies. We present such a study on fetal great arteries on the wildtype mouse from embryonic day 14.5 (E14.5) to near-term (E18.5).MethodsUltrasound bio-microscopy (UBM) was used to measure blood velocity of the great arteries. Subsequently, specimens were cryo-embedded and sectioned using episcopic fluorescent image capture (EFIC) to obtain high-resolution 2D serial image stacks, which were used for 3D reconstructions and quantitative measurement of great artery and aortic arch dimensions. EFIC and UBM data were input into subject-specific computational fluid dynamics (CFD) for modeling hemodynamics.ResultsIn normal mouse fetuses between E14.5–18.5, ultrasound imaging showed gradual but statistically significant increase in blood velocity in the aorta, pulmonary trunk (with the ductus arteriosus), and descending aorta. Measurement by EFIC imaging displayed a similar increase in cross sectional area of these vessels. However, CFD modeling showed great artery average wall shear stress and wall shear rate remain relatively constant with age and with vessel size, indicating that hemodynamic shear had a relative constancy over gestational period considered here.ConclusionOur EFIC-UBM-CFD method allowed reasonably detailed characterization of fetal mouse vascular geometry and fluid mechanics. Our results suggest that a homeostatic mechanism for restoring vascular wall shear magnitudes may exist during normal embryonic development. We speculate that this mechanism regulates the growth of the great vessels.

The influence of anesthesia and fluid–structure interaction on simulated shear stress patterns in the carotid bifurcation of mice

“…Many authors have tried to link local disease patterns to focal zones of locally disturbed shear stress using rigid-walled models of either the aortic arch (Assemat et al, 2014;Feintuch et al, 2007;Suo et al, 2007;Yap et al, 2014), the abdominal aorta (Ford et al, 2011;Greve et al, 2006;Trachet et al, 2011b;Willett et al, 2010) or both (Hoi et al, 2011;Huo et al, 2008;Van Doormaal et al, 2014). The findings of publications that focused on regular WSS patterns (Feintuch et al, 2007;Greve et al, 2006;Huo et al, 2008;Suo et al, 2007;Willett et al, 2010;Yap et al, 2014) are not affected much by our results. However, some findings of publications that focused on the oscillatory patterns of WSS (Assemat et al, 2014;Ford et al, 2011;Hoi et al, 2011;Trachet et al, 2011b;Van Doormaal et al, 2014) might need to be re-interpreted.…”

3D Reconstruction of Chick Embryo Vascular Geometries Using Non-invasive High-Frequency Ultrasound for Computational Fluid Dynamics Studies

“…This (Table 2). We hypothesize that this low wall shear stress may have a role in causing the subsequent natural regression of the carotid duct from HH28 to HH34, 18 based on the popular notion that shear stress influences the growth of vasculature, 42,53,54 whereby higher shear stresses are believed to spur vascular growth and lower shear stresses are believed to cause vascular regression. However, further experimentation on a larger sample size and more CFD simulations have to be conducted before the above hypothesis can be verified.…”

“…27,39 Small animal embryos, such as those of the mouse and chick are invaluable animal models for embryology, 13,41 developmental biology, 11,28 and recently, embryonic fluid mechanics studies. 6,24,48,49,54 Imaging of the embryonic cardiovascular anatomy is an important technique to support these research endeavors. By enabling the visualization of the cardiovasculature development, the anatomy at a particular time point can be correlated to the measurements of the fluid mechanical environment in order to understand the role of mechanical forces in cardiovascular developmental growth.…”

Characterization of Hemodynamics in Great Arteries of Wild-Type Mouse Using Computational Fluid Dynamics Based on Ultrasound Images

“…Note that results from steady flow simulations were little different from unsteady flow simulations at peak flow because the Reynolds and Wormesley numbers in mouse fetal arteries are small. 1 Small animal fetal blood can be considered newtonian under physiological conditions. 15 Steady CFD simulations were performed (maximum inflow velocity, 1.0 m/s).…”

“…1,2 Hemodynamic parameters, particularly those related to WSS, the frictional force of blood flowing in the vessel lumen, 3 have been shown to correlate with the arterial endothelial markers in embryonic outflow tract and aortic branches during early developmental stages. 4Y7 Furthermore, recent investigations showed the presence of primary cilia on the endothelium of fetal mouse aorta, and these cilia have been supposed to serve as vascular mechanosensors for WSS.…”