Studies suggested the effect of blood flow forces in pathogenesis and progression of some congenital heart malformations other than the Tetralogy of Fallot (TOF). It is thus of interest to study the fluid mechanic environment of the malformed prenatal heart, especially when little is known in the fetal TOF. In this study, we performed patient-specific ultrasound-based flow simulations of 3 TOF and 7 normal human fetal hearts. TOF right ventricles (RV) had smaller end-diastolic volumes (EDV) but similar stroke volumes (SV), while TOF left ventricles (LV) had similar EDV but slightly increased SV compared to normal ventricles. Simulation showed that TOF ventricles had elevated systolic intra-ventricular pressure gradient (IVPG), and required additional energy for ejection, but IVPG elevations were considered to be mild relative to arterial pressure. TOF RV and LV had similar pressures due to equalization via ventricular septal defect (VSD). Further, relative to normal, TOF RVs had increased diastolic wall shear stresses (WSS), but TOF LVs were not. This was caused by high tricuspid inflow that exceeded RV stroke volume, leading to right-to-left shunting and chaotic flow with enhanced vorticity interaction with the wall to elevate WSS. Two of the three TOF RVs but none of the LVs had increased thickness. As pressure elevations were mild, we hypothesized that pressure and WSS elevation could play a role in the RV thickening, among other causative factors. Finally, the endocardium surrounding the VSD consistently experienced high WSS due to RV-to-LV flow shunt and high flow rate through the over-riding aorta.

A range of cytological samples are suitable for KRAS and BRAF mutation testing, be it from previously stained preparations or cell blocks. These samples would be highly valuable in cases where cytological samples are the only material available for mutation testing.

The mechanics of intracardiac blood flow and the epigenetic influence it exerts over the heart function have been the subjects of intense research lately. Fetal intracardiac flows are especially useful for gaining insights into the development of congenital heart diseases, but have not received due attention thus far, most likely because of technical difficulties in collecting sufficient intracardiac flow data in a safe manner. Here, we circumvent such obstacles by employing 4D STIC ultrasound scans to quantify the fetal heart motion in three normal 20-week fetuses, subsequently performing 3D computational fluid dynamics simulations on the left ventricles based on these patient-specific heart movements. Analysis of the simulation results shows that there are significant differences between fetal and adult ventricular blood flows which arise because of dissimilar heart morphology, E/A ratio, diastolic-systolic duration ratio, and heart rate. The formations of ventricular vortex rings were observed for both E- and A-wave in the flow simulations. These vortices had sufficient momentum to last until the end of diastole and were responsible for generating significant wall shear stresses on the myocardial endothelium, as well as helicity in systolic outflow. Based on findings from previous studies, we hypothesized that these vortex-induced flow properties play an important role in sustaining the efficiency of diastolic filling, systolic pumping, and cardiovascular flow in normal fetal hearts.

There are 0.6-1.9% of US children who were born with congenital heart malformations. Clinical and animal studies suggest that abnormal blood flow forces might play a role in causing these malformation, highlighting the importance of understanding the fetal cardiovascular fluid mechanics. We performed computational fluid dynamics simulations of the right ventricles, based on four-dimensional ultrasound scans of three 20-wk-old normal human fetuses, to characterize their flow and energy dynamics. Peak intraventricular pressure gradients were found to be 0.2-0.9 mmHg during systole, and 0.1-0.2 mmHg during diastole. Diastolic wall shear stresses were found to be around 1 Pa, which could elevate to 2-4 Pa during systole in the outflow tract. Fetal right ventricles have complex flow patterns featuring two interacting diastolic vortex rings, formed during diastolic E wave and A wave. These rings persisted through the end of systole and elevated wall shear stresses in their proximity. They were observed to conserve ∼25.0% of peak diastolic kinetic energy to be carried over into the subsequent systole. However, this carried-over kinetic energy did not significantly alter the work done by the heart for ejection. Thus, while diastolic vortexes played a significant role in determining spatial patterns and magnitudes of diastolic wall shear stresses, they did not have significant influence on systolic ejection. Our results can serve as a baseline for future comparison with diseased hearts.

Previous studies provided evidence that the mechanical forces of blood flow in embryos and fetuses may play a role in causing congenital cardiovascular. It is thus important to understand the fluid mechanical forces in the human fetuses. In the current study, we present a new technique for performing computational fluid dynamics of the cardiac chambers, based on patient-specific clinical ultrasound scans of human fetuses. Ultrasound images were acquired using the Spatio-Temporal Image Correlation (STIC) mode. The images were segmented for the right ventricle blood space at various time points. A mathematical model of ventricular wall motion was developed and used to define mesh motion for computational fluid dynamics simulation of fluid within the ventricle. The ventricular mesh models created by the mathematical model was shown to satisfactorily agree with the ventricular geometries segmented from ultrasound images. Fluid dynamics simulations successfully provided details of spatial gradients of pressures, ventricular wall shear stresses, and vorticity dynamics in the ventricle. Results showed that the right ventricle diastolic flows featured two prominent vortex rings, which were sustained until systole, when part of the vorticity structures were ejected through the pulmonary outflow tract. Diastolic wall shear stress was in the range of 0.4-1.2 Pa, while systolic shear stress elevated near to the outflow tract at 1.5-3.9 Pa. In conclusion, We have established methodologies for performing patient-specific simulations of the fluid mechanics in the heart chambers of human fetuses, based on clinical ultrasound scans, and demonstrated its feasibility on a 20 weeks human fetus right ventricle.

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