Clinical applications of diffusion tensor magnetic resonance imaging in cardiovascular disease

Diffusion tensor cardiac magnetic resonance (DT-CMR) is an emerging technique capable of characterising myocardial architecture in-vivo, something previously only possible in post-mortem studies. By measuring the velocity of diffusion of water molecules as it is impeded by cell membranes in the myocardium, DT-CMR can measure the mean diffusivity (MD) and fractional anisotropy (FA) - markers of magnitude and anisotropy of diffusion of water molecules. Based on the principle that water diffusion occurs preferentially along the long axis of cardiomyocytes, DT-CMR can infer upon the orientations of myocardial sheetlets by measuring the absolute secondary eigenvector angle (E2A), and the orientations of cardiomyocytes. This offers the potential to elucidate many of the pathophysiological mechanisms of cardiovascular diseases that are currently not well understood, as well as providing diagnostic and prognostic biomarkers which can complement the techniques that are currently available. The overall aim for this thesis was to validate the technical and clinical applications for DT-CMR in cardiovascular diseases. Specifically, this thesis includes work on sequence development, post-processing refinements and clinical studies of patients following ST-elevation myocardial infarction (STEMI) and patients with hypertrophic cardiomyopathy (HCM). Recent advancements in percutaneous coronary intervention have improved survival rates following STEMI, but despite optimal management, up to a third of STEMI survivors develop adverse left ventricular (LV) remodelling in the long-term. This is characterised by progressive cavity dilatation, impaired contractility and is associated with reduced survival. Adverse remodelling is difficult to predict and this maybe in part due to the incomplete understanding of the pathophysiological processes, particularly earlier in the disease pathway. By studying the acute and dynamic changes in microstructure post-injury, DT-CMR may help explain the ensuing maladaptive, mechanical changes in the myocardium. The aims of chapters 3-4 were to examine how DT-CMR parameters are affected following STEMI, comparing infarcted myocardium with adjacent and remote areas. The aim of chapter 5 was to establish the predictive relevance of acute DT-CMR for adverse-remodelling at 12 months post-STEMI. Through our results, we demonstrate that patients are at significantly greater risk if their acutely infarcted myocardium exhibits reduced FA (signifying cardiomyocyte disarray) and reduced E2A (signifying the underlying myocardial sheetlets remain fixed in a hypo-angulated state during systole). These results demonstrate the potential clinical utility of DT-CMR for prognostic risk-stratification following STEMI. These findings encouraged me to explore the behaviour of DT-CMR parameters in patients with HCM. This is another condition where the prognosis is diverse and difficult to predict, again partly owing to incomplete understanding about the underlying pathophysiological mechanisms particularly early on in the disease pathway. The aim of chapter 6 was to compare DT-CMR parameters between healthy volunteers, athletes and HCM patients. Our results demonstrated than HCM patients have globally higher MD (signifying diffusion is more unrestricted), reduced FA (signifying cardiomyocyte disarray) and higher E2A (signifying the myocardial sheetlets adopt a hyper-angular orientation during systole) than athletes and healthy volunteers. In chapter 8, the aim was to establish if these findings are evident beyond areas of macroscopic abnormalities. Our results demonstrate that in comparison with healthy volunteers, HCM patients – even in myocardial segment with normal wall thickness, normal perfusion and no scarring - have reduced FA, increased E2A and increased MD. These results shed light on the sequence of pathology and demonstrate the clinical utility of DT-CMR for early detection of phenotypic expression in HCM. In conclusion, DT-CMR is safe, feasible and can provide quantitative information about the histological state of the myocardium, which can complement clinical and imaging risk factors and improve clinical decision making for managing a range of cardiovascular diseases.