Moving Domain Computational Fluid Dynamics to Interface with an Embryonic Model of Cardiac Morphogenesis

Peristaltic contraction of the embryonic heart tube produces time- and spatial-varying wall shear stress (WSS) and pressure gradients (∇P) across the atrioventricular (AV) canal. Zebrafish (Danio rerio) are a genetically tractable system to investigate cardiac morphogenesis. The use of Tg(fli1a:EGFP)y1 transgenic embryos allowed for delineation and two-dimensional reconstruction of the endocardium. This time-varying wall motion was then prescribed in a two-dimensional moving domain computational fluid dynamics (CFD) model, providing new insights into spatial and temporal variations in WSS and ∇P during cardiac development. The CFD simulations were validated with particle image velocimetry (PIV) across the atrioventricular (AV) canal, revealing an increase in both velocities and heart rates, but a decrease in the duration of atrial systole from early to later stages. At 20-30 hours post fertilization (hpf), simulation results revealed bidirectional WSS across the AV canal in the heart tube in response to peristaltic motion of the wall. At 40-50 hpf, the tube structure undergoes cardiac looping, accompanied by a nearly 3-fold increase in WSS magnitude. At 110-120 hpf, distinct AV valve, atrium, ventricle, and bulbus arteriosus form, accompanied by incremental increases in both WSS magnitude and ∇P, but a decrease in bi-directional flow. Laminar flow develops across the AV canal at 20-30 hpf, and persists at 110-120 hpf. Reynolds numbers at the AV canal increase from 0.07±0.03 at 20-30 hpf to 0.23±0.07 at 110-120 hpf (p< 0.05, n=6), whereas Womersley numbers remain relatively unchanged from 0.11 to 0.13. Our moving domain simulations highlights hemodynamic changes in relation to cardiac morphogenesis; thereby, providing a 2-D quantitative approach to complement imaging analysis. © 2013 Lee et al

Artificial boundaries and formulations for the incompressible Navier-Stokes equations. Applications to air and blood flows.

International audienceWe deal with numerical simulations of incompressible Navier-Stokes equations in truncated domain. In this context, the formulation of these equations has to be selected carefully in order to guarantee that their associated artificial boundary conditions are relevant for the considered problem. In this paper, we review some of the formulations proposed in the literature, and their associated boundary conditions. Some numerical results linked to each formulation are also presented. We compare different schemes, giving successful computations as well as problematic ones, in order to better understand the difference between these schemes and their behaviours dealing with systems involving Neumann boundary conditions. We also review two stabilization methods which aim at suppressing the instabilities linked to these natural boundary conditions

Immersed boundary-finite element model of fluid-structure interaction in the aortic root

It has long been recognized that aortic root elasticity helps to ensure efficient aortic valve closure, but our understanding of the functional importance of the elasticity and geometry of the aortic root continues to evolve as increasingly detailed in vivo imaging data become available. Herein, we describe fluid-structure interaction models of the aortic root, including the aortic valve leaflets, the sinuses of Valsalva, the aortic annulus, and the sinotubular junction, that employ a version of Peskin's immersed boundary (IB) method with a finite element (FE) description of the structural elasticity. We develop both an idealized model of the root with three-fold symmetry of the aortic sinuses and valve leaflets, and a more realistic model that accounts for the differences in the sizes of the left, right, and noncoronary sinuses and corresponding valve cusps. As in earlier work, we use fiber-based models of the valve leaflets, but this study extends earlier IB models of the aortic root by employing incompressible hyperelastic models of the mechanics of the sinuses and ascending aorta using a constitutive law fit to experimental data from human aortic root tissue. In vivo pressure loading is accounted for by a backwards displacement method that determines the unloaded configurations of the root models. Our models yield realistic cardiac output at physiological pressures, with low transvalvular pressure differences during forward flow, minimal regurgitation during valve closure, and realistic pressure loads when the valve is closed during diastole. Further, results from high-resolution computations demonstrate that IB models of the aortic valve are able to produce essentially grid-converged dynamics at practical grid spacings for the high-Reynolds number flows of the aortic root

The relationship between genetic variants associated with primary ovarian insufficiency and lipid profile in women recruited from MASHAD cohort study

Background and aim: Primary Ovarian Insufficiency (POI) is defined by the occurrence of menopause before the age of 40 years. It is often associated with cardiovascular disease (CVD). The purpose of this study was to explore the relationship between POI-associated genotypes cardiometabolic disorder risk factors. Methods: One hundred seventeen women with POI and one hundred eighty-three healthy women without POI were recruited in this study. DNA was extracted and analyzed using ASO-PCR or Tetra ARMS-PCR. Lipid profiles were also assessed. Results: Multivariate logistic regression analysis showed that individuals with GG vs. TT genotype of the rs1046089 SNP were more likely to have a higher serum LDL (p = 0.03) compared to the control group. There was also a significant association between low serum HDL and rs2303369 and rs4806660 SNP genotypes in the POI group. In the POI group, the percentage of those with high total cholesterol was lower in those with a CC genotype compared to those with a TT genotype (p = 0.03). Conclusion: Some SNPs reported to be associated with POI appear to be independently associated with dyslipidemia. These results may be helpful to identify subjects with POI who may be susceptible to CVD

Development of multiscale modeling methods for clinical decision making in single ventricle heart patients /

Infants with single ventricle physiology generally undergo three palliative surgeries starting with stage-one, in which a systemic-to-pulmonary connection is established via a shunt. Mortality is the highest among stage-one patients (up to 23%) due to sub-optimal oxygen delivery, ventricle volume overload, myocardial ischemia, and high risk of shunt blockage. The clinical objective of the present study is to simulate the stage-one circulation, analyze possible surgical options, optimize current surgical methods, and explore a novel alternative surgical option. Simulating the stage-one circulation in single ventricle repair requires a set of numerical tools that are developed in the first part of this dissertation. First, an implicit and modular multidomain framework with excellent stability and convergence properties is introduced that allows multiscale simulation of the circulatory system. Second, a stabilized formulation is presented for treating backflow at Neumann boundaries that is inexpensive, stable, simple, and minimally intrusive, and offers a promising alternative to previous methods. Third, an efficient pre-conditioner for coupled boundary conditions and an efficient iterative algorithm for solving system of equations governing incompressible flows are introduced. Fourth, a scalable parallel data structure is introduced for performing algebraic operations in iterative solvers efficiently. Fifth, an Eulerian formulation is proposed for calculating residence time that lacks mesh dependency and avoids the high computational cost of Lagrangian particle-based approaches. These tools are applicable to other cardiac mechanics and CFD simulations as well. In second part of this dissertation, single ventricle physiology is studied using the tools presented in the first part. First, a multiscale model of single ventricle physiology is simulated and the shunt geometry is optimized to maximize oxygen delivery and improve performance. Second, surgical scenarios single and multiple systemic-to-pulmonary connections are compared, revealing higher thrombotic risk and lower oxygen delivery in the presence of multiple connections. Third, a novel stage one palliative surgery, which provides an alternative source of blood flow in case of shunt blockage and may ultimately reduce the number of open chest surgeries from three to two, is proposed and tested using multiscale modeling. Results reveal the proposed surgical method, the Assisted Bidirectional Glenn, can deliver more oxygen at a reduced heart load with only a modest increase in venous return pressur