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.

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.

PurposeFull‐slice magnetic resonance spectroscopic imaging at ≥7 T is especially vulnerable to lipid contaminations arising from regions close to the skull. This contamination can be mitigated by improving the point spread function via higher spatial resolution sampling and k‐space filtering, but this prolongs scan times and reduces the signal‐to‐noise ratio (SNR) efficiency. Currently applied parallel imaging methods accelerate magnetic resonance spectroscopic imaging scans at 7T, but increase lipid artifacts and lower SNR‐efficiency further. In this study, we propose an SNR‐efficient spatial‐spectral sampling scheme using concentric circle echo planar trajectories (CONCEPT), which was adapted to intrinsically acquire a Hamming‐weighted k‐space, thus termed density‐weighted‐CONCEPT. This minimizes voxel bleeding, while preserving an optimal SNR.Theory and MethodsTrajectories were theoretically derived and verified in phantoms as well as in the human brain via measurements of five volunteers (single‐slice, field‐of‐view 220 × 220 mm2, matrix 64 × 64, scan time 6 min) with free induction decay magnetic resonance spectroscopic imaging. Density‐weighted‐CONCEPT was compared to (a) the originally proposed CONCEPT with equidistant circles (here termed e‐CONCEPT), (b) elliptical phase‐encoding, and (c) 5‐fold Controlled Aliasing In Parallel Imaging Results IN Higher Acceleration accelerated elliptical phase‐encoding.ResultsBy intrinsically sampling a Hamming‐weighted k‐space, density‐weighted‐CONCEPT removed Gibbs‐ringing artifacts and had in vivo +9.5%, +24.4%, and +39.7% higher SNR than e‐CONCEPT, elliptical phase‐encoding, and the Controlled Aliasing In Parallel Imaging Results IN Higher Acceleration accelerated elliptical phase‐encoding (all P < 0.05), respectively, which lead to improved metabolic maps.ConclusionDensity‐weighted‐CONCEPT provides clinically attractive full‐slice high‐resolution magnetic resonance spectroscopic imaging with optimal SNR at 7T. Magn Reson Med 79:2874–2885, 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.

PurposeTo compare a new parallel imaging (PI) method for multislice proton magnetic resonance spectroscopic imaging (1H‐MRSI), termed (2 + 1)D‐CAIPIRINHA, with two standard PI methods: 2D‐GRAPPA and 2D‐CAIPIRINHA at 7 Tesla (T).Methods(2 + 1)D‐CAIPIRINHA is a combination of 2D‐CAIPIRINHA and slice‐CAIPIRINHA. Eight healthy volunteers were measured on a 7T MR scanner using a 32‐channel head coil. The best undersampling patterns were estimated for all three PI methods. The artifact powers, g‐factors, Cramér–Rao lower bounds (CRLB), and root mean square errors (RMSE) were compared quantitatively among the three PI methods. Metabolic maps and spectra were compared qualitatively.Results(2 + 1)D‐CAIPIRINHA allows acceleration in three spatial dimensions in contrast to 2D‐GRAPPA and 2D‐CAIPIRINHA. Thus, this sequence significantly decreased the RMSE of the metabolic maps by 12.1 and 6.9%, on average, for 4 < R < 11, compared with 2D‐GRAPPA and 2D‐CAIPIRINHA, respectively. The artifact power was 22.6 and 8.4% lower, and the CRLB were 3.4 and 0.6% lower, respectively.Conclusion(2 + 1)‐CAIPIRINHA can be implemented for multislice MRSI in the brain, enabling higher accelerations than possible with two‐dimensional (2D) parallel imaging methods. An eight‐fold acceleration was still feasible in vivo with negligible PI artifacts with lipid decontamination, thus decreasing the measurement time from 120 to 15 min for a 64 × 64 × 4 matrix. Magn Reson Med 78:429–440, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

An adiabatic MEscher-GArwood (MEGA)-editing scheme, using asymmetric hyperbolic secant editing pulses, was developed and implemented in a B-insensitive, 1D-semiLASER (Localization by Adiabatic SElective Refocusing) MR spectroscopic imaging (MRSI) sequence for the non-invasive mapping of γ-aminobutyric acid (GABA) over a whole brain slice. Our approach exploits the advantages of edited-MRSI at 7T while tackling challenges that arise with ultra-high-field-scans. Spatial-spectral encoding, using density-weighted, concentric circle echo planar trajectory readout, enabled substantial MRSI acceleration and an improved point-spread-function, thereby reducing extracranial lipid signals. Subject motion and scanner instabilities were corrected in real-time using volumetric navigators optimized for 7T, in combination with selective reacquisition of corrupted data to ensure robust subtraction-based MEGA-editing. Simulations and phantom measurements of the adiabatic MEGA-editing scheme demonstrated stable editing efficiency even in the presence of ±0.15 ppm editing frequency offsets and B variations of up to ±30% (as typically encountered in vivo at 7T), in contrast to conventional Gaussian editing pulses. Volunteer measurements were performed with and without global inversion recovery (IR) to study regional GABA levels and their underlying, co-edited, macromolecular (MM) signals at 2.99 ppm. High-quality in vivo spectra allowed mapping of pure GABA and MM-contaminated GABA (GABA + MM) along with Glx (Glu + Gln), with high-resolution (eff. voxel size: 1.4 cm) and whole-slice coverage in 24 min scan time. Metabolic ratio maps of GABA/tNAA, GABA/tNAA, and Glx/tNAA were correlated linearly with the gray matter fraction of each voxel. A 2.15-fold increase in gray matter to white matter contrast was observed for GABA when enabling IR, which we attribute to the higher abundance of macromolecules at 2.99 ppm in the white matter than in the gray matter. In conclusion, adiabatic MEGA-editing with 1D-semiLASER selection is as a promising approach for edited-MRSI at 7T. Our sequence capitalizes on the benefits of ultra-high-field MRSI while successfully mitigating the challenges related to B/B inhomogeneities, prolonged scan times, and motion/scanner instability artifacts. Robust and accurate 2D mapping has been shown for the neurotransmitters GABA and Glx.

Purpose Proton MR spectroscopic imaging (MRSI) benefits from B0 ≥ 7T and multichannel receive coils, promising substantial resolution improvements. However, MRSI acquisition with high spatial resolution requires efficient acceleration and coil combination. To speed up the already‐fast sampling via concentric rings, we implemented additional, non‐Cartesian, hybrid through‐time/through‐k‐space (tt/tk)‐generalized autocalibrating partially parallel acquisition (GRAPPA). A new multipurpose interleaved calibration scan (interleaved MUSICAL) acquires reference data for both coil combination and PI. This renders the reconstruction process (especially PI) less sensitive to instabilities. Methods Six healthy volunteers were scanned at 7T. Three calibration datasets for coil combination and PI were recorded: a) iMUSICAL, b) static MUSICAL as prescan, c) moved MUSICAL as prescan with misaligned head position. The coil combination performance, including motion sensitivity, of iMUSICAL was compared to MUSICAL for single‐slice free induction decay (FID)‐MRSI. Through‐time/through‐k‐space‐GRAPPA with constant/variable‐density undersampling was evaluated on the same data, comparing the three calibration datasets. Additionally, the proposed method was successfully applied to 3D whole‐brain FID‐MRSI. Results Using iMUSICAL for coil combination yielded the highest signal‐to‐noise ratio (SNR) (+9%) and lowest Cramer‐Rao lower bounds (CRLBs) (‐6%) compared to both MUSICAL approaches, with similar metabolic map quality. Also, excellent mean g‐factors of 1.07 and low residual lipid aliasing were obtained when using iMUSICAL as calibration data for two‐fold, variable‐density undersampling, while significantly degraded metabolic maps were obtained using the misaligned MUSICAL calibration data. Conclusion Through‐time/through‐k‐space‐GRAPPA can accelerate already time‐efficient non‐Cartesian spatial‐spectral 2D/3D‐MRSI encoding even further. Particularly promising results have been achieved using iMUSICAL as a robust, interleaved multipurpose calibration for MRSI reconstruction, without extra calibration prescan.

Purpose In this study, we demonstrate the first combination of 3D FID proton MRSI and spatial encoding via concentric‐ring trajectories (CRTs) at 3T. FID‐MRSI has many benefits including high detection sensitivity, in particular for J‐coupled metabolites (e.g., glutamate/glutamine). This makes it highly attractive, not only for clinical, but also for, potentially, functional MRSI. However, this requires excellent reliability and temporal stability. We have, therefore, augmented this 3D‐FID‐MRSI sequence with single‐echo, imaging‐based volumetric navigators (se‐vNavs) for real‐time motion/shim‐correction (SHMOCO), which is 2× quicker than the original double‐echo navigators (de‐vNavs), hence allowing more efficient integration also in short‐TR sequences. Methods The tracking accuracy (position and B0‐field) of our proposed se‐vNavs was compared to the original de‐vNavs in phantoms (rest and translation) and in vivo (voluntary head rotation). Finally, the intra‐session stability of a 5:40 min 3D‐FID‐MRSI scan was evaluated with SHMOCO and no correction (NOCO) in 5 resting subjects. Intra/inter‐subject coefficients of variation (CV) and intra‐class correlations (ICC) over the whole 3D volume and in selected regions of interest ROI were assessed. Results Phantom and in vivo scans showed highly consistent tracking performance for se‐vNavs compared to the original de‐vNavs, but lower frequency drift. Up to ~30% better intra‐subject CVs were obtained for SHMOCO (P < 0.05), with values of 9.3/6.9/6.5/7.8% over the full VOI for Glx/tNAA/tCho/m‐Ins ratios to tCr. ICCs were good‐to‐high (91% for Glx/tCr in motor cortex), whereas the inter‐subject variability was ~11–19%. Conclusion Real‐time motion/shim corrected 3D‐FID‐MRSI with time‐efficient CRT‐sampling at 3T allows reliable, high‐resolution metabolic imaging that is fast enough for clinical use and even, potentially, for functional MRSI.

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