The current state-of-the-art technique for ventricular tachycardia (VT) ablation utilizes electroanatomic mapping (EAM) and site-specific electrograms to guide delivery of ablation lesions. Although EAM can assist in distinguishing viable tissue from scar in infarcted areas, it does not represent a true gold standard for differentiating scar from viable or healthy myocardium. The limitations of EAM are reflected in the frequent recurrences (~30%) of VT after ablation. The basic insight of this proposal is that 3D imaging of mitochondrial membrane potential (MP) and the size of the extracellular space (ECS) provides a more comprehensive assessment of the arrhythmogenic substrate than EAM. We propose PET/MRI to map both mitochondrial MP and ECS for use in the detection of left ventricular (LV) scar. Our approach provides a full 3D map of myocardial membrane potential, in contrast to the 1-2mm depth beneath the endo- and epicardial surfaces afforded by EAM. The method is noninvasive and well suited to clinical translation for study of a variety of diseases, including ventricular arrhythmias, cardiomyopathy, hypertrophy, skeletal muscle disorders, etc.
We propose to develop and apply a method for quantitative mapping of mitochondrial membrane potential in man using Positron emission Tomography. The importance of this work lies in the fact that existing methods, while useful for planning ablation therapy, have serious limitations that contribute to recurrence of arrhythmias, morbidity and/or sudden death in a large fraction of patients along with concomitant increase in cost from repeat exams. If successful, this work will revolutionize the management and treatment of cardiac arrhythmias and allow the monitoring of drug treatment for ventricular tachycardia
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