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Background: For positron emission tomography (PET) ligands, such as [11C]ABP688, to be able to provide more evidence about the glutamatergic hypothesis in schizophrenia (SZ), quantification bias during dynamic PET studies and its propagation into the estimated values of non-displaceable binding potential (BPND) must be addressed. This would enable more accurate quantification during bolus + infusion (BI) neuroreceptor studies and further our understanding of neurological diseases. Previous studies have shown BPND-related biases can often occur due to overestimated cerebellum activity (reference region). This work investigates whether an alternative framing scheme can minimize quantification biases propagated into BPND, whether confounders, such as smoking status, need to be controlled for during the study, and what the consequences for the data interpretation following analysis are. A group of healthy controls (HC) and a group of SZ patients (balanced and unbalanced number of smokers) were investigated with [11C]ABP688 and a BI protocol. Possible differences in BPND quantification as a function of smoking status were tested with constant 5 min ('Const 5 min') and constant true counts ('Const Trues') framing schemes. In order to find biomarkers for SZ, the differences in smoking effects were compared between groups. The normalized BPND and the balanced number of smokers and non-smokers for both framing schemes were evaluated. Results: When applying F-tests to the 'Const 5 min' framing scheme, effect sizes (η2p) and brain regions which showed significant effects fluctuated considerably with F = 50.106 ± 54.948 (9.389 to 112.607), P-values 0.005 to < 0.001 and η2p = 0.514 ± 0.282 (0.238 to 0.801). Conversely, when the 'Const Trues' framing scheme was applied, the results showed much smaller fluctuations with F = 78.038 ± 8.975 (86.450 to 68.590), P < 0.001 for all conditions and η2p = 0.730 ± 0.017 (0.742 to 0.710), and regions with significant effects were more robustly reproduced. Further, differences, which would indicate false positive identifications between HC and SZ groups in five brain regions when using the 'Const 5 min' framing scheme, were not observed with the 'Const Trues' framing. Conclusions: Based on an [11C]ABP688 PET study in SZ patients, the results show that non-consistent BPND outcomes can be propagated by the framing scheme and that potential bias can be minimized using 'Const Trues' framing. [ABSTRACT FROM AUTHOR]

The glutamate and γ‐aminobutyric acid neuroreceptor subtypes mGluR5 and GABAA are hypothesized to be involved in the development of a variety of psychiatric diseases. However, detailed information relating to their in vivo distribution is generally unavailable. Maps of such distributions could potentially aid clinical studies by providing a reference for the normal distribution of neuroreceptors and may also be useful as covariates in advanced functional magnetic resonance imaging (MR) studies. In this study, we propose a comprehensive processing pipeline for the construction of standard space, in vivo distributions of non‐displaceable binding potential (BPND), and total distribution volume (VT) based on simultaneously acquired bolus‐infusion positron emission tomography (PET) and MR data. The pipeline was applied to [11C]ABP688‐PET/MR (13 healthy male non‐smokers, 26.6 ± 7.0 years) and [11C]Flumazenil‐PET/MR (10 healthy males, 25.8 ± 3.0 years) data. Activity concentration templates, as well as VT and BPND atlases of mGluR5 and GABAA, were generated from these data. The maps were validated by assessing the percent error δ from warped space to native space in a selection of brain regions. We verified that the average δABP = 3.0 ± 1.0% and δFMZ = 3.8 ± 1.4% were lower than the expected variabilities σ of the tracers (σABP = 4.0%–16.0%, σFMZ = 3.9%–9.5%). An evaluation of PET‐to‐PET registrations based on the new maps showed higher registration accuracy compared to registrations based on the commonly used [15O]H2O‐template distributed with SPM12. Thus, we conclude that the resulting maps can be used for further research and the proposed pipeline is a viable tool for the construction of standardized PET data distributions. [ABSTRACT FROM AUTHOR]

Simultaneous trimodal positron emission tomography/magnetic resonance imaging/electroencephalography (PET/MRI/EEG) resting state (rs) brain data were acquired from 10 healthy male volunteers. The rs‐functional MRI (fMRI) metrics, such as regional homogeneity (ReHo), degree centrality (DC) and fractional amplitude of low‐frequency fluctuations (fALFFs), as well as 2‐[18F]fluoro‐2‐desoxy‐d‐glucose (FDG)‐PET standardised uptake value (SUV), were calculated and the measures were extracted from the default mode network (DMN) regions of the brain. Similarly, four microstates for each subject, showing the diverse functional states of the whole brain via topographical variations due to global field power (GFP), were estimated from artefact‐corrected EEG signals. In this exploratory analysis, the GFP of microstates was nonparametrically compared to rs‐fMRI metrics and FDG‐PET SUV measured in the DMN of the brain. The rs‐fMRI metrics (ReHO, fALFF) and FDG‐PET SUV did not show any significant correlations with any of the microstates. The DC metric showed a significant positive correlation with microstate C (rs = 0.73, p =.01). FDG‐PET SUVs indicate a trend for a negative correlation with microstates A, B and C. The positive correlation of microstate C with DC metrics suggests a functional relationship between cortical hubs in the frontal and occipital lobes. The results of this study suggest further exploration of this method in a larger sample and in patients with neuropsychiatric disorders. The aim of this exploratory pilot study is to lay the foundation for the development of such multimodal measures to be applied as biomarkers for diagnosis, disease staging, treatment response and monitoring of neuropsychiatric disorders. [ABSTRACT FROM AUTHOR]

The glutamate and γ-aminobutyric acid neuroreceptor subtypes mGluR 5 and GABA A are hypothesized to be involved in the development of a variety of psychiatric diseases. However, detailed information relating to their in vivo distribution is generally unavailable. Maps of such distributions could potentially aid clinical studies by providing a reference for the normal distribution of neuroreceptors and may also be useful as covariates in advanced functional magnetic resonance imaging (MR) studies. In this study, we propose a comprehensive processing pipeline for the construction of standard space, in vivo distributions of non-displaceable binding potential (BP ND ), and total distribution volume (V T ) based on simultaneously acquired bolus-infusion positron emission tomography (PET) and MR data. The pipeline was applied to [ 11 C]ABP688-PET/MR (13 healthy male non-smokers, 26.6 ± 7.0 years) and [ 11 C]Flumazenil-PET/MR (10 healthy males, 25.8 ± 3.0 years) data. Activity concentration templates, as well as V T and BP ND atlases of mGluR 5 and GABA A , were generated from these data. The maps were validated by assessing the percent error δ from warped space to native space in a selection of brain regions. We verified that the average δ ABP  = 3.0 ± 1.0% and δ FMZ  = 3.8 ± 1.4% were lower than the expected variabilities σ of the tracers (σ ABP  = 4.0%-16.0%, σ FMZ  = 3.9%-9.5%). An evaluation of PET-to-PET registrations based on the new maps showed higher registration accuracy compared to registrations based on the commonly used [ 15 O]H 2 O-template distributed with SPM12. Thus, we conclude that the resulting maps can be used for further research and the proposed pipeline is a viable tool for the construction of standardized PET data distributions., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)