Numerical analysis of the impact of flow rate, heart rate, vessel geometry, and degree of stenosis on coronary hemodynamic indices

Background: The stenosis of the coronary arteries is usually caused by atherosclerosis. Hemodynamic significance of patient-specific coronary stenoses and the risk of its progression may be assessed by comparing the hemodynamic effects induced by flow disorders. The present study shows how stenosis degree and variable flow conditions in coronary artery affect the oscillating shear index, residence time index, pressure drop coefficient and fractional flow reserve. We assume that changes in the hemodynamic indices in relation to variable flow conditions and geometries evaluated using the computational fluid dynamics may be an additional factor for a non-invasive assessment of the coronary stenosis detected on multi-slice computed tomography. Methods: The local-parametrised models of basic shapes of the vessels, such as straight section, bend, and bifurcation as well as the global-patient-specific models of left coronary artery were used for numerical simulation of flow in virtually reconstructed stenotic vessels. Calculations were carried out for vessels both without stenosis, and vessels of 10 to 95% stenosis. The flow rate varied within the range of 20 to 1000 ml/min, and heart rate frequency within the range of 30 to 210 cycles/min. The computational fluid dynamics based on the finite elements method verified by the experimental measurements of the velocity profiles was used to analyse blood flow in the coronary arteries. Results: The results confirm our preliminary assumptions. There is significant variation in the coronary hemodynamic indices value caused by disturbed flow through stenosis in relation to variable flow conditions and geometry of vessels. Conclusion: Variations of selected hemodynamic indexes induced by change of flow rate, heart rate and vessel geometry, obtained during a non-invasive study, may assist in evaluating the risk of stenosis progression and in carrying out the assessment of the hemodynamic significance of coronary stenosis. However, for a more accurate assessment of the variability of indices and coronary stenosis severity both local (near the narrowing) and global (in side branches) studies should be used

Guidewire-mounted thermal sensors to assess coronary hemodynamics

The vessels of the coronary circulation are prone to arteriosclerotic disease, which can lead to the development of obstructions to blood flow. The conventional way to diagnose the severity of this type of disease is by coronary angiography. This method, however, only provides insight into the morphology of the coronary vessels, whereas for an accurate diagnosis a measure for the actual flow impediment is needed. To perform these measurements, sensor-tipped guidewires have been developed to measure intra-coronary pressure and blood flow velocity. Diagnosis of coronary disease based on the time-average of these measurements have been shown to improve the clinical outcome of treatment significantly. However, since the coronary vessels are embedded in the (contracting) cardiac muscle, the interpretation of these indices is complicated and can be improved by simultaneously assessing the dynamics of coronary pressure and flow. The research described in this thesis therefore focusses on the one hand on developing devices for the simultaneous assessment of coronary pressure and flow dynamics and on the other hand on modeling the heart and coronary vessels to support the interpretation of these dynamic measurements. In the development of a device which can measure both coronary pressure and flow, two different strategies have been chosen. In the first strategy, a method has been developed to operate an already clinically used pressure sensor-tipped guidewire (pressure wire) as a thermal anemometer to also measure flow. In an in-vitro model it has been demonstrated that the power required to electrically heat the sensor is a measure for the shear rate at the sensor surface and that the method can be used to assess coronary flow reserve (CFR). By slightly adapting the method and combining it with a continuous thermodilution method, it has also been shown that the dynamics of both pressure and volumetric flow can be measured simultaneously in physiological representative in-vitro and ex-vivo experiments. The main drawbacks of this thermal method with a pressure wire are the relatively high sensor temperature required and the inability to detect flow reversal. In the second strategy, a new flow sensor, embedded in a flexible polyimide chip, has been specially designed to be mounted on a guidewire. The flow sensing element consists of a heater, operated at constant power, and thermocouples measuring the temperature difference up- and downstream from the heater. To gain insight into the working principle and the importance of the different design parameters, an analytical model has been developed. Experiments where upscaled sensors have been subjected to steady and pulsatile flow, indicate that the model is able to reproduce the experimental results fairly well but that the sensitivity to shear rate is rather limited in the physiological range. This sensitivity to shear rate can possibly be improved by operating the heater at constant temperature, which has been investigated with invitro experiments with upscaled sensors and a finite element analysis of the real, small size sensor. These studies have demonstrated that constant temperature operation of the heater is beneficial over constant power operation and that the dynamics of physiological coronary shear rate, including retrograde flow, can be assessed at an overheat temperature of only 5 K. From these characterization studies a new design of the sensor has been proposed, which is currently being manufactured to be tested in both in-vitro and ex-vivo experiments. To support the interpretation of the dynamic pressure and flow measurements, a numerical model of the heart and coronary circulation has been developed. The model is based on the coupling of four interacting parts: A model for the left ventricle which is based on the mechanics of a single myofiber, a 1D wave propagation model for the large epicardial coronary arteries, a stenosis element, and a Windkessel representation of the coronary micro-vessels. Comparison of the results obtained with the model with experimental observations described in literature has shown that the model is able to simulate the effect of different types of disease on coronary hemodynamics. After further validation, the model can be used as a tool to study the effect of combinations of epicardial and/or microcirculatory disease on pressure- and flow-based indices. To model the relation between the pressure and flow waves in the coronary arteries correctly, as well as to assist in the decision-making regarding the mechanical treatment of coronary stenoses, the mechanical behaviour of the coronary arterial wall is required. Therefore, a mixed numerical-experimental method has been employed to fit a micro-structurally based constitutive model to in-situ extensioninflation experiments on porcine coronary arteries. It has been demonstrated that the model can accurately describe the experimental data and, additionally, it has been found that the most influential parameter, describing the collagen fiber orientation, can be considered constant at physiological loading. In further research, this can be used to tackle over-parameterization issues inherent to fitting similar constitutive models to data obtained in a clinical setting. In this thesis, a computational model of the coronary circulation is presented and methods for simultaneous pressure and flow assessment are introduced. By operating an already clinically used pressure wire as a thermal anemometer, a methodology was developed which is close to clinical application, while a new sensor was designed to be more accurate in different flow conditions

Pressure drop and recovery in cases of cardiovascular disease: a computational study

The presence of disease in the cardiovascular system results in changes in flow and pressure patterns. Increased resistance to the flow observed in cases of aortic valve and coronary artery disease can have as a consequence abnormally high pressure gradients, which may lead to overexertion of the heart muscle, limited tissue perfusion and tissue damage. In the past, computational fluid dynamics (CFD) methods have been used coupled with medical imaging data to study haemodynamics, and it has been shown that CFD has great potential as a way to study patient-specific cases of cardiovascular disease in vivo, non-invasively, in great detail and at low cost. CFD can be particularly useful in evaluating the effectiveness of new diagnostic and treatment techniques, especially at early ‘concept’ stages. The main aim of this thesis is to use CFD to investigate the relationship between pressure and flow in cases of disease in the coronary arteries and the aortic valve, with the purpose of helping improve diagnosis and treatment, respectively. A transitional flow CFD model is used to investigate the phenomenon of pressure recovery in idealised models of aortic valve stenosis. Energy lost as turbulence in the wake of a diseased valve hinders pressure recovery, which occurs naturally when no energy losses are observed. A “concept” study testing the potential of a device that could maximise pressure recovery to reduce the pressure load on the heart muscle was conducted. The results indicate that, under certain conditions, such a device could prove useful. Fully patient-specific CFD studies of the coronary arteries are fewer than studies in larger vessels, mostly due to past limitations in the imaging and velocity data quality. A new method to reconstruct coronary anatomy from optical coherence tomography (OCT) data is presented in the thesis. The resulting models were combined with invasively acquired pressure and flow velocity data in transient CFD simulations, in order to test the ability of CFD to match the invasively measured pressure drop. A positive correlation and no bias were found between the calculated and measured results. The use of lower resolution reconstruction methods resulted in no correlation between the calculated and measured results, highlighting the importance of anatomical accuracy in the effectiveness of the CFD model. However, it was considered imperative that the limitations of CFD in predicting pressure gradients be further explored. It was found that the CFD-derived pressure drop is sensitive to changes in the volumetric flow rate, while bench-top experiments showed that the estimation of volumetric flow rate from invasively measured velocity data is subject to errors and uncertainties that may have a random effect on the CFD pressure result. This study demonstrated that the relationship between geometry, pressure and flow can be used to evaluate new diagnostic and treatment methods. In the case of aortic stenosis, further experimental work is required to turn the concept of a pressure recovery device into a potential clinical tool. In the coronary study it was shown that, though CFD has great power as a study tool, its limitations, especially those pertaining to the volumetric flow rate boundary condition, must be further studied and become fully understood before CFD can be reliably used to aid diagnosis in clinical practice.Open Acces

Chronic Mesenteric Ischemia in the Picture : new diagnostic techniques and treatment modalities

This thesis aims to provide insights in different aspects of the diagnosis and therapy of chronic mesenteric ischemia to optimize the diagnostic work-up and treatment for this specific patient group

Multi-scale computational modeling of coronary blood flow: application to fractional flow reserve.

Introduction. Fractional flow reserve (FFR) is presently an invasive coronary clinical index. Non-invasive CT imaging combined with computational coronary flow modelling may reduce the patient’s burden of undergoing invasive testing. Research statement. The ability to obtain information of the hemodynamic significance of detected lesions would streamline decision making in escalation to invasive angiography. Methods. A reduced order (lumped parameter) model of the coronary vasculature was further developed. The model was used in the assessment of the roles of structure and function on the FFR. Sophisticated methods were used to elicit numerical solutions. Further, CT imaging (n = 10) provided multiple porcine geometries based upon algorithms encoded within an existing scientific platform. Results. It was found that the length of large vessel stenosis and presence of microvascular disease are primary regulators of FFR. Further, the CT data provided a basis to investigate relationships between coronary geometry (structure) and blood flow (function) attributes. Discussion. The presented model, upon personalization, may compliment and streamline ongoing imaging efforts by guiding FFR assessment. It is likely to assist in preliminary data generation for future projects. The computational geometries will contribute to an open source service that will be made available to our University’s researchers

Hemodynamics of Diseased Coronary Arteries

Cardiovascular diseases are one of the main causes of death worldwide. A common cardiovascular disease is atherosclerosis, caused by plaque deposition on the arterial wall which leads to the obstruction of the blood ow, known as stenosis. Atherosclerosis can form in any part of the arterial system but it may have serious consequences when located in one of the coronary arteries which supply blood to the heart. Plaque formation inside a coronary artery influences the flow behaviour and leads to the development of turbulence structures with physiological consequences, such as pressure drop. Percutaneous coronary intervention (PCI) is one of the most common treatments for coronary artery diseases (CADs). There are several benefits of PCI over other alternative methods for treatment of CADs including lower risks of complications and much shorter recovery period. However, it can result in thrombosis and in-stent restenosis, which are the major drawbacks of coronary stent placement in patients with CADs. It was shown that the likelihood of occurrence of restenosis and thrombosis is a function of the wall shear stress (WSS) distribution. The motivation for the research presented in this thesis is to develop an understanding of the hemodynamics of stenosed and stented coronary arteries with an ultimate goal of improving patient outcomes. This can only be achieved if the effect of stenoses and stents on the flow behaviour in arteries is well-characterised. Hence, in this thesis the relationship between the shape of stenosis, stent pattern, the downstream transitional ow behaviour, and the hemodynamic parameters is investigated. The research presented in this thesis is focused on the development of an in-depth understanding of the hemodynamics of diseased coronary arteries. Extensive pressure drop measurements, visualisation of the flow using particle image velocimetry (PIV), and computational modelling of the flow were conducted. Attention was mainly given to the stenosed and stented coronary arteries by investigating their influence on the flow behaviour, including velocity profile, pressure drop, time-averaged and -dependent WSS, and turbulent kinetic energy. The need for modelling the temporal geometric variations of the coronary arteries during a cardiac cycle for the investigation of the hemodynamics is discussed. Temporal geometric variations of the coronary arteries during a cardiac cycle are classified as a superposition of the changes in the position, curvature and torsion of the coronary artery and the variations in lumen cross-sectional shape due to distensible wall motion induced by the pulse pressure and/or contraction of the myocardium in a cardiac cycle. A sensitivity analysis was conducted to evaluate the effects of temporal geometric variations of the coronary arteries on the pressure drop and WSS. The results show that neglecting the effects of temporal geometric variations results in less than 5% deviation of the time-averaged pressure drop and WSS values. However, they lead to an approximately 20% deviation in the temporal geometric variations of hemodynamic parameters, such as time-dependent WSS. Based on the presented discussion, the temporal geometric variations of coronary arteries were not modelled in this thesis and the focus was on modelling the flow dynamics to develop an in-depth understanding of the ow features inside the stenosed and stented coronary arteries. In the next stage of the research, a model incorporating the plaque geometry, the pulsatile inlet ow and the induced turbulence in a stenosed coronary artery was developed and validated against numerical and experimental data. The transitional ow behaviour was quantified by investigation of the changes in the turbulent kinetic energy. The results suggest that there is a high risk of the formation of a secondary stenosis at a downstream distance of equal to 10 times the artery diameter in the regions to the side and downstream of the initial stenosis due to existence of the recirculation zones and low shear stresses. The applicability of the obtained results was tested with a patient-specific stenosed coronary artery model. Furthermore, for the non-invasive determination of the pressure drop in a stenosed artery model a mathematical model incorporating different physical parameters such as blood viscosity, artery length and diameter, ow rate and ow profile, and shape and degrees of stenosis, was developed. Extensive experimental pressure measurements were conducted for a wide range of degrees and shapes of stenosis to form a database in the process of the development of this equation. The validity of the developed relationship was also tested for the stenosed coronary artery models with the physiological flow profile of the left and right coronary arteries by comparing the pressure drop obtained from the developed equation and those from the experimental measurements. Moreover, the effect of artery curvature on the pressure drop and fractional ow reserve (FFR) wa investigated. The results show that neglecting the effect of artery curvature results in under-estimation of pressure drop by about 25{35%. The developed equation can determine the pressure drop inside a stenosed coronary artery using the measurement of the flow profle inside the artery as well as the images of the stenosed coronary artery. In order to develop an understanding of the hemodynamic performance of coronary stents, the effect of stent design on the hemodynamics of stented arteries was investigated experimentally and numerically. An innovative PIV technique was implemented for the visualisation of the entire ow and the investigation of WSS within the stent struts without covering the region of interest inside a stented coronary artery model. This novel technique was based on the construction of a transparent stented artery using silicone cast in one piece, instead of inserting a metal or non-metallic stent inside a cast artery model, which are translucent and distort the field of view. The results show that WSS is strongly dependent on the design of the stent. It was also shown that the likelihood of occurrence of restenosis is strongly dependent on strut depth and thickness, the distance between two consecutive struts, and the shape of the connector between the struts. This thesis provides an improved understanding of the hemodynamics of diseased coronary arteries with an ultimate goal of improving patient outcomes. The findings will provide a basis for improvement of the most common CAD diagnostic and treatment methods. Based on the results of this research, the susceptible regions for the formation of a new stenosis downstream of the initial stenosis can be determined. Identification of these locations, which are a function of different physical and geometrical parameters, such as shape, degree and eccentricity of the initial stenosis, can provide the necessary information for prevention of the distal propagation of stenoses. Furthermore, the equation developed to evaluate FFR non-invasively in this research can be used as a gatekeeper to prevent unnecessary FFR procedures for all patients. This will result in better patient outcomes and reduce costs related to unnecessary invasive FFR which will benefit the health system. In addition, the results of this study provide a better understanding of the effect of stents on the flow which can be used to improve stent designs.Thesis (Ph.D.) -- University of Adelaide, School of Mechanical Engineering, 202