In vivo detection and automatic analysis of GABA in the mouse brain with MEGA‐PRESS at 9.4 T

The goals of this study were to develop an acquisition protocol and the analysis tools for Meshcher–Garwood point‐resolved spectroscopy (MEGA‐PRESS) in mouse brain at 9.4 T, to allow the in vivo detection of γ‐aminobutyric acid (GABA) and to examine whether isoflurane alters GABA levels in the thalamus during anesthesia. We implemented the MEGA‐PRESS sequence on a Bruker 94/20 system with ParaVision 6.0.1, and magnetic resonance spectra were acquired from nine male wild‐type C57BL/6 J mice at the thalamus. Four individual scans were obtained for each mouse in a 2‐h time course whilst the mouse was anesthetized with isoflurane. We developed an automated analysis program with improved correction for frequency and phase drift compared with the standard creatine (Cr) fitting‐based method and provided automatic quantification. During MEGA‐PRESS acquisition, a single voxel with a size of 5 × 3 × 3 mm³ was placed at the thalamus to evaluate GABA to Cr (GABA/Cr) ratios during anesthesia. Detection and quantitative analysis of thalamic GABA levels were successfully achieved. We noticed a significant decrease in GABA/Cr during the 2‐h anesthesia (by linear regression analysis: slope < 0, p < 0.0001). In summary, our findings demonstrate that MEGA‐PRESS is a feasible technique to measure in vivo GABA levels in the mouse brain at 9.4 T.     

Quantification of glutamate and glutamine using constant‐time point‐resolved spectroscopy at 3 T

Separate quantification of glutamate (Glu) and glutamine (Gln) using conventional MRS on clinical scanners is challenging. In previous work, constant‐time point‐resolved spectroscopy (CT‐PRESS) was optimized at 3 T to detect Glu, but did not resolve Gln. To quantify Glu and Gln, a time‐domain basis set was constructed taking into account metabolite T₂ relaxation times and dephasing from B₀ inhomogeneity. Metabolite concentrations were estimated by fitting the basis one‐dimensional CT‐PRESS diagonal magnitude spectra to the measured spectrum. This method was first validated using seven custom‐built phantoms containing variable metabolite concentrations, and then applied to in vivo data acquired in rats exposed to vaporized ethanol and controls. Separate metabolite quantification revealed increased Gln after 16 weeks and increased Glu after 24 weeks of vaporized ethanol exposure in ethanol‐treated compared with control rats. Without separate quantification, the signal from the combined resonances of Glu and Gln (Glx) showed an increase at both 16 and 24 weeks in ethanol‐exposed rats, precluding the determination of the independent and differential contribution of each metabolite at each time. Copyright © 2012 John Wiley & Sons, Ltd.     

In silico GABA+ MEGA‐PRESS: Effects of signal‐to‐noise ratio and linewidth on modeling the 3 ppm GABA+ resonance

To investigate the GABA+ modeling accuracy of MEGA‐PRESS GABA+‐edited MRS data with various spectral quality scenarios, the influence of varying signal‐to‐noise ratio (SNR) and linewidth on the model estimates was quantified. MEGA‐PRESS data from 46 volunteers were averaged to generate a template MEGA‐PRESS spectrum, which was modeled and quantified to generate a GABA+ level ground truth. This spectrum was then manipulated by adding 427 combinations of varying artificial noise levels and line broadening, mimicking variations in GABA+ SNR and B₀ homogeneity. GABA+ modeling and quantification was performed with 100 simulated spectra per condition using automated routines in both Gannet 3.0 and Tarquin. The GABA+ estimation error was calculated as the relative deviation to the quantified GABA+ ground truth levels to assess the accuracy of GABA+ modeling. Finally, the accordance between the simulations and different in vivo scenarios was assessed. The GABA+ estimation error was smaller than 5% for all GABA+ SNR values with creatine linewidths lower than 9.7 Hz in Gannet 3.0 or unequal 10.6 Hz in Tarquin. The standard deviation of the GABA+ amplitude over 100 spectra per condition varied between 3.1 and 17% (Gannet 3.0) and between 1 and 11% (Tarquin) over the in vivo relevant GABA+ SNR range between 2.6 and 3.5. GABA+ edited studies might be realized for voxels with low GABA+ SNR at the cost of higher group‐level variance. The accuracy of GABA+ modeling had no relation to commonly used quality metrics. The Tarquin algorithm was found to be more robust against linewidth changes than the fitting algorithm in Gannet.     

Improved resolution of glutamate,glutamine and γ‐aminobutyric acid with optimized point‐resolved spectroscopy sequence timings for their simultaneous quantification at 9.4 T

Glutamine (Gln), glutamate (Glu) and γ‐aminobutyric acid (GABA) are relevant brain metabolites that can be measured with magnetic resonance spectroscopy (MRS). This work optimizes the point‐resolved spectroscopy (PRESS) sequence echo times, TE₁ and TE₂, for improved simultaneous quantification of the three metabolites at 9.4 T. Quantification was based on the proton resonances of Gln, Glu and GABA at ≈2.45, ≈2.35 and ≈2.28 ppm, respectively. Glu exhibits overlap with both Gln and GABA; in addition, the Gln peak is contaminated by signal from the strongly coupled protons of N‐acetylaspartate (NAA), which resonate at about 2.49 ppm. J‐coupling evolution of the protons was characterized numerically and verified experimentally. A {TE₁, TE₂} combination of {106 ms, 16 ms} minimized the NAA signal in the Gln spectral region, whilst retaining Gln, Glu and GABA peaks. The efficacy of the technique was verified on phantom solutions and on rat brain in vivo. LCModel was employed to analyze the in vivo spectra. The average T₂‐corrected Gln, Glu and GABA concentrations were found to be 3.39, 11.43 and 2.20 mM, respectively, assuming a total creatine concentration of 8.5 mM. LCModel Cramér–Rao lower bounds (CRLBs) for Gln, Glu and GABA were in the ranges 14–17%, 4–6% and 16–19%, respectively. The optimal TE resulted in concentrations for Gln and GABA that agreed more closely with literature concentrations compared with concentrations obtained from short‐TE spectra acquired with a {TE₁, TE₂} combination of {12 ms, 9 ms}. LCModel estimations were also evaluated with short‐TE PRESS and with the optimized long TE of {106 ms, 16 ms}, using phantom solutions of known metabolite concentrations. It was shown that concentrations estimated with LCModel can be inaccurate when combined with short‐TE PRESS, where there is peak overlap, even when low (<20%) CRLBs are reported.     

Spatial variability and reproducibility of GABA‐edited MEGA‐LASER 3D‐MRSI in the brain at 3 T

The reproducibility of gamma‐aminobutyric acid (GABA) quantification results, obtained with MRSI, was determined on a 3 T MR scanner in healthy adults. In this study, a spiral‐encoded, GABA‐edited, MEGA‐LASER MRSI sequence with real‐time motion–scanner‐instability corrections was applied for robust 3D mapping of neurotransmitters in the brain. In particular, the GABA⁺ (i.e. GABA plus macromolecule contamination) and Glx (i.e. glutamate plus glutamine contamination) signal was measured. This sequence enables 3D‐MRSI with about 3 cm³ nominal resolution in about 20 min. Since reliable quantification of GABA is challenging, the spatial distribution of the inter‐subject and intra‐subject variability of GABA⁺ and Glx levels was studied via test–retest assessment in 14 healthy volunteers (seven men–seven women). For both inter‐subject and intra‐subject repeated measurement sessions a low coefficient of variation (CV) and a high intraclass correlation coefficient (ICC) were found for GABA⁺ and Glx ratios across all evaluated voxels (intra?/inter‐subject: GABA⁺ ratios, CV ~ 8%–ICC > 0.75; Glx ratios, CV ~ 6%–ICC > 0.70). The same was found in selected brain regions for Glx ratios versus GABA⁺ ratios (CV varied from about 5% versus about 8% in occipital and parietal regions, to about 8% versus about 10% in the frontal area, thalamus, and basal ganglia). These results provide evidence that 3D mapping of GABA⁺ and Glx using the described methodology provides high reproducibility for application in clinical and neuroscientific studies.     

The in vivo J‐difference editing MEGA‐PRESS technique for the detection of n‐3 fatty acids

In this study, we present a method for the detection of n‐3 fatty acid (n‐3 FA) signals using MRS in adipose tissue in vivo. This method (called oMEGA‐PRESS) is based on the selective detection of the CH₃ signal of n‐3 FA using the MEGA‐PRESS (MEshcher–GArwood Point‐RESolved Spectroscopy) J‐difference editing technique. We optimized the envelope shape and frequency of spectral editing pulses to minimize the spurious co‐editing and incomplete subtraction of the CH₃ signal of other FAs, which normally obscure the n‐3 FA CH₃ signal in MR spectra acquired using standard PRESS techniques. The post‐processing of the individual data scans with the phase and frequency correction before data subtraction and averaging was implemented to further improve the quality of in vivo spectra. The technique was optimized in vitro on lipid phantoms using various concentrations of n‐3 FA and examined in vivo at 3 T on 15 healthy volunteers. The proportion of n‐3 FA estimated by the oMEGA‐PRESS method in phantoms showed a highly significant linear correlation with the n‐3 FA content determined by gas chromatography. The signal attributed to n‐3 FA was observed in all subjects. Comparisons with the standard PRESS technique revealed an enhanced identification of the n‐3 FA signal using oMEGA‐PRESS. The presented method may be useful for the non‐invasive quantification of n‐3 FA in adipose tissue, and could aid in obtaining a better understanding of various aspects of n‐3 FA metabolism. Copyright © 2014 John Wiley & Sons, Ltd.     

Simultaneous detection of valine and lactate using MEGA‐PRESS editing in pyogenic brain abscess

Valine and lactate have been recognized as important metabolic markers to diagnose brain abscess by means of MRS. However, in vivo unambiguous detection and quantification is hampered by macromolecular contamination. In this work, MEGA‐PRESS difference editing of valine and lactate is proposed. The method is validated in vitro and applied for quantitative in vivo experiments in one healthy subject and two brain abscess patients. It is demonstrated that with this technique the overlapping lipid signal can be reduced by more than an order of magnitude and thus the robustness of valine and lactate detection in vivo can be enhanced. Quantification of the two abscess MEGA‐PRESS spectra yielded valine/lactate concentration ratios of 0.10 and 0.27. These ratios agreed with the concentration ratios determined from concomitantly acquired short‐T_E PRESS data and were in line with literature values. The quantification accuracy of lactate (as measured with Cramér‐Rao lower bounds in LCModel processing) was better for MEGA‐PRESS than for short‐T_E PRESS in all acquired in vivo datasets. The Cramér‐Rao lower bounds of valine were only better for MEGA‐PRESS in one of the two abscess cases, while in the other case coediting of isoleucine confounded the quantification in the MEGA‐PRESS analysis. MEGA‐PRESS and short‐T_E PRESS should be combined for unambiguous quantification of amino acids in abscess measurements. Simultaneous valine/lactate MEGA‐PRESS editing might benefit the distinction of brain abscesses from tumors, and further categorization of bacteria with reasonable sensitivity and specificity.     

Difference spectroscopy using PRESS asymmetry: application to glutamate,glutamine, and myo‐inositol

A simple, clinically viable technique utilizing PRESS and strong coupling properties is presented for discrimination of coupled brain metabolites. The method relies on signal variation due to alteration of inter‐echo timings (PRESS asymmetry) while maintaining a constant total echo time. Spin response of singlets and weakly coupled spins is unchanged due to PRESS asymmetry, allowing difference spectroscopy to detect unobstructed strongly coupled resonances. No changes to the standard PRESS sequence are required except variation of inter‐echo timings. The procedure is illustrated for the separate detection of glutamate from glutamine and the detection of myo‐inositol in simulation, phantom, and in vivo experiments at 4.7 T. The subtraction yields calculated from the simulation were 53% for glutamate and 75% for myo‐inositol, and a resultant contribution of 96% glutamate to the total glutamate/glutamine multiplet in the 2.04–2.14 ppm range. To extend the treatment to other field strengths and metabolites, an analytical approximation based on a strongly coupled AB system was used to model individual spin groups. Subtraction spectroscopy yields for different combinations of coupling parameters were calculated for the detection of various strongly coupled metabolites at common clinical field strengths. The approximation also predicts adequate glutamate/glutamine discrimination at 3.0 T using the difference spectroscopy method. Copyright © 2009 John Wiley & Sons, Ltd.     

Optimized MEGA‐SPECIAL for in vivo glutamine detection in the rat brain at 14.1 T

Glutamine has multiple roles in brain metabolism and its concentration can be altered in various pathological conditions. An accurate knowledge of its concentration is therefore highly desirable to monitor and study several brain disorders in vivo. However, in recent years, several MRS studies have reported conflicting glutamine concentrations in the human brain. A recent hypothesis for explaining these discrepancies is that a short T₂ component of the glutamine signal may impact on its quantification at long echo times. The present study therefore aimed to investigate the impact of acquisition parameters on the quantified glutamine concentration using two different acquisition techniques, SPECIAL at ultra‐short echo time and MEGA‐SPECIAL at moderate echo time. For this purpose, MEGA‐SPECIAL was optimized for the first time for glutamine detection. Based on the very good agreement of the glutamine concentration obtained between the two measurements, it was concluded that no impact of a short T₂ component of the glutamine signal was detected. Copyright © 2014 John Wiley & Sons, Ltd.     

Maximizing sensitivity for fast GABA edited spectroscopy in the visual cortex at 7 T

The combination of functional MRI (fMRI) and MRS is a promising approach to relate BOLD imaging to neuronal metabolism, especially at high field strength. However, typical scan times for GABA edited spectroscopy are of the order of 6‐30 min, which is long compared with functional changes observed with fMRI. The aim of this study is to reduce scan time and increase GABA sensitivity for edited spectroscopy in the human visual cortex, by enlarging the volume of activated tissue in the primary visual cortex. A dedicated setup at 7 T for combined fMRI and GABA MRS is developed. This setup consists of a half volume multi‐transmit coil with a large screen for visual cortex activation, two high density receive arrays and an optimized single‐voxel MEGA‐sLASER sequence with macromolecular suppression for signal acquisition. The coil setup performance as well as the GABA measurement speed, SNR, and stability were evaluated. A 2.2‐fold gain of the average SNR for GABA detection was obtained, as compared with a conventional 7 T setup. This was achieved by increasing the viewing angle of the participant with respect to the visual stimulus, thereby activating almost the entire primary visual cortex, allowing larger spectroscopy measurement volumes and resulting in an improved GABA SNR. Fewer than 16 signal averages, lasting 1 min 23 s in total, were needed for the GABA fit method to become stable, as demonstrated in three participants. The stability of the measurement setup was sufficient to detect GABA with an accuracy of 5%, as determined with a GABA phantom. In vivo, larger variations in GABA concentration are found: 14‐25%. Overall, the results bring functional GABA detections at a temporal resolution closer to the physiological time scale of BOLD cortex activation.     

Improved detection of lactate and β‐hydroxybutyrate using MEGA‐sLASER at 3 T

Lactate and β‐hydroxybutyrate are important MRS‐visible biomarkers for the energy metabolism of the human brain. A major obstacle for their unambiguous detection and quantification in vivo is their inherently low concentration and spectral overlap with resonances from lipids and macromolecules. In this work, we demonstrate the improved detectability of lactate and β‐hydroxybutyrate with MEGA‐sLASER compared to MEGA‐PRESS at the clinical field strength of 3 T. The method is validated by numerical simulations, in vitro measurements and in vivo experiments on healthy subjects. It is demonstrated that MEGA‐sLASER offers an SNR increase of approximately 70% for lactate and β‐hydroxybutyrate detection compared to MEGA‐PRESS in various brain regions. This increased SNR translates into reduced Cramér‐Rao lower bounds for quantification and enables a more robust detection of subtle changes in the (brain) energy metabolism. The sensitivity of the method for detection of β‐hydroxybutyrate concentration changes is demonstrated through measurements before and during a ketogenic diet while the sensitivity for detection of lactate concentration changes is shown by measurements before and after an intensive anaerobic exercise.     

In vivo magnetic resonance spectroscopy detection of combined glutamate‐glutamine in healthy upper cervical cord at 3 T

The possibility of quantifying the superimposed signal of glutamate and glutamine (Glx) and its components by ¹ H magnetic resonance spectroscopy (MRS) in the spinal cord is an exciting challenge with important clinical applications in neurological conditions. The spinal cord is a particularly difficult region of interest due to its small volume, magnetic field inhomogeneities and physiological motion. In this study, we investigated for the first time the feasibility of obtaining quantitative measurements of Glx in healthy cervical spinal cord by ¹ H MRS at 3 T. The aim of this study was to compare two commercially available MRS sequences by spectral simulations and in vivo. A short echo time (TE) point resolved spectroscopy (PRESS) with TE = 30 ms and a stimulated echo acquisition mode (STEAM) with TE = 11 ms and mixing time (TM) = 17 ms were compared for reliability of Glx fit. Data allowed us to determine sample size estimates for future clinical studies for the first time. Results showed that PRESS provided a reliable fit for Glx in all cases (Cramér Rao lower bounds < 20%) whereas no reliable Glx fits were achieved using STEAM. Neither protocol provided reliable Glu quantification. The power calculations showed that a minimum sample size of 17 subjects per group was needed to detect Glx changes of > 20% using the PRESS sequence. This study proposed a clinically feasible MRS method for Glx detection in the human cervical cord in vivo including sample sizes needed for conclusive clinical studies. Copyright © 2012 John Wiley & Sons, Ltd.     

Simultaneous observation of glutamate, gamma-aminobutyric acid, and glutamine in human brain at 4.7 T using localized two-dimensional constant-time correlation spectroscopy

Localized two-dimensional constant-time correlation spectroscopy (CT-COSY) was used to resolve glutamate (Glu), gamma-aminobutyric acid (GABA), and glutamine (Gln) in the human brain at 4.7 T. In this method, three-dimensional localization was achieved using three radio frequency pulses of the CT-COSY module for slice selection. As this sequence could decouple JHH along the F1 direction, peak resolution of metabolites was improved even on a magnitude-mode display. In experiments on a phantom containing N-acetylaspartate, creatine, Glu, Gln, and GABA with a constant time delay (Tct) of 110 ms, cross peaks of Glu, Gln, and GABA were obtained on a spectrum processed with standard sine-bell windows, which emphasize sine-dependent signals along the t2 direction. In contrast, diagonal peaks of Glu C4H at 2.35 ppm, GABA C2H at 2.28 ppm, and Gln C4H at 2.44 ppm were resolved on a spectrum processed with Gaussian windows, which emphasize cosine-dependent signals along t2. Human brain spectra were obtained from a 27 mL voxel within the parieto-occipital region using a volume transverse electromagnetic (TEM) coil for both transmission and reception. Tct was 110 ms; the total scan time was 30 min. Diagonal peaks of Glu C4H, GABA C2H, and Gln C4H were also resolved on the spectrum processed with Gaussian windows. These results show that the localized two-dimensional CT-COSY method featuring 1H decoupling along the F1 direction could resolve Glu, GABA, and Gln signals in the human brain.     

In vivo GABA T2 determination with J‐refocused echo time extension at 7 T

A method to measure the T₂ relaxation time of GABA with spectral editing techniques is proposed. Spectral editing techniques can be used to unambiguously extract signals of low concentration J‐coupled spins such as γ‐aminobutyric acid (GABA) from overlapping resonances such as creatine and macromolecules. These sequences, however, generally have fixed and relatively long echo times. Therefore, for the absolute quantification of the edited spectrum, the T₂ relaxation time must be taken into account. To measure the T₂ relaxation time, the signal intensity has to be obtained at multiple echo times. However, on a coupled spin system such as GABA this is challenging, since the signal intensity of the target resonances is modulated not only by T₂ decay but also by the J‐coupling, which strongly influences the shapes and amplitudes of the edited signals, depending on the echo time. Here, we propose to refocus the J‐modulation of the edited signal at different echo times by using chemical shift selective refocusing. In this way the echo time can be arbitrarily extended while preserving the shape of the edited signal. The method was applied in combination with the MEGA‐sLASER editing technique to measure the in vivo T₂ relaxation time of GABA (87 ± 11 ms, n = 10) and creatine (109 ± 8 ms, n = 10) at 7 T. The T₁ relaxation time of these metabolites in a single subject was also determined (GABA, 1334 ± 158 ms; Cr, 1753 ± 12 ms). The T₂ decay curve of coupled spin systems can be sampled in an arbitrary fashion without the need for signal shape correction. Furthermore, the method can be applied with any spectral editing technique. The shortest echo time of the method is limited by the echo time of the spectral editing technique. Copyright © 2013 John Wiley & Sons, Ltd.     

Volumetric navigated MEGA‐SPECIAL for real‐time motion and shim corrected GABA editing

Mescher–Garwood (MEGA) editing with spin echo full intensity acquired localization (MEGA‐SPECIAL, MSpc) is a technique to acquire γ‐aminobutyric acid (GABA) without macromolecule (MM) contamination at a T_E of 68 ms. However, due to the requirement of multiple shot‐localization, it is often susceptible to subject motion and B₀ inhomogeneity. A method is presented for real‐time shim and motion correction (ShMoCo) using volumetric navigators to correct for motion and motion‐related B₀ inhomogeneity during MSpc acquisition. A phantom experiment demonstrates that ShMoCo restores the GABA peak and improves spectral quality in the presence of motion and zero‐ and first‐order shim changes. The ShMoCo scans were validated in three subjects who performed up–down and left–right head rotations. Qualitative assessment of these scans indicates effective reduction of subtraction artefacts and well edited GABA peaks, while quantitative analysis indicates superior fitting and spectral quality relative to scans with no correction. Copyright © 2015 John Wiley & Sons, Ltd.     

PRESS timings for resolving 13C4‐glutamate 1H signal at 9.4 T: Demonstration in rat with uniformly labelled 13C‐glucose

MRS of ¹³C₄‐labelled glutamate (¹³C₄‐Glu) during an infusion of a carbon‐13 (¹³C)‐labelled substrate, such as uniformly labelled glucose ([U‐¹³C₆]‐Glc), provides a measure of Glc metabolism. The presented work provides a single‐shot indirect ¹³C detection technique to quantify the approximately 2.51 ppm ¹³C₄‐Glu satellite proton (¹H) peak at 9.4 T. The methodology is an optimized point‐resolved spectroscopy (PRESS) sequence that minimizes signal contamination from the strongly coupled protons of N‐acetylaspartate (NAA), which resonate at approximately 2.49 ppm. J‐coupling evolution of protons was characterized numerically and verified experimentally. A (TE₁, TE₂) combination of (20 ms, 106 ms) was found to be suitable for minimizing NAA signal in the 2.51 ppm ¹H ¹³C₄‐Glu spectral region, while retaining the ¹³C₄‐Glu ¹H satellite peak. The efficacy of the technique was verified on phantom solutions and on two rat brains in vivo during an infusion of [U‐¹³C₆]‐Glc. LCModel was employed for analysis of the in vivo spectra to quantify the 2.51 ppm ¹H ¹³C₄‐Glu signal to obtain Glu C4 fractional enrichment time courses during the infusions. Cramér‐Rao lower bounds of about 8% were obtained for the 2.51 ppm ¹³C₄‐Glu ¹H satellite peak with the optimal TE combination.     

Towards a neurochemical profile of the amygdala using short‐TE 1H magnetic resonance spectroscopy at 3 T

The amygdala plays a key role in emotional learning and in the processing of emotions. As disturbed amygdala function has been linked to several psychiatric conditions, a knowledge of its biochemistry, especially neurotransmitter levels, is highly desirable. The spin echo full intensity acquired localized (SPECIAL) sequence, together with a transmit/receive coil, was used to perform very short‐TE magnetic resonance spectroscopy at 3 T to determine the neurochemical profile in a spectroscopic voxel containing the amygdala in 21 healthy adult subjects. For spectral analysis, advanced data processing was applied in combination with a macromolecule baseline measured in the anterior cingulate for spectral fitting. The concentrations of total N‐acetylaspartate, total creatine, total choline, myo‐inositol and, for the first time, glutamate were quantified with high reliability (uncertainties far below 10%). For these metabolites, the inter‐individual variability, reflected by the relative standard deviations for the cohort studied, varied between 12% (glutamate) and 22% (myo‐inositol). Glutamine and glutathione could also be determined, albeit with lower precision. Retest on four subjects showed good reproducibility. The devised method allows the determination of metabolite concentrations in the amygdala voxel, including glutamate, provides an estimation of glutamine and glutathione, and may help in the study of disturbed amygdala metabolism in pathologies such as anxiety disorder, autism and major depression.     

Glutamate measurement in Parkinson's disease using MRS at 3 T field strength

Loss of nigral dopamine neurons in Parkinson's disease induces abnormal activation of glutamate systems in the basal ganglia. The purpose of this study was to assess these changes in the lentiform nucleus using MRS with optimized glutamate sensitivity (TE-averaged method). Ten patients with Parkinson's disease and 10 healthy controls were examined. Compared with healthy controls, no significant differences in glutamate were measured in patients, but a trend to lower total creatine was observed.     

Quantification of J‐resolved proton spectra in two‐dimensions with LCModel using GAMMA‐simulated basis sets at 4 Tesla

A two‐dimensional, J‐resolved magnetic resonance spectroscopic extraction approach was developed employing GAMMA‐simulated, LCModel basis‐sets. In this approach, a two‐dimensional J‐resolved (2D‐JPRESS) dataset was resolved into a series of one‐dimensional spectra where each spectrum was modeled and fitted with its theoretically customized LCModel template. Metabolite levels were derived from the total integral across the J‐series of spectra for each metabolite. Phantoms containing physiologic concentrations of the major brain chemicals were used for validation. Varying concentrations of glutamate and glutamine were evaluated at and around their accepted in vivo concentrations in order to compare the accuracy and precision of our method with 30 ms PRESS. We also assessed 2D‐JPRESS and 30 ms PRESS in vivo, in a single voxel within the parieto‐occipital cortex by scanning ten healthy volunteers once and a single healthy volunteer over nine repeated measures. Phantom studies demonstrated that serial fitting of 2D‐JPRESS spectra with simulated LCModel basis sets provided accurate concentration estimates for common metabolites including glutamate and glutamine. Our in vivo results using 2D‐JPRESS suggested superior reproducibility in measuring glutamine and glutamate relative to 30 ms PRESS. These novel methods have clear implications for clinical and research studies seeking to understand neurochemical dysfunction. Copyright © 2009 John Wiley & Sons, Ltd.     

Long TE PRESS and STEAM for measuring the triglyceride glycerol CH2 protons at 3 T

The glycerol methylene proton resonances (4–4.5 parts per million, ppm), which arise from the triglyceride backbone, are relevant to fat composition assessment and can be measured with proton MRS. The purpose of the presented work is to determine long TE (echo time) point resolved spectroscopy (PRESS) and stimulated echo acquisition mode (STEAM) values at 3 T to resolve the glycerol resonances from that of overlapping water. The response of the glycerol methylene protons of nine edible oils as a function of PRESS and STEAM TE (mixing time, TM = 20 ms) was investigated. In addition, high resolution NMR spectra of the oils were acquired at 16.5 T. Long TE values where J‐coupling losses were lowest were selected, namely a TE of 180 ms for PRESS (first echo time 17 ms) and a TE of 100 ms for STEAM (mixing time 20 ms). Oil olefinic (≈5.4 ppm) to glycerol ratios were calculated from the long TE spectra and correlated with 16.5 T ratios. The two techniques yielded olefinic/glycerol ratios that correlated with 16.5 T ratios (R² = 0.79 for PRESS and 0.90 for STEAM). The efficacy of the sequences in resolving the glycerol resonance from that of water was verified in vivo on tibial bone marrow of four healthy volunteers. In addition, the potential for using the glycerol methylene signal normalized to the methyl signal (≈0.9 ppm) to assess changes in free fatty acid content was demonstrated by measuring differences in spectra acquired from a triglyceride peanut oil phantom and from a phantom composed of a mixture of peanut oil and free fatty acid oleic acid.