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From metabolic connectivity to molecular connectivity: application to dopaminergic pathways

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Abstract

Introduction

This study aims to reveal the feasibility and potential of molecular connectivity based on neurotransmission in comparison with the metabolic connectivity with an application to dopaminergic pathways. For this purpose, we propose to compare the neurotransmission connectivity findings using 123I-FP-CIT SPECT and 18F-FDOPA PET with the metabolic connectivity findings using 18F-FDG PET.

Methods

18F-FDG PET and 123I-FP-CIT SPECT images from 47 subjects and 18F-FDOPA PET images from 177 subjects, who had no neurological or psychiatric disorders, were studied. Interregional correlation analyses were performed at the group level to determine the midbrain’s connectivity via glucose metabolic rate using 18F-FDG PET and via dopaminergic binding potential using 123I-FP-CIT SPECT and 18F-FDOPA PET. SPM-T maps of each radiotracer were generated, and masks used to highlight the significant differences obtained among the imaging modalities and targets.

Results

The three dopaminergic pathways (i.e., nigrostriatal, mesolimbic, and mesocortical) were identified by 18F-FDG PET (1599 voxels, with a Tmax value of 12.6), 123I-FP-CIT SPECT (1120 voxels, with Tmax value of 5.1), and 18F-FDOPA PET (6054 voxels, with Tmax value of 11.7) for a T voxel threshold of 5.10, 2.80, and 5.10, respectively. Using the same T voxel threshold of 5.10, 18F-FDOPA PET showed more specific findings than 18F-FDG PET with less voxels identified outside these pathways (− 9323 voxels), whereas no significant voxels were obtained with 123I-FP-CIT SPECT at this threshold.

Conclusion

The present study illustrates the feasibility and interest in using molecular connectivity with 18F-FDOPA PET for dopaminergic pathways. Such analyses could be applied to specific diseases involving the dopaminergic system.

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Funding

This work was carried out thanks to the support of the A*MIDEX project (no. ANR-11-IDEX-0001-02) funded by the “Investissements d’Avenir” French Government program, managed by the French National Research Agency (ANR), in the framework of DHU-Imaging.

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Authors and Affiliations

  1. Department of Nuclear Medicine & Nancyclotep Imaging platform, CHRU Nancy, F-54000, Nancy, France

    Antoine Verger, Mohammad B. Chawki & Manon Bordonne

  2. Université de Lorraine, INSERM, IADI, F-54000, Nancy, France

    Antoine Verger

  3. Department of Nuclear Medicine, CHU Timone, AP-HM, Marseille, France

    Tatiana Horowitz & Eric Guedj

  4. Aix-Marseille Université, CNRS, Ecole Centrale Marseille, Institut Fresnel, Marseille, France

    Tatiana Horowitz & Eric Guedj

  5. CERIMED, Aix-Marseille Université, Marseille, France

    Tatiana Horowitz & Eric Guedj

  6. Department of Neurology and Movement Disorders, CHU Timone, AP-HM, Marseille, France

    Alexandre Eusebio & Jean-Philippe Azulay

  7. CNRS, INT, Inst Neurosci Timone, Aix-Marseille Université, Marseille, France

    Alexandre Eusebio & Jean-Philippe Azulay

  8. Department of Neuroradiology, CHU Timone, AP-HM, Marseille, France

    Nadine Girard

  9. CNRS, CRMBM, Aix-Marseille Université, Marseille, France

    Nadine Girard

  10. Service Central de Biophysique et Médecine Nucléaire, Hôpital de la Timone, 264 rue Saint Pierre, 13005, Marseille, France

    Eric Guedj

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  1. Antoine Verger
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  2. Tatiana Horowitz
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  4. Alexandre Eusebio
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Correspondence to Eric Guedj.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Verger, A., Horowitz, T., Chawki, M.B. et al. From metabolic connectivity to molecular connectivity: application to dopaminergic pathways. Eur J Nucl Med Mol Imaging 47, 413–424 (2020). https://doi.org/10.1007/s00259-019-04574-3

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