Biomedical Engineering - Theses

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    A bond graph approach to integrative biophysical modelling
    Pan, Michael ( 2019)
    A major goal of systems biology is to develop comprehensive, multi-scale mathematical models of physiological systems that integrate biological knowledge from the scale of molecules to the scale of tissues and organs. Models on this scale hold great potential in advancing our knowledge of biology and medicine, but they have yet to be achieved in complex biological systems. It is widely acknowledged that constructing large-scale models requires the reuse and integration of existing models; however, model integration is currently challenging because many existing models violate the conservation laws of physics, especially conservation of energy. It is therefore highly desirable to express models in a framework that respects the laws of physics and thermodynamics. Bond graphs are an energy-based modelling framework, initially developed for use in multi-physics engineering systems to help derive equations consistent with the laws of physics. More recently, bond graphs have been applied to the field of biology where they have helped in making models physically and thermodynamically consistent. While bond graphs provide several advantages for large-scale modelling such as thermodynamic consistency and hierarchical modelling, they have yet to be applied to large-scale dynamic models of biological systems. This thesis aims to develop methods based on the bond graph framework to facilitate model reuse and integration. These methods are demonstrated by applying them to biomolecular systems within the cardiac cell. Firstly, bond graphs are applied to membrane transporters, demonstrating that bond graphs can be used to correct thermodynamic inconsistencies within existing models. Secondly, independently developed models of ion channels and transporters are coupled into a model of cardiac electrophysiology, showing that bond graphs can be used to systematically explain the issues of drift and non-unique steady states that affect many existing models. Finally, a generalised method for simplifying models of enzyme kinetics is developed and used to facilitate the development of simple, thermodynamically consistent models of enzymes that are easily incorporated into larger models.
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    Pedalling-based exercise performance and prevention of post-thrombolysis intracerebral haemorrhage in stroke patients
    Soni, Mukesh ( 2019)
    Globally, stroke is the leading cause of disability and the second leading cause of death. Management of ischemic stroke involves rapid administration of thrombolytic therapy (clot dissolving medication) for eligible patients, acute stroke unit care, and rehabilitation therapy to improve function. Pedalling using a stationary exercise bicycle is a safe and effective lower limb rehabilitation strategy in stroke patients that is known to improve aerobic capacity; however, the repetitive nature of pedalling is associated with poor motivation and exercise adherence as well as lack of perceived self-efficacy. Audio-visual engagement and feedback during exercise therapy has been shown to improve satisfaction and adherence; however, little is known about the effect of active visual engagement on exercise performance during pedalling. This thesis proposed an exercise monitoring study in healthy people and stroke patients employing a custom pedalling mechanism that monitored the exercise, provided immediate feedback on pedalling performance, and facilitated engagement through the use of video. The study involved six sessions of pedalling at a set low, and high-speed under exercise feedback and video-based engagement conditions. Heart rate (HR) and blood oxygen saturation (SpO2), as well as pedalling speed deviations, were recorded during the study. Healthy subjects demonstrated improvement in pedalling performance and reduction in exercise-induced changes in HR and SpO2 while pedalling with feedback and engagement. In contrast, stroke patients showed a significant improvement in pedalling performance only. The findings may be useful in prescription of pedalling exercises for rehabilitation, and in improving exercise compliance. Intravenous recombinant tissue plasminogen activator (rt-PA) thrombolysis treatment remains the only FDA approved therapy for acute ischemic stroke, but is associated with symptomatic intracerebral haemorrhage (SICH). Since administration of thrombolytic therapy is time critical, early evaluation of the risk of SICH using readily available patient information before treatment may enable the clinician to identify at-risk rt-PA induced SICH candidates and potentially improve therapeutic outcomes and reduce disability. The thesis proposes development of a predictive model to facilitate prompt estimation of the SICH risk using pre-treatment clinical and demographic patient data that are typically readily available to the clinician. The risk factors associated with SICH were identified using bi-variate analysis on patient records which included those of 1479 ischemic stroke patients treated with thrombolysis at 20 hospitals across 3 Australian states. Odds ratios were computed for each binary variable and stratified continuous variables to create a risk score. The risk score was defined between 0 and 53, and was stratified into 4 categories: very low risk (0 – 6), low risk (7 – 12), moderate risk (13 – 19) and high risk (over 20). The rate of any symptomatic ICH in the cohort was 1.75% (very low risk), 3.47% (low risk), 9.16% (moderate risk), and 15.32% (high risk). The c-statistic was 0.761 for continuous risk score (0 – 53) and 0.717 for stratified risk levels (very low / low / moderate / high risk) in the training dataset. A smaller value of c-statistics, 0.723 and 0.697, were obtained for continuous and stratified risk zones, respectively. A mobile application was developed for computing SICH risk, which may be useful for clinicians as a tool for SICH risk estimation. The findings of this thesis will help to address morbidity of stroke in the community by reducing complications of thrombolytic treatment through better patient selection, as well and increasing participation in exercise therapy through more engaging and satisfying rehabilitation.