scholarly journals Genetic correlates of wall shear stress in a patient-specific 3D-printed cerebral aneurysm model

2019 ◽  
Vol 11 (10) ◽  
pp. 999-1003 ◽  
Author(s):  
Michael R Levitt ◽  
Christian Mandrycky ◽  
Ashley Abel ◽  
Cory M Kelly ◽  
Samuel Levy ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Wall Shear Stress ◽  
Cerebral Aneurysm ◽  
Cell Morphology ◽  
Patient Specific ◽  
Parent Vessel ◽  
3D Printed ◽  
Wall Shear ◽  
Dynamics Simulations

ObjectivesTo study the correlation between wall shear stress and endothelial cell expression in a patient-specific, three-dimensional (3D)-printed model of a cerebral aneurysm.Materials and methodsA 3D-printed model of a cerebral aneurysm was created from a patient’s angiogram. After populating the model with human endothelial cells, it was exposed to media under flow for 24 hours. Endothelial cell morphology was characterized in five regions of the 3D-printed model using confocal microscopy. Endothelial cells were then harvested from distinct regions of the 3D-printed model for mRNA collection and gene analysis via quantitative polymerase chain reaction (qPCR.) Cell morphology and mRNA measurement were correlated with computational fluid dynamics simulations.ResultsThe model was successfully populated with endothelial cells, which survived under flow for 24 hours. Endothelial morphology showed alignment with flow in the proximal and distal parent vessel and aneurysm neck, but disorganization in the aneurysm dome. Genetic analysis of endothelial mRNA expression in the aneurysm dome and distal parent vessel was compared with the proximal parent vessels. ADAMTS-1 and NOS3 were downregulated in the aneurysm dome, while GJA4 was upregulated in the distal parent vessel. Disorganized morphology and decreased ADAMTS-1 and NOS3 expression correlated with areas of substantially lower wall shear stress and wall shear stress gradient in computational fluid dynamics simulations.ConclusionsCreating 3D-printed models of patient-specific cerebral aneurysms populated with human endothelial cells is feasible. Analysis of these cells after exposure to flow demonstrates differences in both cell morphology and genetic expression, which correlate with areas of differential hemodynamic stress.

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

2019 ◽  
Vol 131 (2) ◽  
pp. 442-452 ◽  
Author(s):  
Alexandra Lauric ◽  
James E. Hippelheuser ◽  
Adel M. Malek
Keyword(s):  
Shear Stress ◽  
Wall Shear Stress ◽  
Flow Rate ◽  
Stress Gradient ◽  
Dependent Manner ◽  
Parent Vessel ◽  
Spatial Gradients ◽  
Bifurcation Angle ◽  
Wall Shear ◽  
Dynamics Simulations

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

Effects of Steady Spatial Wall Shear Stress Gradients on Endothelial Cell Morphology in Three-Dimensional Models

2007 ◽  
Author(s):  
Leonie Rouleau ◽  
Monica Farcas ◽  
Jean-Claude Tardif ◽  
Rosaire Mongrain ◽  
Richard Leask
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Endothelial Cell ◽  
Wall Shear Stress ◽  
Cell Morphology ◽  
Flow Direction ◽  
Stress Gradient ◽  
Spatial Gradient ◽  
Stress Gradients ◽  
Wall Shear

Endothelial cell (EC) dysfunction has been linked to atherosclerosis through their response to hemodynamic forces. Flow in stenotic vessels creates complex spatial gradients in wall shear stress. In vitro studies examining the effect of shear stress on endothelial cells have used unrealistic and simplified models, which cannot reproduce physiological conditions. The objective of this study was to expose endothelial cells to the complex shear shear pattern created by an asymmetric stenosis. Endothelial cells were grown and exposed for different times to physiological steady flow in straight dynamic controls and in idealized asymmetric stenosis models. Cells subjected to 1D flow aligned with flow direction and had a spindle-like shape when compared to static controls. Endothelial cell morphology was noticeable different in the regions with a spatial gradient in wall shear stress, being more randomly oriented and of cobblestone shape. This occurred despite the presence of an increased magnitude in shear stress. No other study to date has described this morphology in the presence of a positive wall shear stress gradient or gradient of significant shear magnitude. This technique provides a more realistic model to study endothelial cell response to spatial and temporal shear stress gradients that are present in vivo and is an important advancement towards a better understanding of the mechanisms involved in coronary artery disease.

scholarly journals Flow instability and wall shear stress variation in intracranial aneurysms

2009 ◽  
Vol 7 (47) ◽  
pp. 967-988 ◽  
Author(s):  
H. Baek ◽  
M. V. Jayaraman ◽  
P. D. Richardson ◽  
G. E. Karniadakis
Keyword(s):  
Shear Stress ◽  
Wall Shear Stress ◽  
Intracranial Aneurysms ◽  
Flow Instability ◽  
Hydrodynamic Instability ◽  
Saccular Aneurysm ◽  
High Frequency Oscillation ◽  
Patient Specific ◽  
Parent Vessel ◽  
Wall Shear

We investigate the flow dynamics and oscillatory behaviour of wall shear stress (WSS) vectors in intracranial aneurysms using high resolution numerical simulations. We analyse three representative patient-specific internal carotid arteries laden with aneurysms of different characteristics: (i) a wide-necked saccular aneurysm, (ii) a narrower-necked saccular aneurysm, and (iii) a case with two adjacent saccular aneurysms. Our simulations show that the pulsatile flow in aneurysms can be subject to a hydrodynamic instability during the decelerating systolic phase resulting in a high-frequency oscillation in the range of 20–50 Hz, even when the blood flow rate in the parent vessel is as low as 150 and 250 ml min −1 for cases (iii) and (i), respectively. The flow returns to its original laminar pulsatile state near the end of diastole. When the aneurysmal flow becomes unstable, both the magnitude and the directions of WSS vectors fluctuate at the aforementioned high frequencies. In particular, the WSS vectors around the flow impingement region exhibit significant spatio-temporal changes in direction as well as in magnitude.

scholarly journals Location of Reentry Tears Affects False Lumen Thrombosis in Aortic Dissection Following TEVAR

2020 ◽  
Vol 27 (3) ◽  
pp. 396-404
Author(s):  
Chlöe Harriet Armour ◽  
Claudia Menichini ◽  
Kristijonas Milinis ◽  
Richard G. J. Gibbs ◽  
Xiao Yun Xu
Keyword(s):  
Shear Stress ◽  
Wall Shear Stress ◽  
Stent Graft ◽  
Thrombus Formation ◽  
False Lumen ◽  
Patient Specific ◽  
Landing Zone ◽  
Wall Shear ◽  
Dynamics Simulations

Purpose: To report a study that assesses the influence of the distance between the distal end of a thoracic stent-graft and the first reentry tear (SG-FRT) on the progression of false lumen (FL) thrombosis in patients who underwent thoracic endovascular aortic repair (TEVAR). Materials and Methods: Three patient-specific geometrical models were reconstructed from postoperative computed tomography scans. Two additional models were created by artificially changing the SG-FRT distance in patients 1 and 2. In all 5 models, computational fluid dynamics simulations coupled with thrombus formation modeling were performed at physiological flow conditions. Predicted FL thrombosis was compared to follow-up scans. Results: There was reduced false lumen flow and low time-averaged wall shear stress (TAWSS) in patients with large SG-FRT distances. Predicted thrombus formation and growth were consistent with follow-up scans for all patients. Reducing the SG-FRT distance by 30 mm in patient 1 increased the flow and time-averaged wall shear stress in the upper abdominal FL, reducing the thrombus volume by 9.6%. Increasing the SG-FRT distance in patient 2 resulted in faster thoracic thrombosis and increased total thrombus volume. Conclusion: The location of reentry tears can influence the progression of FL thrombosis following TEVAR. The more distal the reentry tear in the aorta the more likely it is that FL thrombosis will occur. Hence, the distal landing zone of the stent-graft should be chosen carefully to ensure a sufficient SG-FRT distance.

scholarly journals Hemodynamic and morphological characteristics of a growing cerebral aneurysm

2019 ◽  
Vol 47 (1) ◽  
pp. E13 ◽  
Author(s):  
Mahsa Dabagh ◽  
Priya Nair ◽  
John Gounley ◽  
David Frakes ◽  
L. Fernando Gonzalez ◽  
...  
Keyword(s):  
Shear Stress ◽  
Wall Shear Stress ◽  
Cerebral Aneurysm ◽  
Predictive Value ◽  
Patient Specific ◽  
Growth Stages ◽  
Data Set ◽  
Recirculating Flow ◽  
Aneurysm Wall ◽  
Wall Shear

The growth of cerebral aneurysms is linked to local hemodynamic conditions, but the driving mechanisms of the growth are poorly understood. The goal of this study was to examine the association between intraaneurysmal hemodynamic features and areas of aneurysm growth, to present the key hemodynamic parameters essential for an accurate prediction of the growth, and to gain a deeper understanding of the underlying mechanisms. Patient-specific images of a growing cerebral aneurysm in 3 different growth stages acquired over a period of 40 months were segmented and reconstructed. A unique aspect of this patient-specific case study was that while one side of the aneurysm stayed stable, the other side continued to grow. This unique case enabled the authors to examine their aims in the same patient with parent and daughter arteries under the same inlet flow conditions. Pulsatile flow in the aneurysm models was simulated using computational fluid dynamics and was validated with in vitro experiments using particle image velocimetry measurements. The authors’ detailed analysis of intrasaccular hemodynamics linked the growing regions of aneurysms to flow instabilities and complex vortex structures. Extremely low velocities were observed at or around the center of the unstable vortex structure, which matched well with the growing regions of the studied cerebral aneurysm. Furthermore, the authors observed that the aneurysm wall regions with a growth greater than 0.5 mm coincided with wall regions of lower (< 0.5 Pa) time-averaged wall shear stress (TAWSS), lower instantaneous (< 0.5 Pa) wall shear stress (WSS), and high (> 0.1) oscillatory shear index (OSI). To determine which set of parameters can best identify growing and nongrowing aneurysms, the authors performed statistical analysis for consecutive stages of the growing CA. The results demonstrated that the combination of TAWSS and the distance from the center of the vortical structure has the highest sensitivity and positive predictive value, and relatively high specificity and negative predictive value. These findings suggest that an unstable, recirculating flow structure within the aneurysm sac created in the region adjacent to the aneurysm wall with low TAWSS may be introduced as an accurate criterion to explain the hemodynamic conditions predisposing the aneurysm to growth. The authors’ findings are based on one patient’s data set, but the study lays out the justification for future large-scale verification. The authors’ findings can assist clinicians in differentiating stable and growing aneurysms during preinterventional planning.

Endothelial Cell Migration in Patient-Specific Models of Intracranial Aneurysm

2010 ◽  
Author(s):  
Liang-Der Jou
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Wall Shear Stress ◽  
Morphological Changes ◽  
Critical Role ◽  
Endothelial Cell Migration ◽  
Patient Specific ◽  
Shear Stresses ◽  
Wall Shear

Effects of wall shear stress on atherosclerotic disease are widely studied, but its effects on intracranial aneurysms are less clear. In vitro studies have demonstrated that endothelial cells (EC) go through morphological changes under abnormal wall shear stress, and these studies have also shown that abnormal wall shear stresses lead to a non-uniform EC distributions [1, 2]. Since endothelial cells play a critical role in mechanotransduction, a sub-optimal distribution of EC may affect remodeling of vessel wall.

scholarly journals Investigation of Wall Shear Stress in Cardiovascular Research and in Clinical Practice—From Bench to Bedside

2021 ◽  
Vol 22 (11) ◽  
pp. 5635
Author(s):  
Katharina Urschel ◽  
Miyuki Tauchi ◽  
Stephan Achenbach ◽  
Barbara Dietel
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Wall Shear Stress ◽  
Cell Function ◽  
Computational Techniques ◽  
Apical Surface ◽  
Cardiovascular Research ◽  
Endothelial Cell Function ◽  
Wall Shear

In the 1900s, researchers established animal models experimentally to induce atherosclerosis by feeding them with a cholesterol-rich diet. It is now accepted that high circulating cholesterol is one of the main causes of atherosclerosis; however, plaque localization cannot be explained solely by hyperlipidemia. A tremendous amount of studies has demonstrated that hemodynamic forces modify endothelial athero-susceptibility phenotypes. Endothelial cells possess mechanosensors on the apical surface to detect a blood stream-induced force on the vessel wall, known as “wall shear stress (WSS)”, and induce cellular and molecular responses. Investigations to elucidate the mechanisms of this process are on-going: on the one hand, hemodynamics in complex vessel systems have been described in detail, owing to the recent progress in imaging and computational techniques. On the other hand, investigations using unique in vitro chamber systems with various flow applications have enhanced the understanding of WSS-induced changes in endothelial cell function and the involvement of the glycocalyx, the apical surface layer of endothelial cells, in this process. In the clinical setting, attempts have been made to measure WSS and/or glycocalyx degradation non-invasively, for the purpose of their diagnostic utilization. An increasing body of evidence shows that WSS, as well as serum glycocalyx components, can serve as a predicting factor for atherosclerosis development and, most importantly, for the rupture of plaques in patients with high risk of coronary heart disease.

scholarly journals Wall shear stress gradient is independently associated with middle cerebral artery aneurysm development: a case-control CFD patient-specific study based on 77 patients

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Mikołaj Zimny ◽  
Edyta Kawlewska ◽  
Anna Hebda ◽  
Wojciech Wolański ◽  
Piotr Ładziński ◽  
...  
Keyword(s):  
Shear Stress ◽  
Wall Shear Stress ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Case Control ◽  
Independent Effect ◽  
Patient Specific ◽  
Aneurysm Formation ◽  
Wall Shear ◽  
Mca Aneurysm

Abstract Background Previously published computational fluid dynamics (CFD) studies regarding intracranial aneurysm (IA) formation present conflicting results. Our study analysed the involvement of the combination of high wall shear stress (WSS) and a positive WSS gradient (WSSG) in IA formation. Methods We designed a case-control study with a selection of 38 patients with an unruptured middle cerebral artery (MCA) aneurysm and 39 non-aneurysmal controls to determine the involvement of WSS, oscillatory shear index (OSI), the WSSG and its absolute value (absWSSG) in aneurysm formation based on patient-specific CFD simulations using velocity profiles obtained from transcranial colour-coded sonography. Results Among the analysed parameters, only the WSSG had significantly higher values compared to the controls (11.05 vs − 14.76 [Pa/mm], P = 0.020). The WSS, absWSSG and OSI values were not significantly different between the analysed groups. Logistic regression analysis identified WSS and WSSG as significant co-predictors for MCA aneurysm formation, but only the WSSG turned out to be a significant independent prognosticator (OR: 1.009; 95% CI: 1.001–1.017; P = 0.025). Significantly more patients (23/38) in the case group had haemodynamic regions of high WSS combined with a positive WSSG near the bifurcation apex, while in the control group, high WSS was usually accompanied by a negative WSSG (14/39). From the analysis of the ROC curve for WSSG, the area under the curve (AUC) was 0.654, with the optimal cut-off value −0.37 Pa/mm. The largest AUC was recognised for combined WSS and WSSG (AUC = 0.671). Our data confirmed that aneurysms tend to form near the bifurcation apices in regions of high WSS values accompanied by positive WSSG. Conclusions The development of IAs is determined by an independent effect of haemodynamic factors. High WSS impacts MCA aneurysm formation, while a positive WSSG mainly promotes this process.

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