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Characterization and modeling of the human left atrium using optical coherence tomography
With current needs to better understand the interaction between atrial tissue microstructure and atrial fibrillation dynamics, micrometer scale imaging with optical coherence tomography has significant potential to provide further insight on arrhythmia mechanisms and improve treatment guidance. However, optical coherence tomography imaging of cardiac tissue in humans is largely unexplored, and the ability of optical coherence tomography to identify the structural substrate of atrial fibrillation has not yet been investigated. Therefore, the objective of this thesis was to develop an optical coherence tomography imaging atlas of the human heart, study the utility of optical coherence tomography in providing useful features of human left atrial tissues, and develop a framework for optical coherence tomography-informed cardiac modeling that could be used to probe dynamics between electrophysiology and tissue structure.
Human left atrial tissues were comprehensively imaged by optical coherence tomography for the first time, providing an imaging atlas that can guide identification of left atrial tissue features from optical coherence tomography imaging. Optical coherence tomography image features corresponding to myofiber and collagen fiber orientation, adipose tissue, endocardial thickness and composition, and venous media were established. Varying collagen fiber distributions in the myocardial sleeves were identified within the pulmonary veins. A scheme for mapping optical coherence tomography data of dissected left atrial tissues to a three-dimensional, anatomical model of the human left atrium was also developed, enabling the mapping of distributions of imaged adipose tissue and fiber orientation to the whole left atrial geometry. These results inform future applications of structural substrate mapping in the human left atrium using optical coherence tomography-integrated catheters, as well as potential directions of ex vivo optical coherence tomography atrial imaging studies.
Additionally, we developed a workflow for creating optical mapping models of atrial tissue as informed by optical coherence tomography. Tissue geometry, fiber orientation, ablation lesion geometry, and heterogeneous tissue types were extracted from optical coherence tomography images and incorporated into tissue-specific meshes. Electrophysiological propagation was simulated and combined with photon scattering simulations to evaluate the influence of tissue-specific structure on electrical and optical mapping signals. Through tissue-specific modeling of myofiber orientation, ablation lesions, and heterogeneous tissue types, the influence of myofiber orientation on transmural activation, the relationship between fluorescent signals and lesion geometry, and the blurring of optical mapping signals in the presence of heterogeneous tissue types were investigated.
By providing a comprehensive optical coherence tomography image database of the human left atrium and a workflow for developing optical coherence tomography-informed cardiac tissue models, this work establishes the foundation for utilizing optical coherence tomography to improve the structural substrate characterization of atrial fibrillation. Future developments include analysis of optical coherence tomography imaged tissue structure with respect to clinical presentation, development of automated processing to better leverage the large amount of imaging data, enhancements and validation of the modeling scheme, and in vivo evaluation of the left atrial structural substrate through optical coherence tomography-integrated catheter
Optical mapping signal synthesis
Although death due to lethal cardiac arrhythmias is the leading cause of mortality in Western Society, many of the fundamental mechanisms underlying their onset, maintenance and termination, still remain poorly understood. In recent years, experimental techniques such as optical mapping have provided useful high-resolution recordings of cardiac electrical dynamics during complex arrhythmias and defibrillation episodes, which have been combined with detailed computer simulations to further our understanding of these phenomena. However, mechanistic enquiry is severely restricted as the optical mapping technique suffers from a number of distortion effects which compromise the fidelity of the experimental measurements, presenting difficulties in the comparison of experimental data with computational simulations. This Thesis presents a thorough investigation into the distortion effects encountered in optical mapping experiments, guided by the development of a coherent series of computational models. The models presented successfully characterise the specific mechanisms of fluorescent signal distortion due to photon scattering. Photon transport in cardiac tissue is modelled using both continuous (reaction-diffusion) and discrete stochastic (Monte Carlo) approaches to simulate the effects of photon scattering within the myocardium upon the recorded fluorescent signal, which include differing levels of detail and associated computational complexity. Specifically, these models are used to investigate the important role played by the complex ventricular structural anatomy, as well as the specifics of the experimental set-up itself. In addition, a tightly coupled electromechanical model of a contracting cardiac fibre is developed which provides an important first-step towards the development of a model to quantitatively assess the distortion observed when recording from a freely contracting cardiac preparation. Simulation of these distortion effects using the models allows discrimination to be made between those parts of the experimental signal which are due to underlying tissue electrophysiology and those due to artifact, facilitating a more accurate interpretation of experimentally-obtained data. The models presented succeed in two main respects. Firstly, they provide a ‘post-processing’ tool which can be added on to computational simulations of electrical activation, allowing for a more accurate and faithful comparison between simulations and experiments, helping to validate predictions made by electrical models. Secondly, they provide a higher degree of mechanistic insight into the fundemental ways in which optical signals are distorted, showing how this distortion can be maximised or controlled. The understanding and quantification of the fundemental mechanisms of optical mapping signal distortion, provided by this Thesis, therefore fulfils an important role in the study of arrhythmia mechanisms.</p
Optical mapping signal synthesis
EThOS - Electronic Theses Online ServiceGBUnited Kingdo