Abnormal Wall Shear Stress Research Articles

Impact of peripheral venoarterial extracorporeal membrane oxygenation support for heart failure on systemic hemodynamics and aortic blood flow

Peripheral venoarterial extracorporeal membrane oxygenation (VA-ECMO) is an advanced temporary life support system for patients with refractory cardiogenic shock or severe cardiopulmonary failure. However, the reperfusion of oxygenated blood into the arterial system via a peripheral artery will induce substantial hemodynamic changes that might contribute to the development of complications. In this study, we developed two types of computational models to quantify the hemodynamic changes induced by the peripheral VA-ECMO support for systolic heart failure (HF) of various severities. One was a lumped-parameter model used for exploring the optimal workload of extracorporeal membrane oxygenation (ECMO) for a specific severity of HF, whereas the other one was a geometrical multiscale model capable of simulating the detailed flow field in the aorta while accounting for the hemodynamic coupling of VA-ECMO with the cardiovascular system. Numerical results revealed that the retrograde transmission of ECMO-supplied blood flow toward the heart not only considerably inhibited cardiac output but also induced marked flow disturbance and regionally high or oscillatory wall shear stress (WSS) in the aorta that may increase the risk of thrombosis and vascular dysfunction. The major characteristics of flow disturbance and spatial distribution of abnormal WSS were codetermined by the cardiac function and workload of ECMO while less influenced by the morphology of aorta. These findings emphasized the importance of tuning the workload of ECMO based on patient-specific cardiac function to balance the amount of blood oxygenation support by ECMO against the risk of complications associated with hemodynamic abnormalities.

Advances in the Computational Assessment of Disturbed Coronary Flow and Wall Shear Stress: A Contemporary Review.

Coronary artery blood flow is influenced by various factors including vessel geometry, hemodynamic conditions, timing in the cardiac cycle, and rheological conditions. Multiple patterns of disturbed coronary flow may occur when blood flow separates from the laminar plane, associated with inefficient blood transit, and pathological processes modulated by the vascular endothelium in response to abnormal wall shear stress. Current simulation techniques, including computational fluid dynamics and fluid-structure interaction, can provide substantial detail on disturbed coronary flow and have advanced the contemporary understanding of the natural history of coronary disease. However, the clinical application of these techniques has been limited to hemodynamic assessment of coronary disease severity, with the potential to refine the assessment and management of coronary disease. Improved computational efficiency and large clinical trials are required to provide an incremental clinical benefit of these techniques beyond existing tools. This contemporary review is a clinically relevant overview of the disturbed coronary flow and its associated pathological consequences. The contemporary methods to assess disturbed flow are reviewed, including clinical applications of these techniques. Current limitations and future opportunities in the field are also discussed.

Assessment of abnormal transvalvular flow and wall shear stress direction for pediatric/young adults with bicuspid aortic valve: a cross-sectional 4D flow study

BackgroundAortic dilation is seen in pediatric/young adult patients with bicuspid aortic valve (BAV), and hemodynamic markers to predict aortic dilation are necessary for monitoring. Although promising hemodynamic metrics, such as abnormal wall shear stress (WSS) magnitude, have been proposed for adult BAV patients using 4D flow cardiovascular magnetic resonance, those for pediatric BAV patients have less frequently been reported, partly due to scarcity of data to define normal WSS range. To circumvent this challenge, this study aims to investigate if a recently proposed 4D flow-based hemodynamic measurement, abnormal flow directionality, is associated with aortic dilation in pediatric/young adult BAV patients. Methods4D flow scans for BAV patients (<20 years old) and age-matched controls were retrospectively enrolled. Static segmentation for the aorta and pulmonary arteries was obtained to quantify peak systolic hemodynamics and diameters in the proximal aorta. In addition to peak velocity, wall shear stress (WSS), vorticity, helicity, and viscous energy loss, direction of aortic velocity and WSS in BAV patients was compared with that of control atlas using registration technique; angle differences of >60deg and >120deg were defined as moderately and severely abnormal, respectively. Association between the obtained metrics and normalized diameters (Z-scores) were evaluated at the sinotubular junction, mid ascending aorta, and distal ascending aorta. ResultsFifty-three BAV patients, including eighteen with history of repaired aortic coarctation, and seventeen controls were enrolled. Correlation between moderately abnormal velocity/WSS direction and aortic Z-scores was moderate to strong at the sinotubular junction and mid ascending aorta (R=0.62-0.81; p<0.001) while conventional measurements exhibited weaker correlation (|R|=0.003-0.47, p=0.009-0.99) in all subdomains. Multivariable regression analysis found moderately abnormal velocity direction and existence of aortic regurgitation (only for isolated BAV group) were independently associated with mid ascending aortic Z-scores. ConclusionAbnormal velocity and WSS directionality in the proximal aorta was strongly associated with aortic Z-scores in pediatric/young adult BAV patients.

Experimental study on hemodynamics of an end-to-side anastomosis

A three-dimensional and three-component velocity measurement on the flow field in a 45° end-to-side anastomosis model is conducted to investigate the hemodynamics, which is an important factor to the intimal hyperplasia formation and graft failure after surgery. Thanks to the advanced volumetric measurement technology of tomographic particle image velocimetry, the recirculation zone, low-speed region, and the spiral flow structures can be visualized. As a result, the flow field of three cases with the local maximum velocity of 0.15, 0.8, and 1.4 m/s are visible and the inlet velocity profile tends to be skewed as the flow rate increases. The mean vorticity contours indicate that the positive vortex center rotates 6.47°, 50.23°, and 90.4° and the negative vortex center rotates 20.44°, 15.73°, and 68.47°, respectively, in three cases. The instantaneous vortex structures identified by the λci criterion demonstrate two large-scale vortex structures in the distal section. The two vortices have the tendency to intertwine while one of them decays earlier. The wall shear stress (WSS) distributions on the entire model with the local maximum of 0.8, 5.8, and 13.8 Pa in three cases have been quantitatively achieved. The abnormal WSS and WSS gradient can help localize risk areas and understand the intimal hyperplasia formation. A detailed illustration of hemodynamics inside the 45° end-to-side anastomosis model has been provided, which demonstrates more comprehensive large-scale flow structures and abnormal WSS regions. Combined with the information of flow structures and WSS distribution, the understanding of the hemodynamics in the anastomosis can be strengthened.

Kiosk 2R-TC-04 - Assessment of Abnormal Transvalvular Flow and Wall Shear Stress for Pediatric/young Adults with Bicuspid Aortic Valve: A Cross-sectional 4D Flow Study

Kiosk 2R-TC-04 - Assessment of Abnormal Transvalvular Flow and Wall Shear Stress for Pediatric/young Adults with Bicuspid Aortic Valve: A Cross-sectional 4D Flow Study

Detection of Abnormal Wall Shear Stress and Oscillatory Shear Index via Ultrasound Vector Flow Imaging as Possible Indicators for Arteriovenous Fistula Stenosis in Hemodialysis.

The arteriovenous fistula (AVF) is an essential vascular access for hemodialysis patients. AVF stenosis may occur at sites with abnormal wall shear stress (WSS) and oscillatory shear index (OSI), which are caused by the complex flow in the AVF. At present, an effective method for rapid determination of the WSS and OSI of the AVF is lacking. The objective of this study was to apply an ultrasound-based method for determination of the WSS and OSI to explore the risk sites of the AVF. In this study, the ultrasound vector flow imaging technique V Flow was applied to measure the WSS and OSI at four different regions of the AVF to detect and analyze the risk sites: (i) anastomosis region, (ii) curved region, (iii) proximal vein and (iv) distal vein. Twenty-one patients were included in this study. The relative residence time was calculated based on the measured WSS and OSI. The curved region had the lowest WSS; the anastomosis region had a significantly higher OSI (p < 0.05) compared with the venous regions, and the curved region had a significantly higher RRT (p < 0.05) compared with the proximal vein region. V Flow is a feasible tool for studying WSS variations in AVF. The possible risk site in the AVF may be located in the anastomosis and curved regions, where the latter could present a higher risk for AVF stenosis.

Abnormal Wall Shear Stress Area is Correlated to Coronary Artery Bypass Graft Remodeling 1 Year After Surgery.

Coronary artery bypass graft surgery is a common intervention for coronary artery disease; however, it suffers from graft failure, and the underlying mechanisms are not fully understood. To better understand the relation between graft hemodynamics and surgical outcomes, we performed computational fluid dynamics simulations with deformable vessel walls in 10 study participants (24 bypass grafts) based on CT and 4D flow MRI one month after surgery to quantify lumen diameter, wall shear stress (WSS), and related hemodynamic measures. A second CT acquisition was performed one year after surgery to quantify lumen remodeling. Compared to venous grafts, left internal mammary artery grafts experienced lower abnormal WSS (< 1Pa) area one month after surgery (13.8 vs. 70.1%, p = 0.001) and less inward lumen remodeling one year after surgery (- 2.4% vs. - 16.1%, p = 0.027). Abnormal WSS area one month post surgery correlated with percent change in graft lumen diameter one year post surgery (p = 0.030). This study shows for the first time prospectively a correlation between abnormal WSS area one month post surgery and graft lumen remodeling 1year post surgery, suggesting that shear-related mechanisms may play a role in post-operative graft remodeling and might help explain differences in failure rates between arterial and venous grafts.

Wall Shear Stress Differences Between Arterial and Venous Coronary Artery Bypass Grafts One Month After Surgery.

Although coronary artery bypass graft (CABG) surgery is a well-established intervention, graft failure can occur, and the underlying mechanisms remain incompletely understood. The purpose of this prospective study is to utilize computational fluid dynamics (CFD) to investigate how graft hemodynamics one month post surgery may vary among graft types, which have different long-term patency rates. Twenty-four grafts from 10 participants (64.6 ± 8.5years, 9 men) were scanned with coronary CT angiography and 4D flow MRI one month after CABG surgery. Grafts included 10 left internal mammary arteries (LIMA), 3 radial arteries (RA), and 11 saphenous vein grafts (SVG). Image-guided CFD was used to quantify blood flow rate and wall area exposed to abnormal wall shear stress (WSS). Arterial grafts had a lower abnormal WSS area than venous grafts (17.9% vs. 70.1%; p = 0.001), and a similar trend was observed for LIMA vs. SVG (13.8% vs. 70.1%; p = 0.001). Abnormal WSS area correlated positively to lumen diameter (p < 0.001) and negatively to flow rate (p = 0.001). This CFD study is the first of its kind to prospectively reveal differences in abnormal WSS area 1month post surgery among CABG types, suggesting that WSS may influence the differential long-term graft failure rates observed among these groups.

Semi-Automatic Planning and Three-Dimensional Electrospinning of Patient-Specific Grafts for Fontan Surgery.

This paper proposes a semi-automatic Fontan surgery planning method for designing and manufacturing hemodynamically optimized patient-specific grafts. Fontan surgery is a palliative procedure for patients with a single ventricle heart defect by creating a new path using a vascular graft for the deoxygenated blood to be directed to the lungs, bypassing the heart. However, designing patient-specific grafts with optimized hemodynamic performance is a complex task due to the variety of patient-specific anatomies, confined surgical planning space, and the requirement of simultaneously considering multiple design criteria for vascular graft optimization. To address these challenges, we used parameterized Fontan pathways to explore patient-specific vascular graft design spaces and search for optimal solutions by formulating a nonlinear constrained optimization problem, which minimizes indexed power loss (iPL) of the Fontan model by constraining hepatic flow distribution (HFD), percentage of abnormal wall shear stress (%WSS) and geometric interference between Fontan pathways and the heart models (InDep) within clinically acceptable thresholds. Gaussian process regression was employed to build surrogate models of the hemodynamic parameters as well as InDep and [Formula: see text] (conduit model smoothness indicator) for optimization by pattern search. We tested the proposed method on two patient-specific models (n=2). The results showed the automatically optimized (AutoOpt) Fontan models hemodynamically outperformed or at least are comparable to manually optimized Fontan models with significantly reduced surgical planning time (15 hours versus over 2 weeks). We also demonstrated feasibility of manufacturing the AutoOpt Fontan conduits by using electrospun nanofibers.

Abnormal aortic hemodynamics at predilection sites for dissection in patients with Marfan Syndrome: a 4D flow study

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): AMC Foundation Horstingstuit Foundation Introduction Patients with Marfan syndrome (MFS) may develop aneurysmatic dilatation and dissection of the aorta with a consequence of sudden death at relatively young age. We performed an aortic 4D flow MRI analysis, providing a comprehensive quantification and visualization of abnormal aortic velocity and wall shear stress (WSS) magnitude and direction with recently developed techniques (1,2). We hypothesize that abnormal hemodynamics are found at predilection sites for aortic dissection in MFS patients. Methods This prospective study included 56 MFS patients and 25 healthy subjects as controls. Aortic 4D flow MRI was performed on a 3T Philips Ingenia system (Best, Netherlands). The aorta was manually segmented on time-averaged phase contrast MR angiogram images (phase contrast images multiplied by absolute velocity) by thresholding, watershed, and manual voxel in-/exclusion. The segmentations were used to mask the velocities, calculate WSS, and co-registration for quantification of abnormal hemodynamics (3). Abnormally elevated velocity and WSS were defined as higher than the three-dimensional 95% confidence interval as determined in the control group. Abnormally directed velocity and WSS were defined as vector angle differences higher than 120°. The aorta was subdivided in six regions of interest (ROIs) for total multiple linear regression with age, aortic diameter, and blood pressure characteristics. Independent predictors were defined as characteristics that were significant in the total model. Significance was defined as p &amp;lt; 0.05 with Bonferonni correction. The 3D-maps with abnormal hemodynamics were co-registered and added to create 3D-maps that show the incidence of abnormal hemodynamics. Results Figure 1 shows examples of maps with abnormal velocity and WSS magnitude and direction respectively. Ascending elevated velocity was associated with age, aortic diameter and blood pressure characteristics, whereas elevated WSS was associated with blood pressure characteristics only. No independent predictors were found for abnormally directed hemodynamics. Figure 2 shows the incidence maps for abnormally elevated velocity and abnormally directed WSS in two patients. The maximum incidence for elevated velocity and WSS were 32% and 20%, respectively, and found in the ascending aorta. The maxima for abnormally directed velocity and WSS were 18% and 39%, respectively, and found in the inner proximal descending aorta. Conclusion Altered aortic geometry and wall properties in MFS patients cause detectable hemodynamic effects in 30% of our cohort at known predilection sites for aortic dissection in MFS patients: the ascending aorta and proximal descending aorta. Independent measures of altered hemodynamics could possibly indicate individual patients at risk for aortic dissection.

Bicuspid aortic valve disease is associated with abnormal wall shear stress, viscous energy loss, and pressure drop within the ascending thoracic aorta

Bicuspid aortic valve (BAV) disease has significant gaps in its clinical management practices. To highlight the potential utility of advanced hemodynamic biomarkers in strengthening BAV assessment, we used 4-dimentional flow magnetic resonance imaging to investigate altered hemodynamics in the ascending aorta (AAo).A total of 32 healthy controls and 53 age-matched BAV patients underwent cardiac magnetic resonance imaging at 3T, with cine imaging and 4D-flow. Analysis planes were placed along 3D-segmented aortas at the left ventricular outflow tract (LVOT), sinuses of Valsalva, mid-ascending aorta (MAA), and proximal to the first aortic branch. Locations were analyzed for aortic diameter (normalized to body surface area), pressure drop (PD), viscous energy loss (EL), and wall shear stress (WSS) sub-vectors (axial wall shear stress, circumferential wall shear stress [WSSC], magnitude wall shear stress). Student's t tests, or non-parametric equivalents, compared parameters between cohorts. Univariable and multivariable analyses explored the associations of AAo diameter with hemodynamics within the BAV cohort.Compared to control cohort, BAV patients showed significantly greater PD (MAA: 9.5 ± 8.0 vs 2.8 ± 2.4 mm Hg; P < .01), EL (from LVOT-AA1: 7.39 ± 4.57 mW vs 2.90 ± 1.07 mW; P < .01), and WSSC (MAA: 0.3 ± 0.1 vs 0.2 ± 0.06 Pa; P ≤ .01) throughout the AAo. Correlational analyses revealed an inverse association between AAo diameter and both magnitude wall shear stress and axial wall shear stress.BAV patients exhibited increased PD, EL, and WSSC in the AAo, and an inverse association between AAo diameter and WSS sub-vectors. This demonstrated the impact of PD, EL, and WSS in BAV disease and the importance of altered hemodynamics in aortic remodelling.

Three-Dimensional Reconstruction and Numerical Simulation of Intracranial Aneurysm for Sectional Anatomy Based on Computed Tomography Angiography

Objective: The mortality of rebleeding after ruptured intracranial aneurysms was more than 40%. It is essential to identify the intracranial artery in sectional anatomy. However, it is difficult for students to understand the intracranial artery in the section. Therefore, the purpose of this study is to explore the application effect of three-dimensional (3D) reconstruction and numerical simulation of intracranial aneurysm for sectional anatomy based on computed tomography angiography (CTA). Method: Sixty students in medical imaging specialty of our university were divided into two groups. The control group was taught with conventional sectional anatomy and CT images, while the observation group was taught with 3D reconstruction and numerical simulation of intracranial aneurysm. The teaching characteristics and teaching effects were analyzed and compared between the two groups. Result: The 3D reconstruction can accurately express the size, direction, and adjacent relationship of aneurysms. Through rotation of the 3D image, students can easily understand the name and location of cerebral arteries. Combined with the function of 3D positioning, each blood vessel can automatically and accurately locate in the transverse, coronal, and sagittal plane. Abnormal wall shear stress was easily found in the intersection of cerebral artery circle, which was the physiological basis for the occurrence of aneurysms. There was a high shear zone in the root of an aneurysm, which was the physiological factor of rupture. The scores of sectional specimen identification, drawing examination, and theoretical assessment in the observation group were significantly higher than those in the control group (P &lt; 0.05). Conclusion: The 3D reconstruction and numerical simulation can directly display the 3D morphological and physiological characteristics of intracranial aneurysms, which is convenient for students to understand and memorize. It can reach a good teaching effect in sectional anatomy.

Fully quantitative mapping of abnormal aortic velocity and wall shear stress direction in patients with bicuspid aortic valves and repaired coarctation using 4D flow cardiovascular magnetic resonance

BackgroundHelices and vortices in thoracic aortic blood flow measured with 4D flow cardiovascular magnetic resonance (CMR) have been associated with aortic dilation and aneurysms. Current approaches are semi-quantitative or when fully quantitative based on 2D plane placement. In this study, we present a fully quantitative and three-dimensional approach to map and quantify abnormal velocity and wall shear stress (WSS) at peak systole in patients with a bicuspid aortic valve (BAV) of which 52% had a repaired coarctation.Methods4D flow CMR was performed in 48 patients with BAV and in 25 healthy subjects at a spatiotemporal resolution of 2.5 × 2.5 × 2.5mm3/ ~ 42 ms and TE/TR/FA of 2.1 ms/3.4 ms/8° with k-t Principal Component Analysis factor R = 8. A 3D average of velocity and WSS direction was created for the normal subjects. Comparing BAV patient data with the 3D average map and selecting voxels deviating between 60° and 120° and > 120° yielded 3D maps and volume (in cm3) and surface (in cm2) quantification of abnormally directed velocity and WSS, respectively. Linear regression with Bonferroni corrected significance of P < 0.0125 was used to compare abnormally directed velocity volume and WSS surface in the ascending aorta with qualitative helicity and vorticity scores, with local normalized helicity (LNH) and quantitative vorticity and with patient characteristics.ResultsThe velocity volumes > 120° correlated moderately with the vorticity scores (R ~ 0.50, P < 0.001 for both observers). For WSS surface these results were similar. The velocity volumes between 60° and 120° correlated moderately with LNH (R = 0.66) but the velocity volumes > 120° did not correlate with quantitative vorticity. For abnormal velocity and WSS deviating between 60° and 120°, moderate correlations were found with aortic diameters (R = 0.50–0.70). For abnormal velocity and WSS deviating > 120°, additional moderate correlations were found with age and with peak velocity (stenosis severity) and a weak correlation with gender. Ensemble maps showed that more than 60% of the patients had abnormally directed velocity and WSS. Additionally, abnormally directed velocity and WSS was higher in the proximal descending aorta in the patients with repaired coarctation than in the patients where coarctation was never present.ConclusionThe possibility to reveal directional abnormalities of velocity and WSS in 3D provides a new tool for hemodynamic characterization in BAV disease.

Bicuspid aortic valve disease associates with abnormal wall shear stress, viscous energy loss, and pressure drop within the ascending thoracic aorta

Abstract Introduction We use 4D Flow MRI to (1) investigate the effects of bicuspid aortic valve (BAV) disease on downstream pressure drop (PD), wall shear stress (WSS), and viscous energy loss (EL) in the ascending aorta (AAo) and (2) explore the associations between AAo diameter and PD, WSS, and EL. Hypothesis BAV patients show increased PD, WSS, and EL in the AAo compared to age-matched controls Methods 32 healthy controls (41±15 y, 10 female) and 53 BAV patients (44±16 y, 19 female) underwent cardiac MRI at 3T, inclusive of cine imaging and 4D flow. Cross sections were placed along segmented aortas at the: left ventricular outflow tract (LVOT), sinuses of Valsalva (SOV), mid-ascending aorta (MAA), and proximal to first aortic branch (AA1). Locations were analyzed for (i) net flow, (ii) aortic diameter (normalized to BSA), (iii) systolic PD (referenced to LVOT), (iv) systolic EL (measured within LVOT-AA1 volume and normalized by LVOT net flow; mW/mL), and (v) systolic WSS. Sub-vectors of WSS, axial (WSSax) and circumferential (WSScirc), were also analyzed. Results In comparison to controls, BAV patients showed greater PD (e.g. MAA: 9.5±8.0 vs. 2.8±2.4mmHg; p&amp;lt;0.01), EL (0.09±0.05 vs. 0.04±0.01 mW/mL; p≤0.01), and WSScirc (e.g. MAA: 0.3±0.1 vs. 0.2±0.06 Pa; p≤0.01) throughout the AAo (Table 1 and Fig. 1). BAV patients exhibited significantly lower WSS and WSSax only at the SOV. In univariate analyses, AAo diameter was inversely correlated with WSS (R=−0.32, p&amp;lt;0.01) and WSSax (R=−0.51, p≤0.01). In multivariate analyses, AAo diameter was associated with WSS (β=−0.36, p&amp;lt;0.01) and WSSax (β=−0.26, p&amp;lt;0.01). Conclusions BAV patients demonstrate significantly increased PD, EL, and WSScirc in the AAo, and an inverse association between AAo diameter and WSS measures. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Alberta Health Services

Patient-Specific Numerical Analysis of Coronary Flow in Children With Intramural Anomalous Aortic Origin of Coronary Arteries

Unroofing surgery for anomalous aortic origin of a coronary artery (AAOCA) alters coronary anatomy by opening the intramural segment so that the anomalous coronary orifice arises perpendicularly from appropriate aortic sinus. Computational fluid dynamics modeling (CFD) allows for quantification of hemodynamics linked to morbidity such as wall shear stress (WSS), relative to patient-specific features like the angle of origin (AO). We hypothesize that CFD will reveal abnormal WSS indices in unroofed arteries that are related to AO. Six AAOCA patients (3 left, 3 right) status post unroofing (median = 13.5 years, range 9-17) underwent cardiac magnetic resonance imaging. CFD models were created from pre (n = 2) and postunroofing (n = 6) cardiac magnetic resonance imaging data, for the anomalous and contralateral normally-arising arteries. Downstream vasculature was represented by lumped parameter networks. Time-averaged WSS (TAWSS) and oscillatory shear index (OSI) were quantified relative to AO and measured hemodynamics. TAWSS was elevated along the outer wall of the normally-arising left vs right coronary arteries, as well as along unroofed left vs right coronary arteries (n = 6/group). No significant differences were noted when comparing unroofed and same-sided normally-arising coronaries. TAWSS was reduced after unroofing (eg, 276 ± 28 dyne/cm2 vs 91 ± 15 dyne/cm2; n = 2/group). Models with more acute preoperative AO indicated lower TAWSS at the proximity of ostium. Differences in OSI were not significant. Different flow patterns exist natively between right and left coronary arteries. Unroofing may normalize TAWSS but with variance related to the AO. This study suggests CFD may help stratify risk in AAOCA.

SRGN, a new identified shear-stress-responsive gene in endothelial cells.

Endothelial cells (ECs) play an important role in the pathogenesis of cardiovascular disease, especially atherosclerosis (AS). The abnormal wall shear stress (WSS) which directly contacts with ECs is the key stimulating factor leading to AS. However, the underlying mechanism of ECs responding to WSS is still incompletely understood. This study aims to explore the novel mechano-sensitive genes and its potential mechanism in response to WSS in ECs by employing bioinformatics methods based on previously available high-throughput data from zebrafish embryos, both before and after blood flow formation. Six common differentially expressed genes (DEGs) (SRGN, SLC12A3, SLC25A4, PVALB1, ITGAE.2, zgc:198419) were selected out from two high-throughput datasets (GSE126617 and GSE20707) in the GEO database. Among them, SRGN was chosen for further verification through the in vitro shear stress loading experiments with human umbilical vein endothelial cells (HUVECs) and the in vivo partial ligation of carotid artery in mice. Our data indicated that low shear stress (LSS) could enhance the expression of SRGN via the PKA/CREB-dependent signaling pathway. The proportion of Ki67+ cells and the concentration of nitric oxide (NO) were high in SRGN high expression cells, suggesting that SRGN may be involved in the proliferation of HUVECs. Furthermore, in the partial ligation of the carotid artery mice model, we observed that the expression of SRGN was significantly increased in atherosclerotic plaques induced by abnormal shear stress. Taken together, this study demonstrated that SRGN is a key gene in the response of ECs to WSS and could be involved in AS.

Determining Haemodynamic Wall Shear Stress in the Rabbit Aorta In Vivo Using Contrast-Enhanced Ultrasound Image Velocimetry

Abnormal blood flow and wall shear stress (WSS) can cause and be caused by cardiovascular disease. To date, however, no standard method has been established for mapping WSS in vivo. Here we demonstrate wide-field assessment of WSS in the rabbit abdominal aorta using contrast-enhanced ultrasound image velocimetry (UIV). Flow and WSS measurements were made independent of beam angle, curvature or branching. Measurements were validated in an in silico model of the rabbit thoracic aorta with moving walls and pulsatile flow. Mean errors over a cardiac cycle for velocity and WSS were 0.34 and 1.69%, respectively. In vivo time average WSS in a straight segment of the suprarenal aorta correlated highly with simulations (PC = 0.99) with a mean deviation of 0.29 Pa or 5.16%. To assess fundamental plausibility of the measurement, UIV WSS was compared to an analytic approximation derived from the Poiseuille equation; the discrepancy was 17%. Mapping of WSS was also demonstrated in regions of arterial branching. High time average WSS (TAWSSxz = 3.4 Pa) and oscillatory flow (OSIxz = 0.3) were observed near the origin of conduit arteries. In conclusion, we have demonstrated that contrast-enhanced UIV is capable of measuring spatiotemporal variation in flow velocity, arterial wall location and hence WSS in vivo with high accuracy over a large field of view.

NUMERICAL SIMULATION OF DILATION PATTERNS OF THE ASCENDING AORTA IN AORTOPATHIES

Aortic dilation is associated with congenital bicuspid aortic valve (BAV) disease, and its etiology is still not completely understood. The aim of this study is to provide further insight into aortic hemodynamics in a BAV population with different degrees of aortic dilation and regurgitation in comparison with a patient without pathology. A fluid–structure interaction (FSI) numerical approach is implemented regarding patient-specific geometries, where the aortic valves are defined by analytical orifices. Results show that, while the patient without pathology displays a typical hemodynamic behavior of flows in bends, BAV-related aortas present an accelerated flow along the outer aortic wall. Wall shear stress (WSS) overload in the outer curvature is observed, more marked in more dilated aortas. Moreover, helices in the ascending aorta are present in these patients, enhanced with greater dilation. These findings support the fact that hemodynamic factors play an important role in aortic dilation onset and development in BAV patients, caused by a prolonged exposure of the outer ascending aortic curvature to altered WSS. Besides, our results suggest that greater aortic regurgitation may be associated with abnormal WSS distributions in the ascending aorta during diastole, which can facilitate aortic root dilation.

A computational fluid dynamics analysis of a patient with acute non-A-non-B aortic dissection after type I hybrid arch repair

The clinical presentation and natural courses in acute non-A-non-B aortic dissection (AD) are quite different from classical acute type A or type B AD, and the benefit of hybrid technique for this clinical scenario has not been validated. By using computational fluid dynamics (CFD) analysis, we aim to investigate a series of hemodynamic-related changes in aortic morphology in a patient who underwent type I hybrid arch repair (HAR). Computed tomographic angiographies (preoperative, one week, one month and one year after HAR) of a 52-year old male patient with arch-entry type acute non-A-non-B dissection were collected. Three-dimensional models were reconstructed by using an image processing package Mimics (materialize). Morphological and hemodynamic parameters of aorta and its branch vessels were analysed. Post-operatively, the false lumen index (FLI) gradually decreased from 2.02 to 0.38 and the curvature of the aortic arch was also reduced. However, the aortic arch lengthened and the diameter of the distal abdominal aorta expanded. In addition, the blood flow gradually became organised and the pressure in the true lumen (TL) increased over time and eventually approximated the pressure in the false lumen (FL). Moreover, the region of the abnormal wall shear stress (WSS) in the TL progressively decreased while the WSS in most areas of the FL remained below 4 dyne/cm2. The blood supply to most of the aortic branches returned to normal at the one-year follow-up. Type I HAR is an effective procedure for patients with acute non-A-non-B aortic dissection in terms of restoring normal blood flow in TL and facilitating positive remodeling of distal aorta. Long-term surveillance and follow-up is mandatory.

Potential Therapeutic Strategies for Intracranial Aneurysms Targeting Aneurysm Pathogenesis.

Subarachnoid hemorrhage resulting from intracranial aneurysms (IAs) is associated with high rates of morbidity and mortality. Although trigger mechanisms in the pathogenesis of IAs have not been fully elucidated, accumulating evidence has demonstrated that inflammation acts as a critical contributor to aneurysm pathogenesis. IAs is initiated by disruption and dysfunction of endothelial cells (ECs) caused by abnormal wall shear stress (WSS). Subsequently, vascular inflammation can trigger a series of biochemical reactions resulting in vascular smooth muscle cell (VSMC) apoptosis and migration, accompanied by inflammatory cell infiltration, secretion of various cytokines, and inflammatory factors. These changes result in degradation of vascular wall, leading to the progression and eventual rupture of IAs. Increasing our knowledge of the pathogenesis of these lesions will offer physicians new options for prevention and treatment. In this study, we review aneurysmal pathogenesis to seek for safe, effective, and non-invasive therapeutic strategies.