Including Aortic Valve Morphology in Computational Fluid Dynamics Simulations: Initial Findings and Application to Aortic Coarctation

Computational fluid dynamics (CFD) simulations quantifying thoracic aortic flow patterns have not included disturbances from the aortic valve (AoV). 80% of patients with aortic coarctation (CoA) have a bicuspid aortic valve (BAV) which may cause adverse flow patterns contributing to morbidity. Our objectives were to develop a method to account for the AoV in CFD simulations, and quantify its impact on local hemodynamics. The method developed facilitates segmentation of the AoV, spatiotemporal interpolation of segments, and anatomic positioning of segments at the CFD model inlet. The AoV was included in CFD model examples of a normal (tricuspid AoV) and a post-surgical CoA patient (BAV). Velocity, turbulent kinetic energy (TKE), time-averaged wall shear stress (TAWSS), and oscillatory shear index (OSI) results were compared to equivalent simulations using a plug inlet profile. The plug inlet greatly underestimated TKE for both examples. TAWSS differences extended throughout the thoracic aorta for the CoA BAV, but were limited to the arch for the normal example. OSI differences existed mainly in the ascending aorta for both cases. The impact of AoV can now be included with CFD simulations to identify regions of deleterious hemodynamics thereby advancing simulations of the thoracic aorta one step closer to reality

Computational simulations demonstrate altered wall shear stress in aortic coarctation patients previously treated by resection with end-to-end anastomosis

Background.  Atherosclerotic plaque in the descending thoracic aorta (dAo) is related to altered wall shear stress (WSS) for normal patients. Resection with end-to-end anastomosis (RWEA) is the gold standard for coarctation of the aorta (CoA) repair, but may lead to altered WSS indices that contribute to morbidity. Methods.  Computational fluid dynamics (CFD) models were created from imaging and blood pressure data for control subjects and age- and gender-matched CoA patients treated by RWEA (four males, two females, 15 ± 8 years). CFD analysis incorporated downstream vascular resistance and compliance to generate blood flow velocity, time-averaged WSS (TAWSS), and oscillatory shear index (OSI) results. These indices were quantified longitudinally and circumferentially in the dAo, and several visualization methods were used to highlight regions of potential hemodynamic susceptibility. Results.  The total dAo area exposed to subnormal TAWSS and OSI was similar between groups, but several statistically significant local differences were revealed. Control subjects experienced left-handed rotating patterns of TAWSS and OSI down the dAo. TAWSS was elevated in CoA patients near the site of residual narrowings and OSI was elevated distally, particularly along the left dAo wall. Differences in WSS indices between groups were negligible more than 5 dAo diameters distal to the aortic arch. Conclusions.  Localized differences in WSS indices within the dAo of CoA patients treated by RWEA suggest that plaque may form in unique locations influenced by the surgical repair. These regions can be visualized in familiar and intuitive ways allowing clinicians to track their contribution to morbidity in longitudinal studies

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

Moving Domain Computational Fluid Dynamics to Interface with an Embryonic Model of Cardiac Morphogenesis

Peristaltic contraction of the embryonic heart tube produces time- and spatial-varying wall shear stress (WSS) and pressure gradients (∇P) across the atrioventricular (AV) canal. Zebrafish (Danio rerio) are a genetically tractable system to investigate cardiac morphogenesis. The use of Tg(fli1a:EGFP)y1 transgenic embryos allowed for delineation and two-dimensional reconstruction of the endocardium. This time-varying wall motion was then prescribed in a two-dimensional moving domain computational fluid dynamics (CFD) model, providing new insights into spatial and temporal variations in WSS and ∇P during cardiac development. The CFD simulations were validated with particle image velocimetry (PIV) across the atrioventricular (AV) canal, revealing an increase in both velocities and heart rates, but a decrease in the duration of atrial systole from early to later stages. At 20-30 hours post fertilization (hpf), simulation results revealed bidirectional WSS across the AV canal in the heart tube in response to peristaltic motion of the wall. At 40-50 hpf, the tube structure undergoes cardiac looping, accompanied by a nearly 3-fold increase in WSS magnitude. At 110-120 hpf, distinct AV valve, atrium, ventricle, and bulbus arteriosus form, accompanied by incremental increases in both WSS magnitude and ∇P, but a decrease in bi-directional flow. Laminar flow develops across the AV canal at 20-30 hpf, and persists at 110-120 hpf. Reynolds numbers at the AV canal increase from 0.07±0.03 at 20-30 hpf to 0.23±0.07 at 110-120 hpf (p< 0.05, n=6), whereas Womersley numbers remain relatively unchanged from 0.11 to 0.13. Our moving domain simulations highlights hemodynamic changes in relation to cardiac morphogenesis; thereby, providing a 2-D quantitative approach to complement imaging analysis. © 2013 Lee et al

A computational framework for generating patient-specific vascular models and assessing uncertainty from medical images

Patient-specific computational modeling is a popular, non-invasive method to answer medical questions. Medical images are used to extract geometric domains necessary to create these models, providing a predictive tool for clinicians. However, in vivo imaging is subject to uncertainty, impacting vessel dimensions essential to the mathematical modeling process. While there are numerous programs available to provide information about vessel length, radii, and position, there is currently no exact way to determine and calibrate these features. This raises the question, if we are building patient-specific models based on uncertain measurements, how accurate are the geometries we extract and how can we best represent a patient's vasculature? In this study, we develop a novel framework to determine vessel dimensions using change points. We explore the impact of uncertainty in the network extraction process on hemodynamics by varying vessel dimensions and segmenting the same images multiple times. Our analyses reveal that image segmentation, network size, and minor changes in radius and length have significant impacts on pressure and flow dynamics in rapidly branching structures and tapering vessels. Accordingly, we conclude that it is critical to understand how uncertainty in network geometry propagates to fluid dynamics, especially in clinical applications.Comment: 21 pages, 9 figure

Cavopulmonary Support for Failing Fontan Patients: Computational and In Vitro Assessment

Congenital heart defects are responsible for the mortality of approximately 300,000 newborn each year. One study in 2010 estimated that over 2 million patients were living with congenital heart defects in the United States. Congenital heart defects have the highest hospitalization cost among other birth defect categories. The damage on the U.S economy in 2013 was estimated $6.1 billion. The most complex and severe form of these defects results in single ventricle physiology. Fortunately, over the last 50 years, these patients have been able to survive into adulthood as a result of three stages of surgeries culminating with Fontan operation. However, Fontan operation as the current ultimate palliation of single ventricle defects results in significant late complications. Fontan patients will eventually develop circulatory failure and are in desperate need of an immediate therapeutic solution. A rightsided device surgically placed in the cavopulmonary pathway could technically substitute the missing sub-pulmonary ventricle by generating a mild pressure boost. However, currently, there is no device specifically designed for this application due to the small market size. On the other hand, off-label use of an arterial pump (originally designed for left side application) for the cavopulmonary support remains challenging. This is because the hemodynamic impact of a ventricular assist device (VAD) implanted on the right circulation of a Fontan patient is not yet clear. Moreover, further research is needed to identify the physiological consequences of two clinically-considered surgical configurations (IVC and full assisted configurations) for the cavopulmonary VAD installation, with full and IVC support corresponding to the entire venous return or only the inferior venous return, respectively, being routed through the VAD. First objective of this thesis is surgical planning to accurately predict the outcome of cavopulmonary support in failing Fontan patients and findings of this study will help the surgeons in developing coherent clinical strategies for the cavopulmonary support implementation and tuning. Specific objective 2 will investigate the desired operating region for designing a cavopulmonary blood pump that can offer a promising alternative treatment option for a wide range of failing Fontan patients

Relationship between hemodynamics and in-stent restenosis in femoral arteries

Although percutaneous transluminal angioplasty with stenting is one of the preferred treatments of lower extremity peripheral artery disease, this procedure suffers from a 66% 1-year primary patency rate. The unfavorable outcome is mostly attributable to in-stent restenosis, an inflammatory-driven arterial response, characterized by excessive smooth muscle cell proliferative and synthetic activity ultimately leading to lumen re-narrowing. The etiology of in-stent restenosis is multifactorial, involving different systemic, biological and biomechanical drivers. Among the biomechanical factors, a key role has been recognized to the stent-induced hemodynamic alteration, influencing smooth muscle cell activity both directly and through endothelium-dependent mechanisms. In this scenario, computational fluid dynamics simulations of stented femoral arteries allowed quantifying the local hemodynamics and identifying wall shear stress-based hemodynamic predictors of in-stent restenosis. This contributed to enhance the current knowledge of the fluid dynamic-related mechanisms of post-stenting lumen remodeling. However, given the multiscale and multifactorial nature of in-stent restenosis, multiscale mechanobiological modeling relating the intervention-induced mechanical stimuli to the complex network of biological events has recently emerged as a fundamental approach to decipher the underlying pathological pathways. This involves the analysis of interactions, cause-effect relationships, feedback mechanisms and cascade signaling pathways across different spatial and temporal scales, thus allowing tracking the effect of the interventioninduced perturbation to the molecular, cellular and finally tissue response. The present chapter examines the state-of-the-art of computational fluid dynamics studies of in-stent restenosis in femoral arteries and provides an overview on the emerging field of multiscale mechanobiological modeling of arterial adaptation following endovascular procedures

On the major role played by the curvature of intracranial aneurysms walls in determining their mechanical response, local hemodynamics, and rupture likelihood

The properties of intracranial aneurysms (IAs) walls are known to be driven by the underlying hemodynamics adjacent to the IA sac. Different pathways exist explaining the connections between hemodynamics and local tissue properties. The emergence of such theories is essential if one wishes to compute the mechanical response of a patient-specific IA wall and predict its rupture. Apart from the hemodynamics and tissue properties, one could assume that the mechanical response also depends on the local morphology, more specifically, the wall curvature, with larger values at highly-curved wall portions. Nonetheless, this contradicts observations of IA rupture sites more often found at the dome, where the curvature is lower. This seeming contradiction indicates a complex interaction between local hemodynamics, wall morphology, and mechanical response, which warrants further investigation. This was the main goal of this work. We accomplished this by analysing the stress and stretch fields in different regions of the wall for a sample of IAs, which have been classified based on particular local hemodynamics and local curvature. Pulsatile numerical simulations were performed using the one-way fluid-solid interaction strategy implemented in OpenFOAM (solids4foam toolbox). We found that the variable best correlated with regions of high stress and stretch was the wall curvature. Additionally, our data suggest a connection between the local curvature and local hemodynamics, indicating that the curvature is a property that could be used to assess both mechanical response and hemodynamic conditions, and, moreover, to suggest new metrics based on the curvature to predict the likelihood of rupture.Comment: Preprint submitted to Acta Biomaterialia, with 27 pages and 11 figure