# In vivo 3D myocardial membrane potential mapping in humans using PET/MRI

## TL;DR

This study introduces a non-invasive PET/MRI method to map 3D myocardial membrane potential in humans, offering insights into cardiac mitochondrial function.

## Contribution

A novel PET/MRI technique for in vivo 3D myocardial membrane potential mapping in humans is developed and validated.

## Key findings

- Fully 3D membrane potential maps were successfully estimated from all three subjects.
- Estimated whole-heart membrane potentials ranged from -144.7 mV to -165.8 mV.
- The method combines PET and MR imaging with advanced motion correction and kinetic modeling.

## Abstract

The mitochondrial membrane potential is a key biophysical parameter of mitochondrial function, which can be useful for the diagnosis and treatment monitoring of various cardiac diseases. We present a non-invasive PET/MR imaging method for 3D myocardial membrane potential mapping in humans.

An in vivo PET/MR imaging study was performed in three healthy subjects (1 male and 2 females; 48 ± 29 years old) under a study protocol approved by the local Institutional Review Board (IRB). Written informed consent was obtained from all subjects before participation in the study. The [18F](4-Fluorophenyl)triphenylphosphonium ([18F]-FTPP+) PET tracer was administered using a bolus-plus-infusion protocol (bolus activity of 301.2 ± 7.6 MBq, infusion activity of 90.0 ± 4.9 MBq), where an infusion of 120 min was started shortly after the bolus injection (time of infusion, TOI). Dynamic cardiac PET/MR imaging was performed approximately 20 min after the TOI and continued for 100 min. The extracellular volume fraction mapping was performed via cardiac MR with a free-breathing, 3D cardiac T1 mapping sequence before and after the contrast agent injection (gadoterate meglumine, 0.1 mmol/kg). A linear tangent space alignment (LTSA) model-based method was used to reconstruct high-frame-rate dynamic images from sparsely sampled (k,t)-space data for T1. PET motion correction was performed using two steps of rigid image registration in a multi-resolution fashion, followed by a non-rigid image registration with B-spline transform. The tissue membrane potential was calculated using a kinetic model based on the Nernst equation with myocardial tracer concentration, tracer volume of distribution, and extracellular volume fraction measurements. Fully 3D membrane potential maps were successfully estimated from all three subjects. The estimated whole-heart membrane potentials were − 144.7 ± 3.5 mV, − 160.7 ± 5.3 mV, and − 165.8 ± 3.1 mV for each subject.

The proposed method allows 3D myocardial membrane potential mapping in humans in vivo.

The online version contains supplementary material available at 10.1186/s13550-025-01287-7.