Multidirectional Wall Shear Stress Research Articles

Agreement of wall shear stress distribution between two core laboratories using three-dimensional quantitative coronary angiography.

Wall shear stress (WSS) estimated in models reconstructed from intravascular imaging and 3-dimensional-quantitative coronary angiography (3D-QCA) data provides important prognostic information and enables identification of high-risk lesions. However, these analyses are time-consuming and require expertise, limiting WSS adoption in clinical practice. Recently, a novel software has been developed for real-time computation of time-averaged WSS (TAWSS) and multidirectional WSS distribution. This study aims to examine its inter-corelab reproducibility. Sixty lesions (20 coronary bifurcations) with a borderline negative fractional flow reserve were processed using the CAAS Workstation WSS prototype to estimate WSS and multi-directional WSS values. Analysis was performed by two corelabs and their estimations for the WSS in 3mm segments across each reconstructed vessel was extracted and compared. In total 700 segments (256 located in bifurcated vessels) were included in the analysis. A high intra-class correlation was noted for all the 3D-QCA and TAWSS metrics between the estimations of the two corelabs irrespective of the presence (range: 0.90-0.92) or absence (range: 0.89-0.90) of a coronary bifurcation, while the ICC was good-moderate for the multidirectional WSS (range: 0.72-0.86). Lesion level analysis demonstrated a high agreement of the two corelabls for detecting lesions exposed to an unfavourable haemodynamic environment (WSS > 8.24Pa, κ = 0.77) that had a high-risk morphology (area stenosis > 61.3%, κ = 0.71) and were prone to progress and cause events. The CAAS Workstation WSS enables reproducible 3D-QCA reconstruction and computation of WSS metrics. Further research is needed to explore its value in detecting high-risk lesions.

Risk evaluation of type B aortic dissection based on WSS-based indicators distribution in different types of aortic arch

Background and ObjectiveThe underlying mechanism of aortic dissection (AD) remains unclear and the onset of AD is still unpredictable. Although clinical study with statistical analysis has reported that type III aortic arch may have strong correlation with type B AD (TBD), the effects of different arch types on the wall shear stress (WSS) have not been clarified. MethodsAs a complementary work, this study numerically investigated the distribution of five WSS-based indicators in thirty aortic arches without AD, which were classified into three groups based on the arch types. ResultsThe distribution of most WSS indicators, such as time averaged WSS (TAWSS), oscillatory shear index (OSI) and relative residence time (RRT) had no significant difference among different types of aortic arches (P>0.05). However, a multidirectional WSS index, namely CFI, was found its maximum value was positively correlated with type III aortic arch in proximal descending aorta (p<0.001, r = 0.65). ConclusionsIt can be concluded that the enhancement or oscillation of WSS may not be the main reason of TBD is prevalence in type III arches, while the multidirectional WSS distribution may be an important factor. It can be further referred that the CFI may have a potential to predict the onset of TBD.

Smooth muscle cells affect differential nanoparticle accumulation in disturbed blood flow-induced murine atherosclerosis.

Atherosclerosis is a lipid-driven chronic inflammatory disease that leads to the formation of plaques in the inner lining of arteries. Plaques form over a range of phenotypes, the most severe of which is vulnerable to rupture and causes most of the clinically significant events. In this study, we evaluated the efficacy of nanoparticles (NPs) to differentiate between two plaque phenotypes based on accumulation kinetics in a mouse model of atherosclerosis. This model uses a perivascular cuff to induce two regions of disturbed wall shear stress (WSS) on the inner lining of the instrumented artery, low (upstream) and multidirectional (downstream), which, in turn, cause the development of an unstable and stable plaque phenotype, respectively. To evaluate the influence of each WSS condition, in addition to the final plaque phenotype, in determining NP uptake, mice were injected with NPs at intermediate and fully developed stages of plaque growth. The kinetics of artery wall uptake were assessed in vivo using dynamic contrast-enhanced magnetic resonance imaging. At the intermediate stage, there was no difference in NP uptake between the two WSS conditions, although both were different from the control arteries. At the fully-developed stage, however, NP uptake was reduced in plaques induced by low WSS, but not multidirectional WSS. Histological evaluation of plaques induced by low WSS revealed a significant inverse correlation between the presence of smooth muscle cells and NP accumulation, particularly at the plaque-lumen interface, which did not exist with other constituents (lipid and collagen) and was not present in plaques induced by multidirectional WSS. These findings demonstrate that NP accumulation can be used to differentiate between unstable and stable murine atherosclerosis, but accumulation kinetics are not directly influenced by the WSS condition. This tool could be used as a diagnostic to evaluate the efficacy of experimental therapeutics for atherosclerosis.

In-Stent Restenosis Progression in Human Superficial Femoral Arteries: Dynamics of Lumen Remodeling and Impact of Local Hemodynamics

In-stent restenosis (ISR) represents a major drawback of stented superficial femoral arteries (SFAs). Motivated by the high incidence and limited knowledge of ISR onset and development in human SFAs, this study aims to (i) analyze the lumen remodeling trajectory over 1-year follow-up period in human stented SFAs and (ii) investigate the impact of altered hemodynamics on ISR initiation and progression. Ten SFA lesions were reconstructed at four follow-ups from computed tomography to quantify the lumen area change occurring within 1-year post-intervention. Patient-specific computational fluid dynamics simulations were performed at each follow-up to relate wall shear stress (WSS) based descriptors with lumen remodeling. The largest lumen remodeling was found in the first post-operative month, with slight regional-specific differences (larger inward remodeling in the fringe segments, p < 0.05). Focal re-narrowing frequently occurred after 6 months. Slight differences in the lumen area change emerged between long and short stents, and between segments upstream and downstream from stent overlapping portions, at specific time intervals. Abnormal patterns of multidirectional WSS were associated with lumen remodeling within 1-year post-intervention. This longitudinal study gave important insights into the dynamics of ISR and the impact of hemodynamics on ISR progression in human SFAs.

Abstract WMP36: Wall Shear Stress Disturbances May Be Key Requirements for Cerebral Aneurysm Growth: Computational Flow Dynamic Analysis of 15 Cases in NHO CFD ABO Study

Introduction: In 2013, we conducted a multi-institutional prospective observational study in order to identify hemodynamic environments involved in the rupture and growth of unruptured cerebral aneurysms by computational fluid dynamic (CFD) analysis (National Hospital Organization CFD ABO Study: UMIN000013584). There were 461 cases registered and observed for 3 years on the condition that 3DCTA and carotid echocardiography were performed every year. The observation period ended at the end of March this year. There were 32 cases that enlarged, and 209 cases that did not enlarge or rupture after 3 years of observation period. Here, 15 growing cases and 15 non-growing cases were hemodynamically evaluated. Methods: Pulsatile blood flow was simulated using ANSYS-CFX, based on the Navier-Stokes equations for incompressible fluid. Multivariate regression analysis was performed to find differences between growing and non-growing aneurysms in wall shear stress (WSS) magnitude-based metrics (WSS, WSSG, NWSS, NWSSG) and WSS disturbance-based metrics (OSI as a metric for unidirectional WSS disturbance, NtransWSS as a metric for multi-directional WSS disturbance)on the CFD modelling after adjustment for age, sex, hypertension, smoking history, and aneurysm size and location. Results and Conclusions: In the growing and non-growing aneurysms, the average age was 71.8 ± 12.6 and 66.3 ± 11.1 years, the maximum diameter 5.48 ± 2.64 and 5.47 ± 1.85 mm, female 10 and 6 cases, HT 10 and 10, smoking 6 and 11, respectively. Both OSI (p=0.0215) and NtransWSS (p=0.0428) were significantly higher in growing aneurysms compared to non-growing ones, whereas there were no significant differences in WSS magnitude-based metrics(figure). The data suggested that WSS disturbances may be closely associated with the growth of cerebral aneurysms.

The influence of multidirectional shear stress on plaque progression and composition changes in human coronary arteries.

Local wall shear stress (WSS) plays an important role in the onset of atherosclerotic plaque formation; however, it does not fully explain plaque progression and destabilisation. We aimed to investigate for the first time the influence of multidirectional WSS features on plaque progression and plaque composition changes in human coronary arteries. Coronary artery imaging using biplane angiography and virtual histology intravascular ultrasound (VH-IVUS) was performed in twenty patients with coronary artery disease at baseline and after six-month follow-up. Three-dimensional surfaces of the coronary arteries were generated using the coronary imaging and, together with patient-specific flow measurements, different WSS features (multidirectional and conventional time-averaged WSS [TAWSS]) were determined at baseline using computational fluid dynamics (CFD). The changes in plaque component area over the six-month period were determined from VH-IVUS. Changes in plaque composition rather than plaque size were primarily associated with the (multidirectional) WSS at baseline. Interestingly, regions simultaneously exposed to low TAWSS and low multidirectional WSS showed the greatest plaque progression (p<0.001). In this patient study, several multidirectional WSS features were found to contribute significantly to coronary plaque progression and changes in plaque composition.

P3109Coronary vulnerable plaque development is promoted by multidirectional wall shear stress

Abstract Aim Wall shear stress (WSS) has been widely associated with plaque development and destabilization. However, the multidirectionality of WSS, induced by the pulsatile nature of blood flow in combination with the arterial geometry, is rarely taken into account. The purpose of this study was to investigate the influence and predictive value of five (multidirectional) WSS parameters for coronary plaque progression and composition. Methods Familial hypercholesterolemic pigs (n=10, castrated male, 3 years old) were put on a high-fat diet and underwent imaging (near infrared spectroscopy-intravascular ultrasound (NIRS-IVUS), optical coherence tomography (OCT) and CT) of the three main coronary arteries at baseline and 10/12 months follow-up. IVUS-based lumen contours were combined with the centerline of artery as extracted from CT to obtain a 3D reconstruction of the coronary artery. Local flow velocity measurements were combined with the 3D-geometry of the coronary arterial lumen to calculate five multidirectional WSS parameters including: time average wall shear stress (TAWSS), oscilatory shear index (OSI), relative residence time (RRT), trans wall shear stress (TransWSS), cross flow index (CFI). For the analysis, arteries were divided into 3mm/45° sectors (n=3627). Per vessel each segment was classified as low, mid or high for each WSS metric based on the average value in the sector. Changes in wall thickness (WT) and plaque composition were assessed with NIRS-IVUS and OCT, and histology and related to the local (multidirectional) WSS. Results Half of the pigs developed lumen intruding, complex, lipid-rich plaques. In these pigs, coronary segments exposed to low baseline levels of TAWSS exhibited a significantly larger plaque growth per month compared to regions with either mid or high TAWSS (p&lt;0.05, see figure). Furthermore, plaque growth correlated positively with the multidirectional WSS metrics OSI, RRT and CFI, with high multidirectionality resulting in the largest plaque growth (see figure). The positive predictive values (PPV) of the WSS metrics for plaque presence (WT&gt;0.5mm) at follow up were 50% (low TAWSS), 48% (high OSI), 49% (high RRT), 47% (high CFI) and 43% (high transWSS). The PPVs for the presence of a fibroatheroma observed with histology were 61% (low TAWSS), 58% (high OSI), 61% (high RRT), 59% (high CFI) and 49% (high transWSS). Plaque growth vs. multidirectional WSS Conclusions This study shows that both low and multidirectional WSS promote the development of large and complex coronary atherosclerotic plaques with vulnerable characteristics. The high predictive values for fibrous cap atheroma development demonstrate the potential of multidirectional WSS metrics as a predictive clinical marker for vulnerable disease. Acknowledgement/Funding ERC- starter grant (grant agreement 310457)

P3588The synergistic effect of NIRS-detected lipid-rich plaque and 5 different multidirectional wall shear stress metrics on human coronary plaque growth

Abstract Introduction Local wall shear stress (WSS) metrics, high local lipid levels (as detected by near-infrared spectroscopy (NIRS)), as well as systemic lipid levels, have been individually associated with atherosclerotic disease progression. However, a possible synergistic effect remains to be elucidated. This study is the first study to combine WSS metrics with NIRS-detected local lipid content to investigate a potential synergistic effect on plaque progression in human coronary arteries. Methods The IMPACT study is a prospective, single centre study investigating the relation between atherosclerotic plaque progression and WSS in human coronary arteries. Patients with ACS treated with PCI were included. At baseline and after 1-year follow-up, patients underwent near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) imaging and intravascular doppler flow measurements of at least one non-culprit coronary artery. After one month, a CT angiography was made. CT derived centreline combined with IVUS lumen contours resulted in a 3D reconstruction of the vessel. The following WSS metrics were computed using computational fluid dynamics applying the vessel specific invasive flow measurements: time-average wall shear stress (TAWSS), relative residence time (RRT), cross-flow index, oscillatory shear index and transverse wall shear stress. Low TAWSS is known as pro atherogenic, in contrast to all the other shear stress metrics, at which a high magnitude is pro-atherogenic. The arteries were divided into 1.5mm/45° sectors. Based on NIRS-IVUS, wall thickness change over time was determined and NIRS positive sectors detected. Furthermore, per vessel the shear stress was divided into tertiles (low, intermediate, high). To investigate the synergistic effect of local lipids on shear stress related plaque growth, wall thickness change over time was related to the different shear stress metrics comparing the NIRS-positive with the NIRS-negative sectors. Results 15 non-culprit coronary arteries from the first 14 patients were analyzed (age 62±10 years old and 92.9% male). A total of 2219 sectors were studied (5.2%, N=130, NIRS-positive) for wall thickness changes. After studying all five shear stress metrics, we found for TAWSS and RRT that presence of lipids, as detected by NIRS, amplified the effect of shear stress on plaque progression (see figure). Sectors presenting with lipid-rich plaque, compared to NIRS-negative sectors, showed more progression when they were exposed to low TAWSS (p=0.07) or high RRT (p=0.012) and more regression in sectors exposed to high TAWSS (p=0.10) or low RRT (p=0.06). Delta wall thickness vs shear stress Conclusion We presented the first preliminary results of the IMPACT study, showing the synergistic effect of lipid rich plaque and shear stress on plaque progression. Therefore, intravascular lipid-rich plaque (NIRS) assessment has added value to shear stress profiling for the prediction of plaque growth, leading to improved risk stratification. Acknowledgement/Funding ERC starting grant 310457

The effect of multidirectional wall shear stress on plaque characteristics: delving deeper into local shear stress metrics.

The effect of multidirectional wall shear stress on plaque characteristics: delving deeper into local shear stress metrics.

Coronary Vulnerable Plaque Development Is Promoted By Multidirectional Wall Shear Stress – A Pre-Clinical Imaging Study

Coronary Vulnerable Plaque Development Is Promoted By Multidirectional Wall Shear Stress – A Pre-Clinical Imaging Study

Differences in Cerebral Aneurysm Rupture Rate According to Arterial Anatomies Depend on the Hemodynamic Environment.

Cerebral aneurysms have significantly different rupture rates depending on their size and location. The mechanisms underlying these differences are unclear. We examined whether anatomic rupture risks are dependent on the hemodynamic environment on the aneurysmal surface. Patient-specific geometries and flow rates of 84 cerebral aneurysms (42 anterior communicating artery and 42 MCA aneurysms) were acquired from our clinical study, the Computational Fluid Dynamics Analysis of Blood Flow in Cerebral Aneurysms: Prospective Observational Study. Pulsatile blood flow was simulated to calculate hemodynamic metrics with special attention to wall shear stress magnitude and temporal disturbance. Multivariate analyses were performed to identify associations between hemodynamic metrics and known rupture predictors (age, sex, hypertension, smoking history, location, and size). All the wall shear stress magnitude-based metrics showed a significant negative association with size and location (P < .03), but not other risk factors. All the wall shear stress disturbance-based metrics were significantly related to size (P < .001). Only normalized transverse wall shear stress, a metric for multidirectional wall shear stress disturbance, was related to location (P = .03). The normalized transverse wall shear stress had the highest odds ratio for location and size among hemodynamic metrics (odds ratios, 1.275 and 1.579; 95% confidence intervals, 1.020-1.693 and 1.238-2.219, respectively). Among the arterial geometric parameters, the aspect ratio had the second strongest association with all hemodynamic metrics, after our newly proposed aspect ratio-asphericity index. The differences in aneurysm rupture rates according to size and location may reflect differences in hemodynamic environments in qualitatively different ways. An enhanced multidirectional wall shear stress disturbance may be especially associated with aneurysm rupture.

Study of the effect of stenosis severity and non-Newtonian viscosity on multidirectional wall shear stress and flow disturbances in the carotid artery using particle image velocimetry

The development of atherosclerosis at the carotid bifurcation is impacted by local variations in wall shear stress (WSS) magnitude and direction, as well as flow complexity within the vessel. In this study, stereoscopic particle image velocimetry (PIV) was used to investigate multidirectional WSS and disturbed flow for idealized models of the carotid bifurcation with varying eccentric stenosis of the internal carotid artery (ICA) and both Newtonian (N-fluid) and non-Newtonian (nN-fluid) blood analogues. Turbulence intensity (TI) was reduced with the nN-fluid compared to N-fluid for mild to moderate stenosis, and comparable for more severely stenosed (70%) models. Differences in maximum TI due to viscosity model ranged from 0.02 m/s to 0.06 m/s compared to much larger differences due to geometry of up to 0.29 m/s between mild and severe stenosis. The level of time-averaged WSS (TAWSS) increased with stenosis severity from 5 Pa to 32 Pa, and nN-fluid led to higher WSS on average than N-fluid counterparts. Regions of elevated oscillatory shear index (OSI) demarcated recirculation regions, and mean OSI in the ICA branch was reduced for nN-fluid models by 9–19% compared to N-fluid. Transverse WSS (transWSS) increased with WSS magnitude and again was higher in nN-fluid models. Surface area exposure to shear metrics indicated that a Newtonian viscosity assumption predicted larger regions of low and oscillatory WSS, while predicting reduced regions of high transWSS, in comparison to the more physiological shear thinning fluid.

Multidirectional WSS disturbances in stenotic turbulent flows: A pre- and post-intervention study in an aortic coarctation

Wall shear stress (WSS) disturbances are commonly expressed at sites of abnormal flow obstructions and may play an essential role in the pathogenesis of various vascular diseases. In laminar flows these disturbances have recently been assessed by the transverse wall shear stress (transWSS), which accounts for the WSS multidirectionality. Site-specific estimations of WSS disturbances in pulsatile transitional and turbulent type of flows are more challenging due to continuous and unpredictable changes in WSS behavior. In these complex flow settings, the transWSS may serve as a more comprehensive descriptor for assessing WSS disturbances of general nature compared to commonly used parameters. In this study large eddy simulations (LES) were used to investigate the transWSS properties in flows subjected to different pathological turbulent flow conditions, governed by a patient-specific model of an aortic coarctation pre and post balloon angioplasty. Results showed that regions of strong near-wall turbulence were collocated with regions of elevated transWSS and turbulent WSS, while in more transitional-like near-wall flow regions a closer resemblance was found between transWSS and low, and oscillatory WSS. Within the frame of this study, the transWSS parameter demonstrated a more multi-featured picture of WSS disturbances when exposed to different types of flow regimes, characteristics which were not depicted by the other parameters alone.

A rational approach to defining principal axes of multidirectional wall shear stress in realistic vascular geometries, with application to the study of the influence of helical flow on wall shear stress directionality in aorta

The distribution of arterial lesions is attributed by the prevalent mechanistic theory to the proatherogenic role played by low and oscillatory wall shear stress (WSS). However, discrepancies observed when comparing WSS distribution with location of regions with lesion prevalence challenge this theory and have recently stimulated the idea that a role in endothelial mechanosensing is played by WSS multidirectionality, which could contribute to explain the observed discrepancies.Here an approach is presented for analyzing the multidirectional nature of WSS in complex vascular geometries. Using an essential geometric attribute of the vessel (its centerline), the local WSS vector is projected along an “axial” direction (aligned with the tangent to the vessel׳s centerline), and “secondary” direction (orthogonal to centerline׳s tangent), which is related to secondary flow. The WSS projection scheme is applied: (1) to a realistic computational hemodynamic model of human aorta, with the aim to come up with a plausibility checking regarding its consistency; and (2) to investigate if an aortic hemodynamics characterized by different amount and topology of helical flow (HF) could influence WSS directionality.The projection scheme confirmed its consistency and plausibility in realistic arterial geometries and allowed to get insight into the relationship between aortic intravascular fluid structures and WSS directionality. The findings of this study clearly show the potential of the projection scheme as quantitative tool for an in depth investigation of the WSS multidirectional nature. The proposed approach enriches the arsenal of tools available to study and exploit the role played by local hemodynamics in vascular disease.