Quantitative in vivo mapping of myocardial mitochondrial membrane potential

BACKGROUND: Mitochondrial membrane potential (ΔΨ(m)) arises from normal function of the electron transport chain. Maintenance of ΔΨ(m) within a narrow range is essential for mitochondrial function. Methods for in vivo measurement of ΔΨ(m) do not exist. We use (18)F-labeled tetraphenylphosphonium ((18)F-TPP(+)) to measure and map the total membrane potential, ΔΨ(T), as the sum of ΔΨ(m) and cellular (ΔΨ(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 (18)F-TPP(+) volume of distribution, V(T). Fractional extracellular space (f(ECS)) was measured in 3 pigs. We derived equations expressing ΔΨ(T) as a function of V(T) and the volume-fractions of mitochondria and f(ECS). Seventeen segment polar maps and parametric images of ΔΨ(T) were calculated in millivolts (mV). RESULTS: In controls, mean segmental ΔΨ(T) = -129.4±1.4 mV (SEM). In pigs with segmental tissue injury, ΔΨ(T) was clearly separated from control segments but variable, in the range -100 to 0 mV. The quality of ΔΨ(T) maps was excellent, with low noise and good resolution. Measurements of ΔΨ(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 ΔΨ(T) in left ventricular myocardium of pigs. ΔΨ(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, ΔΨ(T).