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Title: Multi-modal imaging of myocardial ischemia and reperfusion in a rat model
Author: O H-Ici, Darach Michael
ISNI:       0000 0004 6058 1417
Awarding Body: King's College London
Current Institution: King's College London (University of London)
Date of Award: 2017
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Myocardial ischaemia causes progressive cellular injury. Initially there is loss of function, followed by formation of oedema. Ischemia, if prolonged, will eventually lead to cell death. Revascularisation of occluded coronary arteries is an efficient tool to reduce infarct size in acute myocardial infarction. However, reperfusion in itself can be associated with a significant amount of myocardial damage. The structural and metabolic changes occurring in myocardial ischemia and reperfusion can now be studied in-vivo using magnetic resonance imaging (MRI) and are targets to optimise the treatment of patients with acute myocardial ischemia. The development of new MRI techniques for T1 mapping allows the study of the evolution of myocardial oedema in both humans and animals. Moreover, hyperpolarised MR spectroscopy (MRS) allows the non-invasive assessment of myocardial metabolism, as injected hyperpolarised molecules can be used to study the function of metabolic pathways and enzymes in the setting of ischaemia and reperfusion. The aims of this project were to develop an animal model to allow the study of myocardial ischemia in real time, and then use this model to study the acute development of oedema and the metabolic changes in the metabolism of pyruvate. With the use of a vascular occluder, we successfully developed a closed-chest model of ischemia in the rat. This model allowed the animals to recover from the stress of surgery while also allowing ischemia experiments to be carried while the animals remain in the bore of the scanner. We then proceeded to validate this model and validate a new MR sequence, which produces cine-MR, T1 mapping and inversion-recovery prepared images. We studied the effects of varying durations of myocardial ischemia on the development of myocardial infarction and used this to validate the Small Animal Look-Locker Inversion Recovery (SALLI) multimodal imaging sequence. We were also able to study the development of myocardial oedema in real time, and demonstrate that preconditioning attenuated the T1 lengthening effects of myocardial ischemia. Following this, the acute changes in pyruvate metabolism occurring in the myocardial area at risk following 15 minutes of myocardial ischemia were investigated. We were able to detect abnormal metabolism in the area at risk for the first 60 minutes following ischemia and demonstrated that metabolism returned to normal 1 week after ischemia. The methods used show much promise in the study of the changes occurring in myocardial ischemia-reperfusion, and study of the effects of treatments such as pre- and postconditioning.
Supervisor: Kozerke, Sebastian Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available