UCLA

Myocardial infarction (MI) is the leading cause of morbidity and death globally. Non-invasive characterization of chronic MIs is of significant clinical importance due to its association with adverse cardiac outcomes such as cardiac arrhythmias, heart failure, and sudden cardiac death. Late Gadolinium Enhancement (LGE) MRI has evolved into a robust non-invasive imaging technique for characterizing chronic MIs and identifying new pathophysiological substrates of adverse cardiac outcomes within chronic MIs. However, the requisite Gadolinium administration in LGE MRI is contra-indicated in nearly 25% of the MI patients due to co-morbidity of chronic kidney disease. In this light, there has been a growing interest to develop non-contrast enhanced MRI techniques for robust characterization of chronic MIs.

This dissertation focuses on the development of novel non-Gadolinium based MRI techniques for robust characterization of chronic MIs and pathological substrates of adverse cardiac outcomes. Using extensive histopathology in an animal model and validation studies in chronic MI patients, native T1 mapping at 3T was shown to characterize chronic MIs with high diagnostic accuracy. The second part of the dissertation focuses on detecting post-reperfusion intramyocardial hemorrhage using non-contrast enhanced MRI techniques, and its role as a potential pathological substrate of adverse cardiac outcomes in chronic MIs. Using histopathology and mass spectrometry analysis, T2* MRI was shown to be a highly sensitive technique for detecting hemorrhage and its degradation byproducts. Hemorrhage was found to persist within chronic MIs for several months post-MI in the form of localized iron deposits, which in turn was found to be associated with prolonged inflammatory burden and adverse left-ventricular remodeling. Using high-resolution electroanatomical maps co-registered with T2*-weighted images, localized iron deposition within chronic MIs was found to be a potential arrhythmogenic substrate. The prognostic value of cardiac T2* MRI for risk-stratifying patients susceptible to malignant ventricular arrhythmias was evaluated.