Development of MRI Techniques for Experimental Models of Cardiovascular Disease

Cardiovascular diseases (CVDs) – including stroke and heart failure – are the leading cause of death worldwide. More people die from CVDs each year than any other cause. Magnetic resonance imaging (MRI) is a powerful technique which is now routinely used for imaging these diseases as it offers high-resolution anatomical detail, exquisite soft-tissue contrast and assessment of function such as tissue water content, oxygenation, metabolism, vascular blood flow and microvascular perfusion. This thesis focuses on the development of MRI techniques for use in pre-clinical animal models of cardiovascular diseases, with a focus on stroke and heart disease. Firstly, in chapter 3, the continued development of an in-house MRI sequence known as extravascular convectography (EVAC) for measuring the flow of interstitial fluid is described. A series of phantom experiments were conducted to assess the sensitivity of the sequence to slow flowing fluid. Next, an in vivo repeatability and reproducibility study was conducted before finally the technique was applied to a rat model of stroke. In chapter 4, a pair of studies was carried out using recently established, advanced cardiac imaging techniques. In the first study, CINE and late gadolinium-enhanced inversion recovery (LGE IR) imaging were used to assess cardiac structure and function in a Prox1-deficient genetic mouse model of dilated cardiomyopathy. In the second part of the chapter, a multi-parametric MRI study – incorporating CINE, LGE IR, arterial spin labeling and T2-mapping – was conducted in a mouse model of reperfused myocardial infarction to assess the extent of area-at-risk and compare with gold-standard histological staining. Finally, in chapter 5, the development of a retrospective high-temporal resolution (HTR) CINE MRI sequence for assessing cardiac diastolic function is described and compared with pulsed wave Doppler ultrasound, which is the currently-accepted standard for measuring diastolic function. The HTR-CINE sequence was established, validated and optimised in phantoms and naïve mouse hearts. Repeatability studies were then carried out to ensure the robustness of the technique before application to a mouse model of myocardial infarction. The overall aim of the research in this thesis is the development of MRI techniques for application to experimental models of cardiovascular disease