A new processing pipeline for mGluR5 and GABAA receptor-specific parametric PET atlases

25th January 2022

Nicolas Kaulen, Ravichandran Rajkumar, Claudia Régio Brambilla, Jörg Mauler, Shukti Ramkiran, Linda Orth, Hasan Sbaihat, Markus Lang, Christine Wyss, Elena Rota Kops, Jürgen Scheins, Bernd Neumaier, Johannes Ermert, Hans R. Herzog Karl-Joseph Langen, Christoph Lerche, N. Jon Shah, Tanja Veselinović and Irene Neuner

Current research indicates that the glutamate and γ-aminobutyric acid neuroreceptor subtypes mGluR5 and GABAA play a substantial role in the development of a variety of psychiatric diseases. However, detailed information relating to their in vivo distribution remains sparse. 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 studies.

Using data from healthy subjects, this study presents a comprehensive processing pipeline for the construction of maps showing the distribution of mGluR5 and GABAA in the brain. The applicability of the proposed pipeline was tested using two radioligands for which no established receptor atlases or activity concentration templates were available: [11C]ABP688 (3-(6-methyl-pyridine-2-ylethynyl)-cyclohex-2-enone-O-[11C]methyloxime) and [11C]Flumazenil.

Following validation by assessing the percent error, δ, of the extracted parametric values from warped space to native space in a selection of brain regions, the average δABP=3.0±1.0% and δFMZ=3.8±1.4% were found to be lower than the expected variabilities, σ, of the tracers (σABP=4.0%-16.0%, σFMZ = 3.9%-9.5%). Moreover, 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.

Based on these promising results, it is anticipated that the acquired maps can be used for further research into the role of mGluR5 and GABAA in the healthy and diseased brain, and, furthermore, it is expected that the proposed pipeline will become a viable tool for the construction of standardised PET data distributions.

Original publication: mGluR5 and GABAA Receptor Specific Parametric PET Atlas Construction - PET/MR Data Processing Pipeline, Validation and Application

The atlas data associated with this publication can be accessed here:In-vivo mGluR5 and GABAA Receptor Specific Parametric PET Atlas of the Human Brain