Strongly coupled versus uncoupled spin response to radio frequency interference effects: application to glutamate and glutamine in spectroscopic imaging

It is well known that comparable radio frequency (RF) wavelengths and human head dimensions at high fields can lead to an inhomogeneous RF field when using standard RF transmission. However, the impact of RF inhomogeneity on potential differences in quantification between coupled and uncoupled spins at longer echo times has not been investigated thoroughly. The consequence of this RF interference on metabolite quantification in spectroscopic imaging at 4.7 T was investigated for the strongly coupled spin systems of glutamate and glutamine at an echo time of 120 ms, and compared with the singlet response of choline. These effects were studied using a single-voxel PRESS sequence (alpha-2alpha-2alpha) with varying flip angle (alpha) from 90 degrees to 65 degrees in simulation, phantom, and in vivo experiments. Phantom metabolite yield decreased to 57% for choline and 27% for glutamate/glutamine in agreement with the simulations. Even a minor reduction from alpha = 85 degrees to 80 degrees produced a large difference between coupled and uncoupled yields, with a reduction of 7% for choline and 17% for glutamate/glutamine. Anecdotal in vivo spectroscopic imaging studies show similar trends, with large differences between choline and glutamate/glutamine yield over a small, 2.2 cm, region. These results demonstrate severe effects on metabolite yield due to RF variation between strongly coupled and uncoupled spin systems at long echo time, which complicates metabolite quantification.     

Regional distributions of brain glutamate and glutamine in normal subjects

Glutamate (Glu) and glutamine (Gln) play an important role in neuronal regulation and are of value as MRS‐observable diagnostic biomarkers. In this study the relative concentrations of these metabolites have been measured in multiple regions in the normal brain using a short‐T_E whole‐brain MRSI measurement at 3 T combined with a modified data analysis approach that used spatial averaging to obtain high‐SNR spectra from atlas‐registered anatomic regions or interest. By spectral fitting of high‐SNR spectra this approach yielded reliable measurements across a wide volume of the brain. Spectral averaging also demonstrated increased SNR and improved fitting accuracy for the sum of Glu and Gln (Glx) compared with individual voxel fitting. Results in 26 healthy controls showed relatively constant Glu/Cr and Gln/Cr throughout the cerebrum, although with increased values in the anterior cingulum and paracentral lobule, and increased Gln/Cr in the superior motor area. The deep gray‐matter regions of thalamus, putamen, and pallidum show lower Glu/Cr compared with cortical white‐matter regions. Lobar measurements demonstrated reduced Glu/Cr and Gln/Cr in the cerebellum as compared with the cerebrum, where white‐matter regions show significantly lower Glu/Cr and Gln/Cr as compared with gray‐matter regions across multiple brain lobes. Regression analysis showed no significant effect of gender on Glu/Cr or Gln/Cr measurement; however, Glx/Cr ratio was found to be significantly negatively correlated with age in some lobar brain regions. In summary, this methodology provides the spectral quality necessary for reliable separation of Glu and Gln at 3 T from a single MRSI acquisition enabling generation of regional distributions of metabolites over a large volume of the brain, including cortical regions. Copyright © 2016 John Wiley & Sons, Ltd.     

Single‐voxel 1H spectroscopy in the human hippocampus at 3 T using the LASER sequence: characterization of neurochemical profile and reproducibility

The hippocampus is crucial for long‐term episodic memory and learning. It undergoes structural change in aging and is sensitive to neurodegenerative and psychiatric diseases. MRS studies have seldom been performed in the hippocampus due to technical challenges. The reproducibility of MRS in the hippocampus has not been evaluated at 3 T. The purpose of the present study was to quantify the concentration of metabolites in a small voxel placed in the hippocampus and evaluate the reproducibility of the quantification. Spectra were measured in a 2.4 mL voxel placed in the left hippocampus covering the body and most of the tail of the structure in 10 healthy subjects across three different sessions and quantified using LCModel. High‐quality spectra were obtained, which allowed a reliable quantification of 10 metabolites including glutamate and glutamine. Reproducibility of MRS was evaluated with coefficient of variation, standard errors of measurement, and intraclass correlation coefficients. All of these measures showed improvement with increased number of averages. Changes of less than 5% in concentration of N‐acetylaspartate, choline‐containing compounds, and total creatine and of less than 10% in concentration of myo‐inositol and the sum of glutamate and glutamine can be confidently detected between two measurements in a group of 20 subjects. A reliable and reproducible neurochemical profile of the human hippocampus was obtained using MRS at 3 T in a small hippocampal volume. Copyright © 2015 John Wiley & Sons, Ltd.     

Which pulse sequence is optimal for myo‐inositol detection at 3T?

Optimized myo‐inositol (mI) detection is important for diagnosing and monitoring a multitude of pathological conditions of the brain. Simulations are presented in this work, performed to decide which pulse sequence has the most significant advantage in terms of improving repeatability and accuracy of mI measurements at 3T over the pulse sequence used typically in the clinic, a TE = 35 ms PRESS sequence. Five classes of pulse sequences, four previously suggested for optimized mI detection (a short TE PRESS, a Carr‐Purcell PRESS sequence, an optimized STEAM sequence, an optimized zero quantum filter), and one optimized for mI detection in this work (a single quantum filter) were compared to a standard, TE = 35 ms pulse sequence. While limiting the SNR of an acquisition to the equivalent SNR of a spectrum acquired in 5 min from an 8 cc voxel, it was found through simulations that the most repeatable mI measurements would be obtained with a Carr‐Purcell sequence. This sequence was implemented in a clinical scanner, and improved mI measurements were demonstrated in vivo. Copyright © 2008 John Wiley & Sons, Ltd.     

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.     

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.     

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.     

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.     

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.     

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.     

Primary immune response to keyhole limpet haemocyanin following trauma in relation to low plasma glutamine

Severe trauma can lead to a compromised immune response, thereby increasing susceptibility to infections. Here we will study to what extent these early changes in the immune status upon trauma affect a primary immune response to keyhole limpet haemocyanin (KLH). Because glutamine is the preferred respiratory substrate for immune competent cells and known to be depleted after trauma, we studied the immune status and the primary sensitization in relation to the glutamine plasma concentration in a group of severe trauma patients [injury severity score (ISS) >17]. Trauma patients (n = 31) were sensitized with KLH within 12 h after trauma; plasma glutamine concentrations and immune parameters were determined, after which KLH-specific immune responsiveness was evaluated on days 9 and 14. Low plasma glutamine concentrations were found after trauma. Significantly elevated numbers of granulocytes and CD14-positive leucocytes were found, whereas the HLA-DR expression on CD14-positive cells was significantly lower in trauma patients than in healthy controls. Trauma did not change the in vitro proliferative capacity of lymphocytes when cultured with glutamine; however, when lymphocytes were cultured without glutamine, trauma resulted in lower proliferation than healthy controls. Phytohaemagglutinin-(PHA)-induced interferon (IFN)-gamma and interleukin (IL)-10 production was significantly lower after trauma, whereas IL-4 production was not affected. KLH sensitization following trauma resulted in poor skin test reactivity and low in vitro KLH-induced lymphocyte proliferation compared to controls. In contrast, the development of anti-KLH IgM, IgG, IgA, IgG1, IgG2, IgG3 and IgG4 production on days 9 and 14 following trauma was not different from that in healthy controls. Major trauma was associated with a reduced cell-mediated immune response, correlating with low plasma glutamine concentrations, while no effects of trauma were found on the development of a primary humoral immune response.     

磁共振波谱（MRS）对胶质瘤切除程度评估的初步研究

目的　探讨术前后MRS在胶质瘤手术切除程度评估的应用价值。 方法　对16例胶质瘤患者术前术后行常规MRI和3D多体素MRS检查,计算术前后的Cho/Cr和Cho/NAA的比值,寻找相等或相近的Cho/Cr和Cho/NAA比值,结合体素所在层面的位置,建立对应关系,从而评价术后切除到达范围。同时术中收集“瘤周组织”作病理检查,评估切除程度,与3D多体素MRS评估结果相比较。 结果　16例病人收集到完整的影像学和病理学资料有11例,病理评估为3例全切除,8例为大部分切除;3D多体素MRS 评估为2例全切除,9例为大部分切除,评估结果与术后病理评估结果无显著性差异（P>0.05）。 结论　无创性评估胶质瘤切除程度是MRS的一项新应用,具有良好的发展前景。     

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.     

定量质子磁共振波谱对鉴别良性与恶性脑膜瘤的价值(英文)

本研究致力于探讨定量质子磁共振波谱(MRS)对鉴别良性与恶性脑膜瘤的价值。研究利用1.5T磁共振仪,对23例脑膜瘤(良性组(WHO I级)19例,恶性组(WHOⅡ～Ⅲ级)4例)进行单体素MRS检查(PRESS序列,TR/TE=2000ms/68,136,272ms),通过指数衰减模型估计组织水和胆碱(Choline,Cho)的T2弛豫时间,并以组织水为内参照计算Cho的绝对浓度,然后按MRS体素内坏死或囊变组织的比例对Cho浓度进行校正。研究发现,良、恶性脑膜瘤的组织水T2弛豫时间分别是(105±41)ms和(151±42)ms,差异有显著性(P=0.033)。良、恶性脑膜瘤的Cho T2弛豫时间分别是(242±73)ms和(316±102)ms,无显著差异(P=0.105)。良、恶性脑膜瘤的Cho浓度在校正前分别是(2.86±0.86)mmol/kg wet weight和(3.53±0.60)mmol/kg wet weight,在校正后分别是(2.98±0.93)mmol/kg wet weight和(4.58±1.22)mmol/kg wet weight,校正后差异具有显著性(P=0.019)。研究...     

The hexosamine biosynthetic pathway couples growth factor-induced glutamine uptake to glucose metabolism

Glucose and glutamine serve as the two primary carbon sources in proliferating cells, and uptake of both nutrients is directed by growth factor signaling. Although either glucose or glutamine can potentially support mitochondrial tricarboxylic acid (TCA) cycle integrity and ATP production, we found that glucose deprivation led to a marked reduction in glutamine uptake and progressive cellular atrophy in multiple mammalian cell types. Despite the continuous presence of growth factor and an abundant supply of extracellular glutamine, interleukin-3 (IL-3)-dependent cells were unable to maintain TCA cycle metabolite pools or receptor-dependent signal transduction when deprived of glucose. This was due at least in part to down-regulation of IL-3 receptor α (IL-3Rα) surface expression in the absence of glucose. Treatment of glucose-starved cells with N-acetylglucosamine (GlcNAc) to maintain hexosamine biosynthesis restored mitochondrial metabolism and cell growth by promoting IL-3-dependent glutamine uptake and metabolism. Thus, glucose metabolism through the hexosamine biosynthetic pathway is required to sustain sufficient growth factor signaling and glutamine uptake to support cell growth and survival.     

Combined (1)H and (31)P spectroscopy provides new insights into the pathobiochemistry of brain damage in multiple sclerosis

¹H MRSI has evolved as an important tool to study the onset and progression of brain damage in multiple sclerosis. Abnormal increases in total creatine, total choline and myoinositol have been noted in multiple sclerosis. However, the pathobiochemical mechanisms related to these changes are still largely unclear. The combination of ¹H MRSI and ¹H‐decoupled ³¹P MRSI can specify to what extent phosphorylated components of total creatine and total choline contribute to this increase. Combined ¹H and ³¹P MRSI data were obtained at 3 T in 22 patients with multiple sclerosis and in 23 healthy controls, and aligned with structural MRI to allow for correction for partial volume effects caused by cerebrospinal fluid and lesion load. A significant increase in total creatine was found in multiple sclerosis, and this was attributed to equal changes in the phosphorylated and unphosphorylated components. The concentrations of the putative glial markers total creatine and myoinositol in lesion‐free ¹H MRSI voxels correlated with the global lesion load. We conclude that changes in total creatine are not related to altered energy metabolism, but rather indicate gliosis. Together with the increase in myoinositol, total creatine can be considered as a biomarker for disease severity. A significant total choline increase was mainly a result of choline components not visible by ³¹P MRS. The origin of this residual choline fraction remains to be investigated. Copyright © 2010 John Wiley & Sons, Ltd.     

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.     

Neurochemical changes in the rat prefrontal cortex following acute phencyclidine treatment: an in vivo localized 1H MRS study

Acute phencyclidine (PCP) administration mimics some aspects of schizophrenia in rats, such as behavioral alterations, increased dopaminergic activity and prefrontal cortex dysfunction. In this study, we used single‐voxel ¹H‐MRS to investigate neurochemical changes in rat prefrontal cortex in vivo before and after an acute injection of PCP. A short‐echo time sequence (STEAM) was used to acquire spectra in a 32‐µL voxel positioned in the prefrontal cortex area of 12 rats anesthetized with isoflurane. Data were acquired for 30 min before and for 140 min after a bolus of PCP (10 mg/kg, n = 6) or saline (n = 6). Metabolites were quantified with the LCModel. Time courses for 14 metabolites were obtained with a temporal resolution of 10 min. The glutamine/glutamate ratio was significantly increased after PCP injection (p < 0.0001, pre‐ vs. post‐injection), while the total concentration of these two metabolites remained constant. Glucose was transiently increased (+70%) while lactate decreased after the injection (both p < 0.0001). Lactate, but not glucose and glutamine, returned to baseline levels after 140 min. These results show that an acute injection of PCP leads to changes in glutamate and glutamine concentrations, similar to what has been observed in schizophrenic patients, and after ketamine administration in humans. MRS studies of this pharmacological rat model may be useful for assessing the effects of potential anti‐psychotic drugs in vivo. Copyright © 2009 John Wiley & Sons, Ltd.