Mark Mikkelsen

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.

Autism spectrum disorder in the scope of tactile processing

Highlights • A thorough review of tactile assessments in autism spectrum disorder (ASD).• A focus on clinical and behavioral assessments in ASD.• Discussion of links to neurophysiological mechanisms.• Critical assessments of the missing links in this research area.

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.

Neurometabolites and associations with cognitive deficits in mild cognitive impairment: A magnetic resonance spectroscopy study at 7 Tesla

The levels of several brain metabolites were investigated in the anterior cingulate cortex (ACC) and posterior cingulate cortex (PCC) in 13 healthy controls (HC) and 13 patients with mild cognitive impairment (MCI) using single-voxel magnetic resonance spectroscopy at 7T. Levels of γ-aminobutyric acid (GABA), glutamate (Glu), glutathione (GSH), N-acetylaspartylglutamate (NAAG), N-acetylaspartate (NAA), and myo-inositol (mI) were quantified relative to total creatine (tCr). The effect of diagnosis on metabolite levels, and relationships between metabolite levels and memory and executive function, correcting for age, were investigated. MCI patients showed significantly decreased GABA/tCr (ACC, PCC), Glu/tCr (PCC), and NAA/tCr (PCC), and significantly increased mI/tCr (ACC). In the combined group, worse episodic verbal memory performance was correlated with lower Glu/tCr (PCC), lower NAA/tCr (PCC), and higher mI/tCr (ACC, PCC). Worse verbal fluency performance was correlated with lower GSH/tCr (PCC). In summary, MCI is associated with decreased GABA and Glu, most consistently in the PCC. Further studies in larger patient samples should be undertaken to determine the utility of 7T magnetic resonance spectroscopy in detecting MCI-related neurochemical changes.

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.

Simultaneous editing of GABA and glutathione at 7T using semi-LASER localization: Simultaneous Editing of GABA and GSH at 7T

To demonstrate simultaneous editing of the two most commonly edited and overlapping signals, γ‐aminobutyric acid (GABA), and glutathione (GSH), with Hadamard encoding and reconstruction of MEGA‐edited spectroscopy (HERMES) using sLASER localization at 7T.

Designing GABA-edited magnetic resonance spectroscopy studies: Considerations of scan duration, signal-to-noise ratio and sample size

BACKGROUND The relationships between scan duration, signal-to-noise ratio (SNR) and sample size must be considered and understood to design optimal GABA-edited magnetic resonance spectroscopy (MRS) studies. NEW METHOD Simulations investigated the effects of signal averaging on SNR, measurement error and group-level variance against a known ground truth. Relative root mean square errors (measurement error) and coefficients of variation (group-level variance) were calculated. GABA-edited data from 18 participants acquired from five voxels were used to examine the relationships between scan duration, SNR and quantitative outcomes in vivo. These relationships were then used to determine the sample sizes required to observe different effect sizes. RESULTS In both simulated and in vivo data, SNR increased with the square root of the number of averages. Both measurement error and group-level variance were shown to follow an inverse-square-root function, indicating no significant impact of cumulative artifacts. Comparisons between the first two-thirds of the data and the full dataset showed no statistical difference in group-level variance. There was, however, some variability across the five voxels depending on SNR, which impacted the sample sizes needed to detect group differences in specific brain regions. COMPARISON WITH EXISTING METHODS Typical scan durations can be reduced if taking into account a statistically acceptable amount of variance and the magnitudes of predicted effects. CONCLUSIONS While scan duration in GABA-edited MRS has typically been considered in terms of SNR, it is more appropriate to think in terms of the amount of measurement error and group-level variance that provides sufficient statistical power.

Effects of eddy currents on selective spectral editing experiments at 3T

To investigate frequency‐offset effects in edited magnetic resonance spectroscopy (MRS) experiments arising from B0 eddy currents.

Comparing the reproducibility of commonly used magnetic resonance spectroscopy techniques to quantify cerebral glutathione: Reproducibility of MRS GSH Levels at 3T

Cerebral glutathione (GSH), a marker of oxidative stress, has been quantified in neurodegenerative diseases and psychiatric disorders using proton magnetic resonance spectroscopy (MRS). Using a reproducible MRS technique is important, as it minimizes the impact of measurement technique variability on the study results and ensures that other studies can replicate the results.