mGluR(5) and GABA(A) receptor-specific parametric PET atlas construction-PET/MR data processing pipeline, validation, and application

The glutamate and gamma-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 (BPND), and total distribution volume (V-T) based on simultaneously acquired bolus-infusion positron emission tomography (PET) and MR data. The pipeline was applied to [C-11]ABP688-PET/MR (13 healthy male non-smokers, 26.6 +/- 7.0 years) and [C-11]Flumazenil-PET/MR (10 healthy males, 25.8 +/- 3.0 years) data. Activity concentration templates, as well as V-T and BPND atlases of mGluR(5) and GABA(A), were generated from these data. The maps were validated by assessing the percent error delta from warped space to native space in a selection of brain regions. We verified that the average delta(ABP) = 3.0 +/- 1.0% and delta(FMZ) = 3.8 +/- 1.4% were lower than the expected variabilities sigma of the tracers (sigma(ABP) = 4.0%-16.0%, sigma(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 [O-15]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.