Critical Transitions in Early Embryonic Aortic Arch Patterning and Hemodynamics

Transformation from the bilaterally symmetric embryonic aortic arches to the mature great vessels is a complex morphogenetic process, requiring both vasculogenic and angiogenic mechanisms. Early aortic arch development occurs simultaneously with rapid changes in pulsatile blood flow, ventricular function, and downstream impedance in both invertebrate and vertebrate species. These dynamic biomechanical environmental landscapes provide critical epigenetic cues for vascular growth and remodeling. In our previous work, we examined hemodynamic loading and aortic arch growth in the chick embryo at Hamburger-Hamilton stages 18 and 24. We provided the first quantitative correlation between wall shear stress (WSS) and aortic arch diameter in the developing embryo, and observed that these two stages contained different aortic arch patterns with no inter-embryo variation. In the present study, we investigate these biomechanical events in the intermediate stage 21 to determine insights into this critical transition. We performed fluorescent dye microinjections to identify aortic arch patterns and measured diameters using both injection recordings and high-resolution optical coherence tomography. Flow and WSS were quantified with 3D computational fluid dynamics (CFD). Dye injections revealed that the transition in aortic arch pattern is not a uniform process and multiple configurations were documented at stage 21. CFD analysis showed that WSS is substantially elevated compared to both the previous (stage 18) and subsequent (stage 24) developmental time-points. These results demonstrate that acute increases in WSS are followed by a period of vascular remodeling to restore normative hemodynamic loading. Fluctuations in blood flow are one possible mechanism that impacts the timing of events such as aortic arch regression and generation, leading to the variable configurations at stage 21. Aortic arch variations noted during normal rapid vascular remodeling at stage 21 identify a temporal window of increased vulnerability to aberrant aortic arch morphogenesis with the potential for profound effects on subsequent cardiovascular morphogenesis.     

Analysis of early embryonic great-vessel microcirculation in zebrafish using high-speed confocal μPIV

In the developing cardiovascular system, hemodynamic vascular loading is critical for angiogenesis and cardiovascular adaptation. Normal zebrafish embryos with transgenically-labeled endothelial and red blood cells provide an excellent in vivo model for studying the fluid-flow induced vascular loading. To characterize the developmental hemodynamics of early embryonic great-vessel microcirculation in the zebrafish embryo, two complementary studies (experimental and numerical) are presented. Quantitative comparison of the wall shear stress (WSS) at the first aortic arch (AA1) of wild-type zebrafish embryos during two consecutive developmental stages is presented, using time-resolved confocal micro-particle image velocimetry (μPIV). Analysis showed that there was significant WSS difference between 32 and 48 h post-fertilization (hpf) wild-type embryos, which correlates with normal arch morphogenesis. The vascular distensibility of the arch wall at systole and the acceleration/deceleration rates of time-lapse phase-averaged streamwise blood flow curves were also analyzed. To estimate the influence of a novel intermittent red-blood cell (RBC) loading on the endothelium, a numerical two-phase, volume of fluid (VOF) flow model was further developed with realistic in vivo conditions. These studies showed that near-wall effects and cell clustering increased WSS augmentation at a minimum of 15% when the distance of RBC from arch vessel wall was less than 3 μm or when RBC cell-to-cell distance was less than 3 μm. When compared to a smooth wall, the WSS augmentation increased by a factor of ~1.4 due to the roughness of the wall created by the endothelial cell profile. These results quantitatively highlight the contribution of individual RBC flow patterns on endothelial WSS in great-vessel microcirculation and will benefit the quantitative understanding of mechanotransduction in embryonic great vessel biology, including arteriovenous malformations (AVM).     

Wall shear stress distribution in a model human aortic arch: assessment by an electrochemical technique

Wall shear stress (WSS) distribution in a human aortic arch model is studied using 130 cathode electrodes flush-mounted on the model walls. Flow visualizations are made in a transparent geometry model to identify the regions of fluid mechanical interests, e.g. regions of flow separation, eddy formation and flow stagnancy. The 130 electrodes are strategically positioned in the arch based on information obtained from the flow visualizations. The measured data indicate that the aortic arch may be categorized into eight regions: three along the inner wall of the arch (A,B,C); and five near the outer wall (D,E,F,G,H). (1) The regions of low WSS are distributed along the inner wall of the ascending aorta A; the inner wall of the descending aorta C; and the upstream inner wall of the innominate and the common carotid branchings F. (2) The high WSS regions are distributed along the outer wall of the arch E; and the inner wall in the arch opposite to the left subclavian branching B. (3) In certain regions, high and low WSS may be found next to each other (e.g. G and H) without a definable boundary in between; and (4) as the Reynolds number increases, the areas of low WSS decrease, while the high WSS areas increase with no obvious change in magnitude of the stress along the inner wall of the arch. At the branchings, the WSS distribution is not affected by the Reynolds number within the range of observations. The measured WSS distribution is compared with Rodkiewicz's map of early atherosclerotic lesions in the aortic arch of cholesterol fed rabbits.     

Approaches for treatment of aortic arch aneurysm,a numerical study

Aortic arch aneurysm is a complex pathology which requires coverage of one or more aortic arch vessels. In this study we explore the hemodynamic behavior of the aortic arch in aneurysmatic and treated cases with three currently available treatment approaches: Surgery Graft, hybrid Stent-Graft and chimney Stent Graft. The analysis included four models of the time-dependent fluid domains of aneurysmatic arch and of the surgery, hybrid and chimney endovascular techniques. Dimensions of the models are based on typical anatomy, and boundary conditions are based on typical physiological flow.The simulations used computational fluid dynamics (CFD) methods to delineate the time-dependent flow dynamics in the four geometric models.Results of velocity vectors, flow patterns, blood pressure and wall shear stress distributions are presented.The results delineate disturbed and recirculating flow in the aortic arch aneurysm accompanied with low wall shear stress and velocities, compared to a uniformly directed flow and nominal wall shear stress (WSS) in the model of Surgery graft. Out of the two endograft procedures, the hybrid procedure clearly exhibits better hemodynamic performances over the chimney model, with lower WSS, lower pressure drop and less disturbed and vortical flow regions. Although the chimney procedure requires less manufacturing time and cost, it is associated with higher risk rates, and therefore, it is recommended only for emergency cases. This study may shed light on the hemodynamic factors for these complications and provide insight into ways to improve the procedure.     

The influence of aortic dimensions on calculated wall shear stress in the mouse aortic arch

In this paper, the influence of the aortic dimensions of an investigated mouse on its resulting wall shear stress (WSS) was studied. A numerical model of a mouse aortic arch was created based on a micro-CT scan of a vascular corrosion cast of an 8-week-old wild type mouse. This model was then rescaled to obtain five models with aortic root diameters corresponding to five different stages in the mouse life cycle varying from late fetal (0.7 mm) to old adult (1.5 mm). Consistent with literature, WSS values much higher than those normally encountered in humans were found. WSS was found to decrease rapidly in early life stages and to reach a plateau in adulthood, thus supporting a mediating role for WSS in arterial growth. Our results show that WSS values for mice should be interpreted very cautiously, and if possible an animal-specific geometry with animal-specific boundary conditions should be used.     

Computational analysis of blood flow in an integrated model of the left ventricle and the aorta

To study the effects of intraventricular flow dynamics on the aortic flow, we created an integrated model of the left ventricle and aorta and conducted a computer simulation of diastolic and systolic blood flow within this model. The results demonstrated that the velocity profile at the aortic annulus changed dynamically, and was influenced by the intraventricular flow dynamics. The profile was almost flat in early systole but became nonuniform as systole progressed, and was skewed toward the posterior side in midsystole and toward the anterior side in later systole. At a distance from the aortic annulus, a different velocity profile was induced by the twisting and torsion of the aorta. In the ascending aorta, the fastest flow was initially located in the posteromedial sector, and it moved to the posterior section along the circumference as systole progressed. The nonuniformity of the aortic inflow gave rise to a complex wall shear stress (WSS) distribution in the aorta. A comparison of the WSS distribution obtained in this integrated analysis with that obtained in flow calculations using an isolated aorta model with Poiseuille and flat inlet conditions showed that intraventricular flow affected the WSS distribution in the ascending aorta. These results address the importance of an integrated analysis of flow in the left ventricle and aorta.     

Aortic valve leaflet wall shear stress characterization revisited: impact of coronary flow

Computational characterizations of aortic valve hemodynamics have typically discarded the effects of coronary flow. The objective of this study was to complement our previous fluid–structure interaction aortic valve model with a physiologic coronary circulation model to quantify the impact of coronary flow on aortic sinus hemodynamics and leaflet wall shear stress (WSS). Coronary flow suppressed vortex development in the two coronary sinuses and altered WSS magnitude and directionality on the three leaflets, with the most substantial differences occurring in the belly and tip regions.     

Measurement of wall shear stress distal to a tri-leaflet valve in a rigid model of the aortic arch with branch flows

Flush mounted hot film anemometer probes were used to measure wall shear stress magnitudes on the inside and outside walls of a rigid model of the human aortic arch. The effects of the presence of an Ionescu-Shiley tri-leaflet bioprosthetic heart valve at the entrance of the aortic arch and the side flows through arteries located in the mid-arch region on wall shear stress magnitudes were determined. It was found that the presence of the tri-leaflet valve leads to an elevation of wall shear stress (relative to the same flow without a valve) over the entire aortic arch region by as much as 50 percent. The valve influence extended to about 180 deg from the entrance to the aorta on the inside wall and even further on the outside wall based on extrapolation of available data. Peak wall shear stress magnitudes measured on the outside wall were in the range of 1.5-4.0 N/m2 (15-40 dynes/cm2) over the length of the aortic arch and took on their highest values in the mid-arch region. Inside wall values were of comparable magnitude. It was observed that the presence of the aortic valve and side flow from the top of the aortic arch reduced wall shear stress reversal in the arch region.     

Numerical simulation of non-Newtonian blood flow dynamics in human thoracic aorta

Three non-Newtonian blood viscosity models plus the Newtonian one are analysed for a patient-specific thoracic aorta anatomical model under steady-state flow conditions via wall shear stress (WSS) distribution, non-Newtonian importance factors, blood viscosity and shear rate. All blood viscosity models yield a consistent WSS distribution pattern. The WSS magnitude, however, is influenced by the model used. WSS is found to be the lowest in the vicinity of the three arch branches and along the distal walls of the branches themselves. In this region, the local non-Newtonian importance factor and the blood viscosity are elevated, and the shear rate is low. The present study revealed that the Newtonian assumption is a good approximation at mid-and-high flow velocities, as the greater the blood flow, the higher the shear rate near the arterial wall. Furthermore, the capabilities of the applied non-Newtonian models appeared at low-flow velocities. It is concluded that, while the non-Newtonian power-law model approximates the blood viscosity and WSS calculations in a more satisfactory way than the other non-Newtonian models at low shear rates, a cautious approach is given in the use of this blood viscosity model. Finally, some preliminary transient results are presented.     

Towards the improved quantification of in vivo abnormal wall shear stresses in BAV-affected patients from 4D-flow imaging: Benchmarking and application to real data

Bicuspid aortic valve (BAV), i.e. the fusion of two aortic valve cusps, is the most frequent congenital cardiac malformation. Its progression is often characterized by accelerated leaflet calcification and aortic wall dilation. These processes are likely enhanced by altered biomechanical stimuli, including fluid-dynamic wall shear stresses (WSS) acting on both the aortic wall and the aortic valve. Several studies have proposed the exploitation of 4D-flow magnetic resonance imaging sequences to characterize abnormal in vivo WSS in BAV-affected patients, to support prognosis and timing of intervention. However, current methods fail to quantify WSS peak values.On this basis, we developed two new methods for the improved quantification of in vivo WSS acting on the aortic wall based on 4D-flow data.We tested both methods separately and in combination on synthetic datasets obtained by two computational fluid-dynamics (CFD) models of the aorta with healthy and bicuspid aortic valve. Tests highlighted the need for data spatial resolution at least comparable to current clinical guidelines, the low sensitivity of the methods to data noise, and their capability, when used jointly, to compute more realistic peak WSS values as compared to state-of-the-art methods.The integrated application of the two methods on the real 4D-flow data from a preliminary cohort of three healthy volunteers and three BAV-affected patients confirmed these indications. In particular, quantified WSS peak values were one order of magnitude higher than those reported in previous 4D-flow studies, and much closer to those computed by highly time- and space-resolved CFD simulations.     

Understanding the fluid mechanics behind transverse wall shear stress

The patchy distribution of atherosclerosis within arteries is widely attributed to local variation in haemodynamic wall shear stress (WSS). A recently-introduced metric, the transverse wall shear stress (transWSS), which is the average over the cardiac cycle of WSS components perpendicular to the temporal mean WSS vector, correlates particularly well with the pattern of lesions around aortic branch ostia. Here we use numerical methods to investigate the nature of the arterial flows captured by transWSS and the sensitivity of transWSS to inflow waveform and aortic geometry. TransWSS developed chiefly in the acceleration, peak systolic and deceleration phases of the cardiac cycle; the reverse flow phase was too short, and WSS in diastole was too low, for these periods to have a significant influence. Most of the spatial variation in transWSS arose from variation in the angle by which instantaneous WSS vectors deviated from the mean WSS vector rather than from variation in the magnitude of the vectors. The pattern of transWSS was insensitive to inflow waveform; only unphysiologically high Womersley numbers produced substantial changes. However, transWSS was sensitive to changes in geometry. The curvature of the arch and proximal descending aorta were responsible for the principal features, the non-planar nature of the aorta produced asymmetries in the location and position of streaks of high transWSS, and taper determined the persistence of the streaks down the aorta. These results reflect the importance of the fluctuating strength of Dean vortices in generating transWSS.     

Some flow visualization and laser-Doppler-velocity measurements in a true-to-scale elastic model of a human aortic arch--a new model technique.

Flow studies were done in an elastic true-to-scale silicone rubber model of an aortic arch to study further hemodynamic influences on atherosclerosis. The model was prepared from a cast of a young woman. A revised model technique was used. The model had a compliance similar to that of the human aortic arch. Velocity measurements were done in the model with a two component laser-Doppler-anemometer in steady and pulsatile flow using a calcium chloride solution with a viscosity of eta = 3.18 mPas and density of rho = 1.28 kg/m3 at 20 degrees C. The time average Reynolds numbers over a whole cycle in the ascending aorta was Re = 1350. The Womersley parameter for pulsatile flow was a = 20. The pulse wave velocity in the ascending aorta was about c = 5.4 m/sec. The secondary flow behavior was discussed for steady and pulsatile flow. Reverse flows were found, especially along the inner radius of the aortic arch in the descending aorta in steady and pulsatile flow and also in small areas of the ascending aorta and at the branches of the aortic arch. The formation of atherosclerotic plaques at preferred local flow regions is discussed.     

On the flow field distortions due to the aortic arch twist

The aortic arch has, on average, an angle of twist of 15 degrees. The purpose of the research conducted was to ascertain if this twist angle has any effect on the flow field of the aortic arch and the distribution of the flow amongst the branches. It was found that the blood flow distribution is practically independent of the angle of twist of the aortic arch. However, the destination of a fluid particle located at a specific point in the cross-section at the entrance to the aortic arch does depend on the angle of twist.     

Numerical simulation of steady flow fields in a model of abdominal aorta with its peripheral branches

In the present study, a numerical calculation procedure based on a finite volume method was developed to simulate steady flow fields in a model of abdominal aorta with its peripheral branches. The study focused on the steady baseline flow fields and the wall shear stress (WSS) distribution as well as the localization of the reversed flow regions and results were compared to those obtained by other investigators. In the case of resting conditions, the existence of a region of reversed flow of about one to two diameters in size and next to the renal arteries and along the posterior wall as observed by other researchers was confirmed. However, under the exercise conditions this region could be wiped out. The flow reversal along the lateral walls proximal to the bifurcation persisted in both rest and exercise conditions. The WSS distribution and the wall shear stress gradient distribution were obtained. The lowest WSS occurred near the ostia of the renal arteries and the lateral walls of the iliac arteries. And the highest is always at the turn to the branch. The results were generally consistent with those obtained experimentally and numerically by other investigators. It was also shown that the steady flow might be used to depict the averaged behavior of pulsatile flow. The present computer code provides a platform for the future more realistic simulations.     

Comparison of hinge microflow fields of bileaflet mechanical heart valves implanted in different sinus shape and downstream geometry

The characterization of the bileaflet mechanical heart valves (BMHVs) hinge microflow fields is a crucial step in heart valve engineering. Earlier in vitro studies of BMHV hinge flow at the aorta position in idealized straight pipes have shown that the aortic sinus shapes and sizes may have a direct impact on hinge microflow fields. In this paper, we used a numerical study to look at how different aortic sinus shapes, the downstream aortic arch geometry, and the location of the hinge recess can influence the flow fields in the hinge regions. Two geometric models for sinus were investigated: a simplified axisymmetric sinus and an idealized three-sinus aortic root model, with two different downstream geometries: a straight pipe and a simplified curved aortic arch. The flow fields of a 29-mm St Jude Medical BMHV with its four hinges were investigated. The simulations were performed throughout the entire cardiac cycle. At peak systole, recirculating flows were observed in curved downsteam aortic arch unlike in straight downstream pipe. Highly complex three-dimensional leakage flow through the hinge gap was observed in the simulation results during early diastole with the highest velocity at 4.7 m/s, whose intensity decreased toward late diastole. Also, elevated wall shear stresses were observed in the ventricular regions of the hinge recess with the highest recorded at 1.65 kPa. Different flow patterns were observed between the hinge regions in straight pipe and curved aortic arch models. We compared the four hinge regions at peak systole in an aortic arch downstream model and found that each individual hinge did not vary much in terms of the leakage flow rate through the valves.     

Experimental investigation of steady flow through a model of the human aortic arch

Steady flow through a model of the human aortic arch has been studied with hot-film anemometry. A three sensor hot-film velocity probe was inserted into an acrylic flow chamber fabricated from the in situ casting of a human aorta, and the axial, radial and tangential velocity profiles were determined for steady flows in the region of the aortic arch. These studies demonstrated the presence of a potential core throughout the arch region, with a concomitant boundary layer adjacent to the inner wall of curvature of the arch. Trapped secondary flows in this fluid layer along the inner wall were quantitatively determined. Our steady flow studies in the model human aortic arch suggests that a shear-dependent mass transfer mechanism may play a significant role in the development and propagation of atherosclerotic lesions in this segment of the human cardiovascular system.     

MRI and CFD studies of pulsatile flow in healthy and stenosed carotid bifurcation models

Pulsatile flow was studied in physiologically realistic models of a normal and a moderately stenosed (30% diameter reduction) human carotid bifurcation. Time-resolved velocity measurements were made using magnetic resonance imaging, from which wall shear stress (WSS) vectors were calculated. Velocity measurements in the inflow and outflow regions were also used as boundary conditions for a computational fluid dynamics (CFD) model. Experimental flow patterns and derived WSS vectors were compared qualitatively with the corresponding CFD predictions. In the stenosed phantom, flow in the bulb region of the "internal carotid artery" was concentrated along the outer wall, with a region of low and recirculating flow near the inner wall. In the normal phantom, the converse was found, with a low flow region near the outer wall of the bulb. Time-averaged WSS and oscillatory shear index were also markedly different for the two phantoms.     

Pulsatile non-Newtonian haemodynamics in a 3D bifurcating abdominal aortic aneurysm model

Numerical prediction of non-Newtonian blood flow in a 3D abdominal aortic aneurysm bifurcating model is carried out. The non-Newtonian Carreau model is used to characterise the shear thinning behaviour of the human blood. A physical inlet velocity waveform incorporating a radial velocity distribution reasonably representative of a practical case configuration is employed. Case studies subject to both equal and unequal outlet pressures at iliac bifurcations are presented to display convincingly the downstream pressure influences on the flow behaviour within the aneurysm. Simulations indicate that the non-Newtonian aspects of the blood cannot at all be neglected or given a cursory treatment. The wall shear stress (WSS) is found to change significantly at both the proximal and distal ends of the aneurysm. At the peak systole, the WSS is peak around the bifurcation point, whereas the WSS becomes zero in the bifurcation point. Differential downstream pressure fields display significant effects regarding the flow evolution in the iliac arteries, whereas little or no effects are observed directly on the flow details in the aneurysm.