Real-time motion and B0 correction for localized adiabatic selective refocusing (LASER) MRSI using echo planar imaging volumetric navigators

A method is presented to correct the effects of motion and motion‐related B₀ perturbations on spectroscopic imaging in real time through the use of a volumetric navigator. It is demonstrated that, for an axial slice, lifting the chin significantly disrupts the B₀ homogeneity in the zero‐order (frequency), first‐order Y (coronal) axis and second‐order ZY term. This volumetric navigator is able to measure and correct in real time both head pose and zero‐ to first‐order B₀ inhomogeneities. The volumetric navigator was validated in six volunteers who deliberately lifted and then dropped their chin during the scan. These scans show that motion correction alone is not sufficient to recover the spectral quality. By applying real‐time shim adjustments, spectral quality was fully recovered to linewidths below 0.08 ppm and the signal‐to‐noise ratio to within acceptable limits in five of six subjects. In the sixth subject, 83% of the spectra within the volume of interest were recovered, compared with the worst case nonshim‐corrected scan, where none of the voxels fell within these quality bounds. It is shown that the use of a volumetric navigator comes at no additional cost to the scan time or spectral signal‐to‐noise ratio. Copyright © 2011 John Wiley & Sons, Ltd.     

On the transmit field inhomogeneity correction of relaxation‐compensated amide and NOE CEST effects at 7 T

High field MRI is beneficial for chemical exchange saturation transfer (CEST) in terms of high SNR, CNR, and chemical shift dispersion. These advantages may, however, be counter‐balanced by the increased transmit field inhomogeneity normally associated with high field MRI. The relatively high sensitivity of the CEST contrast to B₁ inhomogeneity necessitates the development of correction methods, which is essential for the clinical translation of CEST. In this work, two B₁ correction algorithms for the most studied CEST effects, amide‐CEST and nuclear Overhauser enhancement (NOE), were analyzed. Both methods rely on fitting the multi‐pool Bloch‐McConnell equations to the densely sampled CEST spectra. In the first method, the correction is achieved by using a linear B₁ correction of the calculated amide and NOE CEST effects. The second method uses the Bloch‐McConnell fit parameters and the desired B₁ amplitude to recalculate the CEST spectra, followed by the calculation of B₁‐corrected amide and NOE CEST effects. Both algorithms were systematically studied in Bloch‐McConnell equations and in human data, and compared with the earlier proposed ideal interpolation‐based B₁ correction method. In the low B₁ regime of 0.15–0.50 μT (average power), a simple linear model was sufficient to mitigate B₁ inhomogeneity effects on a par with the interpolation B₁ correction, as demonstrated by a reduced correlation of the CEST contrast with B₁ in both the simulations and the experiments.     

MASE‐sLASER,a short‐TE,matched chemical shift displacement error sequence for single‐voxel spectroscopy at ultrahigh field

B₁ inhomogeneity and chemical shift displacement error (CSDE) increase with the main magnetic field strength and are therefore deleterious for magnetic resonance spectroscopy (MRS) at ultrahigh field. A solution is to use adiabatic pulses which operate over a broad range of B₁ and thus are insensitive to B₁ inhomogeneity. Moreover, adiabatic pulses usually have a relatively higher bandwidth, which makes CSDE low to negligible. The use of exclusively adiabatic pulses for single‐voxel spectroscopy (SVS) typically brings the disadvantage of a long echo time (TE), but the advantage of a low and matched CSDE. Herein, we took advantage of short‐duration, low‐power, matched‐phase adiabatic spin echo (MASE) pulses to implement a matched CSDE semi‐localized by adiabatic selective refocusing (sLASER) sequence capable of attaining short TEs, while CSDE is matched and still comparatively low. We also demonstrate here the feasibility of the direct measurement of the γ‐aminobutyric acid (GABA) resonance at 2.28 ppm well separated from the neighboring glutamate resonance at 7 T using the implemented MASE‐sLASER sequence at TEs of 68 and 136 ms. The shorter duration of MASE pulses also made it possible to implement a Mescher–Garwood‐semi‐localized by adiabatic selective refocusing (MEGA‐sLASER) (with MASE) sequence with TE = 68 ms for editing GABA at 7 T, the results for which are also shown.     

Correction of B1‐inhomogeneities for relaxation‐compensated CEST imaging at 7 T

Chemical exchange saturation transfer (CEST) imaging of endogenous agents in vivo is influenced by direct water proton saturation (spillover) and semi‐solid macromolecular magnetization transfer (MT). Lorentzian fit isolation and application of the inverse metric yields the pure CEST contrast AREX, which is less affected by these processes, but still depends on the measurement technique, in particular on the irradiation amplitude B₁ of the saturation pulses. This study focuses on two well‐known CEST effects in the slow exchange regime originating from amide and aliphatic protons resonating at 3.5 ppm or ?3.5 ppm from water protons, respectively. A B₁‐correction of CEST contrasts is crucial for the evaluation of data obtained in clinical studies at high field strengths with strong B₁‐inhomogeneities. Herein two approaches for B₁‐inhomogeneity correction, based on either CEST contrasts or Z‐spectra, are investigated. Both rely on multiple acquisitions with different B₁‐values. One volunteer was examined with eight different B₁‐values to optimize the saturation field strength and the correction algorithm. Histogram evaluation allowed quantification of the quality of the B₁‐correction. Finally, the correction was applied to CEST images of a patient with oligodendroglioma WHO grade 2, and showed improvement of the image quality compared with the non‐corrected CEST images, especially in the tumor region. Copyright © 2015 John Wiley & Sons, Ltd.     

In vivo detection and automatic analysis of GABA in the mouse brain with MEGA‐PRESS at 9.4 T

The goals of this study were to develop an acquisition protocol and the analysis tools for Meshcher–Garwood point‐resolved spectroscopy (MEGA‐PRESS) in mouse brain at 9.4 T, to allow the in vivo detection of γ‐aminobutyric acid (GABA) and to examine whether isoflurane alters GABA levels in the thalamus during anesthesia. We implemented the MEGA‐PRESS sequence on a Bruker 94/20 system with ParaVision 6.0.1, and magnetic resonance spectra were acquired from nine male wild‐type C57BL/6 J mice at the thalamus. Four individual scans were obtained for each mouse in a 2‐h time course whilst the mouse was anesthetized with isoflurane. We developed an automated analysis program with improved correction for frequency and phase drift compared with the standard creatine (Cr) fitting‐based method and provided automatic quantification. During MEGA‐PRESS acquisition, a single voxel with a size of 5 × 3 × 3 mm³ was placed at the thalamus to evaluate GABA to Cr (GABA/Cr) ratios during anesthesia. Detection and quantitative analysis of thalamic GABA levels were successfully achieved. We noticed a significant decrease in GABA/Cr during the 2‐h anesthesia (by linear regression analysis: slope < 0, p < 0.0001). In summary, our findings demonstrate that MEGA‐PRESS is a feasible technique to measure in vivo GABA levels in the mouse brain at 9.4 T.     

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.     

The in vivo J‐difference editing MEGA‐PRESS technique for the detection of n‐3 fatty acids

In this study, we present a method for the detection of n‐3 fatty acid (n‐3 FA) signals using MRS in adipose tissue in vivo. This method (called oMEGA‐PRESS) is based on the selective detection of the CH₃ signal of n‐3 FA using the MEGA‐PRESS (MEshcher–GArwood Point‐RESolved Spectroscopy) J‐difference editing technique. We optimized the envelope shape and frequency of spectral editing pulses to minimize the spurious co‐editing and incomplete subtraction of the CH₃ signal of other FAs, which normally obscure the n‐3 FA CH₃ signal in MR spectra acquired using standard PRESS techniques. The post‐processing of the individual data scans with the phase and frequency correction before data subtraction and averaging was implemented to further improve the quality of in vivo spectra. The technique was optimized in vitro on lipid phantoms using various concentrations of n‐3 FA and examined in vivo at 3 T on 15 healthy volunteers. The proportion of n‐3 FA estimated by the oMEGA‐PRESS method in phantoms showed a highly significant linear correlation with the n‐3 FA content determined by gas chromatography. The signal attributed to n‐3 FA was observed in all subjects. Comparisons with the standard PRESS technique revealed an enhanced identification of the n‐3 FA signal using oMEGA‐PRESS. The presented method may be useful for the non‐invasive quantification of n‐3 FA in adipose tissue, and could aid in obtaining a better understanding of various aspects of n‐3 FA metabolism. Copyright © 2014 John Wiley & Sons, Ltd.     

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.     

Efficient γ-aminobutyric acid editing at 3T without macromolecule contamination: MEGA-SPECIAL

One of the most commonly used methods for in vivo MRS detection of γ‐aminobutyric acid (GABA) is the MEGA‐point‐resolved spectroscopy (MEGA‐PRESS) technique. However, accurate quantification of GABA using MEGA‐PRESS is complicated by spectral co‐editing of macromolecular resonances. In this article, a new pulse sequence is presented which enables GABA editing at 3T with the removal of macromolecule contamination. This sequence combines the conventional MEGA editing scheme with the SPECIAL localisation technique, and is therefore named MEGA‐SPECIAL. Simulations and phantom experiments indicate that this new approach provides improved GABA editing efficiency relative to MEGA‐PRESS, and in vivo results demonstrate effective removal of macromolecule contamination. In a study of the occipital lobe of five healthy volunteers, the macromolecule‐corrected GABA/creatine ratio was found to be 0.093 ± 0.007 (mean ± standard deviation), whereas prior to macromolecule correction, the ratio was found to be 0.173 ± 0.013. Copyright © 2011 John Wiley & Sons, Ltd.     

Improved efficiency on editing MRS of lactate and γ‐aminobutyric acid by inclusion of frequency offset corrected inversion pulses at high fields

γ‐Aminobutyric acid (GABA) and lactate are metabolites which are present in the brain. These metabolites can be indicators of psychiatric disorders or tumor hypoxia, respectively. The measurement of these weakly coupled spin systems can be performed using MRS editing techniques; however, at high field strength, this can be challenging. This is due to the low available B₁⁺ field at high fields, which results in narrow‐bandwidth refocusing pulses and, consequently, in large chemical shift displacement artifacts. In addition, as a result of the increased chemical shift displacement artifacts and chemical shift dispersion, the efficiency of the MRS method is reduced, even when using adiabatic refocusing pulses. To overcome this limitation, frequency offset corrected inversion (FOCI) pulses have been suggested as a mean to substantially increase the bandwidth of adiabatic pulses. In this study, a Mescher–Garwood semi‐localization by adiabatic selection and refocusing (MEGA‐sLASER) editing sequence with refocusing FOCI pulses is presented for the measurement of GABA and lactate in the human brain. Metabolite detection efficiencies were improved by 20% and 75% for GABA and lactate, respectively, when compared with editing techniques that employ adiabatic radiofrequency refocusing pulses. The highly efficient MEGA‐sLASER sequence with refocusing FOCI pulses is an ideal and robust MRS editing technique for the measurement of weakly coupled metabolites at high field strengths. Copyright © 2013 John Wiley & Sons, Ltd.     

Temporal B0 field variation effects on MRSI of the human prostate at 7 T and feasibility of correction using an internal field probe

Spectral degradations as a result of temporal field variations are observed in MRSI of the human prostate. Moving organs generate substantial temporal and spatial field fluctuations as a result of susceptibility mismatch with the surrounding tissue (i.e. periodic breathing, cardiac motion or random bowel motion). Nine patients with prostate cancer were scanned with an endorectal coil (ERC) on a 7‐T MR scanner. Temporal B₀ field variations were observed with fast dynamic B₀ mapping in these patients. Simulations of dynamic B₀ corrections were performed using zero‐ to second‐order shim terms. In addition, the temporal B₀ variations were applied to simulated MR spectra causing, on average, 15% underestimation of the choline/citrate ratio. Linewidth distortions and frequency shifts (up to 30 and 8 Hz, respectively) were observed. To demonstrate the concept of observing local field fluctuations in real time during MRSI data acquisition, a field probe (FP) tuned and matched for the ¹⁹ F frequency was incorporated into the housing of the ERC. The data acquired with the FP were compared with the B₀ field map data and used to correct the MRSI datasets retrospectively. The dynamic B₀ mapping data showed variations of up to 30 Hz (0.1 ppm) over 72 s at 7 T. The simulated zero‐order corrections, calculated as the root mean square, reduced the standard deviation (SD) of the dynamic variations by an average of 41%. When using second‐order corrections, the reduction in the SD was, on average, 56%. The FP data showed the same variation range as the dynamic B₀ data and the variation patterns corresponded. After retrospective correction, the MRSI data showed artifact reduction and improved spectral resolution. B₀ variations can degrade the MRSI substantially. The simple incorporation of an FP into an ERC can improve prostate cancer MRSI without prior knowledge of the origin of the dynamic field distortions. Copyright © 2014 John Wiley & Sons, Ltd.     

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.     

Spatial Hadamard encoding of J‐edited spectroscopy using slice‐selective editing pulses

A new approach for simultaneous dual‐voxel J‐difference spectral editing is described, which uses spatially selective spectral‐editing pulses and Hadamard encoding. A theoretical framework for spatial Hadamard editing and reconstruction for parallel acquisition (SHERPA) was developed, applying gradient pulses during the frequency‐selective editing pulses. Spectral simulations were performed for either one (gamma‐aminobutyric acid, GABA) or two molecules (glutathione and lactate) simultaneously detected in two voxels. The method was tested in a two‐compartment GABA phantom, and finally applied to the left and right hemispheres of 10 normal control subjects, scanned at 3 T. SHERPA was successfully implemented at 3 T and gave results in close agreement with conventional MEGA‐PRESS scans in both the phantom and in vivo experiments. Simulations for GABA editing for (3 cm)³ voxels in the left and right hemispheres suggest that both editing efficiency losses and contamination between voxels are about 2%. Compared with conventional single‐voxel single‐metabolite J‐difference editing, two‐ or fourfold acceleration is possible without significant loss of SNR using the SHERPA method. Unlike some other dual‐voxel methods, the method can be used with single‐channel receiver coils, and there is no SNR loss due to unfavorable receive‐coil geometry factors.     

DYNAmic Multi‐coIl TEchnique (DYNAMITE) shimming of the rat brain at 11.7 T

The in vivo rat model is a workhorse in neuroscience research, preclinical studies and drug development. A repertoire of MR tools has been developed for its investigation; however, high levels of B₀ magnetic field homogeneity are required for meaningful results. The homogenization of magnetic fields in the rat brain, i.e. shimming, is a difficult task because of a multitude of complex, susceptibility‐induced field distortions. Conventional shimming with spherical harmonic (SH) functions is capable of compensating for shallow field distortions in limited areas, e.g. in the cortex, but performs poorly in difficult‐to‐shim subcortical structures or for the entire brain. Based on the recently introduced multi‐coil approach for magnetic field modeling, the DYNAmic Multi‐coIl TEchnique (DYNAMITE) is introduced for magnetic field shimming of the in vivo rat brain and its benefits for gradient‐echo echo‐planar imaging (EPI) are demonstrated. An integrated multi‐coil/radiofrequency (MC/RF) system comprising 48 individual localized DC coils for B₀ shimming and a surface transceive RF coil has been developed that allows MR investigations of the anesthetized rat brain in vivo. DYNAMITE shimming with this MC/RF set‐up is shown to reduce the B₀ standard deviation to a third of that achieved with current shim technology employing static first‐ through third‐order SH shapes. The EPI signal over the rat brain increased by 31%, and a 24% gain in usable EPI voxels could be realized. DYNAMITE shimming is expected to critically benefit a wide range of preclinical and neuroscientific MR research. Improved magnetic field homogeneity, together with the achievable large brain coverage of this method, will be crucial when signal pathways, cortical circuitry or the brain's default network are studied. Together with the efficiency gains of MC‐based shimming compared with SH approaches demonstrated recently, DYNAMITE shimming has the potential to replace conventional SH shim systems in small‐bore animal scanners. Copyright © 2014 John Wiley & Sons, Ltd.     

Quantification of glutamate and glutamine using constant‐time point‐resolved spectroscopy at 3 T

Separate quantification of glutamate (Glu) and glutamine (Gln) using conventional MRS on clinical scanners is challenging. In previous work, constant‐time point‐resolved spectroscopy (CT‐PRESS) was optimized at 3 T to detect Glu, but did not resolve Gln. To quantify Glu and Gln, a time‐domain basis set was constructed taking into account metabolite T₂ relaxation times and dephasing from B₀ inhomogeneity. Metabolite concentrations were estimated by fitting the basis one‐dimensional CT‐PRESS diagonal magnitude spectra to the measured spectrum. This method was first validated using seven custom‐built phantoms containing variable metabolite concentrations, and then applied to in vivo data acquired in rats exposed to vaporized ethanol and controls. Separate metabolite quantification revealed increased Gln after 16 weeks and increased Glu after 24 weeks of vaporized ethanol exposure in ethanol‐treated compared with control rats. Without separate quantification, the signal from the combined resonances of Glu and Gln (Glx) showed an increase at both 16 and 24 weeks in ethanol‐exposed rats, precluding the determination of the independent and differential contribution of each metabolite at each time. Copyright © 2012 John Wiley & Sons, Ltd.     

Navigator based respiratory gating during acquisition and preparation phases for proton liver spectroscopy at 3 T

Proton magnetic resonance spectroscopy (¹H MRS) enables the non‐invasive investigation of the human liver; however, because of technical difficulties it is not regularly used for diagnosis of liver diseases in clinical routine. Breathing motion is one of the major challenges, as it decreases spectral quality and leads to misplacement of the spectroscopic voxel. To overcome this problem, real‐time navigator gating for spectral acquisition and preparation steps (B₀ shimming, water frequency determination, receiver gain optimization, and water suppression) combined with short T_E, optimized first order projection based B₀ shimming, water suppression, and inner‐volume saturated point resolved spectroscopy (PRESS) at 3 T is suggested. Simultaneous lipid and trimethylamine quantification is demonstrated by means of phantom, volunteer, and representative patient measurements. Precise localization of the voxel despite respiratory motion, increased spectral quality (higher signal‐to‐noise ratio and reduced linewidth) compared with measurements without respiratory gating, and the possibility of acquiring data without additional subject instructions regarding breathing enable robust and accurate liver ¹H MRS measurements with this novel acquisition protocol. Copyright © 2014 John Wiley & Sons, Ltd.     

Expression and distribution of GABA and GABAB‐receptor in the rat adrenal gland

The inhibitory effects of gamma‐aminobutyric acid (GABA) in the central and peripheral nervous systems and the endocrine system are mediated by two different GABA receptors: GABA_A‐receptor (GABA_A‐R) and GABA_B‐receptor (GABA_B‐R). GABA_A‐R, but not GABA_B‐R, has been observed in the rat adrenal gland, where GABA is known to be released. This study sought to determine whether both GABA and GABA_B‐R are present in the endocrine and neuronal elements of the rat adrenal gland, and to investigate whether GABA_B‐R may play a role in mediating the effects of GABA in secretory activity of these cells. GABA‐immunoreactive nerve fibers were observed in the superficial cortex. Some GABA‐immunoreactive nerve fibers were found to be associated with blood vessels. Double‐immunostaining revealed GABA‐immunoreactive nerve fibers in the cortex were choline acetyltransferase (ChAT)‐immunonegative. Some GABA‐immunoreactive nerve fibers ran through the cortex toward the medulla. In the medulla, GABA‐immunoreactivity was seen in some large ganglion cells, but not in the chromaffin cells. Double‐immunostaining also showed GABA‐immunoreactive ganglion cells were nitric oxide synthase (NOS)‐immunopositive. However, neither immunohistochemistry combined with fluorescent microscopy nor double‐immunostaining revealed GABA‐immunoreactivity in the noradrenaline cells with blue‐white fluorescence or in the adrenaline cells with phenylethanolamine N‐methyltransferase (PNMT)‐immunoreactivity. Furthermore, GABA‐immunoreactive nerve fibers were observed in close contact with ganglion cells, but not chromaffin cells. Double‐immunostaining also showed that the GABA‐immunoreactive nerve fibers were in close contact with NOS‐ or neuropeptide tyrosine (NPY)‐immunoreactive ganglion cells. A few of the GABA‐immunoreactive nerve fibers were ChAT‐immunopositive, while most of the GABA‐immunoreactive nerve fibers were ChAT‐immunonegative. Numerous ChAT‐immunoreactive nerve fibers were observed in close contact with the ganglion cells and chromaffin cells in the medulla. The GABA_B‐R‐immunoreactivity was found only in ganglion cells in the medulla and not at all in the cortex. Immunohistochemistry combined with fluorescent microscopy and double‐immunostaining showed no GABA_B‐R‐immunoreactivity in noradrenaline cells with blue‐white fluorescence or in adrenaline cells with PNMT‐immunoreactivity. These immunoreactive ganglion cells were NOS‐ or NPY‐immunopositive on double‐immunostaining. These findings suggest that GABA from the intra‐adrenal nerve fibers may have an inhibitory effect on the secretory activity of ganglion cells and cortical cells, and on the motility of blood vessels in the rat adrenal gland, mediated by GABA‐Rs.     

Thermoreversible Order−Order Transition of a Triblock Copolymer Containing a Mesogen‐Jacketed Liquid Crystalline Polymer with a Re‐Entrant Phase Behavior

Poly{2,5‐bis[(4‐butoxyphenyl)‐oxycarbonyl]styrene} (PBPCS) with a re‐entrant phase behavior is used to synthesize a new kind of ABC triblock copolymers (triBCPs), poly(dimethylsiloxane)‐b‐polystyrene‐b‐PBPCS (PDMS‐b‐PS‐b‐PBPCS, DSB). Two well‐defined triBCPs D₁₂₀S₁₀₀B₅₀ and D₁₂₀S₁₀₀B₁₂₀ with different molecular weights (MWs) and narrow MW distributions are synthesized by sequential atom transfer radical polymerization. The volume fractions of PDMS, PS, and PBPCS in D₁₂₀S₁₀₀B₅₀ are 0.24, 0.26, and 0.50, respectively, while the values in D₁₂₀S₁₀₀B₁₂₀ are 0.14, 0.16, and 0.70, respectively. At low temperatures, PBPCS is amorphous. Both samples form a core–shell hexagonally packed cylindrical (CSH) morphology. At high temperatures, PBPCS in the triBCPs can form a liquid crystalline (LC) phase, the transformation of which can induce an order?order transition (OOT) of D₁₂₀S₁₀₀B₁₂₀. The nanostructure changes from a CSH structure to a three‐phase‐four‐layer lamellar structure, and the transition is thermoreversible. The sequence of the OOT is opposite to that of a coil?coil?coil triBCP. The unusual LC behavior of PBPCS plays an important role on the thermoreversible morphological transition of the triBCP.

     

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.