Push-Button Cardiac MRI for Non-Invasive Quantification of Myocardial Energy Consumption in Heart Failure

ABSTRACT Cardiac Energy consumption is the central determinant of cardiac function. Its impairment is the hallmark of heart failure (HF), which accounts for nearly $40 billion in medical costs every year and is the most frequent cause of hospitalization. In HF pathophysiology, the depression of contractile force of the myocardium is not matched by a concomitant depression of energy consumption. This results in the uncoupling between mechanical contraction and energy expenditure of the heart, which drives systolic or diastolic dysfunction of the heart. Thus, the detection of early alterations in cardiac energetics in HF patients can provide critical information on heart health and guide novel therapeutic interventions for HF which are under development. Since the heart relies almost exclusively on aerobic oxidation, the gold standard for staging alterations in cardiac energetics is from invasively measured whole heart myocardial oxygen consumption (MVO2). However, invasive catheterization is not a practical way for repeat surveillance of the disease in the suspect population or the monitoring of therapeutic efficacy. Hence there is an unmet need for a noninvasive approach that can enable repeatable quantitative assessment of cardiac energetics. Significant effort has been made towards developing noninvasive techniques for MVO2 measurement, particularly based on positron emission tomography (PET) and magnetic resonance spectroscopy (MRS). However, they have not made it into the clinical arena due to major technical/practical limitations. An alternative approach, which overcomes key limitations of PET and longstanding technical challenges of MRS for estimating MVO2, employs magnetic resonance oximetry. Nonetheless, this requires simultaneous and reliable mapping of quantitative MR parameters in the rapidly moving coronary sinus, which is nearly impossible for the CMR techniques today. Here, we propose to develop and validate a single, fast, free-breathing, motion-insensitive acquisition to simultaneously derive coronary sinus oxygen saturation and myocardial blood flow for MVO2 measurement. We will test the developed method in detecting the impaired cardiac energy consumption level in an animal model with heart failure. The proposed method is expected to quantify cardiac energy consumption noninvasively, without ionizing radiation, and exogenous contrast agents. Accordingly, forming the foundation toward (1) early detection and classification of HF for target treatments, (2) prognosis of HF without invasive procedures, and (3) longitudinal monitoring of HF progression to guide the development of novel HF therapies.