Improving Cardiovascular Stent Design Using Patient-Specific Models and Shape Optimization

Stent geometry influences local hemodynamic alterations (i.e. the forces moving blood through the cardiovascular system) associated with adverse clinical outcomes. Computational fluid dynamics (CFD) is frequently used to quantify stent-induced hemodynamic disturbances, but previous CFD studies have relied on simplified device or vascular representations. Additionally, efforts to minimize stent-induced hemodynamic disturbances using CFD models often only compare a small number of possible stent geometries. This thesis describes methods for modeling commercial stents in patient-specific vessels along with computational techniques for determining optimal stent geometries that address the limitations of previous studies. An efficient and robust method was developed for virtually implanting stent models into patient-specific vascular geometries derived from medical imaging data. Models of commercial stent designs were parameterized to allow easy control over design features. Stent models were then virtually implanted into vessel geometries using a series of Boolean operations. This approach allowed stented vessel models to be automatically regenerated for rapid analysis of the contribution of design features to resulting hemodynamic alterations. The applicability of the method was demonstrated with patient-specific models of a stented coronary artery bifurcation and basilar trunk aneurysm to reveal how it can be used to investigate differences in hemodynamic performance in complex vascular beds for a variety of clinical scenarios. To identify hemodynamically optimal stents designs, a computational framework was constructed to couple CFD with a derivative-free optimization algorithm. The optimization algorithm was fully-automated such that solid model construction, mesh generation, CFD simulation and time-averaged wall shear stress (TAWSS) quantification did not require user intervention. The method was applied to determine the optimal number of circumferentially repeating stent cells (NC) for a slotted-tube stents and various commercial stents. Optimal stent designs were defined as those minimizing the area of low TAWSS. It was determined the optimal value of NC is dependent on the intrastrut angle with respect to the primary flow direction. Additionally, the geometries of current commercial stents were found to generally incorporate a greater NC than is hemodynamically optimal. The application of the virtual stent implantation and optimization methods may lead to stents with superior hemodynamic performance and the potential for improved clinical outcomes. Future in vivo studies are needed to validate the findings of the computational results obtained from the methods developed in this thesis

Identification of Hemodynamically Optimal Coronary Stent Designs Based on Vessel Caliber

Coronary stent design influences local patterns of wall shear stress (WSS) that are associated with neointimal growth, restenosis, and the endothelialization of stent struts. The number of circumferentially repeating crowns NC for a given stent de- sign is often modified depending on the target vessel caliber, but the hemodynamic implications of altering NC have not previously been studied. In this investigation, we analyzed the relationship between vessel diameter and the hemodynamically optimal NC using a derivative-free optimization algorithm coupled with computational fluid dynamics. The algorithm computed the optimal vessel diameter, defined as minimizing the area of stent-induced low WSS, for various configurations (i.e., NC) of a generic slotted-tube design and designs that resemble commercially available stents. Stents were modeled in idealized coronary arteries with a vessel diameter that was allowed to vary between 2 and 5 mm. The results indicate that the optimal vessel diameter increases for stent configurations with greater NC, and the designs of current commercial stents incorporate a greater NC than hemodynamically optimal stent designs. This finding suggests that reducing the NC of current stents may improve the hemodynamic environment within stented arteries and reduce the likelihood of excessive neointimal growth and thrombus formation

A Rapid and Computationally Inexpensive Method to Virtually Implant Current and Next-Generation Stents into Subject-Specific Computational Fluid Dynamics Models

Computational modeling is often used to quantify hemodynamic alterations induced by stenting, but frequently uses simplified device or vascular representations. Based on a series of Boolean operations, we developed an efficient and robust method for assessing the influence of current and next-generation stents on local hemodynamics and vascular biomechanics quantified by computational fluid dynamics. Stent designs were parameterized to allow easy control over design features including the number, width and circumferential or longitudinal spacing of struts, as well as the implantation diameter and overall length. The approach allowed stents to be automatically regenerated for rapid analysis of the contribution of design features to resulting hemodynamic alterations. The applicability of the method was demonstrated with patient-specific models of a stented coronary artery bifurcation and basilar trunk aneurysm constructed from medical imaging data. In the coronary bifurcation, we analyzed the hemodynamic difference between closed-cell and open-cell stent geometries. We investigated the impact of decreased strut size in stents with a constant porosity for increasing flow stasis within the stented basilar aneurysm model. These examples demonstrate the current method can be used to investigate differences in stent performance in complex vascular beds for a variety of stenting procedures and clinical scenarios

Local Hemodynamic Changes Caused by Main Branch Stent Implantation and Subsequent Side Branch Balloon Angioplasty in a Representative Coronary Bifurcation

Abnormal blood flow patterns promoting inflammation, cellular proliferation, and thrombosis may be established by local changes in vessel geometry after stent implantation in bifurcation lesions. Our objective was to quantify altered hemodynamics due to main vessel (MV) stenting and subsequent virtual side branch (SB) angioplasty in a coronary bifurcation by using computational fluid dynamics (CFD) analysis. CFD models were generated from representative vascular dimensions and intravascular ultrasound images. Time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), and fractional flow reserve (FFR) were quantified. None of the luminal surface was exposed to low TAWSS (/cm2) in the nondiseased bifurcation model. MV stenting introduced eccentric areas of low TAWSS along the lateral wall of the MV. Virtual SB angioplasty resulted in a more concentric region of low TAWSS in the MV distal to the carina and along the lateral wall of the SB. The luminal surface exposed to low TAWSS was similar before and after virtual SB angioplasty (rest: 43% vs. 41%; hyperemia: 18% vs. 21%) and primarily due to stent-induced flow alterations. Sites of elevated OSI (\u3e0.1) were minimal but more impacted by general vessel geometry established after MV stenting. FFR measured at a jailed SB was within the normal range despite angiographic stenosis of 54%. These findings indicate that the most commonly used percutaneous interventional strategy for a bifurcation lesion causes abnormal local hemodynamic conditions. These results may partially explain the high clinical event rates in bifurcation lesions

Immersive Visualization for Enhanced Computational Fluid Dynamics Analysis

Modern biomedical computer simulations produce spatiotemporal results that are often viewed at a single point in time on standard 2D displays. An immersive visualization environment (IVE) with 3D stereoscopic capability can mitigate some shortcomings of 2D displays via improved depth cues and active movement to further appreciate the spatial localization of imaging data with temporal computational fluid dynamics (CFD) results. We present a semi-automatic workflow for the import, processing, rendering, and stereoscopic visualization of high resolution, patient-specific imaging data, and CFD results in an IVE. Versatility of the workflow is highlighted with current clinical sequelae known to be influenced by adverse hemodynamics to illustrate potential clinical utility

Computational Fluid Dynamics Evaluation of Equivalency in Hemodynamic Alterations Between Driver, Integrity, and Similar Stents Implanted Into an Idealized Coronary Artery

We tested the hypothesis that a slight modification in fabrication from the Driver to the Integrity stent (Medtronic) results in nearly equivalent distributions of wall shear stress (WSS) and mean exposure time (MET), reflective of flow stagnation, and that these differences are considerably less than the Multi-Link Vision (Abbott Vascular) or BX Velocity (Cordis) bare metal stents when evaluated by computational fluid dynamics (CFD). Arteries were modeled as idealized straight rigid vessels without lesions. Two vessel diameters (2.25 and 3.0 mm) were studied for each stent and 2.75 mm diameter Integrity stents were also modeled to quantify the impact from best- and worst-case orientations of the stent struts relative to the primary blood flow direction. All stents were 18 mm in length and over-deployed by 10%. The results indicated that, regardless of diameter, the BX Velocity stents had the greatest percentage of the vessel exposed to adverse WSS followed by the Vision, Integrity, and Driver stents. In general, when strut thickness and stent:lumen ratio are similar, the orientation of struts is a determining factor for deleterious flow patterns. For a given stent, the number of struts was a larger determinant of adverse WSS and MET than strut orientation, suggesting that favorable blood flow patterns can be achieved by limiting struts to those providing adequate scaffolding. In conclusion, the Driver and Integrity stents both limit their number of linkages to those which provide adequate scaffolding while also maintaining similar strut thickness and stent:lumen ratios. The Integrity stent also imparts a slight helical velocity component. The modest difference in the fabrication approach between the Driver and Integrity stents is, therefore, not hemodynamically substantial in this idealized analysis, particularly relative to potentially adverse flow conditions introduced by the other stents modeled. This data was used in conjunction with associated regulatory filings and submitted to the FDA as part of the documents facilitating the recent approval for sale of the Resolute Integrity stent in the United States

Optimization of Cardiovascular Stent Design Using Computational Fluid Dynamics

Coronarystent design affects the spatial distribution of wall shear stress(WSS), which can influence the progression of endothelialization, neointimal hyperplasia,and restenosis. Previous computational fluid dynamics (CFD) studies have onlyexamined a small number of possible geometries to identify stentdesigns that reduce alterations in near-wall hemodynamics. Based on apreviously described framework for optimizing cardiovascular geometries, we developed amethodology that couples CFD and three-dimensional shape-optimization for use instent design. The optimization procedure was fully-automated, such that solidmodel construction, anisotropic mesh generation, CFD simulation, and WSS quantificationdid not require user intervention. We applied the method todetermine the optimal number of circumferentially repeating stent cells (NC)for slotted-tube stents with various diameters and intrastrut areas. Optimalstent designs were defined as those minimizing the area oflow intrastrut time-averaged WSS. Interestingly, we determined that the optimalvalue of NC was dependent on the intrastrut angle withrespect to the primary flow direction. Further investigation indicated thatstent designs with an intrastrut angle of approximately 40 degminimized the area of low time-averaged WSS regardless of vesselsize or intrastrut area. Future application of this optimization methodto commercially available stent designs may lead to stents withsuperior hemodynamic performance and the potential for improved clinical outcomes

Optical Coherence Tomography for Patient-specific 3D Artery Reconstruction and Evaluation of Wall Shear Stress in a Left Circumflex Coronary Artery

Image-based computational models for quantifying hemodynamic indices in stented coronary arteries often employ biplane angiography and intravascular ultrasound for 3D reconstruction. Recent advances in guidewire simulation algorithms and the rise of optical coherence tomography (OCT) suggest more precise coronary artery reconstruction may be possible. We developed a patient-specific method that combines the superior resolution of OCT with techniques for imaging wire pathway reconstruction adopted from graph theory. The wire pathway with minimum bending energy was determined by applying a shortest path algorithm to a graph representation of the artery based on prior studies indicating a wire adopts the straightest configuration within a tortuous vessel. Segments from OCT images are then registered orthogonal to the wire pathway using rotational orientation consistent with geometry delineated by computed tomography (CT). To demonstrate applicability, OCT segments within the stented region were combined with proximal and distal CT segments and imported into computational fluid dynamics software to quantify indices of wall shear stress (WSS). The method was applied to imaging data of a left circumflex artery with thrombus acquired immediately post-stenting and after a 6-month follow-up period. Areas of stent-induced low WSS returned to physiological levels at follow-up, but correlated with measurable neointimal thickness in OCT images. Neointimal thickness was negligible in areas of elevated WSS due to thrombus. This novel methodology capable of reconstructing a stented coronary artery may ultimately enhance our knowledge of deleterious hemodynamic indices induced by stenting after further investigation in a larger patient population