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

Hum Brain Mapp. 2022 May;43(7):2148-2163. doi: 10.1002/hbm.25778. Epub 2022 Jan 25.

Abstract

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 [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 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 [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.

Keywords: GABAA; PET atlas construction; mGluR5; multimodal imaging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain / diagnostic imaging
  • Brain / metabolism
  • Brain Mapping / methods
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Positron-Emission Tomography* / methods
  • Receptors, GABA-A* / metabolism
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Receptors, GABA-A
  • gamma-Aminobutyric Acid