Comparison of Fluid Dynamics Variations Between Chimney and Fenestrated Endografts for Pararenal Aneurysms Repair: A Patient Specific Computational Study as Motivation for Clinical Decision-Making.

BACKGROUND-AIM: Limited data exist concerning the fluid dynamic changes induced by endovascular aortic repair with fenestrated and chimney graft modalities in pararenal aneurysms. We aimed to investigate and compare the wall shear stress (WSS) and flow dynamics for the branch vessels before and after endovascular aortic repair with fenestrated and chimney techniques. METHODS: Modeling was done for patient specific pararenal aortic aneurysms employing fenestrated and chimney grafts (Materialise Mimics 10.0) before and after the endovascular procedure, using computed tomography scans of patients. Surface and spatial grids were created using the ANSYS CFD meshing software 2019 R2. Assessment of blood flow, streamlines, and WSS before and after aneurysm repair was performed. RESULTS: The endovascular repair with chimney grafts leaded to a 43% to 53% reduction in perfusion in renal arteries. In fenestrated reconstruction, we observed a 15% reduced perfusion in both renal arteries. In both cases, we observed a decrease in the recirculation phenomena of the aorta after endovascular repair. Concerning the grafts of the renal arteries, we observed in both the transverse and longitudinal axes low WSS regions with simultaneous recirculation of the flow 1 cm distal to the ostium sites in both aortic graft models. High WSS regions appeared in the sites of ostium. CONCLUSIONS: We observed reduced renal perfusion in chimney grafts compared to fenestrated grafts, probably caused by the long and kinked characteristics of these devices.

Identification of regional/layer differences in failure properties and thickness as important biomechanical factors responsible for the initiation of aortic dissections.

Thoracic aortic dissections involving the ascending aorta represent one of the most dramatic and lethal emergencies in cardiovascular surgery. It is therefore critical to identify the mechanisms driving them and biomechanical analyses hold great clinical promise, since rupture/dissection occur when aortic wall strength is unable to withstand hemodynamic stresses. Although several studies have been done on the biomechanical properties of thoracic aortic aneurysms, few data are available about thoracic aortic dissections. Detailed mechanical tests with measurement of tissue thickness and failure properties were performed with a tensile-testing device on 445 standardized specimens, corresponding to 19 measurement sites per inner (intima with most of media)/outer layer (leftover media with adventitia); harvested from twelve patients undergoing emergent surgical repair for type A dissection. Our data suggested inherent differences in tissue properties between the origin of dissection and distal locations, i.e. thinner and stiffer inner layers that might render them more vulnerable to tearing despite their increased strength. The strength of tissue circumferentially was greater than that longitudinally, likely determining the direction of tear. The relative strengths of the inner: ∼{65,40}N/cm2 and outer layer: ∼{350,270}N/cm2 in the two principal directions of dissected tissue were differentiated from the intima: ∼{100,75}N/cm2, media: ∼{150,55}N/cm2, and adventitia: ∼{270,190}N/cm2 of non-dissected ascending aortic aneurysms (Sokolis et al., 2012), in favor of weaker inner and stronger outer layers, allowing an explanation as to why the presently-studied tissue suffered dissection, i.e. tear of the inner layers, and not rupture, i.e. full tearing across the entire wall thickness.

Layer- and region-specific material characterization of ascending thoracic aortic aneurysms by microstructure-based models.

Material characterization of ascending thoracic aortic aneurysms is indispensable for the determination of stress distributions across wall thickness and the different aneurysm regions that may be responsible for their catastrophic rupture or dissection, but only few studies have addressed this issue hitherto. In this article, we are presenting our findings of implementing microstructure-based formulations for characterizing layer- and region-specific variations in wall properties, which is a reasonable consensus today. Together, we performed image-based analysis to derive collagen-fiber orientation angles that may serve as validation of the preferred candidate for a fiber-reinforced constitutive descriptor. We considered a four-fiber model with dispersions of fiber angles about the main directions, based on our histological observations, demonstrating a wide distribution of fiber orientations spanning circumferential to longitudinal directions, and its successful implementation to our biomechanical data from tensile testing. However, an in-depth parametric analysis showed that a condensed model without longitudinal-fiber family described the data just as well and did not omit essential histological organization of collagen fibers, while reserving a smaller number of parameters, which makes it advantageous for computational applications. A major aberration from almost all existing models in the literature is the hypothesis made that fibers can support compressive stresses. Such a hypothesis needs further examination but it has the benefits of allowing improved fits to the vanishing transverse stresses under uniaxial test conditions and of properly reflecting the exponential nature of the compressive stress-strain response of aortic tissue, being consistent with observations of collagen being under compression in the unloaded wall.

Elevated expression of mechanosensory polycystins in human carotid atherosclerotic plaques: association with p53 activation and disease severity.

Atherosclerotic plaque formation is associated with irregular distribution of wall shear stress (WSS) that modulates endothelial function and integrity. Polycystins (PC)-1/-2 constitute a flow-sensing protein complex in endothelial cells, able to respond to WSS and induce cell-proliferation changes leading to atherosclerosis. An endothelial cell-culture system of measurable WSS was established to detect alterations in PCs expression under conditions of low- and high-oscillatory shear stress in vitro. PCs expression and p53 activation as a regulator of cell proliferation were further evaluated in vivo and in 69 advanced human carotid atherosclerotic plaques (AAPs). Increased PC-1/PC-2 expression was observed at 30-60 min of low shear stress (LSS) in endothelial cells. Elevated PC-1 expression at LSS was followed by p53 potentiation. PCs immunoreactivity localizes in areas with macrophage infiltration and neovascularization. PC-1 mRNA and protein levels were significantly higher than PC-2 in stable fibroatherotic (V) and unstable/complicated (VI) AAPs. Elevated PC-1 immunostaining was detected in AAPs from patients with diabetes mellitus, dyslipidemia, hypertension and carotid stenosis, at both arteries (50%) or in one artery (90%). PCs seem to participate in plaque formation and progression. Since PC-1 upregulation coincides with p38 and p53 activation, a potential interplay of these molecules in atherosclerosis induction is posed.

Layer-dependent wall properties of abdominal aortic aneurysms: Experimental study and material characterization.

Mechanical testing and in-depth characterization of the abdominal aortic aneurysm wall from fifteen patients undergoing open surgery was performed to establish the layer-dependent tissue properties that are non-available in the literature. Quantitative microscopic evaluation was performed to identify the spatial organization of collagen-fiber network. Among a number of candidate models, the four-fiber family (microstructure-motivated) model, especially that including dispersions of fiber angles about the main directions, was superior to the Fung- and Gasser-type models in the fitting quality allowed, though it presented a practical difficulty in parameter estimation, so that an analysis was conducted aiding the identification of a more specific diagonal- and circumferential-fiber family model for all three layers. The adventitia was stiffer and stronger than the other layers, owing to its increased collagen content, and its contribution to the response of the intact wall was augmented being under greater residual tension than the media, whereas the intima was under residual compression. All layers were stiffer circumferentially than longitudinally, due to preferential collagen arrangement along that axis. The histologically-guided material characterization of layered wall presented herein is expected to assist clinical decision, by developing reliable criteria to predict the rupture risk of abdominal aortic aneurysms, and optimize endovascular interventions.

Studying the flow dynamics in an aortic endograft with crossed-limbs.

PURPOSE: To evaluate the flow phenomena within an aortic endograft with crossed-limbs, comparing to an endograft with the ordinary limb bifurcation. METHODS: An endograft model with crossed-limbs was computationally reconstructed based on Computed Tomography patient-specific data, using commercially available software. Accordingly, its analogue model was reconstructed in the ordinary fashion (ordinary bifurcation). Computational fluid dynamics analysis was performed to determine and compare the flow fields, velocity profiles, pressure and shear stress distribution throughout the different parts of both endograft configurations, in different phases of the cardiac cycle. RESULTS: The flow patterns between the "Ballerina" and the classic endograft were similar, with flow disturbance near the inlet zone at late diastole and smooth flow patterns during the systolic phase. Both configurations presented similar pressure distribution patterns throughout the cardiac cycle. The highest and lowest pressures were demonstrated in the inlet-main body area and the iliac limbs, respectively. Marked differences were observed in the velocity profiles of the proximal limb segments between the two configurations, mostly in the peak- and end-systolic phase. The regions of lower velocities correlated well to low shear values. Differences in the shear stress distribution were noted between the two configurations in the systolic and, predominantly, in the diastolic phase. CONCLUSIONS: There are differences in the velocity profiles and shear distribution between the limbs of the two endograft configurations. The pathophysiologic implication of our findings and their possible association with clinical events, such as thrombus apposition, deserves further investigation.

Time-course of venous wall biomechanical adaptation in pressure and flow-overload: assessment by a microstructure-based material model.

Arteriovenous fistulae have been previously created by our group, through implantation of e-PTFE grafts between the carotid artery and jugular vein in healthy pigs, to gather comprehensive data on the time-course of the adapted geometry, composition, and biomechanical properties of the venous wall exposed to chronic increases in pressure and flow. The aim of this study was to mathematically assess the biomechanical adaptation of venous wall, by characterizing our previous in vitro inflation/extension testing data obtained 2, 4, and 12 weeks post-fistula, using a microstructure-based material model. Our choice for such a model considered a quadratic function for elastin with a four-fiber family term for collagen, and permitted realistic data characterization for both overloaded and control veins. As structural validation to the hemodynamically-driven differences in the material response, computerized histology was employed to quantitate the composition and orientation of collagen and elastin-fiber networks. The parameter values optimized showed marked differences among the overloaded and control veins, namely decrease in the quadratic function parameters and increase in the four-fiber family parameters. Differences among the two vein types were highlighted with respect to the underlying microstructure, namely the reduced elastin and increased collagen contents induced by pressure and flow-overload. Explicit correlations were found of the material parameters with the two basic scleroprotein contents, substantiating the material model used and the characterization findings presented. Our results are expected to improve the current understanding of the dynamics of venous adaptation under sustained pressure- and flow-overload conditions, for which data are largely unavailable and contradictory.

Geometric factors affecting the displacement forces in an aortic endograft with crossed limbs: a computational study.

PURPOSE: To compare the hemodynamic behavior between an aortic endograft model in the "crossed-limbs" configuration and the customary bifurcated deployment position under the influence of several geometric factors. METHODS: A crossed-limbs graft and its analogue model with uncrossed limbs were computationally reconstructed. The displacement forces acting over the entire endograft and at the bifurcation and iliac sites separately were calculated using a fluid structure interaction simulation under a range of specific geometric characteristics, namely, the lateral and anteroposterior (AP) neck angulation, the iliac bifurcation angulation, and the endograft curvature. RESULTS: The variations of lateral neck angulation caused a constantly higher total displacement force for the crossed-limbs graft, whereas the force at the bifurcation of the two configurations differed only within a narrow range of 30° to 50°. On the contrary, the displacement force at the iliac site was higher in the crossed-limbs configuration only with lateral neck angulation >50°, reaching its highest value at 70°. The variations of AP neck angulation also caused higher total displacement forces in the crossed-limbs graft. Increasing AP neck angulation values caused generally lower forces at the crossed iliac limbs and higher at its bifurcation, respectively, compared to the uncrossed limbs model. Similarly, the influence of high iliac bifurcation angulation and endograft curvature was associated with slightly elevated forces over the entire crossed-limbs graft and its bifurcation, whereas the opposite held true at the iliac site. CONCLUSION: Apart from minor differentiations due to geometric alterations, the customary bifurcated and crossed-limbs endografts present similar hemodynamic performance. Further clinical studies should be conducted to confirm the clinical applicability of these findings.

A computational study of the factors influencing pressure in arteriovenous fistulae venous aneurysms.

PURPOSE: To investigate the factors influencing the hydrostatic pressure exerted within the venous aneurysms (VA) of an arteriovenous fistula (AVF). METHODS: Ideal models of a side-to-end brachial-cephalic AVF were computationally constructed and typical values for the length and the local diameters were considered for both the artery and vein sections of the models. Three VA configurations were reconstructed (spherical, fusiform and curved) and hydrostatic pressure was assessed with respect to different degrees of the outflow vein stenosis, ranging from 25% to 95%, and VA maximum diameters, using validated, commercially available software. RESULTS: The pressure in the VA was steady (1200 Pa) for venous outflow stenoses up to 75%. For stenoses greater than 75% a exponential pressure rise was observed, reaching 1500 Pa for stenoses of 95%. Neither the VA configuration nor its maximum diameter affected the pressure values exerted within the VA or the point of the pressure upstroke. CONCLUSIONS: our study supports the presence of a critical stenotic outflow vein diameter beyond which there is an exponential VA pressure increase, influenced neither by the shape nor the size of the VA. Whether the prompt, non-invasive detection of this finding can contribute or lead to the determination of a criterion for early intervention in VAs before clinical complications are developed, should be investigated by future studies.

Modeling and computational analysis of the hemodynamic effects of crossing the limbs in an aortic endograft ("ballerina" position).

PURPOSE: To evaluate the displacement forces acting on an aortic endograft when the iliac limbs are crossed ("ballerina" position). METHODS: An endograft model was computationally reconstructed based on data from a patient whose infrarenal aortic aneurysm had an endovascular stent-graft implanted with the iliac limbs crossed. Computational fluid dynamics analysis determined the maximum displacement force on the endograft and separately on the bifurcation and iliac limbs. Its analogue model was reconstructed for comparison, assuming the neck, main body, and total length constant but considering the iliac limbs to be deployed in the usual bifurcated mode. Calculations were repeated after developing "idealized" models of both the bifurcated and crossed-limbs endografts with straight main bodies and no neck angulation or curved iliac segments. RESULTS: The vector of the total force was directed anterocaudal for both the typical bifurcated and the crossed-limbs configurations, with the forces in the latter slightly reduced and the vertical component accounting for most of the force in both configurations. Idealized crossed-limbs and bifurcated configurations differed only in the force on the iliac limbs, but this difference disappeared in the realistic models. CONCLUSION: Crossing of the iliac limbs can slightly affect the direction of the displacement forces. Although this configuration can exert larger forces on the limbs than in the bifurcated mode, this effect can be blunted by concomitant modifications in the geometry of the main body and other parts of the endograft, making its hemodynamic behavior resemble that of a typically positioned endograft.

Time course of flow-induced adaptation of carotid artery biomechanical properties, structure and zero-stress state in the arteriovenous shunt.

Numerous studies have provided evidence of diameter adaptation secondary to flow-overload, but with ambiguous findings vis à vis other morphological parameters and information on the biomechanical aspects of arterial adaptation is rather incomplete. We examined the time course of large-artery biomechanical adaptation elicited by long-term flow-overload in a porcine shunt model between the carotid artery and ipsilateral jugular vein. Post-shunting, the proximal artery flow was doubled and retained so until euthanasia (up to three months post-operatively), without pressure change. This hemodynamic stimulus induced lumen diameter enlargement, accommodated by elastin fragmentation and connective tissue accumulation, as witnessed by optical and confocal microscopy. Heterogeneous mass growth of the adventitia was observed at the expense of the media, associated with declining residual strains and opening angle at three months. The in vitro elastic properties of shunted arteries determined by inflation/extension testing were also modified, with the thickness-pressure curves shifted to larger thicknesses and the diameter-pressure curves shifted to larger diameters at physiologic pressures, resulting in normalization of intramural and shear stresses within fifteen and thirty days, respectively. We infer that the biomechanical adaptation in moderate flow-overload leads to normalization of intimal shear, without, however, restoring compliance and distensibility at mean in vivo pressure to control levels.

A novel method for the generation of multi-block computational structured grids from medical imaging of arterial bifurcations.

In this study a description of a new approach, for the generation of multi-block structured computational grids on patient-specific bifurcation geometries is presented. The structured grid generation technique is applied to data obtained by medical imaging examination, resulting in a surface conforming, high quality, multi-block structured grid of the branching geometry. As a case study application a patient specific abdominal aorta bifurcation is selected. For the evaluation of the grid produced by the novel method, a grid convergence study and a comparison between the grid produced by the method and unstructured grids produced by commercial meshing software are carried out.

A methodology to generate structured computational grids from DICOM data: application to a patient-specific abdominal aortic aneurysm (AAA) model.

This study presents the generation of a multi-block structured grid on a real abdominal aortic aneurysm (AAA) acquired from Digital Imaging and Communication in Medicine (DICOM) data. With the use of a computed tomography exam (or medical images in standard DICOM format), the shape of a human organ is extracted and a structured computational grid is created. The structured grid generation is done by utilising Floater's and Gopalsamy et al.'s algorithm. The proposed methodology is applied to the AAA case, but it may also be applied to other human organs, enabling the scientist to develop an advanced patient-specific model. More importantly, the proposed methodology provides a precise reconstruction of the human organs, which is required in an AAA, where small variations in the geometry may alter the flow field, the stresses exerted on the walls and finally the rupture risk of the aneurysm.

Differential histomechanical response of carotid artery in relation to species and region: mathematical description accounting for elastin and collagen anisotropy.

The selection of a mathematical descriptor for the passive arterial mechanical behavior has been long debated in the literature and customarily constrained by lack of pertinent data on the underlying microstructure. Our objective was to analyze the response of carotid artery subjected to inflation/extension with phenomenological and microstructure-based candidate strain-energy functions (SEFs), according to species (rabbit vs. pig) and region (proximal vs. distal). Histological variations among segments were examined, aiming to explicitly relate them with the differential material response. The Fung-type model could not capture the biphasic response alone. Combining a neo-Hookean with a two-fiber family term alleviated this restraint, but force data were poorly captured, while consideration of low-stress anisotropy via a quadratic term allowed improved simulation of both pressure and force data. The best fitting was achieved with the quadratic and Fung-type or four-fiber family SEF. The latter simulated more closely than the two-fiber family the high-stress response, being structurally justified for all artery types, whereas the quadratic term was justified for transitional and muscular arteries exhibiting notable elastin anisotropy. Diagonally arranged fibers were associated with pericellular medial collagen, and circumferentially and longitudinally arranged fibers with medial and adventitial collagen bundles, evidenced by the significant correlations of SEF parameters with quantitative histology.

Local hemodynamics and intimal hyperplasia at the venous side of a porcine arteriovenous shunt.

Venous anastomotic intimal hyperplasia (IH) observed in the arteriovenous shunt (AVS) has been associated with disturbed hemodynamics. This study aims to correlate hemodynamics with wall histology and wall mechanics by examining the flow field in AVS with computational fluid dynamics using experimental data taken from in vivo experiments. Input data to the computational model were obtained in vivo one month after AVS creation; adjacent vessels were submitted to histological and mechanical examination. The 3-D shunt geometry was determined using biplane angiography. Ultrasound measurements of flow rates were performed with perivascular flow probes and pressures were recorded through intravascular catheters. These data were considered as boundary conditions for calculation of the unsteady flow field. Numerical findings are suggestive of strong Dean vortices toward both vein flow exits, verified by color Doppler. The high wall shear stresses (WSSs) and their gradients appear to be related to areas of IH and vessel wall stiffening, as evidenced in preliminary histological and mechanical studies of the venous wall. Additionally, suture line hyperplasia seems to be aggravated by the high WSS gradients noted at the transition line from graft to vein.

Biomechanical, morphological and zero-stress state characterization of jugular vein remodeling in arteriovenous fistulas for hemodialysis.

While the role of hemodynamic variables on the development of intimal hyperplasia in arteriovenous fistulas for hemodialysis has been examined, less is known about the intramural biomechanical factors. In this study, arteriovenous fistulas were created by implantation of e-PTFE grafts between carotid artery and jugular vein in healthy pigs. In vivo recordings exhibited a three-fold pressure and flow elevation in grafted veins after fistula creation, remaining so until sacrifice. The chief morphological observation in grafted vessels was wall thickening at two weeks, serving to restore intramural stresses to homeostatic levels, and a less marked internal diameter enlargement, gradually normalizing intimal shear after four weeks. The residual strains and opening angle, specifying the zero-stress configuration, increased with differences reaching significance at twelve weeks. Association with histomorphological findings on intima, media and adventitia growth disclosed a correlation between intimal hyperplasia and opening angle increase. Elastin and cellular contents diminished opposite to collagen content, most differences occurring within the first four weeks after grafting. Inflation/extension testing showed that post-fistula the vein wall became progressively thicker and stiffer, lacking restoration of compliance to baseline levels. The present data may further our understanding of the dynamics of venous biomechanical remodeling under pressure and flow-overload conditions.

Vascular wall flow-induced forces in a progressively enlarged aneurysm model.

The current study is focused on the numerical investigation of the flow field induced by the unsteady flow in the vicinity of an abdominal aortic aneurysm model. The computational fluid dynamics code used is based on the finite volume method, and it has already been used in various bioflow studies. For modelling the rheological behaviour of blood, the Quemada non-Newtonian model is employed, which is suitable for simulating the two-phase character of blood namely a suspension of blood cells in plasma. For examining its non-Newtonian effects a comparison with a corresponding Newtonian flow is carried out. Furthermore, the investigation is focused on the distribution of the flow-induced forces on the interior wall of the aneurysm and in order to study the development of the distribution with the gradual enlargement of the aneurysm, three different degrees of aneurysm-growth have been assumed. Finally and for examining the effect of the distribution on the aneurysm growth, a comparison is made between the pressure and wall shear-stress distributions at the wall for each growth-degree.