Spectral simplification for resolved glutamate and glutamine measurement using a standard STEAM sequence with optimized timing parameters at 3, 4, 4.7, 7, and 9.4T.

The C4 multiplet proton resonances of glutamate (Glu) around 2.35 ppm and glutamine (Gln) around 2.45 ppm usually overlap in MR spectra, particularly at low- and mid-field strengths (1.5-4.7T). A spectral simplification approach is introduced that provides unobstructed Glu and Gln measurement using a standard STEAM localization sequence with optimized interpulse timings. The underlying idea is to exploit the dependence of response of a coupled spin system on the echo time (TE) and mixing time (TM) to find an optimum timing set (TE, TM), at which the outer-wings of C4 "pseudo-triplet" proton resonances of Glu and Gln are significantly suppressed while the central peaks are maintained. The spectral overlap is thus resolved as the overlap exists exclusively at the outer-wings and the central peaks are readily separated due to the approximate 0.1-ppm difference in chemical shift. Density matrix simulation for Glu, Gln, and other overlapping metabolites at 2.3-2.5 ppm was conducted to predict the optimum timing sets. The simulated, phantom, and in vivo results demonstrated that the C4 multiplet proton resonances of Glu and Gln can be resolved for unobstructed detection at 3T, 4T, and 4.7T. For simplicity, only simulated data are illustrated at 7T and 9.4T.     

Diffusion imaging of the human brain in vivo using high-speed STEAM MRI.

This paper describes a new method for diffusion imaging of the human brain in vivo that is based on a combination of diffusion-encoding gradients with high-speed STEAM MR imaging. The single-shot sequence 90 degrees-TE/2-90 degrees-TM-(alpha-TE/2-STE)n generates n = 32-64 differently phase-encoded stimulated echoes STE yielding image acquisition times of 576 ms for a 48 x 128 data matrix. Diffusion encoding is performed during the first TE/2-interval as well as during each readout period. Phantom studies reveal a quantitative agreement of calculated diffusion coefficients with literature values. EKG triggering completely eliminates motion artifacts from diffusion-weighted single-shot STEAM images of human brain in vivo. While signal attenuation of the cerebrospinal fluid (CSF) is predominantly due to flow, that observed for gray and white matter results from diffusion. Evaluated diffusion coefficients yield (1.0 +/- 0.1) x 10(-5) cm2 s-1 for gray matter, (0.5 +/- 0.1) x 10(-5) cm2 s-1 for white matter with the diffusion encoding parallel to the main orientation of the myelin sheath of the neurofibrils, and (0.3 +/- 0.1) x 10(-5) cm2 s-1 for white matter and a perpendicular orientation. All studies were performed at 2.0 T using a conventional 10 mT m-1 gradient system.     

Very short echo time improves the precision of glutamate detection at 3T in 1H magnetic resonance spectroscopy

Purpose:

To examine the precision of glutamate detection using a very short echo time (TE) phase rotation STEAM (PR‐STEAM) sequence.

Materials and Methods:

Spectrosopic data were acquired from the anterior cingulate gyrus in nine healthy adults using 6.5‐msec TE PR‐STEAM, 40‐msec TE PRESS, 72‐msec TE STEAM, and TE‐Averaging with an effective TE of 105 msec on a clinical 3T magnetic resonance imaging (MRI) system. All data were quantified using LCModel and reported as ratios relative to total creatine.

Results:

Glutamate Cramer‐Rao lower bounds were less than 8% for all sequences. The 6.5‐msec TE PR‐STEAM identified glutamate with the greatest precision (coefficient of variation [CV] of 7.1%), followed by TE‐Averaging (CV of 8.9%), 40‐msec TE PRESS (CV of 11.9%), and 72‐msec TE STEAM (CV of 13.8%).

Conclusion:

In the absence of spectral editing, glutamate is best detected in the human brain at 3T using very short TEs. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.     

Coupling effects in volume selective 1H spectroscopy of major brain metabolites.

The effect of PRESS and STEAM sequences on the spectra of coupled substances are discussed using the examples of weakly coupled AX and A2X systems. Maximum differences compared to uncoupled spins occur if the RF pulses are applied to antiphase magnetization. In this case, the spin echo of the PRESS experiment shows a modified dependence on the refocusing flip angle, which may lead to an attenuation of the acquired signal. In STEAM spectroscopy the evolution within the middle interval tm is dominated by zero quantum coherences and longitudinal polarization, whose maximum efficiencies are 25 and 12.5%, respectively. Zero quantum coherences may lead to strong modulations when the tm value is varied. The effects on the spectra of important coupled metabolites of the human brain such as glutamate, GABA, inositol, and particularly lactate, are demonstrated. The observed modulations seem to make the quantification of the spectra rather difficult at echo times above 50 ms.     

Cerebral glucose is detectable by localized proton NMR spectroscopy in normal rat brain in vivo.

This contribution reports the first direct and noninvasive observation of cerebral glucose in normal anesthetized rats (n = 16) using short-echo-time localized proton NMR spectroscopy (2.35 T, STEAM, TR = 6000 ms, TE = 20 ms, 125 microliters). In addition to resonances from N-acetyl aspartate (NAA), glutamate, total creatine, cholines, taurine, and myoinositol, all spectra exhibit strongly coupled resonances from glucose (3.43, 3.80 ppm) that are readily identifiable using model solutions. The observed level of cerebral glucose in fasted rats covered a range of 15-40% of that of NAA giving absolute concentrations of 1.1-2.8 mM when NAA is taken to be 7 mM. The arterial blood glucose concentration was 7.7 +/- 0.8 mM in the same group of animals.     

Quantification of vitamin C in the rat brain in vivo using short echo-time 1H MRS.

Both ultrashort echo-time STEAM and MEGA-PRESS-edited spectroscopy were used to validate noninvasive quantification of vitamin C (ascorbate) in the developing rat brain, where changes in ascorbate concentration have been reported. Despite strong overlap with resonances from glutamine, glutamate, glutathione, and macromolecules, reliable quantification of ascorbate (Cramer-Rao lower bounds<0.2 micromol/g) by LCModel analysis of STEAM (TE=2 ms) spectra was possible at 9.4 T. Ascorbate concentrations quantified from the STEAM spectra were in very good agreement with concentrations calculated from fully resolved ascorbate resonances in MEGA-PRESS-edited spectra measured from identical volumes of interest. Ascorbate concentrations measured using STEAM decreased with increasing postnatal rat age, in agreement with published brain ascorbate concentrations measured in vitro using high-performance liquid chromatography (HPLC).     

High-resolution fMRI using multislice partial k-space GR-EPI with cubic voxels.

The premises of this work are: 1) the limit of spatial resolution in fMRI is determined by anatomy of the microcirculation; 2) because of cortical gray matter tortuosity, fMRI experiments should (in principle) be carried out using cubic voxels; and 3) the noise in fMRI experiments is dominated by low-frequency BOLD fluctuations that are a consequence of spontaneous neuronal events and are pixel-wise dependent. A new model is proposed for fMRI contrast which predicts that the contrast-to-noise ratio (CNR) tends to be independent of voxel dimensions (in the absence of partial voluming of activated tissue), TE, and scanner bandwidth. These predictions have been tested at 3 T, and results support the model. Scatter plots of fMRI signal intensities and low-frequency fluctuations for activated pixels in a finger-tapping paradigm demonstrated a linear relationship between signal and noise that was independent of TE. The R(2) value was about 0.9 across eight subjects studied. The CNR tended to be constant across pixels within a subject but varied across subjects: CNR = 3.2 +/- 1.0. fMRI statistics at 20- and 40-ms TE values were indistinguishable, and TE values as short as 10 ms were used successfully. Robust fMRI data were obtained across all subjects using 1 x 1 x 1 mm(3) cubic voxels with 10 contiguous slices, although 1.5 x 1.5 x 1.5 mm(3) was found to be optimum. Magn Reson Med 46:114-125, 2001.     

Measurement of GABA and contaminants in gray and white matter in human brain in vivo.

A preliminary study of discrimination between GABA and macromolecules (MMs) in human brain by proton double quantum filtering (DQF) at 3.0 T in vivo is presented. GABA-tuned and MM-tuned DQ filters were designed with dual-band 180 degrees radiofrequency (RF) pulses that were tuned for selective refocusing of GABA (3.0 and 1.9 ppm) and putative MM resonances (3.0 and 1.7 ppm), respectively. GABA and putative MM signals were extracted from a combined analysis of the filtered mixture signals and the calculated editing yields. Unexpectedly, the GABA and putative MM signals exhibited a similar doublet linewidth at the optimized TE = 82 ms. Furthermore, substantial MM-tuned DQF signal remained at TE = 148 ms, indicating the presence of a component other than MM. With water segmentation data, the GABA-tuned and MM-tuned DQF measures from the medial prefrontal and left frontal lobes were combined to give the concentrations of GABA and the additional component as 1.1 +/- 0.1 and 0.8 +/- 0.1 mM (mean +/- SD, N=3) for gray matter (GM) and 0.4 +/- 0.1 and 0.7+/-0.1 mM (N=3) for white matter (WM), respectively.     

Human brain-structure resolved T(2) relaxation times of proton metabolites at 3 Tesla.

The transverse relaxation times, T(2), of N-acetylaspartate (NAA), total choline (Cho), and creatine (Cr) obtained at 3T in several human brain regions of eight healthy volunteers are reported. They were obtained simultaneously in 320 voxels with three-dimensional (3D) proton MR spectroscopy ((1)H-MRS) at 1 cm(3) spatial resolution. A two-point protocol, optimized for the least error per given time by adjusting both the echo delay (TE(i)) and number of averages, N(i), at each point, was used. Eight healthy subjects (four males and four females, age = 26 +/- 2 years) underwent the hour-long procedure of four 15-min, 3D acquisitions (TE(1) = 35 ms, N(1) = 1; and TE(2) = 285 ms, N(2) = 3). The results reveal that across all subjects the NAA and Cr T(2)s in gray matter (GM) structures (226 +/- 17 and 137 +/- 12 ms, respectively) were 13-17% shorter than the corresponding T(2)s in white matter (WM; 264 +/- 10 and 155 +/- 7 ms, respectively). The T(2)s of Cho did not differ between GM and WM (207 +/- 17 and 202 +/- 8, respectively). For the purpose of metabolic quantification, these values justify to within +/-10% the previous use of one T(2) per metabolite for 1) the entire brain and 2) all subjects. These T(2) values (which to our knowledge were obtained for the first time at this field, spatial resolution, coverage, and precision) are essential for reliable absolute metabolic quantification.     

Short‐echo,single‐shot,full‐intensity proton magnetic resonance spectroscopy for neurochemical profiling at 4 T: Validation in the cerebellum and brainstem

A short echo time (TE = 24 ms) semiadiabatic localization by adiabatic selective refocusing (LASER) sequence was designed and optimized for full‐intensity proton magnetic resonance spectroscopy (¹H MRS) at 4 T. The sequence was combined with VAPOR water suppression and three‐dimensional outer volume suppression for improved localization and suppression of unwanted coherences. Artifact‐free, single‐shot spectra were obtained from the human brain with a spectral pattern almost identical to that obtained with an ultra‐short TE (TE = 5 ms) stimulated‐echo acquisition mode (STEAM) sequence as a result of the train of adiabatic refocusing pulses in semi‐LASER that reduce the apparent TE. Approximately 2‐fold higher signal intensity relative to STEAM was demonstrated in phantoms and the human brain. To test the performance of the sequence in clinically relevant brain regions with a volume coil, semi‐LASER spectra were acquired from three cerebellar and brainstem volumes of interest (VOIs) in 23 healthy subjects. Ultra‐short echo STEAM spectra were acquired from the same VOIs to compare neurochemical profiles obtained with semi‐LASER with those obtained with STEAM. Neurochemical profiles of the cerebellum and brainstem acquired by these two techniques were nearly identical, validating the accuracy of the metabolite concentrations obtained with semi‐LASER at the longer TE relative to STEAM. A high correlation between metabolite concentrations obtained by these two proton ¹H MRS techniques indicated the sensitivity to detect intersubject variation in metabolite levels. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Reduced power magnetic resonance spectroscopic imaging of the prostate at 4.0 Tesla

Proton magnetic resonance spectroscopic imaging (MRSI) of the prostate has been described at 1.5 T and 3 T as a means of localizing prostate cancers with high sensitivity and specificity. This technique could be improved by increasing the field strength further; however, it has not been described in detail above 3 T. To address the increase in B₁ and SAR at high field strengths, a new protocol is described for reduced power STEAM MRSI of the prostate at 4.0 Tesla, using a pelvic surface coil array for RF transmission and reception, and a solid, reusable endorectal coil for reception only. The optimal STEAM sequence timing parameters for observation of the strongly coupled citrate spin system were determined through simulation to be echo time (TE) = 27 ms and mixing time (TM) = 27 ms, and the results were verified in vitro. Power reduction was achieved by applying the VERSE method to each of the three slice selective pulses in the STEAM sequence, and the B₁max and SAR were reduced by 43% and 36%, respectively. Finally, in vivo spectroscopic imaging data were acquired from a prostate cancer patient, demonstrating the detection of citrate, choline, and creatine with 0.37 cc nominal resolution in a 10 minute scan. Magn Reson Med 61:273–281, 2009. © 2009 Wiley‐Liss, Inc.     

A new multiple quantum filter design procedure for use on strongly coupled spin systems found in vivo: Its application to glutamate

A numerical procedure is outlined that is appropriate for the design of multiple quantum filter sequences targeted for the strongly coupled, multiple spin systems that occur in metabolites present in brain. The procedure uses numerical methods of solution of the density matrix equations, first, to establish the most appropriate resonance to target with the filter; second, to provide contour plots of a performance index of the filter in terms of critical sequence parameters; and third, to produce the response signals of the target and the background metabolites to the optimized filter. The procedure is exemplified for the AMNPQ spin system of the amino acid glutamate at a field strength of 3 T. The 2.3 ppm peak of the PQ multiplet of glutamate was identified as the target resonance, and the performance of the filter so derived was evaluated experimentally on phantom solutions and in human brain. These experiments clearly demonstrate that a linewidth of £4 Hz is required for full resolution of glutamate from glutamine at 3 T using this double quantum filter. Nevertheless, even at a linewidth of ?7 Hz in vivo, the 2.3 ppm peak of glutamate dominates the filter response and thereby removes a significant cause of uncertainty in measuring changes in glutamate by eliminating most of the background observed in unedited spectra obtained using PRESS or STEAM.     

Comparative reliability of proton spectroscopy techniques designed to improve detection of J‐coupled metabolites

Improved detection of J‐coupled neurometabolites through the use of modified proton magnetic resonance spectroscopy (1H‐MRS) techniques has recently been reported. TE‐averaged point‐resolved spectroscopy (PRESS) uses the J modulation effects by averaging FIDs with differing echo times to improve detection of glutamate, while standard PRESS detection of glutamate can be improved by using an appropriate single echo determined from J‐modulation simulations. In the present study, the reliabilities of TE‐averaged PRESS, standard PRESS with TE = 40 ms, and standard PRESS with TE = 30 ms in detecting metabolite levels in the cingulate gyrus of the human brain at 3T were compared in six subjects. TE‐averaged PRESS measures showed a mean variability of 9% for N‐acetyl aspartate, choline, and creatine, compared with < 4% for the 30‐ and 40‐ms PRESS techniques. The coefficients of variation for glutamate were 10%, 7%, and 5% for TE‐averaged, 30‐ms, and 40‐ms PRESS, respectively. PRESS with a TE of 40 ms also demonstrated improved reliability for GABA and glutamine concentrations. These results show that with the appropriate selection of echo time standard PRESS can be a reliable ¹H‐MRS technique for the measurement of J‐coupled neurometabolites in the human brain and, moreover, compares favorably with at least one J‐edited technique. Magn Reson Med 60:964–969, 2008. © 2008 Wiley‐Liss, Inc.     

Interindividual reproducibility of glutamate quantification using 1.5-T proton magnetic resonance spectroscopy.

The goal of this study was to measure the interindividual reproducibility of glutamate quantification in 1.5-T (1)H MRS of human brains. To determine the effective echo time (TE) for glutamate quantification, spectra from a phantom and 12 participants were obtained with TE = 30, 35, 40, and 144 ms (repetition time (TR) = 2000 ms and volume of interest = 4 cm(3)). The average Cramer-Rao lower bounds for glutamate quantification using LCModel was lowest in two experiments when TE = 40 ms.Twenty-one subjects participated in experiments that measured interindividual reproducibility of glutamate quantification. Spectra were acquired with TR = 6000 ms and TE = 40 ms. Results showed that the coefficients of variance were 11.0 and 13.1% in the anterior cingulate cortex and insula, respectively. This suggests that glutamate can be reproducibly measured from 1.5-T (1)H MRS with long TR, effective TE, and the LCModel.     

Localized 1H NMR spectra of glutamate in the human brain.

Localized 1H NMR spectra at TE = 12 ms were obtained from cerebral cortex of human subjects using ISIS with surface suppression. The 2.29-ppm resonance was assigned to C4 glutamate with contributions from C4 glutamine and GABA using in vivo spectral editing and comparison of chemical shift with pure compounds. The measured intensity ratio between the 2.29 resonance and the creatine resonance at 3.03 ppm was in good agreement with the ratio predicted from previously reported measurements of glutamate, glutamine, and GABA concentrations in biopsied human brain tissue.     

头颈部良性神经源性肿瘤1H MRS的表现特点

目的：探讨头颈部良性神经源性肿瘤在单体素^1H MRS上的表现特点。材料和方法：共收集经单体素。HMRS检查，并经手术病理证实的头颈部神经源性肿瘤14例（神经鞘瘤11例，神经纤维瘤2例，颈动脉体瘤1例）。采用点分析波谱法（PRESS：TE=144ms，14例）和激励回波法（STEAM：TE=30ms，11例）进行。HMRS空间定位，以胆碱和脂质代谢物为标准评价所有肿瘤。波谱图上，胆碱和脂质分别在3．2ppm和0．9—1．4ppm区域识别。结果：采用PRESS后，14例神经源性肿瘤中检测出胆碱代谢物者11例，检出脂质代谢物者6例。胆碱和脂质代谢物同时检出者5例，仅检出胆碱者6例，仅检出脂质者1例，胆碱和脂质均未检出者2例。采用STEAM后，11例肿瘤中检出胆碱代谢物和脂质者分别为3例和8例。结论：头颈部良性神经源性肿瘤的单体素。HMRS表现具有多样性，多数肿瘤以长TEPRESS上胆碱峰的显示为特点，长TEPRESS能较STEAM更好地检出良性神经源性肿瘤内的胆碱代谢物。     

Effect of PRESS and STEAM sequences on magnetic resonance spectroscopic liver fat quantification

Purpose

To compare PRESS and STEAM MR spectroscopy for assessment of liver fat in human subjects.

Materials and Methods

Single‐voxel (20 × 20 × 20 mm) PRESS and STEAM spectra were obtained at 1.5T in 49 human subjects with known or suspected fatty liver disease. PRESS and STEAM sequences were obtained with fixed TR (1500 msec) and different TE (five PRESS spectra between TE 30‐70 msec, five STEAM spectra between TE 20–60 msec). Spectra were quantified and T2 and T2‐corrected peak area were calculated by different techniques. The values were compared for PRESS and STEAM.

Results

Water T2 values from PRESS and STEAM were not significantly different (P = 0.33). Fat peak T2s were 25%–50% shorter on PRESS than on STEAM (P < 0.02 for all comparisons) and there was no correlation between T2s of individual peaks. PRESS systematically overestimated the relative fat peak areas (by 7%–263%) compared to STEAM (P < 0.005 for all comparisons). The peak area given by PRESS was more dependent on the T2‐correction technique than STEAM.

Conclusion

Measured liver fat depends on the MRS sequence used. Compared to STEAM, PRESS underestimates T2 values of fat, overestimates fat fraction, and provides a less consistent fat fraction estimate, probably due to J coupling effects. J. Magn. Reson. Imaging 2009;30:145–152. © 2009 Wiley‐Liss, Inc.     

High-speed STEAM MRI of the human heart.

High-speed STEAM MR images of the normal human heart were obtained from single cardiac cycles using a 2.0-T whole-body system equipped with conventional 10 mT m-1 gradients. The single-shot 90 degrees-TE/2-90 degrees-TM-(alpha-TE/2-Acq)n pulse sequence acquires n differently phase-encoded stimulated echoes. Measuring times of 127-254 ms were achieved using a "repetition time" of 3.96 ms in conjunction with data matrices of 32-64 x 128 pixels covering a field-of-view of 250-350 mm. The sequence provides easy access to anatomical short-axis and long-axis views of the heart by single and double oblique rotation of the image orientation. STEAM images resemble the features of spin-echo images with respect to chemical shifts, susceptibilities, and flow. Thus, no additional techniques are required for the suppression of blood signals. EKG-triggered acquisitions demonstrate that slice-selective STEAM sequences using short TM intervals allow an unambiguous delineation of those parts of the myocardium that remain stationary within the selected plane throughout the entire imaging process. Neither spins leaving nor entering the slice defined by the initial 90 degrees RF pulses give rise to a stimulated echo and therefore do not contribute to the resulting image.     

Metabolite and water apparent diffusion coefficients in the isolated rat heart: effects of ischemia.

A decrease in the apparent diffusion coefficient (ADC) of water is important in the detection of acute brain disorders, yet it is unknown whether changes in myocardial ADCs hold similar potential. Consequently, in this study a STEAM pulse sequence was modified in order to measure the ADCs of water and the (1)H-NMR detectable metabolites, taurine (an inert marker) and creatine, during perfusion, ischemia, and reperfusion in the isolated rat heart. At the short diffusion time of 50 ms, myocardial ADCs were (1.06 +/- 0. 07) x 10(-3) mm(2)/s for water, (0.29 +/- 0.01) x 10(-3) mm(2)/s for taurine and (0.26 +/- 0.01) x 10(-3) mm(2)/s for creatine. Heart water and taurine ADCs remained constant during ischemia, yet the total creatine ADC increased by 35% owing to the hydrolysis of PCr to creatine. The average cardiomyocyte diameter, calculated from taurine ADC values measured at diffusion times between 50 ms and 1510 ms, was 40 microm in the perfused heart and 27 microm by the end of ischemia. It is concluded that the taurine ADC measured at short diffusion times does not reveal ischemic injury in the heart, but at long diffusion times may be used to calculate changes in myocyte diameter. Magn Reson Med 44:208-214, 2000.     

In vivo localized 1H MR spectroscopy of rat testes: stimulated echo acquisition mode (STEAM) combined with short TI inversion recovery (STIR) improves the detection of metabolite signals.

A noninvasive NMR technique for evaluating testicular function was explored in this study. Localized in vivo 1H NMR spectroscopy was performed on rat testes using a stimulated echo acquisition mode (STEAM) sequence with a short echo time (TE). In the 1H spectra, large lipid signals dominated the chemical shift range of 0.89-2.78 ppm, which prevented the observation of metabolite signals in this region. To suppress these lipid signals, short inversion time (TI) inversion recovery (STIR) was combined with STEAM (STIR-STEAM). The optimal TI was typically 320 ms. STIR-STEAM with a TE of 15 ms allowed successful suppression of the lipid signals and the sensitive detection of several new metabolite signals. In normal testes, choline, creatine, glutamate, and glycine signals were identified. In addition to these metabolites, a lactate signal was observed in ischemic testes. To our knowledge, the signals of glutamate, glycine, and lactate have not been previously assigned in 1H MR spectra of testes in vivo. Lipid suppression by STIR aided in the detection of these metabolites, which would otherwise have been masked by the lipid signals.