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Test–retest measurements of dopamine D1-type receptors using simultaneous PET/MRI imaging

  • Simon Kaller
  • Michael Rullmann
  • Marianne Patt
  • Georg-Alexander Becker
  • Julia Luthardt
  • Johanna Girbardt
  • Philipp M. Meyer
  • Peter Werner
  • Henryk Barthel
  • Anke Bresch
  • Thomas H. Fritz
  • Swen Hesse
  • Osama Sabri
Original Article

Abstract

Purpose

The role of dopamine D1-type receptor (D1R)-expressing neurons in the regulation of motivated behavior and reward prediction has not yet been fully established. As a prerequisite for future research assessing D1-mediated neuronal network regulation using simultaneous PET/MRI and D1R-selective [11C]SCH23390, this study investigated the stability of central D1R measurements between two independent PET/MRI sessions under baseline conditions.

Methods

Thirteen healthy volunteers (7 female, age 33 ± 13 yrs) underwent 90-min emission scans, each after 90-s bolus injection of 486 ± 16 MBq [11C]SCH23390, on two separate days within 2–4 weeks using a PET/MRI system. Parametric images of D1R distribution volume ratio (DVR) and binding potential (BPND) were generated by a multi-linear reference tissue model with two parameters and the cerebellar cortex as receptor-free reference region. Volume-of-interest (VOI) analysis was performed with manual VOIs drawn on consecutive transverse MRI slices for brain regions with high and low D1R density.

Results

The DVR varied from 2.5 ± 0.3 to 2.9 ± 0.5 in regions with high D1R density (e.g. the head of the caudate) and from 1.2 ± 0.1 to 1.6 ± 0.2 in regions with low D1R density (e.g. the prefrontal cortex). The absolute variability of the DVR ranged from 2.4% ± 1.3% to 5.1% ± 5.3%, while Bland-Altman analyses revealed very low differences in mean DVR (e.g. 0.013 ± 0.17 for the nucleus accumbens). Intraclass correlation (one-way, random) indicated very high agreement (0.93 in average) for both DVR and BPND values. Accordingly, the absolute variability of BPND ranged from 7.0% ± 4.7% to 12.5% ± 10.6%; however, there were regions with very low D1R content, such as the occipital cortex, with higher mean variability.

Conclusion

The test–retest reliability of D1R measurements in this study was very high. This was the case not only for D1R-rich brain areas, but also for regions with low D1R density. These results will provide a solid base for future joint PET/MRI data analyses in stimulation-dependent mapping of D1R-containing neurons and their effects on projections in neuronal circuits that determine behavior.

Keywords

PET/MRI Dopamine Test–retest [11C]SCH23390 Dopamine receptor D1

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in this study 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. This study was conducted in keeping with the ICH Guideline for Good Clinical Practice (GCP) and approved by the local ethics committee (registration number 083/11) and the German Federal Office for Radiation Protection (number Z5-22461/2-2012-003). Informed consent was obtained from all participants included in the study.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Simon Kaller
    • 1
  • Michael Rullmann
    • 1
    • 2
  • Marianne Patt
    • 1
  • Georg-Alexander Becker
    • 1
  • Julia Luthardt
    • 1
  • Johanna Girbardt
    • 2
  • Philipp M. Meyer
    • 1
  • Peter Werner
    • 1
  • Henryk Barthel
    • 1
  • Anke Bresch
    • 1
  • Thomas H. Fritz
    • 2
    • 3
  • Swen Hesse
    • 1
    • 4
  • Osama Sabri
    • 1
  1. 1.Department of Nuclear MedicineUniversity of LeipzigLeipzigGermany
  2. 2.Max Planck Institute for Human Cognitive and Brain SciencesLeipzigGermany
  3. 3.Institute for Psychoacoustics and Electronic Music (IPEM)University of GentGhentBelgium
  4. 4.Integrated Research and Treatment Centre (IFB) Adiposity DiseasesLeipzig University Medical CentreLeipzigGermany

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