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Hadamard editing of glutathione and macromolecule-suppressed GABA.

ABSTRACT: The primary inhibitory neurotransmitter ?-aminobutyric acid (GABA) and the major antioxidant glutathione (GSH) are compounds of high importance for the function and integrity of the human brain. In this study, a method for simultaneous J-difference spectral-edited magnetic resonance spectroscopy (MRS) of GSH and GABA with suppression of macromolecular (MM) signals at 3 T is proposed. MM-suppressed Hadamard encoding and reconstruction of MEGA (Mescher-Garwood)-edited spectroscopy (HERMES) consists of four sub-experiments (TE = 80 ms), with 20-ms editing pulses applied at: (A) 4.56 and 1.9 ppm; (B) 4.56 and 1.5 ppm; (C) 1.9 ppm; and (D) 1.5 ppm. One Hadamard combination (A + B - C - D) yields GSH-edited spectra, and another (A - B + C - D) yields GABA-edited spectra, with symmetric suppression of the co-edited MM signal. MM-suppressed HERMES, conventional HERMES and separate Mescher-Garwood point-resolved spectroscopy (MEGA-PRESS) data were successfully acquired from a (33 mm)3 voxel in the parietal lobe in 10 healthy subjects. GSH- and GABA-edited MM-suppressed HERMES spectra were in close agreement with the respective MEGA-PRESS spectra. Mean GABA (and GSH) estimates were 1.10 ± 0.15 i.u. (0.59 ± 0.12 i.u.) for MM-suppressed HERMES, and 1.13 ± 0.09 i.u. (0.66 ± 0.09 i.u.) for MEGA-PRESS. Mean GABA (and GSH) differences between MM-suppressed HERMES and MEGA-PRESS were -0.03 ± 0.11 i.u. (-0.07 ± 0.11 i.u.). The mean signal-to-noise ratio (SNR) improvement of MM-suppressed HERMES over MEGA-PRESS was 1.45 ± 0.25 for GABA and 1.32 ± 0.24 for GSH. These results indicate that symmetric suppression of the MM signal can be accommodated into the Hadamard editing framework. Compared with sequential single-metabolite MEGA-PRESS experiments, MM-suppressed HERMES allows for simultaneous edited measurements of GSH and GABA without MM contamination in only half the scan time, and SNR is maintained.

SUBMITTER: Oeltzschner G

PROVIDER: S-EPMC5737628 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Hadamard editing of glutathione and macromolecule-suppressed GABA.

Oeltzschner Georg G Chan Kimberly L KL Saleh Muhammad G MG Mikkelsen Mark M Puts Nicolaas A NA Edden Richard A E RAE

NMR in biomedicine 20171026 1

The primary inhibitory neurotransmitter γ-aminobutyric acid (GABA) and the major antioxidant glutathione (GSH) are compounds of high importance for the function and integrity of the human brain. In this study, a method for simultaneous J-difference spectral-edited magnetic resonance spectroscopy (MRS) of GSH and GABA with suppression of macromolecular (MM) signals at 3 T is proposed. MM-suppressed Hadamard encoding and reconstruction of MEGA (Mescher-Garwood)-edited spectroscopy (HERMES) consist ...[more]

PMID: 29073732

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Project description:PURPOSE:To demonstrate the framework of a novel Hadamard-encoded spectral editing approach for simultaneously detecting multiple low-concentration brain metabolites in vivo at 3T. METHODS:HERCULES (Hadamard Editing Resolves Chemicals Using Linear-combination Estimation of Spectra) is a four-step Hadamard-encoded editing scheme. 20-ms editing pulses are applied at: (A) 4.58 and 1.9?ppm; (B) 4.18 and 1.9?ppm; (C) 4.58?ppm; and (D) 4.18?ppm. Edited signals from ?-aminobutyric acid (GABA), glutathione (GSH), ascorbate (Asc), N-acetylaspartate (NAA), N-acetylaspartylglutamate (NAAG), aspartate (Asp), lactate (Lac), and likely 2-hydroxyglutarate (2-HG) are separated with reduced signal overlap into distinct Hadamard combinations: (A+B+C+D); (A+B-C-D); and (A-B+C-D). HERCULES uses a novel multiplexed linear-combination modeling approach, fitting all three Hadamard combinations at the same time, maximizing the amount of information used for model parameter estimation, in order to quantify the levels of these compounds. Fitting also allows estimation of the levels of total choline (tCho), myo-inositol (Ins), glutamate (Glu), and glutamine (Gln). Quantitative HERCULES results were compared between two grey- and white-matter-rich brain regions (11 min acquisition time each) in 10 healthy volunteers. Coefficients of variation (CV) of quantified measurements from the HERCULES fitting approach were compared against those from a single-spectrum fitting approach, and against estimates from short-TE PRESS data. RESULTS:HERCULES successfully segregates overlapping resonances into separate Hadamard combinations, allowing for the estimation of levels of seven coupled metabolites that would usually require a single 11-min editing experiment each. Metabolite levels and CVs agree well with published values. CVs of quantified measurements from the multiplexed HERCULES fitting approach outperform single-spectrum fitting and short-TE PRESS for most of the edited metabolites, performing only slightly to moderately worse than the fitting method that gives the lowest CVs for tCho, NAA, NAAG, and Asp. CONCLUSION:HERCULES is a new experimental approach with the potential for simultaneous editing and multiplexed fitting of up to seven coupled low-concentration and six high-concentration metabolites within a single 11-min acquisition at 3T.

Project description:Abnormalities in brain γ-aminobutyric acid (GABA) have been implicated in various neuropsychiatric and neurological disorders. However, in vivo GABA detection by (1) H MRS presents significant challenges arising from the low brain concentration, overlap by much stronger resonances and contamination by mobile macromolecule (MM) signals. This study addresses these impediments to reliable brain GABA detection with the J-editing difference technique on a 3-T MR system in healthy human subjects by: (i) assessing the sensitivity gains attainable with an eight-channel phased-array head coil; (ii) determining the magnitude and anatomic variation of the contamination of GABA by MM; and (iii) estimating the test-retest reliability of the measurement of GABA with this method. Sensitivity gains and test-retest reliability were examined in the dorsolateral prefrontal cortex (DLPFC), whereas MM levels were compared across three cortical regions: DLPFC, the medial prefrontal cortex (MPFC) and the occipital cortex (OCC). A three-fold higher GABA detection sensitivity was attained with the eight-channel head coil compared with the standard single-channel head coil in DLPFC. Despite significant anatomical variation in GABA + MM and MM across the three brain regions (p < 0.05), the contribution of MM to GABA + MM was relatively stable across the three voxels, ranging from 41% to 49%, a non-significant regional variation (p = 0.58). The test-retest reliability of GABA measurement, expressed as either the ratio to voxel tissue water (W) or to total creatine, was found to be very high for both the single-channel coil and the eight-channel phased-array coil. For the eight-channel coil, for example, Pearson's correlation coefficient of test vs. retest for GABA/W was 0.98 (R(2) = 0.96, p = 0.0007), the percentage coefficient of variation (CV) was 1.25% and the intraclass correlation coefficient (ICC) was 0.98. Similar reliability was also found for the co-edited resonance of combined glutamate and glutamine (Glx) for both coils. Copyright © 2016 John Wiley & Sons, Ltd.

Project description:An adiabatic MEscher-GArwood (MEGA)-editing scheme, using asymmetric hyperbolic secant editing pulses, was developed and implemented in a B1+-insensitive, 1D-semiLASER (Localization by Adiabatic SElective Refocusing) MR spectroscopic imaging (MRSI) sequence for the non-invasive mapping of ?-aminobutyric acid (GABA) over a whole brain slice. Our approach exploits the advantages of edited-MRSI at 7T while tackling challenges that arise with ultra-high-field-scans. Spatial-spectral encoding, using density-weighted, concentric circle echo planar trajectory readout, enabled substantial MRSI acceleration and an improved point-spread-function, thereby reducing extracranial lipid signals. Subject motion and scanner instabilities were corrected in real-time using volumetric navigators optimized for 7T, in combination with selective reacquisition of corrupted data to ensure robust subtraction-based MEGA-editing. Simulations and phantom measurements of the adiabatic MEGA-editing scheme demonstrated stable editing efficiency even in the presence of ±0.15?ppm editing frequency offsets and B1+ variations of up to ±30% (as typically encountered in vivo at 7T), in contrast to conventional Gaussian editing pulses. Volunteer measurements were performed with and without global inversion recovery (IR) to study regional GABA levels and their underlying, co-edited, macromolecular (MM) signals at 2.99?ppm. High-quality in vivo spectra allowed mapping of pure GABA and MM-contaminated GABA+ (GABA + MM) along with Glx (Glu + Gln), with high-resolution (eff. voxel size: 1.4 cm3) and whole-slice coverage in 24?min scan time. Metabolic ratio maps of GABA/tNAA, GABA+/tNAA, and Glx/tNAA were correlated linearly with the gray matter fraction of each voxel. A 2.15-fold increase in gray matter to white matter contrast was observed for GABA when enabling IR, which we attribute to the higher abundance of macromolecules at 2.99?ppm in the white matter than in the gray matter. In conclusion, adiabatic MEGA-editing with 1D-semiLASER selection is as a promising approach for edited-MRSI at 7T. Our sequence capitalizes on the benefits of ultra-high-field MRSI while successfully mitigating the challenges related to B0/B1+ inhomogeneities, prolonged scan times, and motion/scanner instability artifacts. Robust and accurate 2D mapping has been shown for the neurotransmitters GABA and Glx.

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Hadamard editing of glutathione and macromolecule-suppressed GABA.

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Hadamard editing of glutathione and macromolecule-suppressed GABA.

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