Determination of Brain Metabolite T1 Without Interference From Macromolecule Relaxation.

BACKGROUND: J-coupled metabolites are often measured at a predetermined echo time in the presence of macromolecule signals, which complicates the measurement of metabolite T1 . PURPOSE: To evaluate the feasibility and benefits of measuring metabolite T1 relaxation times without changing the overlapping macromolecule baseline signals. STUDY TYPE: Prospective. SUBJECTS: Five healthy volunteers (three females and two males; age = 27 ± 7 years). FIELD STRENGTH/SEQUENCE: 7T scanner using a point resolved spectroscopy (PRESS)-based spectral editing MR spectroscopy (MRS) sequence with inversion recovery (IR). ASSESSMENT: F-tests were performed to evaluate if the new approach, which fitted all the spectra together and used the same baselines for the three different IR settings, significantly reduced the variances of the metabolite T1 values compared to a conventional fitting approach. STATISTICAL TESTS: Cramer-Rao lower bound (CRLB), within-subject coefficient of variation, and F-test. RESULTS: The T1 relaxation times of N-acetylaspartate (NAA), total creatine (tCr), total choline (tCho), myo-inositol (mI), and glutamate (Glu) were determined with CRLB values below 6%. Glutamine (Gln) T1 was determined with a 17% CRLB, and the T1 of γ-aminobutyric acid (GABA) was determined with a 34% CRLB. The new approach significantly reduced the variances (F-test P < 0.05) of NAA, Glu, Gln, tCr, tCho, and mI T1 s compared to the conventional approach. DATA CONCLUSION: Keeping macromolecule signals intact by using only long IR times allowed the use of a single macromolecule spectral model for different IR settings and significantly reduced the variances of NAA, Glu, Gln, tCr, tCho, and mI T1 s. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 1.

Signal enhancement of glutamine and glutathione by single-step spectral editing.

A single-step spectral editing approach using an always-on editing pulse was proposed to enhance the signals of strongly coupled spins. Specifically, a single-step spectral editing sequence with an always-on editing pulse applied at 2.12 ppm was used to enhance glutamine (Gln) and glutathione (GSH) signals at TE = 56 ms on a 7 T scanner. Density matrix simulations demonstrated that the current method (TE = 56 ms) led to large signal enhancement of at least 61% for Gln and 51% for GSH compared to a previous single-step method (TE = 106 ms). Monte Carlo simulations showed that the current method reduced noise-originated variations by 31% for Gln and 26% for GSH compared to a previous three-step spectral editing method from which the present method was derived.

Effects of carrier frequency mismatch on frequency-selective spectral editing.

OBJECTIVES: This study sought to investigate the effects of carrier frequency mismatch on spectral editing and its correction by frequency matching of basis functions. MATERIALS AND METHODS: Full density matrix computations and Monte-Carlo simulations based on magnetic resonance spectroscopy (MRS) data collected from five healthy volunteers at 7 T were used to analyze the effects of carrier frequency mismatch on spectral editing. Relative errors in metabolite quantification were calculated with and without frequency matching of basis functions. The algorithm for numerical computation of basis functions was also improved for higher computational efficiency. RESULTS: We found significant errors without frequency matching of basis functions when carrier frequency mismatch was generally considered negligible. By matching basis functions with the history of frequency deviation, the mean errors in glutamate, glutamine, γ-aminobutyric acid, and glutathione concentrations were reduced from 3.90%, 1.85%, 11.53%, and 3.43% to 0.18%, 0.34%, 0.40%, and 0.51%, respectively. CONCLUSION: Matching basis functions to frequency deviation history was necessary even when frequency deviations during frequency-selective spectral editing were fairly small. Basis set frequency matching significantly improved accuracy in the quantification of glutamate, glutamine, γ-aminobutyric acid, and glutathione concentrations.

Simultaneous measurement of glutamate, glutamine, GABA, and glutathione by spectral editing without subtraction.

PURPOSE: To simultaneously measure glutamate, glutamine, γ-aminobutyric acid (GABA), and glutathione using spectral editing without subtraction at 7T. METHODS: A novel spectral editing approach was proposed to simultaneously measure glutamate, glutamine, GABA, and glutathione using a TE of 56 ms at 7T. By numerical optimization of sequence timing in the presence of an editing pulse, the 4 metabolites all form relatively intense pseudo singlets with maximized peak amplitudes and minimized peak linewidths in 1 of the 3 interleaved spectra. For measuring glutamate, glutamine, and glutathione, the editing pulse targets the H3 protons of these metabolites near 2.12 parts per million. Both GABA H2 and H4 resonances are fully utilized in spectral fitting. RESULTS: Concentration levels (/[total creatine]) of glutamate, glutamine, GABA, and glutathione from an 8 mL voxel in the pregenual anterior cingulate cortex of 5 healthy volunteers were found to be 1.26 ± 0.13, 0.33 ± 0.06, 0.13 ± 0.03, and 0.27 ± 0.03, respectively, with within-subject coefficient of variation at 3.2%, 8.2%, 7.1%, and 10.2%, respectively. The total scan time was less than 4.5 min. CONCLUSIONS: The proposed new technique does not require data subtraction. The 3 major metabolites of the glutamatergic and GABAergic systems and the oxidative stress marker glutathione were all measured in 1 short scan with high precision.

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

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

13C MRS of occipital and frontal lobes at 3 T using a volume coil for stochastic proton decoupling.

Previously, we devised a novel strategy for in vivo 13C MRS using [2-13C]glucose infusion and low-power proton decoupling, and proposed that this strategy could be used to acquire 13C MR spectra from the frontal lobe of the human brain. Here, we demonstrate, for the first time, in vivo 13C MRS of human frontal lobe acquired at 3 T. Because the primary metabolites of [2-13C]glucose can be decoupled using very-low-radiofrequency power, we used a volume coil for proton decoupling in this study. The homogeneous B(1) field of the volume coil was found to significantly enhance the decoupling efficiency of the stochastic decoupling sequence. Detailed specific absorption rates inside the human head were analyzed using the finite difference time domain method to ensure experimental safety. In vivo 13C spectra from the occipital and frontal lobes of the human brain were obtained. At a decoupling power of 30 W (time-averaged power, 2.45 W), the spectra from the occipital lobe showed well-resolved spectral resolution and excellent signal-to-noise ratio. Although frontal lobe 13C spectra were affected by local B(0) field inhomogeneity, we demonstrated that the spectral quality could be improved using post-acquisition data processing. In particular, we showed that the frontal lobe glutamine C5 at 178.5 ppm and aspartate C4 at 178.3 ppm could be spectrally resolved with effective proton decoupling and B(0) field correction. Because of its large spatial coverage, volume coil decoupling provides the potential to acquire 13C MRS from more than one brain region simultaneously.