Resting-state functional connectivity and quantitation of glutamate and GABA of the PCC/precuneus by magnetic resonance spectroscopy at 7T in healthy individuals.

The default mode network (DMN) is the main large-scale network of the resting brain and the PCC/precuneus is a major hub of this network. Glutamate and GABA (γ-amino butyric acid) are the main excitatory and inhibitory neurotransmitters in the CNS, respectively. We studied glutamate and GABA concentrations in the PCC/precuneus via magnetic resonance spectroscopy (MRS) at 7T in relation to age and correlated them with functional connectivity between this region and other DMN nodes in ten healthy right-handed volunteers ranging in age between 23-68 years. Mean functional connectivity of the PCC/precuneus to the other DMN nodes and the glutamate/GABA ratio significantly correlated with age (r = 0.802, p = 0.005 and r = 0.793, p = 0.006, respectively) but not with each other. Glutamate and GABA alone did not significantly correlate with age nor with functional connectivity within the DMN. The glutamate/GABA ratio and functional connectivity of the PCC/precuneus are, therefore, independent age-related biomarkers of the DMN and may be combined in a multimodal pipeline to study DMN alterations in various disease states.

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

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 cm3 ) 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.

Reproducibility of Glutamate, Glutathione, and GABA Measurements in vivo by Single-Voxel STEAM Magnetic Resonance Spectroscopy at 7-Tesla in Healthy Individuals.

BACKGROUND AND PURPOSE: Derangements in brain glutamate, glutathione, and γ-amino butyric acid (GABA) are implicated in a range of neurological disorders. Reliable methods to measure these compounds non-invasively in vivo are needed. We evaluated the reproducibility of their measurements in brain regions involved in the default mode network using quantitative MRS at 7-Tesla in healthy individuals. METHODS: Ten right-handed healthy volunteers underwent 7-Tesla MRI scans on 2 separate days, not more than 2 weeks apart. On each day two scanning sessions took place, with a re-positioning break in between. High-resolution isotropic anatomical scans were acquired prior to each scan, followed by single-voxel 1H-MRS using the STEAM pulse sequence on an 8 mL midline cubic voxel, positioned over the posterior cingulate and precuneus regions. Concentrations were corrected for partial-volume effects. RESULTS: Maximal Cramér-Rao lower bounds for glutamate, glutathione, and GABA were 2.0, 8.0, and 14.0%, respectively. Mean coefficients of variation within sessions were 5.9 ± 4.8%, 9.3 ± 7.6%, and 11.5 ± 8.8%, and between sessions were 4.6 ± 4.5%, 8.3 ± 5.7%, and 9.2 ± 8.7%, respectively. The mean (±SD) Dice's coefficient for voxel overlap was 90 ± 4% within sessions and 86 ± 7% between sessions. CONCLUSION: Glutamate, glutathione, and GABA can be reliably quantified using STEAM MRS at 7-Tesla from the posterior cingulate and precuneus cortices of healthy human subjects. STEAM MRS at 7-Tesla may be used to study the metabolic behavior of this important resting-state hub in various disease states.

Resting-state functional MRI of the default mode network in epilepsy.

The default mode network (DMN) is a major neuronal network that deactivates during goal-directed tasks. Recent advances in neuroimaging have shed light on its structure and function. Alterations in the DMN are increasingly recognized in a range of neurological and psychiatric conditions including epilepsy. This review first describes the current understanding of the DMN in health, normal aging, and disease as it is acquired via resting-state functional magnetic resonance imaging (MRI), before focusing on how it is affected in various types of focal and generalized epilepsy. These findings support the potential use of DMN parameters as future biomarkers in epilepsy research, diagnosis, and management.

Effect of the 2013 AHA/ASA guidelines on TPA use in acute ischemic stroke at Assaf Harofeh Medical Center in Israel.

BACKGROUND: Use of TPA to treat patients with acute ischemic stroke was introduced in Assaf Harofeh Medical Center (AHMC) in Israel in November 2007 initially with strict adherence to the inclusion/exclusion criteria of the pivotal NINDS TPA studies published in 1995. The treatment window was expanded in 2010 to 4.5h following the results of ECASS-III. Application of the 2013 AHA/ASA Guidelines resulted in further expanded inclusion and relaxed exclusion criteria. DESIGN/METHODS: A retrospective chart review was conducted of patients who received TPA at AHMC to evaluate the additional impact of applying the 2013 guidelines. Number of patients treated, outcomes at discharge, and safety were compared between two periods: May 2011-January 2013 (the 21months preceding the 2013 Guidelines); and February 2013-October 2014 (the 21months after publication of the 2013 Guidelines). Statistical analysis was done using z-tests for differences between proportions, and t-tests to compare means. RESULTS: 63 patients were treated during the immediate pre-2013 Guideline period (36/year, or approximately 5% of patients with ischemic stroke), and 105 during the post-2013 Guidelines period (60/year, approximately 8.3% of patients with ischemic stroke) (p<0.001). During the two periods, respectively: discharges home were 22(34%) and 55(52%) (p<0.05); facility discharges were 29(46%) and 33(31%); and inter-hospital transfers were 6(9%), and 11(10% of treated patients). Most transfers were for endovascular treatment. Total treatment-related symptomatic bleeds in the two periods, respectively, was: 4(6%) and 4(4%), and the number of in-hospital deaths was 6 (9%) and 6 (6%) (unchanged). CONCLUSIONS: Application of the 2013 AHA/ASA Guidelines resulted in a 64% increase in the number of acute ischemic stroke patients treated with TPA at AHMC with no worsening of aggregate outcomes and no increase in bleeds or deaths.