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

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 (BP_ND) 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 BP_ND values. Accordingly, the absolute variability of BP_ND 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: D1R; Dopamine; Dopamine receptor; PET/MRI; Test–retest; [11C]SCH23390.