Comparison of intramyocellular lipid metabolism in patients with diabetes and male athletes.

Despite opposing insulin sensitivity and cardiometabolic risk, both athletes and patients with type 2 diabetes have increased skeletal myocyte fat storage: the so-called "athlete's paradox". In a parallel non-randomised, non-blinded trial (NCT03065140), we characterised and compared the skeletal myocyte lipid signature of 29 male endurance athletes and 30 patients with diabetes after undergoing deconditioning or endurance training respectively. The primary outcomes were to assess intramyocellular lipid storage of the vastus lateralis in both cohorts and the secondary outcomes were to examine saturated and unsaturated intramyocellular lipid pool turnover. We show that athletes have higher intramyocellular fat saturation with very high palmitate kinetics, which is attenuated by deconditioning. In contrast, type 2 diabetes patients have higher unsaturated intramyocellular fat and blunted palmitate and linoleate kinetics but after endurance training, all were realigned with those of deconditioned athletes. Improved basal insulin sensitivity was further associated with better serum cholesterol/triglycerides, glycaemic control, physical performance, enhanced post insulin receptor pathway signalling and metabolic sensing. We conclude that insulin-resistant, maladapted intramyocellular lipid storage and turnover in patients with type 2 diabetes show reversibility after endurance training through increased contributions of the saturated intramyocellular fatty acid pools. Clinical Trial Registration: NCT03065140: Muscle Fat Compartments and Turnover as Determinant of Insulin Sensitivity (MISTY).

Gray matter gamma-hydroxy-butyric acid and glutamate reflect beta-amyloid burden at old age.

Gamma-hydroxy-butyric acid (GABA) and glutamate are neurotransmitters with essential importance for cognitive processing. Here, we investigate relationships between GABA, glutamate, and brain ß-amyloid (Aß) burden before clinical manifestation of Alzheimer's disease (AD). Thirty cognitively healthy adults (age 69.9 ± 6 years) received high-resolution atlas-based 1H-magnetic resonance spectroscopic imaging (MRSI) at ultra-high magnetic field strength of 7 Tesla for gray matter-specific assessment of GABA and glutamate. We assessed Aß burden with positron emission tomography and risk factors for AD. Higher gray matter GABA and glutamate related to higher Aß-burden (ß = 0.60, p < 0.05; ß = 0.64, p < 0.02), with positive effect modification by apolipoprotein-E-epsilon-4-allele (APOE4) (p = 0.01-0.03). GABA and glutamate negatively related to longitudinal change in verbal episodic memory performance (ß = -0.48; p = 0.02; ß = -0.50; p = 0.01). In vivo measures of GABA and glutamate reflect early AD pathology at old age, in an APOE4-dependent manner. GABA and glutamate may represent promising biomarkers and potential targets for early therapeutic intervention and prevention. Highlights: Gray matter-specific metabolic imaging with high-resolution atlas-based MRSI at 7 Tesla.Higher GABA and glutamate relate to ß-amyloid burden, in an APOE4-dependent manner.Gray matter GABA and glutamate identify older adults with high risk of future AD.GABA and glutamate might reflect altered synaptic and neuronal activity at early AD.

1H and 31P magnetic resonance spectroscopy reveals potential pathogenic and biomarker metabolite alterations in Lafora disease.

Lafora disease is a fatal teenage-onset progressive myoclonus epilepsy and neurodegenerative disease associated with polyglucosan bodies. Polyglucosans are long-branched and as a result precipitation- and aggregation-prone glycogen. In mouse models, downregulation of glycogen synthase, the enzyme that elongates glycogen branches, prevents polyglucosan formation and rescues Lafora disease. Mouse work, however, has not yet revealed the mechanisms of polyglucosan generation, and few in vivo human studies have been performed. Here, non-invasive in vivo magnetic resonance spectroscopy (1H and 31P) was applied to test scan feasibility and assess neurotransmitter balance and energy metabolism in Lafora disease towards a better understanding of pathogenesis. Macromolecule-suppressed gamma-aminobutyric acid (GABA)-edited 1H magnetic resonance spectroscopy and 31P magnetic resonance spectroscopy at 3 and 7 tesla, respectively, were performed in 4 Lafora disease patients and a total of 21 healthy controls (12 for the 1H magnetic resonance spectroscopy and 9 for the 31PMRS). Spectra were processed using in-house software and fit to extract metabolite concentrations. From the 1H spectra, we found 33% lower GABA concentrations (P = 0.013), 34% higher glutamate + glutamine concentrations (P = 0.011) and 24% lower N-acetylaspartate concentrations (P = 0.0043) in Lafora disease patients compared with controls. From the 31P spectra, we found 34% higher phosphoethanolamine concentrations (P = 0.016), 23% lower nicotinamide adenine dinucleotide concentrations (P = 0.003), 50% higher uridine diphosphate glucose concentrations (P = 0.004) and 225% higher glucose 6-phosphate concentrations in Lafora disease patients versus controls (P = 0.004). Uridine diphosphate glucose is the substrate of glycogen synthase, and glucose 6-phosphate is its extremely potent allosteric activator. The observed elevated uridine diphosphate glucose and glucose 6-phosphate levels are expected to hyperactivate glycogen synthase and may underlie the generation of polyglucosans in Lafora disease. The increased glutamate + glutamine and reduced GABA indicate altered neurotransmission and energy metabolism, which may contribute to the disease's intractable epilepsy. These results suggest a possible basis of polyglucosan formation and potential contributions to the epilepsy of Lafora disease. If confirmed in larger human and animal model studies, measurements of the dysregulated metabolites by magnetic resonance spectroscopy could be developed into non-invasive biomarkers for clinical trials.

17ß-Estradiol Effects in Skeletal Muscle: A 31P MR Spectroscopic Imaging (MRSI) Study of Young Females during Early Follicular (EF) and Peri-Ovulation (PO) Phases.

The natural variation in estrogen secretion throughout the female menstrual cycle impacts various organs, including estrogen receptor (ER)-expressed skeletal muscle. Many women commonly experience increased fatigue or reduced energy levels in the days leading up to and during menstruation, when blood estrogen levels decline. Yet, it remains unclear whether endogenous 17ß-estradiol, a major estrogen component, directly affects the energy metabolism in skeletal muscle due to the intricate and fluctuating nature of female hormones. In this study, we employed 2D 31P FID-MRSI at 7T to investigate phosphoryl metabolites in the soleus muscle of a cohort of young females (average age: 28 ± 6 years, n = 7) during the early follicular (EF) and peri-ovulation (PO) phases, when their blood 17ß-estradiol levels differ significantly (EF: 28 ± 18 pg/mL vs. PO: 71 ± 30 pg/mL, p < 0.05), while the levels of other potentially interfering hormones remain relatively invariant. Our findings reveal a reduction in ATP-referenced phosphocreatine (PCr) levels in the EF phase compared to the PO phase for all participants (5.4 ± 4.3%). Furthermore, we observe a linear correlation between muscle PCr levels and blood 17ß-estradiol concentrations (r = 0.64, p = 0.014). Conversely, inorganic phosphate Pi and phospholipid metabolite GPC levels remain independent of 17ß-estradiol but display a high correlation between the EF and PO phases (p = 0.015 for Pi and p = 0.0008 for GPC). The robust association we have identified between ATP-referenced PCr and 17ß-estradiol suggests that 17ß-estradiol plays a modulatory role in the energy metabolism of skeletal muscle.

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.

Improving the Effective Spatial Resolution in 1H-MRSI of the Prostate with Three-Dimensional Overdiscretized Reconstructions.

In in vivo 1H-MRSI of the prostate, small matrix sizes can cause voxel bleeding extending to regions far from a voxel, dispersing a signal of interest outside that voxel and mixing extra-prostatic residual lipid signals into the prostate. To resolve this problem, we developed a three-dimensional overdiscretized reconstruction method. Without increasing the acquisition time from current 3D MRSI acquisition methods, this method is aimed to improve the localization of metabolite signals in the prostate without compromising on SNR. The proposed method consists of a 3D spatial overdiscretization of the MRSI grid, followed by noise decorrelation with small random spectral shifts and weighted spatial averaging to reach a final target spatial resolution. We successfully applied the three-dimensional overdiscretized reconstruction method to 3D prostate 1H-MRSI data at 3T. Both in phantom and in vivo, the method proved to be superior to conventional weighted sampling with Hamming filtering of k-space. Compared with the latter, the overdiscretized reconstructed data with smaller voxel size showed up to 10% less voxel bleed while maintaining higher SNR by a factor of 1.87 and 1.45 in phantom measurements. For in vivo measurements, within the same acquisition time and without loss of SNR compared with weighted k-space sampling and Hamming filtering, we achieved increased spatial resolution and improved localization in metabolite maps.

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.

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.

Glutathione in the Pons Is Associated With Clinical Status Improvements in Subacute Spinal Cord Injury.

OBJECTIVES: In spinal cord injury (SCI), the primary mechanical injury is followed by secondary sequelae that develop over the subsequent months and manifests in biochemical, functional, and microstructural alterations, at the site of direct injury but also in the spinal cord tissue above and below the actual lesion site. Noninvasive magnetic resonance spectroscopy (MRS) can be used to assess biochemical modulation occurring in the secondary injury phase, in addition to and supporting conventional MRI, and might help predict and improve patient outcome. In this article, we aimed to examine the metabolic levels in the pons of subacute SCI by means of in vivo proton MRS at 3 T and explore the association to clinical scores. MATERIALS AND METHODS: In this prospective study, between November 2015 and February 2018, single-voxel short-echo MRS data were acquired in healthy controls and in SCI subjects in the pons once during rehabilitation. Besides the single-point MRS examination, in addition, in participants with SCI, the clinical status (ie, motor, light touch, and pinprick scores) was assessed twice: (1) around the MRS session (approximately 10 weeks postinjury) and (2) before discharge (at approximately 9 months postinjury). The group differences were assessed with Kruskal-Wallis test, the post hoc comparison was assessed with Wilcoxon rank sum test, and the clinical correlations were conducted with Spearman rank correlation test. Bayes factor calculations completed the statistical part providing relevant evidence values. RESULTS: Twenty healthy controls (median age, 50 years; interquartile range, 41-55 years; 18 men) and 18 subjects with traumatic SCI (median age, 50 years; interquartile range, 32-58 years; 16 men) are included. Group comparison showed an increase of total N -acetylaspartate and combined glutamate and glutamine levels in complete SCI and a reduction of total creatine in incomplete paraplegic SCI. The proton MRS-based glutathione levels at baseline correlate to the motor score improvement during rehabilitation in incomplete subacute SCI. CONCLUSIONS: This exploratory study showed an association of the metabolite concentration of glutathione in the pons assessed at approximately 10 weeks after injury with the improvements of the motor score during the rehabilitation. Pontine glutathione levels in subjects with traumatic subacute incomplete SCI acquired remote from the injury site correlate to clinical score and might therefore be beneficial in the rehabilitation assessments.

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.

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.

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.

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.

Measurement of glucose metabolism in the occipital lobe and frontal cortex after oral administration of [1-13C]glucose at 9.4 T.

For the first time, labeling effects after oral intake of [1-13C]glucose are observed in the human brain with pure 1H detection at 9.4 T. Spectral time series were acquired using a short-TE 1H MRS MC-semiLASER (Metabolite Cycling semi Localization by Adiabatic SElective Refocusing) sequence in two voxels of 5.4 mL in the frontal cortex and the occipital lobe. High-quality time-courses of [4-13C]glutamate, [4-13C]glutamine, [3-13C]glutamate + glutamine, [2-13C] glutamate+glutamine and [3-13C]aspartate for individual volunteers and additionally, group-averaged time-courses of labeled and non-labeled brain glucose could be obtained. Using a one-compartment model, mean metabolic rates were calculated for each voxel position: The mean rate of the TCA-cycle (Vtca) value was determined to be 1.36 and 0.93 µmol min-1 g-1, the mean rate of glutamine synthesis (Vgln) was calculated to be 0.23 and 0.45 µmol min-1 g-1, the mean exchange rate between cytosolic amino acids and mitochondrial Krebs cycle intermediates (Vx) rate was found to be 0.57 and 1.21 µmol min-1 g-1 for the occipital lobe and the frontal cortex, respectively. These values were in agreement with previously reported data. Altogether, it can be shown that this most simple technique combining oral administration of [1-13C]Glc with pure 1H MRS acquisition is suitable to measure metabolic rates.

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.

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.

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).

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.