Seven‐tesla quantitative magnetic resonance spectroscopy of glutamate, γ‐aminobutyric acid, and glutathione in the posterior cingulate cortex/precuneus in patients with epilepsy

Abstract

Objective: The posterior cingulate cortex (PCC)/precuneus is a key hub of the default mode network, whose function is known to be altered in epilepsy. Glutamate and γ-aminobutyric acid (GABA) are the main excitatory and inhibitory neurotransmitters in the central nervous system, respectively. Glutathione (GSH) is the most important free radical scavenging compound in the brain. Quantification of these molecules by magnetic resonance spectroscopy (MRS) up to 4 T is limited by overlapping resonances from other molecules. In this study, we used ultra-high-field (7 T) MRS to quantify their concentrations in patients with different epilepsy syndromes. Methods: Nineteen patients with temporal lobe epilepsy (TLE) and 16 with idiopathic generalized epilepsy (IGE) underwent magnetic resonance imaging scans using a 7-T research scanner. Single-voxel (8 cm 3) MRS, located in the PCC/precuneus, was acquired via stimulated echo acquisition mode. Their results were compared to 10 healthy volunteers. Results: Mean concentrations of glutamate, GABA, and the glutamate/GABA ratio did not differ between the IGE, TLE, and healthy volunteer groups. The mean ± SD concentration of GSH was 1.9 ± 0.3 mmol•L-1 in healthy controls, 2.0 ± 0.2 mmol•L-1 in patients with TLE, and 2.2 ± 0.4 mmol•L-1 in patients with IGE. One-way analysis of variance with post hoc Tukey-Kramer test revealed a significant difference in the concentration of GSH between patients with IGE and controls (P = .03). Short-term seizure freedom in patients with epilepsy was predicted by an elevated concentration of glutamate in the PCC/precuneus (P = .01). In patients with TLE, the concentration of GABA declined with age (P = .03). Significance: Patients with IGE have higher concentrations of GSH in the PCC/ precuneus than healthy controls. There is no difference in the concentrations of glutamate and GABA, or their ratio, in the PCC/precuneus between patients with IGE, patients with TLE, and healthy controls. Measuring the concentration of glutamate in the PCC/precuneus may assist with predicting drug response.

In Vivo Brain GSH: MRS Methods and Clinical Applications

“…Similarly, a more recent study on 7 T MRS demonstrated increased levels of glutathione in the posterior cingulate cortex (PCC)/precuneus of patients with idiopathic generalized epilepsy compared with the healthy volunteers (2.2 ± 0.4 compared with 2.0 ± 0.2 mM/L, respectively); this controversial finding suggested increased GSH levels as an early response to oxidative stress. No difference was found in the levels of other metabolites such as GABA and glutamate [ 7 ].…”

“…Changes in the GSH brain concentration from oxidative stress may reflect inflammatory processes and mitochondrial dysfunction associated with biological aging [ 3 ] and pathological conditions [ 4 , 5 ]. In particular, as high levels of ROS may lead to cerebral tissue damage, the altered GSH concentration of specific brain areas has been described in several neurologic disorders, including epilepsy [ 6 , 7 ], multiple sclerosis [ 8 , 9 ], Alzheimer’s disease [ 10 ], Parkinson’s disease [ 11 , 12 ], and psychiatric disorders [ 13 , 14 , 15 , 16 ]. In order to provide a clear and thorough understating of GSH metabolism within the brain, an accurate and reliable estimation of cerebral concentrations needs to be performed.…”

Altered Metabolites in the Occipital Lobe in Migraine Without Aura During the Attack and the Interictal Period

“…Several studies have used phantom data to provide evidence that it is possible to measure changes in GSH concentration using 1 H-MRS, and GSH can be quantified reproducibly in vivo ( 28 , 29 ). GSH has been measured by 1 H-MRS in humans in a number of neurological diseases such as Alzheimer's disease ( 30 ), schizophrenia ( 31 ), and epilepsy ( 32 ). To our knowledge, this study was the first to investigate the changes in brain GSH in migraineurs using 1 H-MRS. GSH is the major cellular antioxidant that is essential for cellular function, plays roles in oxidation–reduction reactions, and protects against reactive oxygen species ( 33 , 34 ).…”

Mitochondrial and metabolic dysfunction in Friedreich ataxia: update on pathophysiological relevance and clinical interventions

“…Glutathione has been successfully imaged and quantified using 3T MRS techniques, though images obtained at this field strength may lack the fidelity and accuracy for detecting small changes in clinical trials [ 85 ]. Along with the 3T imaging glutathione, 7T MRS imaging can also assess glutathione as well [ 98 ]. Ultra-high MRI uses 7T scanners that are primarily used for research on human subjects, but it has not been used regularly in clinical studies.…”

“…Ultra-high MRI uses 7T scanners that are primarily used for research on human subjects, but it has not been used regularly in clinical studies. 7T images can be heavily affected by the smallest movements; in some cases, subjects’ heartbeats could move the brain by under a millimeter, altering the results [ 98 ]. Its safety in children is also unknown.…”