Name
Title | ||
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Test-retest reproducibility of quantitative binding measures of [C]Ro15-4513, a PET ligand for GABA receptors containing alpha5 subunits. |
Abstract | ||
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Abstract Introduction Alteration of γ-aminobutyric acid “A” (GABA A ) receptor-mediated neurotransmission has been associated with various neurological and psychiatric disorders. [ 11 C]Ro15-4513 is a PET ligand with high affinity for α5-subunit-containing GABA A receptors, which are highly expressed in limbic regions of the human brain (Sur et al., 1998). We quantified the test-retest reproducibility of measures of [ 11 C]Ro15-4513 binding derived from six different quantification methods (12 variants). Methods Five healthy males (median age 40 years, range 38–49 years) had a 90-min PET scan on two occasions (median interval 12 days, range 11–30 days), after injection of a median dose of 441 MegaBequerels of [ 11 C]Ro15-4513. Metabolite-corrected arterial plasma input functions (parent plasma input functions, ppIFs) were generated for all scans. We quantified regional binding using six methods (12 variants), some of which were region-based (applied to the average time-activity curve within a region) and others were voxel-based: 1) Models requiring arterial ppIFs – regional reversible compartmental models with one and two tissue compartments (2kbv and 4kbv); 2) Regional and voxelwise Logan’s graphical analyses (Logan et al., 1990), which required arterial ppIFs; 3) Model-free regional and voxelwise (exponential) spectral analyses (SA; (Cunningham and Jones, 1993)), which also required arterial ppIFs; 4) methods not requiring arterial ppIFs – voxelwise standardised uptake values (Kenney et al., 1941), and regional and voxelwise simplified reference tissue models (SRTM/SRTM2) using brainstem or alternatively cerebellum as pseudo-reference regions (Lammertsma and Hume, 1996; Gunn et al., 1997). To compare the variants, we sampled the mean values of the outcome parameters within six bilateral, non-reference grey matter regions-of-interest. Reliability was quantified in terms of median absolute percentage test-retest differences (MA-TDs; preferentially low) and between-subject coefficient of variation (BS-CV, preferentially high), both compounded by the intraclass correlation coefficient (ICC). These measures were compared between variants, with particular interest in the hippocampus. Results Two of the six methods (5/12 variants) yielded reproducible data (i.e. MA-TD Conclusion Quantification of [ 11 C]Ro15-4513 binding shows very good to excellent reproducibility with SRTM and with voxelwise SA which, however, requires an arterial ppIF. Quantification in the α5 subunit-rich hippocampus is particularly reliable. The very low expression of the α5 in the cerebellum (Fritschy and Mohler, 1995; Veronese et al., 2016) and the substantial α1 subunit density in this region may hamper the application of reference tissue methods. |
Year | DOI | Venue |
|---|---|---|
2017 | 10.1016/j.neuroimage.2016.12.038 | NeuroImage |
Keywords | Field | DocType |
BPND,BS-CV,FBP,FORE,GABAA,ICC,MAPER,NHS,MA-TD,NNLS,ppIFs,ROI,RPM,SA,SRTM,SUV,TACs,VT,WS-CV | Nuclear medicine,Reproducibility,Coefficient of variation,Grey matter,Psychology,GABAA receptor,Human brain,Positron emission tomography,Brainstem,Intraclass correlation | Journal |
Volume | ISSN | Citations |
152 | 1053-8119 | 0 |
PageRank | References | Authors |
0.34 | 9 | 10 |
Name | Order | Citations | PageRank |
|---|---|---|---|
| Colm J. McGinnity | 1 | 4 | 2.27 |
| Daniela A. Riaño Barros | 2 | 5 | 1.94 |
| Lula Rosso | 3 | 1 | 1.77 |
| Mattia Veronese | 4 | 9 | 4.47 |
| Gaia Rizzo | 5 | 18 | 6.13 |
| Alessandra Bertoldo | 6 | 32 | 10.25 |
| Rainer Hinz | 7 | 14 | 6.12 |
| Federico E. Turkheimer | 8 | 57 | 11.41 |
| M Koepp | 9 | 75 | 7.40 |
| Alexander Hammers | 10 | 935 | 61.73 |