Feasibility of Glutamate and GABA Detection in Pons and Thalamus at 3T and 7T by Proton Magnetic Resonance Spectroscopy

Abstract

Glutamate detection in pons and thalamus using proton magnetic resonance spectroscopy (1 H-MRS) after an intervention is of interest for studying various brain disorders. However, 1 H-MRS in these brain regions is challenging and time-consuming, especially in longitudinal study designs. 1 H-MRS of more cortical structures at the ultrahigh magnetic field strength of 7T yields an improved spectral output, including separation of the glutamate signal from the glutamine signal, in a shorter and more feasible scan time, as compared to conventional clinical field strengths. For this purpose, we compared the feasibility of 1 H-MRS at 3T and 7T in pons and thalamus by applying a longitudinal study design of repeated measures on same day and three separate days at both field strength in five healthy participants. Total 1 H-MRS acquisition time was reduced by a factor 3.75 for pons and by a factor 3 for thalamus at 7T as compared to 3T. We found higher spectral signal-to-noise ratio (SNR) (p < 0.001), lower linewidth (p = 0.001) and lower Cramér-Rao lower bounds (CRLB) (p < 0.001) for the combined glutamate and glutamine signal (Glx) in thalamus at 7T as compared to 3T. In pons, CRLB of Glx and SNR were lower at 7T (p = 0.002 and p = 0.006), with no differences in linewidth compared to 3T. Mean within-subject variability of Glx concentration estimates was lower at 7T compared to 3T for both pons and thalamus. At 7T, it was possible to assess glutamate and γ-aminobutyric acid (GABA) simultaneously in pons and thalamus. In conclusion, 1 H-MRS at 7T resulted in improved spectral quality while allowing shorter scan times than at 3T as well as estimation of the pure glutamate signal in pons and thalamus. This opens up the opportunity for multimodal study designs and multiregional subcortical 1 H-MRS research. Glutamate and GABA measurement at 7T in pons and thalamus is advantageous for future investigations of excitatory-inhibitory mechanisms in brain disorders.

Interictal pontine metabolism in migraine without aura patients: A 3 Tesla proton magnetic resonance spectroscopy study

“…In the current study, we investigated Glx, which represents the combined concentration estimate of glutamate and glutamine, as the signals of these two metabolites are inseparable at 3 Tesla ( Deelchand et al, 2014 , Younis et al, 2020b ). However, majority of the combined concentration (i.e.…”

“…Repeated measurements during the course of a migraine attack may elucidate if alterations in the glutamate levels appear closer to an impending attack, and/or in the early stages of an attack. Future pontine investigation in migraine may be expanded by adding measurement of the major inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), possibly at increased magnetic field strengths ( Younis et al, 2020b ).…”

“…Another common limitation of 3 Tesla 1 H-MRS is the minor contribution of glutamine to the Glx signal ( Tkáč et al, 2009 ). Measurement at higher magnetic field strengths, such as 7 Tesla, allows reliable separation of the glutamate and glutamine signal in the pons ( Younis et al, 2020b ). The 1 H-MRS voxel was larger than the specific nuclei involved in the glutamatergic migraine mechanisms.…”

Add-On MEmaNtine to Dopamine Antagonism to Improve Negative Symptoms at First Psychosis- the AMEND Trial Protocol

“…Our group has established a robust 7T protocol for glutamate MRS at our 7T MR system and validated the protocol in a cohort on healthy individuals in a study on normal cognitive aging ( 71 , 72 ).…”

Application of 7T MRS to High-Grade Gliomas

“…18 Comparisons of spectroscopy at lower field strengths such as 1.5T and 3T versus higher field strengths such as 7T to date have indicated that 7T is associated with substantial gains in SNR and more limited increases in spatial resolution, 19 better spectral separation and therefore additional tumor-specific metabolite information, 20 superior quantification of metabolites with small signals such as Gln, 21 and reduced Cramér-Rao lower bound (CRLB) values. [22][23][24][25] CRLB is a measure of the precision of an estimate, similar to an SD, which is used particularly with LCModel (http://www. lcmodel.com/).…”