Quantitative in vivo mapping of myocardial mitochondrial membrane potential

Nathaniel M. Alpert, Nicolas Guehl, Leon Ptaszek, Matthieu Pelletier-Galarneau, Jeremy Ruskin, Moussa C. Mansour, Dustin Wooten, Chao Ma, Kazue Takahashi, Yun Zhou, Timothy M. Shoup, Marc D. Normandin, Georges El Fakhri

Research output: Contribution to journalArticle

Abstract

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

Original languageEnglish (US)
Article numbere0190968
JournalPLoS One
Volume13
Issue number1
DOIs
StatePublished - Jan 1 2018

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Mitochondrial Membrane Potential
membrane potential
Swine
Membranes
swine
Tissue
Mitochondria
Positron emission tomography
extracellular space
Extracellular Space
Membrane Potentials
Volume fraction
Mitochondrial Size
Wounds and Injuries
electron transport chain
Electric potential
Electron Transport
myocardium
Heart Ventricles
Cicatrix

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Alpert, N. M., Guehl, N., Ptaszek, L., Pelletier-Galarneau, M., Ruskin, J., Mansour, M. C., ... Fakhri, G. E. (2018). Quantitative in vivo mapping of myocardial mitochondrial membrane potential. PLoS One, 13(1), [e0190968]. https://doi.org/10.1371/journal.pone.0190968

Quantitative in vivo mapping of myocardial mitochondrial membrane potential. / Alpert, Nathaniel M.; Guehl, Nicolas; Ptaszek, Leon; Pelletier-Galarneau, Matthieu; Ruskin, Jeremy; Mansour, Moussa C.; Wooten, Dustin; Ma, Chao; Takahashi, Kazue; Zhou, Yun; Shoup, Timothy M.; Normandin, Marc D.; Fakhri, Georges El.

In: PLoS One, Vol. 13, No. 1, e0190968, 01.01.2018.

Research output: Contribution to journalArticle

Alpert, NM, Guehl, N, Ptaszek, L, Pelletier-Galarneau, M, Ruskin, J, Mansour, MC, Wooten, D, Ma, C, Takahashi, K, Zhou, Y, Shoup, TM, Normandin, MD & Fakhri, GE 2018, 'Quantitative in vivo mapping of myocardial mitochondrial membrane potential', PLoS One, vol. 13, no. 1, e0190968. https://doi.org/10.1371/journal.pone.0190968
Alpert NM, Guehl N, Ptaszek L, Pelletier-Galarneau M, Ruskin J, Mansour MC et al. Quantitative in vivo mapping of myocardial mitochondrial membrane potential. PLoS One. 2018 Jan 1;13(1). e0190968. https://doi.org/10.1371/journal.pone.0190968
Alpert, Nathaniel M. ; Guehl, Nicolas ; Ptaszek, Leon ; Pelletier-Galarneau, Matthieu ; Ruskin, Jeremy ; Mansour, Moussa C. ; Wooten, Dustin ; Ma, Chao ; Takahashi, Kazue ; Zhou, Yun ; Shoup, Timothy M. ; Normandin, Marc D. ; Fakhri, Georges El. / Quantitative in vivo mapping of myocardial mitochondrial membrane potential. In: PLoS One. 2018 ; Vol. 13, No. 1.
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abstract = "Background Mitochondrial membrane potential (ΔΨm) arises from normal function of the electron transport chain. Maintenance of ΔΨm within a narrow range is essential for mitochondrial function. Methods for in vivo measurement of ΔΨm do not exist. We use 18F-labeled tetraphenylphosphonium (18F-TPP+) to measure and map the total membrane potential, ΔΨT, as the sum of ΔΨm and cellular (ΔΨc) 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 18F-TPP+ volume of distribution, VT. Fractional extracellular space (fECS) was measured in 3 pigs. We derived equations expressing ΔΨT as a function of VT and the volume-fractions of mitochondria and fECS. Seventeen segment polar maps and parametric images of ΔΨT were calculated in millivolts (mV). Results In controls, mean segmental ΔΨT = -129.4±1.4 mV (SEM). In pigs with segmental tissue injury, ΔΨT was clearly separated from control segments but variable, in the range -100 to 0 mV. The quality of ΔΨT maps was excellent, with low noise and good resolution. Measurements of ΔΨT 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 ΔΨT in left ventricular myocardium of pigs. ΔΨT 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, ΔΨT.",
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N2 - Background Mitochondrial membrane potential (ΔΨm) arises from normal function of the electron transport chain. Maintenance of ΔΨm within a narrow range is essential for mitochondrial function. Methods for in vivo measurement of ΔΨm do not exist. We use 18F-labeled tetraphenylphosphonium (18F-TPP+) to measure and map the total membrane potential, ΔΨT, as the sum of ΔΨm and cellular (ΔΨc) 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 18F-TPP+ volume of distribution, VT. Fractional extracellular space (fECS) was measured in 3 pigs. We derived equations expressing ΔΨT as a function of VT and the volume-fractions of mitochondria and fECS. Seventeen segment polar maps and parametric images of ΔΨT were calculated in millivolts (mV). Results In controls, mean segmental ΔΨT = -129.4±1.4 mV (SEM). In pigs with segmental tissue injury, ΔΨT was clearly separated from control segments but variable, in the range -100 to 0 mV. The quality of ΔΨT maps was excellent, with low noise and good resolution. Measurements of ΔΨT 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 ΔΨT in left ventricular myocardium of pigs. ΔΨT 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, ΔΨT.

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