Test-retest measurements of dopamine D^sub 1^-type receptors using simultaneous PET/MRI imaging

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.