Correcting frequency and phase offsets in MRS data using robust spectral registration

An algorithm for retrospective correction of frequency and phase offsets in MRS data is presented. The algorithm, termed robust spectral registration (rSR), contains a set of subroutines designed to robustly align individual transients in a given dataset even in cases of significant frequency and phase offsets or unstable lipid contamination and residual water signals. Data acquired by complex multiplexed editing approaches with distinct subspectral profiles are also accurately aligned. Automated removal of unstable lipid contamination and residual water signals is applied first, when needed. Frequency and phase offsets are corrected in the time domain by aligning each transient to a weighted average reference in a statistically optimal order using nonlinear least‐squares optimization. The alignment of subspectra in edited datasets is performed using an approach that specifically targets subtraction artifacts in the frequency domain. Weighted averaging is then used for signal averaging to down‐weight poorer‐quality transients. Algorithm performance was assessed on one simulated and 67 in vivo pediatric GABA‐/GSH‐edited HERMES datasets and compared with the performance of a multistep correction method previously developed for aligning HERMES data. The performance of the novel approach was quantitatively assessed by comparing the estimated frequency/phase offsets against the known values for the simulated dataset or by examining the presence of subtraction artifacts in the in vivo data. Spectral quality was improved following robust alignment, especially in cases of significant spectral distortion. rSR reduced more subtraction artifacts than the multistep method in 64% of the GABA difference spectra and 75% of the GSH difference spectra. rSR overcomes the major challenges of frequency and phase correction.     

Hadamard editing of glutathione and macromolecule‐suppressed GABA

The primary inhibitory neurotransmitter γ‐aminobutyric acid (GABA) and the major antioxidant glutathione (GSH) are compounds of high importance for the function and integrity of the human brain. In this study, a method for simultaneous J‐difference spectral‐edited magnetic resonance spectroscopy (MRS) of GSH and GABA with suppression of macromolecular (MM) signals at 3 T is proposed. MM‐suppressed Hadamard encoding and reconstruction of MEGA (Mescher–Garwood)‐edited spectroscopy (HERMES) consists of four sub‐experiments (TE = 80 ms), with 20‐ms editing pulses applied at: (A) 4.56 and 1.9 ppm; (B) 4.56 and 1.5 ppm; (C) 1.9 ppm; and (D) 1.5 ppm. One Hadamard combination (A + B – C – D) yields GSH‐edited spectra, and another (A – B + C – D) yields GABA‐edited spectra, with symmetric suppression of the co‐edited MM signal. MM‐suppressed HERMES, conventional HERMES and separate Mescher–Garwood point‐resolved spectroscopy (MEGA‐PRESS) data were successfully acquired from a (33 mm)³ voxel in the parietal lobe in 10 healthy subjects. GSH‐ and GABA‐edited MM‐suppressed HERMES spectra were in close agreement with the respective MEGA‐PRESS spectra. Mean GABA (and GSH) estimates were 1.10 ± 0.15 i.u. (0.59 ± 0.12 i.u.) for MM‐suppressed HERMES, and 1.13 ± 0.09 i.u. (0.66 ± 0.09 i.u.) for MEGA‐PRESS. Mean GABA (and GSH) differences between MM‐suppressed HERMES and MEGA‐PRESS were –0.03 ± 0.11 i.u. (–0.07 ± 0.11 i.u.). The mean signal‐to‐noise ratio (SNR) improvement of MM‐suppressed HERMES over MEGA‐PRESS was 1.45 ± 0.25 for GABA and 1.32 ± 0.24 for GSH. These results indicate that symmetric suppression of the MM signal can be accommodated into the Hadamard editing framework. Compared with sequential single‐metabolite MEGA‐PRESS experiments, MM‐suppressed HERMES allows for simultaneous edited measurements of GSH and GABA without MM contamination in only half the scan time, and SNR is maintained.     

MRS双量子相干滤波技术在体检测GABA和GSH的研究现状

目的：γ-氨基丁酸（GABA）是维持正常脑功能的一种重要的抑制性神经递质。谷胱甘肽（GSH）是主要的抗氧化剂同时对活性氧分子的解毒起到重要作用。本文综述了双量子相干滤波脉冲序列技术在体检测GABA和GSH的最新研究进展。方法：磁共振频谱（MRS）技术非介入在体检测脑内代谢物是一种无损检测的方法。同时利用磁共振扫描仪的点分辨自旋回波（PRESS）定位方法,结合双量子相干滤波技术对γ-氨基丁酸（GABA）和谷胱甘肽（GSH）浓度进行在体检测。结果：GABA和GSH在人体的相对浓度很低以及与其他信号的重叠,用传统的技术很难检测到。实验证明经过优化的双量子相干方法可以在单次激发中鲁棒性地抑制其它信号（如胆碱、肌酸和天门冬氨酸）,更好地获得GABA和GSH检测信号。结论：本文描述了多量子滤波（MQF）技术和双量子相干（DQC）滤波机制,从定位序列及读出脉冲设计、滤波梯度校准、相位校准三个方面,综述了DQC滤波脉冲序列技术最新研究进展。同时,探讨了双量子滤波方法在临床上的应用,还展望了MRS中双量子相干滤波技术在临床医学的发展方向。     

Sensitivity and specificity of human brain glutathione concentrations measured using short‐TE 1H MRS at 7 T

Although the MR editing techniques that have traditionally been used for the measurement of glutathione (GSH) concentrations in vivo address the problem of spectral overlap, they suffer detriments associated with inherently long TEs. The purpose of this study was to characterize the sensitivity and specificity for the quantification of GSH concentrations without editing at short TE. The approach was to measure synthetically generated changes in GSH concentrations from in vivo stimulated echo acquisition mode (STEAM) spectra after in vitro GSH spectra had been added to or subtracted from them. Spectra from five test subjects were synthetically altered to mimic changes in the GSH signal. To account for different background noise between measurements, retest spectra (from the same individuals as used to generate the altered data) and spectra from five other individuals were compared with the synthetically altered spectra to investigate the reliability of the quantification of GSH concentration. Using STEAM spectroscopy at 7 T, GSH concentration differences on the order of 20% were detected between test and retest studies, as well as between differing populations in a small sample (n = 5) with high accuracy (R² > 0.99) and certainty (p ≤ 0.01). Both increases and decreases in GSH concentration were reliably quantified with small impact on the quantification of ascorbate and γ‐aminobutyric acid. These results show the feasibility of using short‐TE ¹H MRS to measure biologically relevant changes and differences in human brain GSH concentration. Although these outcomes are specific to the experimental approach used and the spectral quality achieved, this study serves as a template for the analogous scrutiny of quantification reliability for other compounds, methodologies and spectral qualities. Copyright © 2016 John Wiley & Sons, Ltd.     

Elevated levels of GABA+ in migraine detected using 1H‐MRS

γ‐Aminobutyric acid (GABA) has been implicated in several pain conditions, yet no study has systematically evaluated GABA levels in migraine using ¹H‐MRS. The accurate detection, separation and quantification of GABA in individuals with migraine could elucidate the role of this neurotransmitter in migraine pathophysiology. Such information may eventually be useful in the diagnosis and development of more effective treatments for migraine. The aims of this study were therefore to compare the concentration of GABA+ in individuals with migraine with that in asymptomatic individuals, and to determine the diagnostic potential of GABA+ in the classification of those with or without migraine. In this case–control study, GABA+ levels in the brain were determined in 19 participants with migraine and 19 matched controls by ¹H‐MRS using Mescher–Garwood point‐resolved spectroscopy (MEGA‐PRESS) sequence. The diagnostic accuracy of GABA+ for the detection of migraine and the optimal cut‐off value were determined by receiver operating characteristic analysis. GABA+ levels were significantly higher (p = 0.002) in those with migraine [median, 1.41 institutional units (IU); interquartile range, 1.31–1.50 IU] than in controls (median, 1.18 IU; interquartile range, 1.12–1.35 IU). The GABA+ concentration appears to have good accuracy for the classification of individuals with or without migraine [area under the curve (95% confidence interval), 0.837 (0.71–0.96); p < 0.001]. The optimal GABA+ cut‐off value for migraine was 1.30 IU, with a sensitivity of 84.2%, specificity of 68.4% and positive likelihood ratio of +2.67. The outcomes of this study suggest altered GABA metabolism in migraine. These results add to the scarce evidence on the putative role of GABA in migraine and provide a basis to further explore the causal relationship between GABA+ and the pathophysiology of migraine. This study also demonstrates that GABA+ concentration has good diagnostic accuracy for migraine. These findings offer new research and practice directions for migraine diagnosis. Copyright © 2015 John Wiley & Sons, Ltd.     

In situ postmortem ethanol quantification in the cerebrospinal fluid by non‐water‐suppressed proton MRS

Determination of the ethanol concentration in corpses with MRS would allow a reproducible forensic assessment by which evidence is collected in a noninvasive manner. However, although MRS has been successfully used to detect ethanol in vivo, it has not been applied to postmortem ethanol quantification in situ. The present study examined the feasibility of the noninvasive measurement of the ethanol concentration in human corpses with MRS. A total of 15 corpses with suspected alcohol consumption before demise underwent examination in a 3 T whole body scanner. To address the partial overlap of the ethanol and lactate signal in the postmortem spectrum, non‐water‐suppressed single voxel spectra were recorded in the cerebrospinal fluid (CSF) of the left lateral ventricle via the metabolite cycling technique. The ethanol signals were quantified using the internal water as reference standard, as well as based on a reference signal acquired in a phantom. The measured values were compared with biochemically determined concentrations in the blood (BAC) and CSF (CSFAC). In 8 of the 15 corpses a BAC above zero was determined (range 0.03–1.68 g/kg). In all of these 8 corpses, ethanol was measured in CSF with the proposed MRS protocol. The two applied MRS calibration strategies resulted in similar concentrations. However, the MRS measurements generally overestimated the ethanol concentration by 0.09 g/kg (4%) to 0.72 g/kg (45%) as compared with the CSFAC value. The presented MRS protocol allows the measurement of ethanol in the CSF in human corpses and provides an estimation of the ethanol concentration prior to autopsy. Observed deviations from biochemically determined concentrations are mainly explained by the approximate correction of the relaxation attenuation of the ethanol signal.     

Simultaneous detection of glutathione and lactate using spectral editing at 3 T

Two spectral editing techniques for the simultaneous detection of glutathione (GSH) and lactate (Lac) in the human brain at 3 T are described and evaluated. These methods, ‘sMEGA’ (sinc‐MEscher and GArwood) and ‘DEW’ (Double Editing With), were optimized to detect GSH and Lac simultaneously at 3 T using density‐matrix simulations and validation in phantoms. Simulations to test for co‐edited metabolites within the detected GSH region of the spectrum were also performed. In vivo data were acquired in the midline parietal region of seven subjects using both methods, and compared with conventional MEGA‐PRESS (MEscher and GArwood‐Point RESolved Spectroscopy) acquisitions of GSH and Lac. Simulations and phantom experiments showed that sMEGA and DEW had a high editing efficiency for both GSH and Lac. In the phantom, the editing efficiency of GSH was >88% relative to a conventional GSH MEGA‐PRESS acquisition, whereas, for Lac, the editing efficiency was >95% relative to a conventional Lac MEGA‐PRESS acquisition. Simulations also showed that the editing efficiency of both methods was comparable with separate MEGA‐PRESS acquisitions of the same metabolites. In addition, simulations and in vivo spectra showed that, at a TE of 140 ms, there was a partial overlap between creatine (Cr) and GSH peaks, and that N‐acetyl aspartate/N‐acetyl aspartyl glutamate (NAA/NAAG) were sufficiently resolved from GSH. In vivo measurements showed that both sMEGA and DEW edited GSH and Lac reliably with the same editing efficiency as conventional MEGA‐PRESS acquisitions of the same metabolites, with measured GSH integrals of 2.23 ± 0.51, 2.31 ± 0.38, 2.38 ± 0.53 and measured Lac integrals of 1.72 ± 0.67, 1.55 ± 0.35 and 1.53 ± 0.54 for MEGA‐PRESS, DEW and sMEGA, respectively. Simultaneous detection of GSH and Lac using sMEGA and DEW is possible at 3 T with high editing efficiency.     

In vivo detection of intermediate metabolic products of [1-(13) C]ethanol in the brain using (13) C MRS

In this study, in vivo ¹³C MRS was used to investigate the labeling of brain metabolites after intravenous administration of [1‐¹³C]ethanol. After [1‐¹³C]ethanol had been administered systemically to rats, ¹³C labels were detected in glutamate, glutamine and aspartate in the carboxylic and amide carbon spectral region. ¹³C‐labeled bicarbonate HCO (161.0 ppm) was also detected. Saturating acetaldehyde C1 at 207.0 ppm was found to have no effect on the ethanol C1 (57.7 ppm) signal intensity after extensive signal averaging, providing direct in vivo evidence that direct metabolism of alcohol by brain tissue is minimal. To compare the labeling of brain metabolites by ethanol with labeling by glucose, in vivo time course data were acquired during intravenous co‐infusion of [1‐¹³C]ethanol and [¹³C₆]‐D ‐glucose. In contrast with labeling by [¹³C₆]‐D ‐glucose, which produced doublets of carboxylic/amide carbons with a J coupling constant of 51 Hz, the simultaneously detected glutamate and glutamine singlets were labeled by [1‐¹³C]ethanol. As ¹³C labels originating from ethanol enter the brain after being converted into [1‐¹³C]acetate in the liver, and the direct metabolism of ethanol by brain tissue is negligible, it is suggested that orally or intragastrically administered ¹³C‐labeled ethanol may be used to study brain metabolism and glutamatergic neurotransmission in investigations involving alcohol administration. In vivo ¹³C MRS of rat brain following intragastric administration of ¹³C‐labeled ethanol is demonstrated. Published in 2011 by John Wiley & Sons, Ltd.     

2DMRS技术在脑内GABA浓度的定量检测的研究进展

目的：探讨定量检测脑内GABA浓度的方法和研究现状。方法：本文从二维磁共振谱的角度，讨论了二维化学位移相关谱（2DCOSY）、双量子滤波谱（DQF2DMRS）以及J分解谱（J—resolved 2D MRS）研究方法。这三种处理方法所得到的谱图均可反映不同代谢物偶合常数与波峰位置的关系。无论那种类型的谱图，都可通过截取某一特殊位置处的一维谱线得到GABA的浓度。结合研究现状，讨论了上述三种方法的差异。结果和结论：相对于传统IDMRS技术而言，2DMRS技术具有明显的优势，包含更为丰富的信息，这对于准确检测脑内GABA的浓度，甚至临床应用，都具有深远的意义。     

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.     

Quantification of γ‐aminobutyric acid (GABA) in 1H MRS volumes composed heterogeneously of grey and white matter

The quantification of γ‐aminobutyric acid (GABA) concentration using localised MRS suffers from partial volume effects related to differences in the intrinsic concentration of GABA in grey (GM) and white (WM) matter. These differences can be represented as a ratio between intrinsic GABA in GM and WM: r_M. Individual differences in GM tissue volume can therefore potentially drive apparent concentration differences. Here, a quantification method that corrects for these effects is formulated and empirically validated. Quantification using tissue water as an internal concentration reference has been described previously. Partial volume effects attributed to r_M can be accounted for by incorporating into this established method an additional multiplicative correction factor based on measured or literature values of r_M weighted by the proportion of GM and WM within tissue‐segmented MRS volumes. Simulations were performed to test the sensitivity of this correction using different assumptions of r_M taken from previous studies. The tissue correction method was then validated by applying it to an independent dataset of in vivo GABA measurements using an empirically measured value of r_M. It was shown that incorrect assumptions of r_M can lead to overcorrection and inflation of GABA concentration measurements quantified in volumes composed predominantly of WM. For the independent dataset, GABA concentration was linearly related to GM tissue volume when only the water signal was corrected for partial volume effects. Performing a full correction that additionally accounts for partial volume effects ascribed to r_M successfully removed this dependence. With an appropriate assumption of the ratio of intrinsic GABA concentration in GM and WM, GABA measurements can be corrected for partial volume effects, potentially leading to a reduction in between‐participant variance, increased power in statistical tests and better discriminability of true effects.     

Reproducibility and effect of tissue composition on cerebellar γ‐aminobutyric acid (GABA) MRS in an elderly population

MRS provides a valuable tool for the non‐invasive detection of brain γ‐aminobutyric acid (GABA) in vivo. GABAergic dysfunction has been observed in the aging cerebellum. The study of cerebellar GABA changes is of considerable interest in understanding certain age‐related motor disorders. However, little is known about the reproducibility of GABA MRS in an aged population. Therefore, this study aimed to explore the feasibility and reproducibility of GABA MRS in the aged cerebellum at 3.0 T and to examine the effect of differing tissue composition on GABA measurements. MRI and ¹H MRS examinations were performed on 10 healthy elderly volunteers (mean age, 75.2 ± 6.5 years) using a 3.0‐T Siemens Tim Trio scanner. Among them, five subjects were scanned twice to assess the short‐term reproducibility. The MEGA‐PRESS (Mescher–Garwood point‐resolved spectroscopy) J‐editing sequence was used for GABA detection in two volumes of interest (VOIs) in the left and right cerebellar dentate. MRS data processing and quantification were performed with LCModel 6.3‐0L using two separate basis sets, generated from density matrix simulations using published values for chemical shifts and J couplings. Raw metabolite levels from LCModel outputs were corrected for cerebrospinal fluid contamination and relaxation. GABA‐edited spectra yielded robust and stable GABA measurements with averaged intra‐individual coefficients of variation for corrected GABA+ between 4.0 ± 2.8% and 13.4 ± 6.3%, and inter‐individual coefficients of variation between 12.6% and 24.2%. In addition, there was a significant correlation between GABA+ obtained with the two LCModel basis sets. Overall, our results demonstrated the feasibility and reproducibility of cerebellar GABA‐edited MRS at 3.0 T in an elderly population. This information might be helpful for studies using this technique to study GABA changes in normal or diseased aging brain, e.g. for power calculations and the interpretation of longitudinal observations. Copyright © 2015 John Wiley & Sons, Ltd.     

Simultaneous spin‐echo and gradient‐echo BOLD measurements by dynamic MRS

This study aimed to dissociate the intravascular and extravascular contributions to spin‐echo (SE) and gradient‐echo (GE) blood oxygenation level‐dependent (BOLD) signals at 7 T, using dynamic diffusion‐weighted MRS. We simultaneously acquired SE and GE data using a point‐resolved spectroscopy sequence with diffusion weightings of 0, 600, and 1200 s/mm². The BOLD signals were quantified by fitting the free induction decays starting from the SE center to a mono‐exponential decay function. Without diffusion weighting, BOLD signals measured with SE and GE increased by 1.6 ± 0.5% (TE_SE = 40 ms) and 5.2 ± 1.4% (nominal TE_GE = 40 ms) during stimulation, respectively. With diffusion weighting, the BOLD increase during stimulation measured with SE decreased from 1.6 ± 0.5% to 1.3 ± 0.4% (P < 0.001), whereas that measured by GE was unaffected (P > 0.05); the post‐stimulation undershoots in the BOLD signal time courses were largely preserved in both SE and GE measurements. These results demonstrated the feasiblity of simultaneous SE and GE measurements of BOLD signals with and without interleaved diffusion weighting. The results also indicated a predominant extravascular contribution to the BOLD signal time courses, including post‐stimulation undershoots in both SE and GE measurements at 7 T.     

Neuroprotection of ethanol against ischemia/reperfusion-induced brain injury through decreasing c-Jun N-terminal kinase 3 (JNK3) activation by enhancing GABA release

Our latest study indicated that ethanol could attenuate cerebral ischemia/reperfusion-induced brain injury through activating Ionotropic glutamate receptors Kainate Family (Gluk1)–kainate (KA) receptors and gamma-aminobutyric acid (GABA) receptors. However, the possible mechanism of the neuroprotective effects of ethanol remains unclear. In this study we report that ethanol shows neuroprotective effects against ischemic brain injury through enhancing GABA release and then decreasing c-Jun N-terminal kinase 3 (JNK3) activation. Electrophysiologic recording indicated that ethanol enhances GABA release from presynaptic neurons and the released GABA subsequently inhibits the KA receptor–mediated whole-cell currents. Moreover, our data show that ethanol can inhibit the increased assembly of the Gluk2–PSD-95–MLK3 (postsynaptic density protein-95, PSD-95 and mixed-lineage kinase 3, MLK3) module induced by cerebral ischemia and the activation of the MLK3-MKK4/7-JNK (mitogen-activated protein kinase kinase 4/7, MKK4/7) cascade. Pretreatment of the GABA_A receptor antagonist bicuculline and antagonist of VGCC (a broad-spectrum blocker of the voltage-gated calcium channel [VGCC]) Chromic (CdCl₂) can demolish the neuroprotective effects of ethanol. The results suggest that during ischemia-reperfusion, ethanol may activate presynaptic Gluk1-KA and facilitate Ca²⁺-dependent GABA release. The released GABA activates postsynaptic GABA_A receptors, which suppress the ischemic depolarization and decrease the association of signaling module Gluk2–PSD-95–MLK3 induced by the activation of postsynaptic Gluk2-KA receptors. There is a raised possibility that ethanol inhibiting the JNK3 apoptotic pathway (MLK3/MKK4/7/JNK3/c-Jun/Fas-L) performs a neuroprotective function against ischemic brain injury.     

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.     

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.     

基于DQF技术定量检测人脑γ-氨基丁酸浓度的序列设计及程序实现

基于磁共振频谱（MRS）定量检测人脑γ-氨基丁酸（GABA）浓度对医学临床意义重大。除了用频谱处理软件包进行处理外,谱分析的方法能更为直接地检测GABA。本研究用双量子滤波技术（DQF）去设计和优化用于检测GABA的脉冲序列,基于乘积算符理论和相干路径选择理论,设计GABA谱编辑序列。通过MRUI模拟实验,本研究证实了优化的序列能压制位于化学位移3.0ppm处的肌酸（Cr）,从而使低浓度的GABA信号明显增强,最后,本研究编程实现了优化的脉冲序列。进一步工作是将该序列的目标程序应用到临床MRI扫描仪上验证,优化其的参数,并通过模型实验和活体实验验证本序列的性能。     

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 reproducibility of MRS regional brain thermometry by 'amplitude-weighted combination'

Brain temperature is important in stroke and trauma. In birth asphyxia, hypothermia improves outcome, but local brain temperature information is needed to optimise therapy. The proton MRS water chemical shift (δ(water) ) is temperature dependent, and the in vivo brain temperature has often been estimated by measuring δ(water) relative to the N-acetylaspartate (NAA) singlet methyl resonance. However, the NAA peak amplitude may be reduced if cerebrospinal fluid occupies part of the MRS voxel and because of the lower concentration in immaturity, pathology and neonatal white matter. These factors can increase random and systematic δ(NAA) errors and also, therefore, MRS brain temperature errors. The aim of this study was to improve MRS brain temperature reproducibility and resilience to pathological, developmental and regional peak amplitude variations by amplitude-weighted combination (AWC) of brain temperatures (T(Cho) , T(Cr) and T(NAA) ) determined using the prominent choline (Cho), total creatine (Cr) and NAA resonances separately as chemical shift references. δ(water) - δ(Cho) , δ(water) - δ(Cr) and δ(water) - δ(NAA) were calibrated against tympanic temperature in piglet brain at 7 T (2.5-cm-diameter surface coil over the parietal lobes; binomial water suppression spin-echo sequence; TE = 540 ms; TR = 5 s). Eight normal human infants underwent thalamic region (Thal) and five occipito-parietal (OP) cerebral MRS at 2.4 T [point-resolved spectroscopy (PRESS) localisation; cubic voxel, 8 mL; water suppression off; TE = 270 ms; TR = 2 s]. AWC with T(Cho) , T(Cr) and T(NAA) weighted by the squared Cho, Cr and NAA peak amplitudes provided the smallest intersubject standard deviations: Thal, 0.45°C; OP, 0.33°C (for T(NAA) values of 0.65°C and 1.12°C, respectively). AWC provided resilience against simulated pathological alterations in Cho, Cr and NAA peak amplitudes, with Thal and OP T(AWC) changing by less than 0.04°C. AWC improves both intersubject reproducibility of MRS temperature estimation and resilience against pathological, anatomical and developmental variation of Cho, Cr and NAA peak amplitudes.