Microfocal X-Ray Computed Tomography Post-Processing Operations for Optimizing Reconstruction Volumes of Stented Arteries During 3D Computational Fluid Dynamics Modeling

Restenosis caused by neointimal hyperplasia (NH) remains an important clinical problem after stent implantation. Restenosis varies with stent geometry, and idealized computational fluid dynamics (CFD) models have indicated that geometric properties of the implanted stent may differentially influence NH. However, 3D studies capturing the in vivo flow domain within stented vessels have not been conducted at a resolution sufficient to detect subtle alterations in vascular geometry caused by the stent and the subsequent temporal development of NH. We present the details and limitations of a series of post-processing operations used in conjunction with microfocal X-ray CT imaging and reconstruction to generate geometrically accurate flow domains within the localized region of a stent several weeks after implantation. Microfocal X-ray CT reconstruction volumes were subjected to an automated program to perform arterial thresholding, spatial orientation, and surface smoothing of stented and unstented rabbit iliac arteries several weeks after antegrade implantation. A transfer function was obtained for the current post-processing methodology containing reconstructed 16 mm stents implanted into rabbit iliac arteries for up to 21 days after implantation and resolved at circumferential and axial resolutions of 32 and 50 μm, respectively. The results indicate that the techniques presented are sufficient to resolve distributions of WSS with 80% accuracy in segments containing 16 surface perturbations over a 16 mm stented region. These methods will be used to test the hypothesis that reductions in normalized wall shear stress (WSS) and increases in the spatial disparity of WSS immediately after stent implantation may spatially correlate with the temporal development of NH within the stented region

VASCULAR CHANGES IN TYPE 2 DIABETES MELLITUS: APPLICATION TO RESTENOSIS AFTER STENTING

Stents used to decrease cardiovascular risk in patients with type 2 diabetes mellitus (T2DM) are prone to increased rates of restenosis. The mechanisms are incompletely elucidated, but low wall shear stress (WSS) and altered intracellular signaling likely contribute. We tested the hypothesis that neointimal hyperplasia (NH) after bare-metal stenting is due to vascular remodeling (enhanced formation of advanced glycation end-products (AGEs), increased downstream vascular resistance (DVR), and decreased WSS), and that decreasing AGEs with ALT-711 (Alagebrium) mitigates this response. Stents were implanted into the abdominal aorta of Zucker lean (ZL), obese (ZO), and diabetic (ZD) rats. After 21 days, the stented region was sectioned for NH quantification or casted and imaged for regional estimation of WSS and local intrastrut WSS by computational fluid dynamics. The thoracic and abdominal aorta, carotid, iliac, femoral and arterioles in cremaster muscle were harvested to detect AGEs related collagen cross-linking, and protein expression including transforming growth factor beta (TGFβ) and receptor for AGE (RAGE). A trend toward elevated DVR was observed, whereas blood flow (BF) and intrastrut TAWSS were significantly decreased in ZD compared to ZL and ZO rats (eg. TAWSS: 14.5 ± 1.9 vs 30.6 ± 1.6 and 25.4 ± 2.2 dyn/cm2, respectively; mean±SEM P\u3c0.05). Intrastrut NH was increased in ZO but not ZD rats. ALT-711 reduced DVR in ZD rats (15.6±2.5x105 to 8.39±0.6x105 dyn∙s/cm5), while decreasing NH (ZL: 7.7±1.0 to 4.3±0.9%; ZO: 12.0±1.5 to 4.9±0.8%; ZD: 9.4±0.7 to 3.7±0.4%) and causing similar regional TAWSS results in all groups. AGEs related collagen cross-linking was elevated in the arterioles of ZD rats, but alleviated by ALT-711. No consistent differences in RAGE or TGFβ expression were observed in treated versus untreated rats. Remodeling of the distal vasculature appears to play an important role in modulating WSS in T2DM, but WSS alone does not predict NH response as observed under normoglycemia. ALT-711 led to similar values for AGEs related arteriolar collagen cross-linking, BF through the stent, and regional WSS, while decreasing NH in all rats. Although TGFβ and RAGE expression did not appear to be modified by ALT-711, other intracellular signaling pathways remain to be explored

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

Immersive Visualization in Biomedical Computational Fluid Dynamics and Didactic Teaching and Learning

Virtual reality (VR) can stimulate active learning, critical thinking, decision making and improved performance. It requires a medium to show virtual content, which is called a virtual environment (VE). The MARquette Visualization Lab (MARVL) is an example of a VE. Robust processes and workflows that allow for the creation of content for use within MARVL further increases the userbase for this valuable resource. A workflow was created to display biomedical computational fluid dynamics (CFD) and complementary data in a wide range of VE’s. This allows a researcher to study the simulation in its natural three-dimensional (3D) morphology. In addition, it is an exciting way to extract more information from CFD results by taking advantage of improved depth cues, a larger display canvas, custom interactivity, and an immersive approach that surrounds the researcher. The CFD to VR workflow was designed to be basic enough for a novice user. It is also used as a tool to foster collaboration between engineers and clinicians. The workflow aimed to support results from common CFD software packages and across clinical research areas. ParaView, Blender and Unity were used in the workflow to take standard CFD files and process them for viewing in VR. Designated scripts were written to automate the steps implemented in each software package. The workflow was successfully completed across multiple biomedical vessels, scales and applications including: the aorta with application to congenital cardiovascular disease, the Circle of Willis with respect to cerebral aneurysms, and the airway for surgical treatment planning. The workflow was completed by novice users in approximately an hour. Bringing VR further into didactic teaching within academia allows students to be fully immersed in their respective subject matter, thereby increasing the students’ sense of presence, understanding and enthusiasm. MARVL is a space for collaborative learning that also offers an immersive, virtual experience. A workflow was created to view PowerPoint presentations in 3D using MARVL. A resulting Immersive PowerPoint workflow used PowerPoint, Unity and other open-source software packages to display the PowerPoint presentations in 3D. The Immersive PowerPoint workflow can be completed in under thirty minutes