Neurometabolic profile of the amygdala in smokers assessed with 1H-magnetic resonance spectroscopy.

Tobacco smoking is one of the main causes of premature death worldwide and quitting success remains low, highlighting the need to understand the neurobiological mechanisms underlying relapse. Preclinical models have shown that the amygdala and glutamate play an important role in nicotine addiction. The aims of this study were to compare glutamate and other metabolites in the amygdala between smokers and controls, and between different smoking states. Furthermore, associations between amygdalar metabolite levels and smoking characteristics were explored. A novel non-water-suppressed proton magnetic resonance spectroscopy protocol was applied to quantify neurometabolites in 28 male smokers (≥15 cigarettes/day) and 21 non-smoking controls, matched in age, education, verbal IQ, and weekly alcohol consumption. Controls were measured once (baseline) and smokers were measured in a baseline state (1-3 h abstinence), during withdrawal (24 h abstinence) and in a satiation state (directly after smoking). Baseline spectroscopy data were compared between groups by independent t-tests or Mann-Whitney-U tests. Smoking state differences were investigated by repeated-measures analyses of variance (ANOVAs). Associations between spectroscopy data and smoking characteristics were explored using Spearman correlations. Good spectral quality, high anatomical specificity (98% mean gray matter) and reliable quantification of most metabolites of interest were achieved in the amygdala. Metabolite levels did not differ between groups, but smokers showed significantly higher glutamine levels at baseline than satiation. Glx levels were negatively associated with pack-years and smoking duration. In summary, this study provides first insights into the neurometabolic profile of the amygdala in smokers with high anatomical specificity. By applying proton magnetic resonance spectroscopy, neurometabolites in smokers during different smoking states and non-smoking controls were quantified reliably. A significant shift in glutamine levels between smoking states was detected, with lower concentrations in satiation than baseline. The negative association between Glx levels and smoking quantity and duration may imply altered glutamate homeostasis with more severe nicotine addiction.

3T 31P/1H calf muscle coil for 1H and 31P MRI/MRS integrated with NIRS data acquisition.

PURPOSE: Our aim was to design and build a 3T 31P/1H calf coil that is capable of providing both good 31P and 1H transmit and receive performance, as well as being capable of accommodating a near-infrared spectroscopy (NIRS) device for simultaneous NIRS data and MRI/MRS acquisition. METHOD: In this work, we propose a new 3T 31P/1H birdcage combination design consisting of two co-centrically positioned birdcages on the same surface to maximize transmit efficiency and sensitivity for both nuclei. The 31P birdcage is a high-pass birdcage, whereas the 1H birdcage is a low-pass one to minimize coupling. The diameter of the 31P/1H birdcage combination was designed to be large enough to accommodate a NIRS device for simultaneous NIRS data and MRI/MRS acquisition. RESULTS: The one-layer coil structure of the birdcage combination significantly streamlines the mechanical design and coil assembly process. Full-wave simulation results show that the 31P and 1H are very well decoupled with each other, and the 1H and 31P SNR surpasses that of their standalone counterparts in the central area. Experiment results show that the inclusion of a NIRS device does not significantly affect the performance of the coil, thus enabling simultaneous NIRS and MRI readouts during exercise. CONCLUSION: Our findings demonstrate the feasibility and effectiveness of this dual-tuned coil design for combined NIRS and MRS measurements, offering potential benefits for studying metabolic and functional changes in the skeletal muscle in vivo.

Mapping of glutamate metabolism using 1H FID-MRSI after oral administration of [1-13C]Glc at 9.4 T.

Glutamate is the major excitatory transmitter in the brain and malfunction of the related metabolism is associated with various neurological diseases and disorders. The observation of labeling changes in the spectra after the administration of a 13C labelled tracer is a common tool to gain better insights into the function of the metabolic system. But so far, only a very few studies presenting the labeling effects in more than two voxels to show the spatial dependence of metabolism. In the present work, the labeling effects were measured in a transversal plane in the human brain using ultra-short TE and TR 1H FID-MRSI. The measurement set-up was most simple: The [1-13C]Glc was administered orally instead of intravenous and the spectra were measured with a pure 1H technique without the need of a 13C channel (as Boumezbeur et al. demonstrated in 2004). Thus, metabolic maps and enrichment curves could be obtained for more metabolites and in more voxels than ever before in human brain. Labeling changes could be observed in [4-13C]glutamate, [3-13C]glutamate+glutamine, [2-13C]glutamate+glutamine, [4-13C]glutamine, and [3-13C]aspartate with a high temporal (3.6 min) and spatial resolution (32 × 32 grid with nominal voxel size of 0.33 µL) in five volunteers.

Test-retest reproducibility of human brain multi-slice 1 H FID-MRSI data at 9.4T after optimization of lipid regularization, macromolecular model, and spline baseline stiffness.

PURPOSE: This study analyzes the effects of retrospective lipid suppression, a simulated macromolecular prior knowledge and different spline baseline stiffness values on 9.4T multi-slice proton FID-MRSI data spanning the whole cerebrum of human brain and the reproducibility of respective metabolite ratio to total creatine (/tCr) maps for 10 brain metabolites. METHODS: Measurements were performed twice on 5 volunteers using a short TR and TE FID MRSI 2D sequence at 9.4T. The effects of retrospective lipid L2-regularization, macromolecular spectrum and different LCModel baseline flexibilities on SNR, FWHM, fitting residual, Cramér-Rao lower bound, and metabolite ratio maps were investigated. Intra-subject, inter-session coefficient of variation and the test-retest reproducibility of the mean metabolite ratios (/tCr) of each slice was calculated. RESULTS: Transversal, sagittal, and coronal slices of many metabolite ratio maps correspond to the anatomically expected concentration relations in gray and white matter for the majority of the cerebrum when using a flexible baseline in LCModel fit. Results from the second measurements of the same subjects show that slice positioning and data quality correlate significantly to the first measurement. L2-regularization provided effective suppression of lipid-artifacts, but should be avoided if no artifacts are detected. CONCLUSION: Reproducible concentration ratio maps (/tCr) for 4 metabolites (total choline, N-acetylaspartate, glutamate, and myoinositol) spanning the majority of the cerebrum and 6 metabolites (N-acetylaspartylglutamate, γ-aminobutyric acid, glutathione, taurine, glutamine, and aspartate) covering 32 mm in the upper part of the brain were acquired at 9.4T using multi-slice FID MRSI with retrospective lipid suppression, a macromolecular spectrum and a flexible LCModel baseline.

Deuterium metabolic imaging of the human brain in vivo at 7 T.

PURPOSE: To explore the potential of deuterium metabolic imaging (DMI) in the human brain in vivo at 7 T, using a multi-element deuterium (2 H) RF coil for 3D volume coverage. METHODS: 1 H-MR images and localized 2 H MR spectra were acquired in vivo in the human brain of 3 healthy subjects to generate DMI maps of 2 H-labeled water, glucose, and glutamate/glutamine (Glx). In addition, non-localized 2 H-MR spectra were acquired both in vivo and in vitro to determine T1 and T2 relaxation times of deuterated metabolites at 7 T. The performance of the 2 H coil was assessed through numeric simulations and experimentally acquired B1 + maps. RESULTS: 3D DMI maps covering the entire human brain in vivo were obtained from well-resolved deuterated (2 H) metabolite resonances of water, glucose, and Glx. The T1 and T2 relaxation times were consistent with those reported at adjacent field strengths. Experimental B1 + maps were in good agreement with simulations, indicating efficient and homogeneous B1 + transmission and low RF power deposition for 2 H, consistent with a similar array coil design reported at 9.4 T. CONCLUSION: Here, we have demonstrated the successful implementation of 3D DMI in the human brain in vivo at 7 T. The spatial and temporal nominal resolutions achieved at 7 T (i.e., 2.7 mL in 28 min, respectively) were close to those achieved at 9.4 T and greatly outperformed DMI at lower magnetic fields. DMI at 7 T and beyond has clear potential in applications dealing with small brain lesions.

Quantitative T1-relaxation corrected metabolite mapping of 12 metabolites in the human brain at 9.4 T.

Magnetic resonance spectroscopic imaging (MRSI) is a non-invasive imaging modality that enables observation of metabolites. Applications of MRSI for neuroimaging have shown promise for monitoring and detecting various diseases. This study builds off previously developed techniques of short TR, 1H FID MRSI by correcting for T1-weighting of the metabolites and utilizing an internal water reference to produce quantitative (mmol kg-1) metabolite maps. This work reports and shows quantitative metabolite maps for 12 metabolites for a single slice. Voxel-specific T1-corrections for water are common in MRSI studies; however, most studies use either averaged T1-relaxation times to correct for T1-weighting of metabolites or omit this correction step entirely. This work employs the use of voxel-specific T1-corrections for metabolites in addition to water. Utilizing averaged T1-relaxation times for metabolites can bias metabolite maps for metabolites that have strong differences between T1-relaxation for GM and WM (i.e. Glu). This work systematically compares quantitative metabolite maps to single voxel quantitative results and qualitatively compares metabolite maps to previous works.

Improved signal-to-noise performance of MultiNet GRAPPA 1 H FID MRSI reconstruction with semi-synthetic calibration data.

PURPOSE: To further develop MultiNet GRAPPA, a neural-network-based reconstruction, for lower SNR proton MRSI (1 H MRSI) data using adapted undersampling schemes and improved training sets. METHODS: 1 H FID-MRSI data and an anatomical image for GRAPPA reconstruction were acquired in two slices in the human brain (n = 6) at 7T. MRSI data were retrospectively undersampled for a 4×, 6×, and 7× acceleration rate. Signal-to-noise, relative error (RE) between accelerated and fully sampled metabolic maps, RMS of the lipid artifacts, and fitting reliability were compared across acceleration rates, to the fully sampled data, and with different kinds and amounts of training images. RESULTS: Training with semi-synthetic images resulted in higher SNR and lower lipid RMS relative to training with acquired images from one or several subjects. SNR increased with the number of semi-synthetic training images and the 4× accelerated data retains ∼30% more SNR than other accelerated data. Spectra reconstructed with 20 semi-synthetic averages retained ∼100% more SNR and had ∼5% lower lipid RMS than those reconstructed with the center k-space points of one image as was originally proposed for very high SNR MRSI data and had higher fitting reliability. The metabolite RE was lowest when training with 20-semi-synthetic training images and highest when training with the center k-space points of one image. CONCLUSION: MultiNet GRAPPA is feasible with lower SNR 1 H MRSI data if 20-semi-synthetic training images are used at a 4× acceleration rate. This acceleration rate provided the best trade-off between scan time and spectral SNR.

Relaxation-corrected macromolecular model enables determination of 1 H longitudinal T1 -relaxation times and concentrations of human brain metabolites at 9.4T.

PURPOSE: Ultrahigh field MRS has improved characterization of the neurochemical profile. To compare results obtained at 9.4T to those from lower field strengths, it is of interest to quantify the concentrations of metabolites measured. Thus, measuring T1 -relaxation times is necessary to correct for T1 -weighting that occurs in acquisitions for single-voxel spectroscopy and spectroscopic imaging. A macromolecule (MM) simulation model was developed to fit MM contributions to the short TE inversion series used to measure T1 -relaxation times. METHODS: An inversion series with seven time points was acquired with metabolite-cycled STEAM to estimate T1 -relaxation times of metabolites. A short TE was employed in this study to retain signals from metabolites with short T2 -relaxation times and J-couplings. The underlying macromolecule spectrum was corrected by developing a sequence-specific, relaxation-corrected simulated MM model. Quantification of metabolite peaks was performed using internal water referencing and relaxation corrections. RESULTS: T1 -relaxation times for metabolites range from approximately 750 to approximately 2000 ms and approximately 1000 to approximately 2400 ms in gray matter (GM)- and white matter (WM)- rich voxels, respectively. Quantification of metabolites was compared between GM and WM voxels, as well as between results that used a simulated MM spectrum against those that used an experimentally acquired MM spectrum. Metabolite concentrations are reported in mmol/kg quantities. CONCLUSION: T1 -relaxation times are reported for nonsinglet resonances for the first time at 9.4T by use of a MM simulation model to account for contributions from the MM spectrum. In addition to T1 -relaxation times, quantification results of metabolites from GM- and WM-rich voxels are reported.

A 32-element loop/dipole hybrid array for human head imaging at 7 T.

PURPOSE: To improve whole-brain SNR at 7 Tesla, a novel 32-element hybrid human head array coil was developed, constructed, and tested. METHODS: Our general design strategy is based on 2 major ideas: Firstly, following suggestions of previous works based on the ultimate intrinsic SNR theory, we combined loops and dipoles for improvement of SNR near the head center. Secondly, we minimized the total number of array elements by using a hybrid combination of transceive (TxRx) and receive (Rx) elements. The new hybrid array consisted of 8 folded-end TxRx-dipole antennas and 3 rows of 24 Rx-loops all placed in a single layer on the surface of a tight-fit helmet. RESULTS: The developed array significantly improved SNR in vivo both near the center (∼20%) and at the periphery (∼20% to 80%) in comparison to a common commercial array coil with 8 transmit (Tx) and 32 Rx-elements. Whereas 24 loops alone delivered central SNR very similar to that of the commercial coil, the addition of complementary dipole structures provided further improvement. The new array also provided ∼15% higher Tx efficiency and better longitudinal coverage than that of the commercial array. CONCLUSION: The developed array coil demonstrated advantages in combining complementary TxRx and Rx resonant structures, that is, TxRx-dipoles and Rx-loops all placed in a single layer at the same distance to the head. This strategy improved both SNR and Tx-performance, as well as simplified the total head coil design, making it more robust.

Phosphorus transversal relaxation times and metabolite concentrations in the human brain at 9.4 T.

A method to estimate phosphorus (31 P) transversal relaxation times (T2 s) of coupled spin systems is demonstrated. Additionally, intracellular and extracellular pH and relaxation-corrected metabolite concentrations are reported. Echo time (TE) series of 31 P metabolite spectra were acquired using stimulated echo acquisition mode (STEAM) localization. Spectra were fitted using LCModel with accurately modeled Versatile Simulation, Pulses and Analysis (VeSPA) basis sets accounting for J-evolution of the coupled spin systems. T2 s were estimated by fitting a single exponential two-parameter model across the TE series. Fitted inorganic phosphate frequencies were used to calculate pH, and estimated relaxation times were used to determine the relaxation-corrected brain metabolite concentrations on an assumption of 3 mM γ-ATP. The method was demonstrated in healthy human brain at a field strength of 9.4 T. T2 times of ATP and nicotinamide adenine dinucleotide (NAD) were shortest between 8 and 20 ms, followed by T2 s of inorganic phosphate between 25 and 50 ms, and phosphocreatine with a T2 of 100 ms. Phosphomonoesters and phosphodiesters had the longest T2 s of about 130 ms. The measured T2 s are comparable with literature values and fit in a decreasing trend with increasing field strengths. Calculated pHs and metabolite concentrations are also comparable with literature values.

OTUP workflow: target specific optimization of the transmit k-space trajectory for flexible universal parallel transmit RF pulse design.

PURPOSE: To optimize transmit k-space trajectories for a wide range of excitation targets and to design "universal pTx RF pulses" based on these trajectories. METHODS: Transmit k-space trajectories (stack of spirals and SPINS) were optimized to best match different excitation targets using the parameters of the analytical equations of spirals and SPINS. The performances of RF pulses designed based on optimized and non-optimized trajectories were compared. The optimized trajectories were utilized for universal pulse design. The universal pulse performances were compared with subject specific tailored pulse performances. The OTUP workflow (optimization of transmit k-space trajectories and universal pulse calculation) was tested on three test target excitation patterns. For one target (local excitation of a central area in the human brain) the pulses were tested in vivo at 9.4 T. RESULTS: The workflow produced appropriate transmit k-space trajectories for each test target. Utilization of an optimized trajectory was crucial for the pulse performance. Using unsuited trajectories diminished the performance. It was possible to create target specific universal pulses. However, not every test target is equally well suited for universal pulse design. There was no significant difference in the in vivo performance between subject specific tailored pulses and a universal pulse at 9.4 T. CONCLUSIONS: The proposed workflow further exploited and improved the universal pulse concept by combining it with gradient trajectory optimization for stack of spirals and SPINS. It emphasized the importance of a well suited trajectory for pTx RF pulse design. Universal and tailored pulses performed with a sufficient degree of similarity in simulations and a high degree of similarity in vivo. The implemented OTUP workflow and the B0 /B1+ map data from 18 subjects measured at 9.4 T are available as open source (https://github.com/ole1965/workflow_OTUP.git).

Double-row dipole/loop combined array for human whole brain imaging at 7 T.

Important issues in designing radiofrequency (RF) coils for human head imaging at ultra-high field (UHF; ≥7 T) are the inhomogeneity and longitudinal coverage (along the magnet axis) of the transmit (Tx) RF field. Both the homogeneity and coverage produced by Tx volume coils can be improved by means of three-dimensional (3D) RF shimming, which requires the use of multirow Tx-arrays. In addition, according to recent findings of the ultimate intrinsic signal-to-noise ratio (UISNR) theory, the loop-only receive (Rx) arrays do not provide optimal SNR near the brain center at UHF. The latter can be obtained by combining complementary conductive structures carrying different current patterns (e.g., loops and dipole antennas). In this work, we developed, constructed, and evaluated a novel 32-element hybrid array design for human head imaging at 7 T. The array consists of 16 transceiver loops placed in two rows circumscribing the head and 16 folded-end Rx-only dipoles positioned in the centers of loops. By placing all elements in a single layer, we increased RF power deposition into the tissue and, thus, preserved the Tx-efficiency. Using this hybrid design also simplifies the coil structure by minimizing the total number of array elements. The array demonstrated whole brain coverage, 3D RF shimming capability, and high SNR. It provided ~15% higher SNR near the brain center and, depending on the RF shim mode, from 20% to 40% higher Tx-efficiency than a common commercial head array coil.

Predicting Antidepressant Effects of Ketamine: the Role of the Pregenual Anterior Cingulate Cortex as a Multimodal Neuroimaging Biomarker.

BACKGROUND: Growing evidence underscores the utility of ketamine as an effective and rapid-acting treatment option for major depressive disorder (MDD). However, clinical outcomes vary between patients. Predicting successful response may enable personalized treatment decisions and increase clinical efficacy. METHODS: We here explored the potential of pregenual anterior cingulate cortex (pgACC) activity to predict antidepressant effects of ketamine in relation to ketamine-induced changes in glutamatergic metabolism. Prior to a single i.v. infusion of ketamine, 24 patients with MDD underwent functional magnetic resonance imaging during an emotional picture-viewing task and magnetic resonance spectroscopy. Changes in depressive symptoms were evaluated using the Beck Depression Inventory measured 24 hours pre- and post-intervention. A subsample of 17 patients underwent a follow-up magnetic resonance spectroscopy scan. RESULTS: Antidepressant efficacy of ketamine was predicted by pgACC activity during emotional stimulation. In addition, pgACC activity was associated with glutamate increase 24 hours after the ketamine infusion, which was in turn related to better clinical outcome. CONCLUSIONS: Our results add to the growing literature implicating a key role of the pgACC in mediating antidepressant effects and highlighting its potential as a multimodal neuroimaging biomarker of early treatment response to ketamine.

Impaired glutamate homeostasis in the nucleus accumbens in human cocaine addiction.

Cocaine addiction is characterized by overwhelming craving for the substance, which drives its escalating use despite adverse consequences. Animal models suggest a disrupted glutamate homeostasis in the nucleus accumbens to underlie addiction-like behavior. After chronic administration of cocaine, rodents show decreased levels of accumbal glutamate, whereas drug-seeking reinstatement is associated with enhanced glutamatergic transmission. However, due to technical obstacles, the role of disturbed glutamate homeostasis for cocaine addiction in humans remains only partially understood, and accordingly, no approved pharmacotherapy exists. Here, we applied a tailored proton magnetic resonance spectroscopy protocol that allows glutamate quantification within the human nucleus accumbens. We found significantly reduced basal glutamate concentrations in the nucleus accumbens in cocaine-addicted (N = 26) compared with healthy individuals (N = 30), and increased glutamate levels during cue-induced craving in cocaine-addicted individuals compared with baseline. These glutamatergic alterations, however, could not be significantly modulated by a short-term challenge of N-acetylcysteine (2400 mg/day on 2 days). Taken together, our findings reveal a disturbed accumbal glutamate homeostasis as a key neurometabolic feature of cocaine addiction also in humans. Therefore, we suggest the glutamatergic system as a promising target for the development of novel pharmacotherapies, and in addition, as a potential biomarker for a personalized medicine approach in addiction.

Acute effects of ketamine on the pregenual anterior cingulate: linking spontaneous activation, functional connectivity, and glutamate metabolism.

Ketamine exerts its rapid antidepressant effects via modulation of the glutamatergic system. While numerous imaging studies have investigated the effects of ketamine on a functional macroscopic brain level, it remains unclear how altered glutamate metabolism and changes in brain function are linked. To shed light on this topic we here conducted a multimodal imaging study in healthy volunteers (N = 23) using resting state fMRI and proton (1H) magnetic resonance spectroscopy (MRS) to investigate linkage between metabolic and functional brain changes induced by ketamine. Subjects were investigated before and during an intravenous ketamine infusion. The MRS voxel was placed in the pregenual anterior cingulate cortex (pgACC), as this region has been repeatedly shown to be involved in ketamine's effects. Our results showed functional connectivity changes from the pgACC to the right frontal pole and anterior mid cingulate cortex (aMCC). Absolute glutamate and glutamine concentrations in the pgACC did not differ significantly from baseline. However, we found that stronger pgACC activation during ketamine was linked to lower glutamine concentration in this region. Furthermore, reduced functional connectivity between pgACC and aMCC was related to increased pgACC activation and reduced glutamine. Our results thereby demonstrate how multimodal investigations in a single brain region could help to advance our understanding of the association between metabolic and functional changes.

Deuterium metabolic imaging in the human brain at 9.4 Tesla with high spatial and temporal resolution.

PURPOSE: To present first highly spatially resolved deuterium metabolic imaging (DMI) measurements of the human brain acquired with a dedicated coil design and a fast chemical shift imaging (CSI) sequence at an ultrahigh field strength of B0 = 9.4 T. 2H metabolic measurements with a temporal resolution of 10 min enabled the investigation of the glucose metabolism in healthy human subjects. METHODS: The study was performed with a double-tuned coil with 10 TxRx channels for 1H and 8TxRx/2Rx channels for 2H and an Ernst angle 3D CSI sequence with a nominal spatial resolution of 2.97 ml and a temporal resolution of 10 min. RESULTS: The metabolism of [6,6'-2H2]-labeled glucose due to the TCA cycle could be made visible in high resolution metabolite images of deuterated water, glucose and Glx over the entire human brain. CONCLUSION: X-nuclei MRSI as DMI can highly benefit from ultrahigh field strength enabling higher temporal and spatial resolutions.

Local excitation universal parallel transmit pulses at 9.4T.

PURPOSE: To demonstrate that the concept of "universal pTx pulses" is applicable to local excitation applications. METHODS: A database of B0 / B1+ maps from eight different subjects was acquired at 9.4T. Based on these maps, universal pulses that aim at local excitation of the visual cortex area in the human brain (with a flip angle of 90° or 7°) were calculated. The remaining brain regions should not experience any excitation. The pulses were designed with an extension of the "spatial domain method." A 2D and a 3D target excitation pattern were tested, respectively. The pulse performance was examined on non-database subjects by Bloch simulations and in vivo at 9.4T using a GRE anatomical MRI and a presaturated TurboFLASH B1+ mapping sequence. RESULTS: The calculated universal pulses show excellent performance in simulations and in vivo on subjects that were not contained in the design database. The visual cortex region is excited, while the desired non-excitation areas produce the only minimal signal. In simulations, the pulses with 3D target pattern show a lack of excitation uniformity in the visual cortex region; however, in vivo, this inhomogeneity can be deemed acceptable. A reduced field of view application of the universal pulse design concept was performed successfully. CONCLUSIONS: The proposed design approach creates universal local excitation pulses for a flip angle of 7° and 90°, respectively. Providing universal pTx pulses for local excitation applications prospectively abandons the need for time-consuming subject-specific B0 / B1+ mapping and pTx-pulse calculation during the scan session.

Comparison of four 31P single-voxel MRS sequences in the human brain at 9.4 T.

PURPOSE: In this study, different single-voxel localization sequences were implemented and systematically compared for the first time for phosphorous MRS (31 P-MRS) in the human brain at 9.4 T. METHODS: Two multishot sequences, image-selected in vivo spectroscopy (ISIS) and a conventional slice-selective excitation combined with localization by adiabatic selective refocusing (semiLASER) variant of the spin-echo full intensity-acquired localized spectroscopy (SPECIAL-semiLASER), and two single-shot sequences, semiLASER and stimulated echo acquisition mode (STEAM), were implemented and optimized for 31 P-MRS in the human brain at 9.4 T. Pulses and coil setup were optimized, localization accuracy was tested in phantom experiments, and absolute SNR of the sequences was compared in vivo. The SNR per unit time (SNR/t) was derived and compared for all four sequences and verified experimentally for ISIS in two different voxel sizes (3 × 3 × 3 cm3 , 5 × 5 × 5 cm3 , 10-minute measurement time). Metabolite signals obtained with ISIS were quantified. The possible spectral quality in vivo acquired in clinically feasible time (3:30 minutes, 3 × 3 × 3 cm3 ) was explored for two different coil setups. RESULTS: All evaluated sequences performed with good localization accuracy in phantom experiments and provided well-resolved spectra in vivo. However, ISIS has the lowest chemical shift displacement error, the best localization accuracy, the highest SNR/t for most metabolites, provides metabolite concentrations comparable to literature values, and is the only one of the sequences that allows for the detection of the whole 31 P spectrum, including ß-adenosine triphosphate, with the used setup. The SNR/t of STEAM is comparable to the SNR/t of ISIS. The semiLASER and SPECIAL-semiLASER sequences provide good results for metabolites with long T2 . CONCLUSION: At 9.4 T, high-quality single-voxel localized 31 P-MRS can be performed in the human brain with different localization methods, each with inherent characteristics suitable for different research issues.

Unshielded bent folded-end dipole 9.4 T human head transceiver array decoupled using modified passive dipoles.

PURPOSE: To develop an unshielded dipole transceiver array for human head imaging at 9.4 Tesla and to improve decoupling of adjacent dipole elements, a novel array design with modified passive dipole antennas was developed, evaluated, and tested. METHODS: The new array consisted of 8 bent folded-end dipole elements placed in a single row and surrounding the head. Adjacent elements of RF transceiver arrays are usually decoupled by introducing circuits electrically connected to elements. These methods are difficult to use for dipole arrays because of the distant location of the adjacent antennas. A recently developed decoupling technique using passive dipoles is simple and does not require any electrical connection. However, common parallel passive dipoles can produce destructive interference with the RF field of the array itself. To minimize this interference, we placed the passive dipoles perpendicularly to the active dipoles and positioned them at the ends of the array. We also evaluated the effect of different passive dipoles on the array transmit performance. Finally, we optimized the array transmit performance by varying the length of the dipole folded portion. RESULTS: By rotating the passive dipoles 90º and moving them toward the ends of the array, we minimized the destructive interference to an acceptable level without compromising decoupling and the transmit efficiency. CONCLUSION: While keeping the benefits of the passive dipole decoupling method, the new modified dipoles produce substantially less destructive interference with the RF field of the array than the common design. The constructed transceiver array demonstrated good decoupling and whole-brain coverage.

In vivo characterization of downfield peaks at 9.4 T: T2 relaxation times, quantification, pH estimation, and assignments.

PURPOSE: Relaxation times are a valuable asset when determining spectral assignments. In this study, apparent T2 relaxation times ( T2app ) of downfield peaks are reported in the human brain at 9.4 T and are used to guide spectral assignments of some downfield metabolite peaks. METHODS: Echo time series of downfield metabolite spectra were acquired at 9.4 T using a metabolite-cycled semi-LASER sequence. Metabolite spectral fitting was performed using LCModel V6.3-1L while fitting a pH sweep to estimate the pH of the homocarnosine (hCs) imidazole ring. T2app were calculated by fitting the resulting relative amplitudes of the peaks to a mono-exponential decay across the TE series. Furthermore, estimated tissue concentrations of molecules were calculated using the relaxation times and internal water as a reference. RESULTS: T2app of downfield metabolites are reported within a range from 16 to 32 ms except for homocarnosine with T2app of 50 ms. Correcting T2app for exchange rates ( T2corr ) resulted in relaxation times between 20 and 33 ms. The estimated pH values based on hCs imidazole range from 7.07 to 7.12 between subjects. Furthermore, analyzing the linewidths of the downfield peaks and their T2app contribution led to possible peak assignments. CONCLUSION: T2app relaxation times were longer for the assigned metabolite peaks compared to the unassigned peaks. Tissue pH estimation in vivo with proton MRS and simultaneous quantification of amide protons at 8.30 ± 0.15 ppm is likely possible. Based on concentration, linewidth, and exchange rates measurements, tentative peak assignments are discussed for adenosine triphosphate (ATP), N-acetylaspartylglutamate (NAAG), and urea.