Background: Accumulated evidence suggests that insulin resistance and impairments in cerebral insulin receptor signaling may contribute to age-related cognitive deficits and Alzheimer's disease. The enhancement of insulin receptor signaling is, therefore, a promising strategy for the treatment of age-related cognitive disorders. The mitochondrial respiratory chain, being involved in insulinstimulated H 2 O 2 production, has been identified recently as a potential target for the enhancement of insulin signaling. The aim of the present study is to examine: (1) whether a specific respiratory substrate, dicholine salt of succinic acid (CS), can enhance insulin-stimulated insulin receptor autophosphorylation in neurons, and (2) whether CS can ameliorate cognitive deficits of various origins in animal models.

Purpose To separately measure N‐acetyl aspartul glutamate (NAAG), N‐acetyl aspartate (NAA), aspartate (Asp), and glutamate (Glu) concentrations in white matter (WM) using J‐editing techniques in patients with mild traumatic brain injury (mTBI) in the acute phase. Methods Twenty‐four patients with closed concussive head injury and 29 healthy volunteers were enrolled in the current study. For extended 1H MRS examination, patients and controls were equally divided into two subgroups. In subgroup 1 (12 patients/15 controls), NAAG and NAA concentrations were measured in WM separately with MEGA‐PRESS (echo time/repetition time [TE/TR] = 140/2000 ms; δONNAA/ δOFFNAA = 4.84/4.38 ppm, δONNAAG/ δOFFNAAG = 4.61/4.15 ppm). In subgroup 2 (12 patients/14 controls), Asp and Glu concentrations were acquired with MEGA‐PRESS (TE/TR = 90/2000 ms; δONAsp/ δOFFAsp = 3.89/5.21 ppm) and TE‐averaged PRESS (TE from 35 ms to 185 ms with 2.5‐ms increments; TR = 2000 ms) pulse sequences, respectively. Results tNAA and NAAG concentrations were found to be reduced, while NAA concentrations were unchanged, after mild mTBI. Reduced Asp and elevated myo‐inositol (mI) concentrations were also found. Conclusion The main finding of the study is that the tNAA signal reduction in WM after mTBI is associated with a decrease in the NAAG concentration rather than a decrease in the NAA concentration, as was thought previously. This finding highlights the importance of separating these signals, at least for WM studies, to avoid misinterpretation of the results. NAAG plays an important role in selectively activating mGluR3 receptors, thus providing neuroprotective and neuroreparative functions immediately after mTBI. NAAG shows potential for the development of new therapeutic strategies for patients with injuries of varying severity.

Purpose Heating of gradient coils and passive shim components is a common cause of instability in the B 0 field, especially when gradient intensive sequences are used. The aim of the study was to set a benchmark for typical drift encountered during MR spectroscopy (MRS) to assess the need for real-time field-frequency locking on MRI scanners by comparing field drift data from a large number of sites. Method A standardized protocol was developed for 80 participating sites using 99 3T MR scanners from 3 major vendors. Phantom water signals were acquired before and after an EPI sequence. The protocol consisted of: minimal preparatory imaging; a short pre-fMRI PRESS; a ten-minute fMRI acquisition; and a long post-fMRI PRESS acquisition. Both pre- and post-fMRI PRESS were non-water suppressed. Real-time frequency stabilization/adjustment was switched off when appropriate. Sixty scanners repeated the protocol for a second dataset. In addition, a three-hour post-fMRI MRS acquisition was performed at one site to observe change of gradient temperature and drift rate. Spectral analysis was performed using MATLAB. Frequency drift in pre-fMRI PRESS data were compared with the first 5:20 minutes and the full 30:00 minutes of data after fMRI. Median (interquartile range) drifts were measured and showed in violin plot. Paired t-tests were performed to compare frequency drift pre- and post-fMRI. A simulated in vivo spectrum was generated using FID-A to visualize the effect of the observed frequency drifts. The simulated spectrum was convolved with the frequency trace for the most extreme cases. Impacts of frequency drifts on NAA and GABA were also simulated as a function of linear drift. Data from the repeated protocol were compared with the corresponding first dataset using Pearson's and intraclass correlation coefficients (ICC). Results Of the data collected from 99 scanners, 4 were excluded due to various reasons. Thus, data from 95 scanners were ultimately analyzed. For the first 5:20 min (64 transients), median (interquartile range) drift was 0.44 (1.29) Hz before fMRI and 0.83 (1.29) Hz after. This increased to 3.15 (4.02) Hz for the full 30 min (360 transients) run. Average drift rates were 0.29 Hz/min before fMRI and 0.43 Hz/min after. Paired t-tests indicated that drift increased after fMRI, as expected (p < 0.05). Simulated spectra convolved with the frequency drift showed that the intensity of the NAA singlet was reduced by up to 26%, 44 % and 18% for GE, Philips and Siemens scanners after fMRI, respectively. ICCs indicated good agreement between datasets acquired on separate days. The single site long acquisition showed drift rate was reduced to 0.03 Hz/min approximately three hours after fMRI. Discussion This study analyzed frequency drift data from 95 3T MRI scanners. Median levels of drift were relatively low (5-min average under 1 Hz), but the most extreme cases suffered from higher ...

The MEGA-PRESS pulse sequence was used for determination of overlapping signals in the (1)H-MRS spectra of the human brain. For the first time, the balance of GABA glutamate/glutamine concentrations was estimated quantitatively in the human brain of patients with ultra-high risk of schizophrenia. It was found that GABA concentration and GABA/GLX ratios were significantly reduced in the left frontal lobe of UHR subjects.