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.

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.

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.

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.