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Title: A computational investigation of the electrocardiogram with healthy and diseased human ventricles
Author: Cardone-Noott, Louie
ISNI:       0000 0004 6499 8228
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2016
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Cardiovascular diseases are the leading cause of death worldwide, and are estimated to kill over 17 million people each year, about 31% of all deaths. In the clinic, the first diagnostic procedure for a suspected cardiac abnormality is often acquisition of an electrocardiogram (ECG), which measures the electrical potential of the heart at the body surface. Understanding the mechanisms underlying generation of the ECG waveforms is crucial for optimal clinical benefit. Computer simulations possess several strengths as a tool to gain this understanding, particularly in terms of human-specificity, flexibility, repeatability, and ethics. The ventricles make up the majority of the cardiac volume and are therefore responsible for the majority of ECG waveforms. Ventricular disorders are the most life-threatening, because the ventricles are responsible for pumping blood to the body. Due to their size it has only recently become possible to perform biophysically detailed simulations of the ventricles and torso using supercomputers. In this thesis, multiscale, mathematical models of the ventricles and torso using the Chaste software library are simulated on high performance computing systems. A description is included of the performance enhancements made in Chaste to improve resource efficiency and accelerate job turnaround, particularly in data storage and the auxiliary tasks of post-processing and data conversion. A novel model of ventricular activation is presented and parametrized using multi-modal human data, and successfully used to simulate normal and pathological QRS complexes. Similarly, repolarization gradients are imposed based on the literature and result in a variety of T waves. Finally, the developed human whole-ventricular and torso models are utilized to gain new insights into possible ionic mechanisms underlying the clinical manifestations of the early repolarization syndrome. Overall, this thesis presents a novel framework for simulation of the human ECG using high performance computers, with possible applications in basic science and computational medicine.
Supervisor: Bueno, Alfonso ; Burrage, Kevin ; Mincholé, Ana ; Rodriguez, Blanca Sponsor: Engineering and Physical Sciences Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Computational biology ; Ventricles ; Simulation ; Activation sequence ; QRS complex ; Electrocardiogram