Improved resolution of glutamate, glutamine and γ-aminobutyric acid with optimized point-resolved spectroscopy sequence timings for their simultaneous quantification at 9.4 T.

Glutamine (Gln), glutamate (Glu) and γ-aminobutyric acid (GABA) are relevant brain metabolites that can be measured with magnetic resonance spectroscopy (MRS). This work optimizes the point-resolved spectroscopy (PRESS) sequence echo times, TE1 and TE2 , for improved simultaneous quantification of the three metabolites at 9.4 T. Quantification was based on the proton resonances of Gln, Glu and GABA at ≈2.45, ≈2.35 and ≈2.28 ppm, respectively. Glu exhibits overlap with both Gln and GABA; in addition, the Gln peak is contaminated by signal from the strongly coupled protons of N-acetylaspartate (NAA), which resonate at about 2.49 ppm. J-coupling evolution of the protons was characterized numerically and verified experimentally. A {TE1 , TE2 } combination of {106 ms, 16 ms} minimized the NAA signal in the Gln spectral region, whilst retaining Gln, Glu and GABA peaks. The efficacy of the technique was verified on phantom solutions and on rat brain in vivo. LCModel was employed to analyze the in vivo spectra. The average T2 -corrected Gln, Glu and GABA concentrations were found to be 3.39, 11.43 and 2.20 mM, respectively, assuming a total creatine concentration of 8.5 mM. LCModel Cramér-Rao lower bounds (CRLBs) for Gln, Glu and GABA were in the ranges 14-17%, 4-6% and 16-19%, respectively. The optimal TE resulted in concentrations for Gln and GABA that agreed more closely with literature concentrations compared with concentrations obtained from short-TE spectra acquired with a {TE1 , TE2 } combination of {12 ms, 9 ms}. LCModel estimations were also evaluated with short-TE PRESS and with the optimized long TE of {106 ms, 16 ms}, using phantom solutions of known metabolite concentrations. It was shown that concentrations estimated with LCModel can be inaccurate when combined with short-TE PRESS, where there is peak overlap, even when low (<20%) CRLBs are reported.

Dobberthien BJ ，Tessier AG ，Yahya A 《-》

PRESS timings for resolving (13) C(4) -glutamate (1) H signal at 9.4 T: Demonstration in rat with uniformly labelled (13) C-glucose.

MRS of 13 C4 -labelled glutamate (13 C4 -Glu) during an infusion of a carbon-13 (13 C)-labelled substrate, such as uniformly labelled glucose ([U-13 C6 ]-Glc), provides a measure of Glc metabolism. The presented work provides a single-shot indirect 13 C detection technique to quantify the approximately 2.51 ppm 13 C4 -Glu satellite proton (1 H) peak at 9.4 T. The methodology is an optimized point-resolved spectroscopy (PRESS) sequence that minimizes signal contamination from the strongly coupled protons of N-acetylaspartate (NAA), which resonate at approximately 2.49 ppm. J-coupling evolution of protons was characterized numerically and verified experimentally. A (TE1 , TE2 ) combination of (20 ms, 106 ms) was found to be suitable for minimizing NAA signal in the 2.51 ppm 1 H 13 C4 -Glu spectral region, while retaining the 13 C4 -Glu 1 H satellite peak. The efficacy of the technique was verified on phantom solutions and on two rat brains in vivo during an infusion of [U-13 C6 ]-Glc. LCModel was employed for analysis of the in vivo spectra to quantify the 2.51 ppm 1 H 13 C4 -Glu signal to obtain Glu C4 fractional enrichment time courses during the infusions. Cramér-Rao lower bounds of about 8% were obtained for the 2.51 ppm 13 C4 -Glu 1 H satellite peak with the optimal TE combination.

Dobberthien BJ ，Tessier AG ，Stanislaus AE ，Sawyer MB ，Fallone BG ，Yahya A ... -  《-》

Quantification of GABA, glutamate and glutamine in a single measurement at 3 T using GABA-edited MEGA-PRESS.

γ-Aminobutyric acid (GABA) and glutamate (Glu), major neurotransmitters in the brain, are recycled through glutamine (Gln). All three metabolites can be measured by magnetic resonance spectroscopy in vivo, although GABA measurement at 3 T requires an extra editing acquisition, such as Mescher-Garwood point-resolved spectroscopy (MEGA-PRESS). In a GABA-edited MEGA-PRESS spectrum, Glu and Gln co-edit with GABA, providing the possibility to measure all three in one acquisition. In this study, we investigated the reliability of the composite Glu + Gln (Glx) peak estimation and the possibility of Glu and Gln separation in GABA-edited MEGA-PRESS spectra. The data acquired in vivo were used to develop a quality assessment framework which identified MEGA-PRESS spectra in which Glu and Gln could be estimated reliably. Phantoms containing Glu, Gln, GABA and N-acetylaspartate (NAA) at different concentrations were scanned using GABA-edited MEGA-PRESS at 3 T. Fifty-six sets of spectra in five brain regions were acquired from 36 healthy volunteers. Based on the Glu/Gln ratio, data were classified as either within or outside the physiological range. A peak-by-peak quality assessment was performed on all data to investigate whether quality metrics can discriminate between these two classes of spectra. The quality metrics were as follows: the GABA signal-to-noise ratio, the NAA linewidth and the Glx Cramer-Rao lower bound (CRLB). The Glu and Gln concentrations were estimated with precision across all phantoms with a linear relationship between the measured and true concentrations: R1 = 0.95 for Glu and R1 = 0.91 for Gln. A quality assessment framework was set based on the criteria necessary for a good GABA-edited MEGA-PRESS spectrum. Simultaneous criteria of NAA linewidth <8 Hz and Glx CRLB <16% were defined as optimum features for reliable Glu and Gln quantification. Glu and Gln can be reliably quantified from GABA-edited MEGA-PRESS acquisitions. However, this reliability should be controlled using the quality assessment methods suggested in this work.

Sanaei Nezhad F ，Anton A ，Michou E ，Jung J ，Parkes LM ，Williams SR ... -  《-》

Improvement of resolution for brain coupled metabolites by optimized (1)H MRS at 7T.

Choi C ，Dimitrov IE ，Douglas D ，Patel A ，Kaiser LG ，Amezcua CA ，Maher EA ... -  《-》

Characterization of the response of taurine protons to PRESS at 9.4 T for Resolving choline and Determining taurine T2.

Point-resolved spectroscopy (PRESS), characterized by two TEs (TE1 and TE2 ), can be employed to perform animal magnetic resonance spectroscopy (MRS) studies at 9.4 T. Taurine (Tau) and choline (Cho) are relevant metabolites that can be measured by MRS. In this work, the response of the J-coupled protons of Tau as a function of PRESS TE1 and TE2 was characterized at 9.4 T to achieve two objectives. The first was to determine two TE1 and TE2 combinations that could be used to obtain T2 -corrected measures of Tau (3.42 ppm) that were minimally influenced by J coupling. The second was to exploit the Tau J coupling to find a timing combination that minimized the 3.25-ppm Tau signal to enable the Cho (3.22 ppm) resonance to be resolved from the overlapping Tau signal. The response of Tau protons was investigated both numerically and experimentally. It was numerically determined that the timings {TE1 , TE2 } = {17 ms, 10 ms} and {TE1 , TE2 } = {80 ms, 70 ms} yielded similar 3.42-ppm Tau resonance areas (5% difference), rendering them suitable for Tau T2 determination. {TE1 , TE2 } = {25 ms, 50 ms} was found to yield minimal 3.25-ppm Tau signal, reducing its interference with Cho. The efficacy of the timings was demonstrated on phantom solutions and in vivo in four Sprague Dawley rats. LCModel was employed to analyse the in vivo spectra and Tau T2 values were estimated by fitting the Tau peak areas obtained with {TE1 , TE2 } = {17 ms, 10 ms} and {TE1 , TE2 } = {80 ms, 70 ms} to a monoexponentially decaying function. An average Tau T2 of 106 ms (standard deviation, 12 ms) was obtained. LCModel analysis of rat spectra obtained with {TE1 , TE2 } = {25 ms, 50 ms} demonstrated negligible levels of Tau signal, compared with that obtained with short TE.

Fisher ME ，Dobberthien BJ ，Tessier AG ，Yahya A ... -  《-》