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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. SHERPA was successfully implemented at 3 T and gave results in close agreement with conventional MEGA-PRESS scans in both the phantom and in vivo experiments. Simulations for GABA editing for (3 cm) 3 voxels in the left and right hemispheres suggest that both editing efficiency losses and contamination between voxels are about 2%. Compared with conventional single-voxel single-metabolite J-difference editing, two- or fourfold acceleration is possible without significant loss of SNR using the SHERPA method. Unlike some other dual-voxel methods, the method can be used with single-channel receiver coils, and there is no SNR loss due to unfavorable receive-coil geometry factors., (Copyright © 2017 John Wiley & Sons, Ltd.)

The Proton magnetic resonance ( 1 H-MRS) spectrum contains information about the concentration of tissue metabolites within a predefined region of interest (a voxel). The conventional spectrum in some cases obscures information about less abundant metabolites due to limited separation and complex splitting of the metabolite peaks. One method to detect these metabolites is to reduce the complexity of the spectrum using editing. This review provides an overview of the one-dimensional editing methods available to interrogate these obscured metabolite peaks. These methods include sequence optimizations, echo-time averaging, J-difference editing methods (single BASING, dual BASING, and MEGA-PRESS), constant-time PRESS, and multiple quantum filtering. It then provides an overview of the brain metabolites whose detection can benefit from one or more of these editing approaches, including ascorbic acid, γ-aminobutyric acid, lactate, aspartate, N-acetyl aspartyl glutamate, 2-hydroxyglutarate, glutathione, glutamate, glycine, and serine. Magn Reson Med 77:1377-1389, 2017. © 2017 International Society for Magnetic Resonance in Medicine., (© 2017 International Society for Magnetic Resonance in Medicine.)

Purpose: 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., Methods: Spatially resolved density-matrix simulations and phantom experiments were performed at a range of TEs to establish the spatial and TE modulation of glutathione signals in editing-on, editing-off, and difference spectra at 3T. In vivo data were acquired in five healthy subjects to compare a TE of 68 ms and a TE of 120 ms. At the longer TE, high-bandwidth, frequency-modulated, slice-selective refocusing pulses were also compared with conventional amplitude-modulated pulses., Results: Simulations and relaxation-corrected phantom experiments suggest that the maximum edited signal occurs at TE 160 ms, ignoring transverse relaxation. Considering in vivo T 2 relaxation times of 67-89 ms, the optimal in vivo TE is estimated to be 120 ms. In vivo measurements showed that this TE yielded 15% more signal than TE 68 ms. A further gain of 57% resulted from using improved slice-selective refocusing pulses., Conclusion: J-difference editing of glutathione using TE 120 ms delivers increased signal due to improved editing efficiency that more than offsets T 2 losses. The additional TE also allows for use of improved slice-selective refocusing pulses, which results in additional signal gains. Magn Reson Med 77:498-504, 2017. © 2016 International Society for Magnetic Resonance in Medicine., (© 2016 International Society for Magnetic Resonance in Medicine.)

Purpose: 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., Methods: PRIAM separates signals from two simultaneously excited voxels using receiver-coil sensitivity profiles. PRIAM was implemented into Mescher-Garwood (MEGA) edited experiments at 3 Tesla (T), and validated by acquiring dual-voxel MEGA-PRIAM (and compared with conventional single-voxel MEGA-PRESS) spectra from a GABA/glutathione phantom, and 11 healthy participants., Results: MEGA-PRIAM effectively separated phantom spectra with ∼3-4% between-voxel contamination. GABA and glutathione measurements agreed well with those obtained using single-voxel MEGA-PRESS (mean difference was below 2% in GABA levels, and below 7% in glutathione levels). In vivo, GABA- and glutathione-edited spectra were successfully reconstructed with a mean in vivo g-factor of 1.025 (typical voxel-center separation: 7-8 cm). MEGA-PRIAM experiments showed higher signal-to-noise ratio than sequential single-voxel experiments of the same total duration (mean improvement 1.38 ± 0.24)., Conclusions: Simultaneous acquisition of J-difference-edited GABA or glutathione spectra from two voxels is feasible at 3 T. MEGA-PRIAM increases data acquisition rates compared with MEGA-PRESS by a factor of 2. Magn Reson Med, 2016. © 2016 International Society for Magnetic Resonance in Medicine., (© 2016 International Society for Magnetic Resonance in Medicine.)

Purpose: 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., Methods: Editing pulses applied according to a Hadamard encoding scheme allow the simultaneous acquisition of multiple metabolites. The method, called HERMES (Hadamard Encoding and Reconstruction of MEGA-Edited Spectroscopy), was optimized to detect NAA and NAAG simultaneously using density-matrix simulations and validated in phantoms at 3T. In vivo data were acquired in the centrum semiovale of 12 normal subjects. The NAA:NAAG concentration ratio was determined by modeling in vivo data using simulated basis functions. Simulations were also performed for potentially coedited molecules with signals within the detected NAA/NAAG region., Results: Simulations and phantom experiments show excellent segregation of NAA and NAAG signals into the intended spectra, with minimal crosstalk. Multiplet patterns show good agreement between simulations and phantom and in vivo data. In vivo measurements show that the relative peak intensities of the NAA and NAAG spectra are consistent with a NAA:NAAG concentration ratio of 4.22:1 in good agreement with literature. Simulations indicate some coediting of aspartate and glutathione near the detected region (editing efficiency: 4.5% and 78.2%, respectively, for the NAAG reconstruction and 5.1% and 19.5%, respectively, for the NAA reconstruction)., Conclusion: The simultaneous and separable detection of two otherwise overlapping metabolites using HERMES is possible at 3T. Magn Reson Med 76:11-19, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Purpose: The conventional spectral-editing experiment used to measure GABA in the human brain also contains a contribution from macromolecules (MM), and the combined GABA plus MM signal is often referred to as "GABA+". More recently, methods have been developed to estimate GABA free from MM contamination. In this study, the relationship between GABA acquired with MM suppression and conventional GABA+ measurements was examined., Methods: GABA-edited MEGA-PRESS experiments with and without MM suppression were performed in the sensorimotor and occipital cortex of 12 healthy subjects at 3 Tesla. The correlation between GABA+ and MM-suppressed GABA measures was then determined., Results: Across all data, a significant correlation between GABA+ and MM-suppressed GABA was found (r = 0.48; P = 0.02). Regionally, the sensorimotor voxel showed a trend toward a correlation of r = 0.53, P = 0.07 and the occipital voxel did not show a correlation, r = 0.058, P = 0.9., Conclusion: GABA+ and MM-suppressed GABA are moderately correlated, but statistical power to reveal this relationship may vary regionally. The MM signal, while often assumed to be functionally irrelevant, appears to show inter-individual and inter-regional variance that impacts the correlation of GABA+ and MM-suppressed GABA., (© 2014 Wiley Periodicals, Inc.)

Purpose: In proton MR spectra of the human brain, relatively broad macromolecule (MM) resonances underlie the narrower signals from metabolites. The purpose of this study was to quantify the MM profile in healthy human brain at 3T and 7T, both in gray matter (anterior cingulate cortex [ACC]) and white matter (centrum semiovale [CSO])., Methods: A water-suppressed, inversion-recovery pulse sequence was used to null metabolite signals and acquire MM spectra in 20 healthy volunteers using very similar methodology at both field strengths (n = 5 per region and field). The MM spectra were fitted with multiple Gaussian functions and quantified relative to the unsuppressed water signal from the same volume., Results: MM proton concentration values were in the range of 5-20 mmol/kg. No significant differences were found between the MM proton concentration measurements by region (P ≈ 0.8) nor by field strength (P ≈ 0.5). Linewidths of the well-resolved M1 peak were slightly more than double at 7T (43.0 ± 4.7 Hz in ACC, 45.6 ± 4.1 Hz in CSO) compared with 3T (19.8 ± 3.5 Hz in ACC, 20.0 ± 4.3 Hz in CSO)., Conclusion: The absence of differences in MM concentrations between white and gray matter implies that a single MM "baseline" may be adequate for spectral fitting of multiple brain regions when determining metabolite concentrations. Visibility of MM signals is similar at 3T and 7T., (© 2014 Wiley Periodicals, Inc.)

Purpose: To investigate the quantitative impact of frequency drift on Gamma-Aminobutyric acid (GABA+)-edited MRS of the human brain at 3 Tesla (T)., Methods: Three sequential GABA+-edited MEGA-PRESS acquisitions were acquired in fifteen sessions; in ten of these, MRS was preceded by functional MRI (fMRI) to induce frequency drift, which was estimated from the creatine resonance at 3.0 ppm. Simulations were performed to examine the effects of frequency drift on the editing efficiency of GABA and co-edited macromolecules (MM) and of subtraction artifacts on GABA+ quantification. The efficacy of postprocessing frequency correction was also investigated., Results: Gradient-induced frequency drifts affect GABA+ quantification for at least 30 min after imaging. Average frequency drift was low in control sessions and as high as -2 Hz/min after fMRI. Uncorrected frequency drift has an approximately linear effect on GABA+ measurements with a -10 Hz drift resulting in a 16% decrease in GABA+, primarily due to subtraction artifacts., Conclusion: Imaging acquisitions with high gradient duty cycles can impact subsequent GABA+ measurements. Postprocessing can address subtraction artifacts, but not changes in editing efficiency or GABA:MM signal ratios; therefore, protocol design should avoid intensive gradient sequences before edited MRS Magn Reson Med 72:941-948, 2014. © 2013 Wiley Periodicals, Inc., (Copyright © 2013 Wiley Periodicals, Inc.)

Purpose: To investigate factors that influence the multiplet pattern observed in J-difference editing of gamma-aminobutyric acid (GABA)., Methods: Density matrix simulations were applied to investigate the shape of the 3 ppm GABA multiplet as a function of the editing sequence's slice-selective refocusing pulse properties, in particular bandwidth, transition width, and flip angle. For comparison to the calculations, experimental measurements were also made at 3 T on a 10 mM GABA solution using the MEGA-PRESS sequence at various refocusing pulse flip angles., Results: Good agreement was found between experiments and simulations. The edited multiplet consists of two outer lines of slightly unequal intensity due to strong coupling, and a smaller central line, the result of the unequal J-couplings between the C4 and C3 protons. The size of the center peak increases with increasing slice-selective refocusing pulse transition width, and deviation of the flip angle from 180°., Conclusion: The 3 ppm GABA multiplet pattern observed in the MEGA-PRESS experiment depends quite strongly on the properties of the slice-selective refocusing pulses used. Under some circumstance, the central peak can be quite large; this does not necessarily indicate inefficient editing, or a subtraction artifact, but should be recognized as a property of the pulse sequence itself., (Copyright © 2012 Wiley Periodicals, Inc.)

Edited magnetic resonance spectroscopy makes possible noninvasive studies of the role of the inhibitory neurotransmitter GABA in the healthy brain and in disease processes. A major limitation of the methodology is coediting of macromolecular signals. Although it has previously been shown that macromolecular signal can be suppressed using a symmetrical editing scheme, this approach is rarely applied at field strength of 3T as insufficiently selective pulses result in loss of GABA signal (in addition to the intended suppression of macromolecular signal). In this article, the authors show that increasing the echo time to 80 ms lets more selective editing pulses be used, allowing for symmetric editing-based suppression of coedited macromolecular signal without loss of GABA signal. The method is applied to acquire macromolecule-suppressed GABA-edited spectra in 10 healthy participants., (Copyright © 2012 Wiley Periodicals, Inc.)

It has previously been demonstrated that there is a negative correlation between the amplitude of the BOLD response and resting γ amino-butyric acid (GABA) concentration in visual cortex. The work here is the first to empirically characterize individual variability in the haemodynamic response functions (HRFs) in response to a simple visual stimulus and baseline GABA concentration in a population of young adult males (n = 15, aged 20-28 years). The results demonstrate that GABA concentration is negatively correlated with BOLD response amplitude (r = -0.64, P < 0.02) and positively correlated with HRF width (r = 0.67, P < 0.002), that is, individuals with higher resting GABA concentration tend to exhibit smaller and wider HRFs. No correlations were observed with resting cerebral blood flow and GABA concentration and similarly, no correlations were observed between GABA and the proportional tissue content of the MRS voxel. We argue that correlation of the height of the HRF is supportive of the view that the previously observed correlations between BOLD amplitudes and GABA are reflective of differences in neuronal activity. However, the changes in HRF shape in individuals with higher baseline GABA levels are suggestive that differing vascular response characteristics may also make a significant contribution. Our results reinforce the view that variability in endogenous factors, such as neurotransmitter concentration, can have a profound effect on the vascular haemodynamic response. This has important implications for between-cohort fMRI studies in which variation in parameters such as GABA concentration may lead to group differences in the BOLD signal., (Copyright © 2011 Wiley Periodicals, Inc.)

There is increasing interest in the J-PRESS technique, an in vivo implementation of two-dimensional J-spectroscopy combined with PRESS localization, for high-field spectroscopy studies of the human brain. The experiment is designed to resolve scalar couplings in the second, indirectly detected dimension, but will only do so if the slice-selective refocusing pulses in the PRESS sequence affect all coupled spins equally. At high magnet field strengths, due to limited RF pulse bandwidth, PRESS-based localization results in spatially dependent evolution of coupling. In some regions of the localized volume, coupling evolves during the PRESS echo time, while in other regions it may be partially or fully refocused. This study investigates the impact of this effect on the appearance of the J-PRESS spectrum for coupled spins, focusing on two commonly observed metabolites, lactate and N-acetyl aspartate, showing that such behavior results in additional peaks in the J-resolved spectrum (termed J-refocused peaks). It is also demonstrated that increasing the bandwidth of refocusing pulses significantly reduces the size of such signals., (Copyright © 2011 Wiley-Liss, Inc.)

A spin echo-based MRSI sequence was developed to acquire edited spectra of γ-aminobutyric acid in an entire slice. Water and lipid signals were suppressed by a dual-band presaturation sequence, which included integrated outer volume suppression pulses for additional lipid suppression. Experiments in three normal volunteers were performed at 3 T using a 32-channel head coil. High signal-to-noise ratio spectra and metabolic images of γ-aminobutyric acid were acquired from nominal 4.5 cm3 voxels (estimated actual voxel size 7.0 cm3) in a scan time of 17 min. The sequence is also expected to co-edit homocarnosine and macromolecules, giving a composite γ-aminobutyric acid+ resonance. The γ-aminobutyric acid+ to water ratio was measured using a companion water MRSI scan and was found to correlate linearly with the % gray matter (GM) of each voxel (γ-aminobutyric acid+/water=(1.5×GM+3.2)×10(-5), R=0.27), with higher γ-aminobutyric acid+ levels in gray matter compared with white. In conclusion, high signal-to-noise ratio γ-aminobutyric acid-MRSI is possible at 3 T within clinically feasible scan times., (Copyright © 2010 Wiley-Liss, Inc.)

T(1) and T(2) were measured for white matter (WM) and gray matter (GM) in the human cervical spinal cord at 3T. T(1) values were calculated using an inversion-recovery (IR) and B(1)-corrected double flip angle gradient echo (GRE) and show significant differences (p = 0.002) between WM (IR = 876 +/- 27 ms, GRE = 838 +/- 54 ms) and GM (IR = 973 +/- 33 ms, GRE = 994 +/- 54 ms). IR showed significant difference between lateral and dorsal column WM (863 +/- 23 ms and 899 +/- 18 ms, respectively, p = 0.01) but GRE did not (p = 0.40). There was no significant difference (p = 0.31) in T(2) between WM (73 +/- 6 ms) and GM (76 +/- 3 ms) or between lateral and dorsal columns (lateral: 73 +/- 6 ms, dorsal: 72 +/- 7 ms, p = 0.59). WM relaxation times were similar to brain structures with very dense fiber packing (e.g., corpus callosum), while GM values resembled deep GM in brain. Optimized sequence parameters for maximal contrast between WM and GM, and between WM and cerebrospinal fluid (CSF) were derived. Since the spinal cord has rostral-caudal symmetry, we expect these findings to be applicable to the whole cord., ((c) 2008 Wiley-Liss, Inc.)

The MEGA-PRESS-IVS method has been developed, which combines MEGA (a frequency-selective editing technique) editing with the point-resolved spectroscopy sequence (PRESS) and inner volume saturation (IVS) localization, reducing the deleterious effects of spatial variation in coupling evolution. The IVS method has been previously described for improved efficiency of lactate detection. The current study demonstrates that the combination of MEGA-PRESS with IVS results in increased sensitivity for edited single-voxel measurements of glutamate and gamma-aminobutyric acid (GABA). A four-compartment model of coupling evolution is investigated through simple product operators and full spin-system simulations and the predicted pattern of signal evolution is demonstrated through MEGA-PRESS-MRSI. MEGA-PRESS-IVS is then compared to MEGA-PRESS in a phantom and an average signal increase of 24% is demonstrated in five healthy volunteers., ((c) 2007 Wiley-Liss, Inc.)

A method is described that allows the in vivo differentiation of N-acetyl aspartate (NAA) from N-acetyl aspartyl glutamate (NAAG) by in vivo MR spectroscopy (MRS) at 3 Tesla (3T). The method, which is based on MEGA-point-resolved spectroscopy (PRESS) editing, selectively targets the aspartyl spin system of one species while deliberately removing the other species from the spectrum. This allows quantitative measurements of NAA and NAAG without the need for fitting of unresolved peaks. White matter concentrations of NAA (6.7 +/- 0.3 mM) and NAAG (2.2 +/- 0.3 mM) were measured in 10 healthy volunteers to demonstrate the method.

Vascular space occupancy (VASO)-dependent functional MRI (fMRI) is a blood-nulling technique capable of generating microvascular cerebral blood volume (CBV)-weighted images. It is shown that at high magnetic field (3.0T) and high spatial resolution (1.89 x 1.89 x 3 mm(3)), the VASO signal changes are too large (6-7%) to originate from CBV effects alone. Additional contributions are investigated theoretically and experimentally as a function of MRI parameters (TR and TE), as well as the signal-to-noise ratio, (SNR) and spatial resolution. First, it is found that an arterial spin labeling (ASL) contribution causes large negative VASO signal changes at short TR. Second, even at high fMRI spatial resolution, CSF volume contributions (7-13%) cause VASO signal changes to become more negative, most noticeably at long TR and TE. Third, white matter (WM) effects reduce signal changes at lower spatial resolution. The VASO technique has been tested using different stimulus paradigms and field strengths (1-3), giving results consistent with comparable tasks investigated using BOLD and cerebral blood flow (CBF)-based techniques. Finally, simulations show that a mixture of fresh and steady-state blood may significantly alter signal changes at short TR (< or =3 s), permitting larger VASO signal changes than expected under pure steady-state conditions. Thus, many competing effects contribute to VASO contrast and care should be taken during interpretation.

In localized proton MR spectroscopy ((1)H-MRS) in vivo, the detection of lactate (Lac) is affected by modulation of its resonances due to homonuclear scalar couplings (J). A simple and convenient way to distinguish Lac from lipids is to set the TE to 1/J so that the Lac signal is inverted while other resonances (such as lipid) remain in-phase. However, at high field strengths, such as 3 Tesla or above, the modulation of the Lac signal is complicated by chemical shift effects that cause modulation patterns to vary within different subregions of the localized volume. Under some conditions the Lac signal may even disappear completely. In this note we introduce the concept of inner volume saturation (IVS), which makes use of high bandwidth spatial pulses to remove the signal corresponding to the regions of the localized volume that contribute unwanted modulation patterns. The method is described theoretically and demonstrated experimentally at 3 Tesla in a phantom and a patient with acute stroke. The phantom measurements indicate that virtually 100% of the Lac signal can be recovered using this method. The method should be feasible at magnetic fields above 3 Tesla, and may also be applied to other coupled spin systems in which modulation effects are important.