Quantitative in vivo mapping of myocardial mitochondrial membrane potential

Background Mitochondrial membrane potential (Delta psi(m)) arises from normal function of the electron transport chain. Maintenance of Delta psi(m) within a narrow range is essential for mitochondrial function. Methods for in vivo measurement of Delta psi(m) do not exist. We use F-18-labeled tetraphenylphosphonium (F-18-TPP+) to measure and map the total membrane potential, Delta psi(T), as the sum of Delta psi(m) and cellular (Delta psi(c)) electrical potentials. Methods Eight pigs, five controls and three with a scar-like injury, were studied. Pigs were studied with a dynamic PET scanning protocol to measure F-18-TPP+ volume of distribution, V-T. Fractional extracellular space (f(Ecs)) was measured in 3 pigs. We derived equations expressing Delta psi(T) as a function of V-T and the volume-fractions of mitochondria and fEcs. Seventeen segment polar maps and parametric images of Delta psi(T) were calculated in millivolts (mV). Results In controls, mean segmental Delta psi(T) = -129.4 +/- 1.4 mV (SEM). In pigs with segmental tissue injury, Delta psi(T) was clearly separated from control segments but variable, in the range -100 to 0 mV. The quality of Delta psi(T) maps was excellent, with low noise and good resolution. Measurements of Delta psi(T) in the left ventricle of pigs agree with previous in in-vitro measurements. Conclusions We have analyzed the factors affecting the uptake of voltage sensing tracers and developed a minimally invasive method for mapping Delta psi(T) in left ventricular myocardium of pigs. Delta psi(T) is computed in absolute units, allowing for visual and statistical comparison of individual values with normative data. These studies demonstrate the first in vivo application of quantitative mapping of total tissue membrane potential, Delta psi(T).