Spatial Wall Shear Stress Gradient Research Articles

A parametric study of the effect of 3D plaque shape on local hemodynamics and implications for plaque instability.

The vast majority of heart attacks occur when vulnerable plaques rupture, releasing their lipid content into the blood stream leading to thrombus formation and blockage of a coronary artery. Detection of these unstable plaques before they rupture remains a challenge. Hemodynamic features including wall shear stress (WSS) and wall shear stress gradient (WSSG) near the vulnerable plaque and local inflammation are known to affect plaque instability. In this work, a computational workflow has been developed to enable a comprehensive parametric study detailing the effects of 3D plaque shape on local hemodynamics and their implications for plaque instability. Parameterized geometric 3D plaque models are created within a patient-specific coronary artery tree using a NURBS (non-uniform rational B-splines)-based vascular modeling pipeline. Realistic blood flow features are simulated by using a Navier-Stokes solver within an isogeometric finite-element analysis framework. Near wall hemodynamic quantities such as WSS and WSSG are quantified, and vascular distribution of an inflammatory marker (VCAM-1) is estimated. Results show that proximally skewed eccentric plaques have the most vulnerable combination of high WSS and high positive spatial WSSG, and the presence of multiple lesions increases risk of rupture. The computational tool developed in this work, in conjunction with clinical data, -could help identify surrogate markers of plaque instability, potentially leading to a noninvasive clinical procedure for the detection of vulnerable plaques before rupture.

Numerical investigation of unruptured middle cerebral artery bifurcation aneurysms: influence of aspect ratio

An aneurysm is a disease condition, which is due to the pathological weakening of an arterial wall. These aneurysms are often found in various branch points and bifurcations of an artery in the cerebral circulation. Most aneurysms come to medical attention, either due to brain hemorrhages caused by rupture or found unruptured. To consider surgically invasive treatment modalities, clinicians need scientific methods such as, hemodynamic analysis to assess rupture risk. The arterial wall loses its structural integrity when wall shear stress (WSS) and other hemodynamic parameters exceed a certain threshold. In the present study, numerical simulations are carried out for unruptured middle cerebral artery (MCA) aneurysms. Three distinct representative sizes are chosen from a larger patient pool of 26 MCA aneurysms. Logically, these aneurysms represent three growth stages of any patient with similar anatomical structure. Simulations are performed to compare the three growth phases (with different aspect ratios) of an aneurysm and correlate their hemodynamic parameters. Simulations with patient specific boundary conditions reveal that, aneurysms with a higher aspect ratio (AR) correspond to an attendant decrease in both time-averaged wall shear stress (TAWSS) and spatial wall shear stress gradients (WSSG). Smaller MCAs were observed to have higher positive wall shear stress divergence (WSSD), exemplifying the tensile nature of arterial wall stretching. Present study identifies positive wall shear stress divergence (PWSSD) to be a potential biomarker for evaluating the growth of an aneurysm.

Association of Shear Stress with Subsequent Lumen Remodeling in Hemodialysis Arteriovenous Fistulas.

Blood flow-induced wall shear stress is a strong local regulator of vascular remodeling, but its effects on arteriovenous fistula (AVF) remodeling are unclear. In this prospective cohort study, we used computational fluid dynamics simulations and statistical mixed-effects modeling to investigate the associations between wall shear stress and AVF remodeling in 120 participants undergoing AVF creation surgery. Postoperative magnetic resonance imaging data at 1 day, 6 weeks, and 6 months were used to derive current wall shear stress by computational fluid dynamic simulations and to quantify subsequent changes in AVF lumen cross-sectional area at 1-mm intervals along the proximal artery and AVF vein. Combining artery and vein data, prior mean wall shear stress was significantly associated with lumen area expansion. Mean wall shear stress at day 1 was significantly associated with change in lumen area from day 1 to week 6 (11% larger area per interquartile range [IQR] higher mean wall shear stress, 95% confidence interval [95% CI], 5% to 18%; n =101), and mean wall shear stress at 6 weeks was significantly associated with change in lumen area from 6 weeks to month 6 (14% larger area per IQR higher, 95% CI, 3% to 28%; n =52). The association of mean wall shear stress at day 1 with lumen area expansion from day 1 to week 6 differed significantly by diabetes ( P =0.009): 27% (95% CI, 17% to 37%) larger area per IQR higher mean wall shear stress without diabetes and 9% (95% CI, -1% to 19%) with diabetes. Oscillatory shear index at day 1 was significantly associated with change in lumen area from day 1 to week 6 (5% smaller area per IQR higher oscillatory shear index, 95% CI, 3% to 7%), and oscillatory shear index at 6 weeks was significantly associated with change in lumen from 6 weeks to month 6 (7% smaller area per IQR higher oscillatory shear index, 95% CI, 2% to 11%). Wall shear stress spatial gradient was not significantly associated with subsequent remodeling. In a joint model, wall shear stress and oscillatory shear index statistically significantly interacted in their associations with lumen area expansion in a complex nonlinear fashion. Higher wall shear stress and lower oscillatory shear index were associated with greater lumen expansion after AVF creation surgery.

Increased focal internal carotid artery angulation in patients with posterior communicating artery aneurysms

BackgroundAneurysms at the posterior communicating artery (PCOM) origin represent the most common location on the internal carotid artery (ICA), and are associated with greater recurrence following endovascular treatment. We evaluate...

Computational fluid dynamics of a novel perfusion strategy during hybrid thoracic aortic repair.

To mitigate the risk of perioperative neurological complications during frozen elephant trunk procedures, we aimed to computationally evaluate the effects of direct cerebral perfusion strategy through a left carotid-subclavian bypass on hemodynamics in a patient-specific thoracic aorta model. Between July 2016 and March 2019, 11 consecutive patients underwent frozen elephant trunk operation using the left carotid-subclavian bypass with a side graft anastomosis and right-axillary cannulation for systemic and brain perfusion. A multiscale model realized coupling three-dimensional computational fluid dynamics was developed and validated with in vivo data. Model comparison with direct antegrade cannulation of all epiaortic vessels was performed. Wall shear stress, wall shear stress spatial gradient, and localized normalized helicity were selected as hemodynamic indicators. Four cerebral perfusion flows were tested (6 to 15 mL/kg/min). Direct cerebral perfusion of the left subclavian bypass resulted in higher flow rates with augmented speeds in all epiaortic vessels in comparison with traditional perfusion model. At the level of the left vertebral artery (LVA), a speed of 22.5 vs 21 mL/min and mean velocity of 3.07 vs 2.93 cm/s were registered, respectively. With a cerebral perfusion flow of 15 mL/kg, lower LVA wall shear stress (1.596 vs 2.030 N/m2 ), and wall shear stress gradient (1445 vs 5882 N/m3 ) were observed. A less disturbed flow considering the localized normalized helicity was documented. No patients experienced neurological/spinal cord damages. Direct perfusion of a left carotid bypass proved to be cerebroprotective, resulting in a more physiological and stable anterior and posterior cerebral perfusion.

Induction of aneurysmogenic high positive wall shear stress gradient by wide angle at cerebral bifurcations, independent of flow rate.

Endothelium adapts to wall shear stress (WSS) and is functionally sensitive to positive (aneurysmogenic) and negative (protective) spatial WSS gradients (WSSG) in regions of accelerating and decelerating flow, respectively. Positive WSSG causes endothelial migration, apoptosis, and aneurysmal extracellular remodeling. Given the association of wide branching angles with aneurysm presence, the authors evaluated the effect of bifurcation geometry on local apical hemodynamics. Computational fluid dynamics simulations were performed on parametric bifurcation models with increasing angles having: 1) symmetrical geometry (bifurcation angle 60°-180°), 2) asymmetrical geometry (daughter angles 30°/60° and 30°/90°), and 3) curved parent vessel (bifurcation angles 60°-120°), all at baseline and double flow rate. Time-dependent and time-averaged apical WSS and WSSG were analyzed. Results were validated on patient-derived models. Narrow symmetrical bifurcations are characterized by protective negative apical WSSG, with a switch to aneurysmogenic WSSG occurring at angles ≥ 85°. Asymmetrical bifurcations develop positive WSSG on the more obtuse daughter branch. A curved parent vessel leads to positive apical WSSG on the side corresponding to the outer curve. All simulations revealed wider apical area coverage by higher WSS and positive WSSG magnitudes, with increased bifurcation angle and higher flow rate. Flow rate did not affect the angle threshold of 85°, past which positive WSSG occurs. In curved models, high flow displaced the impingement area away from the apex, in a dynamic fashion and in an angle-dependent manner. Apical shear forces and spatial gradients are highly dependent on bifurcation and inflow vessel geometry. The development of aneurysmogenic positive WSSG as a function of angular geometry provides a mechanotransductive link for the association of wide bifurcations and aneurysm development. These results suggest therapeutic strategies aimed at altering underlying unfavorable geometry and deciphering the molecular endothelial response to shear gradients in a bid to disrupt the associated aneurysmal degeneration.

Lymphatic endothelial cell calcium pulses are sensitive to spatial gradients in wall shear stress.

Cytosolic calcium (Ca2+) is a ubiquitous second messenger that influences numerous aspects of cellular function. In many cell types, cytosolic Ca2+ concentrations are characterized by periodic pulses, whose dynamics can influence downstream signal transduction. Here, we examine the general question of how cells use Ca2+ pulses to encode input stimuli in the context of the response of lymphatic endothelial cells (LECs) to fluid flow. Previous work shows that fluid flow regulates Ca2+ dynamics in LECs and that Ca2+-dependent signaling plays a key role in regulating lymphatic valve formation during embryonic development. However, how fluid flow might influence the Ca2+ pulse dynamics of individual LECs has remained, to our knowledge, little explored. We used live-cell imaging to characterize Ca2+ pulse dynamics in LECs exposed to fluid flow in an in vitro flow device that generates spatial gradients in wall shear stress (WSS), such as are found at sites of valve formation. We found that the frequency of Ca2+ pulses was sensitive to the magnitude of WSS, while the duration of individual Ca2+ pulses increased in the presence of spatial gradients in WSS. These observations provide an example of how cells can separately modulate Ca2+ pulse frequency and duration to encode distinct forms of information, a phenomenon that could extend to other cell types.

High resolution hemodynamic profiling of murine arteriovenous fistula using magnetic resonance imaging and computational fluid dynamics

BackgroundArteriovenous fistula (AVF) maturation failure remains a major cause of morbidity and mortality in hemodialysis patients. The two major etiologies of AVF maturation failure are early neointimal hyperplasia development and persistent inadequate outward remodeling. Although hemodynamic changes following AVF creation may impact AVF remodeling and contribute to neointimal hyperplasia development and impaired outward remodeling, detailed AVF hemodynamics are not yet fully known. Since murine AVF models are valuable tools for investigating the pathophysiology of AVF maturation failure, there is a need for a new approach that allows the hemodynamic characterization of murine AVF at high resolutions.MethodsThis methods paper presents a magnetic resonance imaging (MRI)-based computational fluid dynamic (CFD) method that we developed to rigorously quantify the evolving hemodynamic environment in murine AVF. The lumen geometry of the entire murine AVF was reconstructed from high resolution, non-contrast 2D T2-weighted fast spin echo MRI sequence, and the flow rates of the AVF inflow and outflow were extracted from a gradient echo velocity mapping sequence. Using these MRI-obtained lumen geometry and inflow information, CFD modeling was performed and used to calculate blood flow velocity and hemodynamic factors at high resolutions (on the order of 0.5 μm spatially and 0.1 ms temporally) throughout the entire AVF lumen. We investigated both the wall properties (including wall shear stress (WSS), wall shear stress spatial gradient, and oscillatory shear index (OSI)) and the volumetric properties (including vorticity, helicity, and Q-criterion).ResultsOur results demonstrate increases in AVF flow velocity, WSS, spatial WSS gradient, and OSI within 3 weeks post-AVF creation when compared to pre-surgery. We also observed post-operative increases in flow disturbances and vortices, as indicated by increased vorticity, helicity, and Q-criterion.ConclusionsThis novel protocol will enable us to undertake future mechanistic studies to delineate the relationship between hemodynamics and AVF development and characterize biological mechanisms that regulate local hemodynamic factors in transgenic murine AVF models.

Abstract 12507: Spatial Gradients in Wall Shear Stress Promote Collective Human Lymphatic Microvascular Endothelial Cell Migration and Alignment Through Sphingosine 1-phosphate Receptor 1

Introduction: Spatial variations in fluid flow are thought to help trigger the formation of valves within the blood and lymphatic circulatory systems during embryonic development. However, how the physical stimulus drives the collective cell movements and changes in gene expression that underlie valve formation is not known. This knowledge gap is of considerable importance since valve failure within the lymphatic and venous vessels is significant in a wide variety of cardiovascular disease states. Methods: In this study, we developed in vitro fluid flow devices that allow us to replicate key aspects of the fluid flow environment found in the vicinity of developing valves within the lymphatic and venous vasculatures. We developed an impinging flow chamber as a model for vessel bifurcations, applying a spatial gradient in wall shear stress (WSS). We have also developed a device which applies flow through a constriction such as is commonly found at sites of valve initiation. Results: Using these devices, we examined the migration of human lymphatic microvascular ECs (MVECs) subjected to spatial gradients in WSS. We found that lymphatic MVECs subjected to a variety of WSS ranges from 0 to 9, 33, or 72 dynes/cm 2 align and collectively migrate against the flow direction over the course of 20 hours. When subjected to flow through a constriction, lymphatic MVECs turned perpendicular to the flow direction at regions near the site of maximum constriction. We determined that the G-Protein Coupled Receptor, Sphingosine 1-Phosphate Receptor 1 (S1PR1) was required for both lymphatic MVEC alignment and collective migration: a 70% S1PR1 mRNA knockdown relative to scrambled siRNA control was sufficient to prevent the collective migration and perpendicular alignment phenotypes we observed in our in vitro flow devices. In addition, these shear stress gradients resulted in higher nuclear levels of Prospero Homeobox Protein 1, a transcription factor known to be required for valvulogenesis, relative to cells in the absence of flow (Impinging Flow; 9.8 +/- 2.2 fold, Constriction; 5.1 +/- 0.8 fold). Conclusions: Our observations implicate S1PR1 as a key component in both the phenotypic and transcriptional responses of LECs to gradients in WSS, such as those at sites of valve formation.

Effect of Different Rotational Directions of BJUT-II VAD on Aortic Swirling Flow Characteristics: A Primary Computational Fluid Dynamics Study.

BackgroundThe BJUT-II VAD is a novel left ventricular assist device (LVAD), which is thought to have significant effects on the characteristics of aortic swirling flow. However, the precise mechanism of the rotational direction of BJTU-II VAD in the aortic swirling flow is unclear.Material/MethodsA patient-specific aortic geometric model was reconstructed based on the CT data. Three pump’s output flow profiles with varied rotational direction, termed “counterclockwise”, “flat profile”, and “clockwise”, were used as the boundary conditions. The helicity density, area-weighted average of helicity density (Ha), localized normalized helicity (LNH), wall shear stress (WSS), and WSS spatial gradient (WSSG) were calculated to evaluate the swirling flow characteristics in the aorta.ResultsThe results demonstrated that the swirling flow characteristics in the aorta and 3 branches are directly affected by the output blood flow of BJUT-II VAD. In the aortic arch, the helicity density, supported by the clockwise case, achieved the highest value. In the 3 branches, the flat profile case achieved the highest helicity density, whereas the maximum WSS and WSSG generated by clockwise case were lower than in other cases.ConclusionsThe outflow of the BJUT-II VAD has significant effects on the aortic hemodynamics and swirling flow characteristics. The helical blood profiles can enhance the strength of aortic swirling flow, and reduce the areas of low WSS and WSSG regions. The clockwise case may have a benefit for preventing development of atherosclerosis in the aorta.

Impact of bifurcation angle and other anatomical characteristics on blood flow – A computational study of non-stented and stented coronary arteries

The hemodynamic influence of vessel shape such as bifurcation angle is not fully understood with clinical and quantitative observations being equivocal. The aim of this study is to use computational modeling to study the hemodynamic effect of shape characteristics, in particular bifurcation angle (BA), for non-stented and stented coronary arteries.Nine bifurcations with angles of 40°, 60° and 80°, representative of ±1 SD of 101 asymptomatic computed tomography angiogram cases (average age 54±8 years; 57 females), were generated for (1) a non-stented idealized, (2) stented idealized, and (3) non-stented patient-specific geometry. Only the bifurcation angle was changed while the geometries were constant to eliminate flow effects induced by other vessel shape characteristics. The commercially available Biomatrix stent was used as a template and virtually inserted into each branch, simulating the T-stenting technique. Three patient-specific geometries with additional shape variation and ±2 SD BA variation (33°, 42° and 117°) were also computed. Computational fluid dynamics (CFD) analysis was performed for all 12 geometries to simulate physiological conditions, enabling the quantification of the hemodynamic stress distributions, including a threshold analysis of adversely low and high wall shear stress (WSS), low time-averaged WSS (TAWSS), high spatial WSS gradient (WSSG) and high Oscillatory Shear Index (OSI) area.The bifurcation angle had a minor impact on the areas of adverse hemodynamics in the idealized non-stented geometries, which fully disappeared once stented and was not apparent for patient geometries. High WSS regions were located close to the carina around peak-flow, and WSSG increased significantly after stenting for the idealized bifurcations. Additional shape variations affected the hemodynamic profiles, suggesting that BA alone has little effect on a patient׳s hemodynamic profile. Incoming flow angle, diameter and tortuosity appear to have stronger effects.This suggests that other bifurcation shape characteristics and stent placement/strategy may be more important than bifurcation angle in atherosclerotic disease development, progression, and stent outcome.

Nanoscale Patterning of Extracellular Matrix Alters Endothelial Function under Shear Stress.

The role of nanotopographical extracellular matrix (ECM) cues in vascular endothelial cell (EC) organization and function is not well-understood, despite the composition of nano- to microscale fibrillar ECMs within blood vessels. Instead, the predominant modulator of EC organization and function is traditionally thought to be hemodynamic shear stress, in which uniform shear stress induces parallel-alignment of ECs with anti-inflammatory function, whereas disturbed flow induces a disorganized configuration with pro-inflammatory function. Since shear stress acts on ECs by applying a mechanical force concomitant with inducing spatial patterning of the cells, we sought to decouple the effects of shear stress using parallel-aligned nanofibrillar collagen films that induce parallel EC alignment prior to stimulation with disturbed flow resulting from spatial wall shear stress gradients. Using real time live-cell imaging, we tracked the alignment, migration trajectories, proliferation, and anti-inflammatory behavior of ECs when they were cultured on parallel-aligned or randomly oriented nanofibrillar films. Intriguingly, ECs cultured on aligned nanofibrillar films remained well-aligned and migrated predominantly along the direction of aligned nanofibrils, despite exposure to shear stress orthogonal to the direction of the aligned nanofibrils. Furthermore, in stark contrast to ECs cultured on randomly oriented films, ECs on aligned nanofibrillar films exposed to disturbed flow had significantly reduced inflammation and proliferation, while maintaining intact intercellular junctions. This work reveals fundamental insights into the importance of nanoscale ECM interactions in the maintenance of endothelial function. Importantly, it provides new insight into how ECs respond to opposing cues derived from nanotopography and mechanical shear force and has strong implications in the design of polymeric conduits and bioengineered tissues.

Characterizations and Correlations of Wall Shear Stress in Aneurysmal Flow.

Wall shear stress (WSS) is one of the most studied hemodynamic parameters, used in correlating blood flow to various diseases. The pulsatile nature of blood flow, along with the complex geometries of diseased arteries, produces complicated temporal and spatial WSS patterns. Moreover, WSS is a vector, which further complicates its quantification and interpretation. The goal of this study is to investigate WSS magnitude, angle, and vector changes in space and time in complex blood flow. Abdominal aortic aneurysm (AAA) was chosen as a setting to explore WSS quantification. Patient-specific computational fluid dynamics (CFD) simulations were performed in six AAAs. New WSS parameters are introduced, and the pointwise correlation among these, and more traditional WSS parameters, was explored. WSS magnitude had positive correlation with spatial/temporal gradients of WSS magnitude. This motivated the definition of relative WSS gradients. WSS vectorial gradients were highly correlated with magnitude gradients. A mix WSS spatial gradient and a mix WSS temporal gradient are proposed to equally account for variations in the WSS angle and magnitude in single measures. The important role that WSS plays in regulating near wall transport, and the high correlation among some of the WSS parameters motivates further attention in revisiting the traditional approaches used in WSS characterizations.

Multiplexed Fluid Flow Device to Study Cellular Response to Tunable Shear Stress Gradients.

Endothelial cells (ECs) line the interior of blood and lymphatic vessels and experience spatially varying wall shear stress (WSS) as an intrinsic part of their physiological function. How ECs, and mammalian cells generally, sense spatially varying WSS remains poorly understood, due in part to a lack of convenient tools for exposing cells to spatially varying flow patterns. We built a multiplexed device, termed a 6-well impinging flow chamber, that imparts controlled WSS gradients to a six-well tissue culture plate. Using this device, we investigated the migratory response of lymphatic microvascular ECs, umbilical vein ECs, primary fibroblasts, and epithelial cells to WSS gradients on hours to days timescales. We observed that lymphatic microvascular ECs migrate upstream, against the direction of flow, a response that was unique among all the cells types investigated here. Time-lapse, live cell imaging revealed that the microtubule organizing center relocated to the upstream side of the nucleus in response to the applied WSS gradient. To further demonstrate the utility of our device, we screenedfor the involvement of canonical signaling pathways in mediating this upstream migratory response. These data highlight the importance of WSS magnitude and WSS spatial gradients in dictating the cellular response to fluid flow.

Evaluation of the hemodynamics in straight 6-mm and tapered 6- to 8-mm grafts as upper arm hemodialysis vascular access.

The present study is intended to investigate and compare the hemodynamics in two different sizes of hemodialysis arteriovenous grafts for upper arm hemodialysis vascular access: 8-mm tapered to 6-mm at the arterial side and straight 6mm. A computational simulation approach is presented for this study, which is validated against the available experimental and numerical pressure measurements in the literature. The imposed boundary conditions at the arterial inlet and venous outlet boundaries of the models are physiological velocity and pressure waveforms, respectively. Blood flow fields and distribution patterns of the hemodynamic indices including wall shear stress (WSS) as one of the major hemodynamic parameters of the cardiovascular system and spatial wall shear stress gradient (SWSSG) as an indicator of disturbed flow patterns and hence susceptible sites of lesion developments are analyzed and compared between the two grafts. The tapered 6- to 8-mm graft seemingly is associated with less disturbed flow patterns within the venous anastomosis (VA) and the vein downstream while benefiting from higher blood flow rates within. Also, it shows a definitive advantage in terms of WSS and SWSSG distribution patterns around the VA and throughout the vein downstream with significantly lower values, which reduce the risk of thrombosis formation and stenotic lesion developments. The only disadvantage encountered in using 6- to 8-mm tapered graft is higher values of hemodynamic parameters at the arterial junction attributable to its significantly higher mean blood flow rate within. The results clearly indicate that the tapered 6- to 8-mm graft entirely outperforms straight 6-mm graft hemodynamically as an upper arm hemodialysis vascular access graft and confirms clinical data in the literature, which suggests advantageous use of tapered 6- to 8-mm grafts in the creation of upper arm brachioaxillary hemodialysis vascular access grafts in selected groups of patients with expectably higher patency rates and lower complications.

High Wall Shear Stress and Spatial Gradients in Vascular Pathology: A Review

Cardiovascular pathologies such as intracranial aneurysms (IAs) and atherosclerosis preferentially localize to bifurcations and curvatures where hemodynamics are complex. While extensive knowledge about low wall shear stress (WSS) has been generated in the past, due to its strong relevance to atherogenesis, high WSS (typically >3Pa) has emerged as a key regulator of vascular biology and pathology as well, receiving renewed interests. As reviewed here, chronic high WSS not only stimulates adaptive outward remodeling, but also contributes to saccular IA formation (at bifurcation apices or outer curves) and atherosclerotic plaque destabilization (in stenosed vessels). Recent advances in understanding IA pathogenesis have shed new light on the role of high WSS in pathological vascular remodeling. In complex geometries, high WSS can couple with significant spatial WSS gradient (WSSG). A combination of high WSS and positive WSSG has been shown to trigger aneurysm initiation. Since endothelial cells (ECs) are sensors of WSS, we have begun to elucidate EC responses to high WSS alone and in combination with WSSG. Understanding such responses will provide insight into not only aneurysm formation, but also plaque destabilization and other vascular pathologies and potentially lead to improved strategies for disease management and novel targets for pharmacological intervention.

High Fluid Shear Stress and Spatial Shear Stress Gradients Affect Endothelial Proliferation, Survival, and Alignment

Cerebral aneurysms develop near bifurcation apices, where complex hemodynamics occur: Flow impinges on the apex, accelerates into branches, then slows again distally, creating high wall shear stress (WSS) and positive and negative spatial gradients in WSS (WSSG). Endothelial responses to these kinds of high WSS hemodynamic environments are not well characterized. We examined endothelial cells (ECs) under elevated WSS and positive and negative WSSG using a flow chamber with constant-height channels to create regions of uniform WSS and converging and diverging channels to create positive and negative WSSG, respectively. Cultured bovine aortic ECs were subjected to 3.5 and 28.4Pa with and without WSSG for 24 and 36h. High WSS inhibited EC alignment to flow, increased EC proliferation assessed by bromodeoxyuridine incorporation, and increased apoptosis determined by terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling. These responses to high WSS were either accentuated or ameliorated by WSSG: Positive WSSG (+980Pa/m) inhibited alignment and stimulated proliferation and apoptosis, whereas negative WSSG (-1120Pa/m) promoted alignment and suppressed proliferation and apoptosis. These results demonstrate that ECs discriminate between positive and negative WSSG under high WSS conditions. EC responses to positive WSSG may contribute to pathogenic remodeling that occurs at bifurcations preceding aneurysm formation.

Hemodynamics of Cerebral Aneurysm Initiation: The Role of Wall Shear Stress and Spatial Wall Shear Stress Gradient

Cerebral aneurysms are preferentially located at arterial curvatures and bifurcations that are exposed to major hemodynamic forces, increasingly implicated in the life cycle of aneurysms. By observing the natural history of aneurysm formation from its preaneurysm state, we aimed to examine the hemodynamic microenvironment related to aneurysm initiation at certain arterial segments later developing an aneurysm. The 3 patients included in the study underwent cerebral angiography with 3D reconstruction before a true aneurysm developed. The arterial geometries obtained from the 3D-DSA models were used for flow simulation by using finite-volume modeling. The WSS and SWSSG at the site of the future aneurysm and the flow characteristics of the developed aneurysms were analyzed. The analyzed regions of interest demonstrated significantly increased WSS, accompanied by an increased positive SWSSG in the adjacent proximal region. The WSS reached values of >5 times the temporal average values of the parent vessel, whereas the SWSSG approximated or exceeded peaks of 40 Pa/mm in all 3 cases. All patients developed an aneurysm within 2 years, 1 of which ruptured. The results of this hemodynamic study, in accordance with the clinical follow-up, suggest that the combination of high WSS and high positive SWSSG focused on a small segment of the arterial wall may have a role in the initiation process of aneurysm formation.

Application of a locally conservative Galerkin (LCG) method for modelling blood flow through a patient‐specific carotid bifurcation

AbstractIn the present work, blood flow through a patient‐specific carotid bifurcation is thoroughly analysed. A locally conservative Galerkin spatial discretization is applied along with an artificial compressibility and characteristic‐based split scheme to solve the 3D incompressible Navier–Stokes equations. Boundary layer meshes are introduced to accurately resolve high near‐wall velocity gradients inside a patient‐specific carotid bifurcation. A total of six haemodynamic wall parameters have been brought together to analyse the regions of possible atherogenesis within the domain. The results show that wall shear stress (WSS) is high (6–15 Pa) near the apex, along with a small region where WSS exceeded 20 Pa. This peak WSS region is close to the inner wall of the external carotid artery (ECA). It is also clear from the results that low WSS occurred in the common carotid artery (CCA). High oscillatory shear occurred in the CCA distal to a local narrowing of the internal carotid artery and along the outer wall, indicating a potential region of atherogenesis. The highest values of wall shear stress angle deviation and wall shear stress angle gradient occur at the apex. The wall shear stress temporal gradient reached 4000 Pa/s near the apex, closer to the ECA. Wall shear stress spatial gradient distribution corresponded with the WSS distribution, with a maximum occurring at the apex. Copyright © 2010 John Wiley & Sons, Ltd.

Numerical simulation of the haemodynamics in end‐to‐side anastomoses

AbstractIn this paper, the commercial CFD package Ansys workbench 11 was used to analyse the three‐dimensional haemodynamics of a typical stenotic Coronary Artery Bypass Grafting (CABG). Two end‐to‐side CABG configurations with anastomosis angle of 20∘ and 40∘ and graft–artery diameter ratios of 1/0.6, 1/1 and 1/1.6 were examined. The flow measurements from in vitro Doppler guide wire technique acquired in left interior mammary artery (LIMA) and grafted to the left anterior descending artery (LAD) were used to impose the physiologically flow conditions at proximal and distal CABG inlet and outlet, respectively. The blood flow was considered to be incompressible, pulsatile, Newtonian, and laminar rheology. The main objective was to determine the effect of anastomosis angle and graft–artery diameter ratio on the flow patterns and the long‐term functionality of the graft. In analysing the results, the distributions of temporal and spatial wall shear stress (WSS) gradient and oscillating shear index (OSI) in the critical regions of CABG such as heel, toe and the centre of the junction were presented and the vortex motions and the occurrence of recirculation zones were examined. The findings showed asymmetrically disturbed flows in the localized regions of the proximal and distal host artery for all models considered and the movement of the recirculation zones from heel to toe was found to depend on the time at the cardiac cycle. These regions are known as susceptible sites to thrombosis and re‐stenosis due to their association with low values of WSS. Copyright © 2010 John Wiley & Sons, Ltd.