Gamma-aminobutyric acid (GABA) and glutamate (Glu) are the major neurotransmitters in the brain. They are crucial for the functioning of healthy brain and their alteration is a major mechanism in the pathophysiology of many neuro-psychiatric disorders. Magnetic resonance spectroscopy (MRS) is the only way to measure GABA and Glu non-invasively in vivo. GABA detection is particularly challenging and requires special MRS techniques. The most popular is MEscher-GArwood (MEGA) difference editing with single-voxel Point RESolved Spectroscopy (PRESS) localization. This technique has three major limitations: a) MEGA editing is a subtraction technique, hence is very sensitive to scanner instabilities and motion artifacts. b) PRESS is prone to localization errors at high fields (≥3T) that compromise accurate quantification. c) Single-voxel spectroscopy can (similar to a biopsy) only probe average GABA and Glu levels in a single location at a time. To mitigate these problems, we implemented a 3D MEGA-editing MRS imaging sequence with the following three features: a) Real-time motion correction, dynamic shim updates, and selective reacquisition to eliminate subtraction artifacts due to scanner instabilities and subject motion. b) Localization by Adiabatic SElective Refocusing (LASER) to improve the localization accuracy and signal-to-noise ratio. c) K-space encoding via a weighted stack of spirals provides 3D metabolic mapping with flexible scan times. Simulations, phantom and in vivo experiments prove that our MEGA-LASER sequence enables 3D mapping of GABA+ and Glx (Glutamate + Gluatmine), by providing 1.66 times larger signal for the 3.02 ppm multiplet of GABA+ compared to MEGA-PRESS, leading to clinically feasible scan times for 3D brain imaging. Hence, our sequence allows accurate and robust 3D-mapping of brain GABA+ and Glx levels to be performed at clinical 3T MR scanners for use in neuroscience and clinical applications.

MRSI in the brain at ≥7 T is a technique of great promise, but has been limited mainly by low B/B-homogeneity, specific absorption rate restrictions, long measurement times, and low spatial resolution. To overcome these limitations, we propose an ultra-high resolution (UHR) MRSI sequence that provides a 128×128 matrix with a nominal voxel volume of 1.7×1.7×8mm in a comparatively short measurement time. A clinically feasible scan time of 10-20min is reached via a short TR of 200 ms due to an optimised free induction decay-based acquisition with shortened water suppression as well as parallel imaging (PI) using Controlled Aliasing In Parallel Imaging Results IN Higher Acceleration (CAIPIRINHA). This approach is not limited to a rectangular region of interest in the centre of the brain, but also covers cortical brain regions. Transversal pulse-cascaded Hadamard encoding was able to further extend the coverage to 3D-UHR-MRSI of four slices (100×100×4 matrix size), with a measurement time of 17min. Lipid contamination was removed during post-processing using L2-regularisation. Simulations, phantom and volunteer measurements were performed. The obtained single-slice and 3D-metabolite maps show the brain in unprecedented detail (e.g., hemispheres, ventricles, gyri, and the contrast between grey and white matter). This facilitates the use of UHR-MRSI for clinical applications, such as measurements of the small structures and metabolic pathologic deviations found in small Multiple Sclerosis lesions.

PurposeShort‐echo‐time proton MR spectra at 7T feature nine to 10 distinct macromolecule (MM) resonances that overlap with the signals of metabolites. Typically, a metabolite‐nulled in vivo MM spectrum is included in the quantification`s prior knowledge to provide unbiased metabolite quantification. However, this MM model may fail if MMs are pathologically altered. In addition, information about the individual MM peaks is lost. In this study, we aimed to create an improved MM model by parameterization of the in vivo MM spectrum into individual components, and to use this new model to quantify free induction decay MR spectroscopic imaging (FID‐MRSI) data.MethodsThe measured in vivo MM spectrum was parameterized using advanced method for accurate, robust, and efficient spectral fitting (AMARES) and Hankel‐Lanczos singular value decomposition algorithms from which six different MM models were derived. Soft constraints were applied to avoid over‐parameterization. All MM models were combined with simulated metabolite spectra to form complete basis sets. FID‐MRSI data from 14 healthy volunteers were quantified via LCModel, and the results were compared between all basis sets.ResultsThe MM model using nine individual AMARES‐parameterized MM components with additional soft constraints achieved the most reliable results. Nine MMs and seven metabolites were mapped simultaneously over the whole slice.ConclusionThe proposed MM model may facilitate studies that involve patients with pathologically altered MMs. Magn Reson Med 79:1231–1240, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

The growing interest in ultra-high field MRI, with more than 35.000 MR examinations already performed at 7 T, is related to improved clinical results with regard to morphological as well as functional and metabolic capabilities. Since the signal-to-noise ratio increases with the field strength of the MR scanner, the most evident application at 7 T is to gain higher spatial resolution in the brain compared to 3 T. Of specific clinical interest for neuro applications is the cerebral cortex at 7 T, for the detection of changes in cortical structure, like the visualization of cortical microinfarcts and cortical plaques in Multiple Sclerosis. In imaging of the hippocampus, even subfields of the internal hippocampal anatomy and pathology may be visualized with excellent spatial resolution. Using Susceptibility Weighted Imaging, the plaque-vessel relationship and iron accumulations in Multiple Sclerosis can be visualized, which may provide a prognostic factor of disease. Vascular imaging is a highly promising field for 7 T which is dealt with in a separate dedicated article in this special issue. The static and dynamic blood oxygenation level-dependent contrast also increases with the field strength, which significantly improves the accuracy of pre-surgical evaluation of vital brain areas before tumor removal. Improvement in acquisition and hardware technology have also resulted in an increasing number of MR spectroscopic imaging studies in patients at 7 T. More recent parallel imaging and short-TR acquisition approaches have overcome the limitations of scan time and spatial resolution, thereby allowing imaging matrix sizes of up to 128×128. The benefits of these acquisition approaches for investigation of brain tumors and Multiple Sclerosis have been shown recently. Together, these possibilities demonstrate the feasibility and advantages of conducting routine diagnostic imaging and clinical research at 7 T.

Objectives Available clinical magnetic resonance spectroscopic imaging (MRSI) sequences are hampered by long scan times, low spatial resolution, strong field inhomogeneities, limited volume coverage, and low signal-to-noise ratio. High-resolution, whole-brain mapping of more metabolites than just N-acetylaspartate, choline, and creatine within clinically attractive scan times is urgently needed for clinical applications. The aim is therefore to develop a free induction decay (FID) MRSI sequence with rapid concentric ring trajectory (CRT) encoding for 7 T and demonstrate its clinical feasibility for mapping the whole cerebrum of healthy volunteers and patients. Materials and Methods Institutional review board approval and written informed consent were obtained. Time-efficient, 3-dimensional encoding of an ellipsoidal k-space by in-plane CRT and through-plane phase encoding was integrated into an FID-MRSI sequence. To reduce scan times further, repetition times were shortened, and variable temporal interleaves were applied. Measurements with different matrix sizes were performed to validate the CRT encoding in a resolution phantom. One multiple sclerosis patient, 1 glioma patient, and 6 healthy volunteers were prospectively measured. For the healthy volunteers, brain segmentation was performed to quantify median metabolic ratios, Cramér-Rao lower bounds (CRLBs), signal-to-noise ratios, linewidths, and brain coverage among all measured matrix sizes ranging from a 32 × 32 × 31 matrix with 6.9 × 6.9 × 4.2 mm3 nominal voxel size acquired in ~3 minutes to an 80 × 80 × 47 matrix with 2.7 × 2.7 × 2.7 mm3 nominal voxel size in ~15 minutes for different brain regions. Results Phantom structures with diameters down to 3 to 4 mm were visible. In vivo MRSI provided high spectral quality (median signal-to-noise ratios, >6.3 and linewidths, <0.082 ppm) and fitting quality. Cramér-Rao lower bounds were ranging from less than 22% for glutamine (highest CRLB in subcortical gray matter) to less than 9.5% for N-acetylaspartate for the 80 × 80 × 47 matrix (highest CRLB in the temporal lobe). This enabled reliable mapping of up to 8 metabolites (N-acetylaspartate, N-acetylaspartyl glutamate, total creatine, glutamine, glutamate, total choline, myo-inositol, glycine) and macromolecules for all resolutions. Coverage of the whole cerebrum allowed visualization of the full extent of diffuse and local multiple sclerosis-related neurochemical changes (eg, up to 100% increased myo-inositol). Three-dimensional brain tumor metabolic maps provided valuable information beyond that of single-slice MRSI, with up to 200% higher choline, up to 100% increased glutamine, and increased glycine in tumor tissue. Conclusions Seven Tesla FID-MRSI with time-efficient CRT readouts offers clinically attractive acquisition protocols tailored either for speed or for the investigation of small pathologic details and low-abundant metabolites. This can complement clinical MR studies of various brain disorders. Significant metabolic anomalies were demonstrated in a multiple sclerosis and a glioma patient for myo-inositol, glutamine, total choline, glycine, and N-acetylaspartate concentrations.