Patient-Specific Modeling of Altered Coronary Artery Hemodynamics to Predict Morbidity in Patients with Anomalous Origin of a Coronary Artery

Anomalous aortic origin of a coronary artery (AAOCA) is a condition where a coronary artery arises from the opposite aortic sinus, often with acute angle of origin (AO). AAOCA is associated with ischemia.1 This is especially concerning when the anomalous coronary artery takes an intramural course within the aortic wall, creating the potential for distortion or compression. Unroofing surgery replaces a restrictive ostium and intramural segment with a large ostium from the appropriate sinus and aims to create a less acute AO. Although these anatomical features may alter coronary artery blood flow patterns, hemodynamic indices such as time averaged wall shear stress (TAWSS), oscillatory shear index (OSI) and fractional flow reserve (FFR) that impact a patient’s future risk for ischemia and morbidity 2–6 remain largely unexplored. We hypothesized that morphology of the anomalous coronary artery has a significant impact on local hemodynamics of AAOCA and aimed to 1) characterize hemodynamic alterations in AAOCA by patient-specific simulation of patients pre-operative and post-unroofing using advanced coronary artery boundary conditions, 2) assess the impact of AO on the severity of hemodynamic alterations, and 3) characterize the hemodynamic effect of proximal narrowing of the anomalous artery and hyperemic resistance of the downstream vasculature (HMR) on FFR. Findings from Aim 1 suggested that different flow patterns exist natively between right and left coronary arteries, a reduction in TAWSS is observed post-unroofing, and that unroofing may normalize TAWSS but with variance related to the AO. Data from Aim 2 indicated that AO alters TAWSS and OSI in simulations run from a patient-specific model with virtually rotated AOs. The arterial wall experienced lower TAWSS for more acute AO near the ostium. Distal to the ostium, arterial wall experienced higher TAWSS for more acute AO. Findings from Aim 3 showed that for a given narrowing, higher HMR resulted in higher FFR thereby mimicking the interaction of the upstream and downstream micro-vasculature resistance to regulate FFR for the first time using computational models of AAOCA. Virtual manipulation of the anomalous artery provided a direct comparison for the effect of the anatomic high-risk features. Collectively, these results serve as the foundation for larger studies of AAOCA that could correlate hemodynamics with outcomes for risk stratification and surgical evaluation

Shear-promoted drug encapsulation into red blood cells: a CFD model and μ-PIV analysis

The present work focuses on the main parameters that influence shear-promoted encapsulation of drugs into erythrocytes. A CFD model was built to investigate the fluid dynamics of a suspension of particles flowing in a commercial micro channel. Micro Particle Image Velocimetry (μ-PIV) allowed to take into account for the real properties of the red blood cell (RBC), thus having a deeper understanding of the process. Coupling these results with an analytical diffusion model, suitable working conditions were defined for different values of haematocrit

Temporal tracking of 3D coronary arteries in projection angiograms

International audienceA method for 3D temporal tracking of a 3D coronary tree model through a sequence of biplane cineangiography images has been developed. A registration framework is formulated in which the coronary tree centerline model deforms in an external potential ¯eld de¯ned by a multiscale analysis response map computed from the angiogram images. To constrain the procedure and to improve convergence, a set of three motion models is hierarchically used: a 3D rigid-body transformation, a 3D a±ne transformation, and a 3D B-spline deformation ¯eld. This 3D motion tracking approach has signi¯cant advantages over 2D methods: (1) coherent deformation of a single 3D coronary reconstruction preserves the topology of the arterial tree; (2) constraints on arterial length and regularity, which lack meaning in 2D projection space, are directly applicable in 3D; and (3) tracking arterial segments through occlusions and crossings in the projection images is simpli¯ed with knowledge of the 3D relationship of the arteries. The method has been applied to patient data and results are presented

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

Three-Dimensional Motion Tracking of Coronary Arteries in Biplane Cineangiogram

International audienceA three-dimensional (3-D) method for tracking the coronary arteries through a temporal sequence of biplane X-ray angiography images is presented. A 3-D centerline model of the coronary vasculature is reconstructed from a biplane image pair at one time frame, and its motion is tracked using a coarse-to-fine hierarchy of motion models. Three-dimensional constraints on the length of the arteries and on the spatial regularity of the motion field are used to overcome limitations of classical two-dimensional vessel tracking methods, such as tracking vessels through projective occlusions. This algorithm was clinically validated in five patients by tracking the motion of the left coronary tree over one cardiac cycle. The root mean square reprojection errors were found to be submillimeter in 93% (54/58) of the image pairs. The performance of the tracking algorithm was quantified in three dimensions using a deforming vascular phantom. RMS 3-D distance errors were computed between centerline models tracked in the X-ray images and gold-standard centerline models of the phantom generated from a gated 3-D magnetic resonance image acquisition. The mean error was 0.69( 0.06) mm over eight temporal phases and four different biplane orientations

Intravascular Ultrasound

Intravascular ultrasound (IVUS) is a cardiovascular imaging technology using a specially designed catheter with a miniaturized ultrasound probe for the assessment of vascular anatomy with detailed visualization of arterial layers. Over the past two decades, this technology has developed into an indispensable tool for research and clinical practice in cardiovascular medicine, offering the opportunity to gather diagnostic information about the process of atherosclerosis in vivo, and to directly observe the effects of various interventions on the plaque and arterial wall. This book aims to give a comprehensive overview of this rapidly evolving technique from basic principles and instrumentation to research and clinical applications with future perspectives

Investigation of blood flow patterns and hemodynamics in the human ascending aorta and major trunks of right and left coronary arteries using magnetic resonance imaging and computational fluid dynamics

Hemodynamic factors play a role in atherogenesis and the localization of atherosclerotic plaques. The human aorta and coronary arteries are susceptible to arterial disease, and there have been many studies of flows in models of these vessels. However, previous work has been limited in that investigations have not modeled both the geometry and flow conditions in specific individuals. The first aim of the research was to develop a methodology that combined computational fluid dynamics (CFD) and magnetic resonance imaging (MRI) to simulate the blood flow patterns found in the human aorta. The methodology included MR image processing, 3D model reconstruction and flow simulation using in vivo velocity boundary conditions obtained from phase contrast (PC)-MRI scanning. The CFD simulations successfully reproduce the unusual right-hand helical flow pattern that has been reported in the ascending aorta, giving confidence in the accuracy of the methodology. The second aim was to investigate the causes of the right-hand helical flow. It was found that the correct flow dynamics could only be produced by including the specific aortic motion caused by the beating heart; and it is concluded that this is a significant factor in producing the observed in vivo helical flow patterns. The entrance flows of coronary arteries are expected to be affected by flow in the aortic root, and the third aim was to explore these effects using models that include aorta and coronary arteries. The simulation results demonstrate that a pair of axial vortexes with different rotating directions exists in the entrance segments of the right and left coronary arteries during systole and early diastole, producing asymmetrical wall shear stress (WSS) distributions. The last aim of the research was to examine possible relationships between WSS distributions induced by the entry flow patterns and the frequency distributions of atherosclerosis in the proximal segments of coronary arteries reported in the clinical literature. A close correspondence between low WSS and higher frequency of plaque occurrence was observed. The tools developed in this study provide a promising avenue for future study of cardiovascular disease because of the ability to investigate phenomena in individual human subjects.Ph.D.Committee Chair: Giddens, P. Don; Committee Member: Bao, Gang; Committee Member: Oshinski, John; Committee Member: Taylor, Robert, W.; Committee Member: Vito, P. Raymon

New perspectives in percutaneous coronary intervention based on an integrated approach of imaging and physiology

In this thesis we investigated: a) the prognostic role of FFR in functional evaluation of epicardial stenosis in different anatomical and clinical settings of patients with stable CAD, heart valve disease and LVD; b) the role of IMR, CFR and absolute coronary flow and microvascular resistances assessment with a new dedicated thermodilution catheter; c) the diagnostic performance of two new angiography-derived FFR technologies for a quantitative and functional assessment of CAD; d) the impact of antiplatelet agents and BVS Absorb™ implantantion on procedure-related microvascular impairment, platelet activation and the related myonecrosis; e) the safety and feasibility of new 2-stent bifurcation techniques and the clinical outcome of known bifurcations techniques. We believe that many answers have been provided by our extensive translational research. FFR remains the milestone in functional assessment of the ischemic burden related to coronary stenoses. Our findings corroborate the strong clinical outcome background of FFR, supporting FFR-guided revascularization strategies above angio-based decision making, and therefore strongly discouraging any purely anatomy guided revascularization attempts in different clinical and anatomical settings. Absolute coronary blood flow (Q) and microvascular resistance (R) can be safely and reproducibly measured with continuous thermodilution, opening new opportunities for the study of the coronary microcirculation. FFRangio and QFR provide both a comprehensive physiological assessment of the entire coronary tree within few minutes, enabling online FFR measurement during the angiographic procedure. This, in turn, may facilitate the adoption of FFR-based clinical decision making regarding coronary revascularization. Both prasugrel and BVS Abosrb™ have proven a beneficial acute effect on peri-procedural coronary microvascular function and platelet activation. Although BVS Absorb™ did not live up to its promise because of the higher events in the mid-term due to greater scaffold thrombosis, our findings are at least reassuring on the acute impact of these devices on the microcirculation. Lastly in PCI of bifurcation lesions, our feasibility results of in vitro tests, offer new solutions for both complex anatomy requiring 2-stent-technique and bailout technique in case of failure of the most consolidated provisional T-stenting

Oscillatory flow in a tube with time-dependent wall deformation and its application to Myocardial Bridges

In this paper we numerically investigate a one-dimensional model of blood flow in the human coronary arteries. The nonlinear hyperbolic system is expressed in terms of the cross-sectional area, flow velocity and pressure (A, u, p). The more widely studied linearised system is also discussed where conservation of static pressure, instead of total pressure, is enforced. The method of outgoing characteristics is used to satisfy the interface conditions, while a three-element windkessel model is adopted as outflow condition at the terminals of the network. Inside the segmental domain the leap-frog method is used for numerical integration. Within the context of this model we pay particular attention to the case when abrupt or smooth, space and time dependent variation of cross-sectional area of an artery is caused by externally prescribed motion of the vessel walls (e.g. myocardial bridge, flow watch). The derivation of the model and the numerical implementation are detailed. They are applied to model numerical experiments of the arterial system. Additionally to a system studied in [10, 15, 22, 28] the coronary arteries are parameterised. The main features of the flow through myocardial bridges are discussed