Spin-echo MRS in humans at high field: LASER localisation using FOCI pulses

Significant improvements in spin-echo MRS are possible when voxel localisation is performed using high bandwidth frequency offset corrected inversion (FOCI) pulses as opposed to more conventional lower bandwidth pulses. The reduced chemical shift displacement errors result in a spectrum that more accurately reflects the actual metabolite distribution within any region of interest that is selected graphically on a series of scout images, and can lead to improved metabolite detection in the case of homonuclear J-coupled spins. At 4.7T, FOCI pulses with a 20 kHz bandwidth result in extremely sharp and uniform selection profiles, and negligible contamination from outside of the voxel of interest, for all signals in the 1H spectral range that is normally studied. A 'FOCI' adiabatic half-passage is observed to provide good excitation over the 1H spectral range. Single shot performance with echo-time (TE)48 ms is reported using a four-port drive birdcage head coil. GAMMA simulations show that, for many detectable metabolites at 4.7 T, LASER localisation using FOCI pulses with TE=48 ms results in 1H anti-phase spectral components that are the same order as would be obtained from a symmetric PRESS sequence with TE=32 ms. Timing schemes are proposed to enable good measurement of lactate with very little signal loss arising from chemical shift displacement errors at TE=144 and 288 ms.     

Proton magnetic resonance spectroscopy in deep human brain structures at 7 T

The increased magnetization and frequency separation at high magnetic field strength, such as 7 T, can provide spectra of high signal-to-noise ratio and spectral resolution. However, most human brain magnetic resonance spectroscopy (MRS) studies at 7 T have employed surface coils and thus limited to superficial brain structures. In this study, volume coil excitation together with volume array reception has been utilized to access deeper brain areas. RF power limitations have been addressed by the use of VERSE-modified pulses, and spectra in parietal and pregenual anterior cingulate cortex (pgACC) have been acquired in eight subjects using STEAM with a short echo time of 20 ms. Spectra were analyzed using LC-model. Therefore, an experimental basis set of in vitro spectra was established from 20 human brain metabolite solutions. An exemplary comparison with an optimized PRESS-based single voxel MRS method at 3 T has been performed. Despite the intrinsically lower signal in STEAM, the 7 T spectra show 1.87 times higher signal-to-noise ratio than at 3 T (using PRESS) and more metabolites could be quantified reliably. The results show that the proposed method can be employed at 7 T in deep brain structures and allows the absolute and relative concentrations of human brain metabolites to be determined with low error levels.     

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.     

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.     

Quality assessment of localization technique performance in small volume in vivo 1H MR spectroscopy

A new phantom and evaluation method for experimental evaluation of 1H-magnetic resonance spectroscopy single volume localization techniques regarding signal contamination (C), defined as the part of the signal originating outside the volume of interest, is presented. The quality assessment method is based on a spherical phantom with an oil/water interface in order to reduce susceptibility effects, and applied for stimulated-echo acquisition method (STEAM) and spin-echo (SE) sequences, echo times of 270, 135, and 10 ms, and cubic volumes of interest (VOI) of 1(3), 1.5(3), 2(3), 2.5(3), and 3(3) cm3. To be able to mimic measurements of the contamination in three dimensions the physical gradients representing the three orthogonal directions for slice selection were shifted in the pulse sequences. Contamination values in one dimension differed between 6.5% and 8.4% in SE sequences, and between 0.7% and 13.8% in STEAM sequences. In STEAM sequences a decrease of C with increasing VOI size was observed while SE sequences showed comparable C values for the different VOI sizes tested. The total contamination in three dimensions were 19% and 18% in SE and STEAM sequences with a TE of 270 ms, and 7% in a STEAM sequence with a TE of 10 ms, respectively. The presented evaluation method is easily applied to the new phantom and showed high reproducibility.     

Quality assessment of localization technique performance in small volume in vivo H MR spectroscopy

A new phantom and evaluation method for experimental evaluation of ¹H-magnetic resonance spectroscopy single volume localization techniques regarding signal contamination (C), defined as the part of the signal originating outside the volume of interest, is presented. The quality assessment method is based on a spherical phantom with an oil/water interface in order to reduce susceptibility effects, and applied for stimulated-echo acquisition method (STEAM) and spin-echo (SE) sequences, echo times of 270, 135, and 10 ms, and cubic volumes of interest (VOI) of 1³, 1.5³, 2³, 2.5³, and 3³ cm³. To be able to mimic measurements of the contamination in three dimensions the physical gradients representing the three orthogonal directions for slice selection were shifted in the pulse sequences. Contamination values in one dimension differed between 6.5% and 8.4% in SE sequences, and between 0.7% and 13.8% in STEAM sequences. In STEAM sequences a decrease of C with increasing VOI size was observed while SE sequences showed comparable C values for the different VOI sizes tested. The total contamination in three dimensions were 19% and 18% in SE and STEAM sequences with a TE of 270 ms, and 7% in a STEAM sequence with a TE of 10 ms, respectively. The presented evaluation method is easily applied to the new phantom and showed high reproducibility.     

Maximizing MR signal for 2D UTE slice selection in the presence of rapid transverse relaxation

Ultrashort TE (UTE) sequences allow direct visualization of tissues with very short T2 relaxation times, such as tendons, ligaments, menisci, and cortical bone. In this work, theoretical calculations, simulations, and phantom studies, as well as in vivo imaging were performed to maximize signal-to-noise ratio (SNR) for slice selective RF excitation for 2D UTE sequences. The theoretical calculations and simulations were based on the Bloch equations, which lead to analytic expressions for the optimal RF pulse duration and amplitude to maximize magnetic resonance signal in the presence of rapid transverse relaxation. In steady state, it was found that the maximum signal amplitude was not obtained at the classical Ernst angle, but at an either lower or higher flip angle, depending on whether the RF pulse duration or amplitude was varied, respectively.     

Simultaneous detection of resolved glutamate, glutamine, and gamma-aminobutyric acid at 4 T

A new approach is introduced to simultaneously detect resolved glutamate (Glu), glutamine (Gln), and gamma-aminobutyric acid (GABA) using a standard STEAM localization pulse sequence with the optimized sequence timing parameters. This approach exploits the dependence of the STEAM spectra of the strongly coupled spin systems of Glu, Gln, and GABA on the echo time TE and the mixing time TM at 4 T to find an optimized sequence parameter set, i.e., {TE, TM}, where the outer-wings of the Glu C4 multiplet resonances around 2.35 ppm, the Gln C4 multiplet resonances around 2.45 ppm, and the GABA C2 multiplet resonance around 2.28 ppm are significantly suppressed and the three resonances become virtual singlets simultaneously and thus resolved. Spectral simulation and optimization were conducted to find the optimized sequence parameters, and phantom and in vivo experiments (on normal human brains, one patient with traumatic brain injury, and one patient with brain tumor) were carried out for verification. The results have demonstrated that the Gln, Glu, and GABA signals at 2.2-2.5 ppm can be well resolved using a standard STEAM sequence with the optimized sequence timing parameters around {82 ms,48 ms} at 4 T, while the other main metabolites, such as N-acetyl aspartate (NAA), choline (tCho), and creatine (tCr), are still preserved in the same spectrum. The technique can be easily implemented and should prove to be a useful tool for the basic and clinical studies associated with metabolism of Glu, Gln, and/or GABA.     

Quantitative evaluation of the lactate signal loss and its spatial dependence in press localized (1)H NMR spectroscopy

Localized (1)H NMR spectroscopy using the 90 degrees -t(1)-180 degrees -t(1)+t(2)-180 degrees -t(2)-Acq. PRESS sequence can lead to a signal loss for the lactate doublet compared with signals from uncoupled nuclei which is dependent on the choice of t(1) and t(2). The most striking signal loss of up to 78% of the total signal occurs with the symmetrical PRESS sequence (t(1)=t(2)) at an echo time of 2/J (approximately 290 ms). Calculations have shown that this signal loss is related to the pulse angle distributions produced by the two refocusing pulses which leads to the creation of single quantum polarization transfer (PT) as well as to not directly observable states (NDOS) of the lactate AX(3) spin system: zero- and multiple-quantum coherences, and longitudinal spin orders. In addition, the chemical shift dependent voxel displacement (VOD) leads to further signal loss. By calculating the density operator for various of the echo times TE=n/J, n=1, 2, 3,..., we calculated quantitatively the contributions of these effects to the signal loss as well as their spatial distribution. A maximum signal loss of 75% can be expected from theory for the symmetrical PRESS sequence and TE=2/J for Hamming filtered sinc pulses, whereby 47% are due to the creation of NDOS and up to 28% arise from PT. Taking also the VOD effect into account (2 mT/m slice selection gradients, 20-mm slices) leads to 54% signal loss from NDOS and up to 24% from PT, leading to a maximum signal loss of 78%. Using RE-BURP pulses with their more rectangular pulse angle distributions reduces the maximum signal loss to 44%. Experiments at 1.5 T using a lactate solution demonstrated a maximum lactate signal loss for sinc pulses of 82% (52% NDOS, 30% PT) at TE=290 ms using the symmetrical PRESS sequence. The great signal loss and its spatial distribution is of importance for investigations using a symmetrical PRESS sequence at TE=2/J.     

Numerical simulation of PRESS localized MR spectroscopy

Numerical simulations of NMR spectra can provide a rapid and convenient method for optimizing acquisition sequence parameters and generating prior spectral information required for parametric spectral analysis. For spatially resolved spectroscopy, spatially dependent variables affect the resultant spectral amplitudes and phases, which must therefore be taken into account in any spectral simulation model. In this study, methods for numerical simulation of spectra obtained using the PRESS localization pulse sequence are examined. A comparison is made between three different simulation models that include different levels of detail regarding the spatial distributions of the excitation functions, and spin evolution during application of the pulses. These methods were evaluated for measurement of spectra from J-coupled spin systems that are of interest for in vivo proton spectroscopy and results compared with experimental data. It is demonstrated that for optimized refocusing pulses it is sufficient to account for chemical shift effects only, although there is some advantage to implementing a more general numerical simulation approach that includes information on RF pulse excitation profiles, which provides sufficient accuracy while maintaining moderate computational requirements and flexibility to handle different spin systems.     

Proton Spectroscopy of Human Brain with Very Short Echo Time Using High Gradient Amplitudes

In localized proton magnetic resonance spectroscopy very short echo times (TE) are achieved to diminish signal loss due to T₂ relaxation and to avoid phase distortions due to J-coupling. A sequence for single volume spectroscopy in human brain is described with a TE as low as 5 ms. Examinations were performed on a 1.5 T whole-body imager with actively shielded gradients. A self-designed stimulated echo acquisition mode (STEAM) sequence with very high amplitude spoiling gradients of 24 mT/m was used to take advantage of the whole potential of the gradient system. Optimization of TE was carried out by controlling spectral quality and localization in both phantom and volunteer measurements. Proton spectra of human brain were acquired in 21 healthy volunteers. Spectra of occipital white matter, parieto-occipital grey/white matter, and cerebellum revealed none or only small eddy current distortions at a TE of 5 ms. The volume of interest was 8–12 ml, repetition time was 1.5 s, and mixing time was 5 ms. Peak ratios of major metabolites referring to creatine were estimated and the relative standard deviations were calculated to determine interindividual reproducibility. The relative standard deviation of myo-inositol ranged from 6% to 11% within these brain regions whereas for glutamine and glutamate 7% to 16% were found.     

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.     

In vivo quantitative 1H MRS of cerebellum and evaluation of quantitation reproducibility by simulation of different levels of noise and spectral resolution

A quantitative analysis of cerebellar metabolites in normal subjects has been performed by proton MR spectroscopy (MRS) with relaxation time correction. Quantitation was carried out in seven healthy human subjects with the well-established LCModel program. The prior knowledge utilized for quantitation was obtained from solutions containing the major brain metabolites and MRS investigated under the same experimental conditions. The tissue water signal was used as an internal standard for the in vivo studies. Both in vitro (for the prior knowledge template) and in vivo data were acquired separately at 1.5 T by PRESS sequence (TR, 1500 ms; TE, 30 ms). The absolute concentration of main cerebellar metabolites was corrected for relaxation time effects. Different noise and line broadening conditions were considered and simulated in the spectral processing in order to evaluate the effect of spectral quality on the concentration estimates.     

Short TE in vivo (1)H MR spectroscopic imaging at 1.5 T: acquisition and automated spectral analysis

Spectral analysis of short TE in vivo proton magnetic resonance spectroscopic imaging (MRSI) data are complicated by the presence of spectral overlap, low signal to noise and uncharacterized signal contributions. In this study, it is shown that an automated data analysis method can be used to generate metabolite images from MRSI data obtained from human brain at TE = 25 ms and 1.5 T when optimized pulse sequences and a priori metabolite knowledge are used. The analysis approach made use of computer simulation methods to obtain a priori spectral information of the metabolites of interest and utilized a combination of parametric spectral modeling and non-parametric signal characterization for baseline fitting. This approach was applied to data from optimized PRESS-SI and multi-slice spin-echo SI acquisitions, for which sample spectra and metabolite images are shown.     

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.     

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.     

The application of phase rotation for localized in Vivo proton spectroscopy with short echo times

Single voxel localization techniques like STEAM or PRESS lead to the generation of unwanted signals, which must be destroyed by spoiling gradients. The duration of these gradients and the eddy currents they produce lead to comparatively long echo times on standard whole-body systems. This paper reports a way to observe the proper spectrum in the presence of large spurious signals. The method uses a phase-cycling scheme which separates all different signal contributions by two-dimensional Fourier transformation. Localized proton spectra from the human brain with echo times of 20 ms using the PRESS localization technique could be acquired on a 2 T whole-body system. Metabolites with short T₂ relaxation times like glutamate or inositol are observed.     

Analysis of 1.5 Tesla proton MR spectra of human brain using LCModel and an imported basis set.

Automated analysis of 1.5 Tesla proton mass MR spectra using the LCModel program with basis sets obtained at other sites is expected to become more widespread, as such basis sets are now generally available. A calibration procedure to estimate absolute concentrations with such imported basis sets is suggested and the implications for differential T2 attenuation are discussed. Based on STEAM localized spectra from parietal gray (n = 51) and white matter (n = 43), of which 28 (18 rsp) were quantified, the evaluation of 30 ms echo time (TE) spectra was validated against published results that were obtained at 2 Tesla and 20 ms TE. Good agreement for both absolute concentrations and metabolite ratios confirmed the usefulness of LCModel analysis with an imported basis set. However, in white matter, glutamine tended to be overestimated, and was assigned either to signal-to-noise depending baseline effects or the use of choline. Mutual interdependence of metabolites inherent to LCModel analysis is discussed in detail.     

Investigation of the effect of a variety of pulse errors on spin I=1 quadrupolar alignment echo spectroscopy

We report on an analysis of a well known three-pulse sequence for generating and detecting spin I=1 quadrupolar order when various pulse errors are taken into account. In the situation of a single quadrupolar frequency, such as the case found in a single crystal, we studied the potential leakage of single and/or double quantum coherence when a pulse flip error, finite pulse width effect, RF transient or a resonance offset is present. Our analysis demonstrates that the four-step phase cycling scheme studied is robust in suppressing unwanted double and single quantum coherence as well as Zeeman order that arise from the experimental artifacts, allowing for an unbiased measurement of the quadrupolar alignment relaxation time, T(1Q). This work also reports on distortions in quadrupolar alignment echo spectra in the presence of experimental artifacts in the situation of a powdered sample, by simulation. Using our simulation tool, it is demonstrated that the spectral distortions associated with the pulse artifacts may be minimized, to some extent, by optimally choosing the time between the first two pulses. We highlight experimental results acquired on perdeuterated hexamethylbenzene and polyethylene that demonstrate the efficacy of the phase cycling scheme for suppressing unwanted quantum coherence when measuring T(1Q). It is suggested that one employ two separate pulse sequences when measuring T(1Q) to properly analyze the short time behavior of quadrupolar alignment relaxation data.     

Quantitative Evaluation of the Lactate Signal Loss and Its Spatial Dependence in PRESS Localized H NMR Spectroscopy

Localized ¹H NMR spectroscopy using the 90°−t₁−180°−t₁+t₂−180°−t₂−Acq. PRESS sequence can lead to a signal loss for the lactate doublet compared with signals from uncoupled nuclei which is dependent on the choice of t₁ and t₂. The most striking signal loss of up to 78% of the total signal occurs with the symmetrical PRESS sequence (t₁=t₂) at an echo time of 2/J (290 ms). Calculations have shown that this signal loss is related to the pulse angle distributions produced by the two refocusing pulses which leads to the creation of single quantum polarization transfer (PT) as well as to not directly observable states (NDOS) of the lactate AX₃ spin system: zero- and multiple-quantum coherences, and longitudinal spin orders. In addition, the chemical shift dependent voxel displacement (VOD) leads to further signal loss. By calculating the density operator for various of the echo times TE=n/J, n=1, 2, 3, …, we calculated quantitatively the contributions of these effects to the signal loss as well as their spatial distribution. A maximum signal loss of 75% can be expected from theory for the symmetrical PRESS sequence and TE=2/J for Hamming filtered sinc pulses, whereby 47% are due to the creation of NDOS and up to 28% arise from PT. Taking also the VOD effect into account (2 mT/m slice selection gradients, 20-mm slices) leads to 54% signal loss from NDOS and up to 24% from PT, leading to a maximum signal loss of 78%. Using RE-BURP pulses with their more rectangular pulse angle distributions reduces the maximum signal loss to 44%. Experiments at 1.5 T using a lactate solution demonstrated a maximum lactate signal loss for sinc pulses of 82% (52% NDOS, 30% PT) at TE=290 ms using the symmetrical PRESS sequence. The great signal loss and its spatial distribution is of importance for investigations using a symmetrical PRESS sequence at TE=2/J.