Intravascular imaging of angioplasty balloon under-expansion during pre-dilation predicts hyperelastic behavior of coronary artery lesions

Introduction: Stent-induced mechanical stimuli cause pathophysiological responses in the coronary artery post-treatment. These stimuli can be minimized through choice of stent, size, and deployment strategy. However, the lack of target lesion material characterization is a barrier to further personalizing treatment. A novel ex-vivo angioplasty-based intravascular imaging technique using optical coherence tomography (OCT) was developed to characterize local stiffness of the target lesion.Methods: After proper institutional oversight, atherosclerotic coronary arteries (n = 9) were dissected from human donor hearts for ex vivo material characterization <48 h post-mortem. Morphology was imaged at the diastolic blood pressure using common intravascular OCT protocols and at subsequent pressures using a specially fabricated perfusion balloon that accommodates the OCT imaging wire. Balloon under-expansion was quantified relative to the nominal balloon size at 8 ATM. Correlation to a constitutive hyperelastic model was empirically investigated (n = 13 plaques) using biaxial extension results fit to a mixed Neo-Hookean and Exponential constitutive model.Results and discussion: The average circumferential Cauchy stress was 66.5, 130.2, and 300.4 kPa for regions with <15, 15–30, and >30% balloon under-expansion at a 1.15 stretch ratio. Similarly, the average longitudinal Cauchy stress was 68.1, 172.6, and 412.7 kPa, respectively. Consequently, strong correlation coefficients >0.89 were observed between balloon under-expansion and stress-like constitutive parameters. These parameters allowed for visualization of stiffness and material heterogeneity for a range of atherosclerotic plaques. Balloon under-expansion is a strong predictor of target lesion stiffness. These findings are promising as stent deployment could now be further personalized via target lesion material characterization obtained pre-operatively

Aortic Coarctation: Recent Developments in Experimental and Computational Methods to Assess Treatments for this Simple Condition

Coarctation of the aorta (CoA) is often considered a relatively simple disease, but long-term outcomes suggest otherwise as life expectancies are decades less than in the average population and substantial morbidity often exists. What follows is an expanded version of collective work conducted by the authors\u27 and numerous collaborators that was presented at the 1st International Conference on Computational Simulation in Congenital Heart Disease pertaining to recent advances for CoA. The work begins by focusing on what is known about blood flow, pressure and indices of wall shear stress (WSS) in patients with normal vascular anatomy from both clinical imaging and the use of computational fluid dynamics (CFD) techniques. Hemodynamic alterations observed in CFD studies from untreated CoA patients and those undergoing surgical or interventional treatment are subsequently discussed. The impact of surgical approach, stent design and valve morphology are also presented for these patient populations. Finally, recent work from a representative experimental animal model of CoA that may offer insight into proposed mechanisms of long-term morbidity in CoA is presented

Quantification of Local Hemodynamic Alterations Caused by Virtual Implantation of Three Commercially Available Stents for the Treatment of Aortic Coarctation

Patients with coarctation of the aorta (CoA) are prone to morbidity including atherosclerotic plaque that has been shown to correlate with altered wall shear stress (WSS) in the descending thoracic aorta (dAo). We created the first patient-specific computational fluid dynamics (CFD) model of a CoA patient treated by Palmaz stenting to date, and compared resulting WSS distributions to those from virtual implantation of Genesis XD and modified NuMED CP stents, also commonly used for CoA. CFD models were created from magnetic resonance imaging, fluoroscopy and blood pressure data. Simulations incorporated vessel deformation, downstream vascular resistance and compliance to match measured data and generate blood flow velocity and time-averaged WSS (TAWSS) results. TAWSS was quantified longitudinally and circumferentially in the stented region and dAo. While modest differences were seen in the distal portion of the stented region, marked differences were observed downstream along the posterior dAo and depended on stent type. The Genesis XD model had the least area of TAWSS values exceeding the threshold for platelet aggregation in vitro, followed by the Palmaz and NuMED CP stents. Alterations in local blood flow patterns and WSS imparted on the dAo appear to depend on the type of stent implanted for CoA. Following confirmation in larger studies, these findings may aid pediatric interventional cardiologists in selecting the most appropriate stent for each patient, and ultimately reduce long-term morbidity following treatment for CoA by stenting

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

Novel Applications of Cardiovascular Magnetic Resonance Imaging-Based Computational Fluid Dynamics Modeling in Pediatric Cardiovascular and Congenital Heart Disease

Cardiovascular diseases (CVDs) afflict many people across the world; thus, understanding the pathophysiology of CVD and the biomechanical forces which influence CVD progression is important in the development of optimal strategies to care for these patients. Over the last two decades, cardiac magnetic resonance (CMR) imaging has offered increasingly important insights into CVD. Computational fluid dynamics (CFD) modeling, a method of simulating the characteristics of flowing fluids, can be applied to the study of CVD through the collaboration of engineers and clinicians. This chapter aims to explore the current state of the CMR-derived CFD, as this technique pertains to both acquired CVD (i.e., atherosclerosis) and congenital heart disease (CHD)

Treating a 20 mm Hg Gradient Alleviates Myocardial Hypertrophy in Experimental Aortic Coarctation

Background Children with coarctation of the aorta (CoA) can have a hyperdynamic and remodeled left ventricle (LV) from increased afterload. Literature from an experimental model suggests the putative 20 mm Hg blood pressure gradient (BPG) treatment guideline frequently implemented in CoA studies may permit irreversible vascular changes. LV remodeling from pressure overload has been studied, but data are limited following correction and using a clinically representative BPG. Materials and methods Rabbits underwent CoA at 10 weeks to induce a 20 mm Hg BPG using permanent or dissolvable suture thereby replicating untreated and corrected CoA, respectively. Cardiac function was evaluated at 32 weeks by magnetic resonance imaging using a spoiled cine GRE sequence (TR/TE/FA 8/2.9/20), 14 × 14-cm FOV, and 3-mm slice thickness. Images (20 frames/cycle) were acquired in 6-8 short axis views from the apex to the mitral valve annulus. LV volume, ejection fraction (EF), and mass were quantified. Results LV mass was elevated for CoA (5.2 ± 0.55 g) versus control (3.6 ± 0.16 g) and corrected (4.0 ± 0.44 g) rabbits, resulting in increased LV mass/volume ratio for CoA rabbits. A trend toward increased EF and stroke volume was observed but did not reach significance. Elevated EF by volumetric analysis in CoA rabbits was supported by concomitant increases in total aortic flow by phase-contrast magnetic resonance imaging. Conclusions The indices quantified trended toward a persistent hyperdynamic LV despite correction, but differences were not statistically significant versus control rabbits. These findings suggest the current putative 20 mm Hg BPG for treatment may be reasonable from the LV\u27s perspective

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

Quantification of Thoracic Aorta Blood Flow by Magnetic Resonance Imaging During Supine Cycling Exercise of Increasing Intensity

Poster presentation from the 16th Annual SCMR Scientific Sessions San Francisco, CA, USA. 31 January - 3 February 2013

Image-based Quantification of 3D Morphology for Bifurcations in the Left Coronary Artery: Application to Stent Design

Background Improved strategies for stent‐based treatment of coronary artery disease at bifurcations require a greater understanding of artery morphology. Objective We developed a workflow to quantify morphology in the left main coronary (LMCA), left anterior descending (LAD), and left circumflex (LCX) artery bifurcations. Methods Computational models of each bifurcation were created for 55 patients using computed tomography images in 3D segmentation software. Metrics including cross‐sectional area, length, eccentricity, taper, curvature, planarity, branching law parameters, and bifurcation angles were assessed using open‐sources software and custom applications. Geometric characterization was performed by comparison of means, correlation, and linear discriminant analysis (LDA). Results Differences between metrics suggest dedicated or multistent approaches should be tailored for each bifurcation. For example, the side branch of the LCX (i.e., obtuse marginal; OM) was longer than that of the LMCA (i.e., LCXprox) and LAD (i.e., first diagonal; D1). Bifurcation metrics for some locations (e.g., LMCA Finet ratio) provide results and confidence intervals agreeing with prior findings, while revised metric values are presented for others (e.g., LAD and LCX). LDA revealed several metrics that differentiate between artery locations (e.g., LMCA vs. D1, LMCA vs. OM, LADprox vs. D1, and LCXprox vs. D1). Conclusions These results provide a foundation for elucidating common parameters from healthy coronary arteries and could be leveraged in the future for treating diseased arteries. Collectively the current results may ultimately be used for design iterations that improve outcomes following implantation of future dedicated bifurcation stents

Gene Expression in Experimental Aortic Coarctation and Repair: Candidate Genes for Therapeutic Intervention?

Coarctation of the aorta (CoA) is a constriction of the proximal descending thoracic aorta and is one of the most common congenital cardiovascular defects. Treatments for CoA improve life expectancy, but morbidity persists, particularly due to the development of chronic hypertension (HTN). Identifying the mechanisms of morbidity is difficult in humans due to confounding variables such as age at repair, follow-up duration, coarctation severity and concurrent anomalies. We previously developed an experimental model that replicates aortic pathology in humans with CoA without these confounding variables, and mimics correction at various times using dissolvable suture. Here we present the most comprehensive description of differentially expressed genes (DEGs) to date from the pathology of CoA, which were obtained using this model. Aortic samples (n=4/group) from the ascending aorta that experiences elevated blood pressure (BP) from induction of CoA, and restoration of normal BP after its correction, were analyzed by gene expression microarray, and enriched genes were converted to human orthologues. 51 DEGs with \u3e6 fold-change (FC) were used to determine enriched Gene Ontology terms, altered pathways, and association with National Library of Medicine Medical Subject Headers (MeSH) IDs for HTN, cardiovascular disease (CVD) and CoA. The results generated 18 pathways, 4 of which (cell cycle, immune system, hemostasis and metabolism) were shared with MeSH ID’s for HTN and CVD, and individual genes were associated with the CoA MeSH ID. A thorough literature search further uncovered association with contractile, cytoskeletal and regulatory proteins related to excitation-contraction coupling and metabolism that may explain the structural and functional changes observed in our experimental model, and ultimately help to unravel the mechanisms responsible for persistent morbidity after treatment for CoA