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.     

Noninvasive quantification of human brain ascorbate concentration using 1H NMR spectroscopy at 7 T

Ascorbate (Asc, vitamin C) was quantified in the human brain noninvasively using two different ¹H NMR spectroscopy methods: short‐echo time STEAM and MEGA‐PRESS homonuclear editing. Taking advantage of increased sensitivity and chemical shift dispersion at 7 T, Asc was quantified with increased reliability relative to our previous study accomplished at 4 T. Asc concentration quantified from short‐echo time spectra measured from the occipital lobe of eight healthy subjects ([Asc] = 1.1 ± 0.3 µmol/g, mean ± SD) was in excellent agreement with Asc concentration quantified from the same volume of interest using homonuclear editing ([Asc] = 1.2 ± 0.2 µmol/g). This agreement indicates that at 7 T, Asc can be reliably quantified in the human brain simultaneously with 15 other metabolites. Additional advantages of the short‐echo time approach were: shorter measurement time than homonuclear editing and minimal effect of T₂ relaxation on Asc quantification. High magnetic field was also beneficial for Asc quantification with MEGA‐PRESS because increased chemical shift dispersion enabled editing with full efficiency, which resulted in a supra‐linear gain in signal‐to‐noise ratio relative to 4 T. Copyright © 2009 John Wiley & Sons, Ltd.     

Measurement of regional variation of GABA in the human brain by optimized point‐resolved spectroscopy at 7 T in vivo

The ¹H resonances of γ‐aminobutyric acid (GABA) in the human brain in vivo are extensively overlapped with the neighboring abundant resonances of other metabolites and remain indiscernible in short‐TE MRS at 7 T. Here we report that the GABA resonance at 2.28 ppm can be fully resolved by means of echo time optimization of a point‐resolved spectroscopy (PRESS) scheme. Following numerical simulations and phantom validation, the subecho times of PRESS were optimized at (TE, TE₂) = (31, 61) ms for detection of GABA, glutamate (Glu), glutamine (Gln), and glutathione (GSH). The in vivo feasibility of the method was tested in several brain regions in nine healthy subjects. Spectra were acquired from the medial prefrontal, left frontal, medial occipital, and left occipital brain and analyzed with LCModel. Following the gray and white matter (GM and WM) segmentation of T₁‐weighted images, linear regression of metabolite estimates was performed against the fractional GM contents. The GABA concentration was estimated to be about seven times higher in GM than in WM. GABA was overall higher in frontal than in occipital brain. Glu was about twice as high in GM as in WM in both frontal and occipital brain. Gln was significantly different between frontal GM and WM while being similar between occipital GM and WM. GSH did not show significant dependence on tissue content. The signals from N‐acetylaspartylglutamate were clearly resolved, giving the concentration more than 10 times higher in WM than in GM. Our data indicate that the PRESS TE = 92 ms method provides an effective means for measuring GABA and several challenging J‐coupled spin metabolites in human brain at 7 T. Copyright © 2014 John Wiley & Sons, Ltd.     

Phase‐adjusted echo time (PATE)‐averaging 1H MRS: application for improved glutamine quantification at 2.89 T

¹H MRS investigations have reported altered glutamatergic neurotransmission in a variety of psychiatric disorders. The unraveling of glutamate from glutamine resonances is crucial for the interpretation of these observations, although this remains a challenge at clinical static magnetic field strengths. Glutamate resolution can be improved through an approach known as echo time (TE) averaging, which involves the acquisition and subsequent averaging of multiple TE steps. The process of TE averaging retains the central component of the glutamate methylene multiplet at 2.35 ppm, with the simultaneous attenuation of overlapping phase‐modulated coupled resonances of glutamine and N‐acetylaspartate. We have developed a novel post‐processing approach, termed phase‐adjusted echo time (PATE) averaging, for the retrieval of glutamine signals from a TE‐averaged ¹H MRS dataset. The method works by the application of an optimal TE‐specific phase term, which is derived from spectral simulation, prior to averaging over TE space. The simulation procedures and preliminary in vivo spectra acquired from the human frontal lobe at 2.89 T are presented. Three metabolite normalization schemes were developed to evaluate the frontal lobe test–retest reliability for glutamine measurement in six subjects, and the resulting values were comparable with previous reports for within‐subject (9–14%) and inter‐subject (14–20%) measures. Using the acquisition parameters and TE range described, glutamine quantification is possible in approximately 10 min. The post‐processing methods described can also be applied retrospectively to extract glutamine and glutamate levels from previously acquired TE‐averaged ¹H MRS datasets. Copyright © 2012 John Wiley & Sons, Ltd.     

Reproducibility of 31P cardiac magnetic resonance spectroscopy at 3 T

The purpose of this work was to take advantage of the new clinical field strength of 3 T to implement and optimize a chemical shift imaging (CSI) acquisition protocol to produce spectra of high quality with high specificity to the myocardium within a clinically feasible scan time. Further, an analysis method was implemented dependent purely on anatomical location of spectra, and as such free from any potential user bias caused by inference from spectral information. Twenty healthy male subjects were scanned on two separate occasions using the optimized CSI protocol at 3 T. Data were analyzed for intra‐ and inter‐subject variability, as well as intra‐ and inter‐observer variability. The average phosphocreatine (PCr)/adenosine triphosphate (ATP) value for scan 1 was 2.07 ± 0.38 and for scan 2 was 2.14 ± 0.46, showing no significant difference between scans. Intra‐subject variability was 0.43 ± 0.35 (percentage difference 20%) and the inter‐subject coefficient of variation was 18%. The intra‐observer variability, assessed as the absolute difference between analyses of the data by a single observer, was 0.14 ± 0.24 with no significant difference between analyses. The inter‐observer variability showed no significant differences between the PCr/ATP value measured by four different observers as demonstrated by an intra‐class correlation coefficient of 0.763. The increased signal available at 3 T has improved spatial resolution and thereby increased myocardial specificity without any significant decrease in reproducibility over previous studies at 1.5 T. We present an acquisition protocol that routinely provides high quality spectra and a robust analysis method that is free from potential user bias. Copyright © 2008 John Wiley & Sons, Ltd.     

In vivo 31P magnetic resonance spectroscopy of the human liver at 7 T: an initial experience

Phosphorus (³¹P) MRS is a powerful tool for the non‐invasive investigation of human liver metabolism. Four in vivo ³¹P localization approaches (single voxel image selected in vivo spectroscopy (3D‐ISIS), slab selective 1D‐ISIS, 2D chemical shift imaging (CSI), and 3D‐CSI) with different voxel volumes and acquisition times were demonstrated in nine healthy volunteers. Localization techniques provided comparable signal‐to‐noise ratios normalized for voxel volume and acquisition time differences, Cramer–Rao lower bounds (8.7 ± 3.3%_1D‐ISIS, 7.6 ± 2.5%_3D‐ISIS, 8.6 ± 4.2%_2D‐CSI, 10.3 ± 2.7%_3D‐CSI), and linewidths (50 ± 24 Hz_1D‐ISIS, 34 ± 10 Hz_3D‐ISIS, 33 ± 10 Hz_2D‐CSI, 34 ± 11 Hz_3D‐CSI). Longitudinal (T₁) relaxation times of human liver metabolites at 7 T were assessed by 1D‐ISIS inversion recovery in the same volunteers (n = 9). T₁ relaxation times of hepatic ³¹P metabolites at 7 T were the following: phosphorylethanolamine – 4.41 ± 1.55 s; phosphorylcholine – 3.74 ± 1.31 s; inorganic phosphate – 0.70 ± 0.33 s; glycerol 3‐phosphorylethanolamine – 6.19 ± 0.91 s; glycerol 3‐phosphorylcholine – 5.94 ± 0.73 s; γ‐adenosine triphosphate (ATP) – 0.50 ± 0.08 s; α‐ATP – 0.46 ± 0.07 s; β‐ATP – 0.56 ± 0.07 s. The improved spectral resolution at 7 T enabled separation of resonances in the phosphomonoester and phosphodiester spectral region as well as nicotinamide adenine dinucleotide and uridine diphosphoglucose signals. An additional resonance at 2.06 ppm previously assigned to phosphoenolpyruvate or phosphatidylcholine is also detectable. These are the first ³¹P metabolite relaxation time measurements at 7 T in human liver, and they will help in the exploration of new, exciting questions in metabolic research with 7 T MR. Copyright © 2014 John Wiley & Sons, Ltd.     

Quantification of GABA,glutamate and glutamine in a single measurement at 3 T using GABA‐edited MEGA‐PRESS

γ‐Aminobutyric acid (GABA) and glutamate (Glu), major neurotransmitters in the brain, are recycled through glutamine (Gln). All three metabolites can be measured by magnetic resonance spectroscopy in vivo, although GABA measurement at 3 T requires an extra editing acquisition, such as Mescher–Garwood point‐resolved spectroscopy (MEGA‐PRESS). In a GABA‐edited MEGA‐PRESS spectrum, Glu and Gln co‐edit with GABA, providing the possibility to measure all three in one acquisition. In this study, we investigated the reliability of the composite Glu + Gln (Glx) peak estimation and the possibility of Glu and Gln separation in GABA‐edited MEGA‐PRESS spectra. The data acquired in vivo were used to develop a quality assessment framework which identified MEGA‐PRESS spectra in which Glu and Gln could be estimated reliably. Phantoms containing Glu, Gln, GABA and N‐acetylaspartate (NAA) at different concentrations were scanned using GABA‐edited MEGA‐PRESS at 3 T. Fifty‐six sets of spectra in five brain regions were acquired from 36 healthy volunteers. Based on the Glu/Gln ratio, data were classified as either within or outside the physiological range. A peak‐by‐peak quality assessment was performed on all data to investigate whether quality metrics can discriminate between these two classes of spectra. The quality metrics were as follows: the GABA signal‐to‐noise ratio, the NAA linewidth and the Glx Cramer–Rao lower bound (CRLB). The Glu and Gln concentrations were estimated with precision across all phantoms with a linear relationship between the measured and true concentrations: R¹ = 0.95 for Glu and R¹ = 0.91 for Gln. A quality assessment framework was set based on the criteria necessary for a good GABA‐edited MEGA‐PRESS spectrum. Simultaneous criteria of NAA linewidth <8 Hz and Glx CRLB <16% were defined as optimum features for reliable Glu and Gln quantification. Glu and Gln can be reliably quantified from GABA‐edited MEGA‐PRESS acquisitions. However, this reliability should be controlled using the quality assessment methods suggested in this work.     

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.     

Effect of J coupling on 1.3‐ppm lipid methylene signal acquired with localised proton MRS at 3 T

The purpose of this work was to investigate the effect of J‐coupling interactions on the quantification and T₂ determination of 1.3‐ppm lipid methylene protons at 3 T. The response of the 1.3‐ppm protons of hexanoic, heptanoic, octanoic, linoleic and oleic acid was measured as a function of point‐resolved spectroscopy (PRESS) and stimulated echo acquisition mode (STEAM) TE. In addition, a narrow‐bandwidth refocusing PRESS sequence designed to rewind J‐coupling evolution of the 1.3‐ppm protons was applied to the five fatty acids, to corn oil and to tibial bone marrow of six healthy volunteers. Peak areas were plotted as a function of TE, and data were fitted to monoexponentially decaying functions to determine M_o (the extrapolated area for TE = 0 ms) and T₂ values. In phantoms, rewinding J‐coupling evolution resulted in 198%, 64%, 44%, 20% and 15% higher T₂ values for heptanoic, octanoic, linoleic and oleic acid, and corn oil, respectively, compared with those obtained with standard PRESS. The narrow‐bandwidth PRESS sequence also resulted in significant changes in M_o, namely ?77%, ?22%, 28%, 23% and 28% for heptanoic, octanoic, linoleic and oleic acid, and corn oil, respectively. T₂ values obtained with STEAM were closer to the values measured with narrow‐bandwidth PRESS. On average, in tibial bone marrow (six volunteers) rewinding J‐coupling evolution resulted in 21% ± 3% and 9 % ± 1% higher M_o and T₂ values, respectively. This work demonstrates that the consequence of neglecting to consider scalar coupling effects on the quantification of 1.3‐ppm lipid methylene protons and their T₂ values is not negligible. The linoleic and oleic acid T₂ results indicate that T₂ measures of lipids with standard MRS techniques are dependent on lipid composition. Copyright © 2015 John Wiley & Sons, Ltd.     

In vivo 1H MRS of human gallbladder bile at 3 T in one and two dimensions: detection and quantification of major biliary lipids

In vitro ¹H MRS of human bile has shown potential in the diagnosis of various hepatopancreatobiliary (HPB) diseases. Previously, in vivo ¹H MRS of human bile in gallbladder using a 1.5 T scanner demonstrated the possibility of quantification of choline‐containing phospholipids (chol‐PLs). However, other lipid components such as bile acids play an important role in the pathophysiology of the HPB system. We have employed a higher magnetic field strength (3 T), and a custom‐built receive array coil, to improve the quality of in vivo ¹H MRS of human bile in the gallbladder. We obtained significant improvement in the quality of 1D spectra (17 healthy volunteers) using a respiratory‐gated PRESS sequence with well distinguished signals for total bile acids (TBAs) plus cholesterol resonating at 0.66 ppm, taurine‐conjugated bile acids (TCBAs) at 3.08 ppm, chol‐PLs at 3.22 ppm, glycine‐conjugated bile acids (GCBAs) at 3.74 ppm, and the amide proton (?NH) arising from GCBAs and TCBAs in the region 7.76–8.05 ppm. The peak areas of these signals were measured by deconvolution, and subsequently the molar concentrations of metabolites were estimated with good accuracy, except for that of TBAs plus cholesterol. The concentration of TBAs plus cholesterol was overestimated in some cases, which could be due to lipid contamination. In addition, we report the first 2D L‐COSY spectra of human gallbladder bile in vivo (obtained in 15 healthy volunteers). 2D L‐COSY spectra will be helpful in differentiating various biliary chol‐PLs in pathological conditions of the HPB system. Copyright © 2014 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.     

In vivo MRI analysis of depth‐dependent ultrastructure in human knee cartilage at 7 T

Signal intensities of T₂‐weighted magnetic resonance images depend on the local fiber arrangement in hyaline cartilage. The aims of this study were to determine whether angle‐sensitive MRI at 7 T can be used to quantify the cartilage ultrastructure of the knee in vivo and to assess potential differences with age. Ten younger (21–30) and ten older (55–76 years old) healthy volunteers were imaged with a T₂‐weighted spin‐echo sequence in a 7 T whole‐body MRI. A “fascicle” model was assumed to describe the depth‐dependent fiber arrangement of cartilage. The R/T boundary positions between radial and transitional zones were assessed from intensity profiles in small regions of interest in the femur and tibia, and normalized to cartilage thickness using logistic curve fits. The quality of our highly resolved (0.3 × 0.3 × 1.0 mm³) MR cartilage images were high enough for quantitative analysis (goodness of fit R² = 0.91 ± 0.09). Between younger and older subjects, normalized positions of the R/T boundary, with value 0 at the bone–cartilage interface and 1 at the cartilage surface, were significantly (p < 0.05) different in femoral (0.51 ± 0.12 versus 0.41 ± 0.10), but not in tibial cartilage (0.65 ± 0.11 versus 0.57 ± 0.09, p = 0.119). Within both age groups, differences between femoral and tibial R/T boundaries were significant. Using a fascicle model and angle‐sensitive MRI, the depth‐dependent anisotropic fiber arrangement of knee cartilage could be assessed in vivo from a single 7 T MR image. The derived quantitative parameter, thickness of the radial zone, may serve as an indicator of the structural integrity of cartilage. This method may potentially be suitable to detect and monitor early osteoarthritis because the progressive disintegration of the anisotropic network is also indicative of arthritic changes in cartilage. Copyright © 2013 John Wiley & Sons, Ltd.     

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.     

Detection of lactate in the striatum without contamination of macromolecules by J‐difference editing MRS at 7 T

Lactate levels are measurable by MRS and are related to neural activity. Therefore, it is of interest to accurately measure lactate levels in the basal ganglia networks. If sufficiently stable, lactate measurements may be used to investigate alterations in dopaminergic signalling in the striatum, facilitating the detection and diagnosis of metabolic deficits. The aim of this study is to provide a J‐difference editing MRS technique for the selective editing of lactate only, thus allowing the detection of lactate without contamination of overlapping macromolecules. As a validation procedure, macromolecule nulling was combined with J‐difference editing, and this was compared with J‐difference editing with a new highly selective editing pulse. The use of a high‐field (7T) MR scanner enables the application of editing pulses with very narrow bandwidth, which are selective for lactate. We show that, despite the sensitivity to B₀ offsets, the use of a highly selective editing pulse is more efficient for the detection of lactate than the combination of a broad‐band editing pulse with macromolecule nulling. Although the signal‐to‐noise ratio of uncontaminated lactate detection in healthy subjects is relatively low, this article describes the test–retest performance of lactate detection in the striatum when using highly selective J‐difference editing MRS at 7 T. The coefficient of variation, σ_w and intraclass correlation coefficients for within‐ and between‐subject differences of lactate were determined. Lactate levels in the left and right striatum were determined twice in 10 healthy volunteers. Despite the fact that the test–retest performance of lactate detection is moderate with a coefficient of variation of about 20% for lactate, these values can be used for the design of new studies comparing, for example, patient populations with healthy controls. Copyright © 2015 John Wiley & Sons, Ltd.     

Unedited in vivo detection and quantification of γ‐aminobutyric acid in the occipital cortex using short‐TE MRS at 3 T

Short‐TE MRS has been proposed recently as a method for the in vivo detection and quantification of γ‐aminobutyric acid (GABA) in the human brain at 3 T. In this study, we investigated the accuracy and reproducibility of short‐TE MRS measurements of GABA at 3 T using both simulations and experiments. LCModel analysis was performed on a large number of simulated spectra with known metabolite input concentrations. Simulated spectra were generated using a range of spectral linewidths and signal‐to‐noise ratios to investigate the effect of varying experimental conditions, and analyses were performed using two different baseline models to investigate the effect of an inaccurate baseline model on GABA quantification. The results of these analyses indicated that, under experimental conditions corresponding to those typically observed in the occipital cortex, GABA concentration estimates are reproducible (mean reproducibility error, <20%), even when an incorrect baseline model is used. However, simulations indicate that the accuracy of GABA concentration estimates depends strongly on the experimental conditions (linewidth and signal‐to‐noise ratio). In addition to simulations, in vivo GABA measurements were performed using both spectral editing and short‐TE MRS in the occipital cortex of 14 healthy volunteers. Short‐TE MRS measurements of GABA exhibited a significant positive correlation with edited GABA measurements (R = 0.58, p < 0.05), suggesting that short‐TE measurements of GABA correspond well with measurements made using spectral editing techniques. Finally, within‐session reproducibility was assessed in the same 14 subjects using four consecutive short‐TE GABA measurements in the occipital cortex. Across all subjects, the average coefficient of variation of these four GABA measurements was 8.7 ± 4.9%. This study demonstrates that, under some experimental conditions, short‐TE MRS can be employed for the reproducible detection of GABA at 3 T, but that the technique should be used with caution, as the results are dependent on the experimental conditions. Copyright © 2013 John Wiley & Sons, Ltd.     

Comparison of reproducibility of single voxel spectroscopy and whole‐brain magnetic resonance spectroscopy imaging at 3T

To date, single voxel spectroscopy (SVS) is the most commonly used MRS technique. SVS is relatively easy to use and provides automated and immediate access to the resulting spectra. However, it is also limited in spatial coverage. A new and very promising MRS technique allows for whole‐brain MR spectroscopic imaging (WB‐MRSI) with much improved spatial resolution. Establishing the reproducibility of data obtained using SVS and WB‐MRSI is an important first step for using these techniques to evaluate longitudinal changes in metabolite concentration. The purpose of this study was to assess and directly compare the reproducibility of metabolite quantification at 3T using SVS and WB‐MRSI in ‘hand‐knob’ areas of motor cortices and hippocampi in healthy volunteers. Ten healthy adults were scanned using both SVS and WB‐MRSI on three occasions one week apart. N‐acetyl aspartate (NAA), creatine (Cr), choline (Cho) and myo‐inositol (mI) were quantified using SVS and WB‐MRSI with reference to both Cr and H₂O. The reproducibility of each technique was evaluated using the coefficient of variation (CV), and the correspondence between the two techniques was assessed using Pearson correlation analysis. The measured mean (range) intra‐subject CVs for SVS were 5.90 (2.65‐10.66)% for metabolites (i.e. NAA, Cho, mI) relative to Cr, and 8.46 (4.21‐21.07)% for metabolites (NAA, Cr, Cho, mI) relative to H₂O. The mean (range) CVs for WB‐MRSI were 7.56 (2.78‐11.41)% for metabolites relative to Cr, and 7.79 (4.57‐14.11)% for metabolites relative to H₂O. Significant positive correlations were observed between metabolites quantified using SVS and WB‐MRSI techniques when the Cr but not H₂O reference was used. The results demonstrate that reproducibilities of SVS and WB‐MRSI are similar for quantifying the four major metabolites (NAA, Cr, Cho, mI); both SVS and WB‐MRSI exhibited good reproducibility. Our findings add reference information for choosing the appropriate ¹H‐MRS technique in future studies.     

Improvement of resolution for brain coupled metabolites by optimized (1)H MRS at 7T

Resolution enhancement for glutamate (Glu), glutamine (Gln) and glutathione (GSH) in the human brain by TE‐optimized point‐resolved spectroscopy (PRESS) at 7 T is reported. Sub‐TE dependences of the multiplets of Glu, Gln, GSH, γ‐aminobutyric acid (GABA) and N‐acetylaspartate (NAA) at 2.2–2.6 ppm were investigated with density matrix simulations, incorporating three‐dimensional volume localization. The numerical simulations indicated that the C4‐proton multiplets can be completely separated with (TE₁, TE₂) = (37, 63) ms, as a result of a narrowing of the multiplets and suppression of the NAA 2.5 ppm signal. Phantom experiments reproduced the signal yield and lineshape from simulations within experimental errors. In vivo tests of optimized PRESS were conducted on the prefrontal cortex of six healthy volunteers. In spectral fitting by LCModel, Cramér–Rao lower bounds (CRLBs) of Glu, Gln and GSH were 2 ± 1, 5 ± 1 and 6 ± 2 (mean ± SD), respectively. To evaluate the performance of the optimized PRESS method under identical experimental conditions, stimulated‐echo spectra were acquired with (TE, TM) = (14, 37) and (74, 68) ms. The CRLB of Glu was similar between PRESS and short‐TE stimulated‐echo acquisition mode (STEAM), but the CRLBs of Gln and GSH were lower in PRESS than in both STEAM acquisitions. Copyright © 2010 John Wiley & Sons, Ltd.     

Multi‐center reproducibility of neurochemical profiles in the human brain at 7 T

The purpose of this work was to harmonize data acquisition and post‐processing of single voxel proton MRS (¹H‐MRS) at 7 T, and to determine metabolite concentrations and the accuracy and reproducibility of metabolite levels in the adult human brain. This study was performed in compliance with local institutional human ethics committees. The same seven subjects were each examined twice using four different 7 T MR systems from two different vendors using an identical semi‐localization by adiabatic selective refocusing spectroscopy sequence. Neurochemical profiles were obtained from the posterior cingulate cortex (gray matter, GM) and the corona radiata (white matter, WM). Spectra were analyzed with LCModel, and sources of variation in concentrations (‘subject’, ‘institute’ and ‘random’) were identified with a variance component analysis. Concentrations of 10–11 metabolites, which were corrected for T₁, T₂, magnetization transfer effects and partial volume effects, were obtained with mean Cramér–Rao lower bounds below 20%. Data variances and mean concentrations in GM and WM were comparable for all institutions. The primary source of variance for glutamate, myo‐inositol, scyllo‐inositol, total creatine and total choline was between subjects. Variance sources for all other metabolites were associated with within‐subject and system noise, except for total N‐acetylaspartate, glutamine and glutathione, which were related to differences in signal‐to‐noise ratio and in shimming performance between vendors. After multi‐center harmonization of acquisition and post‐processing protocols, metabolite concentrations and the sizes and sources of their variations were established for neurochemical profiles in the healthy brain at 7 T, which can be used as guidance in future studies quantifying metabolite and neurotransmitter concentrations with ¹H‐MRS at ultra‐high magnetic field. Copyright © 2015 John Wiley & Sons, Ltd.     

Feasibility and reproducibility of neurochemical profile quantification in the human hippocampus at 3 T

Hippocampal dysfunction is known to be associated with several neurological and neuropsychiatric disorders such as Alzheimer's disease, epilepsy, schizophrenia and depression; therefore, there has been significant clinical interest in studying hippocampal neurochemistry. However, the hippocampus is a challenging region to study using ¹H MRS, hence the use of MRS for clinical research in this region has been limited. Our goal was therefore to investigate the feasibility of obtaining high‐quality hippocampal spectra that allow reliable quantification of a neurochemical profile and to establish inter‐session reproducibility of hippocampal MRS, including reproducibility of voxel placement, spectral quality and neurochemical concentrations. Ten healthy volunteers were scanned in two consecutive sessions using a standard clinical 3 T MR scanner. Neurochemical profiles were obtained with a short‐echo (T_E = 28 ms) semi‐LASER localization sequence from a relatively small (~4 mL) voxel that covered about 62% of the hippocampal volume as calculated from segmentation of T₁‐weighted images. Voxel composition was highly reproducible between sessions, with test–retest coefficients of variation (CVs) of 3.5% and 7.5% for gray and white matter volume fraction, respectively. Excellent signal‐to‐noise ratio (~54 based on the N‐acetylaspartate (NAA) methyl peak in non‐apodized spectra) and linewidths (~9 Hz for water) were achieved reproducibly in all subjects. The spectral quality allowed quantification of NAA, total choline, total creatine, myo‐inositol and glutamate with high scan–rescan reproducibility (CV ≤ 6%) and quantification precision (Cramér–Rao lower bound, CRLB < 9%). Four other metabolites, including glutathione and glucose, were quantified with scan–rescan CV below 20%. Therefore, the highly optimized, short‐echo semi‐LASER sequence together with FASTMAP shimming substantially improved the reproducibility and number of quantifiable metabolites relative to prior reports. In addition, the between‐session variation in metabolite concentrations, as well as CRLB, was lower than the between‐subject variation of the concentrations for most metabolites, indicating that the method has the sensitivity to detect inter‐individual differences in the healthy brain. Copyright © 2015 John Wiley & Sons, Ltd.     

A comparative study of short‐ and long‐TE 1H MRS at 3 T for in vivo detection of 2‐hydroxyglutarate in brain tumors

2‐Hydroxyglutarate (2HG) is produced in gliomas with mutations of isocitrate dehydrogenase (IDH) 1 and 2. The ¹H resonances of the J‐coupled spins of 2HG are extensively overlapped with signals from other metabolites. Here, we report a comparative study at 3 T of the utility of the point‐resolved spectroscopy sequence with a standard short TE (35 ms) and a long TE (97 ms), which had been theoretically designed for the detection of the 2HG 2.25‐ppm resonance. The performance of the methods is evaluated using data from phantoms, seven healthy volunteers and 22 subjects with IDH‐mutated gliomas. The results indicate that TE = 97 ms provides higher detectability of 2HG than TE = 35 ms, and that this improved capability is gained when data are analyzed with basis spectra that include the effects of the volume localizing radiofrequency and gradient pulses. Copyright © 2013 John Wiley & Sons, Ltd.