An Accurate Non-Contrast-Enhanced Cardiac MRI Method for Imaging Chronic Myocardial Infarctions: Technical Developments to Rapid Clinical Validation

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PROJECT SUMMARY Major advances in acute care have now reversed the trend of immediate death from myocardial infarction (MI). However, the long-term morbidity, particularly from heart failure, in these patients has become an epidemic. Currently, ~ 1 in 60 Americans carry a diagnosis of heart failure and face a grim 5-year survival rate (<50%). The therapeutic options available to these patients (medical, surgical and/or device-based) require knowledge of presence of prior (chronic) infarction(s) and its characteristics (location, size and transmurality). American Heart Association guidelines recommend late-enhancement (LGE) cardiac MRI for gathering this information. In spite of its capabilities, LGE cardiac MRI (CMR) has a key limitation – it requires infusion of gadolinium- based contrast agents, which are toxic to patients with late stage chronic kidney disease (CKD). Given the comorbidity of CKD in patients with heart disease, LGE CMR is contraindicated in at least 20% of all heart failure patients (at least 1 million in the US). Importantly, late stage CKD patients who cannot undergo LGE CMR are in great need of chronic MI assessment since the risk of cardiac mortality is substantially elevated in this population. Moreover, multiple, recent, autopsy studies in subjects without CKD who had undergone gadolinium-enhanced MRI studies years before death have found gadolinium (Gd) deposits in the brain. This has led to even greater concern in the imaging community regarding gadolinium use. Thus, there is an unmet and growing need for accurate assessment of chronic MI without contrast agents. Multiple efforts have been made in detecting and characterizing chronic MI without contrast agents using CMR. Although these methods have made significant headway, they have not translated into clinical practice because of limitations in image artifacts, long imaging times, patient safety and inadequate image contrast-to- noise ratio. Importantly, methods that could be safe, performed within reasonable imaging time and yield artifact-free images had an order of magnitude lower CNR than LGE. We propose to develop and validate a CMR approach that is time efficient, will lead to little to no image artifacts and safe. This imaging approach is expected to enable imaging of chronic MIs as well as LGE CMR within the same time it takes to perform LGE CMR in a wide-range of MI patients without contrast agents. Importantly, the proposed non-contrast CMR method has the potential to improve the care for a large segment of heart failure patients, who are currently without a viable option as they are contraindicated for LGE CMR.