High Wall Shear Stress Research Articles

Study the role of vertebral artery tortuosity and hemodynamics in the association with headache and cerebrovascular diseases

The complex and unpredictable path of the vertebral artery is closely related to symptoms such as headaches, dizziness, and cerebrovascular diseases. This study aims to explore the role of vertebral artery tortuosity and hemodynamics in the association with headaches and cerebrovascular lesion by quantitatively analyzing the morphological parameters and hemodynamics of the vertebral artery. A total of 85 patients with headache symptoms and vascular lesions identified through computed tomography (CT) scans were included. A comparative analysis was then conducted to assess how different levels of vascular tortuosity affect these hemodynamic parameters. These findings indicate that vertebral artery tortuosity is more prevalent among the elderly, women, and patients with headache and vascular disease. A multivariate stepwise Logistic regression analysis highlights the ratio of the distal diameter to the tortuosity index of the left vertebral artery (d1) as a significant risk factor for headache symptoms in patients with vascular lesions. Hemodynamic analysis reveals complex flow patterns within the highly tortuous left vertebral artery, including vortices at areas of significant vascular tortuosity. The left vertebral artery with a high degree of distortion presents with high time-averaged wall shear stress (TAWSS), a high oscillatory shear index (OSI) region, and a low relative residence time (RRT). This discovery not only provides essential reference information for the morphological and hemodynamic analysis of the vertebral artery but also offers critical predictive insights for future clinical evaluations and interventions targeting patients with vertebral artery tortuosity, aiding in predicting their risk of experiencing headaches or the onset of cerebrovascular diseases.

High Middle Cerebral Artery Wall Shear Stress in Branch Atheromatous Disease: A Computational Fluid Dynamics Analysis

Branch atheromatous disease (BAD), characterized by the occlusion of perforating branches near the orifice of a parent artery, often develops early neurological deterioration because the mechanisms underlying BAD remain unclear. Abnormal wall shear stress (WSS) is strongly associated with endothelial dysfunction and plaque growth or rupture. Therefore, we hypothesized that computational fluid dynamics (CFD) modeling could detect differences in WSS between BAD and small-vessel occlusion (SVO), both of which result from perforating artery occlusion/stenosis. This cross-sectional observational study included consecutive patients admitted to our institution within 7 days after symptom onset who met the following criteria: absence of stenosis/occlusion in the intracranial major arteries on brain magnetic resonance angiography (MRA) or extracranial carotid arteries on carotid ultrasonography. The WSS and blood flow velocity in the M1 segment of the middle cerebral artery were analyzed using CFD based on MRA. The number of patients with a WSS ratio (ipsilesional/contralesional) of ＞1 was significantly higher in patients with BAD (n = 27) than in those with SVO (n = 27) [20 (74.1%) vs. 11 (40.7%), p = 0.013]. Higher WSS on ipsilesional M1 than on contralesional M1 was an independent risk factor for BAD (adjusted odds ratio 4.38, 95% confidence interval 1.29-14.82, p = 0.018). Blood flow velocity in the M1 segment was not associated with BAD. In patients with BAD, higher M1 segment WSS on CFD can be a risk factor for the development of vulnerable plaques in branch orifices. Moreover, the use of CFD may contribute to the diagnosis of BAD.

Airflow analysis of pediatric upper airway following maxillary expansion using computational fluid dynamics

Purpose: The objective of this study is to numerically analyze and visualize changes in airflow characteristics due to maxillary expansion in pediatric patients using computational fluid dynamics (CFD).Materials and Methods: CBCT data from pediatric patients with an apnea-hypopnea index of over 1, habitual mouth breathing, and a constricted maxilla were used. For orthodontic treatment, maxillary expansion was conducted, and CBCT scans were taken before and after expansion. 3D models of the nasal airway, created from CBCT data, were converted into smoothed, mesh-divided models. CFD analysis was conducted and various parameters which can be used to evaluate flow obstruction, including pressure, velocity, and wall shear stress, were analyzed.Results: In the patient with rapid expansion, constriction sites with high pressure, velocity, and wall shear stress distribution were identified in the anterior and posterior regions of the nasal cavity, while in the slow expansion patient, these high pressure, velocity, and wall shear stress distributed constriction sites were found in the anterior and mid-inferior regions of the nasal cavity. In both patients, after expansion, the flow-related variables that were highly distributed prior to expansion decreased, and their maximum values were also reduced.Conclusion: CFD analysis enabled the identification of constriction sites within upper airway before undergoing expansion, and improvement in airflow was confirmed after both rapid and slow maxillary expansion in pediatric patients. CFD analysis on patient-specific upper airway models is expected to aid in precisely identifying the problematic areas of respiratory obstruction, thereby assisting in the selection of personalized treatment methods.

Impact of Vein Wall Hyperelasticity and Blood Flow Turbulence on Hemodynamic Parameters in the Inferior Vena Cava with a Filter.

Inferior vena cava (IVC) filters are vital in preventing pulmonary embolism (PE) by trapping large blood clots, especially in patients unsuitable for anticoagulation. In this study, the accuracy of two common simplifying assumptions in numerical studies of IVC filters-the rigid wall assumption and the laminar flow model-is examined, contrasting them with more realistic hyperelastic wall and turbulent flow models. Using fluid-structure interaction (FSI) and computational fluid dynamics (CFD) techniques, the investigation focuses on three hemodynamic parameters: time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), and relative residence time (RRT). Simulations are conducted with varying sizes of clots captured in the filter. The findings show that, in regions of high wall shear stress, the rigid wall model predicted higher TAWSS values, suggesting an increased disease risk compared to the hyperelastic model. However, the laminar and turbulent flow models did not show significant differences in TAWSS predictions. Conversely, in areas of low wall shear stress, the rigid wall model indicated lower OSI and RRT, hinting at a reduced risk compared to the hyperelastic model, with this discrepancy being more evident with larger clots. While the predictions for OSI and TAWSS were closely aligned for both laminar and turbulent flows, divergences in RRT predictions became apparent, especially in scenarios with very large clots.

Hemodynamic comparisons of different shunt positions and geometrical model simplification strategies in the simulation of transjugular intrahepatic portosystemic shunt (TIPS)

Transjugular intrahepatic portosystemic shunt (TIPS) is a widely used surgery for portal hypertensive patients, whose potential postoperative complications are closely related to the hemodynamic condition of the portal venous system. The selection of shunt position in the surgery may affect the postoperative hemodynamics; however, it is difficult for clinical studies to investigate the influence. Therefore, this study aims to employ the computational model simulating TIPS to compare the hemodynamic differences resulting from different shunt positions, and also to investigate the influences of different geometrical model simplification strategies used in the TIPS simulation. For this purpose, the clinical data of two representative patients were retrospectively collected, based on which, the computational hemodynamic models of the portal venous systems after TIPS were constructed, incorporating three typical shunt positions (i.e. shunt at the left/main/right portal vein) and three types of geometrical model simplification. Results showed that among the models with different shunt positions, the area-averaged flow velocity magnitudes in the shunts were very similar, while the model with shunt at the main portal vein showed the lowest postoperative portal pressure and the smallest area of high wall shear stress near the portal venous bifurcation. Among the models using different geometrical model simplification strategies, the simulated blood pressures at the main portal veins were very similar, but showed marked differences near the shunt inlets. Moreover, the area-averaged flow velocity magnitudes in the shunts were almost the same, while the velocity distributions differed a lot, leading to the different spatial distributions of wall shear stress near the portal venous bifurcations and shunt walls. These results on one hand suggested that placing the shunt at the main portal vein is more beneficial for the patient; on the other hand, they proved the feasibility of utilizing simplified model to save computational cost without losing the accuracy when the pressure at the main portal vein is mainly focused on. These findings would assist clinical decision-making and promote more accurate and efficient TIPS simulations.

Mechanisms of Enhanced Cooling by Sidewall Modification in a Microtube Cold Plate

Abstract The thermofluidic effectiveness of a microtube cold plate with sidewall modification has been disputed. This study settles the dispute by detailing how such sidewall modification—hemi-circular cavities arranged along a straight circular microtube embedded with a cold plate—enhances cooling. To this end, a series of numerical simulations for a single microtube cold plate in a practical range of Reynolds numbers (20 ≤ ReD ≤ 200) are carried out. For experimental validation, flow development and pressure drop in both reference and modified microtubes are characterized respectively by microparticle image velocimetry and pneumatic pressure measurements, while surface temperatures on both cold plates' substrates subjected to uniform heat flux are measured by infrared thermography. The results agree that the boundary layer development in each throat, a short straight coolant passage that connects successive cavities, indeed enhances the cooling in the cold plate with the wall modification. However, in contrast to its sole contribution argued previously, a non-negligible source of thermal enhancement is identified. The coolant flow approaching each throat noticeably bifurcates across the throat and cavity sidewall. Thereafter, a boundary layer develops along concave sidewalls and subsequently circulates within each cavity, generating high wall shear stresses upstream of each throat and significantly elevating local cooling. In conclusion, the local cooling both “upstream” and “in” throats plays a dominant role in enhancing the overall cooling in the cold plate with wall modification, up to 40% over the reference microtube cold plate in the Reynolds number range considered.

The biomechanical effect of the O-A angle on the aortic valve under left ventricular assist device support: a primary fluid-structure interaction study.

Left ventricular assist device (LVAD) has been widely used as an alternative treatment for heart failure, however, aortic regurgitation is a common complication in patients with LVAD support. And the O-A angle (the angle between LVAD outflow graft and the aorta) is considered as a vital factor associated with the function of aortic valve. To date, the biomechanical effect of the O-A angle on the aortic valve remains largely unknown. The aim of this study was to evaluate the O-A angle how to influence the aortic valve biomechanical properties. The current study employed a novel fluid-structure interaction (FSI) model that integrates the Lattice Boltzmann method (LBM) and the finite element method (FEM) to investigate the biomechanical effect of the O-A angle on the aortic valve under LVAD support. The biomechanical status of the aortic valve was evaluated at three different O-A angles (45, 90 and 135 degrees) and. four indicators, including stress distribution, the mean stress, the axial hemodynamic force (AHF) and the wall shear stress (WSS) distribution were evaluated at three timepoints (28, 133, and 266 ms). The results showed that the stress and the high-stress region on the aortic leaflets increased as the O-A angle increased and as the difference between the left ventricular pressure (LVP) and aortic pressure (AP) increased. And the aortic insufficiency was observed at the 28 ms (systolic phase) in the 135-degree O-A angle. During the systolic phase, significant fluctuation in the mean stress was observed when the O-A angle was 90 or 135 degrees. During the diastolic phase, the mean stress increased in the three O-A angle conditions when the difference between the LVP and AP increased. Regarding to the AHF, an obvious fluctuation was observed during the systolic phase (0-100 ms) in the 135-degree O-A angle. During the diastolic phase, the AHF increased in the three O-A angle conditions when the difference between the LVP and AP increased. For the WSS distribution evaluation, the WSS was increased when the O-A angle increased. At 28 ms (the systolic phase), a high WSS was located on the free edge of the leaflets, and the deformed leaflets were observed in the 135-degree O-A angle. And at 133 ms (the rapid diastolic phase), a high WSS was observed at the free edge of the leaflets when the O-A angles were 45 or 90 degrees, and at both free edge and belly of the leaflets in the 135-degree O-A angle. The O-A angle is closely associated with the biomechanical status of the aortic valve under LVAD support. A large O-A angle caused high stress and WSS on the aortic leaflets, as well as broad stress and WSS distribution, thus leading to deformed leaflets and retrograde flow. Therefore, optimization of the O-A angle will favor to maintain aortic valve function.

High wall shear stress-dependent podosome formation in a novel murine model of intracranial aneurysm

High wall shear stress (HWSS) contributes to intracranial aneurysm (IA) development. However, the underlying molecular mechanisms remain unclear, in part due to the lack of robust animal models that develop IAs in a HWSS-dependent manner. The current study established a new experimental IA model in mice that was utilized to determine HWSS-triggered downstream mechanisms. By a strategic combination of HWSS and low dose elastase, IAs were induced with a high penetrance in hypertensive mice. In contrast, no IAs were observed in control groups where HWSS was absent, suggesting that our new IA model is HWSS-dependent. IA outcomes were assessed by neuroscores that correlate with IA rupture events. Pathological analyses confirmed these experimental IAs resemble those found in humans. Interestingly, HWSS alone promotes the turnover of collagen IV, a major basement membrane component underneath the endothelium, and the formation of endothelial podosomes, subcellular organelles that are known to degrade extracellular matrix proteins. These induced podosomes are functional as they degrade collagen-based substrates locally in the endothelium. These data suggest that this new murine model develops IAs in a HWSS-dependent manner and highlights the contribution of endothelial cells to the early phase of IA. With this model, podosome formation and function was identified as a novel endothelial phenotype triggered by HWSS, which provides new insight into IA pathogenesis.

High wall shear stress is related to complicated AHA lesion type VI plaques in mild to moderate internal carotid artery stenosis - a 3D cardiovascular MRI study.

Complicated American Heart Association (AHA) lesion type VI plaques (cCAPs), characterized by the presence of intraplaque hemorrhage, surface defect or thrombus, are strongly associated with ischemic stroke and stroke recurrence. Hemodynamics seem to play a relevant role for their development. Thus, we investigated the association of 4D flow-MRI derived local wall shear stress (WSS) and oscillatory shear stress (OSI) with the presence of cCAPs in patients with mild to moderate internal carotid artery (ICA) stenosis. From a prospective and consecutive cross-sectional study with 121 patients with high cardiovascular risk, 39 patients (49 carotid arteries) demonstrated a 10-50% ICA-stenosis and were included in this analysis. Plaque composition was determined according to the modified AHA classification of lesions by high-resolution multi-contrast 3T-MRI. We determined WSS (minimum, mean and maximum) and OSI in vivo by 4D flow-MRI at different locations within the stenosis (upstream, stenosis center and downstream). We studied the association of each hemodynamic parameter with the presence cCAPs by logistic regression analysis adjusted for age, sex and plaque thickness. 11 (22.4%) of the 49 ICA-stenosis in our cohort showed cCAP. WSS and OSI at the beginning of the stenosis did not differ between complicated and stable plaques. By contrast, WSS was significantly higher in the stenosis center and poststenotic region in cCAPs. OSI was significantly higher in the stenosis center of stable plaques. Logistic regression analysis revealed a significant association for WSSmean (OR per SD increase 1.97, 95%-CI 1.14-3.39, p=0.015) and for WSSmax (OR per SD increase 1.84; 95%-CI 1.10-3.08; p=0.020), but not for WSSmin and OSI with the presence of cCAPs. Higher wall shear stress in ICA stenosis was significantly associated with the presence of cCAPs underlining the potential role of hemodynamics in their development. cCAP, complicated carotid artery plaque; WSS, wall shear stress; OSI, oscillatory shear index.

Endothelial-derived nitric oxide impacts vascular smooth muscle cell phenotypes under high wall shear stress condition

The Phenotypic states of vascular smooth muscle cells (SMCs) are essential to understanding vascular pathophysiology. SMCs in vessels generally express a specific set of contractile proteins, but decreased contractile protein expression, indicating a phenotypic shift, is a hallmark of vascular diseases. Recent studies have suggested the relation of abnormally high wall shear stress (WSS) of approximately 20 Pa with the aortic disease pathogenesis. However, due to the lack of appropriate experimental models to assess SMC phenotypic states, the details of the phenotypic shift under high WSS conditions remain unclear. In this study, we developed a coculture model where vascular endothelial cells (ECs) were cocultured with SMCs expressing calponin 1, a contractile protein involved in the phenotypic shift of SMCs. We investigated the effects of a pathologically high WSS condition on the phenotypic states of SMCs. Increased calponin 1 expression was found upon exposure to 20 Pa WSS compared with a physiological 2 Pa condition, whereas the expression of another contractile protein, α-smooth muscle actin (αSMA) remained unchanged. Furthermore, the inhibition of EC-derived nitric oxide (NO), which is associated with endothelial dysfunction in vascular diseases, resulted in a trend of decreasing αSMA and Calponin 1 expression under 20 Pa WSS conditions compared with 2 Pa. Our findings suggest that EC-derived NO under pathologically high WSS conditions may impact the expression of contractile proteins implicated in aortic pathophysiology.

Prognostic value of morphology and hemodynamics in moyamoya disease for long-term outcomes and disease progression

To explore the relationship between morphological and hemodynamic parameters, baseline characteristics, and long-term outcomes in patients with moyamoya disease (MMD) using a computational fluid dynamics model. We retrospectively reviewed 129 patients at Beijing Tiantan hospital between July 2020 and December 2021. Perioperative clinical variables and Suzuki stage were recorded. Logistic regression analysis was employed to identify the risk factors for unfavorable long-term outcomes. The association between morphological, CT perfusion parameters, hemodynamic parameters and the Suzuki stage, clinical variables of MMD was also analyzed. Patients with high relative Wall Shear Stress (rWSS) were older and had more cases with higher Suzuki stage and worse follow-up mRS scores (p < 0.05). High rWSS at the terminal ICA and diabetes mellitus were identified as independent predictors of unfavorable long-term outcomes [OR = 3.039(1.191–7.754), p = 0.020; OR = 3.164(1.141–8.723), p = 0.027, respectively]. ROC analysis demonstrated that predictive models incorporating rWSS improved AUC values, with the highest AUC in Model 2 (AUC = 0.889). High rWSS was significantly associated with future TIA and stroke events (p = 0.032). We speculated that high rWSS and diabetes mellitus were independent risk factors for unfavorable long-term outcomes in patients with MMD. rWSS and morphological parameters are crucial for predicting MMD progression and understanding its pathogenesis.

Abstract 4141445: Long-Term Predictive Value of 4D Flow MRI in Bicuspid Aortic Valve Patients: A 10-Year Assessment for Aortic Surgery Risk

Introduction: Bicuspid aortic valve (BAV) is associated with progressive ascending aorta (AAo) dilation, often leading to aneurysms, dissections, and ruptures. Thus, current guidelines recommend preventive surgery for AAo dilation. Recent 4D flow MRI studies show that BAV morphology causes abnormal transvalvular flow patterns, increasing wall shear stress (WSS), a trigger of aortic growth. Further studies have delineated areas of abnormally high WSS by comparing to estimates of matched controls, and show promise in detecting risk for aortic growth. However, since the long-term prognostic significance of this marker is unclear, we aimed to quantify WSS in BAV patients to assess its value in predicting the need for aortic surgery up to 10 years post-4D flow MRI acquisition. Methods: BAV patients without prior surgical intervention scanned before April 1, 2014 were identified. Using medical records, patients were categorized as ‘operated’ if they underwent aortic surgery post-scan and ‘non-operated’ if they were surgery-free for at least 10 years post-scan. 4D flow MRIs were processed with an AI pipeline, including 3D segmentation of the aorta, followed by peak velocity (PV) and WSS quantification in the AAo (Fig. 1A-C). Patient-specific WSS heatmaps were computed relative to a map based on the WSS of 10 or more sex and age-matched controls. Relative areas of elevated WSS in the AAo were then calculated (Fig. 1D-F). Results: 115 patients were included, with 73 non-operated (age: 42.5±11.5y, 49M) and 42 operated patients (age: 53.5±12.1y, 34M). The mean baseline mid-AAo diameters for non-operated and operated patients were 3.8±0.6 cm and 4.1±0.5 cm, respectively. Among operated patients, the mean scan to surgery time was 5.7±3.3y. All three 4D flow metrics were significantly higher in operated compared to non-operated patients: PV: 2.6±0.6 vs. 1.7±0.4 m/s (p&lt;0.01); WSS: 2.2±0.5 vs. 1.6±0.4 Pa (p&lt;0.01); relative area of high WSS on heatmaps: 31±12 vs. 15±13% (p&lt;0.01). Conclusions: 4D flow MRI parameters provide long-term predictive value in BAV patients, as elevated peak velocity, wall shear stress, and relative area of high wall shear stress on heatmaps are associated with subsequent aortic surgery within 10 years post-scan.

Finite element analysis and computational fluid dynamics to elucidate the mechanism of distal stent graft-induced new entry after frozen elephant trunk technique.

Distal stent graft-induced new entry (dSINE), a new intimal tear at the distal edge of the frozen elephant trunk (FET), is a complication of FET. Preventive measures for dSINE have not yet been established. This study aimed to clarify the mechanisms underlying the development of dSINE by simulating the mechanical environment at the distal edge of the FET. The stress field in the aortic wall after FET deployment was calculated using finite element analysis. Blood flow in the intraluminal space of the aorta and FET models was simulated using computational fluid dynamics. The simulations were conducted with various oversizing rates of FET ranging from 0 to 30% under the condition of FET with elastic recoil. The elastic recoil of the FET, which caused its distal edge to push against the greater curvature of the aorta, induced a concentration of circumferential stress and increased wall shear stress (WSS) at the aorta. Elastic recoil also created a discontinuous notch on the lesser curvature of the aorta, causing flow stagnation. An increase in the oversizing rate of the FET widened the large circumferential stress area on the greater curvature and increases the maximum stress. Conversely, a decrease in the oversizing rate of the FET increased the WSS and widened the area with high WSS. Circumferential stress concentration due to an oversized FET and high WSS due to an undersized FET can cause a dSINE. The selection of smaller-sized FET alone might not prevent dSINE.

Prognostic significance of pre-procedure wall shear stress in the ascending aorta in patients with aortic stenosis undergoing transcatheter aortic valve replacement

Abstract Background Accurate prognostication before the procedure is challenging in patients with aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). Recently, blood flow dynamics assessed by four-dimensional flow cardiovascular magnetic resonance imaging (4D-flow CMR) showed a significant reduction in average wall shear stress (WSS) in the ascending aorta (AAo) after TAVR. However, the prognostic value of pre-procedure average WSS in the AAo is controversial. Purpose We aimed to investigate whether pre-procedure average WSS was associated with clinical outcomes in patients with AS undergoing TAVR. Methods We prospectively examined 159 consecutive AS patients who underwent TAVR (57 males, mean age 83.6 ± 4.7 years, median left ventricular ejection fraction 63.4%) between May 2018 and May 2022. We assessed average WSS in the AAo before TAVR using 4D-flow CMR. We divided the patients into high WSS (≥6.60 Pa, n = 79) and low WSS (&amp;lt;6.60 Pa, n = 80) groups according to the median value of pre-TAVR WSS. The primary outcome of interest was a composite of all-cause death and hospitalization for worsening heart failure. Results Patients with high WSS had lower age compared to those with low WSS. There were no significant differences on sex, body mass index, systolic blood pressure, hemoglobin, serum albumin, N-terminal pro b-type natriuretic peptide, left ventricular ejection fraction, mean transaortic valvular gradient, annulus area in aortic valve and AAo diameter between the groups. During a median follow-up period of 19.8 months (interquartile range 6.0-37.1), the primary outcome more frequently occurred in patients with low WSS than in those with high WSS (28% vs 5%, P &amp;lt;0.001) (Figure 1). A multivariable Cox regression showed that lower WSS independently associated with increased risk of the primary outcome (hazard ratio 0.69, 95% confidence interval [CI] 0.53-0.91, P &amp;lt;0.001), even after adjustment for significant prognostic covariates including age, sex, serum albumin, history of chronic obstructive pulmonary disease, peripheral artery disease and malignancy, and estimated glomerular filtration rate. Predictive performance for the primary outcome was improved when adding the value of WSS in the AAo to representative prognostic factors (c-index 0.81 95%CI 0.72-0.90 vs. 0.77 95%CI 0.67-0.88) (Figure 2). Conclusions In patients with AS who underwent TAVR, lower average WSS in the AAo before procedure was associated with higher risk of worse clinical outcomes, suggesting that pre-TAVR average WSS in the AAo would be a surrogate marker and useful for the risk stratification.Survival analysis for primary outcomePredictive performance

Targeting Sphingosine-1-Phosphate Signaling to Prevent the Progression of Aortic Valve Disease.

Aortic valve disease (AVD) is associated with high mortality and morbidity. To date, there is no pharmacological therapy available to prevent AVD progression. Because valve calcification is the hallmark of AVD and S1P (sphingosine-1-phosphate) plays an important role in osteogenic signaling, we examined the role of S1P signaling in aortic stenosis disease. AVD progression and its consequences for cardiac function were examined in a murine wire injury-induced AVD model with and without pharmacological and genetic modulation of S1P production, degradation, and receptor signaling. S1P was measured by LC-MS. Calcification of valvular interstitial cells and their response to biomechanical stress were analyzed in the context of S1P signaling. Human explanted aortic valves from patients undergoing aortic valve replacement and cardiovascular magnetic resonance imaging were analyzed for S1P by LC-MS. Raising S1P concentrations in mice with injury-induced AVD by pharmacological inhibition of its sole degrading enzyme S1P lyase vastly enhanced AVD progression and impaired cardiac function resembling human disease. In contrast, low S1P levels caused by SphK1 (sphingosine kinase 1) deficiency potently attenuated AVD progression. We found S1P/S1PR2 (S1P receptor 2) signaling to be responsible for the adverse S1P effect because S1PR2-deficient mice were protected against AVD progression and its deterioration by high S1P. It is important to note that pharmacological S1PR2 inhibition administered after wire injury successfully prevented AVD development. Mechanistically, biomechanical stretch stimulated S1P production by SphK1 in human valvular interstitial cells as measured by C17-S1P generation, whereas S1P/S1PR2 signaling induced their osteoblastic differentiation and calcification through osteogenic RUNX2/OPG signaling and the GSK3β-Wnt-β-catenin pathway. In patients with AVD, stenotic valves exposed to high wall shear stress had higher S1P content and increased SphK1 expression. Increased systemic or local S1P levels lead to increased valvular calcification. S1PR2 antagonists and SphK1 inhibitors may offer feasible pharmacological approaches to human AVD in prophylactic, disease-modifying or relapse-preventing manners.

Low shear-induced fibrillar fibronectin: comparative analyses of morphologies and cellular effects on bovine aortic endothelial cell adhesion and proliferation

Wall shear stress (WSS) is a critical factor in vascular biology, and both high and low WSS are implicated in atherosclerosis. Fibronectin (FN) is a key extracellular matrix protein that plays an important role in cell activities. Under high shear stress, plasma FN undergoes fibrillogenesis; however, its behavior under low shear stress remains unclear. This study aimed to investigate the formation ofin vitrocell-free fibrillar FN (FFN) under low shear rate conditions and its effect on bovine aortic endothelial cell behavior. FN (500µg ml-1) was perfused through slide chambers at three flow rates (0.16 ml h-1, 0.25 ml h-1, and 0.48 ml h-1), corresponding to low shear rates of 0.35 s-1, 0.55 s-1, and 1.05 s-1, respectively, for 4 h at room temperature. The formed FN matrices were observed using fluorescence microscopy and scanning electron microscopy. Under low shear rates, distinct FN matrix structures were observed. FFN0.48 formed immense fibrils with smooth surfaces, FFN0.25 formed a matrix with a rough surface, and FFN16 exhibited nodular structures. FFN0.25 supported cell activities to a greater extent than native FN and other FFN surfaces. Our study suggests that abnormally low shear conditions impact FN structure and function and enhance the understanding of FN fibrillogenesis in vascular biology, particularly in atherosclerosis.

Exploring the hemodynamic behavior of residual aneurysms after coiling and clipping: A computational flow dynamic analysis.

Residual intracranial aneurysms post-clipping or coiling pose a poorly established risk of rupture. Computational fluid dynamic (CFD) offers insights into hemodynamic changes following such interventions. This study aims to assess hemodynamic parameters in residual aneurysms pre- and post-treatment with surgical clips or coils using CFD. A retrospective analysis of consecutive patients between January 2015 and January 2024 was conducted. Digital subtraction angiography images were reconstructed using 3D modeling techniques, and hemodynamic parameters were analyzed with ANSYS® software. Six aneurysms were analyzed: Five unruptured and one ruptured. The aneurysms were located at the basilar apex (2), middle cerebral artery bifurcation (2), and origin of the posterior communicating artery (2). Post-treatment, there was a significant reduction in both aneurysm area (median reduction of 33.73%) and volume (median reduction of 25.3%). Five of the six cases demonstrated fewer low wall shear stress (WSS) areas, which could indicate a reduction in regions prone to thrombus formation and diminished risk of rupture. In the unruptured aneurysms, there was a median increase of 137.6% in average WSS. Notably, the only case with increased low WSS area also had the highest increase in average WSS. One basilar artery aneurysm showed increased WSS across all parameters, suggesting a higher rupture risk. The increase in average and high WSS area, along with a decrease in low WSS area, reflects a complex balance between factors of stability and rupture risk. However, a simultaneous increase in all WSS parameters may represent the highest rupture risk due to increased mechanical stress on the aneurysm wall, necessitating closer monitoring.

Flow topology and mixing in alveolar edema: Unsteady flow in interconnected cavities with moving walls

The study of alveolar fluid mechanics is critical for comprehending respiratory function and lung diseases, particularly in cases of alveolar lesions that result in significant structural and fluid dynamic changes. This study investigates the flow topology and chaotic mixing within both normal and edematous alveoli, where the alveoli in the edematous model are interconnected by pores. To numerically simulate alveolar flow, a mathematical model is developed to ascertain the key parameters of Reynolds number (Re) and alveolar expansion ratio. Subsequently, the flow fields are analyzed to determine wall shear stress (WSS) and to identify WSS critical points and critical points of velocity vector, with a thorough presentation of the various flow topologies corresponding to these critical points. Moreover, a dynamic mode decomposition-based method is introduced to track particle trajectories, and the exploration of chaotic mixing is conducted through tracer advection, Poincare map, and the calculation of finite-time Lyapunov exponents. Results indicate that the edematous model exhibits a higher Re and higher WSS due to the fluid properties. Within the alveoli, high WSS is usually localized at the pores. The pores increase critical points and alter flow topologies, significantly changing chaotic mixing. Additionally, Re and alveolar locations also affect mixing patterns. These findings are crucial for understanding alveolar physiology and designing inhaled drugs for lung diseases, considering the role of chaos in particle transport in the lung acini.

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.

Alterations in nasal airflow and air conditioning after endoscopic nasopharyngectomy for recurrent nasopharyngeal carcinoma: a pilot computational fluid dynamics study

Endoscopic nasopharyngectomy represents a significant intervention for recurrent nasopharyngeal carcinoma (NPC). Various surgical techniques, including transnasal and transoral approaches, are employed. However, the impact of these procedures on nasal airflow dynamics is not well understood. This computational fluid dynamics (CFD) study aimed to investigate alterations in nasal airflow and air conditioning following endoscopic nasopharyngectomy. A 55-year-old male patient with recurrent NPC was selected, whose CT data were utilized for image reconstruction. A preoperative model and two postoperative models, including the transnasal and transoral approach models, were established. The airflow patterns and various CFD parameters were analyzed. In the postoperative models, the high-speed airflow went along the soft palate and into the nasopharyngeal outlet, and there was the low-speed turbulence in the expanded nasopharyngeal cavity. Compared to the preoperative model, the postoperative models exhibited reductions in surface-to-volume ratio, nasal resistance, airflow velocity and proportion of high wall shear stress regions in nasopharynx. The changing trends of nasopharyngeal air temperature and humidity in the preoperative and transoral models were consistent. The heating and humidification efficiency decreased in the transnasal model compared to the transoral model. The endoscopic nasopharyngectomy for recurrent NPC affects the nasal airflow and warming and humidification function. The transoral approach has less influence on aerodynamics of the upper airway compared to the transnasal approach. From a CFD perspective, the endoscopic nasopharyngectomy does not increase the risk of postoperative complications, including the empty nose syndrome and the carotid blowout syndrome.