Reproducibility measurement of glutathione, GABA, and glutamate: Towards in vivo neurochemical profiling of multiple sclerosis with MR spectroscopy at 7T

Abstract

Purpose To determine the reproducibility of a comprehensive single-session measurement of glutathione (GSH), γ-aminobutyric acid (GABA), glutamate, and other biochemicals implicated in the pathophysiology of multiple sclerosis (MS) in the human brain with 1H MR spectroscopy. Materials and Methods Five healthy subjects were studied twice in separate 1-hour sessions at 7 Tesla. One MS patient was also scanned once. GSH and GABA were measured with J-difference editing using a semi-localized by adiabatic selective refocusing sequence (semi-LASER, TE=72 ms). A stimulated echo acquisition mode sequence (STEAM, TE=10 ms) was used to detect glutamate along with the overall biochemical profile. Spectra were quantified with LCModel. Quantification accuracy was assessed through Cramer-Rao lower bounds (CRLB). Reproducibility of the metabolite quantification was tested using coefficients of variation (CoV). Results CRLB were ≤7% for GSH, GABA, and glutamate and average CoV of 7.8±3.2%, 9.5±7.0%, and 3.2±1.7% were achieved, respectively. The average test/re-test concentration differences at this measurement reproducibility and quantification accuracy were smaller for GABA and glutamate than inter-subject variations in metabolite content with CoV ratios of 0.6 and 0.8, respectively. As proof of principle, GSH, GABA, and glutamate were also detected in an MS patient. Conclusion GSH, GABA, glutamate, and other metabolites relevant in MS can be quantified at 7 Tesla with high accuracy and reproducibility in a single 1-hour session. This methodology might serve as a clinical research tool to investigate biochemical markers associated with MS.

Dephasing optimization through coherence order pathway selection (DOTCOPS) for improved crusher schemes in MR spectroscopy

“…The data‐processing pipeline for all experiments was identical and as follows. The raw data from all individual acquisitions and 8 receivers were stored separately and spectral processing was done with the free MRS software package INSPECTOR . First, eddy current phase correction and sensitivity‐weighted summation of the receive channels were applied.…”

Excitotoxins, Mitochondrial and Redox Disturbances in Multiple Sclerosis

“…Modern research made it possible to quantify GABA, GSH, and glutamate together with other metabolites relevant in MS at 7T with high accuracy and reproducibility in a single 1-h session [205]. This technique helps profile the metabolic changes during the disease course to identify potentially relevant targets.…”

Theoretical description of modern1H in Vivo magnetic resonance spectroscopic pulse sequences

“…Both MEGA and BASING are nearly identical and differ only in their crusher schemes, both of which are sufficient to dephase all unwanted coherence pathways. The name MEGA has become the term of choice for this method and is today used more frequently for JDE than solely for solvent suppression, although it is also used for simultaneous J ‐editing and water suppression …”

“…In principle, JDE techniques can be used to disentangle any two metabolites that overlap in the spectral domain as long as one of their coupling partners does not overlap while exhibiting suitable J ‐coupling. JDE techniques have been used to isolate a variety of metabolites, such as GABA, glutathione, lactate, vitamin C, glutamine and glutamate, glycine, 2‐hydroxyglutarate, N‐acetylaspartylglutamate, and serine . For a more comprehensive description of edited MRS sequences, the reader is directed to the review by Harris et al…”