4D subject-specific inverse modeling of the chick embryonic heart outflow tract hemodynamics

Abstract

Blood flow plays a critical role in regulating embryonic cardiac growth and development, with altered flow leading to congenital heart disease. Progress in the field, however, is hindered by a lack of quantification of hemodynamic conditions in the developing heart. In this study, we present a methodology to quantify blood flow dynamics in the embryonic heart using subject-specific computational fluid dynamics (CFD) models. While the methodology is general, we focused on a model of the chick embryonic heart outflow tract (OFT), which distally connects the heart to the arterial system, and is the region of origin of many congenital cardiac defects. Using structural and Doppler velocity data collected from optical coherence tomography (OCT), we generated 4D (3D + time) embryo-specific CFD models of the heart OFT. To replicate the blood flow dynamics over time during the cardiac cycle, we developed an iterative inverse-method optimization algorithm, which determines the CFD model boundary conditions such that differences between computed velocities and measured velocities at one point within the OFT lumen are minimized. Results from our developed CFD model agree with previously measured hemodynamics in the OFT. Further, computed velocities and measured velocities differ by less than 15% at locations that were not used in the optimization, validating the model. The presented methodology can be used in quantifications of embryonic cardiac hemodynamics under normal and altered blood flow conditions, enabling an in depth quantitative study of how blood flow influences cardiac development.

Removing vessel constriction on the embryonic heart results in changes in valve gene expression, morphology, and hemodynamics

“…The banding process creates a stenotic jet as documented in our earlier work and confirmed eloquently by others (Midgett et al, 2014; Menon et al, 2015; Chivukula et al, 2016). Our measured velocity is close to those reported by other investigators analyzing early stage embryos at the proximal outflow tract (Bharadwaj et al, 2012; Midgett et al, 2014; Liu et al, 2011; Goenezen et al, 2016). We note that at later time points, OFT septation has a dramatic effect on distal hemodynamic analysis and for simplicity purposes, we focused our attention on a consistent but proximal section of the OFT near the OVJ.…”

Effect of Outflow Tract Banding on Embryonic Cardiac Hemodynamics

“…This is because Doppler OCT only measures one component of the 3D velocity vector (the component in the direction of the OCT beam) and limitations in Doppler velocity acquisition make Doppler data noisy and inaccurate in several portions of the OFT. Our CFD models of the heart OFT used lumen geometries and blood flow velocities extracted from 4D OCT images, as described in detail previously [ 24 ]. Briefly, an optimization procedure was employed in the CFD simulations to determine embryo-specific blood flow velocities within the OFT.…”

“…We have developed strategies to reconstruct 4D images (3D + time) of the beating heart using OCT [ 22 ], and to segment the heart layers over time [ 23 ], enabling analysis of heart motion under normal and altered hemodynamic conditions. Further, we have developed a computational fluid dynamics (CFD) model strategy to quantify embryo-specific blood flow conditions in the heart OFT [ 24 ]. CFD modeling was used to complement imaging data in capturing the details of blood flow within the OFT, and in facilitating computation of wall shear stresses, a recognized stimulant of mechanotransduction leading to tissue remodeling [ 2 , 25 , 26 , 27 , 28 ].…”

Fluid dynamics in heart development: effects of hematocrit and trabeculation

“…They found unsteady vortices develop during atrial relaxation at 20-30 hpf and in both the atrium and ventricle at 110-120 hpf. Goenezen et al [19] used subject-specific computational fluid dynamics (CFD) to model flow through a model of the chick embryonic heart outflow tract.…”