Off-resonance effects of the radiofrequency pulses used in spectral editing with double-quantum coherence transfer

Spectral editing using gradient selected double-quantum (DQ) coherence transfer is often used for the selective observation of metabolites in vivo. In attempting to optimize the detection sensitivity of a conventional DQ spectral editing sequence, the effects of using radiofrequency (RF) pulses that are not at the resonance frequency of the observed peaks were investigated both theoretically and experimentally. The results show that spectral editing using pulses at the frequency of the observed resonance does not necessarily give the optimal detection sensitivity. At 7 T, the detection sensitivity of lactate observed using a DQ editing method can be increased by up to 30% by setting the RF pulses off resonance at the proper frequency. The results also suggest that slice selective RF pulses used in DQ spectral editing combined with PRESS localization may have slice profiles different from those when the same pulses are used for standard PRESS spatial localization.     

Simultaneous lactate editing and observation of other metabolites using a stimulated-echo-enhanced double-quantum filter

Conventional double-quantum editing techniques recover only one metabolite at a time, and are thus inefficient for monitoring metabolic changes involving several metabolites. In this paper, a stimulated-echo-enhanced selective double-quantum coherence transfer (STE-SelDQC) sequence is described, which allows simultaneous observation of lactate and other metabolites in a single scan while leaving fat and water signals suppressed. A frequency selective double-quantum filter designed for lactate editing suppresses fat and water resonances and a stimulated-echo window of adjustable frequency and bandwidth is incorporated into the double-quantum filter for simultaneous observation of other metabolites. The performance of the sequence is demonstrated in phantoms and rat brain tissue.     

The effects of slice-selective excitation/refocusing in localized spectral editing with gradient-selected double-quantum coherence transfer

Spectral editing using gradient-selected double-quantum filtering (DQF) with PRESS localization has been used for selective observation of metabolites in vivo. In previous studies using localized DQF sequences, it is generally assumed that the slice-selective pulses used in the sequence have no roles in coherence transfer, and do not interfere with DQF. To validate this assumption, the effects of slice-selective excitation/refocusing on DQF were investigated in DQF lactate editing sequences combined with PRESS localization. Contrary to the previous assumption, the results show that, due to chemical shift displacement artifact and J coupling, slice selection in DQF does interfere with coherence transfer, affecting both the accuracy of spatial localization and the detection sensitivity adversely. In the case of lactate editing, the effects of this interference can be accounted for simply by adjusting the strength of the slice-selection gradients and by using narrowband slice-selective refocusing pulses.     

在体检测γ-氨基丁酸的MEGA-PRESS序列优化设计

γ-氨基丁酸（γ-aminobutyric acid,GABA）含量异常会引发一系列大脑疾病,因此在体检测人脑GABA含量成为一种十分必要的医疗技术.本文基于GABA检测常用的谱编辑方法MEGA-PRESS,引入性能更好的SLR脉冲代替常用的高斯脉冲,并使用单频带和双频带结合的方法激发特定频率的物质,在联影（United Imaging Healthcare,UIH）的uMR780磁共振系统上实现了一种优化的MEGA-PRESS序列.结果表明：SLR脉冲可以减少大分子（macromolecule,MM）信号对GABA信号的干扰;单频带和双频带结合可以更好地抑制残余水信号对GABA^*信号的影响.水模实验和人体实验结果均证实优化的MEGA-PRESS序列可以更好地实现GABA^*含量在体检测.     

人脑GABA测量在临床3 T磁共振成像系统上的实现

γ-氨基丁酸(γ-Aminobutyric Acid，GABA)是人脑中枢神经系统中一种重要的抑制性神经递质，对神经活动的调节起着主导作用.由于人脑GABA固有含量低以及与其他代谢物谱峰的重叠，在临床用磁共振成像系统中使用点分辨波谱(PRESS)序列或受激回波采集模式(STEAM)序列难以直接检测到GABA δ 3.01信号. 该文报道了MEGA-PRESS脉冲序列在临床用3 T磁共振成像系统上的实现，采用J差分谱编辑技术实现了对GABA的检测. 水模实验和人脑在体实验显示，MEGA-PRESS序列对GABA δ 3.01信号具有较好的检测效果.     

Spectral editing of weakly coupled spins using variable flip angles in PRESS constant echo time difference spectroscopy: Application to GABA

A general in vivo magnetic resonance spectroscopy editing technique is presented to detect weakly coupled spin systems through subtraction, while preserving singlets through addition, and is applied to the specific brain metabolite γ-aminobutyric acid (GABA) at 4.7 T. The new method uses double spin echo localization (PRESS) and is based on a constant echo time difference spectroscopy approach employing subtraction of two asymmetric echo timings, which is normally only applicable to strongly coupled spin systems. By utilizing flip angle reduction of one of the two refocusing pulses in the PRESS sequence, we demonstrate that this difference method may be extended to weakly coupled systems, thereby providing a very simple yet effective editing process. The difference method is first illustrated analytically using a simple two spin weakly coupled spin system. The technique was then demonstrated for the 3.01 ppm resonance of GABA, which is obscured by the strong singlet peak of creatine in vivo. Full numerical simulations, as well as phantom and in vivo experiments were performed. The difference method used two asymmetric PRESS timings with a constant total echo time of 131 ms and a reduced 120° final pulse, providing 25% GABA yield upon subtraction compared to two short echo standard PRESS experiments. Phantom and in vivo results from human brain demonstrate efficacy of this method in agreement with numerical simulations.     

Heteronuclear X-Y double quantum MAS NMR in crystalline inorganic solids. Applications for indirect detection and spectral editing of rare-spin resonances.

Heteronuclear double quantum MAS NMR experiments in the solid state, involving pairs of highly abundant 31P spins and the rare spins 113Cd, 77Se, and 29Si, are described for the three crystalline compounds CdSiP2, CdGeP2, and Ag7PSe6. These experiments offer the opportunity of indirectly detecting the rare-spin resonance via chemical shift evolution of heteronuclear double quantum coherence. For suitable cases, this method results in significantly enhanced detection sensitivities. Criteria for favorable indirect detection experiments are established. Besides offering high sensitivity, the pulse sequence also acts as a heteronuclear double quantum filter, hence providing heteronuclear correlation and useful spectral editing for peak assignments.     

MRS定量检测活体γ-氨基丁酸浓度的研究现状

γ-氨基丁酸（GABA）是一种重要的脑代谢物, 磁共振频谱(MRS)技术可以非介入检测活体脑代谢物浓度. 但使用MRS定量检测活体GABA还是会遇到很多困难. 随着谱编辑技术的发展和频谱分析软件的出现, 已提出了很多方法用于定量检测活体GABA浓度. 本文简述了GABA的理论背景, 然后介绍了国内外MRS定量检测活体γ 氨基丁酸浓度的研究现状, 最后分析了MRS定量检测γ 氨基丁酸浓度的方向.      

In vivo GABA detection with improved selectivity and sensitivity by localized double quantum filter technique at 4.1T

Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter for the normal function of mammal and human brain. It is difficult to detect GABA signal with the conventional single quantum technique due to its relatively low concentration and overlapping with other signals from creatine (Cr), glutathione (GSH), as well as macromolecules. Using a high-selective read pulse, DANTE, and at the facility of increased sensitivity and chemical shift resolution at high-field 4.1T, GABA editing by double quantum filter (DQF) with robust suppression of Cr and GSH was achieved. Our editing efficiency of 40-50% was achievable on a GABA phantom (50 mM GABA and 61 mM choline). Furthermore, GABA editing spectra were acquired with echo time TE = 77 ms, and any possible macromolecular contamination to GABA editing spectra was found to be negligible. This high-field DQF setup was applied to 11 healthy volunteers, and the mean GABA level was measured to be 1.12 +/- 0.15 mM in the occipital lobe in reference to 7.1 mM Cr concentration.     

Double-quantum homonuclear correlations of spin I=5/2 nuclei

The challenges associated with acquiring double-quantum homonuclear Nuclear Magnetic Resonance correlation spectra of half-integer quadrupolar nuclei are described. In these experiments the radio-frequency irradiation amplitude is necessarily weak in order to selectively excite the central transition. In this limit only one out of the 25 double-quantum coherences possible for two coupled spin I=5/2 nuclei is excited. An investigation of all the 25 two spins double quantum transitions reveals interesting effects such as a compensation of the first-order quadrupolar interaction between the two single quantum transitions involved in the double quantum coherence. In this paper a full numerical study of a hypothetical two spin I=5/2 system is used to show what happens when the RF amplitude during recoupling is increased. In principle this is advantageous, since the required double quantum coherence should build up faster, but in practice it also induces adiabatic passage transfer of population and coherence which impedes any build up. Finally an optimized rotary resonance recoupling (oR(3)) sequence is introduced in order to decrease these transfers. This sequence consists of a spin locking irradiation whose amplitude is reduced four times during one rotor period, and allows higher RF powers to be used during recoupling. The sequence is used to measure (27)Al DQ dipolar correlation spectra of Y(3)Al(5)O(12) (YAG) and gamma alumina (γAl(2)O(3)). The results prove that aluminium vacancies in gamma alumina mainly occur in the tetrahedral sites.     

Incorporating homonuclear polarization transfer into PRESS for proton spectral editing: illustration with lactate and glutathione

A proton spectral editing pulse sequence for the detection of metabolites with spin systems that involve weak coupling is presented. The sequence is based on homonuclear polarization transfer incorporated into the standard PRESS (Point RESolved Spectroscopy) sequence, which is a volume-selective double spin echo method, to enable spatial localization. All peaks in the region of interest are initially suppressed whether they are peaks from the target metabolite or from contaminating background. The target signal is then restored by polarization transfer from a proton that has a resonance outside the suppressed region and to which the target spins are weakly coupled. This is achieved by the application of a 90 degrees hard pulse with phase orthogonal to that of the PRESS excitation pulse at the location of the first echo in PRESS and by optimizing the two PRESS timings, TE(1) and TE(2), for most efficient yield. Background signal not coupled to any protons outside the initially saturated region remains suppressed. The advantage of this sequence compared to multiple quantum filters is that signal from singlet peaks outside the suppressed area are preserved and can thus be used as a reference. The efficacy of the sequence was verified experimentally on phantom solutions of lactate and glutathione at 3.0 T. For the AX(3) spin system of lactate, the sequence timings were optimized by product operator calculations whereas for the ABX spin system of the cysteinyl group of glutathione numerical calculations were performed for sequence timing optimization.     

人脑GABA磁共振波谱测量中大分子影响的研究

J差分谱编辑技术已广泛用于人脑g-氨基丁酸(γ-amino butyric acid,GABA)的检测,利用MEGA-PRESS序列可以有效编辑GABA在δ_H 3.02处的信号.由于相近的化学位移和J耦合作用,大分子(macromolecule,MM)在δ_H 3.00的信号也同时被编辑,因此测量得到的GABA信号中包含一部分MM信号(GABA+MM,简称GABA+).对称谱编辑技术可以有效抑制大分子,但该方法对编辑脉冲的频率选择性要求较高,因此对称谱编辑技术中编辑脉冲持续时间一般较长.该研究将MEGA-PRESS序列中编辑脉冲持续时间由14 ms增加到20 ms,回波时间(echo time,TE)由68 ms增加到80 ms,分别测量GABA+与对称谱编辑技术抑制大分子后的GABA(简称GABA).结果发现,在较长编辑脉冲作用时间和较长TE条件下,GABA比GABA+含量低27%;长编辑脉冲持续时间可以有效提高编辑脉冲的频率选择性,更好地实现对称谱编辑技术抑制大分子,有助于分析人脑GABA含量测定中大分子信号干扰的影响.纯GABA含量测量,有助于更准确地分析GABA在人脑中的代谢过程,以及GABA含量与各种疾病和功能认知反应之间的相关性.     

Coherence selection in double CP MAS NMR spectroscopy

Applications of double cross-polarization (CP) magic-angle spinning (MAS) NMR spectroscopy, via (1)H/(15)N and then (15)N/(13)C coherence transfers, for (13)C coherence selection are demonstrated on a (15)N/(13)C-labeled N-acetyl-glucosamine (GlcNAc) compound. The (15)N/(13)C coherence transfer is very sensitive to the settings of the experimental parameters. To resolve explicitly these parameter dependences, we have systematically monitored the (13)C{(15)N/(1)H} signal as a function of the rf field strength and the MAS frequency. The data reveal that the zero-quantum coherence transfer, with which the (13)C effective rf field is larger than that of the (15)N by the spinning frequency, would give better signal sensitivity. We demonstrate in one- and two-dimensional double CP experiments that spectral editing can be achieved by tailoring the experimental parameters, such as the rf field strengths and/or the MAS frequency.     

Short echo time in vivo prostate ¹H-MRSI

Visualization of short echo time (TE) metabolites in prostate magnetic resonance spectroscopic imaging is difficult due to lipid contamination and pulse timing constraints. In this work, we present a modified pulse sequence to permit short echo time (TE=40ms) acquisitions with reduced lipid contamination for the detection of short TE metabolites. The modified pulse sequence employs the conformal voxel MRS (CV-MRS) technique, which automatically optimizes the placement of spatial saturation planes to adapt the excitation volume to the shape of the prostate, thus reducing lipid contamination in prostate magnetic resonance spectroscopic imaging (MRSI). Metabolites were measured and assessed using a modified version of LCModel for analysis of in vivo prostate spectra. We demonstrate the feasibility of acquiring high quality spectra at short TEs, and show the measurement of short TE metabolites, myo-inositol, scyllo-inositol, taurine and glutamine/glutamate for both single and multi-voxel acquisitions. In single voxels experiments, the reduction in TE resulted in 57% improvement in the signal-to-noise ratio (SNR). Additional 3D MRSI experiments comparing short (TE=40 ms), and long (TE=130 ms) TE acquisitions revealed a 35% improvement in the number of adequately fitted metabolite peaks (775 voxels over all subjects). This resulted in a 42 ± 24% relative improvement in the number of voxels with detectable citrate that were well-fitted using LCmodel. In this study, we demonstrate that high quality prostate spectra can be obtained by reducing the TE to 40 ms to detect short T2 metabolites, while maintaining positive signal intensity of the spin-coupled citrate multiplet and managing lipid suppression.     

Detection of intracellular lactate with localized diffusion {1H-13C}-spectroscopy in rat glioma in vivo

The aim of this study was to compare the diffusion characteristic of lactate and alanine in a brain tumor model to that of normal brain metabolites known to be mainly intracellular such as N-acetylaspartate or creatine. The diffusion of (13)C-labeled metabolites was measured in vivo with localized NMR spectroscopy at 9.4 T (400 MHz) using a previously described localization and editing pulse sequence known as ACED-STEAM ('adiabatic carbon editing and decoupling'). (13)C-labeled glucose was administered and the apparent diffusion coefficients of the glycolytic products, {(1)H-(13)C}-lactate and {(1)H-(13)C}-alanine, were determined in rat intracerebral 9L glioma. To obtain insights into {(1)H-(13)C}-lactate compartmentation (intra- versus extracellular), the pulse sequence used very large diffusion weighting (50 ms/microm(2)). Multi-exponential diffusion attenuation of the lactate metabolite signals was observed. The persistence of a lactate signal at very large diffusion weighting provided direct experimental evidence of significant intracellular lactate concentration. To investigate the spatial distribution of lactate and other metabolites, (1)H spectroscopic images were also acquired. Lactate and choline-containing compounds were consistently elevated in tumor tissue, but not in necrotic regions and surrounding normal-appearing brain. Overall, these findings suggest that lactate is mainly associated with tumor tissue and that within the time-frame of these experiments at least some of the glycolytic product ([(13)C] lactate) originates from an intracellular compartment.     

Slice-selective J-coupled coherence transfer using symmetric linear phase pulses: applications to localized GABA spectroscopy

Symmetric, linear phase, slice-selective RF pulses were analyzed theoretically for performing slice-selective coherence transfer. It was shown using numerical simulations of product operators that, when a prefocusing gradient of the same area as that of the refocusing gradient is added, these pulses become slice-selective universal rotator pulses, therefore, capable of performing slice-selective coherence transfer. As an example, a slice-selective universal rotator pulse based on a seven-lobe hamming-filtered sinc pulse was applied to in vivo single-shot simultaneous spectral editing and spatial localization of neurotransmitter GABA in the human brain.     

Heteronuclear Double-Quantum MAS NMR Spectroscopy in Dipolar Solids

A new pulse sequence for high-resolution solid-state heteronuclear double-quantum MAS NMR spectroscopy of dipolar-coupled spin-12 nuclei is introduced. It is based on the five-pulse sequence known from solution-state NMR, which is here applied synchronously to both spin species. The heteronuclear double-quantum (HeDQ) spinning-sideband patterns produced by this experiment are shown to be sensitive to the heteronuclear distance, as well as the relative orientations of the chemical-shift and dipolar tensors. In particular, it is shown that the HeDQ patterns exhibit an enhanced sensitivity to the chemical shielding tensors as compared with the single-quantum spinning-sideband patterns. The detection of HeDQ patterns via the I and S spins is discussed. The isolated (13)C-(1)H spin pair in deuterated ammonium formate with (13)C in natural abundance was chosen as a model system, and the perturbing influence of dipolar couplings to surrounding protons on the (13)C-(1)H DQ coherence is discussed. The pulse sequence can also be used as a heteronuclear double-quantum filter, hence providing information about heteronuclear couplings, and thus allowing the differentiation of quaternary and CH(n) bonded carbons. The elucidation of (13)C-(1)H dipolar proximities is presented for a sample of bisphenol A polycarbonate with (13)C in natural abundance, recorded with a broadband version of the synchronized five-pulse sequence.     

In vivo detection of (15)N-coupled protons in rat brain by ISIS localization and multiple-quantum editing.

Three-dimensional image-selected in vivo spectroscopy (ISIS) was combined with phase-cycled (1)H-(15)N heteronuclear multiple-quantum coherence (HMQC) transfer NMR for localized selective observation of protons J-coupled to (15)N in phantoms and in vivo. The ISIS-HMQC sequence, supplemented by jump-return water suppression, permitted localized selective observation of 2-5 micromol of [(15)N(indole)]tryptophan, a precursor of the neurotransmitter serotonin, through the (15)N-coupled proton in 20-40 min of acquisition in vitro at 4.7 T. In vivo, the amide proton of [5-(15)N]glutamine was selectively observed in the brain of spontaneously breathing (15)NH(4)(+)-infused rats, using a volume probe with homogeneous (1)H and (15)N fields. Signal recovery after three-dimensional localization was 72-82% in phantoms and 59 +/- 4% in vivo. The result demonstrates that localized selective observation of (15)N-coupled protons, with complete cancellation of all other protons except water, can be achieved in spontaneously breathing animals by the ISIS-HMQC sequence. This sequence performs both volume selection and heteronuclear editing through an addition/subtraction scheme and predicts the highest intrinsic sensitivity for detection of (15)N-coupled protons in the selected volume. The advantages and limitations of this method for in vivo application are compared to those of other localized editing techniques currently in use for non-exchanging protons.     

Detection of gamma-aminobutyric acid (GABA) by longitudinal scalar order difference editing

Two novel spectral editing techniques for the in vivo detection of gamma-aminobutyric acid (GABA) are presented. The techniques rely on the generation of longitudinal scalar order (LSO) coherences, which in combination with J-difference editing results in the selective detection of GABA. The utilization of LSO coherences makes the editing sequences insensitive to phase and frequency instabilities. Furthermore, the spectral editing selectivity can be increased independent of the echo time, thereby opening the echo time for state-of-the-art water suppression and/or spatial localization techniques. The performance of the LSO editing techniques is theoretically demonstrated with product operator calculations and density matrix simulations and experimentally evaluated on phantoms in vitro and on human brain in vivo.