title: Test-retest measurements of dopamine D1-type receptors using simultaneous PET/MRI imaging.
abstract: OBJECTIVE
  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 BPNDvalues. Accordingly, the absolute variability of BPNDranged 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Nuclear Medicine, University of Leipzig, Liebigstrasse 18, D-04103, Leipzig, Germany.
authors.forename: Simon
authors.identifier: http://orcid.org/0000-0002-7391-4191
authors.initials: S
authors.lastname: Kaller
authors.affiliation: Department of Nuclear Medicine, University of Leipzig, Liebigstrasse 18, D-04103, Leipzig, Germany.|Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Rullmann
authors.affiliation: Department of Nuclear Medicine, University of Leipzig, Liebigstrasse 18, D-04103, Leipzig, Germany.
authors.forename: Marianne
authors.initials: M
authors.lastname: Patt
authors.affiliation: Department of Nuclear Medicine, University of Leipzig, Liebigstrasse 18, D-04103, Leipzig, Germany.
authors.forename: Georg-Alexander
authors.initials: GA
authors.lastname: Becker
authors.affiliation: Department of Nuclear Medicine, University of Leipzig, Liebigstrasse 18, D-04103, Leipzig, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Luthardt
authors.affiliation: Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
authors.forename: Johanna
authors.initials: J
authors.lastname: Girbardt
authors.affiliation: Department of Nuclear Medicine, University of Leipzig, Liebigstrasse 18, D-04103, Leipzig, Germany.
authors.forename: Philipp M
authors.initials: PM
authors.lastname: Meyer
authors.affiliation: Department of Nuclear Medicine, University of Leipzig, Liebigstrasse 18, D-04103, Leipzig, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Werner
authors.affiliation: Department of Nuclear Medicine, University of Leipzig, Liebigstrasse 18, D-04103, Leipzig, Germany.
authors.forename: Henryk
authors.initials: H
authors.lastname: Barthel
authors.affiliation: Department of Nuclear Medicine, University of Leipzig, Liebigstrasse 18, D-04103, Leipzig, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Bresch
authors.affiliation: Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.|Institute for Psychoacoustics and Electronic Music (IPEM), University of Gent, Technicum Blok 2, Sint-Pietersnieuwstraat 41, 9000, Ghent, Belgium.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Fritz
authors.affiliation: Department of Nuclear Medicine, University of Leipzig, Liebigstrasse 18, D-04103, Leipzig, Germany. swen.hesse@medizin.uni-leipzig.de.|Integrated Research and Treatment Centre (IFB) Adiposity Diseases, Leipzig University Medical Centre, Leipzig, Germany. swen.hesse@medizin.uni-leipzig.de.
authors.forename: Swen
authors.initials: S
authors.lastname: Hesse
authors.affiliation: Department of Nuclear Medicine, University of Leipzig, Liebigstrasse 18, D-04103, Leipzig, Germany.
authors.forename: Osama
authors.initials: O
authors.lastname: Sabri
mesh_terms: D000328:Adult; D001552:Benzazepines; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D002250:Carbon Radioisotopes; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D064847:Multimodal Imaging; D049268:Positron-Emission Tomography; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D015203:Reproducibility of Results
chemical_list: D001552:Benzazepines; D002250:Carbon Radioisotopes; D017447:Receptors, Dopamine D1; C534628:SCH 23390
keywords: D1R; Dopamine; Dopamine receptor; PET/MRI; Test–retest; [11C]SCH23390