Multi-scale parameterisation of static and dynamic continuum porous perfusion models using discrete anatomical data

The aim of this thesis is to replace the intractable problem of using discrete flow models within large vascular networks with a suitably parameterised and tractable continuum perfusion model. Through this work, we directly address the hypothesis that discrete vascular data can be incorporated within continuum perfusion models via spatially-averaged parameterisation techniques. Chapter 1 reviews biological perfusion from both clinical and computational modelling perspectives, with a particular focus on myocardial perfusion. In Chapter 2, a synthetic 3D vascular network was constructed, which was controllable in terms of its size and properties. A multi-compartment static Darcy perfusion model of this discrete system was parameterised via a number of techniques. Permeabilities were derived using: (i) porosity-scaled isotropic (ϕI); (ii) Huyghe and Van Campen (HvC); and (iii) projected-PCA parameterisation methods. It was found that HvC permeabilities and pressure-coupling fields derived from the discrete data produced the best comparison to the spatially-averaged Poiseuille pressure. In Chapter 3, the construction and analysis of high-resolution anatomical arterial vascular models was undertaken. In Chapter 4, various anatomically-derived vascular networks were used to parameterise our perfusion model, including a microCT-derived rat capillary network, a single arterial subtree, and canine and porcine whole-organ arterial models. Allowing for general-connectivity (as opposed to strictly-hierarchical connectivity) yielded a significant improvement on the continuum model pressure. For the whole-organ model however, it was found that the best results were obtained by using porosity-scaled isotropic permeabilities and anatomically-derived pressure-coupling fields. It was also discovered that naturally occurring small length but relatively large radius vessels were not suitable for the HvC method. In Chapter 5, the suitability of derived parameters for use within a dynamic perfusion model was examined. It was found that the parameters derived from the original static network were adequate for application throughout the cardiac cycle. Chapter 6 presents a concluding discussion, highlighting limitations and future directions to be investigated.</p

Multi-scale parameterisation of static and dynamic continuum porous perfusion models using discrete anatomical data

The aim of this thesis is to replace the intractable problem of using discrete flow models within large vascular networks with a suitably parameterised and tractable continuum perfusion model. Through this work, we directly address the hypothesis that discrete vascular data can be incorporated within continuum perfusion models via spatially-averaged parameterisation techniques. Chapter 1 reviews biological perfusion from both clinical and computational modelling perspectives, with a particular focus on myocardial perfusion. In Chapter 2, a synthetic 3D vascular network was constructed, which was controllable in terms of its size and properties. A multi-compartment static Darcy perfusion model of this discrete system was parameterised via a number of techniques. Permeabilities were derived using: (i) porosity-scaled isotropic (ϕI); (ii) Huyghe and Van Campen (HvC); and (iii) projected-PCA parameterisation methods. It was found that HvC permeabilities and pressure-coupling fields derived from the discrete data produced the best comparison to the spatially-averaged Poiseuille pressure. In Chapter 3, the construction and analysis of high-resolution anatomical arterial vascular models was undertaken. In Chapter 4, various anatomically-derived vascular networks were used to parameterise our perfusion model, including a microCT-derived rat capillary network, a single arterial subtree, and canine and porcine whole-organ arterial models. Allowing for general-connectivity (as opposed to strictly-hierarchical connectivity) yielded a significant improvement on the continuum model pressure. For the whole-organ model however, it was found that the best results were obtained by using porosity-scaled isotropic permeabilities and anatomically-derived pressure-coupling fields. It was also discovered that naturally occurring small length but relatively large radius vessels were not suitable for the HvC method. In Chapter 5, the suitability of derived parameters for use within a dynamic perfusion model was examined. It was found that the parameters derived from the original static network were adequate for application throughout the cardiac cycle. Chapter 6 presents a concluding discussion, highlighting limitations and future directions to be investigated.This thesis is not currently available in ORA

Effects of Epicardial and Endocardial Cardiac Resynchronization Therapy on Coronary Flow:Insights From Wave Intensity Analysis

BACKGROUND: The increase in global coronary flow seen with conventional biventricular pacing is mediated by an increase in the dominant backward expansion wave (BEW). Little is known about the determinants of flow in the left‐sided epicardial coronary arteries beyond this or the effect of endocardial pacing stimulation on coronary physiology. METHODS AND RESULTS: Eleven patients with a chronically implanted biventricular pacemaker underwent an acute hemodynamic and electrophysiological study. Five of 11 patients also took part in a left ventricular endocardial pacing protocol at the same time. Conventional biventricular pacing, delivered epicardially from the coronary sinus, resulted in a 9% increase in flow (average peak velocity) in the left anterior descending artery (LAD), mediated by a 13% increase in the area under the BEW (P=0.004). Endocardial pacing resulted in a 27% increase in LAD flow, mediated by a 112% increase in the area under the forward compression wave (FCW) and a 43% increase in the area under the BEW (P=0.048 and P=0.036, respectively). There were no significant changes in circumflex parameters. Conventional biventricular pacing resulted in homogenization of timing of coronary flow compared with baseline (mean difference in time to peak in the LAD versus circumflex artery: FCW 39 ms [baseline] versus 3 ms [conventional biventricular pacing], P=0.008; BEW 47 ms [baseline] versus 8 ms [conventional biventricular pacing], P=0.004). CONCLUSIONS: Epicardial and endocardial pacing result in increased coronary flow in the left anterior descending artery and homogenization of the timing of waves that determine flow in the LAD and the circumflex artery. The increase in both the FCW and the BEW with endocardial pacing may be the result of a more physiological activation pattern than that of epicardial pacing, which resulted in an increase of only the BEW