In vivo quantitative mapping of human mitochondrial cardiac membrane potential: a feasibility study

Area of Science:

• Cardiovascular Imaging
• Nuclear Medicine
• Biophysics

Background:

• Mitochondrial membrane potential (ΔΨm) alterations are implicated in various cardiac pathologies like heart failure and cardiotoxicity.
• Accurate in vivo assessment of ΔΨm is crucial for diagnosing and monitoring cardiac diseases.

Purpose of the Study:

• To develop and validate a non-invasive in vivo method for assessing regional ΔΨm in the human myocardium.
• To establish a foundation for using ΔΨm quantification in clinical cardiac diagnostics and therapy monitoring.

Main Methods:

• Utilized [18F]-triphenylphosphonium ([18F]TPP+) PET/MR imaging in 13 healthy subjects.
• Combined PET imaging with MR T1-mapping for extracellular space fraction (fECS) measurement.
• Employed a Nernst equation-based model to calculate tissue membrane potential (ΔΨT), a proxy for ΔΨm.

Main Results:

• Achieved an average ΔΨT of -160.7 ± 3.7 mV in healthy subjects.
• Demonstrated excellent agreement between in vivo measurements and previous in vitro assessments.
• Successfully quantified myocardial ΔΨm non-invasively in a human cohort.

Conclusions:

• In vivo quantification of mitochondrial function offers potential for new diagnostic and prognostic information in cardiac diseases.
• This feasibility study supports the use of PET/MR imaging for assessing cardiac mitochondrial health.
• The developed method lays the groundwork for future clinical investigations and therapy monitoring in cardiovascular conditions.