Application of magnetic resonance imaging and spectroscopy to the assessment of cardiovascular disease

Thesis

Cardiovascular disease encompasses a number of pathologies that confer increased occurrence of morbidity and mortality on the millions of people they affect. Our ability to understand the mechanisms of pathophysiology within cardiovascular disease is enhanced by the enormous scope of preclinical and clinical research that aims to continuously advance our knowledge and ability to treat cardiovascular pathologies. Building from our fundamental understanding of the basal physiology of cardiac structure, function, metabolism and energetics emerges our insight into the maladaptive and errant changes that occur and drive the progression of disease states. Central to this are the techniques we employ to gain these insights. Magnetic resonance imaging (MRI) and spectroscopy (MRS) techniques are uniquely placed to facilitate interrogation of cardiac structure, function, metabolism and energetics within preclinical and clinical studies. MRI has long held a place as a clinical gold-standard for imaging assessment of fundamental and disease physiology, particularly within the field of cardiac physiology where it provides high temporal and spatial resolution insight into cardiac structure and function, and the changes that occur in cardiovascular disease. Novel developments in techniques underlying MRS have made it possible to study inherent aspect of metabolism without the need for tissue samples, rapidly propelling our ability to enhance our understanding of changes occurring in cardiac metabolism in cardiovascular diseases. Diabetes, preceding the development of diabetic cardiomyopathy, and heart failure, are two such examples of cardiovascular diseases where changes in cardiac structure, function, metabolism and energetics are central components of disease pathophysiology. MRI and MRS applications to the study of cardiometabolic disease and heart failure are at the core of the preclinical experimental work presented in this thesis. An emerging central aspect of cardiometabolic disease is inflammation and its potential to provide a mechanistic missing link between changes in cardiac function, metabolism and energetics with systemic changes in immune cell responses to metabolic disorders such as obesity and diabetes. As such, the study of inflammation in cardiometabolic diseases is also explored through characterisation of the cardiac immunophenotype. With the ultimate long term aim of many aspects of cardiovascular research being to improve treatment and management of disease phenotypes, pharmacological modulation of diabetes and heart failure are also studied within this thesis.

Authors: Anderson, S

• DOI: 10.5287/ora-5rrpjnyv4
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: magnetic resonance spectroscopy; diabetes; cardiovascular disease; magnetic resonance imaging
• Subjects: Physiology