Simultaneous quantification of glutamate and glutamine by J-modulated spectroscopy at 3 Tesla.

The echo time (TE) averaged spectrum is the one-dimensional (1D) cross-section of the J-resolved spectrum at J = 0. In multiecho TE-averaged spectroscopy, glutamate (Glu) is differentiated from glutamine (Gln) at 3 Tesla (T). This method, however, almost entirely suppresses Gln resonance lines around 2.35 ppm, leaving Gln undetermined. This study presents a novel method for quantifying both Glu and Gln using multi-echo spectral data. A 1D cross-section of J-resolved spectroscopy at J = 7.5 Hz-referred to as J-modulated spectroscopy-was developed to simultaneously quantify Glu and Gln levels in the human brain. The transverse relaxation times (T2 s) of metabolites were first determined using conventional TE-averaged spectroscopy with different starting echo time and then incorporated into the spectral model for fitting J-modulated data. Simulation and in vivo data showed that the resonance signals of Glu and Gln were clearly separated around 2.35 ppm in J-modulated spectroscopy. In the anterior cingulate cortex, both Glu and Gln levels were found to be significantly higher in gray matter than in white matter in healthy subjects (P < 10(-10) and < 10(-5) , respectively). Gln resonances can be clearly separated from Glu and N-acetyl-aspartate around 2.35 ppm using J-modulated spectroscopy. This method can be used to quantitatively measure Glu and Gln simultaneously at 3T. Magn Reson Med 76:725-732, 2016. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

Zhang Y ，Shen J 《-》

Detection of glutamate, glutamine, and glutathione by radiofrequency suppression and echo time optimization at 7 tesla.

To achieve detection of glutamate (Glu), glutamine (Gln), and glutathione (GSH) by minimizing the N-acetyl-aspartate (NAA) multiplet signals at 2.49 ppm using a echo time (TE) -optimized PRESS pulse sequence and a novel J-suppression radiofrequency pulse. Using density matrix simulations, a PRESS sequence with (TE1 , TE2 ) = (69, 37) ms and an inserted 90° J-suppression pulse were found to minimize the NAA multiplet at 2.49 ppm. NAA phantom experiments confirmed the successful suppression of the NAA multiplet at 2.49 ppm. A study of eight healthy volunteers found both Glu and Gln to be significantly higher in gray matter (GM) dominant medial prefrontal cortex voxels than in white matter (WM) dominant right frontal cortex voxels. Time-course (1) H spectra acquired during intravenous [U-(13) C6 ]glucose infusion showed gradually changing Glu C4 and Gln C4 proton resonance signals in a spectral pattern predicted by numerical simulations. Reliable detection of Glu, Gln, and GSH was achieved. Glu and Gln levels were significantly higher in frontal lobe GM than in frontal lobe WM. It is feasible to use the proposed proton MR spectroscopy method to measure the kinetics of (13) C incorporation into Glu and Gln during infusion of (13) C labeled glucose.

An L ，Li S ，Murdoch JB ，Araneta MF ，Johnson C ，Shen J ... -  《-》

Regional distributions of brain glutamate and glutamine in normal subjects.

Glutamate (Glu) and glutamine (Gln) play an important role in neuronal regulation and are of value as MRS-observable diagnostic biomarkers. In this study the relative concentrations of these metabolites have been measured in multiple regions in the normal brain using a short-TE whole-brain MRSI measurement at 3 T combined with a modified data analysis approach that used spatial averaging to obtain high-SNR spectra from atlas-registered anatomic regions or interest. By spectral fitting of high-SNR spectra this approach yielded reliable measurements across a wide volume of the brain. Spectral averaging also demonstrated increased SNR and improved fitting accuracy for the sum of Glu and Gln (Glx) compared with individual voxel fitting. Results in 26 healthy controls showed relatively constant Glu/Cr and Gln/Cr throughout the cerebrum, although with increased values in the anterior cingulum and paracentral lobule, and increased Gln/Cr in the superior motor area. The deep gray-matter regions of thalamus, putamen, and pallidum show lower Glu/Cr compared with cortical white-matter regions. Lobar measurements demonstrated reduced Glu/Cr and Gln/Cr in the cerebellum as compared with the cerebrum, where white-matter regions show significantly lower Glu/Cr and Gln/Cr as compared with gray-matter regions across multiple brain lobes. Regression analysis showed no significant effect of gender on Glu/Cr or Gln/Cr measurement; however, Glx/Cr ratio was found to be significantly negatively correlated with age in some lobar brain regions. In summary, this methodology provides the spectral quality necessary for reliable separation of Glu and Gln at 3 T from a single MRSI acquisition enabling generation of regional distributions of metabolites over a large volume of the brain, including cortical regions. Copyright © 2016 John Wiley & Sons, Ltd.

Goryawala MZ ，Sheriff S ，Maudsley AA 《-》

Simultaneous detection of resolved glutamate, glutamine, and gamma-aminobutyric acid at 4 T.

Hu J ，Yang S ，Xuan Y ，Jiang Q ，Yang Y ，Haacke EM ... -  《JOURNAL OF MAGNETIC RESONANCE》

Simultaneous observation of glutamate, gamma-aminobutyric acid, and glutamine in human brain at 4.7 T using localized two-dimensional constant-time correlation spectroscopy.

Localized two-dimensional constant-time correlation spectroscopy (CT-COSY) was used to resolve glutamate (Glu), gamma-aminobutyric acid (GABA), and glutamine (Gln) in the human brain at 4.7 T. In this method, three-dimensional localization was achieved using three radio frequency pulses of the CT-COSY module for slice selection. As this sequence could decouple JHH along the F1 direction, peak resolution of metabolites was improved even on a magnitude-mode display. In experiments on a phantom containing N-acetylaspartate, creatine, Glu, Gln, and GABA with a constant time delay (Tct) of 110 ms, cross peaks of Glu, Gln, and GABA were obtained on a spectrum processed with standard sine-bell windows, which emphasize sine-dependent signals along the t2 direction. In contrast, diagonal peaks of Glu C4H at 2.35 ppm, GABA C2H at 2.28 ppm, and Gln C4H at 2.44 ppm were resolved on a spectrum processed with Gaussian windows, which emphasize cosine-dependent signals along t2. Human brain spectra were obtained from a 27 mL voxel within the parieto-occipital region using a volume transverse electromagnetic (TEM) coil for both transmission and reception. Tct was 110 ms; the total scan time was 30 min. Diagonal peaks of Glu C4H, GABA C2H, and Gln C4H were also resolved on the spectrum processed with Gaussian windows. These results show that the localized two-dimensional CT-COSY method featuring 1H decoupling along the F1 direction could resolve Glu, GABA, and Gln signals in the human brain.

Watanabe H ，Takaya N ，Mitsumori F 《-》