The test-retest reliability of 18F-DOPA PET in assessing striatal and extrastriatal presynaptic dopaminergic function

Abstract

Brain presynaptic dopaminergic function can be assessed using 18F-DOPA positron emission tomography (PET). Regional 18F-DOPA utilization may be used to index dopaminergic abnormalities over time or dopaminergic response to treatment in clinical populations. Such studies require prior knowledge of the stability of the 18F-DOPA signal in the brain regions of interest. Test-retest reliability was examined in eight healthy volunteers who each received two 18F-DOPA PET scans, approximately 2 years apart. 18F-DOPA utilization (k(i)(cer)) was determined using graphical analysis relative to a reference tissue input (Patlak and Blasberg, 1985). Reproducibility (measured as the within-subjects variation) and reliability (measured as intraclass correlation coefficients, ICCs) of 18F-DOPA k(i)(cer) were assessed in the structural and functional subdivisions of the striatum and select extrastriatal brain regions. Voxel-based median ICC maps were used to visualize the distribution of 18F-DOPA k(i)(cer) reliability across the brain. The caudate and putamen, and associative and sensorimotor, striatal subdivisions showed good reliability across the two scan sessions with bilateral ICCs ranging from 0.681 to 0.944. Reliability was generally lower in extrastriatal regions, with bilateral ICCs ranging from 0.235 in the amygdala to 0.894 in the thalamus. These data confirm the utility of 18F-DOPA PET in assessing dopaminergic function in the striatum and select extrastriatal areas but highlight the limitations in using this approach to measure dopaminergic function in low uptake extrastriatal brain areas. This information can be used to optimize the experimental design of future studies investigating changes in brain dopaminergic function with 18F-DOPA.

Figure 1

Top panel: Mean parametric 18F-DOPA k_i^cer maps for eight healthy volunteers during the first (test) scanning session. Four representative transaxial slices at z=--12, z=0, z=8 and z=36 are overlaid on an 18F-DOPA template. The high k_i^cer values (yellow areas) obtained in the striatum are clearly visible. Bottom panel: ICC maps of 18F-DOPA k_i^cer for eight healthy volunteers scanned over two sessions. Four representative transaxial slices at z=--12, z=0, z=8 and z=36 show ICC values greater than 0.50 overlaid on the high resolution single subject T1-weighted MRI image in MNI space. The highest reliability (yellow areas) is clearly visible in the large clusters of the striatum.

Figure 2

The figure shows the distribution of median ICC values across voxels in the striatum (blue) and whole brain (green). The skewed distribution of ICC values in striatal voxels compared to the whole brain is clearly visible.