TY - JOUR T1 - Quantitative mapping of mitochondrial membrane potential JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1630 LP - 1630 VL - 57 IS - supplement 2 AU - Nathaniel Alpert AU - Nicolas Guehl AU - Leon Ptaszek AU - Dustin Wooten AU - Timothy Shoup AU - Marc Normandin AU - Georges El Fakhri Y1 - 2016/05/01 UR - http://jnm.snmjournals.org/content/57/supplement_2/1630.abstract N2 - 1630Objectives Abnormal conduction of electrical impulses may cause or accompany a wide range of diseases and conditions, including myocardial pathologies such as arrhythmogenic tissue, reperfusion injury, hypertrophy, myopathy, scar and infarct. Treatment of ventricular tachycardia is currently guided by electroanatomic mapping (EAM) which involves roving catheter contact with the myocardial surface to record local electrograms. But EAM is sensitive only to surface currents and cannot probe the conductive capacity of the full thickness of the myocardium. The questions we ask are: (1) Can PET and a radiolabeled lipophilic cation be used to develop a minimally invasive method for quantitative mapping of myocardial mitochondrial membrane potential (ΔΨm). And (2) can the method be shown valid in pigs with, and without, focal tissue injury?Methods The use of 3H-labeled lipophilic cations such as tetraphenylphosphonium (TPP+) to measure mitochondrial membrane potential in cultured cells and isolated perfused rat hearts was validated as a reference method several decades ago 1-3. However, this classical methodology is highly invasive and destructive, making it inappropriate for direct translation to human investigation. The use of 18F-TPP+ provides a new route for adapting this well-established methodology with PET. Conceptually, the myocardial concentration of 18F-TPP+ is partitioned into two components: extracellular (ECV) and intracellular volumes. The Nernst equation relates the equilibrium concentrations of the intracellular concentrations to ΔΨm. We derived equations relating the total volume of distribution (VT) of 18F-TPP+ , to ΔΨm, ECV, mitochondrial volume fraction and the electric potential across the cell membrane,ΔΨc. We imaged the left ventricles of nine pigs (six controls and three with tissue injury), with 18F-TPP+ and PET. In three pigs ECV was also mapped via contrast CT. VT was estimated voxel-by-voxel from dynamic PET data by Logan graphical analysis and transformed to a quantitative map of ΔΨm. Values of ΔΨm were assayed in 17 short axis segments. Nominal values were used for mitochondrial density and ΔΨc.Results In control pigs ΔΨm was -139.4±0.4 mV. The Figure shows the quality of ΔΨm maps and that ΔΨm was significantly reduced in experimentally induced scar (arrows), in the range -90 to 0 mV. PET measurement of ΔΨm is in excellent agreement with previous measurements in experimental preparations using classical methods.Conclusions We have developed a minimally invasive method for mapping mitochondrial membrane potential of the left ventricle myocardium. ΔΨm is computed in absolute units, mV. The ΔΨm measurements in normal tissue were similar across all pigs, exhibiting low variance with wide separation of ΔΨm in normal tissue versus scar. These results demonstrate the basic validity of the method in a swine model of focal tissue injury and suggest the possibility of clinical translation. ER -