A computational study of the hemodynamic impact of open- versus closed-cell stent design in carotid artery stenting.

The aim of this study is to analyze the shape and flow changes of a patient-specific carotid artery after carotid artery stenting (CAS) performed using an open-cell (stent-O) or a closed-cell (stent-C) stent design. First, a stent reconstructed from micro-computed tomography (microCT) is virtually implanted in a left carotid artery reconstructed from CT angiography. Second, an objective analysis of the stent-to-vessel apposition is used to quantify the lumen cross-sectional area and the incomplete stent apposition (ISA). Third, the carotid artery lumen is virtually perfused in order to quantify its resistance to flow and its exposure to atherogenic or thrombogenic hemodynamic conditions. After CAS, the minimum cross-sectional area of the internal carotid artery (ICA) (external carotid artery [ECA]) changes by +54% (-12%) with stent-O and +78% (-17%) with stent-C; the resistance to flow of the ICA (ECA) changes by -21% (+13%) with stent-O and -26% (+18%) with stent-C. Both stent designs suffer from ISA but the malapposed stent area is larger with stent-O than stent-C (29.5 vs. 14.8 mm(2) ). The untreated vessel is not exposed to atherogenic flow conditions whereas an area of 67.6 mm(2) (104.9) occurs with stent-O (stent-C). The area of the stent surface exposed to thrombogenic risk is 5.42 mm(2) (7.7) with stent-O (stent-C). The computer simulations of stenting in a patient's carotid artery reveal a trade-off between cross-sectional size and flow resistance of the ICA (enlarged and circularized) and the ECA (narrowed and ovalized). Such a trade-off, together with malapposition, atherogenic risk, and thrombogenic risk is stent-design dependent.

Impact of carotid stent cell design on vessel scaffolding: a case study comparing experimental investigation and numerical simulations.

PURPOSE: To quantitatively evaluate the impact of carotid stent cell design on vessel scaffolding by using patient-specific finite element analysis of carotid artery stenting (CAS). METHODS: The study was organized in 2 parts: (1) validation of a patient-specific finite element analysis of CAS and (2) evaluation of vessel scaffolding. Micro-computed tomography (CT) images of an open-cell stent deployed in a patient-specific silicone mock artery were compared with the corresponding finite element analysis results. This simulation was repeated for the closed-cell counterpart. In the second part, the stent strut distribution, as reflected by the inter-strut angles, was evaluated for both cell types in different vessel cross sections as a measure of scaffolding. RESULTS: The results of the patient-specific finite element analysis of CAS matched well with experimental stent deployment both qualitatively and quantitatively, demonstrating the reliability of the numerical approach. The measured inter-strut angles suggested that the closed-cell design provided superior vessel scaffolding compared to the open-cell counterpart. However, the full strut interconnection of the closed-cell design reduced the stent's ability to accommodate to the irregular eccentric profile of the vessel cross section, leading to a gap between the stent surface and the vessel wall. CONCLUSION: Even though this study was limited to a single stent design and one vascular anatomy, the study confirmed the capability of dedicated computer simulations to predict differences in scaffolding by open- and closed-cell carotid artery stents. These simulations have the potential to be used in the design of novel carotid stents or for procedure planning.

The impact of simplified boundary conditions and aortic arch inclusion on CFD simulations in the mouse aorta: a comparison with mouse-specific reference data.

Computational fluid dynamics (CFD) simulations allow for calculation of a detailed flow field in the mouse aorta and can thus be used to investigate a potential link between local hemodynamics and disease development. To perform these simulations in a murine setting, one often needs to make assumptions (e.g. when mouse-specific boundary conditions are not available), but many of these assumptions have not been validated due to a lack of reference data. In this study, we present such a reference data set by combining high-frequency ultrasound and contrast-enhanced micro-CT to measure (in vivo) the time-dependent volumetric flow waveforms in the complete aorta (including seven major side branches) of 10 male ApoE -/- deficient mice on a C57Bl/6 background. In order to assess the influence of some assumptions that are commonly applied in literature, four different CFD simulations were set up for each animal: (i) imposing the measured volumetric flow waveforms, (ii) imposing the average flow fractions over all 10 animals, presented as a reference data set, (iii) imposing flow fractions calculated by Murray's law, and (iv) restricting the geometrical model to the abdominal aorta (imposing measured flows). We found that - even if there is sometimes significant variation in the flow fractions going to a particular branch - the influence of using average flow fractions on the CFD simulations is limited and often restricted to the side branches. On the other hand, Murray's law underestimates the fraction going to the brachiocephalic trunk and strongly overestimates the fraction going to the distal aorta, influencing the outcome of the CFD results significantly. Changing the exponential factor in Murray's law equation from 3 to 2 (as suggested by several authors in literature) yields results that correspond much better to those obtained imposing the average flow fractions. Restricting the geometrical model to the abdominal aorta did not influence the outcome of the CFD simulations. In conclusion, the presented reference dataset can be used to impose boundary conditions in the mouse aorta in future studies, keeping in mind that they represent a subsample of the total population, i.e., relatively old, non-diseased, male C57Bl/6 ApoE -/- mice.

Mixed impact of torsion on LV hemodynamics: A CFD study based on the Chimera technique.

Image-based patient-specific Computational Fluid Dynamics (CFD) models of the Left Ventricle (LV) can be used to quantify hemodynamics-based biomarkers that can support the clinicians in the early diagnosis, follow-up and treatment planning of patients, beyond the capabilities of the current imaging modalities. We propose a workflow to build patient-specific CFD models of the LV with moving boundaries based on the Chimera technique to overcome the convergence issues previously encountered by means of the Arbitrarian Lagrangian Eulerian approach. The workflow was tested while investigating whether the torsional motion has an impact on LV fluid dynamics. Starting from 3D cine MRI scans of a healthy volunteer, six cardiac cycles were simulated in three CFD LV models: with no, physiological, and exaggerated torsion. The Chimera technique was robust in handling the impulsive motion of the LV endocardium, allowing to notice cycle-to-cycle variations in every simulated case. Torsion affected slightly velocity, vorticity, WSS. It did not affect energy loss and induced a double-sided effect in terms of residence time: the particles ejected in one beat decreased, whereas the motility of the particles remaining in the LV was affected only in the exaggerated torsion case, indicating that implementation of torsion can be discarded in case of physiological levels. Nonetheless, caution is warranted when interpreting these results given the absence of the mitral valve, the papillary muscles, and the trabeculae. The effects of the mitral valve will be evaluated within an Fluid Structure Interaction simulation framework as further development of the current model.

Optimization of a Transcatheter Heart Valve Frame Using Patient-Specific Computer Simulation.

PURPOSE: This study proposes a new framework to optimize the design of a transcatheter aortic valve through patient-specific finite element and fluid dynamics simulation. METHODS: Two geometrical parameters of the frame, the diameter at ventricular inflow and the height of the first row of cells, were examined using the central composite design. The effect of those parameters on postoperative complications was investigated by response surface methodology, and a Nonlinear Programming by Quadratic Lagrangian algorithm was used in the optimization. Optimal and initial devices were then compared in 12 patients. The comparison was made in terms of device performance [i.e., reduced contact pressure on the atrioventricular conduction system and paravalvular aortic regurgitation (AR)]. RESULTS: Results suggest that large diameters and high cells favor higher anchoring of the device within the aortic root reducing the contact pressure and favor a better apposition of the device to the aortic root preventing AR. Compared to the initial device, the optimal device resulted in almost threefold lower predicted contact pressure and limited AR in all patients. CONCLUSIONS: In conclusion, patient-specific modelling and simulation could help to evaluate device performance prior to the actual first-in-human clinical study and, combined with device optimization, could help to develop better devices in a shorter period.

From 4D Medical Images (CT, MRI, and Ultrasound) to 4D Structured Mesh Models of the Left Ventricular Endocardium for Patient-Specific Simulations.

With cardiovascular disease (CVD) remaining the primary cause of death worldwide, early detection of CVDs becomes essential. The intracardiac flow is an important component of ventricular function, motion kinetics, wash-out of ventricular chambers, and ventricular energetics. Coupling between Computational Fluid Dynamics (CFD) simulations and medical images can play a fundamental role in terms of patient-specific diagnostic tools. From a technical perspective, CFD simulations with moving boundaries could easily lead to negative volumes errors and the sudden failure of the simulation. The generation of high-quality 4D meshes (3D in space + time) with 1-to-1 vertex becomes essential to perform a CFD simulation with moving boundaries. In this context, we developed a semiautomatic morphing tool able to create 4D high-quality structured meshes starting from a segmented 4D dataset. To prove the versatility and efficiency, the method was tested on three different 4D datasets (Ultrasound, MRI, and CT) by evaluating the quality and accuracy of the resulting 4D meshes. Furthermore, an estimation of some physiological quantities is accomplished for the 4D CT reconstruction. Future research will aim at extending the region of interest, further automation of the meshing algorithm, and generating structured hexahedral mesh models both for the blood and myocardial volume.

Patient-Specific Computer Simulation to Elucidate the Role of Contact Pressure in the Development of New Conduction Abnormalities After Catheter-Based Implantation of a Self-Expanding Aortic Valve.

BACKGROUND: The extent to which pressure generated by the valve on the aortic root plays a role in the genesis of conduction abnormalities after transcatheter aortic valve replacement (TAVR) is unknown. This study elucidates the role of contact pressure and contact pressure area in the development of conduction abnormalities after TAVR using patient-specific computer simulations. METHODS AND RESULTS: Finite-element computer simulations were performed to simulate TAVR of 112 patients who had undergone TAVR with the self-expanding CoreValve/Evolut R valve. On the basis of preoperative multi-slice computed tomography, a patient-specific region of the aortic root containing the atrioventricular conduction system was determined by identifying the membranous septum. Contact pressure and contact pressure index (percentage of area subjected to pressure) were quantified and compared in patients with and without new conduction abnormalities. Sixty-two patients (55%) developed a new left bundle branch block or a high-degree atrioventricular block after TAVR. Maximum contact pressure and contact pressure index (median [interquartile range]) were significantly higher in patients with compared with those without new conduction abnormalities (0.51 MPa [0.43-0.70 MPa] and 33% [22%-44%], respectively, versus 0.29 MPa [0.06-0.50 MPa] and 12% [1%-28%]). By multivariable regression analysis, only maximum contact pressure (odds ratio, 1.35; confidence interval, 1.1-1.7; P=0.01) and contact pressure index (odds ratio, 1.52; confidence interval, 1.1-2.1; P=0.01) were identified as independent predictors for conduction abnormalities, but not implantation depth. CONCLUSIONS: Patient-specific computer simulations revealed that maximum contact pressure and contact pressure index are both associated with new conduction abnormalities after CoreValve/Evolut R implantation and can predict which patient will have conduction abnormalities.

A Novel Tram Stent Method in the Treatment of Coronary Bifurcation Lesions - Finite Element Study.

A novel stent was designed for the treatment of coronary bifurcation lesion, and it was investigated for its performance by finite element analysis. This study was performed in search of a novel method of treatment of bifurcation lesion with provisional stenting. A bifurcation model was created with the proximal vessel of 3.2 mm diameter, and the distal vessel after the side branch (2.3 mm) was 2.7 mm. A novel stent was designed with connection links that had a profile of a tram. Laser cutting and shape setting of the stent was performed, and thereafter it was crimped and deployed over a balloon. The contact pressure, stresses on the arterial wall, stresses on the stent, the maximal principal log strain of the main artery and the side-branch were studied. The study was performed in Abaqus, Simulia. The stresses on the main branch and the distal branch were minimally increased after deployment of this novel stent. The side branch was preserved, and the stresses on the side branch were lesser; and at the confluence of bifurcation on either side of the side branch origin the von-Mises stress was marginally increased. The stresses and strain at the bifurcation were significantly lesser than the stresses and strain of the currently existing techniques used in the treatment of bifurcation lesions though the study was primarily focused only on the utility of the new technology. There is a potential for a novel Tram-stent method in the treatment of coronary bifurcation lesions.

Patient-specific image-based computer simulation for theprediction of valve morphology and calcium displacement after TAVI with the Medtronic CoreValve and the Edwards SAPIEN valve.

AIMS: Our aim was to validate patient-specific software integrating baseline anatomy and biomechanical properties of both the aortic root and valve for the prediction of valve morphology and aortic leaflet calcium displacement after TAVI. METHODS AND RESULTS: Finite element computer modelling was performed in 39 patients treated with a Medtronic CoreValve System (MCS; n=33) or an Edwards SAPIEN XT (ESV; n=6). Quantitative axial frame morphology at inflow (MCS, ESV) and nadir, coaptation and commissures (MCS) was compared between multislice computed tomography (MSCT) post TAVI and a computer model as well as displacement of the aortic leaflet calcifications, quantified by the distance between the coronary ostium and the closest calcium nodule. Bland-Altman analysis revealed a strong correlation between the observed (MSCT) and predicted frame dimensions, although small differences were detected for, e.g., Dmin at the inflow (mean±SD MSCT vs. MODEL: 21.6±2.4 mm vs. 22.0±2.4 mm; difference±SD: -0.4±1.3 mm, p<0.05) and Dmax (25.6±2.7 mm vs. 26.2±2.7 mm; difference±SD: -0.6±1.0 mm, p<0.01). The observed and predicted calcium displacements were highly correlated for the left and right coronary ostia (R2=0.67 and R2=0.71, respectively p<0.001). CONCLUSIONS: Dedicated software allows accurate prediction of frame morphology and calcium displacement after valve implantation, which may help to improve outcome.

Patient-specific computer modelling of coronary bifurcation stenting: the John Doe programme.

John Doe, an 81-year-old patient with a significant distal left main (LM) stenosis, was treated using a provisional stenting approach. As part of an European Bifurcation Club (EBC) project, the complete stenting procedure was repeated using computational modelling. First, a tailored three-dimensional (3D) reconstruction of the bifurcation anatomy was created by fusion of multislice computed tomography (CT) imaging and intravascular ultrasound. Second, finite element analysis was employed to deploy and post-dilate the stent virtually within the generated patient-specific anatomical bifurcation model. Finally, blood flow was modelled using computational fluid dynamics. This proof-of-concept study demonstrated the feasibility of such patient-specific simulations for bifurcation stenting and has provided unique insights into the bifurcation anatomy, the technical aspects of LM bifurcation stenting, and the positive impact of adequate post-dilatation on blood flow patterns. Potential clinical applications such as virtual trials and preoperative planning seem feasible but require a thorough clinical validation of the predictive power of these computer simulations.

Finite element modeling of a novel self-expanding endovascular stent method in treatment of aortic aneurysms.

A novel large self-expanding endovascular stent was designed with strut thickness of 70 µm × 70 µm width. The method was developed and investigated to identify a novel simpler technique in aortic aneurysm therapy. Stage 1 analysis was performed after deploying it in a virtual aneurysm model of 6 cm wide × 6 cm long fusiform hyper-elastic anisotropic design. At cell width of 9 mm, there was no buckling or migration of the stent at 180 Hg. Radial force of the stents was estimated after parametric variations. In stage 2 analysis, a prototype 300 µm × 150 µm stent with a cell width of 9 mm was chosen, and it was evaluated similarly after embedding in the aortic wall, and also with a tissue overgrowth of 1 mm over the stent. The 300/150 µm stent reduced the peak wall stress by 70% in the aneurysm and 50% reduction in compliance after embedding. Stage 3 analysis was performed to study the efficacy of stents with struts (thickness/width) 70/70, 180/100 and 300/150 µm after embedding and tissue overgrowth. The adjacent wall stresses were very minimal in stents with 180/100 and 70/70 µm struts after embedding. There is potential for a novel stent method in aortic aneurysm therapy.

Provisional stenting of coronary bifurcations: insights into final kissing balloon post-dilation and stent design by computational modeling.

OBJECTIVES: This study sought to better understand and optimize provisional main vessel stenting with final kissing balloon dilation (FKBD). BACKGROUND: Main vessel stenting with FKBD is widely used, but many technical variations are possible that may affect the final result. Furthermore, most contemporary stent designs have a large cell size, making the impact of stent platform selection for this procedure unclear. METHODS: Finite element simulations were used to virtually deploy and post-dilate 3 stent platforms in 3 bifurcation models. Two FKBD strategies were evaluated: simultaneous FKBD (n = 27) and modified FKBD (n = 27). In the simultaneous FKDB technique, both balloons were simultaneously inflated and deflated. In the modified FKBD technique, the side branch balloon was inflated first, then partially deflated, followed by main branch balloon inflation. RESULTS: Modified FKBD results in less ostial stenosis compared with simultaneous FKBD (15 ± 9% vs. 20 ± 11%; p < 0.001) and also reduces elliptical stent deformation (ellipticity index, 1.17 ± 0.05 vs. 1.36 ± 0.06; p < 0.001). The number of malapposed stent struts was not influenced by the FKBD technique (modified FKBD, 6.3 ± 3.6%; simultaneous FKBD, 6.4 ± 3.4%; p = 0.212). Stent design had no significant impact on the remaining ostial stenosis (Integrity [Medtronic, Inc., Minneapolis, Minnesota], 16 ± 11%; Omega [Boston Scientific, Natick, Massachusetts], 17 ± 11%; Multi-Link 8 [Abbott Vascular, Santa Clara, California], 19 ± 8%). CONCLUSIONS: The modified FKBD procedure reduces elliptical stent deformation and optimizes side branch access.

Accuracy of carotid strain estimates from ultrasonic wall tracking: a study based on multiphysics simulations and in vivo data.

We used a multiphysics model to assess the accuracy of carotid strain estimates derived from a 1-D ultrasonic wall tracking algorithm. The presented tool integrates fluid-structure interaction (FSI) simulations with an ultrasound simulator (Field II), which allows comparison of the ultrasound (US) images with a ground truth. Field II represents tissue as random points on which US waves reflect and whose position can be updated based on the flow field and vessel wall deformation from FSI. We simulated the RF-signal of a patient-specific carotid bifurcation, including the blood pool as well as the vessel wall and surrounding tissue. Distension estimates were obtained from a wall tracking algorithm using tracking points at various depths within the wall, and further processed to assess radial and circumferential strain. The simulated data demonstrated that circumferential strain can be estimated with reasonable accuracy (especially for the common carotid artery and at the lumen-intima and media-adventitia interface), but the technique does not allow to reliably assess intra-arterial radial strain. These findings were supported by in vivo data of 10 healthy adults, showing similar circumferential and radial strain profiles throughout the arterial wall. We concluded that these deviations are present due to the complex 3-D vessel wall deformation, the presence of specular reflections and, to a lesser extent, the spatially varying beam profile, with the error depending on the phase in the cardiac cycle and the scanning location.

Full-hexahedral structured meshing for image-based computational vascular modeling.

Image-based computational modeling offers a virtual access to spatially and temporally high resolution flow and structural mechanical data in vivo. Due to inter-subject morphological variability, mesh generation represents a critical step in modeling the patient-specific geometry and is usually performed using unstructured tetrahedral meshing algorithms. Although hexahedral structured meshes are known to provide higher accuracy and reduce the computational costs both for Finite Element Analysis and Computational Fluid Dynamics, their application in computational cardiovascular studies is challenging due to the complex 3D and branching topology of vascular territories. In this study, we propose a robust procedure for structured mesh generation, tailoring the mesh structure to the subject-specific vessel topology. The proposed methodology is based on centerline-based synthetic descriptors (i.e. centerlines, radii and centerlines' normals) which are used to solve the meshing problem following a bottom-up approach. First, topologically equivalent block-structures are placed inside and outside the lumen domain. Then, a projection operation is performed, returning a parametric volume mesh which fits the original triangulated model with sub-micrometric accuracy. Additionally, a three-layered arterial wall (resembling the intima, media and adventitia) is artificially generated, with the possibility of setting variable thickness (e.g. proximal-to-distal tapering) and material anisotropy (e.g. position-dependent collagen-fibers' orientation). This new meshing procedure, implemented using open-source software packages only, is demonstrated on two challenging human cases, being an aortic arch and an abdominal aortic aneurysm. High-quality meshes are generated in both cases, according to shape-quality metrics. By increasing the computation accuracy, the developed meshing tool has the potential to further add "confidence" to the use of computational methods in vascular applications.

An integrated framework to quantitatively link mouse-specific hemodynamics to aneurysm formation in angiotensin II-infused ApoE -/- mice.

Locally disturbed flow has been suggested to play a (modulating) role in abdominal aortic aneurysm (AAA) formation, but no longitudinal studies have been performed yet due to (a.o.) a lack of human data prior to AAA formation. In this study we made use of recent advances in small animal imaging technology in order to set up entirely mouse-specific computational fluid dynamics (CFD) simulations of the abdominal aorta in an established ApoE -/- mouse model of AAA formation, combining (i) in vivo contrast-enhanced micro-CT scans (geometrical model) and (ii) in vivo high-frequency ultrasound scans (boundary conditions). Resulting areas of disturbed flow at baseline were compared to areas of AAA at end-stage. Qualitative results showed that AAA dimension is maximal in areas that are situated proximal to those areas that experience most disturbed flow in three out of four S developing an AAA. Although further quantitative analysis did not reveal any obvious relationship between areas that experience most disturbed flow and the end-stage AAA dimensions, we cannot exclude that hemodynamics play a role in the initial phases of AAA formation. Due to its mouse-specific and in vivo nature, the presented methodology can be used in future research to link detailed and animal-specific (baseline) hemodynamics to (end-stage) arterial disease in longitudinal studies in mice.

Patient-specific computational fluid dynamics: structured mesh generation from coronary angiography.

Patient-specific simulations are widely used to investigate the local hemodynamics within realistic morphologies. However, pre-processing and mesh generation are time consuming, operator dependent, and the quality of the resulting mesh is often suboptimal. Therefore, a semi-automatic methodology for patient-specific reconstruction and structured meshing of a left coronary tree from biplane angiography is presented. Seven hexahedral grids have been generated with the new method (50,000-3,200,000 cells) and compared to nine unstructured tetrahedral grids with prismatic boundary layer (150,000-3,100,000 cells). Steady-state blood flow simulation using Computational Fluid Dynamics (CFD) has been used to calculate the Wall Shear Stress (WSS). Our results (99 percentile, area-weighted and local WSS values along a line) demonstrate that hexahedral meshes with respect to tetrahedral/prismatic meshes converge better, and for the same accuracy of the result, six times less cells and 14 times less computational time are required. Hexahedral meshes are superior to tetrahedral/prismatic meshes and should be preferred for the calculation of the WSS.