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.
|Qualification||Doctor of Philosophy|
|Award date||31 May 2012|
|Place of Publication||Eindhoven|
|Publication status||Published - 2012|