Kimberly L. Chan

Prospective frequency correction for macromolecule‐suppressed GABA editing at 3T

To investigate the effects of B0 field offsets and drift on macromolecule (MM)‐suppressed GABA‐editing experiments, and to implement and test a prospective correction scheme. “Symmetric” editing schemes are proposed to suppress unwanted coedited MM signals in GABA editing.

HERMES: Hadamard encoding and reconstruction of MEGA‐edited spectroscopy

To investigate a novel Hadamard‐encoded spectral editing scheme and evaluate its performance in simultaneously quantifying N‐acetyl aspartate (NAA) and N‐acetyl aspartyl glutamate (NAAG) at 3 Tesla.

Echo time optimization for J‐difference editing of glutathione at 3T

To investigate the echo time (TE) dependence of J‐difference editing of glutathione and to determine the optimal TE for in vivo measurements at 3T.

Simultaneous edited MRS of GABA and glutathione

Edited MRS allows the detection of low-concentration metabolites, whose signals are not resolved in the MR spectrum. Tailored acquisitions can be designed to detect, for example, the inhibitory neurotransmitter γ-aminobutyric acid (GABA), or the reduction-oxidation (redox) compound glutathione (GSH), and single-voxel edited experiments are generally acquired at a rate of one metabolite-per-experiment. We demonstrate that simultaneous detection of the overlapping signals of GABA and GSH is possible using Hadamard Encoding and Reconstruction of Mega-Edited Spectroscopy (HERMES). HERMES applies orthogonal editing encoding (following a Hadamard scheme), such that GSH- and GABA-edited difference spectra can be reconstructed from a single multiplexed experiment. At a TE of 80ms, 20-ms editing pulses are applied at 4.56ppm (on GSH),1.9ppm (on GABA), both offsets (using a dual-lobe cosine-modulated pulse) or neither. Hadamard combinations of the four sub-experiments yield GABA and GSH difference spectra. It is shown that HERMES gives excellent separation of the edited GABA and GSH signals in phantoms, and resulting edited lineshapes agree well with separate Mescher-Garwood Point-resolved Spectroscopy (MEGA-PRESS) acquisitions. In vivo, the quality and signal-to-noise ratio (SNR) of HERMES spectra are similar to those of sequentially acquired MEGA-PRESS spectra, with the benefit of saving half the acquisition time.

Dual‐volume excitation and parallel reconstruction for J‐difference‐edited MR spectroscopy

To develop J‐difference editing with parallel reconstruction in accelerated multivoxel (PRIAM) for simultaneous measurement in two separate brain regions of γ‐aminobutyric acid (GABA) or glutathione.

Spatial Hadamard encoding of J‐edited spectroscopy using slice‐selective editing pulses

A new approach for simultaneous dual‐voxel J‐difference spectral editing is described, which uses spatially selective spectral‐editing pulses and Hadamard encoding. A theoretical framework for spatial Hadamard editing and reconstruction for parallel acquisition (SHERPA) was developed, applying gradient pulses during the frequency‐selective editing pulses. Spectral simulations were performed for either one (gamma‐aminobutyric acid, GABA) or two molecules (glutathione and lactate) simultaneously detected in two voxels. The method was tested in a two‐compartment GABA phantom, and finally applied to the left and right hemispheres of 10 normal control subjects, scanned at 3 T.

Simultaneous measurement of Aspartate, NAA, and NAAG using HERMES spectral editing at 3 Tesla

ABSTRACT It has previously been shown that the HERMES method (‘Hadamard Encoding and Reconstruction of MEGA‐Edited Spectroscopy’) can be used to simultaneously edit pairs of metabolites (such as N‐acetyl‐aspartate (NAA) and N‐acetyl aspartyl glutamate (NAAG), or glutathione and GABA). In this study, HERMES is extended for the simultaneous editing of three overlapping signals, and illustrated for the example of NAA, NAAG and Aspartate (Asp). Density‐matrix simulations were performed in order to optimize the HERMES sequence. The method was tested in NAA and Asp phantoms, and applied to the centrum semiovale of the nine healthy control subjects that were scanned at 3 T. Both simulations and phantom experiments showed similar metabolite multiplet patterns with good segregation of all three metabolites. In vivo measurements show consistent relative signal intensities and multiplet patterns with concentrations in agreement with literature values. Simulations indicate co‐editing of glutathione, glutamine, and glutamate, but their signals do not significantly overlap with the detected aspartyl resonances. This study demonstrates that a four‐step Hadamard‐encoded editing scheme can be used to simultaneously edit three otherwise overlapping metabolites, and can measure NAA, NAAG, and Asp in vivo in the brain at 3 T with minimal crosstalk. HIGHLIGHTSHERMES can simultaneously edit three metabolites.Overlapping signals from NAA, NAAG and Asp are resolved by Hadamard editing.Simulated metabolite multiplet patterns agree with phantom experiments.Measured in vivo concentrations in agreement with literature values.

Frequency and phase correction for multiplexed edited MRS of GABA and glutathione: Frequency and Phase Correction for Multiplexed Edited MRS

Detection of endogenous metabolites using multiplexed editing substantially improves the efficiency of edited magnetic resonance spectroscopy. Multiplexed editing (i.e., performing more than one edited experiment in a single acquisition) requires a tailored, robust approach for correction of frequency and phase offsets. Here, a novel method for frequency and phase correction (FPC) based on spectral registration is presented and compared against previously presented approaches.

Advanced Hadamard-encoded editing of seven low-concentration brain metabolites: Principles of HERCULES

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 &ggr;‐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. HighlightsHERCULES can simultaneously edit up to seven low‐concentration metabolites within a single experiment at 3T.HERCULES is based on a novel Hadamard‐encoded spectral editing scheme.Novel multiplexed fitting approach exploits all available spectral information.

Hadamard editing of glutathione and macromolecule-suppressed GABA

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) 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.