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.

Public Health Relevance

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

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL137230-03
Application #
9725734
Study Section
Biomedical Imaging Technology Study Section (BMIT)
Program Officer
Danthi, Narasimhan
Project Start
2017-09-01
Project End
2021-06-30
Budget Start
2019-07-01
Budget End
2020-06-30
Support Year
3
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02114
Guo, Rong; Petibon, Yoann; Ma, Yixin et al. (2018) MR-based motion correction for cardiac PET parametric imaging: a simulation study. EJNMMI Phys 5:3
Alpert, Nathaniel M; Guehl, Nicolas; Ptaszek, Leon et al. (2018) Quantitative in vivo mapping of myocardial mitochondrial membrane potential. PLoS One 13:e0190968
Lee, Euna; Xing, Fangxu; Ahn, Sung et al. (2018) Magnetic resonance imaging based anatomical assessment of tongue impairment due to amyotrophic lateral sclerosis: A preliminary study. J Acoust Soc Am 143:EL248
Han, Paul Kyu; Ma, Chao; Deng, Kexin et al. (2018) A minimum-phase Shinnar-Le Roux spectral-spatial excitation RF pulse for simultaneous water and lipid suppression in 1H-MRSI of body extremities. Magn Reson Imaging 45:18-25