mGluR₅ and GABA_A receptor-specific parametric PET atlas construction-PET/MR data processing pipeline, validation, and...

The glutamate and γ-aminobutyric acid neuroreceptor subtypes mGluR₅ 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 mGluR₅ 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]H₂ 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.