Numerical flow studies in human carotid artery bifurcations: basic discussion of the geometric factor in atherogenesis

In this study fluid dynamic variables are analysed numerically in different human carotid artery bifurcation models in order to clarify the geometric factor in carotid bifurcation atherogenesis. The geometric variations describe healthy human carotid bifurcation anatomy and concern the shape of the carotid sinus and the angle between the branches. The flow conditions remain unchanged. The governing Navier-Stokes equations describing incompressible, pulsatile, three-dimensional viscous flow are approximated using a pressure correction finite element procedure which has been developed for time-consuming, three-dimensional, time-dependent viscous flow problems. The study concentrates on flow velocity, on detailed analysis of flow separation and flow recirculation, and on wall shear stress distribution. The results show that the extension and the location of the recirculation zone in the sinus as well as the duration of separated flow during the pulse cycle are affected by the geometrical variations. In view of the significance of the reversed flow zones and of the accompanied low shear regions in atherogenesis the geometry-dependent flow separation characteristics in the sinus is of substantial interest.     

Carotid bifurcation position and branching angle in patients with atherosclerotic carotid disease

Carotid artery bifurcation (CB) is the preferred site for development of atherosclerosis (AS) in extracranial cerebral arteries; internal carotid artery stenosis is the most common cause of ischemic stroke. The frequent atherosclerotic disease of CB may best be explained by the hemodynamic influence of complex blood flow that results from the unique geometry of the bifurcation. Few papers analyze all possible geometric structural characteristics of this bifurcation. While performing many carotid endarterectomies, we noticed that a certain correlation between CB height in the neck and its angle existed, that a larger angle is accompanied with increased frequency of elongation and kinking and that CB shape influences distribution of atherosclerosis. The purpose of this paper is to quantify and evaluate these clinical observations. Radiogrametric analysis of 154 bi-plane orthogonal aortic arch arteriograms of patients with symptomatic atherosclerotic carotid artery disease was performed and a total of 289 CBs were analyzed. The CB height in relation to cervical spine segments was measured and real angles of each bifurcation were calculated. A positive linear correlation between CB height and angle exists: the CB angle increases /decreases 3.34 degrees for each third of the cervical vertebral body height or intervertebral space height. The CB is positioned a little higher on the left side. The proximal border of the atherosclerotic process is found at the level of intersection of the axes of the common carotid artery branches in 92.6% of examined CBs. In lower CBs (with smaller angles) the proximal border was located in the last segment of the common carotid artery, while in high bifurcations (wider angles) the proximal border of the AS process is more distally in the blood flow, in the beginning of the internal carotid artery, and the process was more extensive. High CBs are more suitable for eversion endarterectomy while normal and low CBs are more suitable for open (classic) carotid endarterectomy. The influence of the geometric risk factor demands further investigation.     

Carotid geometry effects on blood flow and on risk for vascular disease

It has been widely observed that atherosclerotic diseases occur at sites with complex hemodynamics, such as artery bifurcations, junctions, and regions of high curvature. These regions usually have very low or highly oscillatory wall shear stress (WSS). In the present work, 3D pulsatile blood flow through a model of the carotid artery bifurcation was simulated using a finite volume numerical method. The goal was to quantify the risk of atherogenesis associated with different carotid artery geometries. A risk scale based on the average WSS on the sinus wall of the internal carotid artery was proposed-a scale that can be used to quantify the effect of the carotid geometry on the relative risk for developing vascular disease. It was found that the bifurcation angle and the out-of-plane angle of the internal carotid artery affect the formation of low stress regions on the carotid walls. The main conclusions are: (a) larger internal carotid artery angles (theta(IC)) generally increase the frequency and the area of blood recirculation and lower the WSS on the sinus wall, hence increasing the risk of plaque build-up; (b) off-plane angles were found to lower the WSS on the sinus for geometries with theta(IC)25 degrees . Larger off-plane angles generally increase the danger of plague build-up; (c) for theta(IC) < 25 degrees , the off-plane angle does not have an obvious effect on the hemodynamic WSS; (d) symmetric bifurcations were found to increase the WSS on the sinus wall and ease the risk of vascular disease.     

On the influence of vessel planarity on local hemodynamics at the human carotid bifurcation

The human carotid artery bifurcation is a complex, three-dimensional structure exhibiting non-planarity and both in- and out-of-plane curvature. The aim of this study was to determine the relative importance of vessel planarity, a potential geometric risk factor for atherogenesis, in determining the local hemodynamics. A combination of computational fluid dynamics and magnetic resonance imaging was used to reconstruct the subject-specific hemodynamics for three subjects. Planar models were then constructed by translating the centroids of the lumen contours onto a plane defined by the centroids of the vessel branches near the bifurcation apex. A novel "patching" technique was used to convert the continuous arterial surfaces into contiguous but discrete patches according to an objective scheme, making it possible to compare the original and planar models without the need for registration and warping. Results suggest that the planarity of the vessel has a relatively minor effect on the spatial distribution of mean and oscillatory wall shear stress. Out-of-plane curvature was, however, found to have a marked influence on the extent and magnitude of these hemodynamic variables. We conclude that vessel curvature - whether in- or out-of-plane - rather than planarity may deserve further scrutiny as a potential geometric risk for atherogenesis.     

Endothelial nitric oxide synthase and calcium production in arterial geometries: an integrated fluid mechanics/cell model

It is well known that atherosclerosis occurs at very specific locations throughout the human vasculature, such as arterial bifurcations and bends, all of which are subjected to low wall shear stress. A key player in the pathology of atherosclerosis is the endothelium, controlling the passage of material to and from the artery wall. Endothelial dysfunction refers to the condition where the normal regulation of processes by the endothelium is diminished. In this paper, the blood flow and transport of the low diffusion coefficient species adenosine triphosphate (ATP) are investigated in a variety of arterial geometries: a bifurcation with varying inner angle, and an artery bend. A mathematical model of endothelial calcium and endothelial nitric oxide synthase cellular dynamics is used to investigate spatial variations in the physiology of the endothelium. This model allows assessment of regions of the artery wall deficient in nitric oxide (NO). The models here aim to determine whether 3D flow fields are important in determining ATP concentration and endothelial function. For ATP transport, the effects of a coronary and carotid wave form on mass transport is investigated for low Womersley number. For the carotid, the Womersley number is then increased to determine whether this is an important factor. The results show that regions of low wall shear stress correspond with regions of impaired endothetial nitric oxide synthase signaling, therefore reduced availability of NO. However, experimental work is required to determine if this level is significant. The results also suggest that bifurcation angle is an important factor and acute angle bifurcations are more susceptible to disease than large angle bifurcations. It has been evidenced that complex 3D flow fields play an important role in determining signaling within endothelial cells. Furthermore, the distribution of ATP in blood is highly dependent on secondary flow features. The models here use ATP concentration simulated under steady conditions. This has been evidenced to reproduce essential features of time-averaged ATP concentration over a cardiac cycle for small Womersley numbers. However, when the Womersley number is increased, some differences are observed. Transient variations are overall insignificant, suggesting that spatial variation is more important than temporal. It has been determined that acute angle bifurcations are potentially more susceptible to atherogenesis and steady-state ATP transport reproduces essential features of time-averaged pulsatile transport for small Womersley number. Larger Womersley numbers appear to be an important factor in time-dependent mass transfer.     

Sex differences in intracranial arterial bifurcations

Background: Subarachnoid hemorrhage (SAH) is a serious condition, occurring more frequently in females than in males. SAH is mainly caused by rupture of an intracranial aneurysm, which is formed by localized dilation of the intracranial arterial vessel wall, usually at the apex of the arterial bifurcation. The female preponderance is usually explained by systemic factors (hormonal influences and intrinsic wall weakness); however, the uneven sex distribution of intracranial aneurysms suggests a possible physiologic factor—a local sex difference in the intracranial arteries.Objective: The aim of this study was to explore sex variation in the bifurcation anatomy of the middle cerebral artery (MCA) and internal carotid artery (ICA), and the subsequent hemodynamic impact.Methods: Vessel radii and bifurcation angles were measured in patients with MCA and ICA bifurcations. Data from a previously published study of 55 patients undergoing diagnostic cerebral digital subtraction angiography at Dalcross Private Hospital in Sydney, Australia, between 2002 and 2003, were available for analysis. The measurements were used to create idealized, averaged bifurcations of the MCA and ICA for females and males. Computational fluid dynamics simulations were performed to calculate hemodynamic forces in the models.Results: The vessel radii and bifurcation angles of 47 MCA and 52 ICA bifurcations in 49 patients (32 females, 17 males; mean age, 53 years; age range, 14–86 years) were measured. Statistically significant sex differences were found in vessel diameter (males larger than females; P < 0.05), but not in bifurcation angle. Computational fluid dynamics simulations revealed higher wall shear stress in the female MCA (19%) and ICA (50%) bifurcations compared with the male bifurcations.Conclusions: This study of MCA and ICA bifurcations in female and male patients suggests that sex differences in vessel size and blood flow velocity result in higher hemodynamic forces acting on the vessel wall in females. This new hypothesis may partly explain why intracranial aneurysms and SAH are more likely to occur in females than in males.     

Healthy and diseased coronary bifurcation geometries influence near-wall and intravascular flow: A computational exploration of the hemodynamic risk

Local hemodynamics has been identified as one main determinant in the onset and progression of atherosclerotic lesions at coronary bifurcations. Starting from the observation that atherosensitive hemodynamic conditions in arterial bifurcation are majorly determined by the underlying anatomy, the aim of the present study is to investigate how peculiar coronary bifurcation anatomical features influence near-wall and intravascular flow patterns. Different bifurcation angles and cardiac curvatures were varied in population-based, idealized models of both stenosed and unstenosed bifurcations, representing the left anterior descending (LAD) coronary artery with its diagonal branch. Local hemodynamics was analyzed in terms of helical flow and exposure to low/oscillatory shear stress by performing computational fluid dynamics simulations.Results show that bifurcation angle impacts lowly hemodynamics in both stenosed and unstenosed cases. Instead, curvature radius influences the generation and transport of helical flow structures, with smaller cardiac curvature radius associated to higher helicity intensity. Stenosed bifurcation models exhibit helicity intensity values one order of magnitude higher than the corresponding unstenosed cases. Cardiac curvature radius moderately affects near-wall hemodynamics of the stenosed cases, with smaller curvature radius leading to higher exposure to low shear stress and lower exposure to oscillatory shear stress. In conclusion, the proposed controlled benchmark allows investigating the effect of various geometrical features on local hemodynamics at the LAD/diagonal bifurcation, highlighting that cardiac curvature influences near wall and intravascular hemodynamics, while bifurcation angle has a minor effect.     

Blood flow downstream of a two-dimensional bifurcation

Many cardiovascular lesions such as aneurysms, intimal cushions, and atherosclerotic plaques tend to occur near bifurcations. This suggests that hemodynamic factors may be involved. Since measuring devices (such as anemometers) are still too large to allow local measurements of flow disturbances, we have attempted to predict the nature of these factors mathematically. Biological variables include pulsatile flow of a nonNewtonian fluid in distensible branching vessels with different angles and flow rates. Our initial analysis considers the flow in a two-dimensional bifurcation with a symmetrical flow divider perfused with steady flow at variable Reynolds numbers. At all flows, high shear forces develop on either side of the flow divider (i.e. at the apex of the bifurcation). With high flows, regions of sluggish or reverse flow develop near the outer walls of the bifurcation. The analysis confirms that the flow at the apex is quite different from that at the outer angles and that the latter varies more with flow rate than the former.     

Computational study of the effect of geometric and flow parameters on the steady flow field at the rabbit aorto-celiac bifurcation

Arterial hemodynamic forces may play a role in the localization of early atherosclerotic lesions. We have been developing numerical techniques based on overset or "Chimera" type formulations to solve the Navier-Stokes equations in complex geometries simulating arterial bifurcations. This paper presents three-dimensional steady flow computations in a model of the rabbit aorto-celiac bifurcation. The computational methods were validated by comparing the numerical results to previously-obtained flow visualization data. Once validated, the numerical algorithms were used to investigate the sensitivity of the computed flow field and resulting wall shear stress distribution to various geometric and hemodynamic parameters. The results demonstrated that a decrease in the extent of aortic taper downstream of the celiac artery induced looping fluid motion along the lateral walls of the aorta and shifted the peak wall shear stress from downstream of the celiac artery to upstream. Increasing the flow Reynolds number led to a sharp increase in spatial gradients of wall shear stress. The flow field was highly sensitive to the flow division ratio, i.e., the fraction of total flow rate that enters the celiac artery, with larger values of this ratio leading to the occurrence of flow separation along the dorsal wall of the aorta. Finally, skewness of the inlet velocity profile had a profound impact on the wall shear stress distribution near the celiac artery. While not physiological due to the assumption of steady flow, these results provide valuable insight into the fluid physics at geometries simulating arterial bifurcations.     

Parametric geometry exploration of the human carotid artery bifurcation

A parametric computational model of the human carotid artery bifurcation is employed to demonstrate that it is only necessary to simulate approximately one-half of a single heart pulse when performing a global exploration of the relationships between shear stress and changes in geometry. Using design of experiments and surface fitting techniques, a landscape is generated that graphically depicts these multi-dimensional relationships. Consequently, whilst finely resolved, grid and pulse independent results are traditionally demanded by the computational fluid dynamics (CFD) community, this strategy demonstrates that it is possible to efficiently detect the relative impact of different geometry parameters, and to identify good and bad regions of the landscape by only simulating a fraction of a single pulse. Also, whereas in the past comparisons have been made between the distributions of appropriate shear stress metrics, such as average wall shear stress and oscillatory shear index, this strategy requires a figure of merit to compare different geometries. Here, an area-weighted integral of negative time-averaged shear stress, tau , is used as the principal objective function, although the discussion reveals that the extent as well as the intensity of reverse flow may be important. Five geometry parameters are considered: the sinus bulb width, the angles and the outflow diameters of the internal carotid artery (ICA) and external carotid artery (ECA). A survey of the landscape confirms that bulb shape has the dominant effect on tau with maximum tau occurring for large bulb widths. Also, it is shown that different sets of geometric parameters can produce low values of tau by either relatively small intense areas, or by larger areas of less intense reverse flow.     

Common carotid wall shear stress and carotid atherosclerosis in end-stage renal disease patients

Decrease of arterial wall shear stress (WSS) is associated with higher probability of atherosclerotic plaque development in many disease conditions. End-stage renal diseases (ESRD) patients suffer from vascular disease frequently, but its nature differs from general population. This study was aimed at proving an association between common carotid wall shear stress and the presence of carotid bifurcation plaques in a group of ESRD patients. ESRD subjects, planned for the creation of a dialysis access and therapy were included. Wall shear rate (WSR) was used as a surrogate of WSS and was analyzed in the common carotid arteries by duplex ultrasonography. Intima media thickness (IMT) was measured at the same site. The presence/absence of carotid bifurcation plaques was recorded. The endothelial function was estimated by the levels of von Willebrand factor (vWf). 35 ESRD patients were included (19 females, 17 diabetics). Atherosclerotic plaque was present in 53 % of bifurcations. Wall shear rate was lower in arteries with plaques (349+/-148 vs. 506+/-206 s(-1), p=0.005) and was directly related to the height of IMT and inversely to the activity of vWf (r= -0.65, p=0.016). Lower wall shear rate in the common carotid arteries is linked to the endothelial dysfunction and to the presence of atherosclerotic plaques in carotid bifurcations in ESRD subjects. Faster arterial dilatation may facilitate this process in ESRD subjects.     

Diameter asymmetry of porcine coronary arterial trees: structural and functional implications

The coronary vasculature is characterized by highly asymmetric diameters at bifurcations, which may be an important determinant of flow distribution. To facilitate accurate reconstruction of the coronary network for hemodynamic analysis, we introduce a statistical data set of the diameter asymmetry at bifurcations based on morphometric data of the porcine coronary arterial and venous trees. The bifurcation asymmetry data were represented by the diameter ratio of the daughters relative to mother vessel and by an area expansion ratio (AER) at each bifurcation. A novel asymmetry ratio matrix was introduced to describe the diameter asymmetry of daughters to mother vessels. The relations between AER and flow velocity, and asymmetry ratio matrix and flow distribution, were considered. The results indicate that the ratio of large daughter to mother vessel has a minimum value at order 5 (mean diameter of approximately 70 microm), whereas the ratio of small daughter to mother vessel decreases monotonically with increase in order number. The AER was found to be fairly uniform for larger vessels and to increase from order 5 toward the capillaries. At order 5, we observe a transition in asymmetric bifurcation pattern that may mark a hemodynamic transition from transmural to perfusion subnetworks. The functional implications of these structural transitions are considered.     

Atherosclerosis and flow in carotid arteries with authentic geometries

The influence of blood flow on the depositions and development of atherosclerotic lesions have been observed and described since the 19th century. Observations have shown that depositions correlate with regions of low wall shear stress. However, the exact correlations between depositions, vessel geometry and flow parameters are not yet known. The purpose of this study was the quantification of atherosclerosis risk factors in carotid bifurcation. This artery has attracted particular interest because lesions are often found in this bifurcation. Post mortem, the arteries are excised and vessel casts are produced. Afterwards, the arteries are analyzed morphometrically. The vessel casts are used for the assessment of some geometrical parameters. 31 carotid bifurcations were analyzed in this study. Eight vessel casts were digitized and rendered three-dimensional mathematical models of the arteries. These data were imported by the computational fluid dynamics program FLUENT. Further, the blood flow was reconstructed in a computer model based on the individual vessel geometry. The flow parameters, such as velocity, pressure and wall shear stress were computed. At the same time the geometrical parameters and wall alterations are known. This permits the comparison of the anatomical shape and its flow with the distribution and level of the wall alterations.     

Automated and objective removal of bifurcation aneurysms: Incremental improvements,and validation against healthy controls

Abnormal hemodynamic stresses are thought to correlate with aneurysm initiation, growth, and rupture. We have previously investigated the role of wall shear stress (WSS) and WSS gradients (WSSG) in search for a mechanistic link to formation of sidewall aneurysms using an automated and objective tool for aneurysm removal and arterial reconstruction in combination with computational fluid dynamics (CFD). However, we warned against the use of the tool for bifurcation type aneurysms because of a potential unrealistic reconstruction of the apex. We hypothesized that inclusion of additional morphological features from the surrounding vasculature could overcome these constraints. We extended the previously published method for removal and reconstruction of the bifurcation vasculature based on diverging and converging points of the parent and daughter artery centerlines, to also include two new centerlines between the daughter vessels, one of them passed through the bifurcation center. Validation was performed by comparing the efficacy of the two algorithms, using ten healthy models of the internal carotid artery terminus as ground truth. Qualitative results showed that the bifurcation apexes became smoother relative to the original algorithm; more consistent with the reference models. This was reflected quantitatively by a reduced maximum distance between the reference and reconstructed surfaces, although not statistically significant. Furthermore, the modified algorithm also quantitatively improved CFD derived WSS and WSSG, especially the latter. In conclusion, the modified algorithm does not perfectly reconstruct the bifurcation apex, but provides an incremental improvement, especially important for the derived hemodynamic metrics of interest in vascular pathobiology.     

Modeling the effect of blood vessel bifurcation ratio on occlusive thrombus formation

Vascular geometry is a major determinant of the hemodynamics that promote or prevent unnecessary vessel occlusion from thrombus formation. Bifurcations in the vascular geometry are repeating structures that introduce flow separation between parent and daughter vessels. We modelled the blood flow and shear rate in a bifurcation during thrombus formation and show that blood vessel bifurcation ratios determine the maximum shear rate on the surface of a growing thrombus. We built an analytical model that may aid in predicting microvascular bifurcation ratios that are prone to occlusive thrombus formation. We also observed that bifurcation ratios that adhere to Murray’s law of bifurcations may be protected from occlusive thrombus formation. These results may be useful in the rational design of diagnostic microfluidic devices and microfluidic blood oxygenators.     

Coupled fluid–structure interaction hemodynamics in a zero-pressure state corrected arterial geometry

Hemodynamic conditions in large arteries are significantly affected by the interaction of the pulsatile blood flow with the distensible arterial wall. A numerical procedure for solving the fluid–structure interaction problem encountered in cardiovascular flows is presented. We consider a patient-specific carotid bifurcation geometry, obtained from 3D reconstruction of in vivo acquired tomography images, which yields a geometrical representation of the artery corresponding to its pressurized state. To recover the geometry of the artery in its zero-pressure state which is required for a fluid–structure interaction simulation we utilize inverse finite elastostatics. Time-dependent flow simulations with in vivo measured inflow volume flow rate in the 3D undeformed artery are performed through the finite element method. The coupled-momentum method for fluid–structure interaction is adopted to incorporate the influence of wall compliance in the numerical computation of the time varying flow domain. To demonstrate the importance in recovering the zero-pressure state of the artery in hemodynamic simulations we compute the time varying flow field with compliant walls for the original and the zero-pressure state corrected geometric configurations of the carotid bifurcation. The most important resulting effects in the hemodynamic environment are evaluated. Our results show a significant change in the wall shear stress distribution and the spatiotemporal extent of the recirculation regions.