| 1. |
- Matheson, Granville J., et al.
(författare)
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Assessment of simplified ratio-based approaches for quantification of PET [11C] PBR28 data
- 2017
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Ingår i: EJNMMI Research. - : Springer Nature. - 2191-219X. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Kinetic modelling with metabolite-corrected arterial plasma is considered the gold standard for quantification of [C-11] PBR28 binding to the translocator protein (TSPO), since there is no brain region devoid of TSPO that can serve as reference. The high variability in binding observed using this method has motivated the use of simplified ratio-based approaches such as standardised uptake value ratios (SUVRs) and distribution volume (VT) ratios (DVRs); however, the reliability of these measures and their relationship to VT have not been sufficiently evaluated.Methods: Data from a previously published [C-11] PBR28 test-retest study in 12 healthy subjects were reanalysed. VT was estimated using a two-tissue compartment model. SUVR and DVR values for the frontal cortex were calculated using the whole brain and cerebellum as denominators. Test-retest reliability was assessed for all measures. Interregional correlations were performed for SUV and VT, and principal component analysis (PCA) was applied. Lastly, correlations between ratio-based outcomes and VT were assessed.Results: Reliability was high for VT, moderate to high for SUV and SUVR, and poor for DVR. Very high interregional correlations were observed for both VT and SUV (all R-2 > 85%). The PCA showed that almost all variance (> 98%) was explained by a single component. Ratio-based methods correlated poorly with VT (all R-2 < 34%, divided by genotype).Conclusions: The reliability was good for SUVR, but poor for DVR. Both outcomes showed little to no association with VT, questioning their validity. The high interregional correlations for VT and SUV suggest that after dividing by a denominator region, most of the biologically relevant signal is lost. These observations imply that results from TSPO PET studies using SUVR or DVR estimates should be interpreted with caution.
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| 2. |
- Matheson, Granville J, et al.
(författare)
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Reliability of volumetric and surface-based normalisation and smoothing techniques for PET analysis of the cortex : A test-retest analysis using [11C]SCH-23390
- 2017
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Ingår i: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 155, s. 344-353
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Tidskriftsartikel (refereegranskat)abstract
- Parametric voxelwise analysis is a commonly used tool in neuroimaging, as it allows for identification of regions of effects in the absence of a strong a-priori regional hypothesis by comparing each voxel of the brain independently. Due to the inherent imprecision of single voxel measurements, spatial smoothing is performed to increase the signal-to-noise ratio of single-voxel estimates. In addition, smoothing compensates for imprecisions in anatomical registration, and allows for the use of cluster-based statistical thresholding. Smoothing has traditionally been applied in three dimensions, without taking the tissue types of surrounding voxels into account. This procedure may be suitable for subcortical structures, but is problematic for cortical regions for which grey matter often constitutes only a small proportion of the smoothed signal. New methods have been developed for cortical analysis in which voxels are sampled to a surface, and smoothing is restricted to neighbouring regions along the cortical grey matter in two dimensions. This procedure has recently been shown to decrease intersubject variability and bias of PET data. The aim of this study was to compare the variability, bias and test-retest reliability of volumetric and surface-based methods as they are applied in practice. Fifteen healthy young males were each measured twice using the dopamine D1 receptor radioligand [11C]SCH-23390, and analyses were performed at the level of individual voxels and vertices within the cortex. We found that surface-based methods yielded higher BPND values, lower coefficient of variation, less bias, better reliability and more precise estimates of parametric binding. All in all, these results suggest that surface-based methods exhibit superior performance to volumetric approaches for voxelwise analysis of PET data, and we advocate for their use when a ROI-based analysis is not appropriate.
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| 3. |
- Plaven-Sigray, Pontus, et al.
(författare)
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Extrastriatal dopamine D2-receptor availability in social anxiety disorder
- 2017
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Ingår i: European Neuropsychopharmacology. - : Elsevier BV. - 0924-977X .- 1873-7862. ; 27:5, s. 462-469
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Tidskriftsartikel (refereegranskat)abstract
- Alterations in the dopamine system are hypothesized to influence the expression of social anxiety disorder (SAD) symptoms. However, molecular imaging studies comparing dopamine function between patients and control subjects have yielded conflicting results. Importantly, while all previous investigations focused on the striatum, findings from activation and blood flow studies indicate that prefrontal and limbic brain regions have a central role in the pathophysiology. The objective of this study was to investigate extrastriatal dopamine D2-receptor (D2-R) availability in SAD. We examined 12 SAD patients and 16 healthy controls using positron emission tomography and the high-affinity D2-R radioligand [C-11]FLB457. Parametric images of D2-R binding potential were derived using the Logan graphical method with cerebellum as reference region. Two-tailed one-way independent ANCOVAs, with age as covariate, were used to examine differences in D2-R availability between groups using both region-based and voxel-wise analyses. The region-based analysis showed a medium effect size of higher D2-R levels in the orbitofrontal cortex (OFC) in patients, although this result did not remain significant after correction for multiple comparisons. The voxel-wise comparison revealed elevated D2-R availability in patients within OFC and right dorsolateral prefrontal cortex after correction for multiple comparisons. These preliminary results suggest that an aberrant extrastriatal dopamine system may be part of the disease mechanism in SAD.
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