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

Abstract Background 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...

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Main Authors: Felicitas J. Bijari, Paul Kyu Han, Thibault Marin, Wonil Lee, Yanis Chemli, Inna Gertsenshteyn, Ismaël B. G. Mounime, Yanis Djebra, Didi Chi, Marc D. Normandin, Chao Ma, Georges El Fakhri
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Language:English
Published: SpringerOpen 2025-07-01
Series:EJNMMI Research
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Online Access:https://doi.org/10.1186/s13550-025-01287-7
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author Felicitas J. Bijari
Paul Kyu Han
Thibault Marin
Wonil Lee
Yanis Chemli
Inna Gertsenshteyn
Ismaël B. G. Mounime
Yanis Djebra
Didi Chi
Marc D. Normandin
Chao Ma
Georges El Fakhri
author_facet Felicitas J. Bijari
Paul Kyu Han
Thibault Marin
Wonil Lee
Yanis Chemli
Inna Gertsenshteyn
Ismaël B. G. Mounime
Yanis Djebra
Didi Chi
Marc D. Normandin
Chao Ma
Georges El Fakhri
author_sort Felicitas J. Bijari
collection DOAJ
description Abstract Background 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. Results 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 T 1 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 T 1 . 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. Conclusion The proposed method allows 3D myocardial membrane potential mapping in humans in vivo.
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spelling doaj-art-79f99e8e1bd841d08f9a02f9c0e8d6712025-08-20T03:06:05ZengSpringerOpenEJNMMI Research2191-219X2025-07-011511910.1186/s13550-025-01287-7In vivo 3D myocardial membrane potential mapping in humans using PET/MRIFelicitas J. Bijari0Paul Kyu Han1Thibault Marin2Wonil Lee3Yanis Chemli4Inna Gertsenshteyn5Ismaël B. G. Mounime6Yanis Djebra7Didi Chi8Marc D. Normandin9Chao Ma10Georges El Fakhri11Yale Biomedical Imaging Institute, Yale University School of MedicineYale Biomedical Imaging Institute, Yale University School of MedicineYale Biomedical Imaging Institute, Yale University School of MedicineYale Biomedical Imaging Institute, Yale University School of MedicineYale Biomedical Imaging Institute, Yale University School of MedicineIndependent ResearcherYale Biomedical Imaging Institute, Yale University School of MedicineYale Biomedical Imaging Institute, Yale University School of MedicineYale Biomedical Imaging Institute, Yale University School of MedicineYale Biomedical Imaging Institute, Yale University School of MedicineYale Biomedical Imaging Institute, Yale University School of MedicineYale Biomedical Imaging Institute, Yale University School of MedicineAbstract Background 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. Results 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 T 1 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 T 1 . 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. Conclusion The proposed method allows 3D myocardial membrane potential mapping in humans in vivo.https://doi.org/10.1186/s13550-025-01287-7Membrane potential mappingPositron emission tomographyMagnetic resonance imaging3D
spellingShingle Felicitas J. Bijari
Paul Kyu Han
Thibault Marin
Wonil Lee
Yanis Chemli
Inna Gertsenshteyn
Ismaël B. G. Mounime
Yanis Djebra
Didi Chi
Marc D. Normandin
Chao Ma
Georges El Fakhri
In vivo 3D myocardial membrane potential mapping in humans using PET/MRI
EJNMMI Research
Membrane potential mapping
Positron emission tomography
Magnetic resonance imaging
3D
title In vivo 3D myocardial membrane potential mapping in humans using PET/MRI
title_full In vivo 3D myocardial membrane potential mapping in humans using PET/MRI
title_fullStr In vivo 3D myocardial membrane potential mapping in humans using PET/MRI
title_full_unstemmed In vivo 3D myocardial membrane potential mapping in humans using PET/MRI
title_short In vivo 3D myocardial membrane potential mapping in humans using PET/MRI
title_sort in vivo 3d myocardial membrane potential mapping in humans using pet mri
topic Membrane potential mapping
Positron emission tomography
Magnetic resonance imaging
3D
url https://doi.org/10.1186/s13550-025-01287-7
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